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Background/Aims: Exogenous insulin therapy increases systemic exposure to insulin which may promote the development of colorectal neoplasia. We sought to evaluate the association between exogenous insulin therapy and the incidence of advanced adenoma in type 2 diabetes mellitus. Methods: A retrospective cohort study was conducted from January 1, 2007, to January 1, 2018, in a regional health system serving the United States Philadelphia metropolitan area, Central New Jersey, and South Central Pennsylvania. Study patients consisted of a random sample of patients with type 2 diabetes mellitus aged 40–80 years who had undergone two rounds of colonoscopy examinations. The exposure was cumulative duration of insulin therapy (i.e., no use, 1–365 days and > 365 days). The outcome was time to incident advanced adenoma. Results: Of the 975 eligible patients, 184 patients accumulated > 365 days of insulin therapy before the follow-up colonoscopy. The mean (standard deviation) duration between the two rounds of colonoscopy examination was 5.1 (2.9) years among the insulin users and 5.3 (3.9) years among non-users. Compared to no insulin exposure, receiving > 365 days of insulin therapy was associated with an increased incidence of advanced adenoma (adjusted hazard ratio [aHR] 4.84, 95% confidence interval [CI] 2.82–8.30), right-sided advanced adenoma (aHR 5.48, 95% CI 2.90–10.35), and 3 or more adenomas (aHR 2.61, 95% CI 1.46–4.69) at the follow-up colonoscopy examination. Conclusion: Insulin therapy is associated with an increased risk of advanced adenoma and may serve as a novel risk-stratification factor to enhance the efficiency of existing colorectal cancer screening and surveillance programs. [ABSTRACT FROM AUTHOR]

Purpose of Review: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease affecting 30% of the global population. In this article, we summarize current expert guidelines, review clinical practice implications, and provide insight into the utility of non-invasive tests (NITs). Recent Findings: The burden of MASLD is growing with the obesity epidemic, yet disease awareness and diagnosis is low. Patients can progress to metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), which can advance to liver fibrosis, cirrhosis, hepatic decompensation, and liver cancer. NITs help identify high-risk patients who may benefit from specialty referral and MASH-directed therapy. Summary: Global societies offer various recommendations for the screening and diagnosis of MASLD utilizing evidence-based, widely accessible methods such as serum indices, NITs, and liver biopsy. Several targeted steatotic liver disease (SLD) screening tools and novel therapies are under development. [ABSTRACT FROM AUTHOR]

To report a case of concurrent pantothenate kinase-associated neurodegeneration (PKAN) and oculocutaneous albinism (OCA) with dual PANK2 and OCA2 variants in a Chinese patient who presented with early-onset reduced vision, nyctalopia, and neurological symptoms. Based on the ocular phenotype and provisional diagnosis of rod-cone dystrophy, genetic testing was pursued. Peripheral blood DNA extraction was carried out with the next-generation sequencing technique, which involved a population-specific medical exome virtual panel. Pre- and post-test counseling were carried out by clinical geneticists. Homozygous missense variants in PANK2 {NM_153638.3}:c.655 G>A (p.(Gly219Ser)) and OCA2{NM_025160.6}:c.1327 G>A(p.(Val443Ile)) were identified. The molecular diagnoses of pantothenate kinase associated neurodegeneration (OMIM#234200) and albinism, oculocutaneous, type II (OMIM#203200) were supported by clinical findings. Two rare autosomal recessive diseases, pantothenate kinase-associated neurodegeneration (PKAN) and oculocutaneous albinism (OCA) were detected in our patient. Ocular and systemic manifestations, as well as neuroimaging findings were compatible with the diseases identified. Genetic analysis is imperative in making an accurate molecular diagnosis in these rare conditions to allow timely counseling, disease prognostication and management. [ABSTRACT FROM AUTHOR]

Pachychoroid disease spectrum encompasses entities with pathogenesis of choroidal circulatory dysfunction. Advancements in ophthalmic imaging enables better understanding of its structural and functional implications. This perspective article covers clinical features, ocular imaging findings, and management options of pachychoroid spectrum diseases including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy or aneurysmal type 1 neovascularization, focal choroidal excavation, and peripapillary pachychoroid syndrome. [ABSTRACT FROM AUTHOR]

