Lower extremity morphology and alignment and risk of overuse injury.
Lower extremity alignment factors, including tibiofemoral angle, quadriceps angle (Q-angle), and limb length discrepancies, are commonly thought to be clinically relevant as contributing factors to overuse injuries of the lower extremities. To explore the scientific rationale for these clinical beliefs, we conducted a review of the available English language literature from 1966 to July 1997 relating overuse injury to lower extremity alignment. MEDLINE was searched for medical subject headings and title key words to locate published works relating lower extremity morphologic characteristics to risk of overuse injury. Additional references were reviewed from reprint collections and reference lists of published work. Relevant studies were reviewed for strengths and weaknesses in design, analysis, and conclusions. Synthesis across studies concentrated on commonalities and differences of methods in definition of exposure and outcome variables. Six population-based studies have been conducted evaluating some aspect of lower extremity alignment as a risk factor for overuse injury. Three of these studies evaluated military recruits in basic training, two studied mixed groups of athletes and one studied folk dancers. The time frame across studies ranged from 12 weeks to 52 weeks. A key finding was the considerable variation in the measure of lower limb alignment used as the exposure variable, as well as the method of measurement used to quantify the exposure. Some studies relied on visual examination, whereas others used digitized photographic techniques. Moreover, each study varied in the definition used for overuse injury; outcomes ranged from self-reported cases of shin splints to radiographic confirmation of stress fracture. Five of the six studies evaluated some aspect of foot morphology, whereas only one evaluated full leg alignment parameters. Results were conflicting but, in general, did not support clinical beliefs of the detrimental effects of decreased longitudinal foot arch and varus tibiofemoral alignment as risk factors for lower extremity overuse injury. Differences in methodologic rigor and outcome definition prevent a meaningful synthesis of existing work. Directions for future research are suggested.


Gene methylation biomarkers in sputum as a classifier for lung cancer risk.
CT screening for lung cancer reduces mortality, but will cost Medicare ∼2 billion dollars due in part to high false positive rates. Molecular biomarkers could augment current risk stratification used to select smokers for screening. Gene methylation in sputum reflects lung field cancerization that remains in lung cancer patients post-resection. This population was used in conjunction with cancer-free smokers to evaluate classification accuracy of a validated eight-gene methylation panel in sputum for cancer risk. Sputum from resected lung cancer patients (n=487) and smokers from Lovelace (n=1380) and PLuSS (n=718) cohorts was studied for methylation of an 8-gene panel. Area under a receiver operating characteristic curve was calculated to assess the prediction performance in logistic regressions with different sets of variables. The prevalence for methylation of all genes was significantly increased in the ECOG-ACRIN patients compared to cancer-free smokers as evident by elevated odds ratios that ranged from 1.6 to 8.9. The gene methylation panel showed lung cancer prediction accuracy of 82-86% and with addition of clinical variables improved to 87-90%. With sensitivity at 95%, specificity increased from 25% to 54% comparing clinical variables alone to their inclusion with methylation. The addition of methylation biomarkers to clinical variables would reduce false positive screens by ruling out one-third of smokers eligible for CT screening and could increase cancer detection rates through expanding risk assessment criteria.


Molecular cloning, expression, and characterization of rat homolog of human AP-2alpha that stimulates neuropeptide Y transcription activity in response to nerve growth factor.
Neuropeptide Y (NPY) plays an important role in the central regulation of neuronal activity, endocrine and sexual behavior, and food intake. Although transcription activity of the NPY gene in PC12 cells is regulated by a number of agents such as nerve growth factor (NGF), the mechanism responsible for the NGF-elicited increase in the transcription of the NPY gene remains to be explored. In this study, we isolated and characterized a nuclear protein that is bound to NGF-response elements (NGFRE) that lie between nucleotide -87 and -33 of the rat NPY promoter gene. This nuclear protein is identical to the rat homolog of human transcription factor AP-2alpha. We further demonstrated that rat AP-2a promotes efficient NPY transcription activity in response to NGF. Finally, we provide direct evidence that the mice lacking transcription factor AP-2alpha exhibit reduced expression of NPY mRNA compared with wild-type mice, further supporting the hypothesis that AP-2alpha is an important transcription factor in regulating NPY transcription activity.


What does gender affirmation mean to you? An exploratory study.
Gender affirmation lessens mental health disparities among transgender and gender nonbinary (TGNB) persons. However, the concept of what it means to be affirmed in one's gender has not been fully explored, nor has the impact of gender affirmation on other health indicators been determined. The purpose of this study was to explore the meaning of gender affirmation among a sample of TGNB persons. This qualitative, narrative inquiry study consisted of individual, in-depth, semi-structured interviews with a convenience sample of 20 TGNB persons. Descriptive content analysis was conducted to discover themes. This study identified salient themes regarding the multiple levels of affirmation (including internal, external and societal) needed to achieve the overall goal of living an optimal life described as "being seen, heard and even celebrated" as TGNB. Results of this study have clinical, educational, research, and policy implications. Future research should explore the impact of gender affirmation on important health indicators in the TGNB community, differences in the experiences and needs among subgroups of TGNB persons, and the potential impact of nurses on the health experience of TGNB persons across the spectrum of transition.


Natalizumab: risk stratification of individual patients with multiple sclerosis.
At present, three risk factors for the development of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients have been identified: the presence of antibodies against JC virus (JCV); the duration of natalizumab treatment, especially if longer than 2 years; and the use of immunosuppressants prior to receiving natalizumab. The most commonly used strategy to assess the individual PML risk includes serum anti-JCV antibody testing. Based on the knowledge on all known risk factors, an algorithm for PML risk stratification has been proposed, where patients with the highest PML risk are those with positive anti-JCV antibodies, treatment duration longer than 2 years, with or without prior history of immunosuppression. These patients would have an approximate incidence of PML of 11.1 (with prior immunosuppression) or 4.6 (without prior immunosuppression) cases per 1,000 patients treated with natalizumab (and treatment duration longer than 2 years). In this review, new data on PML risk factors and possible new strategies for PML risk stratification are discussed.


Writing for professional publication. Part 8: targeting the right journal.
The previous articles in this series of writing for professional publication focused on the preparation you need to do before starting to write an article, the practicalities of writing the abstract, creating interest in the reader's mind, and how an article for publication differs from an academic essay. Recently we considered the importance of selecting the correct journal for submission. In this article, John Fowler, an experienced nursing lecturer and author, discusses how client case studies can be used within your article.


Retrospective study of radiotherapy-induced skin reactions in breast cancer patients: reduced incidence of moist desquamation with a hydroactive colloid gel versus dexpanthenol.
Dermatitis is a very frequent and distressing side effect of radiation therapy that may necessitate a treatment interruption when evolving towards more severe forms such as moist desquamation (MD). The aim of this study was to compare the efficacy of two topical agents, a dexpanthenol cream vs a hydroactive colloid gel combining absorbing and moisturising properties, in preventing MD in breast cancer patients. This retrospective study compared two successive groups of breast cancer patients undergoing radiotherapy after breast-sparing surgery between 2008 and 2012. A group of 267 patients applied a 5% dexpanthenol cream on the irradiated zone throughout the course of their radiotherapy. Another group of 216 patients applied first the dexpanthenol cream then replaced it by the hydroactive colloid gel after 11-14 days of radiotherapy. Radiation treatment (total dose, technique, and equipment) was the same for the two groups. The clinical outcomes were the occurrence and time to onset of moist desquamation. The overall incidence of MD was significantly lower in patients who applied the hydroactive colloid gel (16%) than in those who applied the dexpanthenol cream (32%, odds-ratio = 0.35). Also, MD occurred significantly later with the hydroactive colloid gel than with the dexpanthenol cream (hazard ratio = 0.39). Compared with the dexpanthenol cream, the hydroactive colloid gel significantly reduced the risk of developing MD in patients undergoing radiotherapy for breast cancer. These promising results warrant further research on the efficacy of hydroactive colloid gels in managing radiation dermatitis.


The immediate effectiveness of electrical nerve stimulation and electrical muscle stimulation on myofascial trigger points.
This study is designed to investigate the immediate effectiveness of electrotherapy on myofascial trigger points of upper trapezius muscle. Sixty patients (25 males and 35 females) who had myofascial trigger points in one side of the upper trapezius muscles were studied. The involved upper trapezius muscles were treated with three different methods according to a random assignment: group A muscles (n = 18) were given placebo treatment (control group); group B muscles (n = 20) were treated with electrical nerve stimulation (ENS) therapy; and group C muscles (n = 22) were given electrical muscle stimulation (EMS) therapy. The effectiveness of treatment was assessed by conducting three measurements on each muscle before and immediately after treatment: subjective pain intensity [(PI) with a visual analog scale], pressure pain threshold [(PT) with algometry], and range of motion [(ROM) with a goniometer] of upper trapezius muscle (lateral bending of cervical spine to the opposite side). When the effectiveness of treatment was compared with that of the placebo group (group A), there was significant improvement in PI and PT in group B (P < 0.01) but not in group C (P > 0.05). The improvement of ROM was significantly more in group C (P < 0.01) as compared with that in group A or group B. When each group was divided into two additional subgroups based on the initial PI, it was found that ENS could reduce PI and increase PT significantly (P < 0.05), but did not significantly (P > 0.05) improve ROM, as compared with the placebo group for both subgroups. EMS could significantly (P < 0.05) improve ROM, but not PT, better than the placebo groups, for either subgroup. It could reduce PI significantly more (P < 0.05) than placebo controls only for the subgroup with mild to moderate pain, but not with severe pain. For pain relief, ENS was significantly better (P < 0.05) than EMS; but for the improvement of ROM, EMS was significantly better (P < 0.05) than ENS. It is concluded that ENS is more effective for immediate relief of myofascial trigger point pain than EMS, and EMS has a better effect on immediate release of muscle tightness than ENS.


