icle Bone Joint Res 2021;10(2)149-155.In this report, a P(NMe2)3-mediated reductive intramolecular annulation reaction has been developed with benzoyl formates bearing a trisubstituted alkene unit. It provides a facile synthesis of highly functionalized 2,2-disubstituted 2H-chromenes with a broad substrate scope and high efficiency. Experimental results suggest this annulation reaction proceeds via a cascade of alkene isomerization/vinyl o-quinone methide formation/6π-electrocyclization. As a key intermediate, the vinyl-substituted o-quinone methide is presumably generated by a Kukhtin-Ramirez adduct initiated O → C vinyl migration.The study of metabolism heterogeneity is essential to understand the role of metabolites in supporting and regulating biological functions. To this end, several mass spectrometry imaging (MSI) approaches have been proposed for the detection of small molecule metabolites. However, high noise from the ionization matrix and low metabolome coverage hinder their applicability for untargeted metabolomics studies across space. In this context, nanostructure imaging (/initiator) mass spectrometry (NIMS) and NIMS with fluorinated gold nanoparticles (f-AuNPs) are attractive strategies for comprehensive MSI of metabolites in biological systems, which can provide heterogeneous metabolome coverage, ultrahigh sensitivity, and high lateral resolution. In particular, NIMS with f-AuNPs permits the simultaneous detection of polar metabolites and lipids in a single and cohesive analytical session, thus allowing the systems-level interpretation of metabolic changes. In this Perspective article, we discuss the use of NIMS and f-AuNPs in the exploration of metabolism heterogeneity and provide a critical outlook on future applications of this technology for revealing the metabolic architecture that supports biological functions in health and disease, from whole organisms to tissues, single cells, and subcellular compartments.The crustacean cardiac neuromuscular system is a useful model for studying how neural circuits generate behavior, as it is comprised of a simple ganglion containing nine neurons, yet acts as a robust central pattern generator. The crustacean heart is neurogenic, receiving input from neuropeptides. However, the specific effects of neuropeptides on cardiac output is not fully understood, and the large degree of comodulation between multiple neuropeptides makes studying these effects more challenging. To address this challenge, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) imaging was used to localize neuropeptides within the cardiac ganglion (CG), providing information about the identity and localization of neuropeptides being present. CG extracts were also profiled using liquid chromatography coupled to tandem mass spectrometry (MS/MS) with a data independent acquisition method, resulting in the confirmation of 316 neuropeptides. Two MS imaging (MSI) platforms were compared to provide comprehensive results, including a MALDI-Orbitrap instrument for high mass spectral resolution for accurate identifications and a MALDI TOF/TOF instrument for improved spatial resolution and sensitivity, providing more descriptive MS images. MS images for 235 putative neuropeptides were obtained, with the identification of 145 of these being confirmed by either complementary MS/MS data or accurate mass matching. The MSI studies demonstrate the sensitivity and power of this MALDI-based in situ analytical strategy for unraveling the chemical complexity present in a small nine-cell neuronal system. The results of this study will enable more informative assays of the functions of neuropeptides within this important neural circuit.Hydrolytic reactions constitute an important pathway of drug metabolism and a significant route of prodrug activation. Many ophthalmic drugs and prodrugs contain ester groups that greatly enhance their permeation across several hydrophobic barriers in the eye before the drugs are either metabolized or released, respectively, via hydrolysis. Thus, the development of ophthalmic drug therapy requires the thorough profiling of substrate specificities, activities, and expression levels of ocular esterases. However, such information is scant in the literature, especially for preclinical species often used in ophthalmology such as rabbits and pigs. Therefore, our aim was to generate systematic information on the activity and expression of carboxylesterases (CESs) and arylacetamide deacetylase (AADAC) in seven ocular tissue homogenates from these two species. The hydrolytic activities were measured using a generic esterase substrate (4-nitrophenyl acetate) and, in the absence of validated substrates for rabbit and pis of systemic drugs, and in translational and toxicity studies.β,γ-Unsaturated esters are building blocks in biologically important compounds, pharmaceuticals, and natural products. Because the current synthetic methods often require transition-metal catalysts or lack general variants, we herein describe a simple NaI-involved photoinduced deaminative alkenylation for their synthesis in the absence of photocatalysts and additives. https://www.selleckchem.com/products/Glycyrrhizic-Acid.html The density functional theory study unveils that the electrostatic interaction of NaI with Katritzky salts is the key to forming the photoactive electron donor-acceptor complex, thus leading to the alkyl radicals for the alkenylation.It has been established that an in situ-generated cationic platinum(II)/rac-BINAP complex catalyzes the intramolecular dearomative 5-endo spirocyclization of N-(methylnaphthalenyl)propiolamides via the deprotonation-protonation sequence (formal aromatic ene reaction). Mechanistic studies revealed that our previously reported dearomative 6-endo cyclization followed by the Friedel-Crafts reaction is kinetically and thermodynamically unfavored, and thus, the 5-endo spirocyclization proceeds selectively.A major challenge in developing biomimetic, high-performance, and sustainable products is the accurate replication of the biological materials' striking properties, such as high strength, self-repair, and stimuli-responsiveness. The rationalization of such features on the microscopic scale, together with the rational design of synthetic materials, is currently hindered by our limited understanding of the sequence-structure-property relationship. Here, employing state-of-the-art nuclear magnetic resonance (NMR) spectroscopy, we link the atomistic structural and dynamic properties of an artificial bioinspired tandem repeat protein TR(1,11) to its stunning macroscopic properties including high elasticity, self-healing capabilities, and record-holding proton conductivity among biological materials. We show that the hydration-induced structural rearrangement of the amorphous Gly-rich soft segment and the ordered Ala-rich hard segment is the key to the material's outstanding physical properties. We found that in the hydrated state both the Ala-rich ordered and Gly-rich disordered parts contribute to the formation of the nanoconfined β-sheets, thereby enhancing the strength and toughness of the material.