Keywords: neuroendocrine tumor; chylous ascites; malignant ascites; dotatate scan EN neuroendocrine tumor chylous ascites malignant ascites dotatate scan 2082 2085 4 06/16/22 20220602 NES 220602 This case was presented as a poster at the Society of General Internal Medicine National Annual Meeting, April 21-24, 2021. Early in the disease course, chylous ascites can be remarkably responsive to dietary modification, diuretics, and medications such as somatostatin or octreotide therapy.[2],[3],[20],[21] Given its extremely rare occurrence, NET and chylous ascites caused by local tumor compression of the pancreatic ductal system can be mistaken for metastatic pancreatic cancer with malignant ascites. Availability bias, having the disposition to overestimate how often an event occurs because information about it is more easily recalled, was also present.[26] Metastatic pancreatic cancer with malignant ascites is much more prevalent than pancreatic NET with chylous ascites, and thus, a diagnosis of the former was determined early on. [Extracted from the article]

Purpose: To compare two-year treatment outcomes of subthreshold micropulse (577 nm) laser and aflibercept for diabetic macular edema (DME). Study design: Retrospective case–control study. Methods: A total 164 eyes in 164 DME patients treated with either micropulse laser (86 eyes) or intravitreal aflibercept monotherapy (78 eyes) were recruited. Main outcome measures included at least five Early Treatment Diabetic Retinopathy Study (ETDRS) letters' improvement from baseline at 6, 12 and 24 months. Results: Rescue aflibercept was initiated in 24% of eyes in micropulse laser group. At 6-month visit the aflibercept group achieved a higher percentage of eyes with at least 5-letter visual acuity improvement than micropulse laser group (56% vs 38%, P = 0.044), however, this was not the case at 12-month (45% vs 49%, P = 0.584) and 24-month visits (49% vs 57%, P = 0.227). At 6-month visit the aflibercept group achieved a higher percentage of eyes with at least 10% improvement of central macular thickness (73% vs 49%, P = 0.005), but this was not the case at 12-month (73% vs 70%, P = 0.995) and 24-month visits (85% vs 84%, P = 0.872). Conclusion: Aflibercept achieved faster and higher rates of anatomical and functional improvement than micropulse laser in DME patients. Long term efficacy of treatment did not result in significant differences between aflibercept monotherapy and micropulse laser in DME patients. Primary treatment of micropulse laser with deferred rescue aflibercept might be the treatment option without reducing the chance of visual improvement in DME eyes. [ABSTRACT FROM AUTHOR]

Background The predicted growth of Canadians aged 65+ and the resultant rise in the demand for specialized geriatric services (SGS) requires physician resource planning. We updated the 2011 Canadian Geriatrics Society physician resource inventory and created projections for 2025 and 2030. Methods The number and full-time equivalents (FTEs) of geriatricians and Care of the Elderly (COE) physicians working in SGS were determined. FTE counts for 2025 and 2030 were estimated by accounting for retirements and trainees. A ratio of 1.25/10,000 population 65+ was used to predict physician resource requirements. Results Between 2011 and 2019 the number of geriatricians and COE physicians increased from 276 (235.8 FTEs) and 128 (89.9 FTEs), respectively, to 376 (319.6 FTEs) and 354 (115.5 FTEs). This increase did not keep pace with the 65+ population growth. The current gap between supply and need is expected to increase. Discussion The physician supply gap is projected to widen in 2025 and 2030. Increased recruitment and interdisciplinary team-based care, supported by enhanced funding models, and full integration of COE physicians in SGS could reduce this increasing gap. In contrast to pediatrician supply in Canada, the specialist physician resources available to the population 65+ reflect a disparity. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to evaluate the efficacy of a required emergency medicine (EM) experience embedded in a new community‐based longitudinal integrated clerkship (LIC) for participating students and faculty. Methods: We developed and implemented a community‐based LIC EM experience. The experience included 10 clinical shifts, one emergency medical services prehospital care shift, four didactic sessions, one reflection, and an emergency medicine simulation session. Students' outcomes were assessed using end‐of‐year surveys, focus groups, an emergency medicine subject examination, simulation performance, and clinical evaluations of the students by faculty. Faculty were recruited, underwent faculty development, and were evaluated by students. Faculty perceptions were gathered from a focus group and faculty retention rates were collected. Results: Three cohorts of LIC students (total N = 61) have completed their core emergency medicine experience in our community‐based LIC. Among students, 76% to 95% rated the overall quality of teaching as very good or excellent and 66% to 100% rated the quality of learning in their community‐based setting as very good or excellent. All students who passed the EM subject examination achieved the clinical competencies of the experience based on clinical evaluations. Among faculty, we have retained greater than 95% each year and they have reflected positively on their precepting experience. Conclusions: Implementing a required EM experience within a community‐based LIC model can be an effective learning experience for students and perceived positively by community‐based faculty. This model may offer an opportunity to expand clinical learning experiences in EM. [ABSTRACT FROM AUTHOR]

