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  • Already famous since the high Middle Ages, the Salernitan Medical School reached its whole scientific role between the 11th and 12th century, declining later due to the rising of modern universities. Information on the earliest period of the School is very poor but, starting from the 10th century, we know that Salernitan physicians were widely recognized as researchers and healers. This paper is focused on the heavy role recognized to the Langobards (first) and Normans (later) on development of the Salernitan Medical School. A special role must be recognized to Alfanus I, Gariopontus and Trotula de Ruggiero they left memories on their enterprises and many manuscripts of great relevance for the development of Middle Ages and Renaissance Medicine. Their multicultural experience dragged the Salernitan School to become the greatest expression of medical science of its age. This role was expressed in the "Regimen Sanitatis Salernitanum" or "Flos Medicinae Salerni", a book that resumes the highest knowledges on general hygiene, dietetics, physiotherapy, comparative anatomy and surgery. The book had a tremendous success, having more than 300 editions in many languages up to 1846. It was an essential reference for western medical literature up to Renaissance. Furthermore, Langobards took care of health laws, mainly in the Rotari edict, which included laws on medical practice and on the physicians' role. (www.actabiomedica.it).
    Locomotive syndrome (LoS) is condition wherein mobility functions such as sit-to-stand or gait are declined due to locomotive organ impairment. The important risk factors for the LoS are ageing and physical factors. Physical factors significantly associated with dental status Aim To investigate the relationships between teeth lost and locomotive syndrome.

    A cross sectional study was carried among (45-90 years) individuals by using Loco Check List. Factors related to demographics (age, sex) and number of teeth lost were assessed. Pearson's chi-square test, multiple logistic regression analysis were performed. p <0.05 was considered to be statistically significant.

