Efficacy of the photobiomodulation therapy in the treatment of the burning mouth syndrome.
This study aims to evaluate the efficacy of the photobiomodulation therapy (PBMT) - in terms of pain and of quality of life- in patients affected by burning mouth syndrome (BMS). This study was designed as a randomised double-blinded prospective study. Patients diagnosed with BMS in the period from June 2015 to June 2018 were recruited. The patients were randomised into two groups and each received treatment once a week for ten weeks: group A received laser therapy (K Laser Cube 3) while group B was given sham therapy (placebo). Pain was evaluated through the Visual Analogue Scale (VAS) and quality of life was assessed with the short form of the Oral Health Impact Profile (OHIP-14). Assessment was done at baseline and after every therapy session. The researchers were blind to the randomised allocations. A total of 85 patients were analysed. Group A (laser treatment) was composed of 43 patients while group B (sham therapy) of 42 patients. Patients treated with PBMT showed a significant decrease in symptoms ( p=0.0008) and improved quality of life related to oral health ( p=0.0002). PBMT has demonstrated to have a positive effect in relieving BMS symptoms and in improving a patient's overall quality of life.


Multipotential hematopoietic progenitor cells from embryos developed in vitro engraft unconditioned W41/W41 neonatal miceB.
The first hematopoietic stem cells (HSC) in the mouse able to give rise to the adult hematopoietic system emerge at embryonic day (E) 10.5 in the intraembryonic aorta-gonads-mesonephros (AGM) region, as demonstrated by transplantation into irradiated adult recipients. It has been shown by transplantation into conditioned neonatal or hematopoietic mutant adult recipients that less potent multipotential hematopoietic progenitors exist in the mouse embryo at E9, one day earlier than the appearance of HSC. Studies of the lineage relationships of multipotential hematopoietic progenitors and HSC in the mouse embryo have been complicated by inaccessibility due to in utero development. Attempts are being made to create an in vitro whole mouse embryo culture system to access the developing mouse embryo for such studies of hematopoietic cell emergence during early and mid-gestational stages. The aim of this study was to compare the development of multipotential hematopoietic progenitors in early in utero and in vitro-developed mouse embryos. To test hematopoietic progentior/stem cell activity in the mouse embryonic tissues obtained from genetically marked in utero and in vitro-developed embryos, transplantations were performed using unconditioned neonatal W41/W41 (c-kit hematopoietic mutant) recipients. Long-term donor-cell reconstitution in transplanted mice was measured by (i) semiquantitative polymerase chain reaction and (ii) flow cytometry on peripheral blood and hematopoietic organs. Our experimental data show that multipotent hematopoietic progenitors from in utero-developed embryos engraft unconditioned W41/W41 neonates. Furthermore, in vitro-developed whole embryos also contain early multipotent hematopoietic progenitor cells that are able to yield high-level, long-term engraftment of W41/W41 neonates. The in vitro culture of whole mouse embryos during mid-gestational stages allows for the normal growth of multipotential hematopoietic progenitors that can be assayed by transplantation into W41/W41 neonatal recipients. Thus, in vitro-developed whole embryos can be used with confidence in future studies to examine the lineage relationships of multipotential hematopoietic progenitors and HSC.


Analytic expressions for ULF wave radiation belt radial diffusion coefficients.
We present analytic expressions for ULF wave-derived radiation belt radial diffusion coefficients, as a function of L and Kp, which can easily be incorporated into global radiation belt transport models. The diffusion coefficients are derived from statistical representations of ULF wave power, electric field power mapped from ground magnetometer data, and compressional magnetic field power from in situ measurements. We show that the overall electric and magnetic diffusion coefficients are to a good approximation both independent of energy. We present example 1-D radial diffusion results from simulations driven by CRRES-observed time-dependent energy spectra at the outer boundary, under the action of radial diffusion driven by the new ULF wave radial diffusion coefficients and with empirical chorus wave loss terms (as a function of energy, Kp and L). There is excellent agreement between the differential flux produced by the 1-D, Kp-driven, radial diffusion model and CRRES observations of differential electron flux at 0.976 MeV-even though the model does not include the effects of local internal acceleration sources. Our results highlight not only the importance of correct specification of radial diffusion coefficients for developing accurate models but also show significant promise for belt specification based on relatively simple models driven by solar wind parameters such as solar wind speed or geomagnetic indices such as Kp. Analytic expressions for the radial diffusion coefficients are presentedThe coefficients do not dependent on energy or wave m valueThe electric field diffusion coefficient dominates over the magnetic.


Polychlorinated biphenyl rhizoremediation by Pseudomonas fluorescens F113 derivatives, using a Sinorhizobium meliloti nod system to drive bph gene expression.
Rhizoremediation of organic chemicals requires high-level expression of biodegradation genes in bacterial strains that are excellent rhizosphere colonizers. Pseudomonas fluorescens F113 is a biocontrol strain that was shown to be an excellent colonizer of numerous plant rhizospheres, including alfalfa. Although a derivative of F113 expressing polychlorinated biphenyl (PCB) biodegradation genes (F113pcb) has been reported previously, this strain shows a low level of bph gene expression, limiting its rhizoremediation potential. Here, a high-level expression system was designed from rhizobial nod gene regulatory relays. Nod promoters were tested in strain F113 by using beta-galactosidase transcriptional fusions. This analysis showed that nodbox 4 from Sinorhizobium meliloti has a high level of expression in F113 that is dependent on an intact nodD1 gene. A transcriptional fusion of a nodbox cassette containing the nodD1 gene and nodbox 4 fused to a gfp gene was expressed in the alfalfa rhizosphere. The bph operon from Burkholderia sp. strain LB400 was cloned under the control of the nodbox cassette and was inserted as a single copy into the genome of F113, generating strain F113L::1180. This new genetically modified strain has a high level of BphC activity and grows on biphenyl as a sole carbon and energy source at a growth rate that is more than three times higher than that of F113pcb. Degradation of PCBs 3, 4, 5, 17, and 25 was also much faster in F113L::1180 than in F113pcb. Finally, the modified strain cometabolized PCB congeners present in Delor103 better than strain LB400, the donor of the bph genes used.


[Epicardial adipose tissue and its role in cardiac physiology and disease].
Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT) has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype) leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.


Efficacy of psychosocial intervention in patients with mild Alzheimer's disease: the multicentre, rater blinded, randomised Danish Alzheimer Intervention Study (DAISY).
To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers. Multicentre, randomised, controlled, rater blinded trial. Primary care and memory clinics in five Danish districts. 330 outpatients with mild Alzheimer's disease and their 330 primary care givers. Participating dyads (patient and primary care giver) were randomised to control support during follow-up or to control support plus DAISY intervention (multifaceted and semi-tailored counselling, education, and support). Primary outcomes at 12 months for patients were change from baseline in mini mental state examination (MMSE) score, Cornell depression scale score, and proxy rated European quality of life visual analogue scale (EQ-VAS) score. For care givers, outcomes were change from baseline in geriatric depression scale (GDS 30 items) score and EQ-VAS score. Because of multiple testing, statistical significance was set at an adjusted P limit of <0.0005. At 12 months there were no significant differences between the two allocation groups in changes from baseline in the primary and secondary outcomes. However, although non-significant with the adjusted P limit, a small difference was observed for one of the primary patient outcomes (Cornell depression scale score) in patients in favour of the DAISY intervention group before and after adjusting for attrition (P = 0.0146 and P = 0.0103 respectively). The multifaceted, semi-tailored intervention with counselling, education, and support for patients with mild Alzheimer's disease and their care givers did not have any significant effect beyond that with well structured follow-up support at 12 months after adjustment for multiple comparisons. The small positive effect found in the unadjusted primary outcome addressing depressive symptoms in patients may call for further research focusing on patients with Alzheimer's disease and comorbid depression. ISRCTN74848736.


PRBS orders required to train ANN equalizer for PAM signal without overfitting.
Artificial neural network (ANN)-based nonlinear equalizers (NLEs) have been gaining popularity as powerful waveform equalizers for intensity-modulation (IM)/direct-detection (DD) systems. On the other hand, the M-ary pulse amplitude modulation (PAM-M) format is now widely used for high-speed IM/DD systems. For the training of ANN-NLE in PAM-M IM/DD systems, it is common to employ pseudorandom binary sequences (PRBSs) for the generation of PAM-M training sequences. However, when the PRBS orders used for training are not sufficiently high, the ANN-NLE might suffer from the overfitting problem, where the equalizer can estimate one or more of the constituent PRBSs from a part of PAM-M training sequence, and as a result, the trained ANN-NLE shows poor performance for new input sequences. In this paper, we provide a selection guideline of the PRBSs to train the ANN-NLE for PAM-M signals without experiencing the overfitting. For this purpose, we determine the minimum PRBS orders required to train the ANN-NLE for a given input size of the equalizer. Our theoretical analysis is confirmed through computer simulation. The selection guideline is applicable to training the ANN-NLE for the PAM-M signals, regardless of symbol coding.


Mechanism of dual specificity kinase activity of DYRK1A.
The function of many protein kinases is controlled by the phosphorylation of a critical tyrosine residue in the activation loop. Dual specificity tyrosine-phosphorylation-regulated kinases (DYRKs) autophosphorylate on this tyrosine residue but phosphorylate substrates on aliphatic amino acids. This study addresses the mechanism of dual specificity kinase activity in DYRK1A and related kinases. Tyrosine autophosphorylation of DYRK1A occurred rapidly during in vitro translation and did not depend on the non-catalytic domains or other proteins. Expression in bacteria as well as in mammalian cells revealed that tyrosine kinase activity of DYRK1A is not restricted to the co-translational autophosphorylation in the activation loop. Moreover, mature DYRK1A was still capable of tyrosine autophosphorylation. Point mutants of DYRK1A and DYRK2 lacking the activation loop tyrosine showed enhanced tyrosine kinase activity. A series of structurally diverse DYRK1A inhibitors was used to pharmacologically distinguish different conformational states of the catalytic domain that are hypothesized to account for the dual specificity kinase activity. All tested compounds inhibited substrate phosphorylation with higher potency than autophosphorylation but none of the tested inhibitors differentially inhibited threonine and tyrosine kinase activity. Finally, the related cyclin-dependent kinase-like kinases (CLKs), which lack the activation loop tyrosine, autophosphorylated on tyrosine both in vitro and in living cells. We propose a model of DYRK autoactivation in which tyrosine autophosphorylation in the activation loop stabilizes a conformation of the catalytic domain with enhanced serine/threonine kinase activity without disabling tyrosine phosphorylation. The mechanism of dual specificity kinase activity probably applies to related serine/threonine kinases that depend on tyrosine autophosphorylation for maturation.