There is an increasing trend of reported laser-induced ocular injury. We aimed to review the literature on the basic principles of laser, clinical management and safety precaution of laser-induced ocular injury. A literature search on the PubMed database was conducted to include articles dated up to April 2020. One example case of laser-induced ocular injury is provided. Clinical presentation of laser-induced ocular injury is variable. The clinical features can be transient and subtle. Appropriate investigations are useful to establish a diagnosis and to evaluate the severity of the injury. Laser-induced ocular injury most commonly involves the macula, which can be complicated by intraocular haemorrhage, macular hole, epiretinal membrane, and choroidal neovascularization. There are currently no evidence-based or well-recognized treatments for laser-induced retinopathy. Surgical intervention might be considered if there is significant intraocular hemorrhage or macular hole. Laser-induced ocular injury may cause permanent visual sequelae and functional disability. Diagnosis of an eye injury should be supported by objective clinical findings and/ or appropriate investigations. As medical and surgical treatment options are currently limited, the key to combat laser ocular injuries lies in prevention and awareness of the general public should be reinforced. [ABSTRACT FROM AUTHOR]

Background Endoscopic placement of hilar stents is an accepted palliative therapy for patients with advanced, unresectable cholangiocarcinoma. However, whether unilateral versus bilateral stent placement provides optimal relief continues to be a subject of debate. The aim of this study was to compare the technical and clinical outcomes in patients with inoperable cholangiocarcinoma who received unilateral or bilateral self-expanding metal stents (SEMS). Methods We conducted a multicenter, international retrospective study of 187 patients with cholangiocarcinoma who received unilateral or bilateral SEMS. Outcomes included, but were not limited to, technical success, clinical success, adverse events, stent occlusion, and survival time. Results were further stratified based on the Bismuth classification. Results Fifty patients received unilateral stents and 137 patients received bilateral stents. All patients achieved technical success. The clinical success rates were 86% for unilateral stents and 82.5% for bilateral stents (P>0.99). Clinical success was not statistically different for either group when stratified by the Bismuth classification (P=0.62 and P=0.72 respectively). There were significantly more adverse events in the bilateral stents group (11.7% vs. 0%, P=0.007). There was no greater risk of stent occlusion when bilateral stents were used (unadjusted P=0.71, adjusted P=0.81). There was a greater risk of death for patients who received bilateral SEMS (hazard ratio 1.78, 95% confidence interval 1.09-2.89; P=0.02). Conclusions Unilateral and bilateral drainage had similar technical and clinical success rates. However, bilateral stents had a higher risk of death and more adverse events. Therefore, unilateral SEMS placement is sufficient for relief of biliary obstruction secondary to cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background With Canada's senior population increasing, there is greater demand for family physicians with enhanced skills in Care of the Elderly (COE). The College of Family Physicians Canada (CFPC) has introduced Certificates of Added Competence (CACs), one being in COE. Our objective is to summarize the process used to determine the Priority Topics for the assessment of competence in COE. Methods A modified Delphi technique was used, with online surveys and face-to-face meetings. The Working Group (WG) of six physicians acted as the nominal group, and a larger group of randomly selected practitioners from across Canada acted as the Validation Group (VG). The WG, and then the VG, completed electronic write-in surveys that asked them to identify the Priority Topics. Responses were compiled, coded, and tabulated to identify the topics and to calculate the frequencies of their selection. The WG used face-toface meetings and iterative discussion to decide on the final topic names. Results The correlation between the initial Priority Topic list identified by the VG and that identified by the WG is 0.6793. The final list has 18 Priority Topics. Conclusion Defining the required competencies is a first step to establishing national standards in COE. [ABSTRACT FROM AUTHOR]