    Out of 322 subjects, majority of subjects (58.7%) hadLoS.Locomotive syndrome was observed high significantly (78.0% P = 0.0000) among >60 years age group. Majority of the subjects with tooth loss more than 10 teeth (92.6%) had a locomotive syndrome followed by the subjects with tooth loss 1-10 teeth (52.1%). Multiple logistic regression analysis revealed Locomotive syndrome was significantly (P= 0.000) higher among older age groups (>60 years) when compared with the 45- 60 years age group (or = 0.732) and subject with more than 10 teeth lost when compared with others (or = .009,or = 0.105) Conclusion Study indicates that older age and number of teeth lost affect the prevalence of locomotive syndrome. Hence, maintaining oral health is necessary to retain more number of teeth throughout life which reduces the risk of locomotive syndrome.
    60 years) when compared with the 45- 60 years age group (or = 0.732) and subject with more than 10 teeth lost when compared with others (or = .009,or = 0.105) Conclusion Study indicates that older age and number of teeth lost affect the prevalence of locomotive syndrome. Hence, maintaining oral health is necessary to retain more number of teeth throughout life which reduces the risk of locomotive syndrome.The study of human anatomy, besides being fundamental to the practice of medicine, has traditionally always been present in the daily life of many Renaissance artists. In this context, the specialized literature has described the famous Renaissance artist Michelangelo Buonarroti (1475-1564) as being among the greatest artist-anatomists of his time. Thus, many researchers have tried to better understand the inspirations of this famous artist, and even the possible diseases that affected this genius of human anatomy. Therefore, for the first time, this manuscript provides evidence that Michelangelo Buonarroti may have concealed letters, numbers, and faces in the anatomy of the Vatican's Pietà [Virgin Mary/************] in 1498-9. The revelation of these findings, besides testifying to the artist's considerable skill in representing the corporeal forms in his sculptures, will also be provide useful insights into the iconographic understanding of a work of art that is undoubtedly one of the most important of the Renaissance. Moreover, the present study shall be important for professionals in the medico-artistic field and those who keep some interest in the history of human anatomy, which is undoubtedly a fundamental discipline for the practice of medicine.Objectives Type Ia endoleak (EL) after endovascular abdominal aortic repair (EVAR) may be misdiagnosed at completion angiography. Intraoperative contrast-enhanced ultrasound (CEUS) may play a role in early detection and immediate treatment of type Ia EL. Methods From January 2017 to April 2018, patients treated with EVAR underwent intraoperative CEUS. After endograft deployment and ballooning, digital subtraction angiography (DSA) and intraoperative CEUS were performed in a blinded fashion. All cases of type Ia EL at DSA or CEUS were considered. Results Type Ia EL detected at intraoperative CEUS and undetected at DSA was defined in 2 patients. The former was solved with intraoperative re-ballooning; in the latter case, a Palmaz stent deployment was required. The resolution of type Ia EL was detected at intraoperative CEUS control and post-operative computed tomography angiography (CTA). In another patient, the DSA detected a type Ia EL, but intraoperative CEUS reveal a type II EL from lumbar arteries. Post-operative CTA confirm the type II EL. Conclusions The reported cases prove the clinical utility of the intraoperative CEUS, permitting the early identification of 2 type Ia EL. In addition, the intraoperative CEUS is useful in case of dubious type Ia EL at DSA, avoiding unnecessary intraoperative adjunctive procedure or post-operative CTA.We read with great interest the article by D'Ettorre et al. on workplace safety and violence against healthcare workers in emergency medicine recently published in your esteemed journal. Authors address one of the critical issues faced in healthcare industry today. We wish to complement the article with some additional thoughts. As authors try to find remedies to minimize workplace violence against the healthcare providers by optimizing number of night shifts and adopting constant forward-rotating shift schedules, we need to augment this effort by continual effort to improve education and sensitivity amongst the colleagues to be able to emotionally support each other. An important aspect to this is to also provide religious and spiritual support to the healthcare staff (and patients) upon request. Evidence supports improvement in overall well-being and a protective benefit against burnout with religious and spiritual beliefs in healthcare providers. https://www.selleckchem.com/products/jg98.html As quite aptly pointed out by other seasoned authors; based on decades of experience, commonality of common sense has been a declining asset in our current set up of medical practice, whether it has a component moral decline associated with it remains debatable.
    Already famous since the high Middle Ages, the Salernitan Medical School reached its whole scientific role between the 11th and 12th century, declining later due to the rising of modern universities. Information on the earliest period of the School is very poor but, starting from the 10th century, we know that Salernitan physicians were widely recognized as researchers and healers. This paper is focused on the heavy role recognized to the Langobards (first) and Normans (later) on development of the Salernitan Medical School. A special role must be recognized to Alfanus I, Gariopontus and Trotula de Ruggiero they left memories on their enterprises and many manuscripts of great relevance for the development of Middle Ages and Renaissance Medicine. Their multicultural experience dragged the Salernitan School to become the greatest expression of medical science of its age. This role was expressed in the "Regimen Sanitatis Salernitanum" or "Flos Medicinae Salerni", a book that resumes the highest knowledges on general hygiene, dietetics, physiotherapy, comparative anatomy and surgery. The book had a tremendous success, having more than 300 editions in many languages up to 1846. It was an essential reference for western medical literature up to Renaissance. Furthermore, Langobards took care of health laws, mainly in the Rotari edict, which included laws on medical practice and on the physicians' role. (www.actabiomedica.it). Locomotive syndrome (LoS) is condition wherein mobility functions such as sit-to-stand or gait are declined due to locomotive organ impairment. The important risk factors for the LoS are ageing and physical factors. Physical factors significantly associated with dental status Aim To investigate the relationships between teeth lost and locomotive syndrome. A cross sectional study was carried among (45-90 years) individuals by using Loco Check List. Factors related to demographics (age, sex) and number of teeth lost were assessed. Pearson's chi-square test, multiple logistic regression analysis were performed. p <0.05 was considered to be statistically significant. Out of 322 subjects, majority of subjects (58.7%) hadLoS.Locomotive syndrome was observed high significantly (78.0% P = 0.0000) among >60 years age group. Majority of the subjects with tooth loss more than 10 teeth (92.6%) had a locomotive syndrome followed by the subjects with tooth loss 1-10 teeth (52.1%). Multiple logistic regression analysis revealed Locomotive syndrome was significantly (P= 0.000) higher among older age groups (>60 years) when compared with the 45- 60 years age group (or = 0.732) and subject with more than 10 teeth lost when compared with others (or = .009,or = 0.105) Conclusion Study indicates that older age and number of teeth lost affect the prevalence of locomotive syndrome. Hence, maintaining oral health is necessary to retain more number of teeth throughout life which reduces the risk of locomotive syndrome. 60 years) when compared with the 45- 60 years age group (or = 0.732) and subject with more than 10 teeth lost when compared with others (or = .009,or = 0.105) Conclusion Study indicates that older age and number of teeth lost affect the prevalence of locomotive syndrome. Hence, maintaining oral health is necessary to retain more number of teeth throughout life which reduces the risk of locomotive syndrome.The study of human anatomy, besides being fundamental to the practice of medicine, has traditionally always been present in the daily life of many Renaissance artists. In this context, the specialized literature has described the famous Renaissance artist Michelangelo Buonarroti (1475-1564) as being among the greatest artist-anatomists of his time. Thus, many researchers have tried to better understand the inspirations of this famous artist, and even the possible diseases that affected this genius of human anatomy. Therefore, for the first time, this manuscript provides evidence that Michelangelo Buonarroti may have concealed letters, numbers, and faces in the anatomy of the Vatican's Pietà [Virgin Mary/Jesus Christ] in 1498-9. The revelation of these findings, besides testifying to the artist's considerable skill in representing the corporeal forms in his sculptures, will also be provide useful insights into the iconographic understanding of a work of art that is undoubtedly one of the most important of the Renaissance. Moreover, the present study shall be important for professionals in the medico-artistic field and those who keep some interest in the history of human anatomy, which is undoubtedly a fundamental discipline for the practice of medicine.Objectives Type Ia endoleak (EL) after endovascular abdominal aortic repair (EVAR) may be misdiagnosed at completion angiography. Intraoperative contrast-enhanced ultrasound (CEUS) may play a role in early detection and immediate treatment of type Ia EL. Methods From January 2017 to April 2018, patients treated with EVAR underwent intraoperative CEUS. After endograft deployment and ballooning, digital subtraction angiography (DSA) and intraoperative CEUS were performed in a blinded fashion. All cases of type Ia EL at DSA or CEUS were considered. Results Type Ia EL detected at intraoperative CEUS and undetected at DSA was defined in 2 patients. The former was solved with intraoperative re-ballooning; in the latter case, a Palmaz stent deployment was required. The resolution of type Ia EL was detected at intraoperative CEUS control and post-operative computed tomography angiography (CTA). In another patient, the DSA detected a type Ia EL, but intraoperative CEUS reveal a type II EL from lumbar arteries. Post-operative CTA confirm the type II EL. Conclusions The reported cases prove the clinical utility of the intraoperative CEUS, permitting the early identification of 2 type Ia EL. In addition, the intraoperative CEUS is useful in case of dubious type Ia EL at DSA, avoiding unnecessary intraoperative adjunctive procedure or post-operative CTA.We read with great interest the article by D'Ettorre et al. on workplace safety and violence against healthcare workers in emergency medicine recently published in your esteemed journal. Authors address one of the critical issues faced in healthcare industry today. We wish to complement the article with some additional thoughts. As authors try to find remedies to minimize workplace violence against the healthcare providers by optimizing number of night shifts and adopting constant forward-rotating shift schedules, we need to augment this effort by continual effort to improve education and sensitivity amongst the colleagues to be able to emotionally support each other. An important aspect to this is to also provide religious and spiritual support to the healthcare staff (and patients) upon request. Evidence supports improvement in overall well-being and a protective benefit against burnout with religious and spiritual beliefs in healthcare providers. https://www.selleckchem.com/products/jg98.html As quite aptly pointed out by other seasoned authors; based on decades of experience, commonality of common sense has been a declining asset in our current set up of medical practice, whether it has a component moral decline associated with it remains debatable.
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  • Electro-biological particle electrode (EBPE) prepared by lithium **** was used to remove salicylic acid in a three-dimensional electrocatalytic biological coupling reactor (3D-EBCR). The physical and chemical properties of the EBPE, the removal performance of salicylic acid and the degradation mechanism were studied. Results revealed as follows (1) the EBPE prepared by lithium **** contained effective catalytic components including Fe2O3, SnO2, ZnO, MnO, Rb2O and TiO2, with stable structure and good adsorption performance; (2) the 3D-EBCR with EBPE had strong adaptability to the current intensity in the range of 0.25-0.40 A, and the removal rates of COD and salicylic acid were maintained above 87.1% and 85.2% respectively; (3) salicylic acid was removed through the synergistic action of adsorption, electrochemical oxidation and biological action.The abundant existence of antibiotics within the effluent of wastewater treatment plant seriously threatened their safety recharging. To investigate the fate and biodegradation of those toxic antibiotics within the soil aquifer system, typical antibiotics of amoxicillin (AMX) and tetracycline (TC) were selected and their removal mechanisms were investigated. Experimental results revealed that totally 93.4% and 87.2% of the AMX and TC recharged (10 μg/L) were, respectively, removed within 1 m depth column operation. Specifically, the aerobic biodegradation, abiotic processes and anoxic/anaerobic microorganism contributed as higher as 37.5%, 33.7% and 28.8% of the AMX reduction, via the controlling tests of NaN3 inhibition and soil sterilisations. By contrast, the percentage contribution of the TC was aerobic (54.3%) ˃abiotic processes (32.7%) ˃anoxic/anaerobic (13.0%), a higher aerobic degradation whereas weaker anoxic/anaerobic microorganism. Column systems (CSs) were constructed to study the effect of redox conditions (methanogenic, sulfate-reducing, nitrate-reducing, aerobic) on antibiotics degradation, and microbial community results revealed that Verrucomicrobia, Actinobacteria, Deinococcus-Thermus and Armatimonadetes contributed to the aerobic biodegradation of TC. For comparison, AMX could be efficiently degraded under nitrate reduction (19.95%) > sulfate reduction (16.64%) > methanogenic (9.53%), and Actinobacteria, Bacteroidetes and Verrucomicrobia were the dominant bacteria for AMX degradation. This study provided optimal directions for antibiotics removal within the groundwater recharging systems and is conducive to obtain highly value-added reclaimed water.Citrate-coated iron oxide nanoparticles (IONPs) have potential use in environmental remediation, with possibilities in decontaminating aquatic environments exposed to toxic substances. This study analyzed IONPs associated to Roundup Original, a glyphosate-based herbicide (GBH), and pure glyphosate (GLY), through ultrastructural and histopathological biomarkers in liver tissue, from females of Poecilia reticulata exposed to iron ions (0.3 mg/L) (IFe) and IONPs (0.3 mgFe/L) associated with GLY (0.65 mg/L) and GBH (0.65 mgGLY/L (IONP + GBH1) and 1.30 mgGLY/L (IONP + GBH2)) for a period of 7, 14 and 21 days, followed by an equal post-exposure period only in reconstituted water. For the assays, the synthetized IONPs had crystalline and rounded shape with an average diameter of 2,90 nm, hydrodynamic diameter 66,6 mV, zeta potential -55,4 and diffraction profile of maghemite (γ-Fe2O3). The data obtained by biomarkers indicated a high inflammatory response in all treatments. These same parameters, considered during the post-exposure period indicated recovery in reaction patterns of circulatory disturbances and regressive changes, resulting in average reductions of 37,53 points in IFe, 21 points in IONP + GBH1, 15 points in IONP + GBH2 and 11 points in IONP + GLY in total histopathological index of liver after 21 days post-exposure. However, although the cellular and tissue responses were significant, there was no change in the condition factor and hepatosomatic index, denoting resilience of the experimental model.River biofilm communities are the first ones to be exposed to all toxic discharges received via run off from agricultural fields. Hence, changes in river biofilm community structure and growth pattern are considered as indicator of overall health of lotic ecosystem. Toxicants have effect on biofilm biomass, photosynthetic efficiency and chlorophyll a concentrations. https://www.selleckchem.com/products/tertiapin-q.html Mathematical models may be applied to estimate the overall vigor of riverine ecosystems considering biofilms as indicators. Herein, previous empirical data of Ricart et al. (2009) on long term effects of environmentally relevant concentrations of diuron on biofilm communities of the River Llobregat, Spain was considered as our model inputs. Our objective is to understand the influence of diuron, chlorophyll a concentrations and photosynthetic efficiency on biovolume using a statistical model. The non-linear relationships between biovolume (dependent variable) and diuron, chlorophyll a concentrations and photosynthetic efficiency (independent variarately estimate the biofilm biovolume.Sludge generated in wastewater treatment facilities is an integral part for the introduction of silver nanoparticles (AgNPs) to the terrestrial environment, which would cause some adverse ecosystem responses. The understanding of silver release process from the sludge is important to evaluate their risks. In this study, the amount and speciation of the released silver were investigated by taking the sludge generated by wastewater coagulation with AgNPs added (denoted as sludgeC-AgNPs) an example, and kinetic analysis and density functional theory (DFT) calculations were first used to explore the controlling steps and pathways about the silver release. The results showed that sludgeC-AgNPs could release the dissolved silver and the colloidal silver. Beside Cl-, Ca2+ in the leaching solution could enhance the silver release of sludgeC-AgNPs, especially for the colloidal silver. The released colloidal silver restricted in size from 40 nm to 100 nm with irregular shape. Although the oxidative dissolution of Ag0 was the origin of the silver release pathways from the sludgeC-AgNPs, the silver diffusion was the controlling step due to the spontaneous binding between silver and the hydrolysates of polyaluminium chloride in sludgeC-AgNPs.