ΔRI before and after the operation was 0.084 and 0.014, respectively. The decrease of ΔRI in the case of pyeloplasty is 0.07 on average (P  less then  0.001), which can be predicted for pyeloplasty success. Discussion Color Doppler ultrasonography can be used as a non-invasive, fast, non-expensive, and available modality for evaluating the outcome of pyeloplasty instead of the nuclear scan or IVP. © 2020 Hamedanchi and Sedokani.Urethral duplication (UD) is a rare-congenital anomaly that can affect the genito-urinary system. The aim of this case report is to show our experience in this case, including the investigation and operative techniques that we utilized. In the literature review, we will show that different types of duplication, radiological investigations, and surgical techniques have been used to treat this condition. © 2020 Suoub et al.Background Advances in data collection provide opportunities to use population samples in identifying risk factors for urinary incontinence (UI), which occurs in up to 71% of men with prostate cancer following prostatectomy. Most studies on patient-centered outcomes use surveys or manual chart abstraction for data collection, which can be costly and difficult to scale. We sought to evaluate rates of and risk factors for UI following prostatectomy using natural language processing on electronic health record (EHR) data. Methods We conducted a retrospective analysis of patients undergoing prostatectomy for prostate cancer between January 2008 and August 2018 using EHR data from an academic medical center. UI incidence for each patient in the cohort was assessed using natural language processing from clinical notes generated pre- and postoperatively. Multivariable logistic regression was used to evaluate potential risk factors for postoperative UI at various time points within 2 years following surgery. Results We identified 3792 patients who underwent prostatectomy for prostate cancer. We found a significant association between preoperative UI and UI in the first (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.24-4.28) and second (OR 2.24, 95% CI 1.04-4.83) years following surgery. Preoperative body mass index was also associated with UI in the second postoperative year (OR 1.11, 95% CI 1.02-1.21). Conclusion We show that a natural language processing approach using clinical narratives can be used to assess risk for UI in prostate cancer patients. Unstructured clinical narrative text can help advance future population-level research in patient-centered outcomes and quality of care. © 2020 Li et al.Ankle-foot orthoses (AFOs) have been described to have positive effects on the gait biomechanics in stroke patients. The plantarflexion resistance of an AFO is considered important for hemiplegic patients, but the evidence is still limited. The purpose of this case series was to design and evaluate the immediate effect of an articulated AFO on kinematics and kinetics of lower-limb joints in stroke patients. The articulated AFO with the adjustment of plantarflexion resistance was designed. The spring generates a plantarflexion resistance of the ankle joint at initial stance phase. The efficacy of orthosis was evaluated on two stroke patients in 2 conditions without an AFO and with the AFO. Results showed the immediate improvements for walking speed, stride length and angular changes of dorsiflexion of the paretic ankle joint during a gait cycle of both subjects using the AFO compared with barefoot walking. The AFO also was able to reduce the paretic knee extension in the single-support phase of the stance and increase the vertical COM displacement during stance phase on the affected leg. In conclusion, the designed AFO affect not only the movement of the ankle joint but also the movements of the knee joint and the vertical COM height. These changes indicate improvement of the first and the second rockers and swing phase gait but not third rocker function. Further investigation is recently underway to compare its effect compared with other AFOs on the gait parameters of hemiplegic patients. Copyright © 2020 Journal of Biomedical Physics and Engineering.A bystander effect is biological changes in non-irradiated cells by transmitted signals from irradiated bystander cells, which causes the radiation toxic effects on the adjacent non-irradiated tissues. This phenomenon occurs by agents such as ionizing radiation, ultraviolet radiation (UVR) and chemotherapy. https://www.selleckchem.com/products/elacridar-gf120918.html The bystander effect includes biological processes such as damage to DNA, cell death, chromosomal abnormalities, delay and premature mutations and micronuclei production. The most involved genes in creating this phenomenon are cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), the nuclear factor of kappa B (NFkB) and Mitogen-Activated Protein Kinases (MAPKs). Radiation generated reactive oxygen species (ROS) can damage DNA, membranes and protein buildings. Studies have shown that Vitamin C, Hesperidin, and melatonin can reduce the number of ROS and have a protective role. Silver nanoparticles (Ag NPs) are the most abundant nanoparticles produced and when they enter cells, they can create DNA damage. Studies have shown that combined treatment with UVR and silver nanoparticles could form γ-H2AX and 8-hydroxy-2'-deoxyguanosine (8-OHdG) synergistically. This article reviews the direct and the bystander effects of UVR on the nuclear DNA, the effect of radioprotectors and Ag NPs on these effects. Copyright © 2020 Journal of Biomedical Physics and Engineering.Background Magnetic resonance imaging (MRI) using nanostructures has been a proper method for tumor targeting purposes. Different MRI nanomaterials, targeting agents and anticancer drugs have been used for targeting of tumors. Objectives This study aims to consider the MRI property of doxorubicin (DOX)-loaded gadolinium/13X zeolite/folic acid (Gd3+/13X/FA) nanocomposite. Material and Methods In this in vitro study, Gd3+/13X/FA/DOX nanocomposite was prepared and the X-ray diffraction, scanning electron microscopy and MTT assay were conducted to evaluate the physicochemical properties of the nanocomposite. MRI was performed at 25°C using a 1.5 T clinical system to determine the T1 relaxation times and subsequently, the T1 relaxivity. Results The size of the nanocomposite was in the range of 80-200 nm. The nanocomposite without DOX loading (Gd3+/13X/FA) showed compatibility for A549 cells for all concentrations while DOX-loaded nanocomposite was toxic for 62% of the cells at the concentration of 0.4 mg/ml. The T1 relaxivity of Gd3+/13X/FA/DOX nanocomposite was 4.