Lifelong learning practices and leisure-time exercise habits of academic and community-based physicians.
This article was migrated. The article was marked as recommended. Objective: Physicians are required to be lifelong learners for the provision of quality patient care. At the same time, physician wellbeing is a critical component in the delivery of such care. This study was designed to examine: (1) lifelong learning practices and leisure-time exercise habits of academic and community-based physicians; and (2) associations of leisure-time exercise with work engagement, exhaustion, and professional life satisfaction. Methods: Using an online survey, quantitative data were collected from physicians practicing in Canada. The survey contained validated scales of physician lifelong learning, leisure-time exercise, work engagement, work exhaustion, and professional life satisfaction. Descriptive, chi-square, t-test, and correlational analyses were performed. Results: Physicians (n=57) reported moderately high levels of lifelong learning, with no significant difference between academic and community-based physicians. To stay current in their practice, the majority of physicians reported exchanging ideas/asking colleagues and searching databases as questions arise (>90%), followed by engaging in clinical teaching and attending conferences and meetings of professional organizations (>80%). Watching podcasts and webinars was the least preferred lifelong learning activity (<50%). With respect to leisure-time exercise habits, more community-based physicians reported engaging in mild and/or moderate forms of exercising, whereas more academic physicians reported engaging in strenuous exercising in a typical week. Correlational analyses revealed that physicians' leisure-time exercise scores were positively correlated with professional life satisfaction (r = 0.25; p = 0.058) and work engagement (r = 0.29; p = 0.028) and negatively correlated with work exhaustion (r = -0.34; p = 0.01). Conclusions: Irrespective of the practice type, physicians tend to engage in lifelong learning activities that offer in-person interactions with colleagues and trainees. Regular participation in leisure-time exercise appears to enhance physicians' professional wellbeing. As such, these activities and habits should be encouraged, supported, and promoted within institutional culture and health systems in general.


Incident pulmonary hypertension in 13 488 cases investigated with repeat echocardiography: a clinical cohort study.
We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension. Adults (n=13 448) undergoing routine echocardiography without initial evidence of pulmonary hypertension (estimated right ventricular systolic pressure, eRVSP <30.0 mmHg) or left heart disease were studied. Incident pulmonary hypertension (eRVSP ≥30.0 mmHg) was detected on repeat echocardiogram a median of 4.1 years apart. Mortality was examined according to increasing eRVSP levels (30.0-39.9, 40.0-49.9 and ≥50.0 mmHg) indicative of mild-to-severe pulmonary hypertension. A total of 6169 men (45.9%, aged 61.4±16.7 years) and 7279 women (60.8±16.9 years) without evidence of pulmonary hypertension were identified (first echocardiogram). Subsequently, 5412 (40.2%) developed evidence of pulmonary hypertension, comprising 4125 (30.7%), 928 (6.9%) and 359 (2.7%) cases with an eRVSP of 30.0-39.9 mmHg, 40.0-49.9 mmHg and ≥50.0 mmHg, respectively (incidence 94.0 and 90.9 cases per 1000 men and women, respectively, per year). Median (interquartile range) eRVSP increased by +0.0 (-2.27 to +2.67) mmHg and +30.68 (+26.03 to +37.31) mmHg among those with eRVSP <30.0 mmHg versus ≥50.0 mmHg. During a median 8.1 years of follow-up, 2776 (20.6%) died from all causes. Compared to those with eRVSP <30.0 mmHg, the adjusted risk of all-cause mortality was 1.30-fold higher in 30.0-39.9 mmHg, 1.82-fold higher in 40.0-49.9 mmHg and 2.11-fold higher in ≥50.0 mmHg groups (all p<0.001). New-onset pulmonary hypertension, as indicated by elevated eRVSP, is a common finding among older patients without left heart disease followed-up with echocardiography. This phenomenon is associated with an increased morality risk even among those with mildly elevated eRVSP.


Implementing the American Academy of Pediatrics attention-deficit/hyperactivity disorder diagnostic guidelines in primary care settings.
To evaluate the feasibility of the San Diego Attention-Deficit/Hyperactivity Disorder Project (SANDAP) protocol, a pediatric community-initiated quality improvement effort to foster implementation of the American Academy of Pediatrics (AAP) attention-deficit/hyperactivity disorder (ADHD) diagnostic guidelines, and to identify any additional barriers to providing evidence-based ADHD evaluative care. Seven research-naïve primary care offices in the San Diego area were recruited to participate. Offices were trained in the SANDAP protocol, which included 1) physician education, 2) a standardized assessment packet for parents and teachers, 3) an ADHD coordinator to assist in collection and collation of the assessment packet components, 4) educational materials for clinicians, parents, and teachers, in the form of handouts and a website, and 5) flowcharts delineating local paths for referral to medical subspecialists, mental health practitioners, and school-based professionals. The assessment packet included the parent and teacher versions of the Vanderbilt ADHD Diagnostic Rating Scales. In this study, we chose a conservative interpretation of the AAP ADHD guidelines for diagnosing ADHD, requiring that a child met criteria for ADHD on both the parent and teacher rating scales. A mixed-method analytic strategy was used to address feasibility and barriers, including quantitative surveys with parents and teachers and qualitative debriefing sessions conducted an average of 3 times per year with pediatricians and office staff members. Between December 2000 and April 2003, 159 children were consecutively enrolled for evaluation of school and/or behavioral problems. Clinically, only 44% of the children met criteria for ADHD on both the parent and teacher scales, and 73.5% of those children were categorized as having the combined subtype. More than 40% of the subjects demonstrated discrepant results on the Vanderbilt scales, with only the parent or teacher endorsing sufficient symptoms to meet the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Other mental health and learning problems were common in the sample; 58.5% of subjects met screening criteria for oppositional defiant disorder/conduct disorder, 32.7% met screening criteria for anxiety/depression, and approximately one-third had an active individualized education program in place or had received an individualized education program in the past. On evaluation, the SANDAP protocol was acceptable and feasible for all stakeholders. However, additional barriers to implementing the AAP ADHD guidelines were identified, including 1) limited information in the guidelines regarding the use of specific ADHD rating scales, the evaluation and treatment of children with discrepant and/or negative results, and the indications for psychologic evaluation of learning problems, 2) families' need for education regarding ADHD and support, 3) characteristics of physical health and mental health plans that limited care for children with ADHD, and 4) limited knowledge and use of potential community resources. Our results indicate that children presenting for evaluation of possible ADHD in primary care offices have complex clinical characteristics. Providers need mechanisms for implementing the ADHD diagnostic guidelines that address the physician education and delivery system design aspects of care that were developed in the SANDAP protocol. Additional barriers were also identified. Careful attention to these factors will be necessary to ensure the sustained provision of quality care for children with ADHD in primary care settings.


The Prognosis of Patients With Type 2 Diabetes and Nonalbuminuric Diabetic Kidney Disease Is Not Always Poor: Implication of the Effects of Coexisting Macrovascular Complications (JDDM 54).
Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing phenotype in patients with type 2 diabetes. However, it remains unclear whether its prognosis is poorer than that of other DKD phenotypes. A total of 2,953 Japanese patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, enrolled in an observational cohort study in 2004, were followed until 2015. On the basis of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 mL/min/1.73 m2) at baseline, participants were classified into the four DKD phenotypes-no-DKD, albuminuric DKD without reduced eGFR, nonalbuminuric DKD with reduced eGFR, and albuminuric DKD with reduced eGFR-to assess the risks of mortality, cardiovascular disease (CVD), and renal function decline. During the mean follow-up of 9.7 years, 113 patients died and 263 developed CVD. In nonalbuminuric DKD, the risks of death or CVD were not higher than those in no-DKD (adjusted hazard ratio 1.02 [95% CI 0.66, 1.60]) and the annual decline in eGFR was slower than in other DKD phenotypes. The risks of death or CVD in nonalbuminuric DKD without prior CVD were similar to those in no-DKD without prior CVD, whereas the risks in nonalbuminuric DKD with prior CVD as well as other DKD phenotypes were higher. Nonalbuminuric DKD did not have a higher risk of mortality, CVD events, or renal function decline than the other DKD phenotypes. In nonalbuminuric DKD, the presence of macrovascular complications may be a main determinant of prognosis rather than the renal phenotype.


Phase-lifetime spectrophotometry of deoxycholate-purified bacteriorhodopsin reconstituted into asolectin vesicles.
A rapid reconstitution procedure has been developed to insert deoxycholate-purified bacteriorhodopsin (bR) into asolectin vesicles. The procedure relies on the ability of the hydrophobic resin Bio-Beads SM-2 to remove octyl glucoside from a mixture of deoxycholate-purified bR, asolectin, and the detergent. Light-dependent acidification of the vesicle interior is observed with the reconstituted preparations as judged by the fluorescence quenching of an entrapped pH indicator, pyranine. Inhibition of proton pumping by the addition of LaCl3 to the external medium indicates that approximately 90% of the bR is oriented such that it pumps protons into the vesicles. Phase-lifetime spectrophotometry was used to study the relaxation processes associated with the intermediate in the photocycle of the reconstituted bR which absorbs at 410 nm. Amplitude spectra indicate that these absorbance changes are associated with the M intermediate in the bR photocycle. Two relaxation processes are observed. One is characterized by a relaxation time of approximately 4 ms and is independent of pH over the range 4.4-9.4. The longer relaxation time varies from 4 to 200 ms in the same pH range. By digitization of transients, which are observable when the actinic source is modulated at a low frequency, information about the dependence of the slower process on the light intensity and carbonyl cyanide m-chlorophenylhydrazone was obtained. The results can be interpreted in terms of two different forms of the M intermediate that decay on parallel kinetic paths. To explain the pH dependence of the decay rate, the slower decaying form must have three coupled protonation states, each with a different decay rate.