A comparison of modified methenamine silver and toluidine blue stains for the detection of Pneumocystis carinii in bronchoalveolar lavage specimens from immunosuppressed patients.
Pneumonia due to Pneumocystis carinii is an increasingly frequent occurrence; a prompt, accurate diagnosis is important to successfully manage this infection. Methenamine silver and toluidine blue stainings of material recovered by bronchoalveolar lavage (BAL) have been the most widely employed techniques for detecting Pneumocystis organisms. The value of these two staining techniques for the detection of Pneumocystis organisms was prospectively compared in 220 BAL specimens obtained from 186 immunosuppressed individuals. The patients included those with disease-related and therapy-related immunosuppression; half of the BAL specimens came from organ transplant recipients. The results indicate that neither method is superior to the other and that both will correctly identify almost all Pneumocystis infections if a sufficient aliquot of BAL material is examined systematically by trained individuals. The toluidine blue method is somewhat simpler to perform, however. The reasons for discrepant results between the two staining methods were analyzed.


Mandibular distraction osteogenesis with multidirectional extraoral distraction device in hemifacial microsomia patients: three-dimensional treatment planning, prediction tracings, and case outcomes.
Distraction osteogenesis of the craniofacial skeleton with the use of several different types of distraction devices (i.e., extraoral, intraoral, unidirectional, multidirectional, and customized) have been documented. However, the details of treatment planning and the method of predicting the distraction of the mandible in patients with hemifacial microsomia have not been published previously. This paper presents a technique for (1) three-dimensional treatment planning for mandibular distraction, (2) three-dimensional prediction tracings with conventional radiographs (panoramic, lateral, and posterior-anterior cephalometric), and (3) correlating the treatment planning and clinical applications. Lastly, 2 patients with hemifacial microsomia planned and treated with this approach are reported.


Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation.
Cytidine triphosphate (CTP) synthetase 1 (CTPS1) deficiency is caused by a unique homozygous frameshift splice mutation (c.1692-1G>C, p.T566Dfs26X). CTPS1-deficient patients display severe bacterial and viral infections. CTPS1 is responsible for CTP nucleotide de novo production involved in DNA/RNA synthesis. Herein, we characterized in depth lymphocyte defects associated with CTPS1 deficiency. Immune phenotyping performed in 7 patients showed absence or low numbers of mucosal-associated T cells, invariant NKT cells, memory B cells, and NK cells, whereas other subsets were normal. Proliferation and IL-2 secretion by T cells in response to TCR activation were markedly decreased in all patients, while other T cell effector functions were preserved. The CTPS1T566Dfs26X mutant protein was found to be hypomorphic, resulting in 80%-90% reduction of protein expression and CTPS activity in cells of patients. Inactivation of CTPS1 in a T cell leukemia fully abolished cell proliferation. Expression of CTPS1T566Dfs26X failed to restore proliferation of CTPS1-deficient leukemia cells to normal, except when forcing its expression to a level comparable to that of WT CTPS1. This indicates that CTPS1T566Dfs26X retained normal CTPS activity, and thus the loss of function of CTPS1T566Dfs26X is completely attributable to protein instability. This study supports that CTPS1 represents an attractive therapeutic target to selectively inhibit pathological T cell proliferation, including lymphoma.


A Systematic Review and Meta-analysis Examining the Impact of Incident Postoperative Delirium on Mortality.
Delirium is an acute and reversible geriatric syndrome that represents a decompensation of cerebral function. Delirium is associated with adverse postoperative outcomes, but controversy exists regarding whether delirium is an independent predictor of mortality. Thus, we assessed the association between incident postoperative delirium and mortality in adult noncardiac surgery patients. A systematic search was conducted using Cochrane, MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature, and Embase. Screening and data extraction were conducted by two independent reviewers. Pooled-effect estimates calculated with a random-effects model were expressed as odds ratios with 95% CIs. Risk of bias was assessed using the Cochrane Risk of Bias Tool for Non-Randomized Studies. A total of 34 of 4,968 screened citations met inclusion criteria. Risk of bias ranged from moderate to critical. Pooled analysis of unadjusted event rates (5,545 patients) suggested that delirium was associated with a four-fold increase in the odds of death (odds ratio = 4.12 [95% CI, 3.29 to 5.17]; I = 24.9%). A formal pooled analysis of adjusted outcomes was not possible due to heterogeneity of effect measures reported. However, in studies that controlled for prespecified confounders, none found a statistically significant association between incident postoperative delirium and mortality (two studies in hip fractures; n = 729) after an average follow-up of 21 months. Overall, as study risk of bias decreased, the association between delirium and mortality decreased. Few high-quality studies are available to estimate the impact of incident postoperative delirium on mortality. Studies that controlled for prespecified confounders did not demonstrate significant independent associations of delirium with mortality.


Epigenetic silencing of miR-708 enhances NF-κB signaling in chronic lymphocytic leukemia.
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and their deregulation is involved in tumor development. Epigenetic gene silencing in cancer by DNA methylation contributes to the silencing of tumor-suppressor genes, including miRNAs. We have recently shown that the promoter of miR-708 is aberrantly methylated in chronic lymphocytic leukemia (CLL). To characterize the molecular signaling networks that are influenced by miR-708, we performed a luciferase-based screen evaluating the effects of ectopic miR-708 expression on leukemia-relevant signaling pathways. We found that miR-708 strongly repressed NF-κB signaling, a pathway known to be deregulated in CLL. Among the predicted miR-708 targets was IKKβ (inhibitor of kappa light polypeptide gene enhancer in B cells, kinase-β/IKBKB), a key kinase facilitating NF-κB signaling. We validated the interaction of miR-708 with the 3'-untranslated region of IKKβ and found that miR-708 overexpression represses endogenous IKKβ. Phosphorylation of the IKKβ target IκBα and expression of known NF-κB target genes were impaired by miR-708. Furthermore, we identified an enhancer region downstream of the miR-708 promoter that displays a distinct DNA methylation status in CLL. High enhancer methylation is significantly correlated with lower miR-708 expression and is predominantly found in patients with poor prognosis and shorter time to treatment. These results demonstrate that miR-708 regulates the NF-κB pathway by targeting IKKβ, and that methylation of a key enhancer region contributes to its suppression in CLL.


Synergistic antiosteoporotic effect of Lepidium sativum and alendronate in glucocorticoid-induced osteoporosis in Wistar rats.
Alendronate belongs to a class of drugs called bisphosphonates. Bisphosphonates (BP) therapy is a vital option to reduce the risk of bone fracture in people who suffer from osteoporosis. Yet, bisphosphonate have displayed several side effects. Lepidium sativum (LS) seeds have been used in traditional folk medicine to heal fractured bones. However, there is a dearth of information on the impact of LS on bone metabolism especially in cases of glucocorticoids induced osteoporosis. Therefore, the aim of the study was to compare the biochemical bone markers and histological responses of LS alone (6 g of LS seeds in diet daily, n=8), ALD (alendronate, 70 mg/kg s.c.; n=8) alone, or LS and ALD combined in a rat model of glucocorticoid-induced osteoporosis (GIO) by injecting rats with methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin, phosphorus (P), bone-specific alkaline phosphatase (b-ALP), and tartrate-resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO. GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO-group also showed significantly decreased serum P and unaltered Ca concentrations. Histological examination of GIO-group tibia bones indicated an osteoporotic change and a concomitant decrease in percentage of trabecular area or bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with either LS and/or ALD ameliorated the above mentioned changes with variable degrees, with a net results of enhanced serum calcium, bone architecture, PTB, b-ALP and decreased TRAP in LS and LS+ALD groups compared to that of animals treated with alendronate alone. In conclusion, our findings present evidence supporting the potential benefits of LS in reducing the burden of GCs on bone health.


MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma.
Autophagy favors both cell survival and cancer suppression, and increasing evidence reveals that microRNAs (MIRs) regulate autophagy. Previously we reported that MIR126 is downregulated in malignant mesothelioma (MM). Therefore, we investigated the role of MIR126 in the regulation of cell metabolism and autophagy in MM models. We report that MIR126 induces autophagic flux in MM cells by downregulating insulin receptor substrate-1 (IRS1) and disrupting the IRS1 signaling pathway. This was specific to MM cells, and was not observed in non-malignant cells of mesothelial origin or in MM cells expressing MIR126-insensitive IRS1 transcript. The MIR126 effect on autophagy in MM cells was recapitulated by IRS1 silencing, and antagonized by IRS1 overexpression or antisense MIR126 treatment. The MIR126-induced loss of IRS1 suppressed glucose uptake, leading to energy deprivation and AMPK-dependent phosphorylation of ULK1. In addition, MIR126 stimulated lipid droplet accumulation in a hypoxia-inducible factor-1α (HIF1α)-dependent manner. MIR126 also reduced pyruvate dehydrogenase kinase (PDK) and acetyl-CoA-citrate lyase (ACL) expression, leading to the accumulation of cytosolic citrate and paradoxical inhibition of pyruvate dehydrogenase (PDH) activity. Simultaneous pharmacological and genetic intervention with PDK and ACL activity phenocopied the effects of MIR126. This suggests that in MM MIR126 initiates a metabolic program leading to high autophagic flux and HIF1α stabilization, incompatible with tumor progression of MM. Consistently, MIR126-expressing MM cells injected into immunocompromised mice failed to progress beyond the initial stage of tumor formation, showing that increased autophagy has a protective role in MM.


