STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis.
This study was aimed to identify the biomarkers for diagnosis and reveal the immune microenvironment changes in ankylosing spondylitis (AS). GSE73754 was downloaded for the co-expression network construction and immune cell analyses. Flow cytometric analysis was performed to validate the results of bioinformatics analysis. Gene set enrichment analysis (GSEA) was performed to investigate the potential biological characteristic between different phenotypes. Pearson correlation analysis between the hub genes and the xCell score of immune cell types was performed. Signal transducer and activator of transcription 3 (STAT3) and Spi-1 proto-oncogene (SPI1) was identified as the hub genes in the datasets GSE73754. And the t-test showed that the expression level of STAT3 and SPI1 in the GSE73754 was significantly higher in AS and human leukocyte antigen (HLA)-B27(+) groups. Flow cytometric analysis showed that natural killer T cells (NKT) cells were upregulated, while Th1 cells were down-regulated in AS, which was consistent with the results obtained from bioinformatics analysis. STAT3 and SPI1 was correlated with the NKT cells and Th1 cells. STAT3 and SPI1 may be a key cytokine receptor in disease progression in AS.


Association between KIF1B rs17401966 polymorphism and hepatocellular carcinoma risk: a meta-analysis involving 17,210 subjects.
Some publications have evaluated the correlation between KIF1B rs17401966 polymorphism and hepatocellular carcinoma (HCC) with conflicting results. We performed this meta-analysis to clarify the association of KIF1B rs17401966 polymorphism and HCC risk. We searched PubMed, ISI Web of Knowledge, ScienceDirect, and Google Scholar. The combined odds ratio (OR) with 95 % confidence interval (CI) was calculated to estimate the strength of the association. Heterogeneity and publication bias were also assessed. In total, 15 case-control studies with 7,596 HCC cases and 9,614 controls were included in the meta-analysis. A significant association between KIF1B rs17401966 polymorphism and HCC risk was detected (OR = 0.81, 95 % CI 0.72-0.91, P < 0.001). We also found a significant association between KIF1B rs17401966 polymorphism and HCC risk in Chinese (OR = 0.77, 95 % CI 0.67-0.89, P < 0.001). In the subgroup analysis by gender, KIF1B rs17401966 polymorphism was significantly associated with HCC risk in man (OR = 0.57, 95 % CI 0.51-0.64, P < 0.001). In the subgroup analyses of age, the similar associations were also observed in young patients (OR = 0.50, 95 % CI 0.39-0.66, P < 0.001) and old patients (OR = 0.66, 95 % CI 0.57-0.77, P < 0.001). However, no association was observed in women subgroup (OR = 0.79, 95 % CI 0.59-1.06, P = 0.11). This meta-analysis showed a significant association between KIF1B rs17401966 polymorphism and HCC.


Trends of age at menarche and association with body mass index in Chinese school-aged girls, 1985-2010.
To estimate the shifts in age at menarche from 1985 to 2010, compare the differences of average age at menarche between urban and rural groups, and determine the association of menarche with body mass index (BMI). The data were obtained from 4 cross-sectional Chinese National Surveys on Students' Constitution and Health (1985, 1995, 2005, and 2010). In this representative sample of Chinese school-aged girls, the average age at menarche was determined using probit analysis and compared between urban and rural areas. Logistic regression was used to assess the association of BMI with the likelihood of having reached menarche. The age at menarche in Chinese girls dropped from 13.41 years to 12.47 years from 1985 to 2010. There was a significant difference in age at menarche between urban and rural girls over time, with urban girls having their menarche earlier than rural girls. Logistic regression showed that a higher BMI was strongly associated with an increased likelihood of having reached menarche, even after controlling for age, urban or rural residence, province, social economic status, and school. The analysis suggests a drop of about 4.5 months per decade in the average age at menarche over the past 25 years, and a significant inverse association between BMI and having reached menarche. Considering that both early menarche and higher BMI are significant risk factors for chronic diseases, and may act together in later years to the detriment of a woman's health, greater attention should be paid to the health of girls with earlier menarche and higher BMI.


In vitro evaluation of surface roughness, adhesion of periodontal ligament fibroblasts, and Streptococcus gordonii following root instrumentation with Gracey curettes and subsequent polishing with diamond-coated curettes.
The objective of the study was to evaluate the efficacy of an additional usage of a diamond-coated curette on surface roughness, adhesion of periodontal ligament (PDL) fibroblasts, and of Streptococcus gordonii in vitro. Test specimens were prepared from extracted teeth and exposed to instrumentation with conventional Gracey curettes with or without additional use of diamond-coated curettes. Surface roughness (Ra and Rz) was measured before and following treatment. In addition, the adhesion of PDL fibroblasts for 72 h and adhesion of S. gordonii ATCC 10558 for 2 h have been determined. Instrumentation with conventional Gracey curettes reduced surface roughness (median Ra before: 0.36 μm/after: 0.25 μm; p < 0.001; median Rz before: 2.34 μm/after: 1.61 μm; p < 0.001). The subsequent instrumentation with the diamond-coated curettes resulted in a median Ra of 0.31 μm/Rz of 2.06 μm (no significance in comparison to controls). The number of attached PDL fibroblasts did not change following scaling with Gracey curettes. The additional instrumentation with the diamond-coated curettes resulted in a two-fold increase in the number of attached PDL fibroblasts but not in the numbers of adhered bacteria. Treatment of root surfaces with conventional Gracey curettes followed by subsequent polishing with diamond-coated curettes may result in a root surface which provides favorable conditions for the attachment of PDL fibroblasts without enhancing microbial adhesion. The improved attachment of PDL fibroblasts and the limited microbial adhesion on root surfaces treated with scaling with conventional Gracey curettes followed by subsequent polishing with diamond-coated curettes may favor periodontal wound healing.


Enhancing the stability of adalimumab by engineering additional glycosylation motifs.
Monoclonal antibodies (mAbs) are of high value in the diagnostic and treatment of many debilitating diseases such as cancers, auto-immune disorders and infections. Unfortunately, protein aggregation is one of the ongoing challenges, limiting the development and application of mAbs as therapeutic products by decreasing half-life, increasing immunogenicity and reducing activity. We engineered an aggregation-prone region of adalimumab, the top selling mAb product worldwide - with additional glycosylation sites to enhance its resistance to aggregation by steric hindrance as a next generation biologic. We found that the addition of N-glycans in the Fab domain significantly enhanced its conformational stability, with some variants increasing the melting temperature of the Fab domain by >6 °C. The mutations tested had minimal impact on antigen binding affinity, or affinity to Fcγ receptors responsible for effector function. Our findings highlight the significant utility of this rational engineering approach for enhancing the conformational stability of therapeutic mAbs and other next-generation antibody formats.


Unraveling the neurophysiology of muscle fatigue.
Despite 100years of research since the seminal work of Angelo Mosso (1846-1910), our understanding of the interactions between the nervous system and muscle during the performance of fatiguing contractions remains rather rudimentary. Although the nervous system simply needs to provide an activation signal that will elicit the net muscle torque required for a prescribed action, changes in the number and diversity of synaptic inputs that must be integrated by the spinal motor neurons to accommodate the changes in the force-producing capabilities of the muscle fibers complicate the process of generating the requisite activation signal. This brief review examines two ways in which the activation signal can be compromised during sustained contractions and thereby contribute to the rate at which the muscles fatigue. These examples provide insight on the types of adjustments that occur in the nervous system during fatiguing contractions, but emphasize that much remains to be learned about the physiological processes that contribute to the phenomenon known as muscle fatigue.


On the course of goal pursuit: The influence of goal progress on explicit judgments of self-agency.
The experience of causing our own actions and resulting outcomes (i.e., self-agency) is essential for the regulation of our actions during goal pursuit. In two experiments, participants indicated experienced self-agency over presented outcomes, which varied in distance to their goal in an agency-ambiguous task. In Study 1, progress was manipulated at trial level (i.e., stimuli moved randomly or sequentially towards the goal). In Study 2, progress was constant at trial level (sequential), but varied at task level (i.e., goal discrepancy of the outcomes was random or decreased over trials). Study 1 showed that self-agency gradually increased in the progress condition as unsuccessful outcomes were objectively closer to the goal, while self-agency increased exponentially upon full goal attainment in the absence of progress. The gradual pattern for the progress condition was replicated in Study 2. These studies indicate that explicit judgments of self-agency are more flexible when there is goal progress.


Assessment of antimicrobial activity of hydrophilic betaines in osmotically stressed bacteria.
A series of hydrophilic aromatic and semi-aromatic betaines related to trigonelline was synthesized and tested for antimicrobial activity. 4-Methylthiazolium betaine was the only one that showed significant antibacterial activity towards Escherichia coli under hyperosmotic conditions. None of the tested betaines showed any evidence of osmoprotection or urea protection.


Outdoor air pollution from industrial chemicals causing new onset of asthma or COPD: a systematic review protocol.
Until today, industrial sources contribute to the multifaceted contamination of environmental air. Exposure to air pollutants has the potential to initiate and promote asthma and chronic obstructive pulmonary disease (COPD). At global scale, both entities cause the majority of about 4 million annual deaths by respiratory disease. However, we identified industrial contamination as a subgroup of air pollution that may be associated with this burden and is underinvestigated in research. Therefore, the aim of this study is to investigate associations between substances industrially released into environmental air and the occurrence of asthma and COPD in the human population. Here we present the protocol for our systematic review of the current evidence. The following determinations will be applied during the systematic review process and are specified in the protocol that complies with the PRISMA-P statement. Populations of children and adults, as well as outdoor workers, exposed to industrially released air pollutants are of interest. Eligible studies may include subjects as controls who are non- or less exposed to the investigated air pollutants. The outcomes new-onset asthma and/or COPD investigated with risk ratio, odds ratio, hazard ratio, incidence rate ratio, cumulative incidence, and incidence rate are eligible. We will search the electronic literature databases EMBASE, MEDLINE, and Web of Science for peer-reviewed reports of incidence studies and incidence case-control studies. After systematic sorting of initial records, included studies will be subjected to quality assessment. Data will be synthesized qualitatively and, if appropriate, quantitatively for risk ratio and odds ratio. We will maintain and provide a PRISMA report. Results of this systematic review may indicate alterations of incidence and risk of asthma and/or COPD in populations within industrial exposure radiuses including outdoor workplaces. Specific causal substances and compositions will be identified, but results will depend on the exposure assessment of the eligible studies. Our approach covers effects of industrial contributions to overall air pollution if studies reportedly attribute investigated emissions to industry. Results of this study may raise the question wether the available higher-level evidence sufficiently covers the current scale of industrial exposure scenarios and their potential harm to respiratory health. This protocol was registered in PROSPERO, registration number CRD42020151573 .