    Electro-biological particle electrode (EBPE) prepared by lithium slag was used to remove salicylic acid in a three-dimensional electrocatalytic biological coupling reactor (3D-EBCR). The physical and chemical properties of the EBPE, the removal performance of salicylic acid and the degradation mechanism were studied. Results revealed as follows (1) the EBPE prepared by lithium slag contained effective catalytic components including Fe2O3, SnO2, ZnO, MnO, Rb2O and TiO2, with stable structure and good adsorption performance; (2) the 3D-EBCR with EBPE had strong adaptability to the current intensity in the range of 0.25-0.40 A, and the removal rates of COD and salicylic acid were maintained above 87.1% and 85.2% respectively; (3) salicylic acid was removed through the synergistic action of adsorption, electrochemical oxidation and biological action.The abundant existence of antibiotics within the effluent of wastewater treatment plant seriously threatened their safety recharging. To investigate the fate and biodegradation of those toxic antibiotics within the soil aquifer system, typical antibiotics of amoxicillin (AMX) and tetracycline (TC) were selected and their removal mechanisms were investigated. Experimental results revealed that totally 93.4% and 87.2% of the AMX and TC recharged (10 μg/L) were, respectively, removed within 1 m depth column operation. Specifically, the aerobic biodegradation, abiotic processes and anoxic/anaerobic microorganism contributed as higher as 37.5%, 33.7% and 28.8% of the AMX reduction, via the controlling tests of NaN3 inhibition and soil sterilisations. By contrast, the percentage contribution of the TC was aerobic (54.3%) ˃abiotic processes (32.7%) ˃anoxic/anaerobic (13.0%), a higher aerobic degradation whereas weaker anoxic/anaerobic microorganism. Column systems (CSs) were constructed to study the effect of redox conditions (methanogenic, sulfate-reducing, nitrate-reducing, aerobic) on antibiotics degradation, and microbial community results revealed that Verrucomicrobia, Actinobacteria, Deinococcus-Thermus and Armatimonadetes contributed to the aerobic biodegradation of TC. For comparison, AMX could be efficiently degraded under nitrate reduction (19.95%) > sulfate reduction (16.64%) > methanogenic (9.53%), and Actinobacteria, Bacteroidetes and Verrucomicrobia were the dominant bacteria for AMX degradation. This study provided optimal directions for antibiotics removal within the groundwater recharging systems and is conducive to obtain highly value-added reclaimed water.Citrate-coated iron oxide nanoparticles (IONPs) have potential use in environmental remediation, with possibilities in decontaminating aquatic environments exposed to toxic substances. This study analyzed IONPs associated to Roundup Original, a glyphosate-based herbicide (GBH), and pure glyphosate (GLY), through ultrastructural and histopathological biomarkers in liver tissue, from females of Poecilia reticulata exposed to iron ions (0.3 mg/L) (IFe) and IONPs (0.3 mgFe/L) associated with GLY (0.65 mg/L) and GBH (0.65 mgGLY/L (IONP + GBH1) and 1.30 mgGLY/L (IONP + GBH2)) for a period of 7, 14 and 21 days, followed by an equal post-exposure period only in reconstituted water. For the assays, the synthetized IONPs had crystalline and rounded shape with an average diameter of 2,90 nm, hydrodynamic diameter 66,6 mV, zeta potential -55,4 and diffraction profile of maghemite (γ-Fe2O3). The data obtained by biomarkers indicated a high inflammatory response in all treatments. These same parameters, considered during the post-exposure period indicated recovery in reaction patterns of circulatory disturbances and regressive changes, resulting in average reductions of 37,53 points in IFe, 21 points in IONP + GBH1, 15 points in IONP + GBH2 and 11 points in IONP + GLY in total histopathological index of liver after 21 days post-exposure. However, although the cellular and tissue responses were significant, there was no change in the condition factor and hepatosomatic index, denoting resilience of the experimental model.River biofilm communities are the first ones to be exposed to all toxic discharges received via run off from agricultural fields. Hence, changes in river biofilm community structure and growth pattern are considered as indicator of overall health of lotic ecosystem. Toxicants have effect on biofilm biomass, photosynthetic efficiency and chlorophyll a concentrations. https://www.selleckchem.com/products/tertiapin-q.html Mathematical models may be applied to estimate the overall vigor of riverine ecosystems considering biofilms as indicators. Herein, previous empirical data of Ricart et al. (2009) on long term effects of environmentally relevant concentrations of diuron on biofilm communities of the River Llobregat, Spain was considered as our model inputs. Our objective is to understand the influence of diuron, chlorophyll a concentrations and photosynthetic efficiency on biovolume using a statistical model. The non-linear relationships between biovolume (dependent variable) and diuron, chlorophyll a concentrations and photosynthetic efficiency (independent variarately estimate the biofilm biovolume.Sludge generated in wastewater treatment facilities is an integral part for the introduction of silver nanoparticles (AgNPs) to the terrestrial environment, which would cause some adverse ecosystem responses. The understanding of silver release process from the sludge is important to evaluate their risks. In this study, the amount and speciation of the released silver were investigated by taking the sludge generated by wastewater coagulation with AgNPs added (denoted as sludgeC-AgNPs) an example, and kinetic analysis and density functional theory (DFT) calculations were first used to explore the controlling steps and pathways about the silver release. The results showed that sludgeC-AgNPs could release the dissolved silver and the colloidal silver. Beside Cl-, Ca2+ in the leaching solution could enhance the silver release of sludgeC-AgNPs, especially for the colloidal silver. The released colloidal silver restricted in size from 40 nm to 100 nm with irregular shape. Although the oxidative dissolution of Ag0 was the origin of the silver release pathways from the sludgeC-AgNPs, the silver diffusion was the controlling step due to the spontaneous binding between silver and the hydrolysates of polyaluminium chloride in sludgeC-AgNPs.
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  • Sesame oil cakes (SOC) produced during sesame oil production can be classified as plant residues. This study aims to use SOC as a composite material for injection molding. A biocomposite containing polypropylene (PP) and SOC, namely PP/SOC, was developed and its mechanical properties were evaluated. PP/SOC is largely divided into Homo-PP/SOC (HPS) based on Homo-PP and Block-PP/SOC (BPS) based on block-PP. The specimens containing 0-50 wt% SOC were prepared through extrusion and injection molding. As a result of the evaluation, SOC acted as a reinforcement in the matrix, and HPS and BPS showed improved flexural modulus by 36.4% and 37.3% compared to the neat PP, respectively. Tensile strength, on the other hand, decreased by 58% and 55.1%, respectively. To analyze the cause of this, cross-section observation was conducted through scanning electron microscope (SEM), and phase separation and voids were confirmed to be the cause of this. Impact strength of PP/SOC tended to vary depending on the type of matrix. HPS increased by 30.9% compared to neat PP, and BPS decreased by 25%. This tendency difference appears to be the result of SOC inhibiting crystallization of PP, and it has been confirmed through x ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis. Moreover, PP/SOC can be manufactured at a low cost and is environmentally friendly because it utilizes SOC, a plant residue. It can also be applied to commercial products, such as food packaging, owing to its good moldability and improved mechanical properties.The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs' persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic **** treated with either BioPersist or BioColoniz as compared to their unmodified parent strains (Escherichia coli Nissle 1917 [EcN] and Lactobacillus reuteri, respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.Targeting celecoxib to the ileo-colonic region could be beneficial for the treatment and prevention of colon cancer. Ileo-colonic targeting can be achieved by using pH-dependent coating systems such as ColoPulse. https://www.selleckchem.com/products/Pomalidomide(CC-4047).html Celecoxib has poor aqueous solubility, which may jeopardize optimal treatment. Therefore, we combined a pH-dependent coating with self-emulsifying drug delivery systems (SEDDS) or with solid dispersion systems (SD); two approaches that are often used to improve the dissolution behavior of lipophilic drugs. The dissolution behavior of various formulations of both systems was investigated. Optimized formulations with and without precipitation inhibitors were coated with the ColoPulse and the release of celecoxib was tested under non-sink conditions using an in vitro dissolution system, simulating the pH gradient of the gastrointestinal tract. The dissolution behavior of SDs with and without precipitation inhibitor (sodium dodecyl sulfate) and the SEDDS without precipitation inhibitor was negatively impacted by the coating. Control experiments indicated that components of the coating released in the dissolution medium acted as precipitation mediators. However, the SEDDS formulation with HPMC 4000 cps as a precipitation inhibitor showed excellent dissolution behavior. We hypothesize that HPMC accumulates at the oil/water interface of the emulsion thereby stabilizing the emulsion resulting in maintenance of the supersaturated state.A full-randomized block design was used for the study of the FA composition and meat quality parameters, considering ageing time as a split-plot factor. Chemical and fatty acid composition of steaks (longissimus thoracis and lumborum muscle) from 15 month old semiextensively reared Hispano-Bretón horses were characterized (day 0), and the effect of vacuum ageing (0, 7, 14 and 21 days) on several meat quality parameters (pH, instrumental color and texture and cook loss) was determined. The average fat content of horse loin was 3.31%, and the n-3 polyunsaturated fatty acid content, although higher than in ruminant meats, suggested that the finishing on a high-grain diet limited muscle n-3 accumulation. Results revealed that ageing affected all meat quality measurements; color started to turn brownish at 14 days of ageing, with a decrease in redness but not in yellowness. Tenderness improved during the first two weeks, and the Warner-Bratzler shear force scores showed that meat aged for 7 days could be considered as 'intermediate tender'. Under the present study conditions, an ageing period between 7 and 14 days is recommended for an optimum horse meat quality.While drug resistance mutations can often be attributed to the loss of direct or solvent-mediated protein-ligand interactions in the drug-mutant complex, in this study we show that a resistance mutation for the picomolar HIV-1 capsid (CA)-targeting antiviral (GS-6207) is mainly due to the free energy cost of the drug-induced protein side chain reorganization in the mutant protein. Among several mutations, M66I causes the most suppression of the GS-6207 antiviral activity (up to ~84,000-fold), and only 83- and 68-fold reductions for PF74 and ZW-1261, respectively. To understand the molecular basis of this drug resistance, we conducted molecular dynamics free energy simulations to study the structures, energetics, and conformational free energy landscapes involved in the inhibitors binding at the interface of two CA monomers. To minimize the protein-ligand steric clash, the I66 side chain in the M66I-GS-6207 complex switches to a higher free energy conformation from the one adopted in the apo M66I. In contrast, the binding of GS-6207 to the wild-type CA does not lead to any significant M66 conformational change.
    Sesame oil cakes (SOC) produced during sesame oil production can be classified as plant residues. This study aims to use SOC as a composite material for injection molding. A biocomposite containing polypropylene (PP) and SOC, namely PP/SOC, was developed and its mechanical properties were evaluated. PP/SOC is largely divided into Homo-PP/SOC (HPS) based on Homo-PP and Block-PP/SOC (BPS) based on block-PP. The specimens containing 0-50 wt% SOC were prepared through extrusion and injection molding. As a result of the evaluation, SOC acted as a reinforcement in the matrix, and HPS and BPS showed improved flexural modulus by 36.4% and 37.3% compared to the neat PP, respectively. Tensile strength, on the other hand, decreased by 58% and 55.1%, respectively. To analyze the cause of this, cross-section observation was conducted through scanning electron microscope (SEM), and phase separation and voids were confirmed to be the cause of this. Impact strength of PP/SOC tended to vary depending on the type of matrix. HPS increased by 30.9% compared to neat PP, and BPS decreased by 25%. This tendency difference appears to be the result of SOC inhibiting crystallization of PP, and it has been confirmed through x ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis. Moreover, PP/SOC can be manufactured at a low cost and is environmentally friendly because it utilizes SOC, a plant residue. It can also be applied to commercial products, such as food packaging, owing to its good moldability and improved mechanical properties.The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs' persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic mice treated with either BioPersist or BioColoniz as compared to their unmodified parent strains (Escherichia coli Nissle 1917 [EcN] and Lactobacillus reuteri, respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.Targeting celecoxib to the ileo-colonic region could be beneficial for the treatment and prevention of colon cancer. Ileo-colonic targeting can be achieved by using pH-dependent coating systems such as ColoPulse. https://www.selleckchem.com/products/Pomalidomide(CC-4047).html Celecoxib has poor aqueous solubility, which may jeopardize optimal treatment. Therefore, we combined a pH-dependent coating with self-emulsifying drug delivery systems (SEDDS) or with solid dispersion systems (SD); two approaches that are often used to improve the dissolution behavior of lipophilic drugs. The dissolution behavior of various formulations of both systems was investigated. Optimized formulations with and without precipitation inhibitors were coated with the ColoPulse and the release of celecoxib was tested under non-sink conditions using an in vitro dissolution system, simulating the pH gradient of the gastrointestinal tract. The dissolution behavior of SDs with and without precipitation inhibitor (sodium dodecyl sulfate) and the SEDDS without precipitation inhibitor was negatively impacted by the coating. Control experiments indicated that components of the coating released in the dissolution medium acted as precipitation mediators. However, the SEDDS formulation with HPMC 4000 cps as a precipitation inhibitor showed excellent dissolution behavior. We hypothesize that HPMC accumulates at the oil/water interface of the emulsion thereby stabilizing the emulsion resulting in maintenance of the supersaturated state.A full-randomized block design was used for the study of the FA composition and meat quality parameters, considering ageing time as a split-plot factor. Chemical and fatty acid composition of steaks (longissimus thoracis and lumborum muscle) from 15 month old semiextensively reared Hispano-Bretón horses were characterized (day 0), and the effect of vacuum ageing (0, 7, 14 and 21 days) on several meat quality parameters (pH, instrumental color and texture and cook loss) was determined. The average fat content of horse loin was 3.31%, and the n-3 polyunsaturated fatty acid content, although higher than in ruminant meats, suggested that the finishing on a high-grain diet limited muscle n-3 accumulation. Results revealed that ageing affected all meat quality measurements; color started to turn brownish at 14 days of ageing, with a decrease in redness but not in yellowness. Tenderness improved during the first two weeks, and the Warner-Bratzler shear force scores showed that meat aged for 7 days could be considered as 'intermediate tender'. Under the present study conditions, an ageing period between 7 and 14 days is recommended for an optimum horse meat quality.While drug resistance mutations can often be attributed to the loss of direct or solvent-mediated protein-ligand interactions in the drug-mutant complex, in this study we show that a resistance mutation for the picomolar HIV-1 capsid (CA)-targeting antiviral (GS-6207) is mainly due to the free energy cost of the drug-induced protein side chain reorganization in the mutant protein. Among several mutations, M66I causes the most suppression of the GS-6207 antiviral activity (up to ~84,000-fold), and only 83- and 68-fold reductions for PF74 and ZW-1261, respectively. To understand the molecular basis of this drug resistance, we conducted molecular dynamics free energy simulations to study the structures, energetics, and conformational free energy landscapes involved in the inhibitors binding at the interface of two CA monomers. To minimize the protein-ligand steric clash, the I66 side chain in the M66I-GS-6207 complex switches to a higher free energy conformation from the one adopted in the apo M66I. In contrast, the binding of GS-6207 to the wild-type CA does not lead to any significant M66 conformational change.
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  • An organophotoredox-catalyzed decarboxylative cross-coupling between azole nucleophiles and aliphatic carboxylic acid-derived redox-active esters is demonstrated. This protocol efficiently installs various tertiary or secondary alkyl fragments onto the nitrogen atom of azole nucleophiles under mild and transition-metal-free conditions. The pyridinium additive successfully inhibits the formation of elimination byproducts from the carbocation intermediate. This reaction is applicable to the synthesis of a protein-degrader-like molecule containing an azole and a thalidomide.An isolable pyridinium trifluoromethoxide salt is prepared from the reaction of 4-dimethylaminopyridine with the commercially available liquid 2,4-dinitro(trifluoromethoxy)benzene. The salt is an effective trifluoromethoxide source for SN2 reactions to form trifluoromethyl ethers.Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effects. However, little is known about this disease-related target. Positron emission tomography (PET) imaging could allow us to achieve in-depth knowledge of the BD2 bromodomain. Herein we describe the radiosynthesis and evaluation of [11C]1 as a BRD4 BD2 bromodomain PET imaging radioligand. Our preliminary PET imaging results in rodents demonstrated that [11C]1 had suitable biodistribution in peripheral organs and tissues. Further blocking studies indicated that [11C]1 had good binding specificity toward the BD2 bromodomain. This study may pave the way for the development of a PET radioligand specifically targeting BD1/2 bromodomains as well as for the biological mechanism investigation of BD1/2 bromodomains.High intake of dietary fibers was found to be inversely associated with type-2 diabetes (T2D), whereas the difference among different dietary fibers on T2D remains unclear. Therefore, we have investigated the effects of different dietary fibers on T2D. Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics. We found that supplementation with β-glucan, arabinogalactan, guar gum, apple pectin, glucomannan, and arabinoxylan significantly reduced the fasting blood glucose, whereas carrageenan, xylan, and xanthan gum did not affect glycemic control in diabetic rats. Also, bioactive dietary fibers (β-glucan, arabinogalactan, guar gum, and apple pectin) associated with the increased butyric acid level and abundance of beneficial bacteria (Lachnobacterium, Parabacteroides, Faecalibacterium, Akkermansia, and some butyric acid-producing bacteria), as well as improved host metabolism by decreasing 12α-hydroxylated bile acids, acylcarnitines, and amino acids (leucine, phenylalanine, citrulline, etc.), thereby exert beneficial effects on T2D. It was also found that β-glucan might attenuate insulin resistance via downregulation of Prevotella copri-mediated biosynthesis of branched-chain amino acids in T2D. https://www.selleckchem.com/products/hydroxychloroquine-sulfate.html Together, our study uncovered the effects of different dietary fibers on T2D, along with their potential mechanism.A robust understanding of the mechanoelectric response of organic semiconductors is crucial for the development of materials for flexible electronics. In particular, the prospect of using external mechanical strain to induce a controlled modulation in the charge mobility of the material is appealing. Here we develop an accurate computational protocol for the prediction of the mechanical strain dependence of charge mobility. Ab initio molecular dynamics simulations with a van der Waals density functional are carried out to quantify the off-diagonal electronic disorder in the system as a function of strain by the explicit calculation of the thermal distributions of electronic coupling matrix elements. The approach is applied to a representative molecular organic semiconductor, single-crystal rubrene. We find that charge mobility along the high-mobility direction a⃗ increases with compressive strain, as one might expect. However, the increase is larger when compressive strain is applied in the perpendicular direction than in the parallel direction with respect to a⃗, in agreement with experimental reports. We show that this seemingly counterintuitive result is a consequence of a significantly greater suppression of electronic coupling fluctuations in the range of 50-150 cm-1, when strain is applied in the perpendicular direction. Thus our study highlights the importance of considering off-diagonal electron-phonon coupling in understanding the mechanoelectric response of organic semiconducting crystals. The computational approach developed here is well suited for the accurate prediction of strain-charge mobility relations and should provide a useful tool for the emerging field of molecular strain engineering.
    To find evidence of the content, construct, and criterion validity of the LABIRINTO scale for the diagnosis of autism spectrum disorder (ASD) in children aged 24-59 months.