Availability of calorie information on online menus from chain restaurants in the USA: current prevalence and legal landscape.
Federal law requires calorie information on chain restaurant menus. We sought to assess the prevalence of calorie disclosures on online menus and determine if the menus are controlled by restaurants subject to US labelling requirements. Cross-sectional. Restaurant websites and mobile apps for restaurant located in New York City, Los Angeles, Chicago, and Houston. US chain restaurants (top seventy-five by number of outlets) and third-party platforms (TPP): Grubhub, Uber Eats, DoorDash. There was at least one calorie disclosure (for at least one food or beverage, in at least one location) on sixty-eight of seventy-two (94 %) menus on restaurant websites or apps, thirty-two of fifty-five (58 %) menus on DoorDash, six of forty-nine (12 %) menus on Grubhub and thirty of fifty-nine (51 %) menus on Uber Eats. There was consistent calorie labelling (all foods and beverages, all locations) on forty-three of seventy-two (60 %) menus on restaurant websites or apps, fifteen of fifty-five (27 %) menus on DoorDash, three of forty-nine (6 %) menus on Grubhub and eleven of fifty-nine (19 %) menus on Uber Eats. Only four restaurant chains consistently labelled calories for all items, in all locations, on all platforms where their menus were found. All three TPP provided restaurants the ability to enter and modify menu items, making the menus subject to US labelling requirements. Only Uber Eats provided guidance to restaurants on entering calorie information. As consumers increasingly rely on TPP for restaurant ordering, menus on these platforms should include calories in order to promote transparency and nutrition.


[Analysis of bile acid-related proteins by mass spectrometry].
We demonstrated the modification of epsilon-amino groups on human histone H3 by deoxycholyl adenylate. When using a small amount of deoxycholyl adenylate, only one adduct fragment, amino acid 3-8 with a deoxycholate adduct, was produced, suggesting that the epsilon-amino group of Lys4 had the highest reactivity. In addition, other proteins in cells also formed protein adducts through flexible lysine residues, and we identified those proteins on a two-dimensional proteome map by MALDI-TOF MS and nanoLC/ESI-MS/MS. Chenodeoxycholic acid, a primary bile acid, abundantly exists in the rat brain, and may tightly bind to some proteins. It is therefore very important for understanding the physiological role of brain bile acids to identify chenodeoxycholate-binding proteins. We have shown the benefit of a new extraction method coupled with a cleavable affinity gel, which consists of a cleavable disulfide linker and a protein-targeting molecule at the end of the linker connected to the polymer. We tried to capture chenodeoxycholate-binding proteins in rat brain tissue by using chenodeoxycholate-immobilized cleavable affinity gel, developed in our laboratory. Tubulin-alpha, tubulin-beta, actin-beta, and 14-3-3 protein were found as candidates for chenodeoxycholate-binding proteins in the cerebrum, midbrain, cerebellum, brain stem, and hippocampus. In addition, growth hormone was also captured with the above proteins in the pituitary; therefore, we focused on growth hormone among these binding protein candidates, and analyzed noncovalent binding of chenodeoxycholate with growth hormone by the affinity labeling method.


What Should a Psychiatrist Know About Genetics? Review and Recommendations From the Residency Education Committee of the International Society of Psychiatric Genetics.
The International Society of Psychiatric Genetics (ISPG) created a Residency Education Committee with the purpose of identifying key genetic knowledge that should be taught in psychiatric training programs. Thirteen committee members were appointed by the ISPG Board of Directors, based on varied training, expertise, gender, and national origin. The Committee has met quarterly for the past 2 years, with periodic reports to the Board and to the members of the Society. The information summarized includes the existing literature in the field of psychiatric genetics and the output of ongoing large genomics consortia. An outline of clinically relevant areas of genetic knowledge was developed, circulated, and approved. This document was expanded and annotated with appropriate references, and the manuscript was developed. Specific information regarding the contribution of common and rare genetic variants to major psychiatric disorders and treatment response is now available. Current challenges include the following: (1) Genetic testing is recommended in the evaluation of autism and intellectual disability, but its use is limited in current clinical practice. (2) Commercial pharmacogenomic testing is widely available, but its utility has not yet been clearly established. (3) Other methods, such as whole exome and whole genome sequencing, will soon be clinically applicable. The need for informed genetic counseling in psychiatry is greater than ever before, knowledge in the field is rapidly growing, and genetic education should become an integral part of psychiatric training.


Predation shapes the impact of cancer on population dynamics and the evolution of cancer resistance.
Cancer is a widespread disease that affects most of the metazoans. However, cancer development is a slow process and, long before causing the death of the individual, may weaken organisms' capacities and impair their interactions with other species. Yet, the impact of cancer development on biotic interactions, and over the dynamics of the whole ecosystem, is still largely unexplored. As well, the feedback of altered biotic interactions on the evolution of resistance against cancer in the context of community ecology has not been investigated. From this new perspective, we theoretically investigate how cancer can challenge expected interaction outcomes in a predator-prey model system, and how, in return, these altered interaction outcomes could affect evolution of resistance mechanism against cancer. First, we demonstrate a clear difference between prey and predator vulnerability to cancer, with cancer having a limited impact on prey populations. Second, we show that biotic interactions can surprisingly lead to a null or positive effect of cancer on population densities. Finally, our evolutionary analysis sheds light on how biotic interactions can lead to diverse resistance levels in predator populations. While its role in ecosystems is mostly unknown, we demonstrate that cancer in wildlife is an important ecological and evolutionary force to consider.


Parkinsonism Improved With Levodopa After Endoscopic Third Ventriculostomy in Shunted Hydrocephalus Due to Aqueductal Stenosis.
Levodopa-responsive parkinsonism has been reported following ventriculoperitoneal (VP) shunt in patients with obstructive hydrocephalus due to aqueductal stenosis. It has been thought to arise from injury to the global rostral midbrain including the nigrostriatal pathway by a transtentorial pressure gradient. We present a similar patient, but his parkinsonism resisted levodopa administration during the initial therapy. A 51-year-old man suffered from hydrocephalus due to secondary aqueductal stenosis presumably attributed to massive bleeding during surgery for a fourth ventricle hemangioblastoma. After resolution of the hydrocephalus with VP shunt, he developed severe parkinsonism, Parinaud syndrome, and hyperreflexia, suggesting global rostral midbrain dysfunction, but high-dosage levodopa therapy was not effective. An inverted transtentorial pressure gradient suggested by his unilateral slit-like ventricle was assumed to be the cause of the levodopa resistance. Also based on an assumption that the absorption of cerebrospinal fluid was impaired due to the intraoperative bleeding, a lumbar peritoneal shunt was added to the preexisting VP shunt, but it failed to control the ventricular size. Instead, endoscopic third ventriculostomy stabilized it, characteristically inducing levodopa responsiveness in our patient. An increase of the levodopa dosage led to clinical improvement, which needed a maintenance dosage because of dependency. The details of this patient suggest that a transtentorial pressure gradient may have impaired more distal basal ganglia connections over a global rostral midbrain including the nigrostriatal pathway, and that aggressive levodopa therapy after endoscopic third ventriculostomy can be effective for refractory parkinsonism.


Age-dependent molecular alterations in the autophagy pathway in HIVE patients and in a gp120 tg mouse model: reversal with beclin-1 gene transfer.
Aged (>50 years old) human immunodeficiency virus (HIV) patients are the fastest-growing segment of the HIV-infected population in the USA and despite antiretroviral therapy, HIV-associated neurocognitive disorder (HAND) prevalence has increased or remained the same among this group. Autophagy is an intracellular clearance pathway for aggregated proteins and aged organelles; dysregulation of autophagy is implicated in the pathogenesis of Parkinson's disease, Alzheimer's disease, and HAND. Here, we hypothesized that dysregulated autophagy may contribute to aging-related neuropathology in HIV-infected individuals. To explore this possibility, we surveyed autophagy marker levels in postmortem brain samples from a cohort of well-characterized <50 years old (young) and >50 years old (aged) HIV+ and HIV encephalitis (HIVE) patients. Detailed clinical and neuropathological data showed the young and aged HIVE patients had higher viral load, increased neuroinflammation and elevated neurodegeneration; however, aged HIVE postmortem brain tissues showed the most severe neurodegenerative pathology. Interestingly, young HIVE patients displayed an increase in beclin-1, cathepsin-D and light chain (LC)3, but these autophagy markers were reduced in aged HIVE cases compared to age-matched HIV+ donors. Similar alterations in autophagy markers were observed in aged gp120 transgenic (tg) mice; beclin-1 and LC3 were decreased in aged gp120 tg mice while mTor levels were increased. Lentivirus-mediated beclin-1 gene transfer, that is known to activate autophagy pathways, increased beclin-1, LC3, and microtubule-associated protein 2 expression while reducing glial fibrillary acidic protein and Iba1 expression in aged gp120 tg mice. These data indicate differential alterations in the autophagy pathway in young versus aged HIVE patients and that autophagy reactivation may ameliorate the neurodegenerative phenotype in these patients.


Glucose Sensing with Phenylboronic Acid Functionalized Hydrogel-Based Optical Diffusers.
Phenylboronic acids have emerged as synthetic receptors that can reversibly bind to cis-diols of glucose molecules. The incorporation of phenylboronic acids in hydrogels offers exclusive attributes; for example, the binding process with glucose induces Donnan osmotic pressure resulting in volumetric changes in the matrix. However, their practical applications are hindered because of complex readout approaches and their time-consuming fabrication processes. Here, we demonstrate a microimprinting method to fabricate densely packed concavities in phenylboronic acid functionalized hydrogel films. A microengineered optical diffuser structure was imprinted on a phenylboronic acid based cis-diol recognizing motif prepositioned in a hydrogel film. The diffuser structure engineered on the hydrogel was based on laser-inscribed arrays of imperfect microlenses that focused the incoming light at different focal lengths and direction resulting in a diffused profile of light in transmission and reflection readout modes. The signature of the dimensional modulation was detected in terms of changing focal lengths of the microlenses due to the volumetric expansion of the hydrogel that altered the diffusion spectra and transmitted beam profile. The transmitted optical light spread and intensity through the sensor was measured to determine variation in glucose concentrations at physiological conditions. The sensor was integrated in a contact lens and placed over an artificial eye. Artificial stimulation of variation in glucose concentration allowed quantitative measurements using a smartphone's photodiode. A smartphone app was utilized to convert the received light intensity to quantitative glucose concentration values. The developed sensing platform offers low cost, rapid fabrication, and easy detection scheme as compared to other optical sensing counterparts. The presented detection scheme may have applications in wearable real-time biomarker monitoring devices at point-of-care settings.