Spearman's bi-variate correlation analysis revealed a significant relation between the type (side) of cleft and bone volume required to fill the defect (p less then 0.05). Although there was clinical difference in bone volume measurement by the three observers, it was insignificant statistically. Clefts on the left side in the patients had significantly more bone required than the right side, whereas age and gender had no relation with bone needed to fill the defect. OsiriX software provided good reliability in measurements of bone volume.In this review, we discuss the major histocompatibility complex (MHC) class II transactivator (CIITA), which is the master regulator of MHC class II gene expression. CIITA is the founding member of the mammalian nucleotide-binding and leucine-rich-repeat (NLR) protein family but stood apart for a long time as the only transcriptional regulator. More recently, it was found that its closest homolog, NLRC5 (NLR protein caspase activation and recruitment domain (CARD)-containing 5), is a regulator of MHC-I gene expression. Both act as non-DNA-binding activators through multiple protein-protein interactions with an MHC enhanceosome complex that binds cooperatively to a highly conserved combinatorial cis-acting module. Thus, the regulation of MHC-II expression is regulated largely through the differential expression of CIITA. In addition to the well-defined role of CIITA in MHC-II GENE regulation, we will discuss several other aspects of CIITA functions, such as its role in cancer, its role as a viral restriction element contributing to intrinsic immunity, and lastly, its very recently discovered role as an inhibitor of Ebola and SARS-Cov-2 virus replication. We will briefly touch upon the recently discovered role of NLRP3 as a transcriptional regulator, which suggests that transcriptional regulation is, after all, not such an unusual feature for NLR proteins.In higher eukaryotes DNA methylation is a prominent epigenetic mark important for chromatin structure and gene expression. Thus, profiling DNA methylation is important for predicting gene expressions associated with specific traits or diseases. DNA methylation is achieved by DNA methyltransferases and can be actively removed by specific enzymes in a replication-independent manner. https://www.selleckchem.com/products/sr-18292.html DEMETER (DME) is a bifunctional 5-methylcytosine (5mC) DNA glycosylase responsible for active DNA demethylation that excises 5mC from DNA and cleaves a sugar-phosphate bond generating a single strand break (SSB). In this study, DME was used to analyze DNA methylation levels at specific epialleles accompanied with gain or loss of DNA methylation. DME treatment on genomic DNA generates SSBs in a nonsequence-specific fashion proportional to 5mC density, and thus DNA methylation levels can be easily measured when combined with the quantitative PCR (qPCR) method. The DME-qPCR analysis was applied to measure DNA methylation levels at the FWA gene in late-flowering Arabidopsis mutants and the CNR gene during fruit ripening in tomato. Differentially methylated epialleles were successfully distinguished corresponding to their expression levels and phenotypes. DME-qPCR is proven a simple yet effective method for quantitative DNA methylation analysis, providing advantages over current techniques based on methylation-sensitive restriction digestion.Docetaxel (DCX) is a highly effective chemotherapeutic drug used in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). The drug is known to have low oral bioavailability due to its low aqueous solubility, poor membrane permeability and susceptibility to hepatic first-pass metabolism. To mitigate these problems, DCX is administered via the intravenous route. Currently, DCX is commercially available as a single vial that contains polysorbate 80 and ethanol to solubilize the poorly soluble drug. However, this formulation causes short- and long-term side effects, including hypersensitivity, febrile neutropenia, fatigue, fluid retention, and peripheral neuropathy. DCX is also a substrate to the drug efflux pump P-glycoprotein (P-gp) that would reduce its concentration within the vicinity of the cells and lead to the development of drug resistance. Hence, the incorporation of DCX into various nanocarrier systems has garnered a significant amount of attention in recent years to overcome these drawbacks. The surfaces of these drug-delivery systems indeed can be functionalized by modification with different ligands for smart targeting towards cancerous cells. This article provides an overview of the latest nanotechnological approaches and the delivery systems that were developed for passive and active delivery of DCX via different routes of administration for the treatment of lung cancer.This study was designed to determine the effect of alpha-lipoic acid on the glutathione status in healthy adult dogs. Following a 15 month baseline period during which dogs were fed a food containing no alpha-lipoic acid, dogs were randomly allocated into four groups. Groups were then fed a nutritionally complete and balanced food with either 0, 75, 150 or 300 ppm of alpha-lipoic acid added for 6 months. Evaluations included physical examination, body weight, food intake, hematology, serum biochemistry profile and measurements of glutathione in plasma and erythrocyte lysates. Throughout, blood parameters remained within reference ranges, dogs were healthy and body weight did not change significantly. A significant increase of 0.05 ng/mL of total glutathione in red blood cell (RBC) lysate for each 1 mg/kg bodyweight/day increase in a-LA intake was observed. In addition, a significant increase was observed for GSH, GSSG and total glutathione in RBC lysate at Month 6. We conclude that alpha-lipoic acid, as part of a complete and balanced food, was associated with increasing glutathione activity in healthy adult dogs.The increasing number of pharmaceuticals in the environment and their difficult biodegradation, can lead to bioaccumulation in different trophic compartments. Their bioaccumulation can have negative consequences, especially in the generation of bacterial resistance by antibiotics, but also in the impairment of plant and animal metabolism. The Tejo estuary in Portugal is the habitat for many plant and animal species, which are also prone to this type of contamination. Therefore, in the present study different classes of emerging pollutants (EPs) were surveyed in water samples in the Tejo estuary, including antibiotics, anticonvulsants, antidepressants, lipid-lowering drugs, anti-inflammatory drugs, beta-blockers and analgesics. According to the results, only four compounds were detected in water samples collected at the three selected salt marshes, including carbamazepine, fluoxetine hydrochloride, venlafaxine hydrochloride and acetaminophen. Having the detected substances as a basis, a subsequent study was performed aiming to investigate the uptake and biodegradation capacity of halophytes, using Tripolium pannonicum as a model plant cultivated under controlled conditions with different concentrations of the found EPs.