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson-Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants. [ABSTRACT FROM AUTHOR]

Although the current low workforce availability of care of the elderly (COE) physicians, geriatric medicine specialists, and geriatric psychiatrists is undeniable, the ongoing demographic shift means this situation will only worsen. This evolving crisis is outlined clearly in the article "Updated Inventory and Projected Requirements for Specialist Physicians in Geriatrics" by Basu et al. [ABSTRACT FROM AUTHOR]

The poly(ADP-ribose) polymerase (PARP) family represents a new class of therapeutic targets with diverse potential disease indications. PARP1 and PARP2 inhibitors have been developed for breast and ovarian tumors manifesting double-stranded DNA-repair defects, whereas tankyrase 1 and 2 (TNKS1 and TNKS2, also known as PARP5a and PARP5b, respectively) inhibitors have been developed for tumors with elevated β-catenin activity. As the clinical relevance of PARP inhibitors continues to be actively explored, there is heightened interest in the design of selective inhibitors based on the detailed structural features of how small-molecule inhibitors bind to each of the PARP family members. Here, the high-resolution crystal structures of the human TNKS2 PARP domain in complex with 16 various PARP inhibitors are reported, including the compounds BSI-201, AZD-2281 and ABT-888, which are currently in Phase 2 or 3 clinical trials. These structures provide insight into the inhibitor-binding modes for the tankyrase PARP domain and valuable information to guide the rational design of future tankyrase-specific inhibitors. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies for identifying patients with Parkinson's disease (PD) or Parkinsonism (PKM) have been limited by their nonrandom sampling techniques and mainly veteran populations. This reduces their use for health services planning. The purpose of this study was to validate algorithms for the case ascertainment of PKM from administrative databases using primary care patients as the reference standard. Methods: We conducted a retrospective chart abstraction using a random sample of 73,003 adults aged ≥20 years from a primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Physician diagnosis in the EMR was used as the reference standard and population-based administrative databases were used to identify patients with PKM from the derivation of algorithms. We calculated algorithm performance using sensitivity, specificity, and predictive values and then determined the population-level prevalence and incidence trends with the most accurate algorithms. Results: We selected, '2 physician billing codes in 1 year' as the optimal administrative data algorithm in adults and seniors (≥65 years) due to its sensitivity (70.6-72.3%), specificity (99.9-99.8%), positive predictive value (79.5-82.8%), negative predictive value (99.9-99.7%), and prevalence (0.28-1.20%), respectively. Conclusions: Algorithms using administrative databases can reliably identify patients with PKM with a high degree of accuracy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Highlights: [•] We report the first crystal structures of SUV420H1 and SUV420H2. [•] SUV420H1 and SUV420H2 exhibit unique N-terminal and Zn-binding post-SET domains. [•] We developed the first in vitro assay for characterizing and screening SUV420H1 and SUV420H2 in a 384-well format. [Copyright &y& Elsevier]

