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Introduction: Infertility, marked by the inability to conceive after a year of unprotected intercourse, is a pressing global issue. This study aims to delve into the causes and presentation patterns of male factor infertility, which constitutes 40% of infertility cases worldwide. Despite its significance, male infertility often receives less attention in research. Understanding its etiology and clinical manifestations is vital for effective management, making this study's focus on male infertility crucial. Materials and Methodology: This retrospective study was conducted at a tertiary care center in India from July 2020 to December 2022. Semen analysis was performed on partners of infertile females attending the gynecological outpatient department. Participants aged 25-40 years with male factor infertility were included. Data were collected through questionnaires and clinical examinations. Statistical analysis was performed using EPI INFO software. Result: Among 152 infertile couples, 50 were identified with male factor infertility. The mean age of participants was 34.5 years. A significant proportion of couples (38.15%) had been married for less than five years. The main cause of infertility in the study population was male factor infertility (33%). Secondary infertility was observed in 22% of cases. Participants were predominantly educated at the university level (55.3%) and employed (63.2%). Environmental and social exposures, such as alcohol consumption and cigarette smoking, were reported by a minority of participants. Conclusion: Male factor infertility remains a prevalent issue, with unexplained infertility comprising a significant proportion of cases. Variability in semen analysis standards and potential recall bias among patients were identified as study limitations. Investment in diagnostic technologies and health education initiatives targeting men are essential for addressing male infertility effectively. Further research is needed to explore the complexities of male factor infertility and improve diagnosis and management strategies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a liver malignancy that affects more than a million people worldwide with a complex multifactorial etiology. After the diagnosis of HCC is made, physicians establish management using the Barcelona Clinic Liver Cancer (BCLC) guidelines revolving around tumor stage, liver function, performance status, and patient preferences. According to recent updates to these guidelines, thermal ablation is the second-best curative option apart from surgical resection for small HCC (< 2 cm). While thermal ablation is standard of care, recent studies have suggested that radiation segmentectomy (RS) has similar outcomes, limited hepatotoxicity, and ultimately a cost-efficient approach. Although there is limited literature on RS, this article compares ablation techniques against radiation segmentectomy for small HCC tumors. [ABSTRACT FROM AUTHOR]

Uterine fibroids and adenomyosis are prevalent benign neoplasms that can lead to serious deleterious health effects including life-threatening anemia, prolonged menses, and pelvic pain; however, up to 40% of women remain undiagnosed. Traditional treatment options such as myomectomy or hysterectomy can effectively manage symptoms but may entail longer hospital stays and hinder future fertility. Endovascular treatment, such as uterine artery embolization (UAE), is a minimally invasive procedure that has emerged as a well-validated alternative to surgical options while preserving the uterus and offering shorter hospital stays. Careful patient selection and appropriate techniques are crucial to achieving optimal outcomes. There have been advancements in recent times that encompass pre- and postprocedural care aimed at enhancing results and alleviating discomfort prior to, during, and after UAE. Furthermore, success and reintervention rates may also depend on the size and location of the fibroids. This article reviews the current state of endovascular treatments of uterine fibroids and adenomyosis. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies such as sickle cell disease (SCD) are traditionally considered a relative contraindication to free tissue transfer, due to concerns that erythrocyte sickling will increase the risk of microvascular thrombosis and flap failure. This article describes a case report with the successful use of free tissue transfer in a patient with SCD and provides a systematic literature review on free tissue transfer in SCD. A retrospective chart review was performed of a patient with SCD who underwent free tissue transfer at the authors' institution. A systematic literature review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using the keywords "free tissue transfer," "free flap," or "microsurgery" and "sickle cell" on PubMed, Ovid/Medline, and Scopus. A 29-year-old male with delayed presentation of an electrical burn to the face and scalp underwent wound closure with a free anterolateral thigh flap. Key management principles included red blood cell transfusion to keep hemoglobin S under 30% and hemoglobin greater than 10 g/dL, maintenance of hydration, normothermia, adequate analgesia, and postoperative anticoagulation. Systematic literature review identified 7 articles describing 13 cases of free tissue transfer in 10 patients with SCD, with combined complete free flap success in 10 of the 13 flaps. Free tissue transfer can be successfully performed in patients with SCD. However, evidence on the optimal management of this unique patient population in the perioperative period after free tissue transfer is limited to case reports in the literature. [ABSTRACT FROM AUTHOR]

Infliximab gehört zur Familie der Tumornekrosefaktor (TNF)-alpha-Inhibitoren und hat seit seiner Entwicklung die Behandlung von rheumatischen Erkrankungen und chronisch entzündlichen Darmerkrankungen (CED) revolutioniert. Insbesondere bei CED hat sich gezeigt, dass es zu einer symptomatischen, endoskopischen und histologischen Remission führt. Die Behandlung mit Infliximab ist daher eine der am häufigsten eingesetzten Therapien bei mittelschweren bis schweren CED. Häufige Nebenwirkungen sind Infektionen durch Immunsuppression, Zytopenien und Hepatotoxizität, aber auch interstitielle Lungenerkrankungen (ILD) wurden in seltenen Fällen als Folge der Einnahme von Inflixiamb berichtet. Wir stellen den Fall eines Patienten mit Colitis ulcerosa (CU) vor, der mit Infliximab eine Remission erreichte, aber nach etwa 2 Jahren mit Infusionen Anzeichen einer unspezifischen interstitiellen Pneumonitis (UIP) entwickelte. Umfangreiche Untersuchungen wurden durchgeführt, um Infektionen, gemischte Bindegewebserkrankungen und Hypersensitivitätspneumonitis auszuschließen. Obwohl die Lungenbiopsie nach wie vor der Goldstandard für die Diagnose von UIP ist, reichten die klinischen, laborchemischen und radiologischen Befunde aus, um die Diagnose zu stellen. Der Beginn einer empirischen Therapie mit hochdosierten Steroiden und das Absetzen der Infliximab-Infusionen zeigten eine Verbesserung des respiratorischen Status und eine Rückbildung der pulmonalen Befunde. Dieser Fall unterstreicht, wie wichtig es ist, die unerwünschten Wirkungen von Infliximab auf den Lungenstatus von CED-Patienten zu erkennen, da die Infliximab-vermittelte ILD keinem bestimmten Zeitplan folgt. Da die Atemfunktion nach einer beliebigen Anzahl von Infusionen beeinträchtigt sein kann, ist es wichtig, die Atembeschwerden der Patienten zu erkennen und unverzüglich eine Untersuchung und Bewertung dieser seltenen Komplikation einzuleiten. [ABSTRACT FROM AUTHOR]

Reports of cognitive impairment in inflammatory bowel disease (IBD) have been mixed. IBD and cardiovascular disease are often co-morbid, yet it remains unknown whether vascular comorbidity confers a risk for decreased cognitive functioning, as observed in other populations. Participants with IBD were recruited from a longitudinal study of immune-mediated disease. Participants were administered a standardized neuropsychological test protocol, evaluating information processing speed, verbal learning and memory, visual learning and memory, and verbal fluency/executive function. Cognitive test scores were standardized using local regression-based norms, adjusting for age, sex, and education. Vascular risk was calculated using a modified Framingham Risk Score (FRS). We tested the association between FRS and cognitive test scores using a quantile regression model, adjusting for IBD type. Of 84 IBD participants, 54 had ulcerative colitis and 30 had Crohn's disease; mean (SD) age was 53.36 (13.95) years, and a high proportion were females (n = 58). As the risk score (FRS) increased, participants demonstrated lower performance in information processing speed (β = − 0.12; 95% CI − 0.24, − 0.006) and verbal learning (β = − 0.14; 95% CI − 0.28, − 0.01) at the 50th percentile. After adjusting for IBD type and disease activity, higher FRS remained associated with lower information processing speed (β = − 0.14; 95% CI − 0.27, − 0.065). Vascular comorbidity is associated with lower cognitive functioning in persons with IBD, particularly in the area of information processing speed. These findings suggest that prevention, identification, and treatment of vascular comorbidity in IBD may play a critical role for improving functional outcomes in IBD. [ABSTRACT FROM AUTHOR]