Pathogenetic Mechanisms Underlying Major Adverse Cardiac Events in Personality Type D Patients after Percutaneous Coronary Intervention: The Roles of Cognitive Appraisal and Coping Strategies.
This paper aimed to study the association of type D personality, coping strategies, and cognitive appraisal with annual prognosis after a percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). The prospective study included 111 CAD patients who underwent a PCI. All participants, before the PCI, completed questionnaires designed to collect information about type D personality, cognitive appraisal, and coping styles. Information was also collected on the clinical and demographic characteristics of the patients. After 1 year of follow-up, the presence of major adverse cardiac events (MACEs) was assessed. The presence of a MACE was noted in 38 patients, and the absence of a MACE was noted in 53 patients. In patients with type D personality, higher incidences of MACEs (54.1% versus 33.3%; p = 0.0489) and hospitalization rates (29.7% versus 7.4%; p = 0.004) were revealed. Patients with poor prognoses preferred a moderate use of the confrontation strategy than patients without a MACE (78.4% vs. 50.9%; p = 0.0082). Patients with MACEs had statistically significantly lower indicators of strong emotions (11.92 ± 5.32 versus 14.62 ± 4.83 points; p = 0.005) and future prospects (11.36 ± 3.81 versus 13.21 ± 3.41 points; p = 0.015) than patients without a MACE. In a multiple binary logistic regression model, the following factors had significant associations with MACE development: type D, moderate use of confrontation coping, moderate use of self-control coping, and strong emotions in cognitive appraisal. This study showed that not only personality type D, but also certain coping strategies and cognitive appraisals increase the likelihood of developing a MACE after a PCI. This provides a theoretical basis for understanding the mechanism underlying type D personality and MACEs in patients after a PCI.


Extensive calcification in a tumor of the glomus jugulare.
Extensive calcification in the intracranial portion of a glomus jugulare tumor is reported. This finding has not been reported previously in the literature. The patient probably was afflicted with this process for many years and presented with a subarachnoid hemorrhage. The combination of this tumor with subarachnoid hemorrhage is rare.


Dysregulation of IGF-1/GLP-1 signaling in the progression of ALS: potential target activators and influences on neurological dysfunctions.
The prominent causes for motor neuron diseases like ALS are demyelination, immune dysregulation, and neuroinflammation. Numerous research studies indicate that the downregulation of IGF-1 and GLP-1 signaling pathways plays a significant role in the progression of ALS pathogenesis and other neurological disorders. In the current review, we discussed the dysregulation of IGF-1/GLP-1 signaling in neurodegenerative manifestations of ALS like a genetic anomaly, oligodendrocyte degradation, demyelination, glial overactivation, immune deregulation, and neuroexcitation. In addition, the current review reveals the IGF-1 and GLP-1 activators based on the premise that the restoration of abnormal IGF-1/GLP-1 signaling could result in neuroprotection and neurotrophic effects for the clinical-pathological presentation of ALS and other brain diseases. Thus, the potential benefits of IGF-1/GLP-1 signal upregulation in the development of disease-modifying therapeutic strategies may prevent ALS and associated neurocomplications.


Healthcare staff perceptions towards influenza and potential COVID-19 vaccination in the 2020 pandemic context.
The COVID-19 pandemic generated renewed focus on infectious disease transmission in healthcare settings. This study aimed to evaluate staff perceptions towards influenza vaccination in the COVID-19 context. All healthcare workers within a major UK tertiary referral hospital were invited to answer a survey conducted from September 2nd to 13th, 2020. In all, 593 responses were received across a spectrum of roles; 44% reported they were more likely to get an influenza vaccine this year due to COVID-19; however, 10% felt that an influenza vaccine was less important due to social distancing. Additional questions evaluated intention to receive COVID-19 vaccination. There were substantial differences of opinion between staff groups.


CS-VIBE accelerates cranial nerve MR imaging for the diagnosis of facial neuritis: comparison of the diagnostic performance of post-contrast MPRAGE and CS-VIBE.
We aimed to compare the diagnostic performance of post-contrast 3D compressed sensing volume-interpolated breath-hold examination (CS-VIBE) and 3D T1 magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) in detecting facial neuritis. Between February 2019 and September 2019, 60 patients (30 facial palsy patients and 30 controls) who underwent contrast-enhanced cranial nerve MRI with both conventional MPRAGE and CS-VIBE (scan time: 6 min 8 s vs. 2 min 48 s) were included in this retrospective study. All images were independently reviewed by three radiologists for the presence of facial neuritis. In patients with facial palsy, signal-to-noise ratio (SNR) of the pons, enhancement degree and contrast-to-noise ratio (CNRnerve-CSF) of the facial nerve were measured. The overall image quality, artifacts, and facial nerve discrimination were analyzed. The sensitivity and specificity of both sequences were calculated with the clinical diagnosis as a reference. CS-VIBE had comparable performance in the detection of facial neuritis to that of MPRAGE (sensitivity and specificity, 97.8% and 99.4% vs. 100.0% and 99.4% in pooled analysis; 97.8% and 98.9% vs. 100.0% and 98.9% in patents with facial palsy, p value > 0.05 for all). CS-VIBE showed significantly lower SNR (p value < 0.001 for all), but significantly higher CNRnerve-CSF (p value < 0.05 for all) than MPRAGE. CS-VIBE also performed better in the overall image quality, artifacts, and facial nerve discrimination than MPRAGE (p value < 0.001 for all). CS-VIBE achieved comparable diagnostic performance for facial neuritis compared to the conventional MPRAGE, with the scan time being half of that of MPRAGE. • Post-contrast 3D CS-VIBE MRI is a reliable method for the diagnosis of facial neuritis. • CS-VIBE reduces the scan time of cranial nerve MRI by more than half compared to conventional T1-weighted image. • CS-VIBE had better performance in contrast-to-noise ratio and favorable image quality compared with conventional T1-weighted image.


Recent trends in cerebral palsy survival. Part I: period and cohort effects.
To determine whether the trend of improved survival among individuals with cerebral palsy (CP) in California during the 1980s and 1990s has continued during the most recent decade. In an observational cohort study we evaluated individuals with CP, aged 4 years and older, who were clients of the California Department of Developmental Services. Medical diagnoses, functional disabilities, and special health care requirements were assessed with Client Development Evaluation Reports made between 1983 and 2010. Trends in birth cohort survival were analyzed with Kaplan-Meier curves and Cox regression. Calendar year period effects were analyzed with Poisson regression. A total of 51,923 persons with CP (28,789 males [55%], 23,134 females [45%]; mean age 14y 11mo, SD 14y 1mo, range 4y 0mo to 96y 10mo) collectively contributed 662,268 years of follow-up. There were 7690 deaths for an overall mortality rate of 11.6 per 1000 persons per year. No significant birth cohort effects on survival were observed in 4-year-olds who had no severe disabilities. By contrast, children who did not lift their heads in prone position who were born in more recent years had significantly lower mortality rates (Cox hazard ratio 0.971, p<0.001) than those with comparable disabilities born earlier. With regard to calendar year period effects, we found that age-, sex-, and disability-specific mortality rates declined by 1.5% (95% CI 0.9-2.1) year-over-year from 1983 to 2010. The estimate increased to 2.5% (95% CI 1.9-3.1) per year when we additionally controlled for tube-feeding status. Mortality rates in tube fed adolescents and adults, ages 15 to 59 years, declined by 0.9% (95% CI, 0.4-1.4) per year. No improvement was observed for adolescents or adults who fed orally or for those over age 60. In fact, the ratio of age-specific mortality rates for these latter groups to those in the general population, increased by 1.7% (95% CI 1.3-2.0) per year during the study period. The trend toward improved survival has continued throughout the most recent decade. Declines in CP childhood mortality are comparable to the improvements observed in the United States general population (i.e. the mortality ratio in childhood has remained roughly constant over the last three decades). In contrast, the mortality ratio for most adolescents and adults with CP, relative to the general population, has increased.


Fluid overload is a determinant for cardiac structural and functional impairments in type 2 diabetes mellitus and chronic kidney disease stage 5 not undergoing dialysis.
Fluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease. Bioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy. Fluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e' ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e' ratio and LVMI after adjustment for multiple confounding factors. Fluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.


[Gastroesophageal reflux (II). Surgical interventions: results and indications].
ANTIREFLUX SURGERY: Peri and postoperative morbidity is higher with Nissen fundoplication than with a 180 degrees posterior fundoplasty (Toupet procedure) which carries the risk of a compromised result with time. Although a 270 degrees posterior gastric valve may be the best technique, the surgeon's skill looks more important than the procedure used, especially for laparoscopic surgery. Its advantages include reduced postoperative pain, shorter hospital stay and convalescent time. Surgery must only be entertained in patients with severe GOR disease, especially those who require continuous PPI treatment. Excluding cases of esophagitis with deep ulcers and/or stenosis, severity criteria to be taken into account are mainly symptomatic and not anatomical. Age is an important decision-making factor. Patients over 60 years of age or with any surgical risk and patients with associated severe motor disorders such as sclerodermia should be given drug therapy unless high-dose PPI are unsuccessful. Conversely, laparoscopic surgery performed by a skilled surgeon should be preferred in younger subjects, especially under 40. In the intermediate age range, patients should be informed about the advantages and drawbacks of the various methods as patient participation is essential in the decision making process.