Meta-analysis of randomised controlled trials testing behavioural interventions to promote household action on climate change.
No consensus exists regarding which are the most effective mechanisms to promote household action on climate change. We present a meta-analysis of randomised controlled trials comprising 3,092,678 observations, which estimates the effects of behavioural interventions holding other factors constant. Here we show that behavioural interventions promote climate change mitigation to a very small degree while the intervention lasts (d = -0.093 95% CI -0.160, -0.055), with no evidence of sustained positive effects once the intervention ends. With the exception of recycling, most household mitigation behaviours show a low behavioural plasticity. The intervention with the highest average effect size is choice architecture (nudges) but this strategy has been tested in a limited number of behaviours. Our results do not imply behavioural interventions are less effective than alternative strategies such as financial incentives or regulations, nor exclude the possibility that behavioural interventions could have stronger effects when used in combination with alternative strategies.


Trainable rule-based algorithm for the measurement of joint space width in digital radiographic images of the knee.
The progression of osteoarthritis (OA) can be monitored by measuring the minimum joint space width (mJSW) between the edges of the femoral condyle and the tibial plateau on radiographs of the knee. This is generally performed by a trained physician using a graduated magnifying lens and is prone to the subjectivity and variation associated with observer measurement. We have developed software that performs this measurement automatically on digitized radiographs. The test data consisted of 180 digitized radiographs of the knee (90 duplicate acquisitions) from 18 normal (nonarthritic) subjects and 38 images from 10 subjects with OA. These were digitized and manually cropped so that the images were free of nonanatomical structures and the knee was approximately centered. The software first determined the edge of the femoral condyle on 400 microm pixel subsampled images. Contours marking the location of the tibial plateau in the medial compartment were found on 100 microm images using the femoral edge as a reference. The algorithm was trained using an independent but similar data set and using a jackknife approach with the test data. The results were compared to contours drawn by a trained reader and the duplicate acquisitions were used to measure the reproducibility of the mJSW measurement. The reproducibility was 0.16 mm and 0.18 mm for normal and osteoarthritic knees, respectively, representing an improvement of approximately a factor of 2 over manual measurement. The algorithm also showed excellent agreement with the hand-drawn contours and with mJSW determined by the manual method.


Stab Injury of the Petrosal Bone: Case Report and Literature Review.
Penetrating traumas of the head are generally life-threatening injuries, whose management poses a substantial challenge for emergency department teams. These injuries are characteristically violence-associated and frequently accompanied by damage of essential organs including brain, meninges, large vessels, cranial nerves, eyes, viscerocranium, internal ear, and/or labyrinth. Here, we present an exceptional case of head trauma caused by a knife blade, which was stuck deep inside in the petrous bone. After the extraction of the knife, the patient had very few immediate and no long-term post-traumatic complications. In conclusion, high-end technical equipment as well as an interdisciplinary team of specialized physicians is recommended for the management of penetrating head trauma to optimize the outcome.


Exploring housing insecurity in relation to student success.
The relative high rates of homelessness and housing insecurity among college students has become a public health concern within the U.S. This study explores the relationship between housing instability in relation to academic and mental health outcomes. College students attending a larger public university (N = 1,416 students; M age = 22.54; 47.2% Pell Eligible; 54.6% racially/ethnically minoritized students) were surveyed employing cluster-sampling in the Fall Semester of 2019. Participants completed validated measures of housing instability, mental health outcomes, and demographics. Additional measures were matched with survey responses through the Office of Institutional Research (i.e., GPA, Pell Grant eligibility). Students who experienced housing insecurity and homelessness were more likely to have a lower GPA as well as poorer mental health outcomes. Findings highlight implications surrounding the need for housing programs and additional financial support in an effort to bolster students' academic performance and mental well-being.


Fibric acid derivatives in cardiovascular disease prevention: results from the large clinical trials.
Results from five large placebo-controlled trials with second-generation fibrates have shown varying success in reducing cardiovascular events. This review focuses on a number of extended analyses from these trials that may relate to the success or failure of fibrate therapy and indicate who might likely benefit from this therapy. Results have been far from uniform and several trials have been adversely impacted by high off-trial statin use. Collective evidence suggests, however, that fibrates have optimum cardiovascular benefit in diabetes or other manifestations of insulin resistance. Much of this evidence comes from posttrial analysis in subgroups with more sharply defined clinical characteristics than in the overall trial population. Analyses also suggest that different fibrates have a different range of favorable clinical properties, that the cardiovascular benefit of fibrates may not be readily measured or mostly predicted by changes in traditional lipid measurements, and that other nonlipid properties of fibrates as peroxisome proliferator-activated receptor agents might explain some of the benefit of these drugs. Results of major clinical endpoint trials with fibrates, although not uniformly positive, provide substantial evidence for a selective therapeutic role of these drugs in cardiovascular event reduction in diabetes or insulin resistance.


Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways.
Hydrogen-rich saline has been reported to prevent neointimal hyperplasia induced by carotid balloon injury. The purpose of the present study was to further investigate the molecular mechanisms underlying this phenomenon. Daily injection of a hydrogen-rich saline solution (HRSS) in rats was employed to study the effect of hydrogen on balloon injury-induced neointimal hyperplasia and the neointima/media ratio was assessed. HRSS significantly decreased the neointima area and neointima/media ratio in a dose-dependent manner. In vitro effects of hydrogen on fetal bovine serum (FBS)-induced vascular smooth muscle cell (VSMC) proliferation were also investigated. Hydrogen-rich medium (HRM) inhibited rat VSMC proliferation and migration induced by 10% FBS. FBS-induced reactive oxygen species (ROS) production and activation of intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), Akt were significantly inhibited by HRM. In addition, HRM blocked FBS-induced progression from the G0/G1 to the S-phase and increased the apoptosis rate of VSMCs. These results showed that hydrogen-rich saline was able to attenuate FBS-induced VSMC proliferation and neointimal hyperplasia by inhibiting ROS production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways. Thus, HRSS may have potential therapeutic relevance for the prevention of human restenosis.


IA-2 and IA-2beta: the immune response in IDDM.
Pancreatic islet cell autoantigens associated with insulin-dependent diabetes mellitus (IDDM) include a recently identified family of protein tyrosine phosphatase-like molecules, notably IA-2 and IA-2beta. IA-2 is a 979 amino acid transmembrane protein located on human chromosome 2q35, whereas IA-2beta is 986 amino acids long located on human chromosome 7q36. Comparison of human IA-2 and IA-2beta showed 74% identity within the intercellular domains, but only 27% indentify within the extracellular domains. These IA-2 molecules are expressed predominantly in cells of neuroendocrine origin, particularly pancreatic islets and brain. Radioimmunoprecipitation with recombinant IA-2 and IA-2beta has been used to measure autoantibodies to these molecules and their intracellular fragments. Autoantibodies to IA-2 are detected in the majority (60% to 80%) of newly diagnosed IDDM patients and in less than 2% of controls. The major antigenic determinants of both IA-2 and IA-2beta reside within the C-terminus of their intracellular domains. In first-degree relatives of IDDM patients, the presence of autoantibodies to IA-2 is predictive of IDDM and in combination with autoantibodies to glutamic acid decarboxylase (GAD) the positive predictive value is in the 50% range. The role of IA-2 and IA-2beta in the pathogenesis of IDDM is still unclear. Identification of these antigens has extended our ability to predict the disease and may be valuable in the search for antigen-specific therapies to prevent IDDM.


Cloning, expression in Escherichia coli and nucleotide sequence of a tetracycline-resistance gene from Streptomyces rimosus.
Determinants of tetracycline resistance have been cloned from two different tetracycline-producing industrial strains of Streptomyces into Streptomyces lividans using the plasmid vector pUT206. Three plasmids, pUT250 and pUT260 with a 9.5 and a 7.5 kb insert respectively of Streptomyces rimosus DNA, and pUT270 with a 14.0 kb insert of Streptomyces aureofaciens DNA, conferring resistance to tetracycline, have been isolated. By in vitro sub-cloning, a similar fragment of 2.45 kb containing the tetracycline resistance gene (tet347) was further localized on these plasmids. The S. rimosus gene has been cloned into Escherichia coli and expressed under the control of lambda pL or Lpp promoters. Differential protein extraction of E. coli cells revealed the presence of an additional membrane-embedded protein in tetracycline-resistant cells. On the basis of available restriction endonuclease maps, the tet347 gene is probably identical to the tetB gene from S. rimosus recently identified by T. Ohnuki and co-workers as responsible for the reduced accumulation of tetracycline. The nucleotide sequence of a 2052 bp DNA fragment containing the TcR structural gene from S. rimosus has been determined. The amino acid sequence of the tet347 protein (Mr35818) deduced from the nucleotide sequence shows a limited but significant homology to other characterized tetracycline transport acting determinants from pathogenic bacteria.


Screening for hepatocellular carcinoma: being old is not all bad.
There has been a remarkable rise in incidence of hepatocellular carcinoma (HCC) in the United States and the developed Western world over the last few decades (1). This has been attributed largely to the emergence of hepatitis C over the same period of time. Other possible factors operative in the United States contributing to this rise in incidence include chronic hepatitis B virus (HBV) infection among immigrants from countries with a high prevalence of HBV and a rise in prevalence of nonalcoholic fatty liver disease (NAFLD). Thus, specialized liver centers have to deal with larger number of patients with HCC.


Purification and characterisation of a protease (tamarillin) from tamarillo fruit.
A protease from tamarillo fruit (Cyphomandra betacea Cav.) was purified by ammonium sulphate precipitation and diethylaminoethyl-Sepharose chromatography. Protease activity was determined on selected peak fractions using a casein substrate. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis showed that the peak with the highest protease activity consisted of one protein of molecular mass ca. 70 kDa. The protease showed optimal activity at pH 11 and 60 °C. It was sensitive to phenylmethylsulphonyl fluoride while ethylenediaminetetraacetic acid and p-chloromercuribenzoic acid had little effect on its activity, indicating that this enzyme was a serine protease. Hg2+ strongly inhibited enzyme activity, possibly due to formation of mercaptide bonds with the thiol groups of the protease, suggesting that some cysteine residues may be located close to the active site. De novo sequencing strongly indicated that the protease was a subtilisin-like alkaline serine protease. The protease from tamarillo has been named 'tamarillin'.


