Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic.
To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3-2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.


Systematic Review on Magnetic Resonance Angiography with Vessel Wall Imaging for the Characterization of Symptomatic Carotid Artery Plaque.
To perform a systematic literature review to assess the usefulness of performing magnetic resonance angiography (MRA) with vessel wall imaging (VWI) sequences for the assessment of symptomatic carotid artery plaques and the identification of risky plaque features predisposing for stroke. We performed a systematic review of the literature pertaining to MRA with VWI techniques in patients with carotid artery disease, focusing on symptomatic patients' plaque features and morphology. Independent reviewers screened and analyzed data extracted from eligible studies, and a modified Newcastle-Ottawa Scale was used to appraise the quality of the design and content of the selected manuscripts to achieve an accurate interpretation. This review included nineteen peer-reviewed manuscripts, all of them including MRA and VWI assessments of the symptomatic carotid artery plaque. We focused on patients' comorbidities and reviewed plaque features, including intraplaque hemorrhage, a lipid-rich necrotic core, a ruptured fibrous cap, and plaque ulceration. MRA with VWI is a useful tool in the evaluation of carotid artery plaques. This imaging technique allows clinicians to identify plaques at risk of causing a neurovascular event. The presence of intraplaque hemorrhage, plaque ulceration, a ruptured fibrous cap, and a lipid-rich necrotic core are associated with neurovascular symptoms. The timely identification of these features could have a positive impact on neurovascular event prevention.


Expression of the epidermal growth factor receptor in astrocytic tumours is specifically associated with glioblastoma multiforme.
Epidermal growth factor and its receptor (EGFR) constitute an important and well-characterized mitogenic system in various ectodermal tissues including glial cells. Over-expression of the EGFR due to gene amplification has been reported in primary brain tumours of glial origin. Using a monoclonal antibody to the EGFR and immunohistochemical analysis, we examined the expression and distribution of EGFR in 103 astrocytic tumours. In addition, selected tumours were studied by Western blotting using a polyclonal antibody to EGFR and by Southern blot analysis. Glioblastomas (WHO grade IV) showed EGFR expression in 37% of cases, whereas pilocytic (WHO grade I), low-grade (WHO grade II) or anaplastic astrocytoma (WHO grade III) were invariably EGFR negative. Generally, there was a close correlation between the presence of EGFR gene amplification and over-expression of receptor protein. Different patterns of immunoreactive cells and significant intratumour heterogeneity of EGFR expression were observed in glioblastomas. The specific association of EGFR over-expression with glioblastoma may provide a useful diagnostic tool for distinguishing anaplastic astrocytoma (WHO grade III) and glioblastoma multiforme (WHO grade IV).


Metabolic Signatures of Performance in Elite World Tour Professional Male Cyclists.
Metabolomics studies of recreational and elite athletes have been so far limited to venipuncture-dependent blood sample collection in the setting of controlled training and medical facilities. However, limited to no information is currently available to determine if findings in laboratory settings are translatable to a real-world scenario in elite competitions. The goal of this study was to define molecular signatures of exertion under controlled exercise conditions and use these signatures as a framework for assessing cycling performance in a World Tour competition. To characterize molecular profiles of exertion in elite athletes during cycling, we performed metabolomics analyses on blood isolated from 28 international-level, elite, World Tour professional male athletes from a Union Cycliste Internationale World Team taken before and after a graded exercise test to volitional exhaustion and before and after a long aerobic training session. Moreover, established signatures were then used to characterize the metabolic physiology of five of these cyclists who were selected to represent the same Union Cycliste Internationale World Team during a seven-stage elite World Tour race. Using dried blood spot collection to circumvent logistical hurdles associated with field sampling, these studies defined metabolite signatures and fold change ranges of anaerobic or aerobic exertion in elite cyclists, respectively. Blood profiles of lactate, carboxylic acids, fatty acids, and acylcarnitines differed between exercise modes. The graded exercise test elicited significant two- to three-fold accumulations in lactate and succinate, in addition to significant elevations in free fatty acids and acylcarnitines. Conversely, the long aerobic training session elicited a larger magnitude of increase in fatty acids and acylcarnitines without appreciable increases in lactate or succinate. Comparable signatures were revealed after sprinting and climbing stages, respectively, in a World Tour race. In addition, signatures of elevated fatty acid oxidation capacity correlated with competitive performance. Collectively, these studies provide a unique view of alterations in the blood metabolome of elite athletes during competition and at the peak of their performance capabilities. Furthermore, they demonstrate the utility of dried blood sampling for omics analysis, thereby enabling molecular monitoring of athletic performance in the field during training and competition.