Poultry disease occurrences and their impacts in Ethiopia.
Poultry production contributes significantly to the livelihoods of Ethiopian farmers and to the national economy although it is hampered by different factors, including poultry diseases. There is scarcity of published evidences on the occurrence and impacts of poultry diseases although such evidences are important for policy makers in designing appropriate interventions. A total of 595 households were interviewed and 11 FGDs were conducted to collect data on the occurrence of diseases and the number of dead chickens in the last 12 months. Hence, respiratory diseases, sudden death, and eye-face-head diseases were mentioned in all of the FGDs as the most frequently occurring disease in the districts. Of households interviewed, 86.1% reported poultry disease occurrence in the last 12 months, and gastrointestinal, eye-face-head, and neurological diseases were identified to be the top three ranked diseases of chickens in the districts. Flocks with access to diagnostic services (Adj. OR = 4.16; P = 0.004) and/or access to animal health providers (Adj. OR = 10.50; P = 0.001) were more likely to report disease occurrence. In the studied population, the diseases resulted in deaths of 2219 chickens valued at 352,219.5 Birr (11,740.65 USD) and a mean crude mortality of 31.87%. Female-lead households (mean difference = 5.95%; P = 0.018) and multiple age units present on the farm (mean difference = 20.92%; P = < 0.000) had higher chicken mortality. Similarly, higher mortality was reported in flocks without access to diagnosis (mean difference = 9.97%; P = < 0.000) and vaccination (mean difference = 12.34%; P = < 0.000) services. The high occurrence of disease and mortalities might be explained by a lack of an organized poultry health service delivery system in the country. Therefore, a carefully designed health service delivery system addressing needs of poultry producers, supported by relevant policy and corresponding strategies, is recommended to address the indicated challenges. Moreover, private health providers with well-defined roles need to be engaged to successfully and sustainably solve the poultry disease problems.


Electromagnetic fields as first messenger in biological signaling: Application to calmodulin-dependent signaling in tissue repair.
The transduction mechanism for non-thermal electromagnetic field (EMF) bioeffects has not been fully elucidated. This study proposes that an EMF can act as a first messenger in the calmodulin-dependent signaling pathways that orchestrate the release of cytokines and growth factors in normal cellular responses to physical and/or chemical insults. Given knowledge of Ca(2+) binding kinetics to calmodulin (CaM), an EMF signal having pulse duration or carrier period shorter than bound Ca(2+) lifetime may be configured to accelerate binding, and be detectable above thermal noise. New EMF signals were configured to modulate calmodulin-dependent signaling and assessed for efficacy in cellular studies. Configured EMF signals modulated CaM-dependent enzyme kinetics, produced several-fold increases in key second messengers to include nitric oxide and cyclic guanosine monophosphate in chondrocyte and endothelial cultures and cyclic adenosine monophosphate in neuronal cultures. Calmodulin antagonists and downstream blockers annihilated these effects, providing strong support for the proposed mechanism. Knowledge of the kinetics of Ca(2+) binding to CaM, or for any ion binding specific to any signaling cascade, allows the use of an electrochemical model by which the ability of any EMF signal to modulate CaM-dependent signaling can be assessed a priori or a posteriori. Results are consistent with the proposed mechanism, and strongly support the Ca/CaM/NO pathway as a primary EMF transduction pathway. The predictions of the proposed model open a host of significant possibilities for configuration of non-thermal EMF signals for clinical and wellness applications that can reach far beyond fracture repair and wound healing.


No sweat: managing menopausal symptoms at work.
Menopause usually occurs between the ages of 45 and 55, a time when women are likely to be in the paid workforce. Most women have menopausal symptoms and these may impact on daytime function and work performance. This study examines the relationship between reproductive stage, menopausal symptoms and work, and advises how employers can best support menopausal women. An online and paper-based survey was completed in 2015-16 by 1092 women (22% response rate) aged 40 years plus employed in three hospitals in metropolitan Australia. Survey questions examined demographics, health and lifestyle variables, menopausal symptom reporting, and work-related variables. Reproductive stage was determined using modified STRAW +10 principal and descriptive criteria. Reproductive stage was not significantly associated with work engagement, organizational commitment, job satisfaction, work limitations and perceived supervisor support. Postmenopausal women had lower intention to leave their organizations than pre- and peri-menopausal women. While sleep problems were the most commonly reported menopausal symptom by peri-menopausal women, for postmenopausal women it was joint and muscular discomfort. Only hot flushes and vaginal dryness were significantly more frequent in peri- and post, compared to pre-menopausal women. In general, women rated their work performance as high and did not feel that menopausal symptoms impaired their work ability. Most women would appreciate greater organizational support, specifically temperature control, flexible work hours and information about menopause for employees and managers. Most women did not believe that menopausal symptoms negatively impacted on their work. Organizational changes may reduce the burden of menopausal symptoms in the workplace.


Orbiniidae polychaetes (Polychaeta: Scolecida) from Coiba Island, eastern Pacific of Panama, with description of a new species.
Santa Cruz and El Gambute, two mangrove systems with associated tidal flats, were sampled in Coiba National Park, Coiba Island, Pacific of Panama. At each site, two samplings were done at low, middle and high intertidal levels in February and November of 1997. A new orbiniid species were found: Orbinia oligopapillata n. sp. is characterized by having 15-16 thoracic chaetigers with four or five rows of uncini and up to three papilliform postchaetal processes on neuropodial lobes by the abdominal parapodia bearing flail-tipped neurochaetae, and by the presence on anterior-most abdominal chaetigers of interramal cirri and a low number of subpodial and stomach papillae. A specimen belonging to genus Leitoscoloplos Day, 1977 is described as "Leitoscoloplos sp.", characterized by the lateral pouches on its abdominal chaetigers, a unique case for the family because these brooding structures have only been previously cited in two species of Scoloplos. Naineris sp. is characterized by the number of its thoracic chaetigers, branchiae, uncini and bilobed abdominal neuropodia with protruding aciculae.


Hands-on-ground in a new country: a community-based participatory evaluation with immigrant communities in Southern Alberta.
Immigrants experience a high risk of mental health deterioration following settlement in Canada. Immigrant communities benefit from health-promoting interventions that stimulate social inclusion and belonging as protective factors. In this context, community gardens have been recognized as interventions that promote healthy behaviours, place attachment and belonging.This article summarizes our experience conducting a community-based participatory evaluation (CBPE), engaging community stakeholders in planning, implementing and evaluating a community garden for immigrants. We conducted a CBPE to provide relevant and timely feedback to inform programme adaptation and development. Participants, interpreters and organizers were engaged through surveys, focus groups and semi-structured interviews. Participants expressed a range of motivations, benefits, challenges and recommendations. The garden was a place that fostered learning and promoted healthy behaviours, including physical activity and socialization. However, there were challenges in organization and communication with participants. Findings were used to adapt the activities to immigrants' needs and expand the programming of collaborating organizations. Stakeholder engagement facilitated capacity building and direct use of findings. This approach may catalyse sustainable community action with immigrant communities.


Safety of long-acting beta-agonists in stable COPD: a systematic review.
Some studies have suggested that use of long-acting beta(2)-agonists (LABAs) leads to an increased risk for adverse events in patients with stable COPD. The purpose of this review was to assess the safety, and secondarily the efficacy of LABAs. The authors conducted a systematic review with metaanalysis of randomized clinical trials (> or = 1 month in duration) in the published literature that have compared LABAs with placebo or anticholinergics in stable poorly reversible and reversible COPD. MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched to identify 27 studies. LABAs reduced severe exacerbations compared with placebo (relative risk [RR], 0.78; 95% confidence interval [CI], 0.67 to 0.91). There was no significant difference between LABA and placebo groups in terms of respiratory deaths (RR, 1.09; 95% CI, 0.45 to 2.64). Use of LABAs with inhaled corticosteroids reduced the risk of respiratory death compared with LABAs alone (RR, 0.35; 95% CI, 0.14 to 0.93). Patients receiving LABAs showed significant benefits in airflow limitation measures, health-related quality of life, and use of rescue medication. Finally, tiotropium decreased the incidence of severe COPD exacerbations compared with LABAs (RR, 0.52; 95% CI, 0.31 to 0.87). This review supports the beneficial effects of the use of LABAs in patients with stable moderate-to-severe COPD, and did not confirm previous data about an increased risk for respiratory deaths. Also, our analysis suggests the superiority of tiotropium over LABAs for the treatment of stable COPD patients.