The impact of disease distribution on survival in patients with stage III epithelial ovarian cancer cytoreduced to microscopic residual: a Gynecologic Oncology Group study.
To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual. We reviewed data from 417 stage III EOC patients cytoreduced to microscopic disease and given adjuvant intravenous platinum/paclitaxel on one of three randomized Gynecologic Oncology Group (GOG) trials. We subdivided patients into three groups based on preoperative disease burden: (1) minimal disease (MD) defined by pelvic tumor and retroperitoneal metastasis (2) abdominal peritoneal disease (APD) with disease limited to the pelvis, retroperitoneum, lower abdomen and omentum; and (3) upper abdominal disease (UAD) with disease affecting the diaphragm, spleen, liver or pancreas. We assessed the survival impact of potential prognostic factors, focusing on initial disease distribution using a proportional hazards model and estimated Kaplan-Meier survival curves. The study groups had similar clinicopathologic characteristics. Median overall survival (OS) was not reached in MD patients compared to 80 and 56 months in the APD and UAD groups (P<0.05). The five-year survival percentages for MD, APD, and UAD were 67%, 63%, and 45%. In multivariate analysis, the UAD group had a significantly worse prognosis than MD and APD both individually and combined (Progression Free Survival (PFS) Hazards Ratio (HR) 1.44; P=0.008 and OS HR 1.77; P=0.0004 compared to MD+APD). Stage III EOC patients with initial disease in the upper abdomen have a worse prognosis despite cytoreductive surgery to microscopic residual implying that factors beyond cytoreductive effort are important in predicting survival.


Neural Pathway for Gut Feelings: Vagal Interoceptive Feedback From the Gastrointestinal Tract Is a Critical Modulator of Anxiety-like Behavior.
Anxiety disorders are associated with an altered perception of the body's internal state. Therefore, understanding the neuronal basis of interoception can foster novel anxiety therapies. In rodents, the feeding status bidirectionally modulates anxiety-like behavior but how the sensing of gastrointestinal state affects anxiety remains unclear. We combined chemogenetics, neuropharmacology, and behavioral approaches in male and female rats to test whether vagal afferents terminating in the gastrointestinal tract mediate feeding-induced tuning of anxiety. Using saporin-based lesions and transcriptomics, we investigated the chronic impact of this gut-brain circuit on anxiety-like behavior. Both feeding and selective chemogenetic activation of gut-innervating vagal afferents increased anxiety-like behavior. Conversely, chemogenetic inhibition blocked the increase in anxiety-like behavior induced by feeding. Using a selective saporin-based lesion, we demonstrate that the loss of gut-innervating vagal afferent signaling chronically reduces anxiety-like behavior in male rats but not in female rats. We next identify a vagal circuit that connects the gut to the central nucleus of the amygdala, using anterograde transsynaptic tracing from the nodose ganglia. Lesion of this gut-brain vagal circuit modulated the central amygdala transcriptome in both sexes but selectively affected a network of GABA (gamma-aminobutyric acid)-related genes only in males, suggesting a potentiation of inhibitory control. Blocking GABAergic signaling in the central amygdala re-established normal anxiety levels in male rats. Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. Our results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety disorders.


SDH deficiency is very common in carotid body paragangliomas: Genetic counseling and testing should be offered to all patients.
Collectively, germline pathogenic variants in succinate dehydrogenase (SDH) genes are the most common cause of hereditary paragangliomas. Loss of immunohistochemical expression of SDHB protein (termed SDH deficiency) occurs whenever there is biallelic inactivation of any SDH gene. We sought to estimate the prevalence of SDH deficiency in patients with carotid body paragangliomas. We identified all carotid body paragangliomas that had undergone surgical excision at our institution over the last 30 years. If SDHB immunohistochemistry was not performed at the time of excision, it was performed on archived material. There were 64 carotid body paragangliomas identified in the 62 patients. Two-thirds of the patients were female, and 43 (67%) were SDH-deficient. Up to two-thirds of all carotid body paragangliomas are associated with SDH deficiency. Therefore, genetic testing and counseling should be offered to all patients with carotid body paragangliomas, regardless of age or family history.


Erratum regarding missing Declaration of Competing Interest statements in previously published articles.
[This corrects the article DOI: 10.1016/j.ebr.2019.100355.][This corrects the article DOI: 10.1016/j.ebr.2020.100380.][This corrects the article DOI: 10.1016/j.ebr.2019.100346.][This corrects the article DOI: 10.1016/j.ebr.2019.100332.].


Standardized isolation and culture of murine liver sinusoidal endothelial cells.
Isolation of murine liver sinusoidal endothelial cells (LSECs) is an exacting and finicky procedure. After exhaustive standardization, we were able to devise an easily reproducible protocol which produced consistent results. Moreover, we scripted a protocol which clarifies even the smallest of steps, following which isolation of LSECs is made significantly easier. Using the standardized LSEC isolation protocol herein, we demonstrated that the bacterial toxin pyocyanin (from Pseudomonas aeruginosa) induced a significant dose-dependent reduction in LSEC porosity, this being preventable by the enzyme catalase, but not by the enzyme superoxide dismutase.


Optimization of a quadrature birdcage coil for functional imaging of squirrel monkey brain at 9.4T.
A quadrature transmit/receive birdcage coil was optimized for squirrel monkey functional imaging at the high field of 9.4 T. The coil length was chosen to gain maximum coil efficiency/signal-to-noise ratio (SNR) and meanwhile provide enough homogenous RF field in the whole brain area. Based on the numerical simulation results, a 16-rung high-pass birdcage coil with the optimal length of 9 cm was constructed and evaluated on phantom and in vivo experiments. Compared to a general-purpose non-optimized coil, it exhibits approximately 25% in vivo SNR improvement. In addition to the volume coil, details about how to design and construct the associated animal preparation system were provided.


Ureteroneocystostomy without ureteral remodeling for grade III-V vesicoureteral reflux treatment.
Ureteral remodeling (tapering or tailoring) is often performed alongside ureteroneocystostomy (ureteric reimplantation) procedures despite limited evidence on its role in promoting reflux resolution. To investigate the efficacy of ureteroneocystostomy in the absence of adjuvant ureteral remodeling for promoting reflux resolution in grade III-V vesicoureteral reflux. A retrospective analysis identified pediatric patients who underwent open or robotic assisted ureteroneocystostomy (OUN and RAUN, respectively) without ureteral remodeling (tailoring or tapering) at a single tertiary care center. The primary endpoint of reflux resolution was defined as no reflux on latest follow up postoperative voiding cystourethrogram (VCUG). Ureteral dilation was analyzed using the ureteral diameter ratio (UDR), which normalized for image characteristics. Inclusion criteria was as follows: grade III-V reflux, accessible postoperative VCUG scan, RAUN after June 2013 following technique optimization, and no other structural urologic abnormality or associated neurogenic bladder. A total of 68 ureters were analyzed (Grade III = 28, Grade IV = 27, Grade V = 13, OUN = 23, RAUN = 45). Complete reflux resolution was achieved postoperatively in 96% (27/28) of grade III, 100% (27/27) of grade IV and 100% (13/13) grade V cases, for a combined resolution rate of 99%. In the one failed case, the preoperative UDR was in the second quartile and postoperatively, reflux diminished from grade III to grade I. Notably, no cases with UDRs in the largest quartile required tapering/tailoring for complete reflux resolution. Ureteral tapering and tailoring were unnecessary to achieve reflux resolution in grade III-V VUR by both OUN and RAUN. Additionally, the unsuccessful case was classified as grade III with a UDR value in the second quartile, suggesting that high grade reflux (IV-V) can be repaired without tapering with equal success rates to that of grade III VUR repair, which is classically not tapered. Tapering was unnecessary for complete reflux resolution in the cases with the largest ureteral diameter ratios (UDR). These findings are limited by the single center retrospective nature of the study. This study demonstrates that vesicoureteral reimplantation for resolution of grade III-V reflux is successful in the absence of ureteral remodeling techniques.


Inhibition of protein phosphatase-1 and -2A decreases the chemosensitivity of leukemic cells to chemotherapeutic drugs.
The phosphorylation of key proteins balanced by protein kinases and phosphatases are implicated in the regulation of cell cycle and apoptosis of malignant cells and influences anticancer drug actions. The efficacy of daunorubicin (DNR) in suppression of leukemic cell survival was investigated in the presence of tautomycin (TM) and calyculin A (CLA), specific membrane permeable inhibitors of protein phosphatase-1 (PP1) and -2A (PP2A), respectively. CLA (50 nM) or TM (1μM) suppressed viability of THP-1 and KG-1 myeloid leukemia cell lines to moderate extents; however, they significantly increased survival upon DNR-induced cell death. CLA increased the phosphorylation level of Erk1/2 and PKB/Akt kinases, the retinoblastoma protein (pRb), decreased caspase-3 activation by DNR and increased the phosphorylation level of the inhibitory sites (Thr696 and Thr853) in the myosin phosphatase (MP) target subunit (MYPT1) as well as in a 25kDa kinase-enhanced phosphatase inhibitor (KEPI)-like protein. TM induced enhanced phosphorylation of pRb only, suggesting that this event may be a common factor upon CLA-induced PP2A and TM-induced PP1 inhibitory influences on cell survival. Silencing PP1 by siRNA in HeLa cells, or overexpression of Flag-KEPI in MCF-7 cells coupled with inducing its phosphorylation by PMA or CLA, resulted in increased phosphorylation of pRb. Our results indicate that PP1 directly dephosphorylates pRb, while PP2A might have an indirect influence via mediating the phosphorylation level of PP1 inhibitory proteins. These data imply the importance of PP1 inhibitory proteins in controlling the phosphorylation state of key proteins and regulating drug sensitivity and apoptosis in leukemic cells.


The presence of arginine vasopressin and its mRNA in rat choroid plexus epithelium.
Arginine vasopressin (AVP) plays an important role in the regulation of secretory function and hemodynamics of choroid plexus, the primary site of cerebrospinal fluid (CSF) production. In the present study, localization of AVP and its transcripts in choroid plexus of adult male Sprague-Dawley rats was studied by immunohistochemistry and in situ hybridization histochemistry, respectively. For immunohistochemical analysis, AVP-specific polyclonal rabbit antibody was employed. Plasmid, pGrVP, containing a 232-bp fragment of rat AVP cDNA encoding the C-terminus of proAVP, was used as a probe to detect AVP mRNA. AVP-immunoreactive product was predominantly localized close to the apical (CSF-facing) membrane of choroidal epithelium while AVP transcripts were distributed throughout the cytoplasm of the cells. Our findings indicate that AVP is synthesized in choroid plexus epithelium, which suggests autocrine and/or paracrine actions of this peptide in choroidal tissue.