Xiaflex for Treatment of Peyronie's Disease.
Xiaflex or collagenase Clostridium histolyticum intralesional injections are safe and effective as first-line treatment for Peyronie's disease.


Enhanced photo-H2 production of R. faecalis RLD-53 by separation of CO2 from reaction system.
The effect of different gases, CO(2) concentration, and separation of CO(2) from reaction system on photo-fermentation H(2) production was investigated by batch culture in this study. Experimental results showed that different gases (Ar,N(2),CO(2), and air) as gas phase have obviously affected on photo-H(2) production and a high concentration of CO(2) can inhibit the growth and H(2) evolution of Rhodopseudomonas faecalis RLD-53. When CO(2) concentration at 5%, cell increased most rapidly the specific growth rate of 0.489 g/l/h and the specific growth rate fell to be 0.265 g/l/h when CO(2) concentration at 40%. However, the growth of RLD-53 at CO(2) concentration of 60-100% was almost completely inhibited. At CO(2) concentrations of 5% and 10%, the maximum H(2) yield was 2.54 and 2.59 mol-H(2)/mol acetate, respectively, and it was similar with the control (2.61 mol-H(2)/mol acetate). H(2) not produced when CO(2) concentration at 60-100%. In conclusion, separation of CO(2) from reaction system can stimulate H(2) production in the entire photo-H(2) production process and H(2) yield increased about 12.8-18.85% than the control.


Determination of molecular forms of brain acetylcholinesterase: technical considerations.
Sucrose density centrifugation has been used to characterize the relative levels of AChE molecular forms in different parts of the brain, during development, or in various disease states. We have examined the influence of various tissue or sample storage and handling techniques on the abundance of the 4S and 10S molecular forms of AChE in rat forebrain. Our results demonstrate that freezing either a subcellular fraction or the intact tissue causes dramatic shifts in the level of the 4S and 10S molecular forms as compared to the values obtained in fresh tissue. Total AChE activity was unchanged suggesting that 4S and 10S forms are equally active and that 4S AChE is easily dissociated from 10S. These observations suggest that 4S and 10S molecular forms in brain are extremely labile and that great care should be taken when studying the factors that regulate these forms.


Healing of Planar Defects in 2D Materials via Grain Boundary Sliding.
Understanding the mechanisms and kinetics of defect annihilations, particularly at the atomic scale, is important for the preparation of high-quality crystals for realizing the full potential of 2D transition metal dichalcogenides (TMDCs) in electronics and quantum photonics. Herein, by performing in situ annealing experiments in an atomic resolution scanning transmission electron microscope, it is found that stacking faults and rotational disorders in multilayered 2D crystals can be healed by grain boundary (GB) sliding, which works like a "wiper blade" to correct all metastable phases into thermodynamically stable phases along its trace. The driving force for GB sliding is the gain in interlayer binding energy as the more stable phase grows at the expanse of the metastable ones. Density functional theory calculations show that the correction of 2D stacking faults is triggered by the ejection of Mo atoms in mirror twin boundaries, followed by the collective migrations of 1D GB. The study highlights the role of the often-neglected interlayer interactions for defect repair in 2D materials and shows that exploiting these interactions has significant potential for obtaining large-scale defect-free 2D films.


Preparing of pellets by extrusion/spheronization using different types of equipment and process conditions.
The focus of this work was to produce matrix pellets made by extrusion/ spheronization using two types of equipment. The aim was to accomplish the laboratory-scale I process that has been already optimized and accepted with another type of equipment (laboratory-scale II). A matrix pellet formulation consisting of MCC, Eudragit NE 30D and diclofenac sodium was used in the two types of equipment. Physico-chemical parameters and the dissolution profiles of the pellets in phosphate buffer pH 6.8 were compared. Pellets from both processes were similar in shape and tensile strength. They differed in particle size and dissolution profile. This may be contributed to different spheronization conditions.


Slice-shape artifact changes with precession angle in rapid MR imaging.
One possible method of measuring T1 in rapidly acquired magnetic resonance images using variants of the FLASH technique is by the manipulation of the magnetization precession angle. It is suggested here that this method is as prone to slice-shape artifacts as many other approaches.