Purpose Family physicians provide the majority of elderly patient care in Canada. Many experience significant challenges in serving this cohort. This study aimed to examine the medical problems of patients referred to a care of the elderly physician, to better understand the geriatric continuing medical education (CME) needs of family doctors. Methods A retrospective chart review of patients assessed at an urban outpatient seniors' clinic between 2003 and 2008 was conducted. Data from 104 charts were analyzed and survey follow-up with 28 of the referring family physicians was undertaken. Main outcomes include the type and frequency of medical problems actually referred to a care of the elderly physician. Clarification of future geriatric CME topics of need was also assessed. Results Preventive care issues were addressed with 67 patients. Twentyfour required discussion of advance directives. The most common medical problems encountered were osteoarthritis (42), hypertension (34), osteoporosis (32), and depression or anxiety (23). Other common problems encountered that have not been highly cited as being a target of CME included musculoskeletal and joint pain (41), diabetes (23), neck and back pain (20), obesity (11), insomnia (11), and neuropathic, fibromyalgia and "leg cramps" pain (10). The referring family physicians surveyed agreed that these were topics of need for future CME. Conclusions The findings support geriatric CME for the common medical problems encountered. Chronic pain, diabetes, obesity and insomnia continue to be important unresolved issues previously unacknowledged by physicians as CME topics of need. Future CME focusing more on process of geriatric care may also be relevant. [ABSTRACT FROM AUTHOR]

The versatility of nanodiamonds (NDs) as a polymer-embedded therapeutic vehicle was demonstrated by the development of a hybrid material consisting of a poly(ethylene glycol) diacrylate (PEGDA) hydrogel embedded with ND-drug complexes. A wide range of PEGDA structures, including single and multiple drug reservoirs, exhibited high loading capabilities and stable slow-release, augmented with the addition of ND conjugates. ND-PEGDA hydrogels were compared to unmodified, drug-embedded PEGDA hydrogels to demonstrate their robust drug sequestering capacity in vitro. Remarkably, ND-embedded hydrogels were capable of mitigating the harmful effects of burst-release by displaying slow and controlled administration of therapeutic compounds, an improvement over standard diffusion-based release profiles. The tunable customization of PEGDA hydrogel, both in structure and content, as well as its facile methods of synthesis, make this material an effective multi-therapeutic complement to the drug delivery abilities of NDs. A hybrid material that utilizes the synergy of PEGDA and ND components has the potential for applications toward a diverse array of biomedical challenges. [ABSTRACT FROM AUTHOR]

Abstract: The human PHD finger protein 20 (PHF20) is a putative transcription factor. While little is known about its cognate cellular role, antibodies against PHF20 are present in sera from patients with hepatocellular carcinoma, glioblastoma and childhood medulloblastula. PHF20 comprises two N-terminal Tudor domains, a central C2H2-link zinc finger domain and a C-terminal zinc-binding PHD domain, and is a component of some MLL methyltransferase complexes. Here, we report the crystal structures of the N-terminal Tudor domains of PHF20 and highlight the novel structural features of each domain. We also confirm previous studies suggesting that the second Tudor domain of PHF20 exhibits preference for dimethylated histone substrates. [Copyright &y& Elsevier]

Abstract: We present here the crystal structures of human lamin B1 globular tail domain and coiled 2B domain, which adopt similar folds to Ig-like domain and coiled-coil domain of lamin A, respectively. Despite the overall similarity, we found an extra intermolecular disulfide bond in the lamin B1 coil 2B domain, which does not exist in lamin A/C. In addition, the structural analysis indicates that interactions at the lamin B1 homodimer interface are quite different from those of lamin A/C. Thus our research not only reveals the diversely formed homodimers among lamin family members, but also sheds light on understanding the important roles of lamin B1 in forming the nuclear lamina matrix. Structured summary of protein interactions: Lamin-B and Lamin-B bind by x-ray crystallography (View interaction) [Copyright &y& Elsevier]

SMN (Survival motor neuron protein) was characterized as a dimethyl-arginine binding protein over ten years ago. TDRD3 (Tudor domain-containing protein 3) and SPF30 (Splicing factor 30 kDa) were found to bind to various methyl-arginine proteins including Sm proteins as well later on. Recently, TDRD3 was shown to be a transcriptional coactivator, and its transcriptional activity is dependent on its ability to bind arginine-methylated histone marks. In this study, we systematically characterized the binding specificity and affinity of the Tudor domains of these three proteins quantitatively. Our results show that TDRD3 preferentially recognizes asymmetrical dimethylated arginine mark, and SMN is a very promiscuous effector molecule, which recognizes different arginine containing sequence motifs and preferentially binds symmetrical dimethylated arginine. SPF30 is the weakest methyl-arginine binder, which only binds the GAR motif sequences in our library. In addition, we also reported high-resolution crystal structures of the Tudor domain of TDRD3 in complex with two small molecules, which occupy the aromatic cage of TDRD3. [ABSTRACT FROM AUTHOR]