    The scale was constructed in four stages 1) items were defined based on an extensive literature review and discussions with autism and child development specialists; 2) child development specialists evaluated each item; 3) a preliminary version of the scale was applied to children diagnosed with ASD to enable any necessary adjustments; 4) the scale was then applied to 27 children with typical development and no neurodevelopmental disorder and 48 children with ASD. According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the Childhood Autism Rating Scale (CARS), clinical diagnosis constitutes the gold standard.

    The scale's psychometric indexes were appropriate for construct validity, with Kaiser-Meyer-Olkin = 0.94 and root mean square error of approximation = 0.000. Only one factor on the scale had a Cronbach alpha of 0.97. The receiver operating characteristic curve indicated a cutoff of 12, with a sensitivity of 100% and specificity of 100% for distinguishing children with ASD from those with typical development.

    This study confirmed the validity of the LABIRINTO scale.
    This study confirmed the validity of the LABIRINTO scale.
    An organophotoredox-catalyzed decarboxylative cross-coupling between azole nucleophiles and aliphatic carboxylic acid-derived redox-active esters is demonstrated. This protocol efficiently installs various tertiary or secondary alkyl fragments onto the nitrogen atom of azole nucleophiles under mild and transition-metal-free conditions. The pyridinium additive successfully inhibits the formation of elimination byproducts from the carbocation intermediate. This reaction is applicable to the synthesis of a protein-degrader-like molecule containing an azole and a thalidomide.An isolable pyridinium trifluoromethoxide salt is prepared from the reaction of 4-dimethylaminopyridine with the commercially available liquid 2,4-dinitro(trifluoromethoxy)benzene. The salt is an effective trifluoromethoxide source for SN2 reactions to form trifluoromethyl ethers.Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effects. However, little is known about this disease-related target. Positron emission tomography (PET) imaging could allow us to achieve in-depth knowledge of the BD2 bromodomain. Herein we describe the radiosynthesis and evaluation of [11C]1 as a BRD4 BD2 bromodomain PET imaging radioligand. Our preliminary PET imaging results in rodents demonstrated that [11C]1 had suitable biodistribution in peripheral organs and tissues. Further blocking studies indicated that [11C]1 had good binding specificity toward the BD2 bromodomain. This study may pave the way for the development of a PET radioligand specifically targeting BD1/2 bromodomains as well as for the biological mechanism investigation of BD1/2 bromodomains.High intake of dietary fibers was found to be inversely associated with type-2 diabetes (T2D), whereas the difference among different dietary fibers on T2D remains unclear. Therefore, we have investigated the effects of different dietary fibers on T2D. Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics. We found that supplementation with β-glucan, arabinogalactan, guar gum, apple pectin, glucomannan, and arabinoxylan significantly reduced the fasting blood glucose, whereas carrageenan, xylan, and xanthan gum did not affect glycemic control in diabetic rats. Also, bioactive dietary fibers (β-glucan, arabinogalactan, guar gum, and apple pectin) associated with the increased butyric acid level and abundance of beneficial bacteria (Lachnobacterium, Parabacteroides, Faecalibacterium, Akkermansia, and some butyric acid-producing bacteria), as well as improved host metabolism by decreasing 12α-hydroxylated bile acids, acylcarnitines, and amino acids (leucine, phenylalanine, citrulline, etc.), thereby exert beneficial effects on T2D. It was also found that β-glucan might attenuate insulin resistance via downregulation of Prevotella copri-mediated biosynthesis of branched-chain amino acids in T2D. https://www.selleckchem.com/products/hydroxychloroquine-sulfate.html Together, our study uncovered the effects of different dietary fibers on T2D, along with their potential mechanism.A robust understanding of the mechanoelectric response of organic semiconductors is crucial for the development of materials for flexible electronics. In particular, the prospect of using external mechanical strain to induce a controlled modulation in the charge mobility of the material is appealing. Here we develop an accurate computational protocol for the prediction of the mechanical strain dependence of charge mobility. Ab initio molecular dynamics simulations with a van der Waals density functional are carried out to quantify the off-diagonal electronic disorder in the system as a function of strain by the explicit calculation of the thermal distributions of electronic coupling matrix elements. The approach is applied to a representative molecular organic semiconductor, single-crystal rubrene. We find that charge mobility along the high-mobility direction a⃗ increases with compressive strain, as one might expect. However, the increase is larger when compressive strain is applied in the perpendicular direction than in the parallel direction with respect to a⃗, in agreement with experimental reports. We show that this seemingly counterintuitive result is a consequence of a significantly greater suppression of electronic coupling fluctuations in the range of 50-150 cm-1, when strain is applied in the perpendicular direction. Thus our study highlights the importance of considering off-diagonal electron-phonon coupling in understanding the mechanoelectric response of organic semiconducting crystals. The computational approach developed here is well suited for the accurate prediction of strain-charge mobility relations and should provide a useful tool for the emerging field of molecular strain engineering. To find evidence of the content, construct, and criterion validity of the LABIRINTO scale for the diagnosis of autism spectrum disorder (ASD) in children aged 24-59 months. The scale was constructed in four stages 1) items were defined based on an extensive literature review and discussions with autism and child development specialists; 2) child development specialists evaluated each item; 3) a preliminary version of the scale was applied to children diagnosed with ASD to enable any necessary adjustments; 4) the scale was then applied to 27 children with typical development and no neurodevelopmental disorder and 48 children with ASD. According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the Childhood Autism Rating Scale (CARS), clinical diagnosis constitutes the gold standard. The scale's psychometric indexes were appropriate for construct validity, with Kaiser-Meyer-Olkin = 0.94 and root mean square error of approximation = 0.000. Only one factor on the scale had a Cronbach alpha of 0.97. The receiver operating characteristic curve indicated a cutoff of 12, with a sensitivity of 100% and specificity of 100% for distinguishing children with ASD from those with typical development. This study confirmed the validity of the LABIRINTO scale. This study confirmed the validity of the LABIRINTO scale.
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  • Clinical research supporting US Food and Drug Administration (FDA) drug approvals is largely conducted outside the US.

    To characterize where drugs were tested for FDA approval and to determine how commonly and quickly these drugs received marketing approval in the countries where they were tested, both overall and by country income level and geographical region.

    This cross-sectional analysis of trials supporting FDA approval of novel drugs in 2012 and 2014, sponsored by large drug companies, did not involve human participants. The settings were the countries hosting trials supporting US drug approval. Data sources included Drugs@FDA, ClinicalTrials.gov, PubMed, Google Scholar, EMBASE, and drug regulatory agency websites. Data analysis was completed March through September 2020.

    The primary outcomes were the proportion of drugs approved for marketing in the countries where they were tested for FDA approval within 1, 2, 3, 4, and 5 years of FDA approval and the proportion of countries contributing partiies, 0 of 22 upper-middle-income countries (0%), and 0 of 9 lower-middle-income countries (0%), whereas at 5 years access rates were 46% (18 of 39 countries), 9% (2 of 22 countries), and 22% (2 of 9 countries), respectively. Approvals were faster in high-income countries (median [IQR], 8 [0-11] months) than in upper-middle-income countries (median [IQR], 11 [5-29] months) or lower-middle-income countries (median [IQR], 17 [11-27] months) after FDA approval. Access was lowest in African countries.

    These findings suggest that substantial gaps exist between where FDA-approved drugs are tested and where they ultimately become available to patients, raising concerns about the equitable distribution of research benefits at the population level.
    These findings suggest that substantial gaps exist between where FDA-approved drugs are tested and where they ultimately become available to patients, raising concerns about the equitable distribution of research benefits at the population level.
    While surfactant therapy for respiratory distress syndrome (RDS) in preterm infants has been evaluated in clinical trials, less is known about how surfactant is used outside such a framework.

    To evaluate registered use, off-label use, and omissions of surfactant treatment by gestational age (GA) and associations with outcomes, mainly among very preterm infants (GA <32 weeks).

    This population-based cohort study used registry data for 97 377 infants born in Sweden between 2009 and 2018. Infants did not have malformations and were admitted for neonatal care. Data analysis was conducted from June 2019 to June 2020.

    Timing and number of surfactant administrations, off-label use, and omission of use. Registered use was defined by drug label (1-3 administrations for RDS). Omissions were defined as surfactant not administered despite mechanical ventilation for RDS.

    In-hospital survival, pneumothorax, intraventricular hemorrhage grade 3 to 4, duration of mechanical ventilation, use of postnatal systemic c
    Spontaneous (nontraumatic) intracerebral hemorrhage (ICH) is the most severe complication of antithrombotic drug use.

    To estimate the strength of association between use of antithrombotic drugs and risk of ICH and to examine major changes in the incidence of ICH in the general population.

    This case-control study of patients with a first-ever ICH from January 1, 2005, to December 31, 2018, matched by age, sex, and calendar year with general population controls (140 ratio), assessed case and control patients 20 to 99 years of age in population-based nationwide registries in Denmark (population of 5.8 million).

    Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC).

    Association of ICH with antithrombotic drug use, annual age- and sex-standardized incidence rate of ICH, and prevalence of treatment with antithrombotic drugs. Conditional logistic regression models estimated adjusted odds ratios (aORs) (95% CIs) for the association of antithrombotic drugs ized incidence rate of ICH decreased from 33 per 100 000 person-years in 2005 to 24 per 100 000 person-years in 2018 (P < .001 for trend).

    In Denmark from 2005 to 2018, use of antithrombotic drugs, especially VKAs, was associated with ICH. https://www.selleckchem.com/products/Pomalidomide(CC-4047).html Although use of oral anticoagulation increased substantially during the study period, the incidence rate of ICH decreased.
    In Denmark from 2005 to 2018, use of antithrombotic drugs, especially VKAs, was associated with ICH. Although use of oral anticoagulation increased substantially during the study period, the incidence rate of ICH decreased.
    A retinopathy of prematurity (ROP) diagnosis currently relies on indirect ophthalmoscopy assessed by experienced ophthalmologists. A deep learning algorithm based on retinal images may facilitate early detection and timely treatment of ROP to improve visual outcomes.

    To develop a retinal image-based, multidimensional, automated, deep learning platform for ROP screening and validate its performance accuracy.

    A total of 14 108 eyes of 8652 preterm infants who received ROP screening from 4 centers from November 4, 2010, to November 14, 2019, were included, and a total of 52 249 retinal images were randomly split into training, validation, and test sets. Four main dimensional independent classifiers were developed, including image quality, any stage of ROP, intraocular hemorrhage, and preplus/plus disease. Referral-warranted ROP was automatically generated by integrating the results of 4 classifiers at the image, eye, and patient levels. DeepSHAP, a method based on DeepLIFT and Shapley values (solution conc0.9956. Fine-grained and class-discriminative heat maps were generated by DeepSHAP in real time. The platform achieved a Cohen unweighted κ of 0.86 to 0.98 compared with a Cohen κ of 0.93 to 0.98 by the ROP experts.