Characterization of AT-1 cardiomyocytes as a model for studies of T3 effects on cardiac cells.
AT-1 cardiomyocyte derive from atrial tumors in transgenic mice. Earlier studies have indicated a highly differentiated, contracting, cardiac phenotype in primary cultures and the AT-1 cardiomyocyte may thus be an excellent in vitro model in cardiac research. Thyroid hormone (T3) has positive inotropic and chronotropic effects and is clinically known to be relevant in various pathological heart conditions. Thyroid Hormone Receptors (TR) are ligand regulated transcriptional activators who mediate the effects of T3. The aim of this study was to determine whether AT-1 cardiomyocytes express TR. Regular binding competition assays showed a Kd of 370 +/- 105 for 125I-T3 binding to TR. Reverse transcription-PCR in mouse showed that TRalpha1, alpha2, beta1 and beta2 mRNA were expressed in AT-1 cardiomyocytes and mouse myocardium. Western blot with polyclonal rabbit antibodies against human TR revealed the presence of TRalpha1, beta2 and low levels of TRbeta1 while TRalpha2 was not detectable. Generally, for the detected subtypes the intensities of the bands were weaker for AT-1 cardiomyocytes in comparison to mouse heart. We conclude that the AT-1 cardiomyocytes express both protein and mRNA for TR and may provide a useful model for studying T3 effects in cultured cardiac myocytes.


Structure and function of aspartate transcarbamoylase studied using chymotrypsin as a probe.
Aspartate transcarbamoylase from Escherichia coli is composed of six catalytic (c) and six regulatory (r) polypeptides. We have studied the structure and function of this enzyme using chymotrypsin as a probe. The protease inactivates the isolated catalytic subunit (c3) but has not effects on the native enzyme (c6r6). Under identical conditions, the c3r6 complex is inactivated at a much slower rate than c3. The presence of the substrate analogue succinate together with carbamoyl phosphate reduces substantially the rate of inactivation. Extended exposure to chymotrypsin converts the catalytic subunit into a partially active derivative with a fourfold higher Michaelis constant. This derivative is indistinguishable from the unmodified catalytic subnit in gell electrophoresis under nondenaturing conditions. However, in the presence of sodium dodecyl sulfate, the major fragment in the electropherogram is smaller than that of the intact catalytic polypeptide. The results could be explained by postulating the presence of a chymotrypsin-sensitive peptide bond at or near the active site. Since X-ray crystallographic studies have indicated that the active sites are located in a central cavity, the resistance of the native enzyme towards inactivation may be due to the inability of chymotrypsin to enter this cavity.


Genetic analysis and clinical picture of severe congenital neutropenia in Israel.
The relative frequency of mutated genes among patients with severe congenital neutropenia (SCN) may differ between various ethnic groups. To date, few population-based genetic studies have been reported. This study describes the genetic analysis of 32 Israeli patients with SCN. Clinical data were retrieved from the prospective Israeli Inherited Bone Marrow Failure Registry. Recruitment included living and deceased patients who were diagnosed between 1982 and 2012, for whom molecular diagnosis was performed. ELANE, HAX1 and G6PC3 genes were sequenced in all patients, and GFI-1 and WAS genes were sequenced if other genes were wildtype. Eleven patients (34%) had heterozygous mutations in ELANE (10 kindreds), eight (25%) had homozygous mutations in G6PC3 (5 kindreds) and 13 (41%) had no detected mutations. No patients had mutations in HAX1 or WAS. Four of the eight patients with G6PC3 mutations had congenital anomalies. The probability of survival for all patients was 50% at age of 18. Deaths were mainly due to sepsis (5 patients, 4/5 not responding to G-CSF, none with G6PC3 mutation). Two patients developed acute myelogenous leukemia (AML) and one myelodysplastic syndrome (MDS), none with G6PC3 mutation. We found a unique pattern of SCN mutations in Israel with homozygous G6PC3 mutations in eight (25%) patients, the highest frequency described so far. HAX1 mutations, reported mainly in Sweden and Iran, were absent. Patients with G6PC3 mutations had congenital anomalies, appeared to have a better response to G-CSF, and so far have not developed AML or MDS.


Synchronization of Bloch oscillations by a ring cavity.
We consider Bloch oscillations of ultracold atoms stored in a one-dimensional vertical optical lattice and simultaneously interacting with a unidirectionally pumped optical ring cavity whose vertical arm is collinear with the optical lattice. We find that the feedback provided by the cavity field on the atomic motion synchronizes Bloch oscillations via a mode-locking mechanism, steering the atoms to the lowest Bloch band. It also stabilizes Bloch oscillations against noise, and even suppresses dephasing due to atom-atom interactions. Furthermore, it generates periodic bursts of light emitted into the counter-propagating cavity mode, providing a non-destructive monitor of the atomic dynamics. All these features may be crucial for future improvements of the design of atomic gravimeters based on recording Bloch oscillations.


Location of the Glenoid Defect in Shoulders With Recurrent Posterior Glenohumeral Instability.
Posterior glenoid bone deficiency is an increasingly recognized entity in the setting of recurrent posterior shoulder instability; however, little is known about the subject. Due to the paucity of literature on posterior bone loss, historical comparisons with anterior bone loss may not be fully accurate. To systematically describe the morphology of posterior bone defects in the setting of recurrent posterior shoulder instability based on several quantitative parameters, including the mean location, orientation, and extent of bone loss on a clockface model, as well as the angle of the defect relative to the long axis of the glenoid. Cross-sectional study; Level of evidence, 4. Three-dimensional reconstructed computed tomography scans of serially collected patients with a history of recurrent posterior shoulder instability were evaluated by 3 separate reviewers. The posterior glenoid bone defect was characterized using the following measures: (1) the mean lesion location and orientation based on a clockface model with 6 o'clock denoted as inferior and 9 o'clock as directly posterior for all patients; (2) the total extent of the posterior bone defect based on the clockface; and (3) the average angle of the bone loss relative to the long axis of the glenoid. A total of 70 male patients and 1 female patient with a mean age of 29.3 years (range, 24.4-35.1 years) were included in the analysis. The mean clockface location of the posterior glenoid defect originated at 6:44 (range, 4:16-8:12) and extended to a mean of 9:28 (range, 7:02-10:38). The mean extent of the posterior glenoid defect was 2:43 (range, 1:08-4:50), which corresponds to a mean total bone loss arc of 81.5° (range, 34.2°-144.9°), nearly 1 quadrant of the glenoid. Posterior bone loss occurred in a posteroinferior direction at a mean angle of 30.7° (range, 8.0°-80.0°) relative to the long axis of the glenoid. Posterior bone defects in the setting of posterior shoulder instability most commonly occur in the posteroinferior quadrant of the glenoid and extend on average from 6:44 to 9:28 (81.5° total degrees of arc) on a clockface model. Posterior bone loss occurs at a mean of 30° off the long axis of the glenoid in a posteroinferior direction, which is historically different from anterior bone loss, which occurs parallel to the long axis of the glenoid. This study serves to highlight the location and orientation of bone loss that one can expect in a patient with recurrent posterior shoulder instability, although additional work is needed to assess why this develops.


Evaluating incorporation of drug restrictions into computerized drug order entries after transition to an electronic health record.
Incorporation of drug restriction policy into electronic drug order entries (DOEs) can promote responsible medication use and resource utilization when implemented systematically. To identify drugs that require further incorporation of formulary restriction policy into their DOEs after migration to an electronic health record with computerized prescriber order entry (CPOE). After transition to CPOE, test orders for formulary restricted drugs were entered in the CPOE environment. Data were collected about rationale for drug restriction, type of formulary restriction, presence of incorporation of restriction policy into the DOE, and whether incorporation was consistent with a recommended method. Restricted drugs requiring revision of policy incorporation into their DOEs were analyzed to create a prioritized task list based on rationale for the restriction. Of all restricted drugs, 63.6% (287/451) did not have restriction policy incorporated into their DOEs consistent with the recommended method and therefore required revision. Eighteen percent (81/451) of restricted drugs had no incorporation of restriction policy in their DOEs. Safety was the rationale for restriction in 21% (17/81) of these, which received highest priority for revision. When drugs were orderable but restricted, 61.9% (78/126) lacked optimal incorporation of policy in DOEs to promote adherence. When drugs were not orderable, 64% (206/322) did not provide guidance to formulary alternatives in DOEs when they should have. After transition to CPOE, almost two-thirds of all analyzed restricted drugs lacked optimal incorporation of formulary restriction policies in their DOEs. DOEs with restrictions related to safety reasons were among those most frequently requiring revision. Some DOEs can better promote adherence and provide guidance to prescribers through revision. Predefined, systematic implementation strategies should be used during changes in computerized drug use processes.


Classic form of eosinophilic pustular folliculitis in an immunocompetent girl: rapid and complete resolution after low-dose oral indomethacin treatment.
Eosinophilic pustular folliculitis (EPF) is a rare noninfectious pruritic dermatosis, first described by Ise and Ofuji in 1965. We report the case of a 15-year oldimmunocompetent girl that presented with a widespread papulopustular eruption four days after her arrival in Japan. The clinical diagnosis of the classicform of EPF was confirmed by histological examination of the lesional skin that revealed an intense, mainly eosinophilic, dermal infiltrate within and aroundpilosebaceous units. Oral administration of lowdose indomethacin (25 mg/day) led to a complete resolution of the eruption within 6 weeks without causing any side effects. The patient is presently completing a 15-month follow-up and remains free ofrelapses. To the best of our knowledge, it is the first time that low-dose oral indomethacin is reported to be capable of causing a rapid and complete resolutionof the classic form of EPF.