[Antilymphocyte-globulin and cytostatic therapy in the case of sympathetic ophthalmia (author's transl)].
The authors make known a combined immunosuppresive treatment in a case of sympathetic ophthalmia, which could not be healed by preliminary corticosteroid therapy. The authors recommend in addition to a high dosage of corticosteroids an optimal combination of cytostatics and administration of ALG.


Controversies in Fetal Surgery: Prenatal Repair of Myelomeningocele in the Modern Era.
Fetal surgery is a constantly evolving field that showed noticeable progress with the treatment of myelomeningocele (MMC) using prenatal repair. Despite this success, there are ongoing questions regarding the optimal approach for fetal myelomeningocele repair, as well as which patients are eligible. Expansion of the inclusion and exclusion criteria is an important ongoing area of study for myelomeningocele including the recent Management of Myelomeningocele Plus trial. The significant personal and financial burden required of families seeking treatment has likely limited its accessibility to the general population.


Diffuse melanosis in metastatic malignant melanoma.
The skin of a patient with diffuse melanosis as a result of malignant melanoma was examined by light microscopy, immunohistochemistry, and electron microscopy. Our findings indicate that the slate-blue discoloration in this patient was due to pigment deposition in dermal macrophages and endothelial cells. Multiple attempts to identify disseminated metastatic melanoma cells were unsuccessful.


Chinese and Indian interpretations of pain: A qualitative evidence synthesis to facilitate chronic pain management.
People from minority ethnicities often have a greater impact of chronic pain, are underrepresented at pain services, and may not benefit from treatment to the same extent as dominant cultures. The aim of this study was to review Indian and Chinese cultural views of pain and pain management, as a basis for improving management of chronic pain in migrant populations from these ethnicities. A systematic review of qualitative studies addressing pain beliefs and experiences involving Indian and Chinese participants was conducted. Thematic synthesis was used to identify themes across the studies, and the quality of the articles was appraised. Twenty-six articles were included, most of which were appraised as high quality. Five themes were identified: Making meaning of pain described the holistic interpretation of the meaning of pain; Pain is disabling and distressing described the marked physical, psychological, and spiritual impact of pain; Pain should be endured described the cultural expectation to suppress responses to pain and not be a burden; Pain brings strength and spiritual growth described the enrichment and empowerment some people experienced through living with pain, and Management of pain goes beyond a traditional or Western approach described the factors that guided people in their use of healthcare. The review identified a holistic interpretation and impact of pain in Indian and Chinese populations, with pain management guided by multiple factors that transcended a single cultural framework. Several strength-based management strategies are recommended based on preferences for traditional treatments and respect for Western healthcare.


The periphilin 1-like BFAR isoform 3 is highly expressed in transcriptionally silent oocytes and involved in RNA metabolism.
The mouse 3110001I22Rik gene located in the first intron of Bfar is considered as a Bfar variant coding for the BFARv3 protein. However, it differs from other BFAR isoforms and resembles periphilin 1 (PPHLN1) due to its two (Lge1 and serine-rich) conserved domains. We identified the BFARv3/EGFP-interacting proteins by co-immunoprecipitation coupled to mass spectrometry, which revealed 40S ribosomal proteins (RPS3, RPS14, RPS19, RPS25, RPS27), histones (H1.2, H1.4, H3.3C), proteins involved in RNA processing and splicing (SFPQ, SNRPA1, HNRNPA3, NONO, KHDRBS3), calcium signaling (HPCAL1, PTK2B), as well as HSD17B4, GRB14, POSTN, and MYO10. Co-immunoprecipitation revealed that both Lge1 and Ser-rich domains of BFARv3 were necessary for binding to RNA-interacting factors NONO and SFPQ, known to be components of paraspeckles. Reciprocal co-immunoprecipitation and the proximity ligation assay confirmed that both BFARv3 and PPHLN1 could interact with NONO and SFPQ, suggesting a new function for PPHLN1 as well. BFARv3 and its Lge1 or Ser-rich-deficient mutants preferentially localize in the nucleus. We found an accumulation of BFARv3/EGFP (but not its mutated forms) in the nuclear granules, which was enhanced in response to arsenite treatment and ionizing radiation. Although Bfar v3 is expressed ubiquitously in mouse tissues, its expression is the highest in metaphase II oocytes. The BFARv3 interactome suggests its role in RNA metabolism, which is critical for the transcriptionally silent MII oocyte. Mouse BFARv3 has no ortholog in the human genome, thus it may contribute to the differences between these two species observed in oocyte maturation and early embryonic development.


Variability in inpatient management of children hospitalized with bronchiolitis.
To determine the variability between hospitals in diagnostic testing and management interventions for children with bronchiolitis admitted to inpatient wards and identify its association with patient characteristics. A prospective, multicenter (16 hospitals), multiyear (2007-2010) observational study of children (age <2 years) hospitalized with bronchiolitis. Outcomes included variability in diagnostic testing (complete blood count, chest radiographs) and medications or interventions (bronchodilator, systemic corticosteroid, antibiotic, IV placement) by hospital. A modified Respiratory Distress Severity Score was utilized to assess severity of illness. For all outcomes, intraclass correlation coefficient (ICC) was calculated from a model to estimate the random effects of hospital without added covariates and compared to ICCs from a second model that adjusted for demographic and clinical patient characteristics. A second unadjusted and adjusted model was created for age ≥ 2 months. Of 2207 subjects, 1715 were identified as admitted to inpatient wards. We observed wide variations in the proportion of patients who received diagnostic testing (complete blood count 21-75%, chest radiograph 36-85%) and medications/interventions (bronchodilators 19-91%, systemic corticosteroids 8-44%, antibiotics 17-43%, IV placement 38-93%). Adjusting for demographic and clinical patient characteristics did not materially affect the proportion of variability attributable to hospitals (differences in ICCs with and without model adjustment <4%). Wide variations in diagnostic test utilization and management interventions seen among children with bronchiolitis treated on the inpatient wards at 16 US hospitals were not attributable to demographic or clinical patient characteristics. These results further support efforts to standardize care for bronchiolitis through active quality improvement strategies.


Lévy flights and cooperation among mobile individuals.
Mobility is a general feature of human and animal populations living in physical space. In particular, it has been observed that often these movements are of the Lévy flight type. In this paper we study the effect of such power-law distributed displacements on the evolution of cooperation in simple games played on diluted two-dimensional grids. Using numerical simulations, our results show that unconditional Lévy flights do not favor the evolution of cooperation. However, when Lévy jumps are performed as a reaction to a growing number of defectors in an individual׳s neighborhood, all games studied here, including the harder Prisoner׳s Dilemma, remarkably benefit from this simple heuristics and cooperation can evolve in the population.


Risk-Taking and Delinquent Behaviors Among Youth with and without Intellectual Disabilities.
Youth with intellectual disabilities (ID) demonstrate higher rates of disruptive behavior disorders (DBDs) than youth with typical development (TD). DBDs such as oppositional defiant disorder (ODD) predict higher rates of delinquency during adolescence. Yet, few studies have examined risk-taking and delinquency among youth with ID. We used a self-report measure to determine whether 13-year-old youth with ID (n= 23) reported higher rates of risk-taking and delinquent behavior than their TD peers (n=77). We also examined whether or not youth had a previous diagnosis of ODD. Our results suggest that youth with ID reported fewer rule-breaking and risk-taking behaviors than their TD peers. In contrast, youth with a previous diagnosis of ODD reported more of these behaviors. Our results appear discrepant from previous studies, which find higher rates of risk-taking and delinquency among youth with ID. As such, we discuss the factors that may explain our discrepant results, including our definition and assessment of ID, and the age of our participants.


Effect of phenylpiperidine opioid antagonists on food consumption and weight gain of the obese Zucker rat.
Meal-fed Zucker rats were used to determine the acute and chronic s.c. effect of certain trans-3,4-dimethyl-4-phenylpiperidines (opioid antagonists) on food consumption. In acute studies, the active compounds suppressed food intake significantly of lean and obese meal-fed Zucker rats. LY117413 was the most effective over the 4-hr period immediately after the s.c. administration of the drug. Long-term chronic s.c. administration to the meal-fed obese Zucker rat showed that LY88329 and LY117413 significantly reduced food consumption for as long as the drug was administered and resulted in a significant decrease in body weight gain when compared to nontreated control obese rats. There was no evidence for the development of tolerance to these effects of LY88329 and LY117413 in this genetically obese rat model.


Moving fast and seeing slow? The visual consequences of vigorous movement.
In active agents, sensory and motor processes form an inevitable bond. This wedding is particularly striking for saccadic eye movements - the prime target of Shadmehr and Ahmed's thesis - which impose frequent changes on the retinal image. Changes in movement vigor (latency and speed), therefore, will need to be accompanied by changes in visual and attentional processes. We argue that the mechanisms that control movement vigor may also enable vision to attune to changes in movement kinematics.


Effect of acute aluminum phosphide exposure on rats: a biochemical and histological correlation.
Aluminum phosphide (AlP), a widely used fumigant and rodenticide leads to high mortality if ingested. Its toxicity is due to phosphine liberated when it comes in contact with moisture. The exact mechanism of action of phosphine is not known. In this study male Wistar rats were used. The animals received a single dose (20mg AlP/kg body weight i.g.) orally. Basic serum biochemical parameters, activity of mitochondrial complexes, antioxidant enzymes and parameters of oxidative stress, individual mitochondrial cytochrome levels were measured along with tissue histopathology and immunostaining for cytochrome c and compared with controls. The serum levels of creatinine kinase-MB, lactate dehydrogenase, magnesium and cortisol were higher (p<0.01); the activities of mitochondrial complexes I, II, IV were observed to be significantly decreased in liver tissue in treated rats (p<0.01). The activity of catalase was lower (p<0.05) with a significant increase in lipid peroxidation (p<0.05) whereas superoxide dismutase and glutathione peroxidase were unaffected in them. There was a significant decrease in all the cytochromes in brain and liver tissues (p<0.05) with the exception of cytochrome b in brain, the levels of which remained same. Histopathology revealed congestion in most organs with centrizonal hemorrhagic necrosis in liver. Ultra structural changes indicating mitochondrial injury was observed in heart, liver and kidney tissues. There was also a marked reduction in the cytochrome-c immunostaining compared to the controls. Toxicity due to AlP appears to result as a consequence of both-energy insufficiency and oxidative stress, with a possible and preferential interaction with the tissue cytochromes.