Modified inverted internal limiting membrane flap technique for macular hole closure.
To investigate the efficacy of modified internal limiting membrane (ILM) flap technique combined with vitreous surgery for treating macular holes and examine the outcomes in visual function and anatomic macular hole closure. Retrospective, observational. Between July 1, 2015, and October 1, 2019, the modified inverted ILM flap technique combined with vitreous surgery was used to treat idiopathic macular holes, postoperative progression was then followed for at least 6 months in 96 participants (98 eyes). We modified the method by removing the lower half of the ILM while peeling and inverting the upper half. The mean age of the participants was 65.9 ± 11.9 years (41 men (42.7%) and 55 women (57.3%)). Retrospective evaluations of macular hole diameter, corrected visual acuity, and macular hole closure rates were performed using data from medical records. The mean macular hole diameter was 623.6 ± 207.4 μm. The mean corrected visual acuity (logMAR) was 0.79 ± 0.27 before surgery and 0.46 ± 0.35 at 1, 0.35 ± 0.39 at 3, and 0.31 ± 0.36 at 6 months Post surgery, showing significant differences before and after surgery (p = 2.30 × 10- 2). The macular hole closure rate was 98%. The modified inverted ILM flap technique combined with vitreous surgery was an effective method for treating macular holes, resulting in improvement in closure and visual acuity.


The role of ALPPS in intrahepatic cholangiocarcinoma.
Surgical resection constitutes the mainstay of curative treatment for intrahepatic cholangiocarcinoma (iCCA). Complete tumor clearance can only be achieved with extended liver resections and as such, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) may facilitate surgical resectability. The present study aims to evaluate the technical feasibility and oncologic outcome of ALPPS in iCCA. A set of 14 patients who underwent ALPPS in a single center between 2011 and 2017 were statistically analyzed for perioperative and oncologic outcome. Of all patients undergoing stage 1 of ALPPS, 12 (86%) patients were subsequently completed in stage 2 surgery. Patients who completed the ALPPS procedure showed a median overall survival (OS) of 4.2 years and a 3-year survival of 64%. Individuals without lymphatic metastases (n = 7) were all alive 1 year after surgery and if deceased, they died more than 4 years after surgery, while no patient with lymphatic metastases (n = 5) was alive 1 year after surgery. This is the largest single-center experience of ALPPS in iCCA currently available in the literature showing excellent technical feasibility and encouraging overall survival in these patients.


Female scent accelerates growth of juvenile male mice.
Exposing female house mice (Mus musculus) to male urinary scent accelerates their sexual development (Vandenbergh effect). Here, we tested whether exposing juvenile male mice to females' urine similarly influences male growth and size of their sexual organs. We exposed three-week old male house mice to female urine or water (control) for ca. three months. We found that female-exposed males grew significantly faster and gained more body mass than controls, despite all males being reared on a controlled diet, but we detected no differences in males' muscle mass or sexual organs. In contrast, exposing juvenile males to male urine had no effect their growth. We tested whether the males' accelerated growth imposed functional trade-offs on males' immune resistance to an experimental infection. We challenged the same male subjects with an avirulent bacterial pathogen (Salmonella enterica), but found no evidence that faster growth impacted their bacterial clearance, body mass or survival during infection compared to controls. Our results provide the first evidence to our knowledge that juvenile male mice accelerate their growth when exposed to the urine of adult females, though we found no evidence that increased growth had negative trade-offs on immune resistance to infectious disease.


New insights into the genomic organization and origin of the major histocompatibility complex: role of chromosomal (genome) duplication in the emergence of the adaptive immune system.
Recently, it became clear that the human and mouse genomes contain at least three regions paralogous to the major histocompatibility complex (MHC) region. This observation led us to the proposal that the MHC region emerged as a result of chromosomal duplication that took place at an early stage of vertebrate evolution. Here I briefly review this proposal. Accumulating evidence indicates that (a) genome-wide duplication(s) took place close to the origins of vertebrates. Taking this and others into account, I suggest that the duplication(s) involving the MHC region probably took place as a part of the genome-wide duplication(s). The human T cell receptor (TCR) and immunoglobulin (Ig) genes also appear to be located on paralogous chromosomal segments. These findings raise the possibility that the genome-wide duplication provided a major impetus not only to the emergence of the full-fledged MHC system, but also to the appearance of other key molecules of the adaptive immune system such as TCR and Ig.


Angiotensin-I converting enzyme (ACE) inhibitory mechanism of tripeptides containing aromatic residues.
Angiotensin-I converting enzyme (ACE) plays important roles in the regulation of blood pressure, and ACE inhibitory peptides in food materials have attracted attention for their antihypertensive function. In this study, the function of amino acids in ACE inhibitory tripeptides was clarified.