Objective Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (LGI1-LE) is a rare autoimmune condition that affects the structural integrity and functioning of the brain's limbic system. Little is known about its impact on long-term neuropsychological functioning and the structural integrity of the medial temporal lobe. Here we examined the long-term neuropsychological and neuroanatomical outcomes of a 68-year-old male who acquired LGI1-LE. Methods Our case patient underwent standardized neuropsychological testing at two time points. Volumetric analyses of T1-weighted images were undertaken at four separate time points and qualitatively compared with a group of age-matched healthy controls. Results At the time of initial assessment, our case study exhibited focal impairments in verbal and visual episodic memory and these impairments continued to persist after undergoing a course of immunotherapy. Furthermore, in reference to an age-matched healthy control group, over the course of 11 months, volumetric brain imaging analyses revealed that areas of the medial temporal lobe including specific hippocampal subfields (e.g. CA1 and dentate gyrus) underwent a subacute period of volumetric enlargement followed by a chronic period of volumetric reduction in the same regions. Conclusions In patients with persisting neurocognitive deficits, LGI1-LE may produce chronic volume loss in specific areas of the medial temporal lobe; however, this appears to follow a subacute period of volume enlargement possibly driven by neuro-inflammatory processes. [ABSTRACT FROM AUTHOR]

The United States is changing, and its democratic process must change with it. A new nonwhite majority is emerging after decades of demographic shift. Federal voting rights doctrine, developed throughout the Civil Rights Era, is premised on a biracial conception of American society. Withering under sustained attack, federal protections have also become antiquated in a rapidly developing multiracial society. Congressional inaction, along with the Supreme Court’s seeming hostility to federally enforced voting rights protections, has left states as the primary means to create fairer democratic processes, especially when it comes to redistricting. While some states have taken the vital step to improve their map drawing processes by creating independent redistricting commissions, there have been limited new state-level protections aimed at defending minority voters’ electoral power in redistricting. Independent redistricting commissions are an attractive vector to create additional protections. Such protections can both protect minority voters’ electoral power during the map drawing process, and give minority voters the evidentiary record necessary to enforce these new protections through litigation. By targeting both redistricting requirements and the process’s transparency and accessibility, independent redistricting commissions could be a robust tool to ensure multiracial democracy. [ABSTRACT FROM AUTHOR]

Background: The initial phases of robotic surgical skills acquisition are associated with poor technical performance, such as low knot-tensile strength (KTS). Transcranial direct-current stimulation (tDCS) can improve force and accuracy in motor tasks but research in surgery is limited to open and laparoscopic tasks in students. More recently, robotic surgery has gained traction and is now the most common approach for certain procedures (e.g. prostatectomy). Early-phase robotic suturing performance is dependent on prefrontal cortex (PFC) activation, and this study aimed to determine whether performance can be improved with prefrontal tDCS. Methods: Fifteen surgical residents were randomized to either active then sham tDCS or sham then active tDCS, in two counterbalanced sessions in a double-blind crossover study. Within each session, participants performed a robotic suturing task repeated in three blocks: pre-, intra- and post-tDCS. During the intra-tDCS block, participants were randomized to either active tDCS (2 mA for 15 min) to the PFC or sham tDCS. Primary outcome measures of technical quality included KTS and error scores. Results: Significantly faster completion times were observed longitudinally, regardless of active (p < 0.001) or sham stimulation (p < 0.001). KTS was greater following active compared to sham stimulation (median: active = 44.35 N vs. sham = 27.12 N, p < 0.001). A significant reduction in error scores from "pre-" to "post-" (p = 0.029) were only observed in the active group. Conclusion: tDCS could reduce error and enhance KTS during robotic suturing and warrants further exploration as an adjunct to robotic surgical training. [ABSTRACT FROM AUTHOR]

Thyrotoxic hypokalaemic Periodic Paralysis (TPP) is a medical emergency usually seen in Grave's disease, commonly in persons of oriental descent. The present case is a rare first time presentation of TPP in association with acute viral hepatitis A. A 46-yearold female presented with weakness, vomiting, fever, altered sensorium and yellow discolouration for 20 days. She was diagnosed to have hepatic failure due to viral hepatitis A. Her serum potassium level was 1.79 mmol/L. Treatment for hepatic failure and i.v. potassium chloride replacement was started. Sensorium improved but severe hypokalaemia and flaccid paralysis persisted. Thyroid functions were assessed and thyrotoxicosis due to Grave's disease was diagnosed. Carbimazole and systemic corticosteroids were also started and potassium infusion was continued. Serum potassium became normal only after thyroid hormones reached normal limits followed by improvement in muscle weakness. TPP can be precipitated in conditions of stress, thyroid functions should be assessed in cases of hypokalaemic periodic paralysis even in absence of overt thyroid disease. [ABSTRACT FROM AUTHOR]

Forecasts from NOAA's Global Forecast System (GFS) and the High‐Resolution Rapid Refresh (HRRR) weather models are matched to surface observations for the winter season of November 2019 to March 2020 at 210 airports across the United States. The 2‐m temperature errors, conditioned on observed weather conditions such as cloud cover amount and wind speed, are used to determine the nature of systematic model biases. We observe a strong diurnal cycle in 2‐m temperature errors in the GFS in conditions with ≤50% and ≤25% sky cover, with a 1°C warm bias at night and a 2°C cold bias during the day. The HRRR, which uses a different set of physical parameterizations, does not have a clear diurnal cycle in errors under the same conditions. These results highlight the utility of weather‐conditional comparisons across the diurnal cycle to diagnose sources of model weaknesses and to target model improvements. Plain Language Summary: We evaluate the output from weather forecast models compared to observations at 210 airports across the United States during the November 2019 to March 2020 winter season. We focus on near‐surface air temperature errors in the Global Forecast System (GFS) and High‐Resolution Rapid Refresh (HRRR) weather models for different times of day and subsets of observed weather conditions. The GFS is 1°C too warm at night and 2°C too cold during the day in conditions with ≤50% and ≤25% cloud cover. The daily high and low temperatures have smaller errors in the HRRR model, which has different algorithms than the GFS model. Model refinement and development efforts would benefit from a focus on accurate representation of the diurnal cycle of temperatures as this basic characteristic of weather can reveal strengths and weaknesses in the model physics. Key Points: National Oceanic and Atmospheric Administration (NOAA)'s global forecast system (GFS) model struggles to adequately represent the diurnal cycle of temperatures under observed conditions of ≤50% and 25% cloud coverNOAA's high‐resolution rapid refresh (HRRR) model uses a different physics suite and does not have a strong diurnal cycle of temperature errors under the same conditionsExamination of errors using similar weather conditions helps to constrain the portion of model physics that can yield larger forecast errors [ABSTRACT FROM AUTHOR]