[Chromametry, a promising technique for the quantification of skin changes in chronic venous disorders].
The development and validation of new clinimetric tools is essential for the progress of clinical research in the field of chronic venous insufficiency. Chromametry is a simple, quick and non-invasive technique that measures the color of the skin. The aim of this study was to evaluate the ability of this technique to quantify skin pigmentation as a marker of severity of chronic venous disease and to assess the variability of measurements obtained in this condition. Chomametry was performed on three different sites on each lower limb in 42 patients undergoing a spa treatment in La Léchère (Savoie) for chronic venous disorders (CVD). Four series of measurements were taken by two investigators for each patient, at two sessions two to four days apart. The chromameter readily measured the pigmentation index (PI). The PI increased with higher clinical class (CEAP classification) for measurements made at the malleolar level (r=0.48; P<0.001) and the supra-malleolar area (r=0.55; P<0.001), but not at the level of the anterior tibial tuberosity (r=-0.09; P=0.45). The repeatability and the intra- and inter-observer reproducibility of this PI index were 15%, 18% and 21% respectively of the mean of the observed difference at the malleolar level. The chromameter also provided an erythema index, which appears to be less relevant and more variable than the PI, but which might add potentially useful information regarding the characterization of skin inflammation related to the venous disease. This study shows that chromametry can be used in clinical research studies to quantify skin changes associated with CVD. Whether it can also be useful for early detection and follow-up of patients with venous trophic changes remains to be investigated.


Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia.
Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy.


Excited-state properties of the 16kDa red carotenoid protein from Arthrospira maxima.
We have studied spectroscopic properties of the 16kDa red carotenoid protein (RCP), which is closely related to the orange carotenoid protein (OCP) from cyanobacteria. Both proteins bind the same chromophore, the carotenoid 3'-hydroxyechinenone (hECN), and the major difference between the two proteins is lack of the C-terminal domain in the RCP; this results in exposure of part of the carotenoid. The excited-state lifetime of hECN in the RCP is 5.5ps, which is markedly longer than in OCP (3.3ps) but close to 6ps obtained for hECN in organic solvent. This confirms that the binding of hECN to the C-terminal domain in the OCP changes conformation of hECN, thereby altering its excited-state properties. Hydrogen bonds between the C-terminal domain and the carotenoid are also absent in the RCP. This allows the conformation of hECN in the RCP to be similar to that in solution, which results in comparable excited-state properties of hECN in solution. The red-shift of the RCP absorption spectrum is most likely due to aggregation of RCP induced by hydrophobic nature of hECN that, when exposed to buffer, stimulates formation of assemblies minimizing contact of hECN with water. We suggest that the loss of the C-terminal domain renders the protein amphipathic, containing both hydrophobic (the exposed part of hECN) and hydrophilic (N-terminal domain) regions, and may help the RCP to interact with lipid membranes; exposed hECN can penetrate into the hydrophobic environment of the lipid membrane, possibly to provide additional photoprotection.


Diffuse cystic bronchiectasis associated with left microtia and external auditory canal atresia: a very rare coincidence.
To present a case in which diffuse cystic bronchiectasis was associated with left microtia/external auditory canal atresia. A 10-year-old girl suffering from cough, fever, dyspnea and sputum for 6 months was transferred to our clinic due to the diagnosis of bronchopneumonia. She had recurrent episodes of bronchopneumonia. On examination, left microtia and left external auditory canal atresia were detected. Thorax CT revealed diffuse cystic bronchiectasis on the left lung. Radiological examination showed atresia of the left external auditory canal. We could not find any etiopathological reason causing bronchiectasis. The patient underwent left pneumonectomy and postoperative histopathology was reported as bronchiectasis. This report shows a unique case in which an association of diffuse cystic bronchiectasis and left microtia/external auditory canal atresia was observed. Hence in newborns with microtia and/or external auditory canal atresia, the probability of development of bronchiectasis should be borne in mind and such patients should be followed up more carefully regarding this rare association.


Improving ethanol yield in acetate-reducing Saccharomyces cerevisiae by cofactor engineering of 6-phosphogluconate dehydrogenase and deletion of ALD6.
Acetic acid, an inhibitor of sugar fermentation by yeast, is invariably present in lignocellulosic hydrolysates which are used or considered as feedstocks for yeast-based bioethanol production. Saccharomyces cerevisiae strains have been constructed, in which anaerobic reduction of acetic acid to ethanol replaces glycerol formation as a mechanism for reoxidizing NADH formed in biosynthesis. An increase in the amount of acetate that can be reduced to ethanol should further decrease acetic acid concentrations and enable higher ethanol yields in industrial processes based on lignocellulosic feedstocks. The stoichiometric requirement of acetate reduction for NADH implies that increased generation of NADH in cytosolic biosynthetic reactions should enhance acetate consumption. Replacement of the native NADP(+)-dependent 6-phosphogluconate dehydrogenase in S. cerevisiae by a prokaryotic NAD(+)-dependent enzyme resulted in increased cytosolic NADH formation, as demonstrated by a ca. 15% increase in the glycerol yield on glucose in anaerobic cultures. Additional deletion of ALD6, which encodes an NADP(+)-dependent acetaldehyde dehydrogenase, led to a 39% increase in the glycerol yield compared to a non-engineered strain. Subsequent replacement of glycerol formation by an acetate reduction pathway resulted in a 44% increase of acetate consumption per amount of biomass formed, as compared to an engineered, acetate-reducing strain that expressed the native 6-phosphogluconate dehydrogenase and ALD6. Compared to a non-acetate reducing reference strain under the same conditions, this resulted in a ca. 13% increase in the ethanol yield on glucose. The combination of NAD(+)-dependent 6-phosphogluconate dehydrogenase expression and deletion of ALD6 resulted in a marked increase in the amount of acetate that was consumed in these proof-of-principle experiments, and this concept is ready for further testing in industrial strains as well as in hydrolysates. Altering the cofactor specificity of the oxidative branch of the pentose-phosphate pathway in S. cerevisiae can also be used to increase glycerol production in wine fermentation and to improve NADH generation and/or generation of precursors derived from the pentose-phosphate pathway in other industrial applications of this yeast.


Antiarrhythmic surgery for treatment of atrial fibrillation--new concepts.
Curative treatment of atrial fibrillation is one of the main challenges of todays electrophysiology. The ideal treatment strategy should be effective, safe, and easy to apply to allow a widespread use. In addition, curative treatment should not only aim on the restoration of sinus rhythm but also restore mechanical atrial function to improve hemodynamics thereby avoiding anticoagulation. With respect to percutaneous catheter ablation no treatment concept with proven efficiency to cure chronic permanent atrial fibrillation is currently available. Surgical techniques such as the Corridor operation and the left atrial isolation procedure have been shown to effectively store sinus rhythm but these procedures do not restore biatrial transport function. Cox's Maze procedure is highly effective, however, it is an extensive and very time consuming technique which precludes the widespread application of this operation. Thus, new intraoperative treatment concepts are currently under intense clinical investigation. Most new concepts aim on the application of contiguous radiofrequency-induced lesion lines in the atria. Some of the new treatment strategies are based on the replacement of the surgical incisions of the Maze procedure using inrtraoperative radiofrequency coagulation thereby preventing functional determined reentrant circuits. Other new concepts aim on the induction of contiguous atrial lesion lines to eliminate anatomical determined atrial reentrant circuits. The main advantage of these new concepts when compared to the Maze procedure is a significantly shorter treatment time of approximately 20 minutes. In addition, some treatment strategies can also be applied in conjunction with minimally invasive cardiac surgery. The initial results reported with application of new treatment concepts indicate that approximately 60-80% of patients operated on can be cured from atrial fibrillation. Randomised studies with these new treatment strategies are necessary to validate the results and to outline which treatment concept may prove superior to others. Based on the progress made, it can be expected that intraoperative ablation of chronic permanent atrial fibrillation will become an important curative treatment strategy.


Characterization of the late-gene regulatory region of phage 21.
A segment of Escherichia coli bacteriophage 21 DNA encoding the late-gene regulator, Q21, and the late-gene leader RNA segment was sequenced; its structure is similar to those of the related phages lambda and 82. The leader RNA is about 45 nucleotides long and consists essentially entirely of sequences encoding the p-independent terminator that is the putative target of the antitermination activity of Q21. Like the corresponding regions of lambda and 82, the 21 late-gene promoter segment encodes an early transcription pause in vitro, at about nucleotide 18, during which Q21 presumably acts to modify RNA polymerase. The 21 Q gene, cloned in isolation, is active on the late-gene leader segment in trans, and its purified product is active as an antiterminator in vitro; Q21 represents a third late-gene antiterminator, in addition to those of lambda and 82. There is little evident similarity in the primary sequences of the three Q genes.


Endometrial expression of progesterone-induced blocking factor and galectins-1, -3, -9, and -3 binding protein in the luteal phase and early pregnancy in cattle.
Progesterone-induced blocking factor (PIBF) and galectins modulate the maternal immune response during pregnancy. We hypothesized that the relative transcript abundance of the above genes would be different during the luteal phase/early pregnancy and would be affected by progesterone supplementation. To further test this, hypothesis protein expression analyses were carried out to evaluate the abundance and localization of LGALS9 and PIBF. Following estrus synchronization, heifers were inseminated (n = 140) or not (n = 70). Half the heifers in each status (cyclic or potentially pregnant) were randomly assigned to receive a progesterone-releasing intravaginal device (PRID) on day 3 after estrus, which elevated progesterone concentrations from day 3.5 to 8 (P < 0.05), resulting in four treatment groups: cyclic and pregnant heifers, each with normal and high progesterone. After confirmation of pregnancy status in inseminated animals, uterine tissue was collected on days 5, 7, 13, or 16 of the luteal phase of the cycle/pregnancy. Gene and protein expression was determined using Q-RT-PCR and IHC, respectively, on 5 heifers per treatment per time point (i.e., 80 in total). Progesterone concentrations did not affect expression of any of the genes (P > 0.05). LGALS9 and LGALS3BP were expressed at low levels in both cyclic and pregnant endometria until day 13. On day 16, expression increased only in the pregnant heifers (P < 0.0001). LGALS1 and LGALS3 decreased on day 7 (P < 0.0001) and remained low until day 16. Pregnancy had no effect on the expression of LGALS1, LGALS3, and PIBF. Additionally, LGALS9 and PIBF proteins were expressed in distinct uterine cell types. These results indicate that the galectins may be involved in uterine receptivity and/or implantation in heifers.