Cloning and sequence analysis of mRNA for mouse aspartate aminotransferase isoenzymes.
The nucleotide sequences of mRNAs for the mouse mitochondrial and cytosolic aspartate aminotransferase isoenzymes (mAspAT and cAspAT) (EC 22.214.171.124) were determined from complementary DNAs. The mAspAT mRNA comprises minimally 2460 nucleotides and codes for a polypeptide of 430 amino acid residues corresponding to the precursor form of the mAspAT (pre-mAspAT). The cAspAT mRNA comprises minimally 2086 nucleotides and codes for a polypeptide of 413 amino acid residues. The region coding for the mature mAspAT and that for the cAspAT show about 53% overall homology. The former shares 49% and the latter 48% of homology, respectively, with that of the Escherichia coli aspC gene, which has been shown to code for the E. coli AspAT (Kuramitsu, S., Okuno, S., Ogawa, T., Ogawa, H., and Kagamiyama, H. (1985) J. Biochem. (Tokyo) 97, 1259-1262). When the deduced amino acid sequence of the mouse pre-mAspAT was compared with that of the pig pre-mAspAT polypeptide, we found that they share a 94% homology and that the mouse pre-mAspAT yields a presequence consisting of 29 amino acid residues and a mature mAspAT, consisting of 401 amino acid residues. These numbers and the amino acid residues present at the putative cleavage site are all in complete agreement in these two species. The deduced amino acid sequence of the mouse cAspAT shares 91% homology with that of the pig cAspAT. Comparisons of the nucleotide and deduced amino acid sequences between the mouse and E. coli AspATs suggest that the mammalian mAspAT gene is more closely related to the E. coli aspC gene than is the mammalian cAspAT gene.


Posttraumatic learning deficits correlate with initial trauma severity and chronic cellular reactions after closed head injury in male mice.
Traumatic brain injury (TBI) is often associated with sustained attention and memory deficits. As persisting neuroinflammation and neurodegeneration may contribute to posttraumatic psychomotor dysfunction, we studied the relationship of brain cellular reactions three months after a weight-drop closed head injury in male mice with posttraumatic learning and memory using automated home-cage monitoring of socially housed mice in IntelliCages as well as tests for locomotor activity, anxiety and forepaw fine motor skills. One month after TBI, deficits in place learning and cognitive flexibility in reverse learning were clearly detectable in IntelliCages and these memory deficits correlated with the initial trauma severity on the functional neuroscore. While sucrose preference or its extinction were not influenced by TBI, traumatized mice performed significantly worse in a complex episodic memory learning task. In consecutive locomotor and forepaw skilled use tests, posttraumatic hyperactivity and impairment of contralateral paw use were evident. Analysis of cellular reactions to TBI three months after injury in selected defined regions of interest in the immediate lesion, ipsi- and contralateral frontoparietal cortex and hippocampus revealed a persistent microgliosis and astrogliosis which were accompanied by iron-containing macrophages and myelin degradation in the lesion area as well as with axonal damage in the neighboring cortical regions. Microglial and astroglial reactions in cortex showed a positive correlation with the initial trauma severity and a negative correlation with the spatial and episodic memory indicating a role of brain inflammatory reactions in posttraumatic memory deficits.


FUSION regimen: ranibizumab in treatment-naïve patients with exudative age-related macular degeneration and relatively good baseline visual acuity.
To investigate the safety and efficacy of a combined fixed-interval and pro re nata regimen of ranibizumab (FUSION regimen) for treatment of exudative age-related macular degeneration in patients with good visual acuity at baseline. To establish whether similar efficacy to monthly regimens can be achieved with fewer injections, even in patients with good visual acuity. This was a prospective, open-label, consecutive interventional case series in treatment-naïve patients with exudative age-related macular degeneration. The FUSION regimen consists of three phases: 1) a loading phase of two or three injections, depending on presence or absence of choroidal neovascularization activity at first follow-up, 2) administration of one injection on disappearance of exudation, and 3) subsequent administration of two separate injections at intervals 2 months apart, and then an injection every 3 months. Endpoints included visual acuity, presence of fluid, adverse events and number of injections administered. Seventeen eyes of 17 Caucasian patients were included. Mean patient age was 76 years, and 15 patients were female. Mean baseline visual acuity was 67.5 letters (median 67), with Snellen equivalent 20/50++, ranged between 45 (20/125) and 83 (20/20--). At 3 months, mean change in best-corrected visual acuity (BCVA) was +2.3 letters (median +9) compared with baseline (p = 0.3). At 6 months, mean change in BCVA was +4.2 letters (median +9) compared with baseline (p = 0.02). At 12 months, one patient had discontinued the study. Mean change in BCVA was 5.6 (median +10) compared with baseline (p = 0.04). No patient lost ≥15 letters, and 14 patients (87.5%) lost <5 letters. The mean number of injections was 6.9. One patient experienced a retinal pigment epithelium tear; no other complications were observed. The FUSION regimen for ranibizumab has the potential to maintain visual gains achieved during the loading phase, as reported in studies with monthly injections, even in eyes with a relatively good visual acuity at baseline. These 12-month results warrant validation in a larger, randomized controlled trial.


Evaluation of matrix metalloproteinase-9 plasma levels in untreated new Relapsing-remitting multiple sclerosis patients and their first-degree family.
Matrix metalloproteinase, especially Matrix metalloproteinase-9 (MMP-9) has vital roles in the disruption of blood barrier, neuroinflammation and pathogenesis of multiple sclerosis (MS) patients. The goal of this study is to estimate the plasma levels of MMP-9 in the first-degree family of MS patients. 35 untreated patients with definite RRMS (Relapsing-Remitting Multiple sclerosis) according to the McDonald criteria, 24 healthy controls (HC) and 26 high-risk families of untreated RRMS patients were enrolled in the study. Plasma levels of MMP-9 were analyzed by ELISA (enzyme-linked immunosorbent assay). Although the plasma protein levels of MMP-9 were elevated significantly in the untreated RRMS group (P < 0.05, P = 0.0203) as compared to the control group, but the family of MS patients was not significance (P = 0.208). The mean plasma MMP-9 concentration for HC, untreated RRMS and high-risk group was 322.268 pg/ml, 611.926 pg/ml and 518.939 pg/ml respectively. MMP-9 was used to understand the role of this biomarker in the pathogenesis of MS in the high-risk group. It found that plasma levels of MMP-9 in the new cases of MS were increased considerably. Confirming the importance of MMP-9 as a predictive marker in the high-risk group will be needed more researches.


NF-kappaB promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells.
The transcription factor NF-kappaB is constitutively active in pancreatic adenocarcinoma. Here we explore the contribution of NF-kappaB to the malignant phenotype of pancreatic cancer cells in addition to its anti-apoptotic role. Block of NF-kappaB signalling by non-destructible IkappaBalpha rendered cells resistant to TGF-beta-induced epithelial-mesenchymal transition (EMT). In contrast, NF-kappaB activation by TNF-alpha or expression of constitutively active IKK2 induced an EMT-phenotype with up-regulation of vimentin and ZEB1, and down-regulation of E-cadherin. EMT could also be induced in cells with defective TGF-beta signalling. Functional assays demonstrated reduced or strongly enhanced migration and invasion upon NF-kappaB inhibition or activation, respectively.


Ambulatory Gynecologic Surgery
A retrospective study evaluated the feasibility and safety of operative gynecologic procedures performed in an ambulatory surgical center. Between July 1993 and December 1995, 5766 women (mean age 36.9 yrs, range 13-95 yrs) who were referred to our center underwent surgery. The most common preoperative diagnoses were dysfunctional bleeding, missed abortion, postmenopausal bleeding, cervical dysplasia, mullerian duct malformation, infertility, endometriosis, adhesions, desire for sterilization, adnexal mass, lower abdominal pain, ectopic pregnancy, and fibroids. A total of 2351 laparoscopies, 2 laparotomies, and 3415 vaginal procedures were performed. The most common procedures were dilatation and curettage, 1455; hysteroscopy, 1051; adnexal surgery, 810; tubal ligation, 679; abdominal myomectomy, 186; operative hysteroscopy, 145; and cone biopsy, 118. The duration of surgery was 10 to 210 minutes. Most patients (99.51%) were discharged between 2 and 8 hours after surgery. Only 28 (0.49%) had to be admitted to the hospital; 18 women had preoperatively planned admissions and 10 were unexpectedly admitted postoperatively. The intraoperative and postoperative complication rate was 0.50% (29). We believe that ambulatory surgery is safe and efficient with proper patient selection and when the surgeon and the anesthetist have significant expertise.


Flexural vibration analyses of piezoelectric ceramic tubes with mass loads in ultrasonic actuators.
Based on Timoshenko beam model, a theoretical model of radially polarized piezoelectric ceramic tubes is investigated. In the model, the piezoelectric effects are considered, and the shear correction factor is introduced which reveals effects of the size of the cross-section and Poisson's ratio. Based on the model, the particular attentions are devoted to effects of the boundary conditions at two ends on flexural resonance frequencies of the piezoelectric ceramic tubes. Changing the sizes of the tubes and the mass loads at both free ends, the variations of the flexural resonance frequencies of free-free piezoelectric ceramic tubes are calculated theoretically. Besides, the flexural resonance frequencies of the piezoelectric ceramic tube cantilevers with mass loads at one free end are also investigated theoretically. To verify accuracy of the theoretical mode, the flexural resonance frequencies for different lengths of the piezoelectric ceramic tubes and different loaded masses are measured experimentally. The theoretical results agree well with the experimental measurement, which demonstrates that the model is accurate for analyzing the flexural resonance frequencies of the piezoelectric ceramic tubes with mass loads.


Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases during Apical Periodontitis Development.
Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice. AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods. MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP.