Drug-device combination products should be safe and effective for intended uses by intended users under intended use environment during human factor (HF) studies. All known use errors and use-related problems should be considered during design of device and use-related risk analysis. Availability of such information in a compiled manner is scarce. This review compiles information of use errors reported during HF validation studies of biological combination products (drug + device) approved by USFDA's Centre for Drug Evaluation and Research between 21 June 2011 and 31 December 2019. Information regarding product, indication, type of devices, use errors, root causes and mitigation strategies were collected from published documents. Total 280 use errors were reported during HF validation studies of 39 devices across 5 categories. Overall approach and methodology for use error data collection during HF validation studies was in line with the US FDA recommendations. Performance of participants for critical and essential tasks was evaluated during HF validation studies via simulated use assessment, knowledge task assessment and interview. The root causes for use errors reported during HF validation studies were identified and use errors were mitigated by suitable corrective measures. Instructions for use clarification/improvement and labelling improvement were the most common mitigation strategies implemented across devices. [ABSTRACT FROM AUTHOR]

Rotator cuff calcific tendinopathy and arthrofibrosis of the shoulder (adhesive capsulitis) are debilitating musculoskeletal disorders that significantly impact joint function and impair quality of life. Despite its high prevalence and common clinical presentation, the metabolic mechanisms underlying these conditions characterized by pain, and reduced mobility, remain poorly understood. This review aims to elucidate the role of metabolic processes implicated in the pathogenesis of calcific tendinopathy and shoulder arthrofibrosis. We will be focusing on the mechanistic role of how these processes contribute to disease progression and can direct potential therapeutic targets. Calcific tendinopathy is marked by aberrant calcium deposition within tendons, influenced by disrupted calcium and phosphate homeostasis, and altered cellular responses. Key molecular pathways, including bone morphogenetic proteins (BMPs), Wnt signaling, and transforming growth factor-beta (TGF-β), play crucial roles in the pathophysiology of calcification, calcium imbalance, and muscle fibrosis. In contrast, shoulder arthrofibrosis involves excessive collagen deposition and fibrosis within the shoulder joint capsule, driven by metabolic dysregulation and inflammation. The TGF-β signaling pathway and inflammatory cytokines, such as interleukin-6 (IL-6), are central to the fibrotic response. A comparative analysis reveals both shared and distinct metabolic pathways between these conditions, highlighting the interplay between inflammation, cellular metabolism, extracellular matrix remodeling, calcific deposition, and calcium migration to the glenohumeral joints, resulting in adhesive capsulitis, thereby providing insights into their pathophysiology. This review discusses current therapeutic approaches and their limitations, advocating for the development of targeted therapies that address specific metabolic dysregulations. Future therapeutic strategies focus on developing targeted interventions that address the underlying metabolic dysregulation, aiming to improve patient outcomes and advance clinical management. This review offers a comprehensive overview of the metabolic mechanisms involved in calcific tendinopathy and shoulder arthrofibrosis, providing a foundation for future research and therapeutic development. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies assessing depression and anxiety effects on cognition in multiple sclerosis (MS) are limited. Objective: We tested whether within-person fluctuations in symptoms of depression or anxiety over time affect cognition in persons with MS, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and a lifetime history of depression/anxiety disorders (DEP/ANX) but without an immune-mediated inflammatory diseases (IMID). Methods: We followed participants (MS: 255, IBD: 247, RA: 154, and DEP/ANX: 306) for 3 years. Annually, they completed the hospital anxiety and depression scale (HADS) and cognitive tests including the symbol digit modalities test (SDMT). We evaluated associations of elevated symptoms (scores ⩾ 11) of anxiety (HADS-A) and depression (HADS-D) with SDMT z -scores using multivariable linear models—estimating between-person and within-person effects. Results: Participants with MS performed worse on the SDMT than participants in the DEP/ANX cohort (β = −0.68; 95% CI: −0.88, −0.48). Participants with elevated HADS-A scores performed worse on the SDMT than those without elevated scores (β = −0.43; 95% CI: −0.65, −0.21), particularly those with RA. Time-varying within-person elevations in depressive symptoms were associated with worse SDMT performance (β = −0.12; 95% CI: −0.21, −0.021). Conclusions: Across persons, elevated symptoms of anxiety adversely affected information processing. Elevated symptoms of depression within-persons over time were associated with declines in information processing speed. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common form of neurodegenerative disease. It is an irreversible condition marked by irreversible cognitive loss, commonly attributed to the loss of hippocampal neurons due to the formation of senile plaques and neurofibrillary tangles. Although the sporadic form is the most prevalent, the presence of familial form (involving several genes such as APP, PSEN1, and PSEN2) of the disease is commonly used as a model for understanding the pathophysiology of the disease. The aim of this study is to investigate the effect of a mutation on PSEN1 and PSEN2 genes on the BBB function using induced pluripotent stem cells (iPSCs). Methods: iPSC lines from patients suffering from a familial form of Alzheimer's disease and harboring mutations in PSEN1 or PSEN2 were used in this study and compared to a control iPSC line. Cells were differentiated into brain microvascular endothelial cells (BMECs) following established differentiation protocols. Barrier function was assessed by measuring TEER and fluorescein permeability, drug transporter activity was assessed by uptake assay, glucose uptake and metabolism assessed by cell flux analyzer, mitochondrial potential by JC-1, and lysosomal acidification by acridine orange. Results: iPSC-derived BMECs from the FAD patient presenting a mutation in the PSEN1 gene showed impaired barrier function compared to the FAD patient harboring a mutation in PSEN2 and to the control group. Such impaired barrier function correlated with poor tight junction complexes and reduced drug efflux pump activity. In addition, both PSEN1 and PSEN2-BMECs displayed reduced bioenergetics, lysosomal acidification, autophagy, while showing an increase in radical oxygen species (ROS) production. Finally, PSEN1- and PSEN2-BMECs showed an elevated secretion of Aβ1–40 peptides compared to control-BMECs. Conclusions: Our study reports that iPSC-derived BMECs obtained from FAD patients showed impaired barrier properties and BMEC metabolism. In particular, mutation in the PSEN1 gene was associated with a more detrimental phenotype than mutation in PSEN2, as noted by a reduced barrier function, reduced drug efflux pump activity, and diminished glucose metabolism. Therefore, assessing the contribution of genetic mutations associated with Alzheimer's disease will allow us to better understand the contribution of the BBB in dementia, but also other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE. [ABSTRACT FROM AUTHOR]