Transforming growth factor-beta induces extracellular matrix protein cross-linking lysyl oxidase (LOX) genes in human trabecular meshwork cells.
The profibrotic cytokine TGFβ is associated with glaucoma and plays an important role in the regulation of extracellular matrix metabolism in the trabecular meshwork (TM). The purpose of this study was to determine whether expression of ECM cross-linking LOX genes is regulated by TGFβ in TM cells. Expression of the five LOX genes (LOX, LOXL1, LOXL2, LOXL3, and LOXL4) was examined in cultured human TM cells by using RT-PCR, quantitative RT-PCR, and Western immunoblot analysis. TM cells were treated with recombinant TGFβ1, -2, and -3, to determine the effects on LOX and LOXL1 to -4 expression. The TM cells were pretreated with TGFBR inhibitors (LY364947, SB431542), canonical Smad signaling pathway (SIS3 or Smad2, -3, and -4 siRNAs) inhibitors, or inhibitors of the non-Smad signaling pathways (SP600125, SR11302), to identify the signaling pathway(s) involved in TGFβ induction of LOX and LOXL gene and protein expression. A novel LOX activity assay was used to determine the effects of the LOX inhibitor BAPN on tropoelastin cross-linking. All five LOX genes (LOX, LOXL1 to -4) were expressed in cultured human TM cells and were induced by all three isoforms of TGFβ. This TGFβ induction of LOX and LOXL expression was blocked by TGFβ inhibitors as well as by inhibitors of the canonical Smad2, -3, and -4 signaling and non-Smad JNK/AP-1 signaling pathways (P < 0.05). Both Smad and non-Smad signaling pathways are involved in TGFβ-mediated LOX induction, suggesting complex regulation of these important extracellular matrix cross-linking enzymes. Increased LOX activity may be at least partially responsible for TGFβ-mediated IOP elevation and increased aqueous humor outflow resistance.


Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder.
Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.


Detection and Control of Biofilm Formation by Staphylococcus aureus from Febrile Neutropenic Patient.
Febrile neutropenia (FN) is the evolution of fever in a patient with neutropenia over 38.0°C. Neutropenia is diagnosed when absolute neutrophil count (ANC) <1500 cells/µL. FN represents a common complication of cancer treatment. Hence, it is featured to be a major cause of morbidity and mortality in cancer patients. Staphylococcus aureus is one of the most important microorganisms isolated from the blood of febrile neutropenic patients. Infections caused by S. aureus range from mild to life-threatening diseases. Biofilm production by S. aureus is one of the most significant virulence factors of the bacterium as it prevents the penetration of antibiotics. Recently, it has been shown that S. aureus carries the ica operon responsible for biofilm production. The aim of the work is to determine a genotypic characterization that includes not only the detection of icaA and icaD genes in S. aureus but also the determination of their relation to clinical and microbiological features. Empiric antibacterial treatment was recommended for cancer patients receiving chemotherapy. The relation between the presence of icaA and icaD and biofilm production was determined in a collection of 66 S. aureus samples from febrile neutropenic patients. Biofilm-forming ability was tested on Congo Red agar plates. Also, the effect of the most sensitive antibiotics on the bacterial cells was determined by an electron microscope. Of the bacterial samples, 48 were biofilm-productive and 18 were non-biofilm productive. For the biofilm productive bacteria, 37.5% were positive for icaA, 22.9% were positive for icaD and 10.4% were positive for both. Linezolid was the most effective antibiotic and it is highly recommended for the treatment of febrile neutropenia caused by biofilm-productive S. aureus. Severe changes were found on the bacterial cell after being treated with Linezolid. The icaA and icaD genes were present in only 50% of biofilm-productive bacteria. The ica operon is present in only 50% of biofilm-productive S. aureus and Linezolid is the best antibiotic against these bacteria.


Chronic Stress and Endothelial Dysfunction: The Multi-Ethnic Study of Atherosclerosis (MESA).
Endothelial dysfunction may represent an important link between chronic stress and cardiovascular disease (CVD) risk. However, few studies have examined the impact of chronic stress on endothelial dysfunction. The purpose of this study was to examine whether chronic stress was associated with flow-mediated dilation (FMD) and 2 biomarkers of endothelial dysfunction (intercellular adhesion molecule-1 (ICAM-1) and E-selectin) in a multiethnic sample of adults (ages 45-84 years). Data come from the baseline examination of Multi-Ethnic Study of Atherosclerosis participants. Chronic stress was assessed based on self-report of the presence and severity of ongoing problems in 5 domains. FMD was obtained using high-resolution ultrasound; biomarkers were assayed in different subsets of participants. Higher chronic stress was associated with lower absolute FMD (mm FMD) in models adjusted for demographic and socioeconomic characteristics (0.169mm in high-stress participants vs. 0.178 and 0.179mm in medium and low-stress participants; P for trend = 0.04). This association remained unchanged with further adjustment for behavioral and biological CVD risk factors. Higher stress was related to higher ICAM-1 in models adjusted for sociodemographic characteristics and biological risk factors (P for trend = 0.005), but this association attenuated with adjustment for cigarette smoking (P for trend = 0.07). Chronic stress was not associated with E-selectin. Our findings suggest chronic stress is related to endothelial dysfunction, possibly in part through other stress-associated CVD risk factors such as cigarette smoking.


Genotyping of infectious bronchitis viruses identified in Canada between 2000 and 2013.
Infectious bronchitis virus (IBV) was detected in 185 samples originating from chicken flocks of various commodity groups in Canada. Flocks with clinical signs such as respiratory challenge, sudden death, egg production problems, or nephropathogenic conditions, and randomly selected flocks sampled at slaughter as part of an Ontario broiler surveillance project, were included. Most samples were from Ontario and Québec; however, a small number from British Columbia, Nova Scotia, and Newfoundland and Labrador were also analysed. The nucleotide sequence of the spike (S) protein gene was compared with sequences available in GenBank. Based on their S gene sequence similarities, Canadian IBVs could be divided into nine genotypes belonging to four groups: Canadian variant virus, strain Qu_mv; the classic, vaccine-like viruses, Connecticut and Massachusetts; US variant-like virus strains, California 1734/04, California 99, CU_82792, Pennsylvania 1220/98 and Pennsylvania Wolg/98; and non-Canadian, non-US virus, strain 4/91. Based on the field situation, the effectiveness of current vaccination practices mostly based on Massachusetts and Connecticut-type vaccines appeared generally satisfactory for minimizing the damage due to infection with Canadian variant and US variant-like viruses. However, the recent outbreaks of severe respiratory disease and production problems in Ontario chicken flocks related to the incursion of IBV strain 4/91 were not prevented by standard vaccination protocols. It appears that IBV strain 4/91 has now become endemic in Ontario and the need for 4/91-type vaccines must be evaluated.


Assessment of Extrapyramidal Symptoms Associated with Psychotropics Pharmacological Treatments, and Associated Risk Factors.
Extrapyramidal Symptoms (EPS) are unwanted symptoms commonly originating from the use of certain medications. The symptoms can range from minimal discomfort to permanent involuntary muscular movements. The aims of the study were to examine the incidence of drug-induced extrapyramidal symptoms (di-EPS), associated risk factors, and clinical characteristics. This is a retrospective, observational study of di-EPS conducted in outpatient clinics of Jordan using the longitudinal health database (Hakeem®) for data collection. Patients who received drugs with the risk of EPS during the period 2010-2020 were included and followed. Patients with any of the known underlying conditions that may cause EPS or were currently taking drugs that may mask the symptoms were excluded. Gender and age-matched control subjects were included in the study. The Statistical Package for Social Science (SPSS®) version 26 was used for data analysis. The final dataset included 34898 exposed patients and 69796 matched controls. The incidence of di-EPS ranged from 9.8% [Amitriptyline 25mg] to 28.9% (Imipramine 25mg). Baseline factors associated with a significantly higher risk of developing di-EPS were age {HR: 1.1 [95%CI: 0.8-1.2, p=0.003], smoking {HR: 1.7 (95%CI: 1.3-2.2), p=0.02}, tremor history {HR: 7.4 (95%CI: 5.9-8.3), p=.002} and history of taking antipsychotics {HR: 3.9, (95% CI: 2.5-4.6), p=0.001}. Patients taking paroxetine {HR: 8.6 [95%CI: 7.4-9.8], p=.0002},imipramine {HR: 8.3, [7.1-10.5], p=0.01}, or fluoxetine {HR: 8.2 (95%CI: 6.8-9.3), p=.006} had a significantly higher risk of developing di-EPS compared to patients taking citalopram. Myoclonus, blepharospasm, symptoms of the basal ganglia dysfunction, and organic writers' cramp were reported among participants. Patients treated with paroxetine, imipramine, fluoxetine, or clomipramine had a higher risk of developing di-EPS than patients treated with citalopram. The difference in gender was not significantly related to di-EPS development. Whereas age, smoking, and history of taking antipsychotics were significantly associated with di-EPS development. • High incidence of drug-induced extrapyramidal symptoms (di-EPS) was reported• Age, smoking, tremor history, and history of taking antipsychotics were risk factors of drug-induced extrapyramidal symptoms.• Patients taking paroxetine, imipramine or fluoxetine had a significantly higher risk of developing di-EPS compared to patients taking citalopram.


Uterine leiomyosarcoma: a rare clinical entity.
Leiomyosarcoma is a rare aggressive malignant mesenchymal tumour, accounting for 1% of all uterine malignancies. It spreads rapidly through the intraperitoneal and haematogenous pathways. It is often diagnosed postoperatively following myomectomy, hysterectomy or supracervical hysterectomy for presumed benign disease. It has a predilection for perimenopausal women with a median age of 50 years. Individuals may describe symptoms of vaginal or abdominal pressure. Physical examination may reveal a large palpable pelvic mass, which may haemorrhage. Surgery remains the mainstay of treatment. Hysterectomy and a bilateral salpingo-oophorectomy may be considered, depending on the individual's menopausal status. Ovarian preservation can be considered in young patients. Adjuvant systemic treatment and radiotherapy are of no benefit. Gemcitabine/docetaxel and doxorubicin have shown benefit in the treatment of advanced or recurrent disease. The authors present the case of a 44-year-old woman with lower abdominal pain, vaginal bleeding and a uterine fibroid. Laboratory investigations confirmed a leucocytosis, neutrophilia and a thrombocythaemia. Further investigation with an MRI pelvis showed a very large, heterogeneous, malignant appearing pelvic mass compressing the right ureter and it appeared uterine in nature. Her staging CT showed multiple lung metastases. The diagnosis of uterine leiomyosarcoma was subsequently established. Due to the aggressive behaviour of this sarcoma subtype, novel early detection strategies and targeted therapies are required.