Respiratory symptoms and spirometric abnormalities among welders in the welding workplace of the Indian unorganized sector.
Welding is one of the most hazardous professions across the globe. Several risk factors are associated with Indian unorganized welding units such as welding gases, fumes and dust particles resulting in various respiratory health problems. The objective of the present study is to examine the prevalence of respiratory symptoms, their associated factors and lung function impairment amongst the welders of the unorganized sector in India. A cross-sectional study was conducted across 283 welders of age group 18-55 years from Punjab, India who responded to the interviewer-administrated respiratory symptoms questionnaire. Also, the lung function parameters of 50 male welders (exposed group) and 50 male non-welders (control group) working in the same environment were evaluated. The prevalence of respiratory symptoms such as chronic cough (38.86%), phlegm (38.86%), shortness of breath (33.56%), wheezing (32.15%), chest tightness (36.40%,) and sputum (34.27%) was reported by the welders. The observed mean values of forced vital capacity (FVC), forced expiratory volume in 1s (FEV1) and FEV1/FVC ratio of welders were (3.37±0.175), (2.59±0.16) and (76.63±6.16) respectively and that of non-welders were (3.70±0.15), (3.05±0.25) and (82.49±7.62) respectively. The welders were found to be at significant risk of developing pulmonary diseases. Long working hours, low level of education, hazardous working conditions, lack of implementation of safety laws make welders more vulnerable to health risks. The welders of Indian unorganized sector work without any technical training related to welding and safety. Proper orientation sessions about the workplace hazards and to maintain hygiene at their workplace should be organized. Welders must be provided with Personal Protective Equipment (PPE). Welders should take proper health check-up and medication to sustain healthiness.


Quantitative histochemical investigations of semipermeable membrane techniques for the assay of acid phosphatase in skeletal muscle. III. A modified simultaneous coupling technique.
Meijer's semipermeable membrane technique for acid phosphatase was modified by treating sections immediately after incubation with 70% ethanol for 30 min at room temperature instead of with formalin. The modification improved the validity of the technique considerably, by stabilising the specific final reaction product formed in presumed enzyme-containing sites. The modified technique thus seems promising for assaying the activity of acid phosphatase in sections of skeletal muscle.


Featuring amyloids with Fourier transform infrared and circular dichroism spectroscopies.
Amyloids are fibrillar aggregates of proteins characterized by a basic scaffold consisting of cross β-sheet structure that can exert physiological or pathological effects. Both far-UV circular dichroism and Fourier transform infrared (FTIR) spectroscopies are techniques used for the fast analysis of protein secondary structure. Both techniques are complementary and preferentially used depending on the physical state of the analyte, the major secondary structure element and the relative abundance of given amino acids. Although there are special setups for working with films, circular dichroism is best suited for ideal diluted solutions of polypeptides exhibiting α-helix as major structural element and low content of aromatic residues. During the last decade, a related technique, linear dichroism, has been applied to study the orientation of protein subunits within amyloid oligomers or fibrils in solution. Alternatively, FTIR works best with concentrated solutions, solids and films, and resolves with accuracy the β-sheet composition, but it is affected by contributions of amide groups. The advent of new infrared techniques based on correlation analysis of time-dependent variations induced by external perturbations that generates two-dimensional IR maps has enabled to greatly increase spectral resolution and to extend its applicability to protein secondary structure characterization in a variety of physical environments. Within the amyloid field, conjunction of both spectroscopies has provided the first filter step for amyloid detection and has contributed to decipher the structural aspects of the amyloid formation mechanism.


Agonist-induced endocytosis of muscarinic cholinergic receptors: relationship to stimulated phosphoinositide turnover.
The ability of muscarinic cholinergic receptors to activate phosphoinositide turnover following agonist-induced internalization has been investigated. Incubation of SH-SY5Y neuroblastoma cells with oxotremorine-M resulted in a time-dependent endocytosis of both muscarinic receptors and alpha subunits of G0 and G11, but not of isoforms of phosphoinositide-specific phospholipase C, into a subfraction of smooth endoplasmic reticulum (V1). Agonist-induced increases in diacylglycerol mass and in 32P-phosphatidate labeling, much of which was of the tetraenoic species, were also observed in the V1 fraction, but these increases persisted when the agonist-induced translocation of receptors into the V1 fraction was blocked. All enzymes of the phosphoinositide cycle were detectable in the V1 fraction. However, with the exception of phosphatidylinositol 4-kinase, none was enriched when compared with cell lysates. Both 32P-labeling studies and enzyme assays point to a very limited capacity of this fraction to synthesize phosphatidylinositol 4,5-bisphosphate, whereas the synthesis of phosphatidylinositol 4-phosphate is robust. These results indicate that endocytosed receptors do not appear to retain their ability to activate phosphoinositide turnover. The availability of the substrate for phospholipase C, phosphatidylinositol 4,5-bisphosphate, may be one factor that limits the activity of muscarinic receptors in this subcellular compartment.


Raltitrexed's effect on the development of neural tube defects in mice is associated with DNA damage, apoptosis, and proliferation.
The causal metabolic pathway and the underlying mechanism between folate deficiency and neural tube defects (NTDs) remain obscure. Thymidylate (dTMP) is catalyzed by thymidylate synthase (TS) using the folate-derived one-carbon unit as the sole methyl donor. This study aims to examine the role of dTMP biosynthesis in the development of neural tube in mice by inhibition of TS via a specific inhibitor, raltitrexed (RTX). Pregnant mice were intraperitoneally injected with various doses of RTX on gestational day 7.5, and embryos were examined for the presence of NTDs on gestational day 11.5. TS activity and changes of dUMP and dTMP levels were measured following RTX treatment at the optimal dose. DNA damage was determined by detection of phosphorylated replication protein A2 (RPA2) and γ-H2AX in embryos with NTDs induced by RTX. Besides, apoptosis and proliferation were also analyzed in RTX-treated embryos with NTDs. We found that NTDs were highly occurred by the treatment of RTX at the optimal dose of 11.5 mg/kg b/w. RTX treatment significantly inhibited TS activity. Meanwhile, dTMP was decreased associated with the accumulation of dUMP in RTX-treated embryos. Phosphorylated RPA2 and γ-H2AX were significantly increased in RTX-treated embryos with NTDs compared to control. More apoptosis and decreased proliferation were also found in embryos with NTDs induced by RTX. These results indicate that impairment of dTMP biosynthesis caused by RTX led to the development of NTDs in mice. DNA damage and imbalance between apoptosis and proliferation may be potential mechanisms.


The impact of online synchronous simulated clinical immersions on nursing students' pharmacology self-efficacy: A pre-test post-test intervention pilot study.
Medication errors are fatally significant, posing considerable threats to patient safety. To date, there is a lack of literature and no consistent recommended nursing pharmacology curriculum design to improve nursing students' pharmacology self-efficacy. The purpose of this pilot study is to examine the effects of nursing pharmacology synchronous online scrabbling active learning classroom design with simulated clinical immersion experiences on the students' self-efficacy and perceived pharmacology knowledge acquisition. A pretest-posttest intervention design was used with a convenience sample of (n = 34) accelerated nursing students. The intervention included an online synchronous scrabbling active learning classroom design with simulated clinical immersion experiences for eight weeks. The Motivated Strategies for Learning Self-Efficacy Subscale (MSLQ-SE) questionnaire was applied before and after the intervention. The Survey for Knowledge Acquisition and Application (SKAA) was used post-intervention. The students also provided narrative, open-ended responses regarding their perceptions of the synchronous simulated clinical experiences. The results of the simulated clinical immersions presented an improvement in self-efficacy scores. A one tailed paired t-test presented a significant increase from MSLQ-SE pre-test scores (M = 31.2, SD = 4.8) to MSLQ-SE post-test scores (M = 32.9, SD = 4.3); (t(33) = -2.1, p = .02). The SKAA results presented that the students perceived that simulated clinical immersions were promoting authentic learning and confidence. The finding of this study is significant to nursing pharmacology education. The online synchronous simulated clinical immersion experiences improved overall self-efficacy scores and provide an authentic teaching approach to connect pharmacology theory to the clinical practice.


Outcomes following treatment of veterans for substance and tobacco addiction.
Persons who use tobacco in addition to alcohol and other drugs have increased health risks and mortality rates. The purpose of this study was to evaluate the impact of participation in a tobacco cessation program on tobacco, alcohol, and other drug use in a population seeking treatment for substance use disorders (SUDs). Tobacco, alcohol, and other drug use were assessed by urine drug screens, breathalyzer readings, and self-report. Veterans (N=137) with a tobacco use disorder enrolled in inpatient program for the treatment of SUDs at the Salem Veterans Affairs Medical Center participated in tobacco cessation education as part of their treatment programming. Use of tobacco, drugs and/or alcohol was evaluated upon admission, 2 weeks following admission, at discharge and 1 month following graduation. The 1-month follow-up rate was 70.8%, with 97 veterans completing the follow-up assessment. Of those 97 veterans, 90.7% (n=88) reported abstinence from alcohol and 91.8% (n=89) reported abstinence from other drugs of abuse. Fourteen veterans (14.4%) reported abstinence from tobacco at the 1-month follow-up. The veterans reporting abstinence from tobacco use also reported abstinence from alcohol and other drugs at the 1-month follow-up.


Mesenchymal Stem/Stromal Cells May Decrease Success of Cancer Treatment by Inducing Resistance to Chemotherapy in Cancer Cells.
The tumour microenvironment, which is comprised of various cell types and the extracellular matrix, substantially impacts tumour initiation, progression, and metastasis. Mesenchymal stem/stromal cells (MSCs) are one of the key stromal cells in the tumour microenvironment, and their interaction with cancer cells results in the transformation of naïve MSCs to tumour-associated MSCs. The latter has an important impact on tumour growth and progression. Recently, it has been shown that they can also contribute to the development of chemoresistance in cancer cells. This review provides an overview of 42 studies published between 1 January 2001 and 1 January 2022 that examined the effect of MSCs on the susceptibility of cancer cells to chemotherapeutics. The studies showed that MSCs affect various signalling pathways in cancer cells, leading to protection against chemotherapy-induced damage. Promising results emerged from the use of inhibitors of various signalling pathways that are affected in cancer cells due to interactions with MSCs in the tumour microenvironment. These studies present a good starting point for the investigation of novel treatment approaches and demonstrate the importance of targeting the stroma in the tumour microenvironment to improve treatment outcomes.