Background: The variable anatomy and controversy of the anterolateral ligament (ALL) reflect the complex relationship among the anterolateral knee structures. Purpose/Hypothesis: The purpose was to quantify the microstructural and mechanical properties of the ALL as compared with the anterolateral capsule (ALC) and lateral collateral ligament (LCL). The primary hypotheses were that (1) there is no difference in these properties between the ALL and ALC and (2) the LCL has significantly different properties from the ALL and ALC. Study Design: Descriptive laboratory study. Methods: The LCL, ALL, and ALC were harvested from 25 cadaveric knees. Mechanical testing and microstructural analyses were performed using quantitative polarized light imaging. The average degree of linear polarization (AVG DoLP; mean strength of collagen alignment) and standard deviation of the angle of polarization (STD AoP; degree of variation in collagen angle orientation) were calculated. Results: Linear region moduli were not different between the ALC and ALL (3.75 vs 3.66 MPa, respectively; P >.99). AVG DoLP values were not different between the ALC and ALL in the linear region (0.10 vs 0.10; P >.99). Similarly, STD AoP values were not different between the ALC and ALL (24.2 vs 21.7; P >.99). The LCL had larger modulus, larger AVG DoLP, and smaller STD AoP values than the ALL and ALC. Of 25 knee specimens, 3 were observed to have a distinct ALL, which exhibited larger modulus, larger AVG DoLP, and smaller STD AoP values as compared with nondistinct ALL samples. Conclusion: There were no differences in the mechanical and microstructural properties between the ALL and ALC. The ALC and ALL exhibited comparably weak and disperse collagen alignment. However, when a distinct ALL was present, the properties were suggestive of a ligamentous structure. Clinical Relevance: The properties of the ALL are similar to those of a ligament only when a distinct ALL is present, but otherwise, for the majority of specimens, ALL properties are closer to those of the capsule. Variability in the ligamentous structure of the ALL suggests that it may be more important in some patients than others and reconstruction may be considered in selective patients. Further study is needed to better understand its selective role and optimal indications for reconstruction. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate pharmacokinetic (PK) equivalence and to compare safety of INTP24 (bevacizumab biosimilar) with that of US-bevacizumab and EU-bevacizumab in healthy male subjects.Methods: In this randomized, parallel-group, double-blind study, male subjects were randomized (1:1:1) to receive a single 1 mg/kg intravenous infusion of either INTP24, US-bevacizumab, or EU-bevacizumab. The primary endpoint was area under serum concentration (AUC) from time zero to infinity (AUC0-∞). Secondary endpoints were AUC from time zero to last quantifiable concentration (AUC0-t), maximum concentration (Cmax), other PK parameters, immunogenicity, and safety.Results: A total of 117 subjects (39/group) were dosed; 113 subjects (37, 37, and 39 in INPT24, US-bevacizumab, and EU-bevacizumab groups, respectively) completed the study and were included in the PK analysis. Baseline demographics were similar across the three groups. The 90% confidence intervals (CI) of geometric mean ratios (GMR) of ln-transformed AUC0-∞ and Cmax of INTP24 relative to US-bevacizumab and EU-bevacizumab were within the acceptance range of 80%-125% (INTP24 vs. US-bevacizumab, 96.55-112.51% and 99.16-112.79%: INTP24 vs. EU-bevacizumab, 94.84-110.17% and 96.32-109.28%). The 90% CIs of GMRs for AUC0-t was also within 80-125% for INTP24 vs. US-bevacizumab and INTP24 vs. EU-bevacizumab. Safety and immunogenicity profiles were similar across the three groups. Twenty-one (17.95%) subjects experienced at least one AE and 9 (7.69%) were ADA positive. One treatment-related serious adverse event (varicella zoster infection) was reported in INTP24 group.Conclusion: This study demonstrated PK bioequivalence of INTP24 to US-bevacizumab and EU-bevacizumab in healthy male subjects and showed similar safety and immunogenicity profiles across the treatment groups. [ABSTRACT FROM AUTHOR]

The thermodynamic analysis of Ca-looping sorption enhanced steam reforming of renewable energy source bio-butanol was carried out. The effect of reformer temperature, steam to carbon molar ratio and CaO to carbon molar ratio were investigated on the production rate of H2, CO, CO2 and CH4. The favorable reformer conditions were proposed as 600°C reformer temperature, steam to carbon molar ratio = 4 and CaO to carbon molar ratio = 1 with respect to hydrogen production rate and utility requirement of Ca-looping process. A process was developed for the application of reformer exhaust gases for solid oxide fuel cell. Performance of different reforming processes (sorption enhanced steam reforming, steam reforming and auto-thermal reforming) was evaluated in terms of overall energy efficiency. Among all these processes the auto-thermal reforming exhibited the highest overall energy efficiency of 77.30% followed by steam reforming (66.57%) and sorption enhanced steam reforming (66.04%). [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD), among the most heritable psychiatric conditions, is associated with increased pro-inflammatory blood markers and pro-inflammatory gene expression in post-mortem brain. We therefore examined the effects of pro-inflammatory single nucleotide polymorphism interleukin-1β (IL-1β) rs16944 on brain structure in adolescents with BD and healthy control (HC) adolescents. T 1 -weighted 3-T magnetic resonance imaging data were acquired for 38 adolescents with BD and 32 HC adolescents (14–20 years). Using FreeSurfer, a priori regions of interest analyses, examining hippocampus, amygdala, dorsolateral prefrontal cortex (DLPFC), and caudal anterior cingulate cortex, were complemented by exploratory whole-brain vertex-wise analyses. General linear models assessed the association between IL-1β rs16944 and the ROIs, controlling for sex, age, and intracranial volume. There was an IL-1β rs16944 polymorphism-by-diagnosis interaction effect on the DLPFC; T-carriers with BD had greater surface area compared to non-carriers with BD. Whereas, HC T-carriers had smaller DLPFC volume compared to HC non-carriers. In vertex-wise analyses, similar interactions were evident in a pars triangularis surface area cluster and a lateral occipital cortex volume cluster. Whole-brain analyses also yielded a main effect of IL-1β rs16944 polymorphism, whereby T-carriers had greater lateral occipital cortex surface area and volume. The IL-1β rs16944 polymorphism is associated with neurostructural phenotypes in cognitive and visual regions that subserve functions, including facial recognition and response inhibition, which are known to be aberrant in BD. Future studies are warranted to evaluate whether the observed rs16944-related structural differences are relevant to neurocognitive function, functional neuroimaging phenotypes and IL-1β protein levels. [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) constitutes the most abundant extracellular matrix component during brain development, only to become a minor component rapidly after birth and in adulthood to remain in specified regions. HA signaling has been associated with several neurological disorders, yet the impact of HA signaling at the blood–brain barrier (BBB) function remains undocumented. In this study, we investigated the impact of HA on BBB properties using human-induced pluripotent stem cell (iPSC) -derived and primary human and rat BMECs. The impact of HA signaling on developmental and mature BMECs was assessed by measuring changes in TEER, permeability, BMECs markers (GLUT1, tight junction proteins, P-gp) expression and localization, CD44 expression and hyaluronan levels. In general, HA treatment decreased barrier function and reduced P-gp activity with effects being more prominent upon treatment with oligomeric forms of HA (oHA). Such effects were exacerbated when applied during BMEC differentiation phase (considered as developmental BBB). We noted a hyaluronidase activity as well as an increase in CD44 expression during prolonged oxygen–glucose deprivation stress. Inhibition of HA signaling by antibody blockade of CD44 abrogated the detrimental effects of HA treatment. These results suggest the importance of HA signaling through CD44 on BBB properties. [ABSTRACT FROM AUTHOR]

Radiation-associated sarcomas are rare and aggressive types of sarcomas that can occur after exposure to ionizing radiation. We examine a case of radiation-associated undifferentiated/unclassified soft-tissue sarcoma with primary disease in the chest wall. The optimal treatment of these patients is surgical resection if possible; however, the role of chemotherapy has not been well defined. The patient described herein had a central tumor in the chest wall. Since many of these patients have borderline resectable tumors, the use of neoadjuvant chemotherapy may be helpful to downstage the tumors for possible surgical resection. In this case, doxorubicin plus ifosfamide chemotherapy was employed with a favorable therapeutic effect prior to being resected. To our knowledge this is the first report of greater than 90% necrosis in a patient with radiation-associated undifferentiated/unclassified soft-tissue sarcoma treated with chemotherapy for a borderline resectable mass. [ABSTRACT FROM AUTHOR]

Case: A 48-year-old man from North Africa with a history of infection after fixation of a humeral fracture presented 8 years later with an infected nonunion. After operative debridement, Mycobacterium tuberculosis grew on culture. Following a 2-stage surgical procedure and medical management of the tuberculosis (TB), successful union had been achieved at the 1-year follow-up. Conclusion: Nonunion of the humerus caused by TB is a rare entity, but careful attention to patient demographics can forewarn the care provider. Irrigation and debridement with the Masquelet technique followed by compression plating and an iliac crest autograft can provide positive results. [ABSTRACT FROM AUTHOR]