Background  Habituation deficit is considered as a neurophysiological abnormality among migraineurs in the interictal period. For clear comprehension and clarity about the mechanism underlying habituation in migraine, a sophisticated method, i.e., high frequency oscillations (HFOs) evoked potentials, have been utilized. However, studies pertaining to this in the Indian context are rare. Objective  The aim of the study is to determine the utility of HFO of somatosensory evoked potential (SSEP) in deciphering the pathophysiology of migraine. Materials and Methods  Sixty subjects including 30 migraineurs in the interictal period and 30 healthy controls were considered for the study. Median nerve SSEP was recorded in patients and controls by standard protocols. HFO was extracted offline using the Digital zero-phase shift band-pass filtering at 450 and 750 Hz. The early and late HFOs were determined with respect to the N20 peak and were compared between the groups. Results  Of total 30 migraineurs, 18 had hemicranial headache and 12 had holocranial headache. N20 latency, P25 latency, N20 onset to peak amplitude, and N20 onset to P25 amplitude were comparable in migraineurs and controls. The intraburst frequency of early HFOs in migraineurs was significantly higher ( p = 0.04), whereas the peak-to-peak amplitude was significantly lower ( p = 0.001). Conclusion  Early HFOs on SSEP represent the thalamocortical excitatory drive in migraineurs. Overall, the study reports that reduced amplitude of early HFOs in the interictal period suggest reduced thalamocortical drive in migraineurs. Search algorithms used to identify patients with alopecia areata (AA) need to be validated prior to use in large databases. The aim of the study is to assess whether patients with an International Statistical Classification of Diseases and Related Health Problems (ICD) 9 or 10 code for AA have a true diagnosis of AA. A multicenter retrospective review was performed at Columbia University Irving Medical Center, Brigham and Women's Hospital, and Massachusetts General Hospital to determine whether patients with an ICD 9 codes (704.01 - AA) or ICD 10 codes (L63.0 -Alopecia Totalis, L63.1 - Alopecia Universalis, L63.2 - Ophiasis, L63.8 - other AA, and L63.9 - AA, unspecified) for AA met diagnostic criteria for the disease. Of 880 charts, 97.5% had physical examination findings consistent with AA, and 90% had an unequivocal diagnosis. AA was diagnosed by a dermatologist in 87% of the charts. The positive predictive value (PPV) of the ICD 9 code 704.01 was 97% (248/255). The PPV for the ICD 10 codes were 64% (75/118) for L63.0, 86% (130/151) for L63.1, 50% (1/2) for L63.2, 91% (81/89) for L63.8, and 93% (247/265) for L63.9. Overall, 89% (782/880) of patients with an ICD code for AA were deemed to have a true diagnosis of AA. Patients whose medical records contain an AA-associated ICD code have a high probability of having the condition. Patients whose medical records contain an AA-associated ICD code have a high probability of having the condition. Alopecia areata (AA) is an autoimmune disease with an incidence of 2% globally and plays a key role in the quality of life (QOL) of patients with AA. It has been recently shown that there are no sufficient disease-specific questionnaires to assess the QOL in patients with AA. This study tried to evaluate the validity and reliability of the Persian version of AA-Quality of Life Index (AA-QLI) and compare it with the Dermatology Life Quality Index (DLQI) questionnaire. During 1 year, 100 individuals were enrolled in this study and asked to complete the DLQI questionnaire and AA-QLI questionnaire. First of all, we enrolled 25 individuals for evaluating the validity of the Persian version of the questionnaire, and after achieving the proper validity, 75 additional patients were enrolled in this project. The results showed that the test had an appropriate validity ( < 0.001, R = 0.76), reliability ( < 0.001 , internal stability R = 0.89), and (α = 0.91). In this study, we observed that the scores of both questionnaires are quite close. In this regard, in both questionnaires, females had higher scores in comparison to males ( = 0.03), and also both of them correlated with age, age of onset of disease, and skin involvement percentage. The Persian version of the AA-QLI questionnaire is valid and reliable. The QOL of AA patients needs to be considered more seriously. Psychological evaluation of patients is one of the important suggestions in this study. The Persian version of the AA-QLI questionnaire is valid and reliable. The QOL of AA patients needs to be considered more seriously. Psychological evaluation of patients is one of the important suggestions in this study. Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia that frequently is treatment resistance to both topical and systemic therapies. The object of this pilot study was to assess the effectiveness of topical mechlorethamine 0.016% gel (Valchlor®) in decreasing disease activity in LPP and the related clinical variant frontal fibrosing alopecia (FAA). Twelve patients with biopsy-proven LPP/FAA who failed prior topical or systemic therapy with active disease were included. Participants applied mechlorethamine 0.016% gel to involved areas daily for 24 weeks. Outcome measures included LPP Activity Index (LPPAI) score, Physician Global Assessment (PGA) score, Dermatology Quality of Life Index (DQLI) score, and phototrichograms assessing follicular counts before and after six months of therapy. LPP Activity Index (LPPAI) before and after treatment was significantly different (5.0 before treatment, 2.0 after treatment; p value=0.006). Mean follicular density and follicular units were unchanged during the treatment period. Treatment with mechlorethamine 0.016% gel for 24 weeks resulted in statistically significant improvement of LLP/FFA with no change in phototrichogram parameters. Treatment duration was limited by high rate of contact dermatitis. https://www.selleckchem.com/products/abbv-2222.html Further investigation to optimize dosing frequency and to assess the role of combination topical therapy is needed. Treatment with mechlorethamine 0.016% gel for 24 weeks resulted in statistically significant improvement of LLP/FFA with no change in phototrichogram parameters. Treatment duration was limited by high rate of contact dermatitis. Further investigation to optimize dosing frequency and to assess the role of combination topical therapy is needed.