    In this diagnostic study, an automated ROP screening platform was able to identify and classify multidimensional pathologic lesions in the retinal images. This platform may be able to assist routine ROP screening in general and children hospitals.
    In this diagnostic study, an automated ROP screening platform was able to identify and classify multidimensional pathologic lesions in the retinal images. This platform may be able to assist routine ROP screening in general and children hospitals.
    Clinical research supporting US Food and Drug Administration (FDA) drug approvals is largely conducted outside the US. To characterize where drugs were tested for FDA approval and to determine how commonly and quickly these drugs received marketing approval in the countries where they were tested, both overall and by country income level and geographical region. This cross-sectional analysis of trials supporting FDA approval of novel drugs in 2012 and 2014, sponsored by large drug companies, did not involve human participants. The settings were the countries hosting trials supporting US drug approval. Data sources included Drugs@FDA, ClinicalTrials.gov, PubMed, Google Scholar, EMBASE, and drug regulatory agency websites. Data analysis was completed March through September 2020. The primary outcomes were the proportion of drugs approved for marketing in the countries where they were tested for FDA approval within 1, 2, 3, 4, and 5 years of FDA approval and the proportion of countries contributing partiies, 0 of 22 upper-middle-income countries (0%), and 0 of 9 lower-middle-income countries (0%), whereas at 5 years access rates were 46% (18 of 39 countries), 9% (2 of 22 countries), and 22% (2 of 9 countries), respectively. Approvals were faster in high-income countries (median [IQR], 8 [0-11] months) than in upper-middle-income countries (median [IQR], 11 [5-29] months) or lower-middle-income countries (median [IQR], 17 [11-27] months) after FDA approval. Access was lowest in African countries. These findings suggest that substantial gaps exist between where FDA-approved drugs are tested and where they ultimately become available to patients, raising concerns about the equitable distribution of research benefits at the population level. These findings suggest that substantial gaps exist between where FDA-approved drugs are tested and where they ultimately become available to patients, raising concerns about the equitable distribution of research benefits at the population level. While surfactant therapy for respiratory distress syndrome (RDS) in preterm infants has been evaluated in clinical trials, less is known about how surfactant is used outside such a framework. To evaluate registered use, off-label use, and omissions of surfactant treatment by gestational age (GA) and associations with outcomes, mainly among very preterm infants (GA <32 weeks). This population-based cohort study used registry data for 97 377 infants born in Sweden between 2009 and 2018. Infants did not have malformations and were admitted for neonatal care. Data analysis was conducted from June 2019 to June 2020. Timing and number of surfactant administrations, off-label use, and omission of use. Registered use was defined by drug label (1-3 administrations for RDS). Omissions were defined as surfactant not administered despite mechanical ventilation for RDS. In-hospital survival, pneumothorax, intraventricular hemorrhage grade 3 to 4, duration of mechanical ventilation, use of postnatal systemic c Spontaneous (nontraumatic) intracerebral hemorrhage (ICH) is the most severe complication of antithrombotic drug use. To estimate the strength of association between use of antithrombotic drugs and risk of ICH and to examine major changes in the incidence of ICH in the general population. This case-control study of patients with a first-ever ICH from January 1, 2005, to December 31, 2018, matched by age, sex, and calendar year with general population controls (140 ratio), assessed case and control patients 20 to 99 years of age in population-based nationwide registries in Denmark (population of 5.8 million). Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC). Association of ICH with antithrombotic drug use, annual age- and sex-standardized incidence rate of ICH, and prevalence of treatment with antithrombotic drugs. Conditional logistic regression models estimated adjusted odds ratios (aORs) (95% CIs) for the association of antithrombotic drugs ized incidence rate of ICH decreased from 33 per 100 000 person-years in 2005 to 24 per 100 000 person-years in 2018 (P < .001 for trend). In Denmark from 2005 to 2018, use of antithrombotic drugs, especially VKAs, was associated with ICH. https://www.selleckchem.com/products/Pomalidomide(CC-4047).html Although use of oral anticoagulation increased substantially during the study period, the incidence rate of ICH decreased. In Denmark from 2005 to 2018, use of antithrombotic drugs, especially VKAs, was associated with ICH. Although use of oral anticoagulation increased substantially during the study period, the incidence rate of ICH decreased. A retinopathy of prematurity (ROP) diagnosis currently relies on indirect ophthalmoscopy assessed by experienced ophthalmologists. A deep learning algorithm based on retinal images may facilitate early detection and timely treatment of ROP to improve visual outcomes. To develop a retinal image-based, multidimensional, automated, deep learning platform for ROP screening and validate its performance accuracy. A total of 14 108 eyes of 8652 preterm infants who received ROP screening from 4 centers from November 4, 2010, to November 14, 2019, were included, and a total of 52 249 retinal images were randomly split into training, validation, and test sets. Four main dimensional independent classifiers were developed, including image quality, any stage of ROP, intraocular hemorrhage, and preplus/plus disease. Referral-warranted ROP was automatically generated by integrating the results of 4 classifiers at the image, eye, and patient levels. DeepSHAP, a method based on DeepLIFT and Shapley values (solution conc0.9956. Fine-grained and class-discriminative heat maps were generated by DeepSHAP in real time. The platform achieved a Cohen unweighted κ of 0.86 to 0.98 compared with a Cohen κ of 0.93 to 0.98 by the ROP experts. In this diagnostic study, an automated ROP screening platform was able to identify and classify multidimensional pathologic lesions in the retinal images. This platform may be able to assist routine ROP screening in general and children hospitals. In this diagnostic study, an automated ROP screening platform was able to identify and classify multidimensional pathologic lesions in the retinal images. This platform may be able to assist routine ROP screening in general and children hospitals.
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  • A number of mislabelled butterfly specimens in the Suffert collection purporting to be from Lindi in southeast Tanzania belong to taxa restricted to the Usambara Mountains in northeast Tanzania thus suggesting patria falsa. The history of Suffert's collection and the possible reasons behind this mislabelling event are discussed in more detail. One of the mislabelled specimens, the holotype of Papilio illyris hamatus Joicey Talbot, 1918 described from Tanzania, is the senior name for Graphium illyris girardeaui Guilbot Plantrou, 1978, the latter name formally synonymised herein with the former. A brief biography of the little-known Ernst Suffert is presented.The further collection and study of Chinese wolf spiders, family Lycosidae Sundevall, 1833, expand the known distribution of the subfamily Artoriinae Framenau, 2007 from Yunnan to Guangxi, Guizhou, and Sichuan Provinces of South China. Sinartoria gen. nov. is described to include two new species, S. damingshanensis sp. nov. (type species) and S. zhuangius sp. nov. In addition, a new Artoria species, A. hamata sp. nov. is described and new distribution records for A. ligulacea (Qu, Peng Yin, 2009) and A. parvula Thorell, 1877 are provided. Within the Artoriinae, Sinartoria gen. nov. appears to be most similar to the South American Lobizon Piacentini Grismado, 2009, but their relationship will remain contentious without a comprehensive phylogenetic analysis of artoriine genera.Bolboceras bopdevense Kalawate Hillert, new species and Bolboceras trimbakense Kalawate Hillert, new species, both classified in the Bolboceras nigricans Westwood, 1848 species group are described from India. Illustrations and comparison with known members of the B. nigricans species group are given. The new described species are included in an updated identification key of the species group. Finally, known localities of this species group are mapped. For the Oriental and east Palearctic regions, all known localities of the genus Bolboceras Kirby, 1819 are listed, and associated coordinates are given.In the present study, bivalves belonging to the superfamily Solenoidea that inhabit the Argentinean Sea are redescribed. The specimens studied in this work were collected by scuba diving in the Gulf of San José, Argentina. Additional specimens from different malacological collections were revised to update the geographical distribution of valid species. According to the literature, there exist two species for the "Argentinean" and "Magellan" biogeographical provinces. However, ten nominal taxa, with uncertain taxonomic status, have been mentioned for the study area. Field work, local collection survey and type material examination allow confirming two valid species Solen (Ensisolen) tehuelchus Hanley (Solenidae) and Ensis macha (Molina) (Pharidae). A morphological comparison between S. tehuelchus and S. gaudichaudi Chenu and S. obliqua Spengler is provided as well type locality, repository and synonymy list. The type material of all related species are illustrated whenever possible. Establishing the valid names of these species is the first step towards more integrative studies including genetic and zoogeographical analyses.Dewlap morphology and body ratios are two of the main morphological characters used in delimiting Sitana spp. It becomes a statistical limitation when small samples are used in species descriptions, as outliers can be picked to be described as a distinct species. Genetic data has been used to support the distinctness of a species in Sitana. However, species with shallow genetic divergence becomes a problem if not thoroughly examined. We examine and report our findings on morphological and genetic differences in two populations of Sitana marudhamneydhal and one population of S. attenboroughii. The shallow genetic divergence and overlapping morphology shows that Sitana attenboroughii is a junior synonym of Sitana marudhamneydhal.Ten new species of Odontepyris Kieffer from China are described and illustrated O. angustus sp. nov., O. ecarinatus sp. nov., O. eminens sp. nov., O. flavipedis sp. nov., O. hirtus sp. nov., O. latifrontalis sp. nov., O. occiputalis sp. nov., O. xiaoi sp. nov., O. xui sp. nov., and O. yunnanensis sp. nov.. A key to the known Chinese species is provided.We describe four upper Lower Triassic to lower Middle Triassic clam shrimp-bearing intervals from Mallorca, which include the clam shrimp species Hornestheria sp. aff. Hornestheria sollingensis and several other forms of carapace valve morphology Hornestheria? Morphotype 1, Hornestheria? Morphotype 2, and other undetermined carapace valves. All of this material was obtained from red-bed units cropping out in the Serra de Tramuntana mountains of Mallorca (western Mediterranean). Except for a few morphologically similar carapace valves of Middle Triassic age from China, Hornestheria is known only from the type locality of its type species, Hornestheria sollingensis Kozur et Lepper, in the Solling Formation (Middle Buntsandstein Subgroup) in the German part of the Central European Basin. According to its original definition, the larval carapace valve of Hornestheria Kozur et Lepper is characterized by a radial sculpture, but this characteristic apparently is only variably developed. Due to both a limited number of previously known occurrences of Hornestheria and its poorly known carapace valve morphology, open nomenclature is applied to the taxonomy herein. The studied specimens were freshly collected from outcrop sections composed of greyish-green to greyish-red laminated claystones and siltstones that accumulated in a fluvial facies. The clam shrimp specimens are accompanied by remains of insects and fishes, invertebrate and tetrapod ichnofossils, and micro-/macroplant remains, all of which either have been described by previous workers or are currently part of a separate study.The type specimens of the New World Stigmoderini deposited in the Natural History Museum in London are catalogued and illustrated. Twenty-eight lectotypes are designated, one of which is a new lectotype, since the previous one is considered invalid under the article 74.2. (ICZN 1999). Holotype and in some cases, paratypes, are recognized for the following taxa Conognatha nanula Hoscheck, 1934, Conognatha blairi Hoscheck, 1934, Hiperantha decorata var. insignata Hoscheck, 1928 and Hiperantha saundersi Théry, 1928. In addition, Lasionota oberthuri (Kerremans, 1897) rev. stat. is reinstated as a valid species, having been considered to be a junior synonym of Lasionota tetrazonus (Chevrolat, 1838) since 1997. The comparison of the reinstated species, with the recently described species Lasionota inca Moore Diéguez, 2019 showed that both are conspecific and hence L. inca syn. nov. https://www.selleckchem.com/products/lw-6.html is proposed as a junior synonym of L. oberthuri.
    A number of mislabelled butterfly specimens in the Suffert collection purporting to be from Lindi in southeast Tanzania belong to taxa restricted to the Usambara Mountains in northeast Tanzania thus suggesting patria falsa. The history of Suffert's collection and the possible reasons behind this mislabelling event are discussed in more detail. One of the mislabelled specimens, the holotype of Papilio illyris hamatus Joicey Talbot, 1918 described from Tanzania, is the senior name for Graphium illyris girardeaui Guilbot Plantrou, 1978, the latter name formally synonymised herein with the former. A brief biography of the little-known Ernst Suffert is presented.The further collection and study of Chinese wolf spiders, family Lycosidae Sundevall, 1833, expand the known distribution of the subfamily Artoriinae Framenau, 2007 from Yunnan to Guangxi, Guizhou, and Sichuan Provinces of South China. Sinartoria gen. nov. is described to include two new species, S. damingshanensis sp. nov. (type species) and S. zhuangius sp. nov. In addition, a new Artoria species, A. hamata sp. nov. is described and new distribution records for A. ligulacea (Qu, Peng Yin, 2009) and A. parvula Thorell, 1877 are provided. Within the Artoriinae, Sinartoria gen. nov. appears to be most similar to the South American Lobizon Piacentini Grismado, 2009, but their relationship will remain contentious without a comprehensive phylogenetic analysis of artoriine genera.Bolboceras bopdevense Kalawate Hillert, new species and Bolboceras trimbakense Kalawate Hillert, new species, both classified in the Bolboceras nigricans Westwood, 1848 species group are described from India. Illustrations and comparison with known members of the B. nigricans species group are given. The new described species are included in an updated identification key of the species group. Finally, known localities of this species group are mapped. For the Oriental and east Palearctic regions, all known localities of the genus Bolboceras Kirby, 1819 are listed, and associated coordinates are given.In the present study, bivalves belonging to the superfamily Solenoidea that inhabit the Argentinean Sea are redescribed. The specimens studied in this work were collected by scuba diving in the Gulf of San José, Argentina. Additional specimens from different malacological collections were revised to update the geographical distribution of valid species. According to the literature, there exist two species for the "Argentinean" and "Magellan" biogeographical provinces. However, ten nominal taxa, with uncertain taxonomic status, have been mentioned for the study area. Field work, local collection survey and type material examination allow confirming two valid species Solen (Ensisolen) tehuelchus Hanley (Solenidae) and Ensis macha (Molina) (Pharidae). A morphological comparison between S. tehuelchus and S. gaudichaudi Chenu and S. obliqua Spengler is provided as well type locality, repository and synonymy