Aim: To determine the risk factors for developing phacomorphic glaucoma in eyes with mature cataracts.Materials and Methods: This is a case-control study comprising of 90 eyes with phacomorphic glaucoma and 90 age- and sex-matched control eyes with mature cataracts without phacomorphic glaucoma. Patients with pre-existing glaucoma, previous intraocular surgery and /or absence of documented axial lengths were excluded from this study. Binary logistic regression analysis of the variables, axial length and anterior chamber depth, was performed. Anterior chamber depth of the contralateral eye was used as a proxy measure of the pre-phacomorphic state in the eye with phacomorphic glaucoma as majority of them first presented to our center during the phacomorphic attack without prior measurements of the pre-phacomorphic ACD or lens thickness; therefore, their anterior chamber depth would not be representative of their pre-phacomorphic state. Axial length of 23.7 mm was selected as a cut-off for dichotomized logistic regression based on the local population mean from published demographic data.Results: The mean age was 73.1 ± 10.2 years. All phacomorphic and control eyes were ethnic Chinese. The mean presenting intraocular pressures were 49.5 ± 11.8 mmHg and 16.7 ± 1.7 mmHg in the phacomorphic and control eyes respectively (P< 0.0001), whilst the median Snellen best corrected visual acuity were light perception and hand movement in the phacomorphic and control eyes respectively. Eyes with phacomorphic glaucoma had shorter axial length of 23.1 ± 0.9 mm median when compared with that of control eyes, 23.7 ± 1.5 mm (P = 0.0006). Eyes with AL ≤ 23.7 mm were 4.3 times as likely to develop phacomorphic glaucoma when compared with AL > 23.7 mm (P = 0.003).Conclusion: Axial length less than ≤ 23.7 mm was a risk factor for developing phacomorphic glaucoma. Eyes with AL shorter than the population mean were 4.3 times as likely to develop phacomorphic glaucoma compared with eyes with longer than average AL. In an area where phacomorphic glaucoma is prevalent and medical resources are limited, patients with AL shorter than their population mean may be considered for earlier elective cataract extraction as a preventive measure. [ABSTRACT FROM AUTHOR]

To determine the risk factors for developing phacomorphic glaucoma in eyes with mature cataracts. Materials and Methods: This is a case-control study comprising of 90 eyes with phacomorphic glaucoma and 90 age- and sex-matched control eyes with mature cataracts without phacomorphic glaucoma. Patients with pre-existing glaucoma, previous intraocular surgery and /or absence of documented axial lengths were excluded from this study. Binary logistic regression analysis of the variables, axial length and anterior chamber depth, was performed. Anterior chamber depth of the contralateral eye was used as a proxy measure of the pre-phacomorphic state in the eye with phacomorphic glaucoma as majority of them fi rst presented to our center during the phacomorphic att ack without prior measurements of the prephacomorphil ACD or lens thickness; therefore, their anterior chamber depth would not be representative of their pre-phacomorphic state. Axial length of 23.7 mm was selected as a cut-off for dichotomized logistic regression based on the local population mean from published demographic data. Results: The mean age was 73.1 ± 10.2 years. All phacomorphic and control eyes were ethnic Chinese. The mean presenting intraocular pressures were 49.5 ± 11.8 mmHg and 16.7 ± 1.7 mmHg in the phacomorphic and control eyes respectively (P< 0.0001), whilst the median Snellen best corrected visual acuity were light perception and hand movement in the phacomorphic and control eyes respectively. Eyes with phacomorphic glaucoma had shorter axial length of 23.1 ± 0.9 mm median when compared with that of control eyes, 23.7 ± 1.5 mm (P = 0.0006). Eyes with AL = 23.7 mm were 4.3 times as likely to develop phacomorphic glaucoma when compared with AL > 23.7 mm (P = 0.003). Conclusion: Axial length less than = 23.7 mm was a risk factor for developing phacomorphic glaucoma. Eyes with AL shorter than the population mean were 4.3 times as likely to develop phacomorphic glaucoma compared with eyes with longer than average AL. In an area where phacomorphic glaucoma is prevalent and medical resources are limited, patients with AL shorter than their population mean may be considered for earlier elective cataract extraction as a preventive measure. [ABSTRACT FROM AUTHOR]