while having a normal body mass index was found to be a protective factor of preeclampsia occurrence. To improve early detection and timely management of preeclampsia, the clinician should give attention to women who have no previous childbirth and whose close relatives had a history of chronic hypertension, as well as working on the protective factor is recommended. To assess injection patterns and vision outcomes in patients receiving intravitreal ranibizumab injections for diabetic macular edema in a real-world clinical setting. Retrospective chart review involving 74 eyes of 62 patients who started ranibizumab treatment for diabetic macular edema at the Hospital of the Lithuanian University of Health Sciences Kauno Klinikos. Data collected included follow-up visits, injections administered, and best-corrected visual acuity (BCVA). Median follow-up duration was 652.5 days (min 365; max 914). https://www.selleckchem.com/products/anisomycin.html Over the first year, eyes received a median of 4 injections (min 1; max 10). Among eyes with 2-year follow-up and injections during the second year, there was a median of 3 injections (min 1; max 6) over the second year. The BCVA improved by a median of 5 letters 365 ± 60 days and 730 ± 60 days after baseline. At the first visit ≥365 days after baseline, 13.5% of eyes gained ≥15 letters from baseline while 6.8% of eyes lost ≥15 letters. For 74.3% of eyes, BCVA improved (gain of ≥5 letters) or remained stable (gain/loss of ≤4 letters). Intravitreal ranibizumab for diabetic macular edema was effective in a real-world clinical setting, with most eyes gaining or maintaining vision. Compared with randomized prospective clinical trials, patients received less frequent injections and achieved lower vision gains. Intravitreal ranibizumab for diabetic macular edema was effective in a real-world clinical setting, with most eyes gaining or maintaining vision. Compared with randomized prospective clinical trials, patients received less frequent injections and achieved lower vision gains. To compare the clinical results of standard corneal cross-linking (SCXL) with transepithelial corneal cross-linking (TECXL) in progressive keratoconus using a meta-analysis. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched up to June 2020 to identify relevant studies. The PRISMA guidelines were followed. Primary outcomes were change in uncorrected distance visual acuity and maximum keratometry ( ) after CXL. Secondary outcomes were change in corrected distance visual acuity, mean refractive spherical equivalent (MRSE), spherical and cylindrical error, endothelial cells density (ECD), and central corneal thickness (CCT). Sixteen studies with a total of 690 eyes (SCXL 332 eyes; TECXL 358 eyes) were included. At the last follow-up, SCXL provided a greater decrease in maximum keratometry ( ) than TECXL (weighted mean difference (WMD) -1.12; 95% confidence interval (CI) -1.96, -0.29). For the other outcomes, there were no statistically significant differences. Except for a greater decrease in Kmax with SCXL group, both groups have a comparable effect on visual, pachymetric, and endothelial parameters at 24 months after surgery. Larger studies with a longer follow-up time are necessary to determine whether these techniques are comparable in the long term. Except for a greater decrease in Kmax with SCXL group, both groups have a comparable effect on visual, pachymetric, and endothelial parameters at 24 months after surgery. Larger studies with a longer follow-up time are necessary to determine whether these techniques are comparable in the long term. To investigate the retinal thickness asymmetry parameters of circumpapillary retinal nerve fiber layer (cpRNFL) and macular layers measured by spectral-domain optical coherence tomography in highly myopic (HM) patients with an early stage of normal-tension glaucoma (NTG). This cross-sectional study included 55 eyes of HM patients with early NTG and 37 eyes of HM normal participants. High myopia was defined as spherical equivalence more myopic than -6 diopters. Thickness differences and asymmetry indices (AIs) of cpRNFL between superior and inferior corresponding parts and thickness differences and AIs of the total macular layer (TML) and inner macular layers between superior and inferior hemispheres were calculated. The areas under the receiver operating characteristic curves (AROCs) were analyzed and compared. In the cpRNFL asymmetry analysis, the thickness differences and AIs of cpRNFL between temporal-superior and temporal-inferior sectors (  < 0.0001 and  < 0.0001, respectively) and betweeness, mRNFL thickness, and mGCL thickness. Asymmetry analysis of retinal thickness can be an adjunctive tool for the early detection of HM NTG. In our study, HM NTG patients had retinal thickness asymmetry in cpRNFL, TML, and mGCL. The diagnostic capabilities for thickness asymmetry of TML and mGCL were comparable to the diagnostic capabilities for cpRNFL thickness, mRNFL thickness, and mGCL thickness. Asymmetry analysis of retinal thickness can be an adjunctive tool for the early detection of HM NTG. To correlate optical coherence tomography (OCT) measurements with clinical parameters in idiopathic intracranial hypertension (IIH). A cross-sectional study was conducted with 22 patients with IIH and 11 controls. All participants underwent comprehensive ophthalmological examination followed by spectral-domain OCT (SD-OCT) and standard automated perimetry using the 30-2 program of the Humphrey visual field analyzer. Correlations between ganglion cell complex (GCC) thickness and retinal nerve fiber layer (RNFL) thickness, as measured by SD-OCT, and clinical parameters were assessed using generalized estimating equations. The mean age of the participants was 35.0 ± 10.83 years. The groups were similar regarding age, but were significantly different regarding sex and visual acuity ( =0.001 and =0.038, respectively). The GCC was significantly thinner in the IIH group, with a mean of 90.535 ± 9.766  m compared to 98.119 ± 6.988  m for the controls ( =0.023). There was a significant association between GCC thickness and optic disc pallor ( =0.

ght, weight or BMI from naturally conceived once they reach adolescence. Research Council of Norway; Medical Research Council; National Institute of Environmental Health Sciences. The authors have no competing interest. N/A. N/A.Single-molecule tracking (SMT) allows the study of transcription factor (TF) dynamics in the nucleus, giving important information regarding the diffusion and binding behavior of these proteins in the nuclear environment. Dwell time distributions obtained by SMT for most TFs appear to follow bi-exponential behavior. This has been ascribed to two discrete populations of TFs-one non-specifically bound to chromatin and another specifically bound to target sites, as implied by decades of biochemical studies. However, emerging studies suggest alternate models for dwell-time distributions, indicating the existence of more than two populations of TFs (multi-exponential distribution), or even the absence of discrete states altogether (power-law distribution). Here, we present an analytical pipeline to evaluate which model best explains SMT data. We find that a broad spectrum of TFs (including glucocorticoid receptor, oestrogen receptor, FOXA1, CTCF) follow a power-law distribution of dwell-times, blurring the temporal line between non-specific and specific binding, suggesting that productive binding may involve longer binding events than previously believed. From these observations, we propose a continuum of affinities model to explain TF dynamics, that is consistent with complex interactions of TFs with multiple nuclear domains as well as binding and searching on the chromatin template. College students who drink are at an increased risk of driving after drinking and alcohol-involved traffic accidents and deaths. Furthermore, the persistence of driving after drinking over time underscores a need for effective interventions to prevent future drunk driving in adulthood. The present study examined whether brief alcohol interventions (BAIs) for college students reduce driving after drinking. A two-step meta-analysis of individual participant data (IPD) was conducted using a combined sample of 6801 college students from 15 randomized controlled trials (38% male, 72% White and 58% first-year students). BAIs included individually delivered Motivational Interviewing with Personalized Feedback (MI+PF), Group Motivational Interviewing (GMI), and stand-alone Personalized Feedback (PF) interventions. Two outcome