Egg consumption and coronary heart disease: an epidemiologic overview.
Serum cholesterol has been established as a modifiable risk factor for coronary heart disease. Experimental feeding studies show that saturated fat and cholesterol increase serum cholesterol levels; thus, dietary recommendations for lowering the risk of heart disease proscribe the intake of both substances. Recommendations have also included limits on the intake of eggs because of their high cholesterol content. In free-living populations, diet reflects a pattern of associated choices. Increases in one food may lead to changes in the consumption of other foods that may modulate disease risk. Epidemiologic data are helpful in assessing the importance of foods and nutrients in the context in which they are actually consumed. We review epidemiologic data relating dietary cholesterol and eggs to coronary disease risk. Cholesterol intake was associated with a modest increase in the risk of coronary events. The true magnitude of the association is difficult to estimate because most studies fail to account for potential confounding by other features of the diet. When a full-range of confounding factors was considered, the association between cholesterol intake and heart disease risk was small (6% increase in risk for 200mg/1,000kcal/day difference in cholesterol intake). Several studies have examined egg intake and its relationship with coronary outcomes. All but one failed to consider the role of other potentially confounding dietary factors. When dietary confounders were considered, no association was seen between egg consumption at levels up to 1 + egg per day and the risk of coronary heart disease in non-diabetic men and women.


Can Economic Model Transparency Improve Provider Interpretation of Cost-effectiveness Analysis? Evaluating Tradeoffs Presented by the Second Panel on Cost-effectiveness in Health and Medicine.
The Second Panel on Cost-Effectiveness in Health and Medicine convened on December 7, 2016 at the National Academy of Medicine to disseminate their recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses (CEAs). Following its summary, panel proceedings included lengthy discussions including the field's struggle to disseminate findings efficiently through peer-reviewed literature to target audiences. With editors of several medical and outcomes research journals in attendance, there was consensus that findings of cost-effectiveness analyses do not effectively reach other researchers or health care providers. The audience members suggested several solutions including providing additional training to clinicians in cost-effectiveness research and requiring that cost-effectiveness models are made publicly available. However, there remains the questions of whether making economic modelers' work open-access through journals is fair under the defense that these models remain one's own intellectual property, or whether journals can properly manage the peer-review process specifically for cost-effectiveness analyses. In this article, we elaborate on these issues and provide some suggested solutions that may increase the dissemination and application of cost-effectiveness literature to reach its intended audiences and ultimately benefit the patient. Ultimately, it is our combined view as economic modelers and clinicians that cost-effectiveness results need to reach the clinician to improve the efficiency of medical practice, but that open-access models do not improve clinician access or interpretation of the economics of medicine.


Solitary neurofibroma of the adrenal gland not associated with type-1 neurofibromatosis.
Neurofibromas are tumors of neural origin. They can be solitary or may be associated with neurofibromatosis type-1 (NF-1). These are mostly seen in the head and neck region, upper extremities or along the nerves. Visceral neurofibromas are extremely rare. In this paper, we present an unusual case of solitary neurofibroma of the adrenal gland not associated with NF-1.


Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene.
Glucocorticoids act in part via glucocorticoid receptor binding to hormone response elements (HREs), but their direct target genes in vivo are still largely unknown. We developed the criterion that genomic occurrence of paired HREs at an inter-HRE distance less than 200 bp predicts hormone responsiveness, based on synergy of multiple HREs, and HRE information from known target genes. This criterion predicts a substantial number of novel responsive genes, when applied to genomic regions 10 kb upstream of genes. Multiple-tissue in situ hybridization showed that mRNA expression of 6 out of 10 selected genes was induced in a tissue-specific manner in mice treated with a single dose of corticosterone, with the spleen being the most responsive organ. Caveolin-1 was strongly responsive in several organs, and the HRE pair in its upstream region showed increased occupancy by glucocorticoid receptor in response to corticosterone. Our approach allowed for discovery of novel tissue specific glucocorticoid target genes, which may exemplify responses underlying the permissive actions of glucocorticoids.


Human milk oligosaccharides differ between HIV-infected and HIV-uninfected mothers and are related to necrotizing enterocolitis incidence in their preterm very-low-birth-weight infants.
The heavy burden of maternal HIV infection has resulted in a high prevalence of premature birth and associated necrotizing enterocolitis (NEC). Human milk oligosaccharides (HMOs) were recently associated with HIV infection and transmission through breastfeeding and were also shown to reduce NEC in an animal model, particularly the HMO disialyllacto-N-tetraose (DSLNT). The primary aim of this study was to verify differences in HMO composition between HIV-infected and HIV-uninfected women. The secondary aim was to assess whether the HMO composition in the milk of mothers whose infants were diagnosed with NEC differs from that of mothers whose infants did not develop NEC. This study forms part of a larger clinical trial conducted at the Tygerberg Children's Hospital, Cape Town, South Africa, which recruited HIV-infected and HIV-uninfected mothers and their preterm infants (<34 wk gestation; ≥500 and ≤1250 g). Eighty-two mother-infant pairs were selected for the substudy. Mother-infant pairs were stratified according to the mother's HIV (infected/uninfected) and secretor status (secretor/nonsecretor). HMOs in 4- and 28-d postpartum milk samples were analyzed by HPLC and compared between groups. Our results confirm previous reports that HIV-infected mothers have higher relative abundances of 3'-sialyllactose in their milk compared with HIV-uninfected mothers (10.7% vs. 6.8%; P < 0.01). Most intriguingly, the data also indicated that low concentrations of DSLNT in the 4-d milk samples in the mother's milk increased the infant's risk of NEC (200 ± 126 vs. 345 ± 186 μg/mL; P < 0.05), which is in accordance with results from previously published animal studies and warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01868737.


Genome-wide analysis of the cyclin family in Arabidopsis and comparative phylogenetic analysis of plant cyclin-like proteins.
Cyclins are primary regulators of the activity of cyclin-dependent kinases, which are known to play critical roles in controlling eukaryotic cell cycle progression. While there has been extensive research on cell cycle mechanisms and cyclin function in animals and yeasts, only a small number of plant cyclins have been characterized functionally. In this paper, we describe an exhaustive search for cyclin genes in the Arabidopsis genome and among available sequences from other vascular plants. Based on phylogenetic analysis, we define 10 classes of plant cyclins, four of which are plant-specific, and a fifth is shared between plants and protists but not animals. Microarray and reverse transcriptase-polymerase chain reaction analyses further provide expression profiles of cyclin genes in different tissues of wild-type Arabidopsis plants. Comparative phylogenetic studies of 174 plant cyclins were also performed. The phylogenetic results imply that the cyclin gene family in plants has experienced more gene duplication events than in animals. Expression patterns and phylogenetic analyses of Arabidopsis cyclin genes suggest potential gene redundancy among members belonging to the same group. We discuss possible divergence and conservation of some plant cyclins. Our study provides an opportunity to rapidly assess the position of plant cyclin genes in terms of evolution and classification, serving as a guide for further functional study of plant cyclins.


Composite quality measures of abdominal surgery at a population level: systematic review.
Measurement of surgical quality at a population level is challenging. Composite quality measures derived from administrative and clinical information systems could support system-wide surgical quality improvement by providing a simple metric that can be evaluated over time. The aim of this systematic review was to identify published studies of composite measures used to assess the overall quality of abdominal surgical services at a hospital or population level. A search was conducted in PubMed and MEDLINE for references describing measurement instruments evaluating the overall quality of abdominal surgery. Instruments combining multiple process and quality indicators into a single composite quality score were included. The identified instruments were described in terms of transparency, justification, handling of missing data, case-mix adjustment, scale branding and choice of weight and uncertainty to assess their relative strengths and weaknesses (PROSPERO registration: CRD42022345074). Of 5234 manuscripts screened, 13 were included. Ten unique composite quality measures were identified, mostly developed within the past decade. Outcome measures such as mortality rate (40 per cent), length of stay (40 per cent), complication rate (60 per cent) and morbidity rate (70 per cent) were consistently included. A major challenge for all instruments is the reliance of valid administrative data and the challenges of assigning appropriate weights to the underlying instrument components. A conceptual framework for composite measures of surgical quality was developed. None of the composite quality measures identified demonstrated marked superiority over others. The degree to which administrative and clinical data influences each composite measure differs in important ways. There is a need for further testing and development of these measures.


An Extended Minimal Model of OGTT: Estimation of Alpha- and Beta-Cell Dysfunction, Insulin Resistance, and the Incretin Effect.
Loss of insulin sensitivity, alpha- and beta-cell dysfunction, and impairment in incretin effect have all been implicated in the pathophysiology of type 2 diabetes (T2D). Parsimonious mathematical models are useful in quantifying parameters related to the pathophysiology of T2D. Here we extend the minimum model developed to describe the glucose-insulin-glucagon dynamics in the intravenous glucose infusion (IIGI) experiment to the oral glucose tolerance test (OGTT). The extended model describes glucose and hormone dynamics in OGTT including the contribution of the incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), to insulin secretion. A new function describing glucose arrival from the gut is introduced. The model is fitted to OGTT data from 8 patients with T2D and 8 weight-matched control subjects (CS) without diabetes to obtain parameters related to insulin sensitivity, beta- and alpha-cell function. The parameters, i.e., measures of insulin sensitivity, a1, suppression of glucagon secretion, k1, magnitude of glucagon secretion, g2, and incretin-dependent insulin secretion, g3, were found to be significantly different between CS and T2D with p values < .002, < .017, < .009, < .004, respectively. A new rubric for estimating the incretin effect directly from modeling the OGTT is presented. The average incretin effect correlated well with the experimentally determined incretin effect with a Spearman Rank test correlation coefficient of .67 (p < .012). The average incretin effect was found to be significantly different between CS and T2D (p <.032). The developed model is shown to be effective in quantifying the factors relevant to T2D pathophysiology.