Gummatous lesions in men infected with human immunodeficiency virus and syphilis.
Two HIV-infected men are reported who developed gummatous lesions more than 12 months after appropriate treatment of presumptive syphilis. In one patient the lesions developed without any change in the VDRL titre. The most likely explanation for these lesions is reactivation of syphilis in the context of HIV infection. As these lesions respond to penicillin, the possible reactivation of appropriately treated syphilis, or even yaws, should now be considered in any ulcerative lesion in HIV infected individuals at risk from treponemal infection.


Validation of Legionella pneumophila indirect immunofluorescence assay with epidemic sera.
Sera from six outbreaks of legionellosis and four outbreaks of pneumonia of other etiologies were tested with the indirect immunofluorescence assay (IFA) as currently performed. The current IFA is at least as sensitive as the original test in detecting cases of Legionnaires disease (78 to 91%). By using Center for Disease Control criteria for a positive (fourfold increase in titer during convalescence to greater than or equal to 128) or presumptive (single titer greater than or equal to 256) serological test, the specificity exceeded 99%. No cross-reactions against Legionella pneumophila antigens were observed among sera from epidemic cases of Q fever, tularemia, and psittacosis; the only positive L. pneumophila IFA titer among the epidemic Mycoplasma pneumonia sera was reduced to a negative titer with an immunosorbent extracted from Escherichia coli strain O13:K92:H4. The slight increase in specificity (to 100%), however, was offset by a slight decrease in sensitivity. The sensitivity of the IFA was maximal when a conjugate that detected immunoglobulins G, M, and A was used. IFA titers were not significantly altered by replacing the monovalent serogroup 1 antigen with a polyvalent antigen (serogroups 1 through 4) nor by the presence of rheumatoid factor or heat-labile serum factors.


[Cement augmentation on the spine : Biomechanical considerations].
Vertebral compression fractures are the most common osteoporotic fractures. Since the introduction of vertebroplasty and screw augmentation, the management of osteoporotic fractures has changed significantly. The biomechanical characteristics of the risk of adjacent fractures and novel treatment modalities for osteoporotic vertebral fractures, including pure cement augmentation by vertebroplasty, and cement augmentation of screws for posterior instrumentation, are explored. Eighteen human osteoporotic lumbar spines (L1-5) adjacent to vertebral bodies after vertebroplasty were tested in a servo-hydraulic machine. As augmentation compounds we used standard cement and a modified low-strength cement. Different anchoring pedicle screws were tested with and without cement augmentation in another cohort of human specimens with a simple pull-out test and a fatigue test that better reflects physiological conditions. Cement augmentation in the osteoporotic spine leads to greater biomechanical stability. However, change in vertebral stiffness resulted in alterations with the risk of adjacent fractures. By using a less firm cement compound, the risk of adjacent fractures is significantly reduced. Both screw augmentation techniques resulted in a significant increase in the withdrawal force compared with the group without cement. Augmentation using perforated screws showed the highest stability in the fatigue test. The augmentation of cement leads to a significant change in the biomechanical properties. Differences in the stability of adjacent vertebral bodies increase the risk of adjacent fractures, which could be mitigated by a modified cement compound with reduced strength. Screws that were specifically designed for cement application displayed greatest stability in the fatigue test.


An ensemble-based serial cascaded attention network and improved variational auto encoder for breast cancer prognosis prediction using data.
Breast cancer is one of the most common types of cancer in women and it produces a huge amount of death rate in the world. Early recognition is lessening its impact. The early recognition of breast cancer could convince patients to receive surgical therapy, which will significantly improve the chance of restoration. This information is used by the machine learning technique to find links between them and appraise our forecasts of fresh occurrences. Later recognition of breast cancer can lead to death. An accurate prescient framework for breast cancer prediction is urgently needed in the current era. In order to accomplish the objective, an adaptive ensemble model is proposed for breast cancer prognosis prediction using data. At the initial stage, the raw data are fetched from benchmark datasets. It is then followed by data cleaning and preprocessing. Subsequently, the pre-processed data is fed into the Improved Variational Autoencoder (IVAE), where the deep features are extracted. Finally, the resultant features are given as input to the Ensemble-based Serial Cascaded Attention Network (ESCANet), which is built with Deep Temporal Convolution Network (DTCN), Bi-directional Long Short-Term Memory (BiLSTM), and Recurrent Neural Network (RNN). The effectiveness of the model is validated and compared with conventional methodologies. Therefore, the results elucidate that the proposed methodology achieves extensive results; thus, it increases the system's efficiency.


Work-related tetraplegia: cause of injury and annual medical costs.
Descriptive study. To describe the demographics, cause of injury, and annual-paid medical costs for the 5 years following injury for cases of work-related tetraplegia. A single United States workers' compensation (WC) claims database. Tetraplegia cases with initial date of injury from 1 January 1989 to 31 December 1999 were selected by cross-referencing word search terms pertaining to body part injured and nature of injury. The main outcome measures were injury causes and annual-paid medical payments (adjusted to year 2000 medical consumer price index) of work-related tetraplegia by injury group for each year postinjury over a 5-year time period. A total of 62 claimants with work-related tetraplegia injured between 1 January 1989 and 31 December 1999. The vast majority of those identified were male claimants (92%) and more than a quarter worked in the construction industry (26%). Other highly represented industries included transportation and retail (15% each), manufacturing (13%), and agriculture and utility (11% each). The majority of injuries were the result of falls (36%) and vehicular accidents (34%). The mean Year 1 cost was US dollars 560524 for those with a high-level tetraplegia (C2-4 ASIA A-C), US dollars 431033 for a low-level injury (C5-8 ASIA A-C), and US dollars 178041 for those with an ASIA D tetraplegia injury. The mean cost of subsequent years (Years 2-5) was US dollars 130992 for a high-level, US dollars 129250 for a low-level, and Us dollars 34352 for an ASIA D tetraplegia injury. Mean costs for Year 1 postinjury in WC cases are similar to previously published estimates. Comparing the current results with those of previous spinal cord injury cost studies suggests that those with work-related tetraplegia may receive more injury-related paid medical benefits after the first year postinjury than cases who do not receive WC-supported benefits. Supported, in part, by a grant from the National Institute on Disability and Rehabilitation Research (NIDDR) (Grant # H133N00024).


The effect of dietary starch level on postprandial glucose and insulin concentrations in cats and dogs.
A charge made against feeding dry foods to cats is that the high carbohydrate (i.e. starch) content results in high blood glucose levels which over time may have detrimental health effects. The present study determined the post-meal concentrations of plasma glucose and insulin in adult cats (seven males and four females) and dogs (Labrador retrievers; four males and five females) fed dry diets with low-starch (LS), moderate-starch (MS) or high-starch (HS) levels. In a cross-over design with at least 7 d between the test meals, plasma glucose and insulin concentrations were measured following a single meal of a LS, MS and HS diet (209 kJ/kg bodyweight). Only the HS diet resulted in significant post-meal increases in plasma glucose concentration in cats and dogs although the time-course profiles were different between the species. In cats, plasma glucose concentration was significantly increased above the pre-meal concentration from 11 h until 19 h after the meal, while in dogs, a significant increase above baseline was seen only at the 7 h time point. Plasma insulin was significantly elevated in dogs 4-8 h following the MS diet and 2-8 h after the HS diet. In cats, plasma insulin was significantly greater than baseline from 3-7 and 11-17 h after the HS diet. The time lag (approximately 11 h) between eating the HS diet and the subsequent prolonged elevation of plasma glucose concentration seen in cats may reflect metabolic adaptations that result in a slower digestive and absorptive capacity for complex carbohydrate.


Epidemiological and clinical characteristics of monkeypox cases in Brazil in 2022: a cross-sectional study.
to describe epidemiological and clinical characteristics of monkeypox (MPX) in Brazil, from the identification of the first case, on June 7, 2022, to Epidemiological Week (EW) 39, ending on October 1, 2022. this was a descriptive study of cases notified to the Ministry of Health; trends were analyzed based on the number of confirmed and probable cases per EW; the cases were also described according to demographic and clinical variables. out of 31,513 notifications, 23.8% were confirmed; 91.8% were male; 70.6% were cis men; and median age was 32 years. Fever (58.0%), adenomegaly (42.4%), headache (39.9%) and rash (37.0%) were the most frequent symptoms; 27.5% reported being immunosuppressed, 34.6% were living with HIV and 10.5% had a sexually transmitted infection; three deaths were recorded. the MPX case profile was similar to that of other countries; surveillance actions must be strengthened to control the outbreak.


[Clinical nutrition training in medical schools of Mexico].
To describe the efforts carried out to strengthen nutrition education in Mexican medical schools. Emphasis was placed on the status previous to the program implementation, the design of a new basic curriculum, and the description of the main program strategies implemented. a) Analysis of available medical curricula; b) Application of a questionnaire to the school deans; c) Assessment of knowledge of nutrition of advanced medical students; d) Design of a basic curriculum of clinical nutrition; e) Edition of a textbook; f) Design and implementation of program strategies to strengthen nutrition education. Clinical nutrition was not a topic included in most curricula analyzed and, when present, it was incorporated to related clinical subjects. Usually, emphasis was placed on basic topics of nutrition while clinical and applied subjects were considered less frequently. Lack of a specialized faculty and weakness of teaching infrastructure were some problems identified. A basic curriculum adaptable to different contexts was designed, and a textbook on clinical nutrition was edited and published. Training and formation of nutrition specialists were among the key programs implemented.