Gene expression of types I and III collagen, decorin, matrix metalloproteinases and tissue inhibitors of metalloproteinases in skin fibroblasts from patients with systemic sclerosis.
Cultured fibroblasts from patients with systemic sclerosis (SSc) and normal individuals were examined for gene expression of types I and III collagen, decorin, matrix metalloproteinases (MMP) MMP-1, MMP-2, and MMP-3, tissue inhibitors of metalloproteinases (TIMP) TIMP-1 and TIMP-2, urokinase- and tissue-type plasminogen activators (u-PA and t-PA). Fibroblasts from patients with early stage SSC (less than 1 year duration of disease) exhibited higher levels of types I and III procollagen, decorin, MMP-1, MMP-3, TIMP-1, and PAs than those from normal individuals. The gene expression of procollagen alpha 1(I) and TIMP-1 mRNAs were increased, but those of decorin, MMP-1, MMP-2, and MMP-3 were decreased, in fibroblasts from SSc patients with mid-stage SSc (2 to 4 years duration) as compared with those from normal individuals. In contrast, no significant difference in gene expression was found between fibroblasts from normal individuals and from patients with late-stage SSc (more than 6 years duration). These results suggest that gene expression of collagen, decorin, and degrading factors is dynamically modulated during fibrillogenesis. The responses of procollagen alpha 1(I) mRNA to IL-1 and TGF-beta were lower in fibroblasts from SSc patients with early and mid-stage disease, but not in those from patients with-late stage disease, than in control fibroblasts, which indicates that these cytokines may be involved in the earlier phases of fibrosis in SSc.


Cancer: Lynch syndrome--how should colorectal cancer be managed?
An international consortium (the Colon Cancer Family Registry) has recently published interesting data on the risk of developing metachronous colorectal cancer (CRC) after treatment of primary CRC in patients with Lynch syndrome. The findings are clinically important as they might justify more extensive surgery to treat primary CRC in these patients.


Pubertal alterations in growth and body composition. VI. Pubertal insulin resistance: relation to adiposity, body fat distribution and hormone release.
To investigate the independent influence of alterations in fat mass, body fat distribution and hormone release on pubertal increases in fasting serum insulin concentrations and on insulin resistance assessed by the homeostasis model (HOMA). Cross-sectional investigation of pre- (n=11, n=8), mid- (n=10, n=11), and late-pubertal (n=10, n=11) boys and girls with normal body weight and growth velocity. Body composition (by a four-compartment model), abdominal fat distribution and mid-thigh interfascicular plus intermuscle (extramyocellular) fat (by magnetic resonance imaging), total body subcutaneous fat (by skinfolds), mean nocturnal growth hormone (GH) release and 06:00 h samples of serum insulin, sex steroids, leptin and insulin-like growth factor-I (IGF-I). Pubertal insulin resistance was suggested by greater (P<0.001) fasting serum insulin concentrations in the late-pubertal than pre- and mid-pubertal groups while serum glucose concentrations were unchanged and greater (P<0.001) HOMA values in late-pubertal than pre- and mid-pubertal youth. From univariate correlation fat mass was most related to HOMA (r=0.59, P<0.001). Two hierarchical regression models were developed to predict HOMA. In one approach, subject differences in sex, pubertal maturation, height and weight were held constant by adding these variables as a block in the first step of the model (r(2)=0.36). Sequential addition of fat mass (FM) increased r(2) (r(2)((inc)remental)=0.08, r(2)=0.44, P<0.05) as did the subsequent addition of a block of fat distribution variables (extramyocellular fat, abdominal visceral fat, and sum of skinfolds; r(2)(inc)=0.11, r(2)=0.55, P<0.05). Sequential addition of a block of hormone variables (serum IGF-I and log((10)) leptin concentrations; r(2)(inc)=0.04, P>0.05) did not reliably improve r(2) beyond the physical characteristic and adiposity variables. In a second model, differences in sex and pubertal maturation were again held constant (r(2)=0.25), but body size differences were accounted for using percentage fat data. Sequential addition of percentage body fat (r(2)((inc)remental)=0.11, r(2)=0.36, P<0.05), then a block of fat distribution variables (percentage extramyocellular fat, percentage abdominal visceral fat, and percentage abdominal subcutaneous fat; r(2)(inc)=0.08, r(2)=0.44, P=0.058), and then a block of serum IGF-I and log((10)) leptin concentrations (r(2)(inc)=0.07, r(2)=0.51, P<0.05) increased r(2). Mean nocturnal GH release was not related to HOMA (r=-0.04, P=0.75) and therefore was not included in the hierarchical regression models. Increases in insulin resistance at puberty were most related to FM. Accumulation of fat in the abdominal visceral, subcutaneous and muscular compartments may increase insulin resistance at puberty beyond that due to total body fat. Serum concentrations of leptin and IGF-I may further modulate HOMA beyond the effects of adiposity and fat distribution. However, the results are limited by the cross-sectional design and the use of HOMA rather than a criterion measure of insulin resistance.


VASCULAR STENOSIS DETECTION USING TEMPORAL-SPECTRAL DIFFERENCES IN CORRELATED ACOUSTIC MEASUREMENTS.
Central venous stenosis is often undiagnosed in patients with hemodialysis vascular access, partly due to imaging difficulties. Noninvasive, point-of-care detection could rely on detecting regions of turbulent blood flow caused by blood velocity changes. Here we present flexible microphone arrays for time-correlated measures of blood flow sounds and a new signal processing approach to calculate time correlation between spectral features. Continuous wavelet transform was used to produce an auditory spectral flux analytic signal, which was thresholded to identify systolic start and end phases. Microphone arrays were tested on pulsatile flow phantoms with blood flow rates of 850-1,200 mL/min and simulated stenosis from 10-85%. Measured results showed an inversion in the time onset of systolic spectral content for sites proximal and distal to stenosis for hemodynamically significant stenoses (+22 ms for stenosis<50% and -20 to -38 ms for stenosis>50%). Equivalent blood velocity increases were calculated as 142-155 cm/s in stenotic phantoms, which are within the physiologic range as measured by ultrasound.


Pretreatment of sperm with low hypo-osmotic swelling tests with chymotrypsin prior to intrauterine insemination (IUI) and avoidance of unprotectected intercourse results in pregnancy rates comparable to IUI for other male factor problems.
To carry out a retrospectively performed matched controlled study to determine the efficacy of pretreatment of sperm having low hypo-osmotic swelling (HOS) test scores with chymotrypsin galactose prior to intrauterine insemination (IUI) compared to IUI for other types of male factor problems. The women with male partners with low HOS scores were advised not to have unprotected intercourse. All cycles having IUI with chymotrypsin treated sperm for low HOS scores were matched with the very next woman having IUI for sperm with other male factor problems but with normal HOS scores. There was a significantly higher clinical pregnancy rate with chymotrypsin treated sperm (32.3% per IUI) vs. 21.9% for other male factor cases. The live birth rate per IUI cycle was not significantly different (21.2% vs. 15.4%). These results now show that pretreatment of sperm with low HOS scores allows very good pregnancy rates following IUI as long as the couple is cautioned about unprotected intercourse. These data support the concept that sperm with low HOS test scores impair fertility by transferring a toxic factor from the sperm to the zona pellucida to the embryo membrane which impairs the embryos from implanting.


Evaluation of results in flexor tendon repair: a critical analysis of five methods in ninety-five digits.
The development of an internationally accepted system of assessment of results after flexor tendon repair is important. In a prospective study of ninety-five digits, gross discrepancies were demonstrated between five popular methods of assessment: Buck-Gramcko, linear measurement, Grossman, American Society for Surgery of the Hand, and Strickland. The relative merits of each systems were studied and modifications for the Buck-Gramcko system are suggested.


Impact of respiration on stroke volumes in paediatric controls and in patients after Fontan procedure assessed by MR real-time phase-velocity mapping.
Blood flow rate quantification using two-dimensional phase-contrast MRI (PC-MRI) results in averaging of flow information due to long acquisition times precluding the examination of short-term effects. The aim of this study was to determine respiration-related flow rate variations by non-electrocardiographic triggered real-time phase-contrast MRI (PC-MRI). Real-time PC-MRI was applied to study respiration-driven blood flow fluctuations in the ascending aorta (AAo), superior vena cava (SVC), and inferior vena cava (IVC) under normal and forced breathing in 33 healthy children and 10 Fontan patients. Respiration-dependent flow rates were virtually generated by dividing the respiration curve into four segments: expiration, end-expiration, inspiration, and end-inspiration. Whereas in volunteers aortic flow rate was elevated during end-expiration (5.6 ± 3.0%) and decreased during end-inspiration (-5.8 ± 3.5%) in relation to mean blood flow (P < 0.05), highest flow was detected during inspiration in SVC (10.5 ± 14.1%) and IVC (22.5 ± 12.1%) and lowest flow during expiration (-11.6 ± 13.5%, -13.2 ± 14.1%, P < 0.05). Differences were increased under forced breathing in AAo (10.4 ± 5.5%, -7.4 ± 6.5%, P < 0.05) and SVC (40.0 ± 30.3%, -30.0 ± 19.2%, P < 0.05), whereas were unchanged in IVC (16.5 ± 23.6%, -13.7 ± 21.6%, P = n.s.). Regarding patients, respiratory-dependent flow rate variability was increased and had to be related to the patient's individual quality of Fontan circulation. Real-time PC-MRI allows a physiological assessment of respiratory-related flow rate fluctuations in healthy subjects as well as in Fontan patients. Its capability for detection of short-term effects in clinical routine was demonstrated.


Polymers containing isonitrile functional groups as supports for the covalent fixation of biologically active molecules.
1) Isonitrile derivatives of synthetic polyamides, polyesters and polyalcohols, of polysaccharides such as cellulose, cross-linked dextran and agarose, linear dextran and of cross-linked and linear polyacrylamide were prepared. 2) Proteins and low-molecular-weight ligands were bound covalently to these materials by four-component reactions involving the -NC function on the polymer, amino or carboxyl groups deriving from the ligand, aldehyde and the complementary fourth component (-COOH or - NH2) being added to the aqueous reaction medium. 3) Supports of modified surface properties could be prepared by grafting of water-soluble macromolecules containing -NC groups onto preformed polymeric structures. 4) The isonitrile functional groups on polymers could be transformed into other types of functional groups by simple one-step reactions.