Can a postgraduate course for general practitioners deliver perceived benefit for learners, patients and the NHS?: a qualitative study.
The focus of continuing professional development in general practice is shifting towards professional development and away from following personal areas of interest. Previous work has suggested that much CPD has not had an obvious impact in the three areas of professional development: the needs of individual doctors, patients and the needs of the NHS. We report on the results of a programme of study where developments in all three were perceived as being achieved. This outcome was realized by basing learning around real problems course members encountered in their daily work, using these real situations to identify theory, then reinforcing this learning through practical application.


Heart failure with normal ejection fraction.
Heart failure with normal ejection fraction (HFNEF) is a complex syndrome that has been broadly studied since the last decade. It is caused by diastolic ventricular dysfunction demonstrated by complementary methods, such as hemodynamic study or echocardiogram, in the presence of a normal ejection fraction (EF). It affects primarily elderly individuals with comorbidities, such as systemic arterial hypertension, coronary failure and obesity. The physiopathological mechanisms are complex and multifactorial, involving the myocardial passive stiffness, the ventricular geometry, the pericardial restraint and the interaction between the ventricles. The main objectives of the treatment were to decrease the pulmonary venous congestion and the heart rate and control the comorbidities. There is no strong evidence that the use of specific medications, such as the angiotensin-converting enzyme inhibitors or beta-blockers can influence mortality. The poorer prognostic factors include advanced age, presence of kidney dysfunction, diabetes, functional class III and IV (NYHA) and advanced-stage diastolic dysfunction, with a restrictive pattern of ventricular filling. Another aspect that has been increasingly cited in the literature is the analysis of the role of the systolic function in HFNEF cases. All these aspects are analyzed in detail in the present review.


Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure.
Developing alternative approaches to evaluating absolute efficacy of new HIV prevention interventions is a priority, as active-controlled designs, whereby individuals without HIV are randomized to the experimental intervention or an active control known to be effective, are increasing. With this design, however, the efficacy of the experimental intervention to prevent HIV acquisition relative to placebo cannot be evaluated directly. One proposed approach to estimate absolute prevention efficacy is to use an HIV exposure marker, such as incident rectal gonorrhea, to infer counterfactual placebo HIV incidence. We formalize a statistical framework for this approach, specify working regression and likelihood-based estimation approaches, lay out three assumptions under which valid inference can be achieved, evaluate finite-sample performance, and illustrate the approach using a recent active-controlled HIV prevention trial. We find that in finite samples and under correctly specified assumptions accurate and precise estimates of counterfactual placebo incidence and prevention efficacy are produced. Based on data from the DISCOVER trial in men and transgender women who have sex with men, and assuming correctly specified assumptions, the estimated prevention efficacy for tenofovir alafenamide plus emtricitabine is 98.1% (95% confidence interval: 96.4%-99.4%) using the working model approach and 98.1% (95% confidence interval: 96.4%-99.7%) using the likelihood-based approach. Careful assessment of the underlying assumptions, study of their violation, evaluation of the approach in trials with placebo arms, and advancement of improved exposure markers are needed before the HIV exposure marker approach can be relied upon in practice.


Out-of-hospital pediatric airway management in the United States.
The objective of this study was to characterize pediatric out-of-hospital airway management interventions, success rates, and complications in the United States using the 2012 National Emergency Medical Services Information System (NEMSIS) dataset. In 2012, NEMSIS collected data from Emergency Medical Services (EMS) encounters in 40 states. We included all patients less than 18 years of age and identified all patients who had airway interventions including endotracheal intubation (ETI), bag-valve-mask ventilation (BVM), continuous positive airway pressure/bilevel positive airway pressure (CPAP/BiPAP) and alternate airways (Combitube, King LT, Laryngeal Mask Airway (LMA), esophageal obturator airway, and cricothyroidotomy). Success and complication rates were analyzed and compared across pediatric age groups, by race, ethnicity, clinical condition, and geographic region. We identified a total of 949,301 pediatric patient care events in the NEMSIS 2012 dataset. 4.5% had airway management procedures (42,936 events). Invasive airway management or ventilation (ETI, cricothyroidotomy, alternate airway, CPAP/BiPAP, BVM and other ventilation) took place in 1.5% of patient care events (14,107). Of those who had invasive airway management, 29.9% were less than 1 year of age, 58.1% were male, 42.3% were white, and 83.6% were in urban areas. ETI occurred in 3124 of patient care events (329 per 100,000; 95% CI 318-341). Overall success of ETI was 81.1% (95% CI 79.7-82.6). Lower success was noted in patients with cardiac arrest (75.5%, 95% CI 72.6-78.3) and those aged 1-12 months (72.1%, 95% CI 68.3-75.6). Out-of-hospital pediatric advanced airway procedures were infrequently performed. Success rates are lowest in patients aged 1-12 months.


The impact of extended-cycle vaginal ring contraception on migraine aura: a retrospective case series.
To determine whether extended-cycle dosing of an ultralow dose vaginal ring contraceptive decreases frequency of migraine aura and prevents menstrual related migraine (MRM). Many women are denied therapy with combined hormonal contraceptives due to published guidelines that recommend against their use in migraine with aura (MwA). The concern is that these products might further elevate the risk of ischemic stroke that accompanies aura. Stroke risk has been reported to vary directly with aura frequency, and aura frequency in turn has been shown to have a direct relationship to estrogen concentration. With the evolution of increasingly lower dosed combined hormonal contraceptives, we now have formulations that--provided that ovulation is inhibited--result in lower peak levels of estrogen than the concentrations attained during the native menstrual cycle. These formulations would thus be expected to result in a lower frequency of migraine aura. Furthermore, as extended-cycle therapy eliminates monthly estrogen withdrawals, this therapy would likewise be expected to prevent MRM. This pilot study is an institutional review board-approved retrospective database review. We queried our database of 830 women seen in a subspecialty menstrual migraine clinic to identify women who met all inclusion criteria: (1) current history of MwA; (2) confirmed diagnosis of MRM; and (3) treatment with extended-cycle dosing of a transvaginal ring contraceptive containing 0.120 mg etonogestrel/15 µg ethinyl estradiol. Standardized calendars that specifically document bleeding patterns, headache details, and occurrence of aura are required of all patients in this clinic. Twenty-eight women met study criteria, none of whom were smokers. Of these, 5 discontinued use of etonogestrel/ethinyl estradiol within the first month, leaving 23 evaluable subjects. At baseline, subjects averaged 3.23 migraine auras/month (range: 0.1-12). With extended dosing of the vaginal ring contraceptive, median frequency was reduced to 0.23 auras per month following treatment after a mean observation of 7.8 months (P < .0005). No subject reported an increase in aura frequency. On this regimen, MRM was eliminated in 91.3% of the evaluable subjects. In this sample of women with both MwA and MRM, use of an extended-cycle vaginal ring contraceptive was associated with a reduced frequency of migraine aura and with resolution of MRM. This cannot be extrapolated to suggest that stroke risk in MwA will be similarly reduced. Studies to evaluate this relationship are warranted.


An Iterative Curve-Fitting Baseline Correction Method for Raman Spectra Driven by Neural Network.
Baseline correction is a vital part of spectral preprocessing, especially for Raman spectra. Iterative polynomial fitting is an easy but less accurate way to find baselines compared to other methods such as wavelet transform and penalized least squares (PLS) methods. The polynomial fitting methods can also get distorted results in certain conditions. In this paper, a neural network model for detecting the trend of the baseline was proposed to improve the correction accuracy of the fitting methods. The model selects the function basis according to the baseline trend instead of using a fixed polynomial function to match the baseline for a more precise fit. We also propose a way to generate simulation data, these data can be used to train the neural network model. The model provides reliable results for real spectral data with noise. Our method provides a new idea to correct the baseline with a strange shape. In addition, we examine the limitations of conventional iterative polynomial fitting, adaptive iteratively reweighted PLS and explain why our approach surpasses these methods.


Restoration of Chemosensitivity in P-Glycoprotein-Dependent Multidrug-Resistant Cells by Dihydro-β-agarofuran Sesquiterpenes from Celastrus vulcanicola.
Multidrug resistance (MDR) caused by the overexpression of ABC drug transporters is a major obstacle in clinical cancer chemotherapy and underlines the urgent need for the development of new, potent, and safe reversal agents. Toward this goal, reported herein are the structure elucidation and biological activity of nine new (1-9) and four known (10-13) dihydro-β-agarofuran sesquiterpenes, isolated from the leaves of Celastrus vulcanicola, as reversers of MDR mediated by human P-glycoprotein expression. The structures of these compounds were elucidated by extensive NMR spectroscopic and mass spectrometric analysis, and their absolute configurations were determined by circular dichroism studies, chemical correlations (1a, 8a, and 8b), and biogenetic means. Four compounds from this series were discovered as potent chemosensitizers for MDR1-G185 NIH-3T3 murine cells (3, 4, 6, and 7), showing higher efficacies than the classical P-glycoprotein inhibitor verapamil, a first-generation chemosensitizer, when reversing resistance to daunomycin and vinblastine at the lowest concentration tested of 1 μM.


Light-Activated Liposomes Coated with Hyaluronic Acid as a Potential Drug Delivery System.
Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA-lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.