Parental genetic contributions to neonatal temperament in a nonhuman primate (Macaca mulatta) model.
Temperament is an individual's nature and is widely believed to have a heritable foundation. Few studies, however, have evaluated paternal and maternal contributions to the triadic dimensions of temperament. Rhesus monkeys are widely utilized to model genetic contributions to human development due to their close genetic-relatedness and common temperament structure, providing a powerful translational model for investigating paternal and maternal genetic influences on temperament. The temperament of rhesus monkey infants born to 19 different sires and 50 different dams was assessed during the first month of life by comparing the temperament of paternal or maternal half-siblings reared with their mothers in species-normative conditions or reared in a neonatal nursery. Factor scores from three dimensions of temperament were obtained (Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion) and ANOVAs were used to assess genetic effects. For paternal half-siblings, results showed a statistically significant paternal contribution to Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion factor scores. For maternal half-siblings, results showed a statistically significant contribution to Orienting/Regulation factor scores. When parsed by early rearing condition, results showed a paternal contribution Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion scores for paternal half-siblings reared in the neonatal nursery, while there was only a paternal contribution to Surgency/Extraversion for paternal half-siblings reared by their mothers. There was only a maternal contribution to Orienting/Regulation for maternal half-siblings reared by their mothers. These results show that paternal and maternal contributions to temperament vary by environmental context, and that mothers may environmentally buffer their infants from paternal contributions to their temperament.


Progressive thrombosis of brain arteriovenous malformations after embolization with isobutyl 2-cyanoacrylate.
Embolization of brain arteriovenous malformations (AVMs) with isobutyl 2-cyanoacrylate (IBCA) is an alternative to surgical treatment when dealing with large AVMs with multiple arterial feeders. The deposition of IBCA in the nidus of the AVM may produce an active and progressive thrombosis that may lead to complete occlusion of the nidus and/or to progressive thrombosis of the draining veins. Four clinical examples of progressive thrombosis after IBCA embolization are demonstrated, including two cases in which late follow-up angiography showed complete obliteration of a partly embolized AVM.


Mass Gatherings and the Spread of Respiratory Infections. Lessons from the Hajj.
The mass gathering of people is a potential source for developing, propagating, and disseminating infectious diseases on a global scale. Of the illnesses associated with mass gatherings, respiratory tract infections are the most common, the most easily transmitted, and the most likely to be spread widely beyond the site of the meeting by attendees returning home. Many factors contribute to the spread of these infections during mass gatherings, including crowding, the health of the attendees, and the type and location of meetings. The annual Hajj in the Kingdom of Saudi Arabia is the largest recurring single mass gathering in the world. Every year more than 10 million pilgrims attend the annual Hajj and Umrah. Attendees assemble in confined areas for several days. People with a wide range of age, health, susceptibility to illness, and hygiene sophistication come in close contact, creating an enormous public health challenge. Controlling respiratory infections at the Hajj requires surveillance, rapid diagnostic testing, and containment strategies. Although the Hajj is without equal, other mass gatherings can generate similar hazards. The geographic colocalization of the Zika virus epidemic and the 2016 Summer Olympic Games in Brazil is a current example of great concern. The potential of international mass gatherings for local and global calamity calls for greater global attention and research.


Genetic and environmental risk indicators in canine non-Hodgkin's lymphomas: breed associations and geographic distribution of 608 cases diagnosed throughout France over 1 year.
The etiology of non-Hodgkin's lymphomas (NHL) is multifactorial. Environmental and genetic factors are frequently incriminated both in humans and dogs. Our purpose was to study the geographic distribution of canine NHL (CNHL) in France and to evaluate genetic and environmental influences. Six hundred and eight cases of CNHL, diagnosed throughout France over 1 year, were collected from 7 Veterinary Histopathologic Laboratories. Retrospective study. Breeds affected by lymphomas were compared with the national population and associations between breed and immunophenotype were studied. The distribution of CNHL and canine T-cell NHL per 100,000 dogs per department was compared with the distribution of waste incinerators, polluted sites, and radioactive waste. The breeds significantly overrepresented among lymphoma cases were Boxer, Setter, and Cocker Spaniel (P < .001). There was a significant association between Boxer and T-cell NHL (P < .001), and between German Shepherd and Rottweiler and B-cell NHL (P < .01). The geographic distribution of CNHL and canine T-cell NHL indicated significant heterogeneity. Significant association between distributions of CNHL and waste incinerators (rho= 0.25, P < .05), polluted sites (rho= 0.36, P < .001), and radioactive waste (rho= 0.51, P < .001) was found. Influence of genetics in the development of CNHL was supported by the existence of an association between breed and immunophenotype. Waste incinerators, polluted sites, and radioactive waste could just be considered as risk indicators of CNHL, but not as risk factors. Case-control studies around critical sites are necessary to confirm the implication of those environmental factors in the development of CNHL.


New prognostic factors in breast cancer.
For many years, the age of the patient, the condition of axillar lymph nodes, the size of the tumour, histological traits (in particular histological grade of malignancy and invasion of lymphatic vessels), condition of hormonal receptors and HER2 represented principal factors used for the stratification of breast cancer patients for the purposes of evaluating the prognosis and determining the appropriate strategy of treatment. Although the variables are useful for the prognostic evaluation of individual groups of breast cancer patients, their role in determining the individual risk level of the patient and in the selection of supplementary treatment is quite restricted. This article shows the prognostic value of additional parameters, whose expression is associated with chemioresistance (MRP2, BCRP, YB1) or individual assessment of the dynamics of tumor progression (S100P, BUBR1). In addition, it describes the role of an online database of "The Kaplan-Meier plotter" which contains the assessment of the effects of expression of various genes on the clinical outcome of patients with breast cancer.


Kinetics and longevity of ΦC31 integrase in mouse liver and cultured cells.
The ΦC31 integrase system provides genomic integration of plasmid DNA that may be useful in gene therapy. For example, the ΦC31 system has been used in combination with hydrodynamic injection to achieve long-term expression of factor IX in mouse liver. However, a concern is that prolonged expression of ΦC31 integrase within cells could potentially stimulate chromosome rearrangements or an immune response. Western blot and immunofluorescence analyses were performed to investigate the duration of ΦC31 integrase expression in mouse liver. Integrase was expressed within 2 to 3 hr after hydrodynamic injection of a plasmid expressing ΦC31 integrase. Expression peaked between 8 and 16 hr and fell to background levels by 24-48 hr postinjection. Analysis of the amount of integrase plasmid DNA present in the liver over time suggested that the brief period of integrase expression could largely be accounted for by rapid loss of the bulk of the plasmid DNA, as well as by silencing of plasmid expression. PCR analysis of integration indicated that ΦC31 integrase carried out genomic integration of a codelivered attB-containing plasmid by 3 hr after plasmid injection. Integrase was expressed for longer times and at higher levels in transfected cultured cells compared with liver. Inhibitor studies suggested that the enzyme had a short half-life and was degraded by the 26S proteasome. The short duration of integrase expression in liver and rapid integration reaction appear to be features favorable for use in gene therapy.


Prenatal exposure to TiO2 nanoparticles in mice causes behavioral deficits with relevance to autism spectrum disorder and beyond.
Environmental factors are involved in the etiology of autism spectrum disorder (ASD) and may contribute to the raise in its incidence rate. It is currently unknown whether the increasing use of nanoparticles such as titanium dioxide (TiO2 NPs) in consumer products and biomedical applications may play a role in these associations. While nano-sized TiO2 is generally regarded as safe and non-toxic, excessive exposure to TiO2 NPs may be associated with negative health consequences especially when occurring during sensitive developmental periods. To test if prenatal exposure to TiO2 NPs alters fetal development and behavioral functions relevant to ASD, C57Bl6/N dams were subjected to a single intravenous injection of a low (100 µg) or high (1000 µg) dose of TiO2 NPs or vehicle solution on gestation day 9. ASD-related behavioral functions were assessed in the offspring using paradigms that index murine versions of ASD symptoms. Maternal exposure to TiO2 NPs led to subtle and dose-dependent impairments in neonatal vocal communication and juvenile sociability, as well as a dose-dependent increase in prepulse inhibition of the acoustic startle reflex of both sexes. These behavioral alterations emerged in the absence of pregnancy complications. Prenatal exposure to TiO2 NPs did not cause overt fetal malformations or changes in pregnancy outcomes, nor did it affect postnatal growth of the offspring. Taken together, our study provides a first set of preliminary data suggesting that prenatal exposure to nano-sized TiO2 can induce behavioral deficits relevant to ASD and related neurodevelopmental disorders without inducing major changes in physiological development. If extended further, our preclinical findings may provide an incentive for epidemiological studies examining the role of prenatal TiO2 NPs exposure in the etiology of ASD and other neurodevelopmental disorders.


Forage type and fish oil cause shifts in rumen bacterial diversity.
Despite evidence supporting improved incorporation of beneficial polyunsaturated fatty acids (PUFA) into ruminant products, such as meat and milk, following red clover and fish oil (FO) inclusion in the ruminant diet, little is known regarding the concomitant bacterial diversity. We evaluated the effects of feeding grass vs. red clover silage with incremental FO inclusion on known lipolytic, biohydrogenating, cellulolytic and proteolytic rumen bacterial communities of steers. Following 14 days of dietary adaptation, liquid-associated (LAB) and solid-associated (SAB) bacterial communities were harvested, DNA extracted and bacterial denaturing gradient gel electrophoresis (DGGE) and specific-bacterial quantitative PCR (QPCR) were undertaken. DGGE-derived dendrograms showed that diet caused the greatest change in LAB and SAB bacterial diversity, with FO inclusion at the 2% and 3% dry matter intake also causing some changes. QPCR revealed that diet resulted in changes in the DNA concentration of Anaerovibrio lipolytica, the Butyrivibrio proteoclasticus group, Fibrobacter succinogenes, Ruminococcus albus and Ruminococcus flavefaciens. FO inclusion caused changes in A. lipolytica, F. succinogenes and R. flavefaciens DNA concentration only. In the B. proteoclasticus group, which are the only known bacteria with the capacity to biohydrogenate PUFA to 18:0, DNA concentration did not correlate to 18:0 flow to the duodenum, however, suggesting that other bacteria may play a role in biohydrogenation. A greater understanding of microbial changes that accompany beneficial dietary changes will lead to novel strategies to improve ruminant product quality.