The article offers a design of the X-CHIP device and the accompanying tools for setting up crystallization trials and mounting the chip for data collection and the benefits, limitations and implications inherent to this platform. The protein kinase domain of human ephrin receptor tyrosine kinase and the Pseudomonas aeruginosa alkylhydroperoxidase D protein were chosen as model proteins to show the feasibility of crystal growth using X-CHIP. It concludes that X-CHIP increases efficiency and offers the opportunity for full automation.

The rational design of novel antibiotics for bacteria involves the identification of inhibitors for enzymes involved in essential biochemical pathways in cells. In this study, the cloning, expression, purification, crystallization and structure of the enzyme peptidyl-tRNA hydrolase from Francisella tularensis, the causative agent of tularemia, was performed. The structure of F. tularensis peptidyl-tRNA hydrolase is comparable to those of other bacterial peptidyl-tRNA hydrolases, with most residues in the active site conserved amongst the family. The resultant reagents, structural data and analyses provide essential information for the structure-based design of novel inhibitors for this class of proteins. [ABSTRACT FROM AUTHOR]

Background: Expansion of the CGG trinucleotide repeat in the 5′-untranslated region of the FMR1, fragile X mental retardation 1, gene results in suppression of protein expression for this gene and is the underlying cause of Fragile X syndrome. In unaffected individuals, the FMRP protein, together with two additional paralogues (Fragile X Mental Retardation Syndrome-related Protein 1 and 2), associates with mRNA to form a ribonucleoprotein complex in the nucleus that is transported to dendrites and spines of neuronal cells. It is thought that the fragile X family of proteins contributes to the regulation of protein synthesis at sites where mRNAs are locally translated in response to stimuli. Methodology/Principal Findings: Here, we report the X-ray crystal structures of the non-canonical nuclear localization signals of the FXR1 and FXR2 autosomal paralogues of FMRP, which were determined at 2.50 and 1.92 Å, respectively. The nuclear localization signals of the FXR1 and FXR2 comprise tandem Tudor domain architectures, closely resembling that of UHRF1, which is proposed to bind methylated histone H3K9. Conclusions: The FMRP, FXR1 and FXR2 proteins comprise a small family of highly conserved proteins that appear to be important in translational regulation, particularly in neuronal cells. The crystal structures of the N-terminal tandem Tudor domains of FXR1 and FXR2 revealed a conserved architecture with that of FMRP. Biochemical analysis of the tandem Tudor doamins reveals their ability to preferentially recognize trimethylated peptides in a sequence-specific manner. Enhanced version: This article can also be viewed as an enhanced version (http://plosone.org/enhanced/pone.0013559/) in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1. [ABSTRACT FROM AUTHOR]

Urease plays a central role in the pathogenesis of Helicobacter pylori in humans. Maturation of this nickel metalloenzyme in bacteria requires the participation of the accessory proteins UreD (termed UreH in H. pylori), UreF, and UreG, which form sequential complexes with the urease apoprotein as well as UreE, a metallochaperone. Here, we describe the crystal structure of C-terminal truncated UreF from H. pylori (residues 1-233), the first UreF structure to be determined, at 1.55 Å resolution using SAD methods. UreF forms a dimer in vitro and adopts an all-helical fold congruent with secondary structure prediction. On the basis of evolutionary conservation analysis, the structure reveals a probable binding surface for interaction with other urease components as well as key conserved residues of potential functional relevance. Proteins 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