Large series examining laparoscopic adjustable gastric banding as a salvage solution for failed gastric bypass.
The Roux-en-Y gastric bypass (RYGB) has long been considered the gold standard of weight loss procedures. However, there is limited evidence on revisional options with both minimal risk and long-term weight loss results. To examine percent excess weight loss, change in body mass index (BMI), and complications in patients who underwent laparoscopic adjustable gastric banding (LAGB) over prior RYGB. Academic hospital. Retrospective analysis of a single-center prospectively maintained database. Three thousand ninety-four LAGB placements were reviewed; 139 were placed in patients with prior RYGB. At the time of LAGB, the median BMI was 41.3. After LAGB, we observed weight loss or stabilization in 135 patients (97%). The median maximal weight loss after LAGB was 37.7% excess weight loss and -7.1 change in BMI (P < .0001). At last follow-up visit, the median weight loss was 27.5% excess weight loss and -5.3 change in BMI (P < .0001). Median follow-up was 2.48 years (.01-11.48): 68 of 132 eligible (52%) with 3-year follow-up, 12 of 26 eligible (44%) with 6-year eligible follow-up, and 3 of 3 eligible (100%) with >10-year follow-up. Eleven bands required removal, 4 for erosion, 4 for dysphagia, and 3 for nonband-related issues. LAGB over prior RYGB is a safe operation, which reduces the surgical risks and nutritional deficiencies often seen in other accepted revisional operations. Complication rates were consistent with primary LAGB. Weight loss is both reliable and lasting, and it can be considered as the initial salvage procedure in patients with failed gastric bypass surgery.


Treatment of taste and odor causing compounds 2-methyl isoborneol and geosmin in drinking water: a critical review.
Problems due to the taste and odor in drinking water are common in treatment facilities around the world. Taste and odor are perceived by the public as the primary indicators of the safely and acceptability of drinking water and are mainly caused by the presence of two semi-volatile compounds--2-methyl isoborneol (MIB) and geosmin. A review of these two taste and odor causing compounds in drinking water is presented. The sources for the formation of these compounds in water are discussed along with the health and regulatory implications. The recent developments in the analysis of MIB/geosmin in water which have allowed for rapid measurements in the nanogram per liter concentrations are also discussed. This review focuses on the relevant treatment alternatives, that are described in detail with emphasis on their respective advantages and problems associated with their implementation in a full-scale facility. Conventional treatment processes in water treatment plants, such as coagulation, sedimentation and chlorination have been found to be ineffective for removal of MIB/geosmin. Studies have shown powdered activated carbon, ozonation and biofiltration to be effective in treatment of these two compounds. Although some of these technologies are more effective and show more promise than the others, much work remains to be done to optimize these technologies so that they can be retrofitted or installed with minimal impact on the overall operation and effectiveness of the treatment system.


Reclinomonas americana N. G., N. Sp., a new freshwater heterotrophic flagellate.
A new heterotrophic flagellate has been discovered from sites in Maryland, Michigan and Wyoming. The flagellate resides within a lorica constructed of a meshwork of intertwined fibrils with the outer surface invested with nail-shaped spines. The organism "reclines" within the lorica with its ventral aspect directed upward, and has two heterodynamic flagella, neither of which bears mastigonemes. One flagellum is directed upward and the other is arched over the ventral aspect of the body. Ingestion of bacteria takes place at the left posterior half of the cell. The organism is anchored to the lorica on the right posterior side by a series of regularly spaced cytoplasmic bridges and at the left anterior of the cell by a cytoplasmic appendage similar to the "languette cytoplasmique" found in some bicosoecids. The right side of the cell is raised into a flattened lip with the outer margin reinforced by a ribbon of microtubules. The new flagellate has mitochondria with tubular cristae and lacks a Golgi. A new genus is created to accommodate both the new flagellate described herein and Histiona campanula Penard. A new family is proposed to include the new genus and Histiona.


Replica-Exchange Umbrella Sampling Combined with Gaussian Accelerated Molecular Dynamics for Free-Energy Calculation of Biomolecules.
We have developed an enhanced conformational sampling method combining replica-exchange umbrella sampling (REUS) with Gaussian accelerated molecular dynamics (GaMD). REUS enhances the sampling along predefined reaction coordinates, while GaMD accelerates the conformational dynamics by adding a boost potential to the system energy. The method, which we call GaREUS (Gaussian accelerated replica-exchange umbrella sampling), enhances the sampling more efficiently than REUS or GaMD, while the computational resource for GaREUS is the same as that required for REUS. The two-step reweighting procedure using the multistate Bennett acceptance ratio method and the cumulant expansion for the exponential average is applied to the simulation trajectories for obtaining the unbiased free-energy landscapes. We apply GaREUS to the calculations of free-energy landscapes for three different cases: conformational equilibria of N-glycan, folding of chignolin, and conformational change of adenyl kinase. We show that GaREUS speeds up the convergences of free-energy calculations using the same amount of computational resources as REUS. The free-energy landscapes reweighted from the trajectories of GaREUS agree with previously reported ones. GaREUS is applicable to free-energy calculations of various biomolecular dynamics and functions with reasonable computational costs.


Early mechanical selection of cell extrusion and extrusion signaling in cancer.
Epithelial cells use the process of extrusion to promote cell death while preserving a tight barrier. To extrude, a cell and its neighbors contract actin and myosin circumferentially and basolaterally to seamlessly squeeze it out of the epithelium. Recent research highlights how early apical pulsatile contractions within the extruding cell might orchestrate contraction in three dimensions so that a cell extrudes out apically. Along with apical constrictions, studies of ion channels and mathematical modeling reveal how differential contraction between cells helps select specific cells to extrude. In addition, several studies have offered new insights into pathways that use extrusion to eliminate transformed cells or cause an aberrant form of extrusion that promotes cell invasion.


Fossil reptilian gelatins.
1. Studies have been made of products obtained by treating several reptilian fossil bones with dilute formic acid. 2. Their amounts and compositions have been compared with those of similarly treated fresh and Pleistocene bones. 3. Fewer and small peptides are obtained from the older fossils but in only one instance was the composition significantly different from that of the total protein. 4. For the collagenous proteins aspartic acid was the most readily freed by hydrolysis; for these older proteins it is alanine. 5. Unlike the Pleistocene proteins, the chromatograms from these older proteins have always had peaks in the position of beta-alanine, and usually others of unidentified origin.


Real Life Data of Treat and Extend Intravitreal Ranibizumab and Aflibercept Therapy in Wet Age-related Macular Degeneration Patients: 3-Year Results.
To compare functional and anatomic outcome of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) treatments in neovascular age-related macular degeneration by using the treat and extend (TE) protocol. In this retrospective chart study, treatment naïve 74 eyes of 74 age-related macular degeneration patients treated with IVR and IVA (38 eyes in IVR and 36 eyes in IVA group) with TE protocol were included. Following three consecutive monthly intravitreal injections, TE protocol was applied to each group. Patients were followed up for at least 36 months. Mean change in best-corrected visual acuity (BCVA), central macula thickness (CMT) and injection numbers over 3 years were compared. Among 36 months period, the mean number of injections was 17 ± 4 for both groups (p > 0.05). In terms of CMT, there was no statistically significant difference between groups at 36 months compared to baseline. A decrease of 72.55 ± 39.37 μm in CMT was detected in IVR group, whereas the decrease was 70.58 ± 33.96 μm in IVA group (p > 0.05). There was a significant increase in BCVA at 36 months of measurements. In addition, BCVA demonstrated an increase of 4.1 ± 0.44 letters in IVR group and 4.36 ± 0.67 letters in IVA group after 36 months compared to the baseline (p > 0.05). Both IVR and IVA injections provided significant improvements and stability in BCVA and CMT, however there was no significant difference between IVR and IVA injections with TE protocol of 36 months.


Apathy and executive functioning among non-demented community-dwelling elderly individuals in an everyday environment: the mediating effect of impulsivity.
Apathy is common in normal ageing and widely recognized as a predictor of cognitive decline, especially in executive functions. Much less characterized than apathy in the elderly is impulsivity, which increases with ageing. It is also frequently described in comorbidity with apathy in various clinical populations, in whom it is associated with poorer executive functioning. In the present study, by capitalizing on a multidimensional approach, we explore the mediating role of facets of impulsivity on the bidirectional relationships between apathy dimensions and executive functioning in non-demented community-dwelling elderly individuals in daily life. A sample of non-demented community-dwelling older adults (n = 101) completed self-rated questionnaires. Apathy was measured by the Apathy Evaluation Scale; impulsivity was examined through the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency (UPPS-P) Impulsive Behaviour Scale; and executive functioning in daily life was assessed by the Behaviour Rating Inventory of Executive Function-Adult (BRIEF-A). Two models positing mediation were tested using conditional process modelling. Hierarchical regressions controlling for depressive symptoms indicated that the cognitive apathy dimension was associated with the UPPS-P facets sensation seeking, lack of perseverance, and premeditation. Among the UPPS-P facets, lack of perseverance and negative urgency were found to contribute significantly to BRIEF-A Metacognitive index variance. Finally, in both models, lack of perseverance was found to totally mediate the relationship between cognitive apathy and the BRIEF-A Metacognitive index. These preliminary findings suggest that, in normal ageing, apathy may share an overlap with impulsivity, contradicting the notion they represent opposite ends of a single behavioural spectrum. Our results argue for bidirectional relationship between a specific apathy dimension (i.e. cognitive apathy) and executive functioning. Moreover, they shed new light on the underlying psychological process implicated (i.e. lack of perseverance) among older adults without dementia and represent an interesting prospect for psychological interventions.


Quetiapine-induced peripheral edema.
Quetiapine fumarate is an atypical antipsychotic with relatively benign side-effect profile. Here we report a rare side-effect of quetiapine use. This is the second reported case of peripheral edema with quetiapine use. Unaware of this rare side-effect, patient had to endure extensive investigations.