Long-term survival in patients with para-aortic lymph node metastasis with systematic retroperitoneal lymphadenectomy followed by adjuvant chemotherapy in endometrial carcinoma.
The purposes of this study were to assess modified radical hysterectomy including systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy in patients with para-aortic lymph node (PAN) metastasis in endometrial carcinoma and to identify the multivariate independent prognostic factors for long-term survival during the past 10 years. Between December 1987 and December 2002, we performed modified radical hysterectomy with bilateral salpingo-oophorectomy including systematic pelvic and para-aortic lymphadenectomy and peritoneal cytology in 284 endometrial carcinoma patients according to the classification of the International Federation of Gynecology and Obstetrics (stage IA, n = 66; stage IB, n = 96; stage IC, n = 33; stage IIA, n = 5; stage IIB, n = 20; stage IIIA, n = 28; stage IIIC, n = 28; and stage IV, n = 8) who gave informed consents at our institute. Patients with tumor confined to the uterus (stages IC and II) were treated by 3 courses of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, and cisplatin 75 mg/m2 regimen 3 to 4 weeks apart, and patients with extrauterine lesions involving adnexa and/or pelvic lymph node (PLN) were treated by 5 courses. In addition, 10 courses were given to patients with PAN metastasis. Patients with PLN metastasis received adjuvant chemotherapy, and adjuvant radiation was not part of our institutional protocol. For multivariate regression modeling with proportional hazards, the regression model of Cox was used. Survival curves were analyzed by the Kaplan-Meier method, and analysis of the differences was performed by the log-rank test. The overall incidence of retroperitoneal lymph node metastasis assessed by systematic pelvic and para-aortic lymphadenectomy was 12.0% (34/284) in stages I to IV endometrial carcinoma, and incidences of PLN and PAN metastases were 9.2% (26/284) and 7.4% (21/284), respectively. However, PAN metastasis rate is 50% (13/26) in patients with PLN metastasis. Univariate analysis of prognostic factors revealed that International Federation of Gynecology and Obstetrics clinical stage (P < 0.0001), histological finding (P = 0.0292), myometrial invasion (P < 0.0001), adnexal metastasis (P < 0.0001), lymphovascular space invasion (P < 0.0001), tumor diameter (P = 0.0108), peritoneal cytology (P = 0.0001), and retroperitoneal lymph node metastasis (P < 0.0001) were significantly associated with 10-year overall survival. Survival was not associated with age (P = 0.1558) or cervical involvement (P = 0.1828). A multivariate analysis showed that adnexal metastasis (P = 0.0418) and lymphovascular space invasion (P = 0.0214) were significantly associated with 10-year overall survival. The 5- and 10-year overall survival rates in patients with negative PAN were 96% and 93% versus 72% and 62% in patients with positive PAN (P = 0.006). It is suggested that surgery with systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy could improve long-term survival in patients with PAN metastasis, although there are only 21 patients with PAN metastasis.


Highlights from Studies Presented at the American Heart Association Scientific Session 2020: Navigating New Roads in Prevention.
This review highlights late-breaking science presented at the American Heart Association Scientific Session 2020 that demonstrated advancements in preventative cardiology and introduced novel treatment approaches for the management of chronic kidney disease, type 2 diabetes, and/or heart failure. The studies reviewed include clinical trials that assessed the use of omecamtiv in the treatment of heart failure with reduced heart failure (GALACTIC-HF); effects of sotagliflozin in patients with diabetes and recent heart failure exacerbation; cardiovascular outcomes with the use of omega-3 carboxylic acids in patients with high vascular risk and atherogenic dyslipidemia (STRENGTH) and omega-3 fatty acids in elderly patients with recent myocardial infarction (OMEMI); efficacy and safety of evinacumab in patients with refractory hypercholesterolemia; and the use of coronary computed tomography angiography for the assessment of suspected acute coronary syndrome. In addition, we review the results of the International Polycaps Study (TIPS-3) on the use of a polypill for the primary prevention of cardiovascular disease in intermediate-risk people. Finally, we discuss the SAMSON trial-a three-arm-N-of-1 trial-to identify the root cause of the symptoms contributing to patient nonadherence to statin therapy. The studies presented at the American Heart Association Scientific Session 2020 represent remarkable contributions in the field of cardiovascular disease and prevention.


Antimicrobial activity of Hedeoma drummondii against opportunistic pathogens.
Hedeoma drummondii is a medicinal plant with diverse properties; however, validations of its medicinal uses are scarce. To evaluate its antimicrobial properties H. drummondii, was tested against opportunistic pathogens of medical importance. Antimicrobial tests were performed by the microdilution method in order to determine the Minimal Inhibitory Concentration (MIC) for each extract. Extracts of this plant showed relevant antimicrobial activity, results revealed that the hexanic extract has stronger activity and broader spectrum compared to acetone and methanol extracts. The activity of hexanic extract may be attributed mainly to the presence of the monoterpenes pulegone and menthol. In conclusion, the hexanic extract possess relevant antibacterial properties which suggests that H. drummondii have bioactive principles; these new data provide scientific support for the use of this plant in traditional medicine, particularly for gastrointestinal diseases.


Nasal prongs in the detection of sleep-related disordered breathing in the sleep apnoea/hypopnoea syndrome.
Conventional systems to monitor oronasal flow in sleep studies have traditionally relied on a thermistor signal. Our study was designed to verify whether nasal prongs (NP) connected to a pressure transducer could improve respiratory events detection in patients with sleep apnoea/hypopnoea syndrome (SAHS) compared to traditional systems. Sleep episodes from a 2 h conventional polysomnographic record plus NP signal obtained at random from eight patients (age: mean(+/-SD) 53(+/-12) yrs; body mass index (BMI): 29(+/-6) kg x m(-2); apnoea/hypopnoea index (AHI): 27(+/-20) events x h(-1)) were identified and used for analysis. An abnormal change in the pattern of any of the respiratory or neurological variables occurring during the observation period was defined as an episode. Each episode was registered and scored with concomitant scoring of the remaining variables. According to the episode definition three different profiles were established: 1) periods of reduction of ventilation in either variable without an arousal or cyclical desaturation, named nonpathological episode (NPE); 2) an idiopathic or nonrespiratory arousal (IA); and 3) a true respiratory event (TRE) defined as reduction or absence of flow demonstrated by either thermistor, thoraco-abdominal bands or NP accompanied by cyclical desaturation and/or arousal. For each TRE, its detection by thermistor, thoraco-abdominal bands or NP was established. A total of 877 sleep episodes were observed (42 NPE, 30 IA and 805 TRE). When compared to single or combined thermistor and bands approach, NP had the highest respiratory events detection rate, 779 (96.8%) versus 673 events (83.6%), respectively. Detection of respiratory-related arousals was also improved by NP and only 3% could account for mouth breathing respiration. It is concluded that nasal prongs improve the detection of respiratory events in patients with sleep respiratory disorders.


Graded-field autoconfocal microscopy.
Autoconfocal microscopy (ACM) is a simple implementation of a transmitted-light confocal microscopy where a nonlinear detector plays the role of a virtual self-aligned pinhole. We report here a significant improvement of ACM based on the use of graded-field (GF) imaging. The technique of GF imaging involves introducing partial beam blocks in the illumination and detection apertures of an imaging system. These partial beam blocks confer phase-gradient sensitivity to the imaging system and allow control over its background level. We present the theory of the GF contrast in the context of ACM, comparing it to GF contrast in a non-scanning widefield microscope, and discuss various performance characteristics of GF-ACM in terms of resolution, sectioning strength, and an "under-detection" light collection geometry. An advantage of ACM is that it can be readily combined with two-photon excited fluorescence (TPEF) microscopy. We present images of rat brain hippocampus using simultaneous GF-ACMand TPEF microscopy. These images are inherently co-registered.


Genetic Mapping for Agronomic Traits in IAPAR 81/LP97-28 Population of Common Bean (Phaseolus vulgaris L.) under Drought Conditions.
One of the significant challenges of common bean breeding is developing cultivars with high yields under drought conditions. The present study attempted to map quantitative trait loci (QTLs) and identify molecular markers that are linked to drought tolerance in the common bean. We evaluated 160 recombinant inbred lines (RILs), derived from the cross between the carioca cultivars IAPAR 81 (drought tolerant) and LP97-28 (susceptible to drought). In 2014 and 2015, two experiments were conducted (DS-drought stress, and NS-no drought stress). In the DS experiment, water suppression was performed at the flowering stages R5 to R6. The results of our experiments showed that drought conditions play an essential role in reducing most of the traits that were evaluated. RILs under drought conditions reduced the grain yield by 62.03% and 24% in 2014 and 2015, respectively. We identified 15 quantitative trait loci distributed on the chromosomes Pv01, Pv02, Pv03, Pv07, Pv08, Pv09, Pv10, and Pv11, related to grain yield, seed yield per day, 100-seed weight, number of pods per plant, plant height, number of days for flowering, and number of days to maturity. The characteristics of seed yield per day, 100-seed weight, and number of days to maturity showed that QTLs colocalized on Pv07. Identifying QTLs that are linked to drought tolerance in the RIL population IAPAR 81 × LP97-28 is of particular importance for common bean breeding programs seeking to improve carioca beans that are cultivated in regions with drought conditions, such as Brazil.


An overview of Spanish studies on appropriateness of hospital use.
This paper is an overview of hospital utilization review in Spain. Most of the hospital utilization studies have used the Appropriateness Evaluation Protocol as the review instrument. The studies, mainly retrospective, started in the late 1980s and used different adaptations of the medical-surgical version of the protocol. The level of inappropriate use detected ranges between 2.1 and 44.8% for admissions, and from 15 to 43.9% for inappropriate days of stay. The variability in the detected degree of inappropriateness may be due to the differences in the review instrument, the use of the override option, the patients included in the study, or the setting. The determinants of inappropriate hospitalization in Spain are mainly related to access to the different levels of care and to the conservative attitude of the physicians. Future utilization review in Spain should be followed by the development of specific interventions to correct the current pattern of overutilization.