Radiation-associated sarcomas are rare and aggressive types of sarcomas that can occur after exposure to ionizing radiation. We examine a case of radiation-associated undifferentiated/unclassified soft-tissue sarcoma with primary disease in the chest wall. The optimal treatment of these patients is surgical resection if possible; however, the role of chemotherapy has not been well defined. The patient described herein had a central tumor in the chest wall. Since many of these patients have borderline resectable tumors, the use of neoadjuvant chemotherapy may be helpful to downstage the tumors for possible surgical resection. In this case, doxorubicin plus ifosfamide chemotherapy was employed with a favorable therapeutic effect prior to being resected. To our knowledge this is the first report of greater than 90% necrosis in a patient with radiation-associated undifferentiated/unclassified soft-tissue sarcoma treated with chemotherapy for a borderline resectable mass. [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum (F. nucleatum) is a commensal Gram‐negative anaerobic bacterium that lives in the oral cavity and gastrointestinal tract of humans. While it is a regular resident of the human oral cavity, F. nucleatum has been implicated in various infections and inflammatory conditions. This case report highlights an unusual association between F. nucleatum and isolated superior mesenteric vein (SMV) thrombosis. [ABSTRACT FROM AUTHOR]

Thermodynamic analysis of hydrogen production by steam reforming and autothermal reforming of bio-butanol was investigated for solid oxide fuel cell applications. The effects of reformer operating conditions, e.g., reformer temperature, steam to carbon molar ratio, and oxygen to carbon molar ratio, were investigated with the objective to maximize hydrogen production and to reduce utility requirements of the process and based on which favorable conditions of reformer were proposed. Process flow diagram for steam reforming and autothermal reforming integrated with solid oxide fuel cell was developed. Heat integration with pinch analysis method was carried out for both the processes at favorable reformer conditions. Power generation, electrical efficiency, useful energy for co-generation application, and utility requirements for both the processes were compared. [ABSTRACT FROM AUTHOR]

Two-stage revision total knee arthroplasty (TKA) is the standard of care for prosthetic joint infections. The first stage involves removal of the infected prosthesis and placement of an antibiotic impregnated cement spacer; following a period ranging from 4 weeks to 6 months, the spacer is then removed and replaced with a permanent prosthesis. The advantage to this approach is that antibiotic impregnated spacers provide supratherapeutic levels in the joint without toxic accumulation in serum. However, it remains important for physicians and pharmacists to be aware of antibiotic associated complications in knee revisions. We present a case of a two-stage revision total knee arthroplasty in which a cement antibiotic spacer caused acute renal failure and ultimately resulted in persistent chronic kidney disease without hemodialysis at 2 months’ follow-up. Our case reports the third highest serum tobramycin (13.7 mcg/ml) and second highest serum creatinine (8.62 mg/dl) for patients experiencing ARF due to an antibiotic spacer in two-stage revision TKA. [ABSTRACT FROM AUTHOR]

The anterolateral ligament (ALL) of the knee has gained attention recently for its potential role in rotational stability of the knee, especially in association with anterior cruciate ligament (ACL) injuries. Anatomic studies have characterized the ALL as it runs in an anteroinferior and oblique direction from the lateral distal femur to the anterolateral proximal tibia, although the prevalence and variance of this ligament are not well understood. Magnetic resonance imaging and ultrasound have identified the ligament and linked it with the classically described Segond fracture. While the ALL likely plays a role in rotational stability of the knee, further studies investigating the significance of ALL injuries and the role of ALL reconstruction in combination with ACL reconstruction are warranted. [ABSTRACT FROM AUTHOR]

Aims: Scottish Intercollegiate Guidelines Network (SIGN) guidelines require patients with colorectal cancer to wait no longer than 62 days from first referral to initiation of definitive treatment. We previously demonstrated that failure to meet with these guidelines did not appear to lead to poor outcomes in the short term. This study investigates whether this holds true over a longer period. Methods: The survival status of 1,012 patients treated for colorectal cancer between January 1999 and June 2005 was reviewed. As in the previous audit, patients were placed into four groups, standard met (elective), standard met (emergency), standard failed (elective) and standard failed (emergency). Parameters analysed were pathological staging, 30-day mortality, long-term survival and cause of death. Data was analysed using log rank and chi-squared tests. Results: Operative mortality was higher in patients meeting the standard (7% elective, 20% emergency) compared to those who did not meet the standard (4% elective, 7% emergency). The proportion of early stage disease (Dukes' A and B) was highest in elective patients who failed the standard (50%) and lowest in emergencies meeting the standard (30%). Long-term survival was greatest in elective patients who failed the standard with 52% alive in October 2011 compared to 34% of elective cases meeting the standard. The most common cause of recorded death was colorectal cancer in all groups. Conclusions: Patients who were not treated within the time frame set by the SIGN guidelines survived for longer following surgery. Reasons for this are likely to be multifactorial and include pathological cancer stage. [ABSTRACT FROM AUTHOR]

Introduction: Aim of this study is to identify and describe the MRI findings in patients with Transient Global Amnesia (TGA), specifically on Diffusion Weighted Imaging (DWI) sequence. Methods: MRI findings in 12 patients with clinical diagnosis of TGA were retrospectively analysed. MRI brain was performed with a 3T scanner on 11 patients and 1.5T scanner on 1 patient. DWI were acquired at B value of 1000 s/mm2 in 4 patients, 2000 s/mm2 in 2 patients and both 1000 and 2000 s/mm2 in 6 patients. Results: There were 7 female and 5 male patients. The mean age was 65.67 years (range 61-74 years). The median time interval between the onset of symptom and MRI scan was 47.5 hours, range 25-114 hours. 11 of the 12 patients showed punctate foci of restricted diffusion in hippocampus (mean size 3.7 mm (range 2-6.5 mm). 10 patients showed foci in left hippocampus. Nine patients showed a single focus, 1 patient showed three foci and 1 patient showed four foci. In 6 patients who had DWI MRI at both B values, scans at B value of 1000 s/mm2 revealed abnormality in 4 patients, while higher B value imaging improved sensitivity in one patient and one patient had a negative scan at both B values. Conclusion: We have highlighted the MRI finding of typical punctate foci of bright signal in hippocampus seen on DWI in patients diagnosed with TGA. Detection on a routine stroke MRI protocol can avoid need for dedicated TGA protocols or repeat scan, improving the workflow. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases share certain pathophysiological hallmarks that represent common targets for drug discovery. In particular, dysfunction of proteostasis and the resultant apoptotic death of neurons represent common pathways for pharmacological intervention. A library of aromatic carbamate derivatives based on the clinically available drug flupirtine was synthesized to determine a structure-activity relationship for neuroprotective activity. Several derivatives were identified that possess greater protective effect in human induced pluripotent stem cell-derived neurons, protecting up to 80% of neurons against etoposide-induced apoptosis at concentrations as low as 100 nM. The developed aromatic carbamates possess physicochemical properties desirable for CNS therapeutics. The primary known mechanisms of action of the parent scaffold are not responsible for the observed neuroprotective activity. Herein, we demonstrate that neuroprotective aromatic carbamates function to increase the Bcl-2/Bax ratio to an antiapoptotic state and activate autophagy through induction of beclin 1. [ABSTRACT FROM AUTHOR]