list. The type material of all related species are illustrated whenever possible. Establishing the valid names of these species is the first step towards more integrative studies including genetic and zoogeographical analyses.Dewlap morphology and body ratios are two of the main morphological characters used in delimiting Sitana spp. It becomes a statistical limitation when small samples are used in species descriptions, as outliers can be picked to be described as a distinct species. Genetic data has been used to support the distinctness of a species in Sitana. However, species with shallow genetic divergence becomes a problem if not thoroughly examined. We examine and report our findings on morphological and genetic differences in two populations of Sitana marudhamneydhal and one population of S. attenboroughii. The shallow genetic divergence and overlapping morphology shows that Sitana attenboroughii is a junior synonym of Sitana marudhamneydhal.Ten new species of Odontepyris Kieffer from China are described and illustrated O. angustus sp. nov., O. ecarinatus sp. nov., O. eminens sp. nov., O. flavipedis sp. nov., O. hirtus sp. nov., O. latifrontalis sp. nov., O. occiputalis sp. nov., O. xiaoi sp. nov., O. xui sp. nov., and O. yunnanensis sp. nov.. A key to the known Chinese species is provided.We describe four upper Lower Triassic to lower Middle Triassic clam shrimp-bearing intervals from Mallorca, which include the clam shrimp species Hornestheria sp. aff. Hornestheria sollingensis and several other forms of carapace valve morphology Hornestheria? Morphotype 1, Hornestheria? Morphotype 2, and other undetermined carapace valves. All of this material was obtained from red-bed units cropping out in the Serra de Tramuntana mountains of Mallorca (western Mediterranean). Except for a few morphologically similar carapace valves of Middle Triassic age from China, Hornestheria is known only from the type locality of its type species, Hornestheria sollingensis Kozur et Lepper, in the Solling Formation (Middle Buntsandstein Subgroup) in the German part of the Central European Basin. According to its original definition, the larval carapace valve of Hornestheria Kozur et Lepper is characterized by a radial sculpture, but this characteristic apparently is only variably developed. Due to both a limited number of previously known occurrences of Hornestheria and its poorly known carapace valve morphology, open nomenclature is applied to the taxonomy herein. The studied specimens were freshly collected from outcrop sections composed of greyish-green to greyish-red laminated claystones and siltstones that accumulated in a fluvial facies. The clam shrimp specimens are accompanied by remains of insects and fishes, invertebrate and tetrapod ichnofossils, and micro-/macroplant remains, all of which either have been described by previous workers or are currently part of a separate study.The type specimens of the New World Stigmoderini deposited in the Natural History Museum in London are catalogued and illustrated. Twenty-eight lectotypes are designated, one of which is a new lectotype, since the previous one is considered invalid under the article 74.2. (ICZN 1999). Holotype and in some cases, paratypes, are recognized for the following taxa Conognatha nanula Hoscheck, 1934, Conognatha blairi Hoscheck, 1934, Hiperantha decorata var. insignata Hoscheck, 1928 and Hiperantha saundersi Théry, 1928. In addition, Lasionota oberthuri (Kerremans, 1897) rev. stat. is reinstated as a valid species, having been considered to be a junior synonym of Lasionota tetrazonus (Chevrolat, 1838) since 1997. The comparison of the reinstated species, with the recently described species Lasionota inca Moore Diéguez, 2019 showed that both are conspecific and hence L. inca syn. nov. https://www.selleckchem.com/products/lw-6.html is proposed as a junior synonym of L. oberthuri.
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  • Blastomycosis is the fungal disease caused by thermally dimorphic fungi in the genus Blastomyces, with B dermatitidis complex causing most cases. It is considered hyperendemic in areas adjacent to the Great Lakes and along the St. Lawrence, Mississippi, and Ohio rivers, but definitive geographic distribution of blastomycoses remains obscure. Clinical presentation is variable. Disseminated blastomycosis with extrapulmonary manifestations is more common in immunosuppressed individuals. Culture positivity is required for definitive diagnosis, but compatible histology is often sufficient for presumptive diagnosis and initiation of treatment. Treatment should be provided to all symptomatic cases to prevent progression or recurrence.Cryptococcosis is an invasive fungal infection of global significance caused by yeasts of the genus Cryptococcus. The prevalence of HIV in certain areas of the world and the expanding population of immunocompromised patients contribute to the ongoing global disease burden. Point-of-care serologic testing has allowed for more rapid diagnosis and implementation of screening programs in resource-limited settings. Management involves therapy aimed at reduction in fungal burden, maintenance of intracranial pressure, and optimization of host immunity. Despite diagnostic and therapeutic advances, cryptococcosis continues to be a disease with unacceptably high incidence and mortality, particularly in resource-limited settings.Histoplasmosis is one of the commonest endemic mycoses in the Americas yet is often underdiagnosed and neglected as a public health priority. This review outlines the evolving understanding of its epidemiology and the clinical syndromes of histoplasmosis, in addition to up-to-date diagnostic and treatment guidelines. A focus on histoplasmosis in advanced HIV is included. The challenges pertinent to histoplasmosis management in Latin America, with recommendations made through international expert consensus are discussed.Coccidioidomycosis, caused by the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadassi, is endemic to the southwestern United states and Central and South America. The incidence of coccidioidomycosis continues to increase. Coccidioidomycosis is typically a self-limiting influenza-like respiratory illness; however, it can lead to disseminated disease outside of the lungs. Not all nondisseminated cases require therapy, but antifungal therapy is typically beneficial requiring treatment ranging from months to lifelong. Clinical factors related to treatment decisions include severity of symptoms, radiography, coccidioidomycosis serologic results, and concurrent medical problems including immunosuppression. This review summarizes the epidemiology, clinical manifestations, and treatment options.Mucormycosis is a rare but aggressive fungal disease that mainly affects patients with poorly controlled diabetes mellitus and those who are severely immunocompromised, including patients with hematological malignancies and solid organ transplant recipients. Early recognition of infection is critical for treatment success, followed by prompt initiation of antifungal therapy with lipid formulation amphotericin B. Posaconazole and isavuconazole should be used for stepdown and salvage therapy. Surgical debridement is key for tissue diagnosis and treatment and should be pursued urgently whenever possible. In addition to surgery and antifungal therapy, reverting the underlying risk factor for infection is important for treatment response.The spectrum of disease produced by Aspergillus species ranges from allergic syndromes to chronic pulmonary conditions and invasive infections. Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients. Risk factors continue to evolve and include newer biological agents that target the immune system and postinfluenza infection; and it has been observed following COVID-19 infection. Diagnosis remains a challenge but non-culture-based methods are available. Antifungal resistance has emerged. Voriconazole remains the treatment of choice but isavuconazole and posaconazole have similar efficacy with less toxicity. Combination therapy is used with extensive infection and in severe immunosuppression.Invasive candidiasis (IC) is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 6 of which cause most cases globally. Candidemia is probably the most commonly recognized syndrome associated with IC; however, Candida can cause invasive infection of any organ, especially visceral organs, vasculature, bones and joints, the eyes and central nervous system. Targeted prevention and empirical therapy are important interventions for patients at high risk for IC, and the current approach should be based on a combination of clinical risk factors and non-culture-based diagnostics, when available.Complex processes mediate immunity to fungal infections. https://www.selleckchem.com/products/jg98.html Responses vary depending on the organism, morphogenic state, and infection site. Innate immune effectors such as epithelia, phagocytes, and soluble molecules detect pathogens, kill fungi, release cytokines, and prime the adaptive response. Adaptive responses to mucocutaneous or invasive disease are markedly different but intersect at certain pathways (molecules required for IL-23 and IL-12 signaling). Many of these pathways have been elucidated from the study of inborn errors of immunity. This review explores the general aspects of antifungal immunity and delves into the mechanisms that mediate protection from frequently encountered fungi.Over the past 15 years, there has been an increase in the development and utilization of newer antifungal agents. The ideal antifungal, however, in regard to spectrum of activity, pharmacokinetic/pharmacodynamic properties, development of resistance, safety, and drug interaction profile remains elusive. This article reviews pharmacologic aspects of Food and Drug Administration-approved polyenes, flucytosine, azoles, and echinocandins as well as promising pipeline antifungal agents. Unique properties of these newer agents are highlighted. The clinical role of established and investigational antifungal agents as treatment and/or prevention of invasive fungal infections is discussed.
    Blastomycosis is the fungal disease caused by thermally dimorphic fungi in the genus Blastomyces, with B dermatitidis complex causing most cases. It is considered hyperendemic in areas adjacent to the Great Lakes and along the St. Lawrence, Mississippi, and Ohio rivers, but definitive geographic distribution of blastomycoses remains obscure. Clinical presentation is variable. Disseminated blastomycosis with extrapulmonary manifestations is more common in immunosuppressed individuals. Culture positivity is required for definitive diagnosis, but compatible histology is often sufficient for presumptive diagnosis and initiation of treatment. Treatment should be provided to all symptomatic cases to prevent progression or recurrence.Cryptococcosis is an invasive fungal infection of global significance caused by yeasts of the genus Cryptococcus. The prevalence of HIV in certain areas of the world and the expanding population of immunocompromised patients contribute to the ongoing global disease burden. Point-of-care serologic testing has allowed for more rapid diagnosis and implementation of screening programs in resource-limited settings. Management involves therapy aimed at reduction in fungal burden, maintenance of intracranial pressure, and optimization of host immunity. Despite diagnostic and therapeutic advances, cryptococcosis continues to be a disease with unacceptably high incidence and mortality, particularly in resource-limited settings.Histoplasmosis is one of the commonest endemic mycoses in the Americas yet is often underdiagnosed and neglected as a public health priority. This review outlines the evolving understanding of its epidemiology and the clinical syndromes of histoplasmosis, in addition to up-to-date diagnostic and treatment guidelines. A focus on histoplasmosis in advanced HIV is included. The challenges pertinent to histoplasmosis management in Latin America, with recommendations made through international expert consensus are discussed.Coccidioidomycosis, caused by the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadassi, is endemic to the southwestern United states and Central and South America. The incidence of coccidioidomycosis continues to increase. Coccidioidomycosis is typically a self-limiting influenza-like respiratory illness; however, it can lead to disseminated disease outside of the lungs. Not all nondisseminated cases require therapy, but antifungal therapy is typically beneficial requiring treatment ranging from months to lifelong. Clinical factors related to treatment decisions include severity of symptoms, radiography, coccidioidomycosis serologic results, and concurrent medical problems including immunosuppression. This review summarizes the epidemiology, clinical manifestations, and treatment options.Mucormycosis is a rare but aggressive fungal disease that mainly affects patients with poorly controlled diabetes mellitus and those who are severely immunocompromised, including patients with hematological malignancies and solid organ transplant recipients. Early recognition of infection is critical for treatment success, followed by prompt initiation of antifungal therapy with lipid formulation amphotericin B. Posaconazole and isavuconazole should be used for stepdown and salvage therapy. Surgical debridement is key for tissue diagnosis and treatment and should be pursued urgently whenever possible. In addition to surgery and antifungal therapy, reverting the underlying risk factor for infection is important for treatment response.The spectrum of disease produced by Aspergillus species ranges from allergic syndromes to chronic pulmonary conditions and invasive infections. Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients. Risk factors continue to evolve and include newer biological agents that target the immune system and postinfluenza infection; and it has been observed following COVID-19 infection. Diagnosis remains a challenge but non-culture-based methods are available. Antifungal resistance has emerged. Voriconazole remains the treatment of choice but isavuconazole and posaconazole have similar efficacy with less toxicity. Combination therapy is used with extensive infection and in severe immunosuppression.Invasive candidiasis (IC) is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 6 of which cause most cases globally. Candidemia is probably the most commonly recognized syndrome associated with IC; however, Candida can cause invasive infection of any organ, especially visceral organs, vasculature, bones and joints, the eyes and central nervous system. Targeted prevention and empirical therapy are important interventions for patients at high risk for IC, and the current approach should be based on a combination of clinical risk factors and non-culture-based diagnostics, when available.Complex processes mediate immunity to fungal infections. https://www.selleckchem.com/products/jg98.html Responses vary depending on the organism, morphogenic state, and infection site. Innate immune effectors such as epithelia, phagocytes, and soluble molecules detect pathogens, kill fungi, release cytokines, and prime the adaptive response. Adaptive responses to mucocutaneous or invasive disease are markedly different but intersect at certain pathways (molecules required for IL-23 and IL-12 signaling). Many of these pathways have been elucidated from the study of inborn errors of immunity. This review explores the general aspects of antifungal immunity and delves into the mechanisms that mediate protection from frequently encountered fungi.Over the past 15 years, there has been an increase in the development and utilization of newer antifungal agents. The ideal antifungal, however, in regard to spectrum of activity, pharmacokinetic/pharmacodynamic properties, development of resistance, safety, and drug interaction profile remains elusive. This article reviews pharmacologic aspects of Food and Drug Administration-approved polyenes, flucytosine, azoles, and echinocandins as well as promising pipeline antifungal agents. Unique properties of these newer agents are highlighted. The clinical role of established and investigational antifungal agents as treatment and/or prevention of invasive fungal infections is discussed.
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  • ake adaptations, allowing fulfilling lives with psychosocial functioning similar to their peers.
    To describe healthcare professionals' and volunteers' experiences of a pathway for movement on a hospice ward.