variables, driving after two+/three+ drinks and driving after four+/five+ drinks, were checked, harmonized and analyzed separately for each study and then combined for meta-analysis and metae the outcome assessment and reporting to demonstrate its effect.Studies of inflammation in alcohol use disorder (AUD) are overwhelmingly preclinical, and translation to clinical samples is necessary. Endotoxin administration has been used successfully in humans to study mood disorders, offering a translational, reliable and safe model that may be validated in AUD research. We argue for the use of endotoxin challenge to elucidate the interplay between AUD and inflammation.Risk-taking propensity has been crucial to the investigation of alcohol use and consequences. One measure, the balloon analogue risk task (BART), has been used consistently over the past two decades. However, it is unclear how this measure is related to alcohol outcomes. This paper systematically reviews the literature on the BART and alcohol outcomes. First, direct associations between the BART and alcohol use are reviewed including correlations, group comparisons, the BART's prediction of alcohol outcomes and BART performance after consuming alcohol. Then, potential moderators that explain when and for whom the BART is related to alcohol outcomes are reviewed. Finally, potential mechanisms that explain how the BART and alcohol outcomes are related are reviewed. This review reveals patterns in the BART suggesting risk-taking propensity may be related to changes in alcohol use over time; however, there is little evidence to suggest BART scores increase after consuming alcohol. Yet, additional research suggests adjusted average pump scores may be too simplistic for the amount of information the BART captures and understanding individual's patterns of responses on the BART is important for investigating its relation to alcohol outcomes. https://www.selleckchem.com/products/Dihydroartemisinin(DHA).html Finally, this review opens up several future directions for research to understand how risk-taking propensity is related to alcohol outcomes. This study evaluated the performance of GeneXpert MTB/RIF (Xpert) and ProbeTec ET (PTec-ET) assays in diagnosing extrapulmonary tuberculosis (EPTB) in Kuwait. We tested nonrespiratory clinical specimens (n = 3,995) collected from 3,995 patients suspected to have EPTB. These included cavitary fluids (n = 2,054), fine-needle aspirate (FNA)/pus/tissue biopsy (n = 1,461), urine (n = 302), cerebrospinal fluid (CSF, n = 118), and others (n = 60). All specimens were processed for acid-fast bacilli (AFB), culture in mycobacteria growth indicator tube 960 system, and nucleic acid detection by Xpert and PTec-ET according to manufacturer's instructions. Of 3,995 specimens, 95 were AFB-positive, 403 were culture-positive, and an additional 86 samples had histopathology suggestive of TB. Using culture as reference, the sensitivity and specificity values were 88.33 and 97.3% for Xpert and 72.95 and 97.80% for PTec-ET, respectively. Although performance of both tests was comparable in AFB-positive samples, Xpert detecile Xpert was positive in all 6 culture-positive CSF specimens for rapid diagnosis of TB meningitis. Xpert was thus superior to PTec-ET or smear microscopy in rapid diagnosis of EPTB.The advent of integrated intraoperative ocular coherence tomography (i2OCT) has opened the door for safer more complex surgeries of the retina and cornea. However, to limit its use to just two subspecialties within ophthalmology is an opportunity lost for many other subspecialties. Here, we describe the use of i2OCT in strabismus surgery. It can be used to identify extraocular muscles, especially in cases of strabismus reoperations, thereby augmenting the surgical technique. Its use to help train strabismus surgery is invaluable, allowing the trainee to understand the depth of the scleral pass during strabismus surgery. The authors describe these scenarios of training and augmenting the surgical technique.

Black and Hispanic patients and controls had lower SDMT scores than white participants even after controlling for age, sex, and education. However, no interaction between race/ethnicity and MS case status on SDMT scores was detected. Easy-to-use reference scores stratified by age and educational attainment for black and Hispanic patients are provided. CONCLUSION Persons with newly diagnosed MS/CIS are more likely to have subtly impaired cognitive function than controls regardless of race/ethnicity. Lower absolute SDMT scores among black and Hispanic patients compared to white patients highlight underlying US population differences rather than differences in MS disease severity. © 2020 American Academy of Neurology.Among all of the Super Elongation Complex (SEC) components, ELL1 (also known as ELL) is the only bona fide elongation factor that directly stimulates transcription elongation by RNA polymerase II. However, the mechanism(s) of functional regulation of ELL1 (referred to as ELL hereafter), through its stabilization, is completely unknown. Here, we report a function of human DBC1 in regulating ELL stability involving HDAC3, p300, and Siah1. Mechanistically, we show that p300-mediated site-specific acetylation increases, whereas HDAC3-mediated deacetylation decreases, ELL stability through polyubiquitylation by the E3 ubiquitin ligase Siah1. DBC1 competes with HDAC3 for the same binding sites on ELL and thus increases its acetylation and stability. Knockdown of DBC1 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism. Consistently, Type 2 diabetes patient-derived peripheral blood mononuclear cells show reduced expression of DBC1 and ELL and associated key target genes required for glucose homeostasis. Thus, we describe a pathway of regulating stability and functions of key elongation factor ELL for expression of diverse sets of genes, including ones that are linked to Type 2 diabetes pathogenesis. Copyright © 2020 the Author(s). Published by PNAS.Most digital information today is encoded in the magnetization of ferromagnetic domains. The demand for ever-increasing storage space fuels continuous research for energy-efficient manipulation of magnetism at smaller and smaller length scales. Writing a bit is usually achieved by rotating the magnetization of domains of the magnetic medium, which relies on effective magnetic fields. An alternative approach is to change the magnetic state directly by acting on the interaction between magnetic moments. Correlated oxides are ideal materials for this because the effects of a small external control parameter are amplified by the electronic correlations. Here, we present a radical method for reversible, light-induced tuning of ferromagnetism at room temperature using a halide perovskite/oxide perovskite heterostructure. We demonstrate that photoinduced charge carriers from the [Formula see text] photovoltaic perovskite efficiently dope the thin [Formula see text] film and decrease the magnetization of the ferromagnetic state, allowing rapid rewriting of the magnetic bit. This manipulation could be accomplished at room temperature; hence this opens avenues for magnetooptical memory devices.Polarity decisions are central to many processes, including mitosis and chemotropism. In Saccharomyces cerevisiae, budding and mating projection (MP) formation use an overlapping system of cortical landmarks that converges on the small G protein Cdc42. However, pheromone-gradient sensing must override the Rsr1-dependent internal polarity cues used for budding. Using this model system, we asked what happens when intrinsic and extrinsic spatial cues are not aligned. Is there competition, or collaboration? By live-cell microscopy and microfluidics techniques, we uncovered three previously overlooked features of this signaling system. First, the cytokinesis-associated polarization patch serves as a polarity landmark independently of all known cues. Second, the Rax1-Rax2 complex functions as a pheromone-promoted polarity cue in the distal pole of the cells. Third, internal cues remain active during pheromone-gradient tracking and can interfere with this process, biasing the location of MPs. Yeast defective in internal-cue utilization align significantly better than wild type with artificially generated pheromone gradients.Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-like vacuole through activation of a Dot/Icm-type IVB secretion system and subsequent translocation of effectors that remodel the host cell. Here a genome-wide small interfering RNA screen and reporter assay were used to identify host proteins required for Dot/Icm effector translocation. Significant, and independently validated, hits demonstrated the importance of multiple protein families required for endocytic trafficking of the C. burnetii-containing vacuole to the lysosome. Further analysis demonstrated that the degradative activity of the lysosome created by proteases, such as TPP1, which are transported to the lysosome by receptors, such as M6PR and LRP1, are critical for C. burnetii virulence. Indeed, the C. burnetii PmrA/B regulon, responsible for transcriptional up-regulation of genes encoding the Dot/Icm apparatus and a subset of effectors, induced expression of a virulence-associated transcriptome in response to degradative products of the lysosome. Luciferase reporter strains, and subsequent RNA-sequencing analysis, demonstrated that particular amino acids activate the C. burnetii PmrA/B two-component system. This study has further enhanced our understanding of C. burnetii pathogenesis, the host-pathogen interactions that contribute to bacterial virulence, and the different environmental triggers pathogens can sense to facilitate virulence. Copyright © 2020 the Author(s). Published by PNAS.We present an approach to response around arbitrary out-of-equilibrium states in the form of a fluctuation-response inequality (FRI). https://www.selleckchem.com/products/mg-101-alln.html We study the response of an observable to a perturbation of the underlying stochastic dynamics. We find that the magnitude of the response is bounded from above by the fluctuations of the observable in the unperturbed system and the Kullback-Leibler divergence between the probability densities describing the perturbed and the unperturbed system. This establishes a connection between linear response and concepts of information theory. We show that in many physical situations, the relative entropy may be expressed in terms of physical observables. As a direct consequence of this FRI, we show that for steady-state particle transport, the differential mobility is bounded by the diffusivity. For a "virtual" perturbation proportional to the local mean velocity, we recover the thermodynamic uncertainty relation (TUR) for steady-state transport processes. Finally, we use the FRI to derive a generalization of the uncertainty relation to arbitrary dynamics, which involves higher-order cumulants of the observable.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important cause of multi-organ dysfunction and can mimic other disorders including sepsis. We describe a patient presenting with septic shock and accompanying high procalcitonin. Although initially treated empirically with antibiotics, the emergence of eosinophilia during the admission lead to a revised diagnosis of DRESS syndrome, presumed secondary to acetazolamide. This case highlights the importance of regular clinical assessment and re-evaluation is key in identifying emerging features such as eosinophilia, rash and organ dysfunction, which can secure the diagnosis. Furthermore, the case also highlights that acetazolamide may be a rare cause of DRESS syndrome.A 75-year-old man was admitted with a 3-month history of worsening diarrhoea and weight loss. He was on long-term immunosuppression following cardiac transplantation. Investigations revealed herpes simplex oesophagitis and stool samples were positive for norovirus. Treatment with acyclovir and nitazoxanide resulted in a complete resolution of symptoms. Norovirus is a common cause of infectious gastroenteritis, but immunosuppressed patients may present with chronic diarrhoea rather than an acute illness. This case highlights the importance of a low clinical threshold for testing for norovirus infection in immunocompromised patients.Pontocerebellar hypoplasia type 1B (PCH1B) describes an autosomal recessive neurological condition that involves hypoplasia or atrophy of the cerebellum and pons, resulting in neurocognitive impairments. Although there is phenotypic variability, this is often an infantile lethal condition, and most cases have been described to be congenital and neurodegenerative. PCH1B is caused by mutations in the gene EXOSC3, which encodes exosome component 3, a subunit of the human RNA exosome complex. A range of pathogenic variants with some correlation to phenotype have been reported. https://www.selleckchem.com/products/hg6-64-1.html The most commonly reported pathogenic variant in EXOSC3 is c.395A>C, p.(Asp132Ala); homozygosity for this variant has been proposed to lead to milder phenotypes than compound heterozygosity. In this case, we report two siblings with extraordinarily mild presentations of PCH1B who are compound heterozygous for variants in EXOSC3 c.155delC and c.80T>G. These patients drastically expand the phenotypic variability of PCH1B and raise questions about genotype-phenotype associations.Solitary neurofibromas of the larynx are extremely rare, with a total of 15 cases described in the literature. Nonetheless, acquaintance with this diagnosis is important, as misdiagnoses can have negative consequences. Presenting symptoms are non-specific and depend on tumour size and location. As well-defined submucosal masses with a broad differential diagnosis, they remain a clinical and radiological challenge. While some characteristics might favour a benign nature and subtle signs might help narrow the differential diagnosis, imaging alone is not sufficient for differentiation and definitive diagnosis requires a biopsy. Complete surgical resection and long-term follow-up is indicated. We share our experience on a case of a solitary laryngeal neurofibroma in a middle-aged woman, presenting with a large well-defined paraglottic lesion.Orbital complications after endoscopic sinus surgery are serious problems. Inadvertent contamination of the eye by pharmacological solution can lead to early postoperative anxiety to patients and high concern to surgeons. This is a rare case report of retrograde epinephrine flow through lacrimal duct in sinus surgery with learning tips during postoperative assessment for reassurance in temporary pharmacological effect rather than serious complication.Primary cardiac valve tumours are rare. This is a case report of a 32-year-old non-smoker man with a history of stroke 1 year prior and no other cardiovascular risk factors. The patient was admitted to our acute stroke ward for recurrent left hemiparesis, slurring of speech, facial asymmetry and central retinal artery occlusion. Initial laboratory investigations and ECG were normal. An urgent CT brain showed a large hypodense area at the right frontal, parietal, temporal, occipital region with effaced sulci and right lateral ventricle with midline shift and cerebral oedema in keeping with acute infarction. We proceeded with CT angiography of the cerebral and carotid on the following day, which revealed no evidence of thrombosis, aneurysm or arteriovenous malformation. There were no abnormal beaded vessels to suggest vasculitis. Transthoracic echocardiography revealed a large mobile mass in the left atrium. Meanwhile, MRI cardiac confirmed a large ill-defined mobile solid mass attached to the mitral valve's inferoseptal component suggestive of mitral valve myxoma. This case report highlights the significance of considering a cardiogenic source of emboli in patients with large cerebral infarcts and other cardiac embolic phenomena. Imaging modalities such as echocardiography and cardiac MRI will help detect treatable conditions, such as valvular myxoma and prevent further complications.Leptomeningeal carcinomatosis is a devastating sequelae of metastatic cancer. It has protean manifestations on imaging. An elderly woman presented to our tertiary centre with symptoms suggestive of a cerebrovascular accident. Investigations revealed no evidence of this. There was clinical, contextual and radiological evidence of an underlying neoplasm.Magnetic resonance imaging (MRI) demonstrated evidence of a rare morphology (anterolateral pontine leptomeningeal enhancement) in the presence of a probable concomitant lung adenocarcinoma. Other reports have previously described this same neuroradiology, seemingly always in association with lung adenocarcinoma.The purpose of this report is to highlight an unusual case and discuss its peculiarity and pathophysiology. Our patient is the latest documented of a small cohort with this constellation of clinical and neuroradiological features.This study demonstrates the importance of differential diagnosis in stroke medicine, specifically the need to consider neoplastic phenomena in patients admitted following putative cerebrovascular events.

Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001). Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. https://www.selleckchem.com/products/lazertinib-yh25448-gns-1480.html Moreover, PCS is significantly associated with decreased HRQOL. Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL. In drug-resistant temporal lobe epilepsy (TLE) patients, the authors evaluated early and late outcomes for decline in visual object naming after dominant temporal lobe resection (TLR) according to the resection status of the basal temporal language area (BTLA) identified by cortical stimulation during stereoelectroencephalography (SEEG). Twenty patients who underwent SEEG for drug-resistant TLE met the inclusion criteria. During language mapping, a site was considered positive when stimulation of two contiguous contacts elicited at least one naming impairment during two remote sessions. After TLR ipsilateral to their BTLA, patients were classified as BTLA+ when at least one positive language site was resected and as BTLA- when all positive language sites were preserved. Outcomes in naming and verbal fluency tests were assessed using pre- and postoperative (means of 7 and 25 months after surgery) scores at the group level and reliable change indices (RCIs) for clinically meaningful changes at the individual level. BTLA+ patients (n = 7) had significantly worse naming scores than BTLA- patients (n = 13) within 1 year after surgery but not at the long-term evaluation. No difference in verbal fluency tests was observed. When RCIs were used, 5 of 18 patients (28%) had naming decline within 1 year postoperatively (corresponding to 57% of BTLA+ and 9% of BTLA- patients). A significant correlation was found between BTLA resection and naming decline. BTLA resection is associated with a specific and early naming decline. Even if this decline is transient, naming scores in BTLA+ patients tend to remain lower compared to their baseline. SEEG mapping helps to predict postoperative language outcome after dominant TLR. BTLA resection is associated with a specific and early naming decline. Even if this decline is transient, naming scores in BTLA+ patients tend to remain lower compared to their baseline. SEEG mapping helps to predict postoperative language outcome after dominant TLR. Primary central nervous system lymphoma (PCNSL) is a rare CNS tumor with a poor prognosis. It is usually diagnosed by needle biopsy and treated mainly with high-dose chemotherapy. Resection is currently not considered a standard treatment option. A possible prolonged survival after resection of PCNSL lesions in selected patients has been suggested, but selection criteria for surgery, especially for solitary lesions, have never been established. The authors retrospectively searched their patient database for records of adult patients (≥ 18 years) who were diagnosed and treated for a solitary PCNSL between 2005 and 2019. Patients were divided into groups according to whether they underwent resection or needle biopsy. Statistical analyses were performed in an attempt to identify variables affecting outcome and possible survival advantage and to characterize subgroups of patients who would benefit from resection of their tumor compared with undergoing biopsy only. A total of 113 patients with a solitary lestimes than those who underwent needle biopsy (median survival 34.3 months vs 8.9 months, p = 0.014). Patients younger than 70 years who had a superficial tumor and underwent resection had significantly prolonged survival, with a median survival of 35.0 months compared with 8.9 months in patients from the same group who underwent needle biopsy (p = 0.007). Specific subgroups of patients with a solitary PCNSL lesion might gain a survival benefit from resection compared with undergoing only a diagnostic biopsy. Specific subgroups of patients with a solitary PCNSL lesion might gain a survival benefit from resection compared with undergoing only a diagnostic biopsy. The management of hydrocephalus resulting from intraventricular hemorrhage related to extreme prematurity remains demanding. Given the complexities of controlling hydrocephalus in this population, less commonly used procedures may be required. The authors examined the utility of ventriculogallbladder (VGB) shunts in a series of such children. The authors retrospectively reviewed the medical records of all children who underwent surgery for hydrocephalus in the period from 2011 through 2019 at Children's Healthcare of Atlanta. Six patients who underwent VGB shunt placement were identified among a larger cohort of 609 patients who had either a new shunt or a newly changed distal terminus site. The authors present an analysis of this series, including a case of laparoscopy-assisted distal VGB shunt revision. The mean age at initial shunt placement was 5.1 months (range 3.0-9.4 months), with patients undergoing a mean of 11.8 shunt procedures (range 5-17) prior to the initial VGB shunt placement at a mean ae armamentarium of procedures that may be used in the particularly difficult cohort of children with hydrocephalus related to extreme prematurity. VGB shunts show utility as both a definitive treatment and as a "bridge" procedure until the patient is larger and comorbid abdominal and/or vascular issues have resolved sufficiently to allow conversion back to ventriculoperitoneal or ventriculoatrial shunts, if needed. Placement of VGB shunts should be considered in the armamentarium of procedures that may be used in the particularly difficult cohort of children with hydrocephalus related to extreme prematurity. VGB shunts show utility as both a definitive treatment and as a "bridge" procedure until the patient is larger and comorbid abdominal and/or vascular issues have resolved sufficiently to allow conversion back to ventriculoperitoneal or ventriculoatrial shunts, if needed.