Striatal Acetylcholine Helps to Preserve Functional Outcomes in a Mouse Model of Stroke.
Acetylcholine (ACh) has been suggested to facilitate plasticity and improve functional recovery after different types of brain lesions. Interestingly, numerous studies have shown that striatal cholinergic interneurons are relatively resistant to acute ischemic insults, but whether ACh released by these neurons enhances functional recovery after stroke is unknown. We investigated the role of endogenous striatal ACh in stroke lesion volume and functional outcomes following middle cerebral artery occlusion to induce focal ischemia in striatum-selective vesicular acetylcholine transporter-deficient mice (stVAChT-KO). As transporter expression is almost completely eliminated in the striatum of stVAChT-KO mice, ACh release is nearly abolished in this area. Conversely, in other brain areas, VAChT expression and ACh release are preserved. Our results demonstrate a larger infarct size after ischemic insult in stVAChT-KO mice, with more pronounced functional impairments and increased mortality than in littermate controls. These changes are associated with increased activation of GSK-3, decreased levels of β-catenin, and a higher permeability of the blood-brain barrier in mice with loss of VAChT in striatum neurons. These results support a framework in which endogenous ACh secretion originating from cholinergic interneurons in the striatum helps to protect brain tissue against ischemia-induced damage and facilitates brain recovery by supporting blood-brain barrier function.


The effects of contemporary processes in maintaining the genetic structure of western song sparrows (Melospiza melodia).
Historic events and contemporary processes work in concert to create and maintain geographically partitioned variation and are instrumental in the generation of biodiversity. We sought to gain a better understanding of how contemporary processes such as movement and isolation influence the genetic structure of widely distributed vagile species such as birds. Song sparrows (Melospiza melodia) in western North America provide a natural system for examining the genetics of populations that have different patterns of geographic isolation and migratory behavior. We examined the population genetics of 576 song sparrows from 23 populations using seven microsatellite loci to assess genetic differentiation among populations and to estimate the effects of drift and immigration (gene flow) on each population. Sedentary, isolated populations were characterized by low levels of immigration and high levels of genetic drift, whereas those populations less isolated displayed signals of high gene flow and little differentiation from other populations. Contemporary dispersal rates from migratory populations, estimated by assignment test, were higher and occurred over larger distances than dispersal from sedentary populations but were also probably too low to counter the effects of drift in most populations. We suggest that geographic isolation and limited gene flow facilitated by migratory behavior are responsible for maintaining observed levels of differentiation among Pacific coastal song sparrow populations.


VIAMD: a Software for Visual Interactive Analysis of Molecular Dynamics.
The typical workflow in molecular dynamics (MD) analysis requires several separate tools, often resulting in a lack of synergy and interaction between the individual analysis steps. This article presents VIAMD, an application designed to address this issue by integrating a 3D visualization of molecular trajectories with flexible analysis components. VIAMD uses an interactive scripting interface, allowing for property definition and evaluation. The application provides context-aware suggestions and expression feedback through information and visualizations. The user-defined properties can be explored and analyzed through the various components. This enables correlation with spatial conformations, statistical analysis of distributions, and powerful aggregation of multidimensional properties such as spatial distribution functions. VIAMD has the potential to advance research in many scientific disciplines and is a promising solution for improving the workflow of MD visualization and analysis.


Guidelines and controversies in the management of diabetic ketoacidosis - A mini-review.
Diabetic ketoacidosis (DKA) is a complication seen in patients with both type 1 and type 2 diabetes. Due to its large, growing economic impact with associated morbidity, closer look at proper management is important. Factors involved in appropriate management involves fluid resuscitation, insulin regimen, and electrolyte replacement including types of fluid and insulin treatment. The caveat with generalized protocol is application to special populations such as renal or heart failure patients the sequelae of complications due to pathophysiology of the disease processes. This leads to complications and longer length of stay in the hospital, therefore, possibly increased cost and resource utilization during the hospitalization. This review takes a closer look at current guidelines of DKA management and resource utilization, the drawbacks of current management protocols and the cost associated with it. Therefore, a need for amendment to existing protocol or initiation of a newer guideline that properly manages DKA should incorporate special populations and appropriate regimen of fluid resuscitation, insulin therapy and electrolyte management.


Transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region from p&pmacr; collisions at sqrt
The transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region of 66<M(ee)<116 GeV/c(2) from p&pmacr; collisions at sqrt[s] = 1.8 TeV are measured using 110 pb(-1) of collisions taken by the Collider Detector at Fermilab during 1992-1995. The total cross section is measured to be 248+/-11 pb. The differential transverse momentum cross section is compared with calculations that match quantum chromodynamics perturbation theory at high transverse momentum with the gluon resummation formalism at low transverse momentum.


Sepsis-related anemia in a pediatric intensive care unit: transfusion-associated outcomes.
Pediatric patients with sepsis in intensive care units are at high risk of developing anemia, which might have adverse effects on their prognosis. This study aimed to evaluate the impact of red blood cell (RBC) transfusion on the outcomes of patients admitted to a pediatric intensive care unit (PICU) with sepsis. We conducted a prospective randomized clinical trial, enrolling 67 children, aged 2 to 144 months who were admitted to a PICU with a new episode of sepsis from November 2017 to April 2018. Patients were allocated randomly to two groups: Group 1, liberal transfusion strategy group, including 33 patients who had initial hemoglobin (Hb) between 7 or greater and less than 10 g/dL and received an RBC top-up transfusion to 12 g/dL; and Group 2, restrictive strategy group, including 34 patients who had the same Hb range and did not receive RBCs. Patients with Hb less than 7 or greater than 10 g/dL were excluded. Of 33 patients who received liberal transfusions, 31 (93.94%) required ventilation, and 29 (87.88%) had multiorgan dysfunction. They had a significantly lengthier hospital stay and a higher incidence of acute respiratory distress syndrome and acute lung injury. Moreover, mortality was significantly higher in the liberal transfusion group (42.4% vs. 17.6%). Compared to the restrictive transfusion strategy, liberal transfusion might be associated with a worse outcome. However, the possible role of other known and unknown confounding factors and minor protocol violations should be taken into consideration. We recommend minimizing factors worsening anemia in PICU patients to reduce the need for transfusion.


Variant rs1906591 on chromosome 4q25 confers increased risk of cardioembolic stroke in Chinese patients.
Ischemic stroke (IS) is a heterogeneous multifactorial disorder caused by both genetic and environmental factors. A genome-wide association study on stroke in Caucasians identified a variant on chromosome 4q25 that is significantly associated with IS, with the strongest risk for cardioembolic stroke (CES). The current study aims to investigate the association of the rs1906591 variant on 4q25 with IS through a case-control study in a Chinese Han population. A total of 712 IS patients and 774 control subjects were involved in the current research. Stroke subtyping was performed according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The genotypes were determined using the SNaPshot technique. The association of the genotypes with the risk of IS was estimated using logistic regression analysis. The rs1906591 single nucleotide polymorphism variant was associated with the CES subtype in both recessive and additive models (recessive model: odds ratio [OR]=2.58, 95% confidence interval [CI] 1.47-4.53, p=0.001, adjusted OR=2.71, 95% CI 1.48-4.96, p=0.001; additive model: OR=2.50, 95% CI 1.19-5.25, p=0.015, adjusted OR=2.83, 95% CI 1.24-6.50, p=0.013). This result indicates that patients with the AA genotype have a higher rate of CES than other genotypes. However, the rs1906591 variant was not significantly associated with the overall incidence of stroke or other stroke subtypes. The rs1906591 variant is significantly associated with CES in the Chinese Han population, but not with other stroke subtypes.


[MODY type diabetes: overview and recent findings].
We present an update of knowledge on diabetes MODY (maturity onset diabetes of the young), including the recent molecular discoveries, and new diagnostic strategies. Considerable progress has been made in understanding the different molecular abnormalities that cause MODY and the phenotypic consequences resulting therefrom. MODY diabetes is very heterogeneous and is the most common form of monogenic diabetes. Its distribution is worldwide. MODY is an autosomal dominant diabetes mellitus, nonketotic and occurs at an early age (usually before 25 years). To date, at least seven genes are associated with MODY, with frequencies that differ from one population to another. Both 2 and 3 subtypes predominate, while other subtypes (1, 4, 5, 6 and 7) concern only a few families. Since its discovery in the sixties, studies have succeeded to fully clarify the epidemiological, molecular and clinical diagnosis of each subtype, to provide better care for patients. However, the subject of MODY has not yet revealed all its secrets. Indeed, it remains to identify other genes that are associated with MODY X.


[Structural equation modeling on quality of life in stroke survivors].
This study was designed to test structural equation modeling of the quality of life of stroke survivors in order to provide guidelines for development of interventions and strategies to improve their quality of life. The participants in the study were patients who visited the neurology outpatient department of a tertiary hospital in Seoul between June 25 and October 15, 2009. Data collection was carried out through one-on-one interviews. Demographic factors, functional independence, social support, nutritional status, post-stroke biobehavioral changes and quality of life were investigated. The final analysis included 215 patients. Fitness of the hypothetical model was appropriate (χ(2)=111.5, p=.000, GFI=.926, AGFI=.880, RMSA=.068, NFI=.911, CFI=.953). Functional dependency, social support and post-stroke biobehavioral changes were found to be significant explaining variance in quality of life. Post-stroke biobehavioral changes had the strongest direct influence on quality of life. Nutritional status had an indirect effect on the quality of life. To improve the quality of life of stroke survivors, comprehensive interventions are necessary to manage post-stroke biobehavioral changes, and strengthening social support networks that can contribute to enhancing the quality of life of stroke survivors.


The use of an analog type apex locator to assess the position of dentine pins.
An analog type apex locator was used to check the position of dentine pins. The teeth restored with the pins were reviewed. The analog type apex locator was easy to use and the readings obtained correlated well with the presence or absence of later symptoms from the tooth. This electrical method of checking pin position was more discerning than the method of direct observation.