    This was a qualitative study with an inductive approach. Data were collected in a hospice setting through 4 focus group interviews with healthcare professionals and volunteers (n = 12). The focus group participants varied in age, profession, and length of experience in palliative care. The interviews were audio recorded, transcribed and analyzed with qualitative content analysis.

    Dignity through movement at the end of life was the main theme, complemented by 4 sub-themes. Two descriptive sub-themes "A practical tool to facilitate physical activity" and "Companionship and goals give meaning to the day," and 2 interpretative sub-themes "Regaining control and having a choice" and "Feeling normal and alive" based on participants' views of patient experiences.

    Indications are that the pathway for movement addresses a wide range of experiences related to different aspects of being human in a difficult situation. Experiences of movement and physical activity can promote wellbeing, dignity, and a sense of feeling "at home" for patients within hospice care. The pathway for movement is simple to set up, offers access to appropriate physical activity and seems to benefit patients both in the early and later phases of palliative care.
    Indications are that the pathway for movement addresses a wide range of experiences related to different aspects of being human in a difficult situation. Experiences of movement and physical activity can promote wellbeing, dignity, and a sense of feeling "at home" for patients within hospice care. The pathway for movement is simple to set up, offers access to appropriate physical activity and seems to benefit patients both in the early and later phases of palliative care.Inflammatory lesions such as osteomyelitis of the jaw may share some of the radiographic features of malignancy; however, a demonstrable dental cause for it usually exists. In addition, inflammatory lesions generally stimulate a sclerotic bone reaction, which is uncommon in malignancy. The imaging modality of choice for aiding in the differential diagnosis is computed tomography imaging because of its ability to clearly delineate sequestra and periosteal new bone formation.Although vaccination uptake is high in most countries, pockets of suboptimal coverage remain, such as those observed among ultra-orthodox Jews in Israel and elsewhere, posing a threat to both individual and public immunity. Drawing on the Precaution Adoption Process Model (PAPM), this study proposes a Non-Vaccination Stage Model (NVSM) to analyze the decision-making process among Non-Vaccinating Parents (NVPs), focusing on the ultra-orthodox Jewish population of Israel. In-depth interviews were conducted with 10 Israeli ultra-orthodox Jewish NVPs (mothers). The interviews revealed five stages in the participants' decision-making process Being good mothers who vaccinate their children; Emergence of doubts regarding the risks of vaccination; Personal vaccination policy-hesitancy concerning vaccination; Decision not to vaccinate; Confirmation signs of what participants perceive as a wise decision. NVSM can help understand parents who consider non-vaccination to be healthier behavior and explore the various stages of their decision-making process. Differentiating among the various stages of NVPs' decision-making processes enables application of different intervention approaches by policymakers and healthcare practitioners.With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in body mass index (BMI) among ART-experienced, virologically suppressed PLWH. ART-experienced, virologically suppressed PLWH ≥18 years of age in the Observational Pharmacoepidemiology Research and Analysis (OPERA) cohort were included for analysis if prescribed a new regimen containing one of the following core agents dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017. Multivariable linear regression was used to assess the association between regimen and mean changes in BMI at 6, 12, and 24 months after switch. In unadjusted analyses, BMI increases ranged from 0.30 kg/m2 (bDRV) to 0.83 kg/m2 (RPV) at 24 months following switch, but gains were observed with every regimen. In adjusted analyses, compared to DTG, only bDRV was associated with a smaller increase in BMI at all time points, while EVG/c and RAL were associated with smaller increases in BMI at 6 months only. https://www.selleckchem.com/products/mptp-hydrochloride.html Overall, results were consistent in analyses stratified by baseline BMI category. BMI increases were relatively small but followed an upward trend over time in this cohort of treatment-experienced, suppressed PLWH. Gains were attenuated with a longer period of follow-up. BMI gains did not differ by regimens, except for bDRV regimens, which were consistently associated with smaller BMI increases than DTG.The present study uses a novel approach to assess the publics' ability to cope with priority setting and rationing in health care by asking what the public is willing to forego. Items for disinvestment were presented in three separated dimensions Categories of medical care, quality of service, and items representing social values. A telephone survey was conducted among a representative sample of the Israeli public (N = 609). The response rate was 51%. We identify a few items that a high proportion of the population express readiness to forgo a drug for smoking cessation, budgets for improving appearance and comfort in medical facilities, and a product for preventing surgical scars. Furthermore, over a quarter of the public was ready to forgo many other items. We found that less than 10% justified their selection in terms of "personally not important to me," while most respondents evaluated the items they chose to forgo as "less effective or less essential in comparison to others." The study found that most respondents, when exposed to a range of health system components, were able to identify at least one item that they will be willing to forgo in a time of economic crisis.
    ake adaptations, allowing fulfilling lives with psychosocial functioning similar to their peers. To describe healthcare professionals' and volunteers' experiences of a pathway for movement on a hospice ward. This was a qualitative study with an inductive approach. Data were collected in a hospice setting through 4 focus group interviews with healthcare professionals and volunteers (n = 12). The focus group participants varied in age, profession, and length of experience in palliative care. The interviews were audio recorded, transcribed and analyzed with qualitative content analysis. Dignity through movement at the end of life was the main theme, complemented by 4 sub-themes. Two descriptive sub-themes "A practical tool to facilitate physical activity" and "Companionship and goals give meaning to the day," and 2 interpretative sub-themes "Regaining control and having a choice" and "Feeling normal and alive" based on participants' views of patient experiences. Indications are that the pathway for movement addresses a wide range of experiences related to different aspects of being human in a difficult situation. Experiences of movement and physical activity can promote wellbeing, dignity, and a sense of feeling "at home" for patients within hospice care. The pathway for movement is simple to set up, offers access to appropriate physical activity and seems to benefit patients both in the early and later phases of palliative care. Indications are that the pathway for movement addresses a wide range of experiences related to different aspects of being human in a difficult situation. Experiences of movement and physical activity can promote wellbeing, dignity, and a sense of feeling "at home" for patients within hospice care. The pathway for movement is simple to set up, offers access to appropriate physical activity and seems to benefit patients both in the early and later phases of palliative care.Inflammatory lesions such as osteomyelitis of the jaw may share some of the radiographic features of malignancy; however, a demonstrable dental cause for it usually exists. In addition, inflammatory lesions generally stimulate a sclerotic bone reaction, which is uncommon in malignancy. The imaging modality of choice for aiding in the differential diagnosis is computed tomography imaging because of its ability to clearly delineate sequestra and periosteal new bone formation.Although vaccination uptake is high in most countries, pockets of suboptimal coverage remain, such as those observed among ultra-orthodox Jews in Israel and elsewhere, posing a threat to both individual and public immunity. Drawing on the Precaution Adoption Process Model (PAPM), this study proposes a Non-Vaccination Stage Model (NVSM) to analyze the decision-making process among Non-Vaccinating Parents (NVPs), focusing on the ultra-orthodox Jewish population of Israel. In-depth interviews were conducted with 10 Israeli ultra-orthodox Jewish NVPs (mothers). The interviews revealed five stages in the participants' decision-making process Being good mothers who vaccinate their children; Emergence of doubts regarding the risks of vaccination; Personal vaccination policy-hesitancy concerning vaccination; Decision not to vaccinate; Confirmation signs of what participants perceive as a wise decision. NVSM can help understand parents who consider non-vaccination to be healthier behavior and explore the various stages of their decision-making process. Differentiating among the various stages of NVPs' decision-making processes enables application of different intervention approaches by policymakers and healthcare practitioners.With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in body mass index (BMI) among ART-experienced, virologically suppressed PLWH. ART-experienced, virologically suppressed PLWH ≥18 years of age in the Observational Pharmacoepidemiology Research and Analysis (OPERA) cohort were included for analysis if prescribed a new regimen containing one of the following core agents dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017. Multivariable linear regression was used to assess the association between regimen and mean changes in BMI at 6, 12, and 24 months after switch. In unadjusted analyses, BMI increases ranged from 0.30 kg/m2 (bDRV) to 0.83 kg/m2 (RPV) at 24 months following switch, but gains were observed with every regimen. In adjusted analyses, compared to DTG, only bDRV was associated with a smaller increase in BMI at all time points, while EVG/c and RAL were associated with smaller increases in BMI at 6 months only. https://www.selleckchem.com/products/mptp-hydrochloride.html Overall, results were consistent in analyses stratified by baseline BMI category. BMI increases were relatively small but followed an upward trend over time in this cohort of treatment-experienced, suppressed PLWH. Gains were attenuated with a longer period of follow-up. BMI gains did not differ by regimens, except for bDRV regimens, which were consistently associated with smaller BMI increases than DTG.The present study uses a novel approach to assess the publics' ability to cope with priority setting and rationing in health care by asking what the public is willing to forego. Items for disinvestment were presented in three separated dimensions Categories of medical care, quality of service, and items representing social values. A telephone survey was conducted among a representative sample of the Israeli public (N = 609). The response rate was 51%. We identify a few items that a high proportion of the population express readiness to forgo a drug for smoking cessation, budgets for improving appearance and comfort in medical facilities, and a product for preventing surgical scars. Furthermore, over a quarter of the public was ready to forgo many other items. We found that less than 10% justified their selection in terms of "personally not important to me," while most respondents evaluated the items they chose to forgo as "less effective or less essential in comparison to others." The study found that most respondents, when exposed to a range of health system components, were able to identify at least one item that they will be willing to forgo in a time of economic crisis.
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  • The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11chigh CD95high) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.In optical metrological protocols to measure physical quantities, it is, in principle, always beneficial to increase photon number n to improve measurement precision. However, practical constraints prevent the arbitrary increase of n due to the imperfections of a practical detector, especially when the detector response is dominated by the saturation effect. In this work, we show that a modified weak measurement protocol, namely, biased weak measurement significantly improves the precision of optical metrology in the presence of saturation effect. This method detects an ultra-small fraction of photons while maintains a considerable amount of metrological information. The biased pre-coupling leads to an additional reduction of photons in the post-selection and generates an extinction point in the spectrum distribution, which is extremely sensitive to the estimated parameter and difficult to be saturated. Therefore, the Fisher information can be persistently enhanced by increasing the photon number. In our magnetic-sensing experiment, biased weak measurement achieves precision approximately one order of magnitude better than those of previously used methods. The proposed method can be applied in various optical measurement schemes to remarkably mitigate the detector saturation effect with low-cost apparatuses.BACKGROUND The care and management of brain-dead pregnant women is surrounded by legal and ethical controversies. Gestational age is directly proportional to newborn survival. We report a case of a brain-dead pregnant woman at the 16th week of gestation and the successful delivery of a healthy child after 117 days of maternal somatic support. CASE REPORT A 27-year-old pregnant woman at 16 weeks' gestation with large intracerebral hematoma after rupture of an arteriovenous malformation was admitted to our intensive care unit. Signs of brain death developed early, and the woman was confirmed to be brain dead after day 6 of hospitalization. The decision-making process regarding course of medical treatment was complex and accompanied by uncertainties arising from the absence of a legal, ethical, and professional framework. A complex multidisciplinary approach was followed. https://www.selleckchem.com/products/fht-1015.html The main aim was to maintain the brain-dead woman's homeostasis to allow for proper development of the fetus. Monitoring of fetal growth was considered the best endpoint, and satisfactory fetus development was achieved. A healthy child was delivered with a birth weight of 2140 g. Her Apgar score was 10/10/10 at 1, 5, and 10 minutes, respectively, and favorable outcomes were observed at a 1-year follow-up. CONCLUSIONS Brain death during pregnancy is an extremely rare but increasingly common condition. Guidelines for care management are lacking, and reporting these cases may help establish medical treatment in future cases. We show that somatic support of the body of a brain-dead pregnant woman for an extended period of time can lead to successful delivery of a healthy child.BACKGROUND Wilson's disease (WD) manifesting as acute liver failure (ALF) is a life-threatening condition, and spontaneous recovery is rare. Diagnostic scores like the alkaline phosphatase elevation/total bilirubin elevation ratio and aspartate aminotransferase/alanine aminotransferase ratio can distinguish WD from other ALF etiologies. Liver transplantation plays a major role in treating these patients, and the revised Wilson Index is useful in patient selection for this procedure. The aim of this study was to evaluate diagnostic scores, treatments, and outcomes of a large cohort of patients with WD-ALF. MATERIAL AND METHODS Twenty adult patients of a historical cohort admitted from January 2001 to December 2017 were prospectively observed. Demographic, clinical, laboratory, and radiology data, and treatment, time on the waiting list for liver transplantation, and outcomes were recorded. RESULTS No diagnostic laboratory scores were 100% positive in patients with WD-ALF. Cut-off values for the alkaline phosphatase/total bilirubin ratio and aspartate aminotransferase/alanine aminotransferase ratio were met by 65.
    The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11chigh CD95high) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.In optical metrological protocols to measure physical quantities, it is, in principle, always beneficial to increase photon number n to improve measurement precision. However, practical constraints prevent the arbitrary increase of n due to the imperfections of a practical detector, especially when the detector response is dominated by the saturation effect. In this work, we show that a modified weak measurement protocol, namely, biased weak measurement significantly improves the precision of optical metrology in the presence of saturation effect. This method detects an ultra-small fraction of photons while maintains a considerable amount of metrological information. The biased pre-coupling leads to an additional reduction of photons in the post-selection and generates an extinction point in the spectrum distribution, which is extremely sensitive to the estimated parameter and difficult to be saturated. Therefore, the Fisher information can be persistently enhanced by increasing the photon number. In our magnetic-sensing experiment, biased weak measurement achieves precision approximately one order of magnitude better than those of previously used methods. The proposed method can be applied in various optical measurement schemes to remarkably mitigate the detector saturation effect with low-cost apparatuses.BACKGROUND The care and management of brain-dead pregnant women is surrounded by legal and ethical controversies. Gestational age is directly proportional to newborn survival. We report a case of a brain-dead pregnant woman at the 16th week of gestation and the successful delivery of a healthy child after 117 days of maternal somatic support. CASE REPORT A 27-year-old pregnant woman at 16 weeks' gestation with large intracerebral hematoma after rupture of an arteriovenous malformation was admitted to our intensive care unit. Signs of brain death developed early, and the woman was confirmed to be brain dead after day 6 of hospitalization. The decision-making process regarding course of medical treatment was complex and accompanied by uncertainties arising from the absence of a legal, ethical, and professional framework. A complex multidisciplinary approach was followed. https://www.selleckchem.com/products/fht-1015.html The main aim was to maintain the brain-dead woman's homeostasis to allow for proper development of the fetus. Monitoring of fetal growth was considered the best endpoint, and satisfactory fetus development was achieved. A healthy child was delivered with a birth weight of 2140 g. Her Apgar score was 10/10/10 at 1, 5, and 10 minutes, respectively, and favorable outcomes were observed at a 1-year follow-up. CONCLUSIONS Brain death during pregnancy is an extremely rare but increasingly common condition. Guidelines for care management are lacking, and reporting these cases may help establish medical treatment in future cases. We show that somatic support of the body of a brain-dead pregnant woman for an extended period of time can lead to successful delivery of a healthy child.BACKGROUND Wilson's disease (WD) manifesting as acute liver failure (ALF) is a life-threatening condition, and spontaneous recovery is rare. Diagnostic scores like the alkaline phosphatase elevation/total bilirubin elevation ratio and aspartate aminotransferase/alanine aminotransferase ratio can distinguish WD from other ALF etiologies. Liver transplantation plays a major role in treating these patients, and the revised Wilson Index is useful in patient selection for this procedure. The aim of this study was to evaluate diagnostic scores, treatments, and outcomes of a large cohort of patients with WD-ALF. MATERIAL AND METHODS Twenty adult patients of a historical cohort admitted from January 2001 to December 2017 were prospectively observed. Demographic, clinical, laboratory, and radiology data, and treatment, time on the waiting list for liver transplantation, and outcomes were recorded. RESULTS No diagnostic laboratory scores were 100% positive in patients with WD-ALF. Cut-off values for the alkaline phosphatase/total bilirubin ratio and aspartate aminotransferase/alanine aminotransferase ratio were met by 65.
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