Drug-induced diabetes is one of the factors contributing to the increasing incidence of diabetes worldwide. This review considers the frequency, pathogenesis and treatment of drug-induced diabetes. Drugs that induce diabetes include hormonal therapy, especially glucocorticoids and androgen blockers, cardiovascular drugs, especially statins, beta-blockers and diuretics, antipsychotics, especially clozapine, olanzapine and quetiapine, antiretrovirals (protease inhibitors and non-reverse transcriptase inhibitors - NRTIs) and other drugs (mechanistic target of rapamycin inhibitors -mTORs, post organ transplantation drugs, tyrosine kinase inhibitors and interferon-alpha). Abnormalities of the distal gluco-regulatory pathways of hyperglycemia involve decreased insulin secretion and frequent insulin resistance, whereas the proximal defects are unknown, thus limiting targeted treatment. Drug-induced diabetes is potentially reversible and the risk is underestimated. There is little information on its long-term effects on microvascular complications as clinical trials have not been long enough and neither have they focused on these factors. Overall management includes awareness of a drug's diabetogenic potential, underlying diabetes risk, benefits and risks of continuing vs discontinuing the drug, plus a consideration of drug duration and dose. While diabetes and its severity can be identified and controlled, the likelihood of future diabetes complications frequently cannot. This, balanced against the predicted benefit of the drug, results in clinical uncertainty. Empirical approaches to drug-related hyperglycemia include decreasing the dose or selecting an alternative treatment, if possible. In the absence of drug-specific evidence, treatment of drug-induced hyperglycemia and diabetes is similar to comprehensive standard diabetes care, including lifestyle modifications, oral/injectable antidiabetic agents and insulin. Important clinical considerations include surveillance of glucose before and during treatment and, in some cases, institution of diabetes preventive measures like lifestyle modification and early treatment. Future research is needed to elucidate pathophysiology and optimal targeted treatment for drug-induced diabetes and its long-term complications. [ABSTRACT FROM AUTHOR]

The blood-brain barrier ( BBB) constitutes an important component of the neurovascular unit formed by specialized brain microvascular endothelial cells ( BMECs) surrounded by astrocytes, pericytes, and neurons. Recently, isogenic in vitro models of the BBB based on human pluripotent stem cells have been documented, yet the impact of inter-individual variability on the yield and phenotype of such models remains to be documented. In this study, we investigated the impact of inter-individual variability on the yield and phenotype of isogenic models of the BBB, using patient-derived induced pluripotent stem cells ( iPSCs). Astrocytes, BMECs, and neurons were differentiated from four asymptomatic patient-derived iPSCs (two males, two females). We differentiated such cells using existing differentiation protocols and quantified expression of cell lineage markers, as well as BBB phenotype, barrier induction, and formation of neurite processes. iPSC-derived BMECs showed barrier properties better than hCMEC/D3 monolayers; however, we noted differences in the expression and activity among iPSC lines. In addition, we noted differences in the differentiation efficiency of these cells into neural stem cells and progenitor cells (as noted by differences in expression of cell lineage markers). Such differences were reflected later in the terminal differentiation, as seen as ability to induce barrier function and to form neurite processes. Although we demonstrated our ability to obtain an isogenic model of the BBB with different patients' iPSCs, we also noted subtle differences in the expression of cell lineage markers and cell maturation processes, suggesting the presence of inter-individual polymorphisms. [ABSTRACT FROM AUTHOR]

Background: The success of the clinical use of sequencing based tests (from single gene to genomes) depends on the accuracy and consistency of variant interpretation. Aiming to improve the interpretation process through practice guidelines, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) have published standards and guidelines for the interpretation of sequence variants. However, manual application of the guidelines is tedious and prone to human error. Web-based tools and software systems may not only address this problem but also document reasoning and supporting evidence, thus enabling transparency of evidence-based reasoning and resolution of discordant interpretations. Results: In this report, we describe the design, implementation, and initial testing of the Clinical Genome Resource (ClinGen) Pathogenicity Calculator, a configurable system and web service for the assessment of pathogenicity of Mendelian germline sequence variants. The system allows users to enter the applicable ACMG/AMP-style evidence tags for a specific allele with links to supporting data for each tag and generate guideline-based pathogenicity assessment for the allele. Through automation and comprehensive documentation of evidence codes, the system facilitates more accurate application of the ACMG/AMP guidelines, improves standardization in variant classification, and facilitates collaborative resolution of discordances. The rules of reasoning are configurable with gene-specific or disease-specific guideline variations (e.g. cardiomyopathy-specific frequency thresholds and functional assays). The software is modular, equipped with robust application program interfaces (APIs), and available under a free open source license and as a cloud-hosted web service, thus facilitating both stand-alone use and integration with existing variant curation and interpretation systems. The Pathogenicity Calculator is accessible at http://calculator. clinicalgenome.org. Conclusions: By enabling evidence-based reasoning about the pathogenicity of genetic variants and by documenting supporting evidence, the Calculator contributes toward the creation of a knowledge commons and more accurate interpretation of sequence variants in research and clinical care. [ABSTRACT FROM AUTHOR]

Background: Recurrent glenohumeral instability is often a result of underlying bony defects in the glenoid and/or humeral head. Anterior glenoid augmentation with a coracoid bone block (ie, Latarjet procedure) has been recommended for glenoid bone loss in the face of recurrent instability. However, no study has investigated the effect of Latarjet augmentation in the setting of both glenoid and humeral head defects (Hill-Sachs defects). Purpose: To evaluate the glenohumeral kinematics of the Latarjet procedure in the presence of combined bony defects. Study Design: Controlled laboratory study. Methods: Eighteen fresh-frozen cadaveric specimens void of all surrounding soft tissue were tested at all combinations of glenohumeral abduction (ABD) angles of 20°, 40°, and 60° and 3 external rotation (ER) levels of 0°, 40°, and 80°. Each experiment comprised anterior dislocation by translating the glenoid under a 50-N medial load applied on the humerus, simulating the static load of soft tissue. The primary outcome measurement was defined as the percentage of intact translation (normalized distance to dislocation). Specimens were tested in an intact condition (no defect), with different combinations of defects, and with Latarjet augmentation. The Latarjet procedure was performed for 20% and 30% glenoid defects by transferring the specimen′s coracoid process anterior to the glenoid so that it was flush with the articulating surface. Results: Results depended on the position of the arm. At 20° of ABD and 0° of ER, a 20% glenoid defect decreased the percentage of intact translation regardless of the humeral head defect size (P ≤ .0001). In this same setting, Latarjet reconstruction restored translation to dislocation greater than the native intact joint for all sizes of humeral head defects. At 60° of ABD and 80° of ER, a 20% glenoid defect led to an overall decrease in translation to dislocation with increasing humeral head defects. While Latarjet augmentation resulted in increased translation to dislocation for all humeral head defect sizes, it was not able to restore translation greater than the native intact joint for large humeral head defects (31% and 44%); the normalized percentages of intact translation to dislocation were 65% and 30%, respectively. Conclusion: These results demonstrate that some degree of translation can be regained for combined bony glenoid and humeral head defects with the Latarjet procedure. However, for humeral defects larger than 31%, the rotational effect of the humeral head defect led to persistent decreased translation and to dislocation despite glenoid augmentation. Thus, directly addressing the humeral defect to restore the articular surface should be considered in these cases. Clinical Relevance: This study provides a critical value limit for combined anterior glenoid bone loss and humeral head defects. While this is a biomechanical study, the results indicate that in patients with humeral head defects greater than 31%, additional humeral-sided surgery may be needed. [ABSTRACT FROM AUTHOR]