IpaH proteins are E3 ubiquitin ligases delivered by the type III secretion apparatus into host cells upon infection of humans by the Gram-negative pathogen Shigella flexneri. These proteins comprise a variable leucine-rich repeat–containing N-terminal domain and a conserved C-terminal domain harboring an invariant cysteine residue that is crucial for activity. IpaH homologs are encoded by diverse animal and plant pathogens. Here we demonstrate that the IpaH C-terminal domain carries the catalytic activity for ubiquitin transfer and that the N-terminal domain carries the substrate specificity. The structure of the IpaH C-terminal domain, determined to 2.65-Å resolution, represents an all-helical fold bearing no resemblance to previously defined E3 ubiquitin ligases. The conserved and essential cysteine residue lies on a flexible, surface-exposed loop surrounded by conserved acidic residues, two of which are crucial for IpaH activity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the reporting quality of key methodological items in randomized controlled trials (RCTs) in four general clinical ophthalmology journals.Methods: The reporting of 11 key methodological items in RCTs published in American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology and Ophthalmology in the year 2005 was assessed. Results : Sixty-seven eligible RCTs were assessed and the mean number of items reported was 6.3 per RCT. No significant difference in the mean number of items reported was found between the four journals (P = 0.20). The most frequently reported item was ethics approval and informed consent (97.0%), followed by masking status (85.1%), description of withdrawals (76.1%), adverse events (73.1%), and intention-to-treat analysis (71.6%). Details on sequence generation, randomization restriction, allocation concealment, allocation implementation, patient flow diagrams, and sample size calculation were reported in < 50% of the RCTs assessed. Both sample size and page length of the RCTs correlated with the number of methodological items reported (P = 0.024 and P = 0.008, respectively). Conclusions: Similar to other specialties, rooms for improvement exist in the reporting of key methodological items of RCTs in clinical ophthalmic journals. Stricter adoption of the CONSORT statement might enhance the reporting quality of RCTs in ophthalmic journals. [ABSTRACT FROM AUTHOR]

Purpose: Extensive efforts have been devoted to determining the macular pigment optical density (MPOD) in Caucasian subjects. Unfortunately, no such data in ethnic groups with naturally dark irises are currently available. In this study, we report the values in a sample of Chinese subjects.Methods: The MPOD was measured psychophysically using a densitometer at 0.25?, 0.50? 1.00?, and 2.00? eccentricity from the foveal center in 92 Chinese subjects. Results: The spatial profile for the averaged MPOD was approximately exponential in form and showed a decline with age (r = ?0.23). Subjects aged below 60 years had significantly higher averaged MPOD than those aged 60 years or above. Significant gender differences, in favor of males, were also found in the middle-age groups. Conclusions: Our study reports for the first time the MPOD in a Chinese population. Baseline information on MPOD would aid future research in preventive measures against age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Muir-Torre syndrome is a rare, autosomal dominant condition characterized by the presence of a skin tumor of sebaceous differentiation and visceral malignancies. We reviewed the case of a 46-year-old Chinese man who had a bleeding mass over the right upper eyelid. He had a history of colon cancer and a family history satisfying the Amsterdam criteria for hereditary non-polyposis colorectal cancer syndrome with germline mutation in the MutS homolog-2 gene. The eyelid lesion was excised completely and submitted for histopathologic examination which showed sebaceous carcinoma. Frozen section and conjunctival map biopsy showed no residual malignancy or local metastasis. Post-operative positron-emission tomography with combined computed tomography did not reveal any residual or visceral malignancy. He had no recurrence in the 32-month follow-up period. We should consider Muir-Torre syndrome in patients with sebaceous carcinoma, especially in the presence of personal and/or family history of visceral malignancies. [ABSTRACT FROM PUBLISHER]

Mathematical models for predicting the temperature and thermal degradation have been developed, which include all important phenomena during the engagement of wet friction clutch. The thermal model consists of heat balance for the separator, friction lining, core plate, and ATF in the clearance. The degradation mechanism and constants for the selected friction material obey the zeroth order reaction. The model predictions show good agreement with experimental measurements. [ABSTRACT FROM AUTHOR]

Assesses depressive symptomatology and its correlates in a sample of Chinese American elderly residing in a mid-western city. Results showing increased prevalence of depressive symptomatology; Views regarding the relationship between acculturation and depression in Chinese Americans; Impact of English language proficiency.