Background: Patient-derived induced pluripotent stem cells (iPSCs) are an innovative source as an in vitro model for neurological diseases. Recent studies have demonstrated the differentiation of brain microvascular endothelial cells (BMECs) from various stem cell sources, including iPSC lines. However, the impact of the culturing conditions used to maintain such stem cell pluripotency on their ability to differentiate into BMECs remains undocumented. In this study, we investigated the effect of different sources of Matrigel and stem cell maintenance medium on BMEC differentiation efficiency. Methods: The IMR90-c4 iPSC line was maintained on mTeSR1 or in essential-8 (E-8) medium on growth factorreduced (GFR) Matrigel from three different manufacturers. Cells were differentiated into BMECs following published protocols. The phenotype of BMEC monolayers was assessed by immunocytochemistry. Barrier function was assessed by transendothelial electrical resistance (TEER) and permeability to sodium fluorescein, whereas the presence of drug efflux pumps was assessed by uptake assay using fluorescent substrates. Results: Stem cell maintenance medium had little effect on the yield and barrier phenotype of IMR90-derived BMECs. The source of GFR-Matrigel used for the differentiation process significantly impacted the ability of IMR90- derived BMECs to form tight monolayers, as measured by TEER and fluorescein permeability. However, the Matrigel source had minimal effect on BMEC phenotype and drug efflux pump activity. Conclusion: This study supports the ability to differentiate BMECs from iPSCs grown in mTeSR1 or E-8 medium and also suggests that the origin of GFR-Matrigel has a marked inpact on BMEC barrier properties. [ABSTRACT FROM AUTHOR]

Background: The vast majority of functional neuroimaging studies in posttraumatic stress disorder (PTSD) have examined the amygdala as a unitary structure. However, an emerging body of studies indicates that separable functions are subserved by discrete amygdala subregions. The basolateral subdivision (BLA), as compared with the centromedial amygdala (CMA), plays a unique role in learning and memory-based processes for threatening events, and alterations to the BLA have been implicated in the pathogenesis of PTSD. We assessed whether PTSD is associated with differential involvement of the BLA versus the CMA during successful encoding of emotionally charged events. Methods: Participants with PTSD ( n = 11) and a trauma-exposed comparison (TEC) group ( n = 11) viewed a series of photos that varied in valence (negative versus positive) and arousal (high versus low) while undergoing functional magnetic resonance imaging (fMRI). Subsequently, participants completed an old/new recognition memory test. Results: Using analytic methods based on probabilistic cytoarchitectonic mapping, PTSD was associated with greater activation of the BLA, as compared to the CMA, during successful encoding of negative scenes, a finding which was not observed in the TEC group. Moreover, this memory-related activity in the BLA independently predicted PTSD status. Contrary to hypotheses, there was no evidence of altered BLA activity during memory encoding of high arousing relative to low arousing scenes. Conclusions: Task-related brain activation in PTSD does not appear to be consistent across the entire amygdala. Importantly, memory-related processing of negative information in PTSD is associated with preferential recruitment of the BLA. [ABSTRACT FROM AUTHOR]

Background: Combined defects of the glenoid and humeral head are often a cause for recurrent shoulder instability. Purpose/Hypothesis: The aim of this study was to evaluate the influence of combined bony lesions on shoulder instability through varying glenohumeral positions. The hypothesis was that instability due to combined defects would be magnified with increasing abduction and external rotation. Study Design: Controlled laboratory study. Methods: Eighteen cadaveric shoulders were tested. Experiments were performed at combinations of glenohumeral abduction angles of 20°, 40°, and 60° and external rotations of 0°, 40°, and 80°. The various glenoid defect sizes created were 10%, 20%, and 30% of the glenoid width. Four humeral head defects were created based on humeral head diameter (6%, 19%, 31%, and 44%). Each experiment consisted of translating the glenoid in a posterior direction to simulate an anterior dislocation under a 50-N load. The instability was measured as a percentage of intact translation (ie, loss in translational distance normalized to the no-defect condition). Results: At 20° of abduction, instability increased from 100% to 85%, 70%, and 43% with increasing glenoid defect sizes of 10%, 20% and 30%, respectively, with a 6% humeral head defect. However, at a functional arm position of apprehension, these values were significantly decreased (P < .05) for humeral head defect sizes of 19%, 31%, and 44%, with translation values of 49%, 27%, and 2%, respectively. Conclusion: A humeral defect leads to rotational instability with the arm rotated into a functional position rather than a resting position. However, a significant glenoid defect can lead to loss of translation independent of changes in arm position. Combined defects as large as 44% of humeral head and 20% glenoid did not show instability at 20° of abduction and neutral position; however, defects as small as 19% humeral defect and 10% glenoid defect led to significant instability in the position of apprehension. Clinical Relevance: Instability at lower levels of abduction and external rotation clinically indicates larger bony defects and may need to be directly addressed, depending on the patient’s age and function. [ABSTRACT FROM AUTHOR]

Lornoxicam is a BCS class- II non-steroidal anti-inflammatory drug (NSAID) of oxicam class that exhibits analgesic, anti-pyretic and anti-inflammatory activities. The aim of study was to enhance the solubility of lornoxicam using different solubility enhancement techniques. Three approaches viz; hydrotropy, cosolvency and mixed solvency techniques were carried out to enhance the solubility of lornoxicam. Many hydrotropes like sodium acetate, sodium salicylate, sodium ascorbate, sodium citrate, sodium benzoate, urea and nicotinamide in different molar concentration and cosolvents like polyethylene glycol (PEG), propylene glycol and glycerin in different percentage were used to enhance the solubility of poorly soluble drug. In addition to that, a mixed solvency technique was also adopted to study maximum solubility of drug. A 7.25 fold and 26 fold increase in solubility of drug was observed compared to water by using 2M nicotinamide and 40% PEG 600, respectively. Similarly, A 358 fold solubility enhancement was obtained with mixed solvency technique using mixture of 10% sodium citrate, 10% sodium benzoate, 10% nicotinamide, 5% PEG 600, 5% PEG 400 and 5% propylene glycol. The study concluded that suitable solvent system can be developed using hydrotropy, cosolvency or mixed solvency techniques for BCS class- II category drug like lornoxicam to design suitable liquid dosage form. [ABSTRACT FROM AUTHOR]

The lateral septum (LS) is implicated in behavioral defense. We tested whether bilateral infusions of the GABA A receptor agonist muscimol into the LS suppress rats’ defensive responses to cat odor. Rats received intra-LS infusions of either saline or muscimol (40 ng/rat) and were exposed to either a piece of a cat collar that had been previously worn by a cat or to a control (cat odor free) collar. Rats exposed to the cat odor collar displayed more head-out postures, while intra-LS application of muscimol reduced the number of head-out postures. However, this reduction was also present in rats exposed to a control (cat odor free) collar. This latter finding suggests that despite its involvement in other defensive behaviors (e.g., open arm avoidance in the elevated plus maze), the LS does not selectively regulate rats’ receptor defensive responding to the olfactory cues present in our cat odor stimulus. [ABSTRACT FROM AUTHOR]

In this work, the effect of nanoparticle confinement on the magnetic relaxation of iron oxide (Fe3O4) nanoparticles (NP) was investigated by measuring the hyperthermia heating behavior in high frequency alternating magnetic field. Three different Fe3O4 nanoparticle systems having distinct nanoparticle configurations were studied in terms of magnetic hyperthermia heating rate and DC magnetization. All magnetic nanoparticle (MNP) systems were constructed using equivalent ~ 10 nm diameter NP that were structured differently in terms of configuration, physical confinement, and interparticle spacing. The spatial confinement was achieved by embedding the Fe3O4 nanoparticles in the matrices of the polystyrene spheres of 100 nm, while the unconfined was the free Fe3O4 nanoparticles well-dispersed in the liquid via PAA surface coating. Assuming the identical core MNPs in each system, the heating behavior was analyzed in terms of particle freedom (or confinement), interparticle spacing, and magnetic coupling (or dipole-dipole interaction). DC magnetization data were correlated to the heating behavior with different material properties. Analysis of DC magnetization measurements showed deviation from classical Langevin behavior near saturation due to dipole interaction modification of the MNPs resulting in a high magnetic anisotropy. It was found that the Specific Absorption Rate (SAR) of the unconfined nanoparticle systems were significantly higher than those of confined (the MNPs embedded in the polystyrene matrix). This increase of SAR was found to be attributable to high Néel relaxation rate and hysteresis loss of the unconfined MNPs. It was also found that the dipole-dipole interactions can significantly reduce the global magnetic response of the MNPs and thereby decrease the SAR of the nanoparticle systems. [ABSTRACT FROM AUTHOR]

Abstract: A correlation between the DC magnetization and hyperthermia heating rate in high frequency magnetic fields was established for two distinctively different magnetic nanoparticle (MNP) systems: (1) polystyrene (PS)/Fe3O4 based composites, consisting of 10nm diameter Fe3O4 nanoparticles embedded in the matrix of polystyrene (PS) spheres (~100nm), and (2) similar Fe3O4 nanoparticles coated with polyacrylic acid (PAA) and dispersed in water. Due to physical confinement of Fe3O4 nanoparticles in the former, the PS/Fe3O4 composite exhibited much lower magnetic hyperthermia heating compared to the latter. The reduced magnetic hyperthermia heating in the polystyrene (PS)/Fe3O4 based composites was found to be associated with strong dipolar interactions. [Copyright &y& Elsevier]

Motivation: Generating accurate transcription factor (TF) binding site motifs from data generated using the next-generation sequencing, especially ChIP-seq, is challenging. The challenge arises because a typical experiment reports a large number of sequences bound by a TF, and the length of each sequence is relatively long. Most traditional motif finders are slow in handling such enormous amount of data. To overcome this limitation, tools have been developed that compromise accuracy with speed by using heuristic discrete search strategies or limited optimization of identified seed motifs. However, such strategies may not fully use the information in input sequences to generate motifs. Such motifs often form good seeds and can be further improved with appropriate scoring functions and rapid optimization.Results: We report a tool named discriminative motif optimizer (DiMO). DiMO takes a seed motif along with a positive and a negative database and improves the motif based on a discriminative strategy. We use area under receiver-operating characteristic curve (AUC) as a measure of discriminating power of motifs and a strategy based on perceptron training that maximizes AUC rapidly in a discriminative manner. Using DiMO, on a large test set of 87 TFs from human, drosophila and yeast, we show that it is possible to significantly improve motifs identified by nine motif finders. The motifs are generated/optimized using training sets and evaluated on test sets. The AUC is improved for almost 90% of the TFs on test sets and the magnitude of increase is up to 39%.Availability and implementation: DiMO is available at http://stormo.wustl.edu/DiMOContact: rpatel@genetics.wustl.edu, ronakypatel@gmail.com [ABSTRACT FROM AUTHOR]

The objective of this study was to present the characteristics of non-spinal musculoskeletal malpractice suits with attention to rates, anatomic location, and payments in a survey of 8,265 radiologists. The malpractice histories of 8,265 radiologists from 36 states were evaluated from credentialing data required of all radiologists participating in the network of One Call Medical, Inc., a broker for imaging tests in workmen's compensation cases. Twenty six hundred of the 8,265 radiologists (31.5 %) had at least one suit. Of the 4,741 total claims, 627 (13.2 %) were related to the bones and soft tissues. Four hundred seventeen (66.1 %) of them involved the musculoskeletal system other than the spine. A cause was known for 400. Of these, 91.8 % (367/400) resulted from an alleged failure to diagnose. The foot was the most common site with a rate 6.00 cases/1,000 radiologist's person years (95 % confidence interval (CI), 4.68-7.68), and the hip was second with a rate of 5.30 cases/1,000 person years (95 % CI, 4.15-6.76). The highest median payment related to ankle injuries with a median settlement of $72,500 (interquartile range (IQR), $40,000-$161,250). The state in which the highest median settlement occurred was Maryland ($125,000; IQR, $95,000-$230,000)) whereas Utah had the highest rate of suits (5.24 cases per 1,000 person years; CI, 3.03-9.04). Claims regarding foot and hip injury were the most common, but ankle settlements incurred the highest awards. [ABSTRACT FROM AUTHOR]

The objective of this study was to present the characteristics of non-spinal musculoskeletal malpractice suits with attention to rates, anatomic location, and payments in a survey of 8,265 radiologists. The malpractice histories of 8,265 radiologists from 36 states were evaluated from credentialing data required of all radiologists participating in the network of One Call Medical, Inc., a broker for imaging tests in workmen's compensation cases. Twenty six hundred of the 8,265 radiologists (31.5 %) had at least one suit. Of the 4,741 total claims, 627 (13.2 %) were related to the bones and soft tissues. Four hundred seventeen (66.1 %) of them involved the musculoskeletal system other than the spine. A cause was known for 400. Of these, 91.8 % (367/400) resulted from an alleged failure to diagnose. The foot was the most common site with a rate 6.00 cases/1,000 radiologist's person years (95 % confidence interval (CI), 4.68-7.68), and the hip was second with a rate of 5.30 cases/1,000 person years (95 % CI, 4.15-6.76). The highest median payment related to ankle injuries with a median settlement of $72,500 (interquartile range (IQR), $40,000-$161,250). The state in which the highest median settlement occurred was Maryland ($125,000; IQR, $95,000-$230,000)) whereas Utah had the highest rate of suits (5.24 cases per 1,000 person years; CI, 3.03-9.04). Claims regarding foot and hip injury were the most common, but ankle settlements incurred the highest awards. [ABSTRACT FROM AUTHOR]

The phenomenon of Internet memes pictures with juxtaposed text that are replicated by derivative authors to the point where the pictures transcend the importance of the original posting and its underlying work-has become a pervasive component of mass Internet culture. Yet, there is little legal scholarship on the subject. This Article seeks to fill that void or at least, a small part of it-by exploring whether or not an Internet meme could survive an action for copyright infringement by asserting a fair use defense. To that end, this Article considers what Internet memes are and compares them to "actual" memes, as the term was originally conceived in Richard Dawkins's The Selfish Gene. Positing that Internet memes share many characteristics with actual memes as described by Dawkins, the Article goes on to show how those memes serve the functions of the theoretical concepts that ground the fair use defense (namely, cultural interchange, market failure, and productive consumption). The Article ultimately argues that a meme user will likely prevail if he asserts the fair use defense. [ABSTRACT FROM AUTHOR]

A simple, precise, and accurate HPLC method has been developed and validated for assay of combined dosage form of Cefixime Trihydrate and Moxifloxacin Hydrochloride in commercial pharmaceutical dosage form. Reversed-Phase liquid chromatographic analysis was performed on a BDS hypersil C18, 250mm × 4.6mm, 5μ(particle size), Thermo scientific column using standard buffer (0.1Mkh2po4 with 0.1%Tea ph4. 3) methanol 40-60v/v as eluent. The flow rate of the mobile phase was adjusted to 1.0 ml/min and the injection volume was 20 μl. Detection performed at 285nm. The retention time of Cefixime and Moxifloxacin were found to be 3.55 and 4.69 respectively. The method was validated for linearity, precision, accuracy, robustness. Response was a linear function of drug concentration in the range with 5-15 μg/ml. Intraday and Interday precision were determined. Accuracy of Cefixime was found between 98-101% and Moxifloxacin was found between 98-101%. All analytical validation parameters were determined by following the ICH guidelines and its limit. The developed method proclaimed to be precise and robust for the estimation of Cefixime and Moxifloxacin in their combined dosage form. [ABSTRACT FROM AUTHOR]