Pre-transplant evaluation completion for Black/African American renal patients: Two theoretical frameworks.
Black/African Americans (B/AA) are less likely to complete the pre-transplant evaluation for kidney transplantation despite higher prevalence rates of end-stage renal disease (ESRD). To better understand the barriers and motivators to completing the evaluation process, two qualitative studies were conducted to categorize and elucidate the relationships between these factors. In Phase I, semi-structured interviews were conducted with a stratified purposeful sample of transplant professionals (N = 23). Focus groups were conducted during Phase II with a purposeful sample of B/AA patients (N = 30). Thematic analyses assessed using grounded theory revealed a multitude of factors at individual and systemic levels, including health and informational/educational-related factors. Two comprehensive theoretical frameworks, a socio-ecological model of barriers and a model of motivators are presented. Medical mistrust is an example of a community factor identified as impeding completion rates. Systemic motivators included compressed time for testing and fewer intervals between doctor's appointments. This study offers a structure for understanding impediments to and facilitators of pre-transplant evaluation completion as seen through the eyes of both B/AA ESRD patients seeking transplant and the providers who work with them. Recommendations for intervention and systemic changes to narrow health disparities are discussed.


Predicting recklessness in emerging adults: a test of a psychosocial model.
Emerging adults--people aged 18-25 years--frequently behave recklessly. This study sheds light on the role of 4 psychosocial predictors of recklessness: (a) impulsivity, (b) peer pressure, (c) perceived risk, and (d) perceived benefits. The authors obtained self-report data from 208 emerging adults. All predictors were significantly correlated, in the expected directions, with 3 forms of reckless behavior: (a) reckless substance use, (b) reckless driving, and (c) reckless sexual behavior. Regression analyses revealed that, controlling for gender, relationship status, and social desirability, impulsivity predicted reckless substance use and sexual practices, peer pressure predicted reckless substance use, perceived risk predicted reckless driving, and perceived benefits predicted all three recklessness types. The authors' psychosocial model of emerging adult recklessness gained additional support from the finding that all 4 predictors explained unique variance in overall recklessness.


Utility of new bioabsorptive screws in cervical anterior fusion.
The aim of this study is to report our use of new bioabsorbable screws in cervical anterior fusion. These screws need not be removed because they are completely absorbed by resolution in vivo. We describe our method and the new bioabsorbable screws. We used PLLA screws until September 2004 and uncalcined uHA-PLLA screws thereafter. They are completely absorbed by resolution to water and carbon dioxide upon in vivo hydrolysis. The uHA-PLLA screws are x-ray impenetrable, and their uHA content renders them osteoconductive. In cervical anterior fusion, the graft is inserted in the area of deletion resulting from decompression. The screws are inserted in the 4 corners of the vertebral body and graft. In long fusion, they are introduced in the 2 lateral wings of the bone graft on each vertebral body and in the 4 corners. Our method eliminates the need for plates or mesh. We have used this method in 62 patients and encountered no complications. There were no screw or graft extrusions and no surgery-related infections. The patients were able to walk a few hours after the operation and wore a simple neck collar for a few days. This safe and easy method shortens the hospital stay and reduces the risk of graft extrusion and complications associated with the use of nonabsorbable devices.


Trends in sensitivity analysis practice in the last decade.
The majority of published sensitivity analyses (SAs) are either local or one factor-at-a-time (OAT) analyses, relying on unjustified assumptions of model linearity and additivity. Global approaches to sensitivity analyses (GSA) which would obviate these shortcomings, are applied by a minority of researchers. By reviewing the academic literature on SA, we here present a bibliometric analysis of the trends of different SA practices in last decade. The review has been conducted both on some top ranking journals (Nature and Science) and through an extended analysis in the Elsevier's Scopus database of scientific publications. After correcting for the global growth in publications, the amount of papers performing a generic SA has notably increased over the last decade. Even if OAT is still the most largely used technique in SA, there is a clear increase in the use of GSA with preference respectively for regression and variance-based techniques. Even after adjusting for the growth of publications in the sole modelling field, to which SA and GSA normally apply, the trend is confirmed. Data about regions of origin and discipline are also briefly discussed. The results above are confirmed when zooming on the sole articles published in chemical modelling, a field historically proficient in the use of SA methods.


Hepatic repopulation with stably transduced conditionally immortalized hepatocytes in the Gunn rat.
Conditionally immortalized hepatocytes offer a renewable source of hepatocytes, but although preparative maneuvers have been developed for hepatic repopulation with primary hepatocytes, extensive proliferation of transplanted immortalized hepatocytes has not been accomplished heretofore. Our aim was to achieve ex vivo gene therapy of uridinediphosphoglucuronate glucuronosyltransferase-1A1 (UGT1A1)-deficient jaundiced Gunn rats (model of Crigler-Najjar syndrome type-1) by hepatic repopulation with genetically modified and conditionally immortalized hepatocytes. Gunn rat hepatocytes were conditionally immortalized by stable transduction with a thermolabile mutant simian virus 40 T-antigen ((ts)Tag(A58)) and further transduced with UGT1A1. These hepatocytes proliferate at 33 degrees C, but at 37 degrees C the (ts)Tag(A58) is degraded and the cells become quiescent. The cells were transplanted into Gunn rat livers after preparative hepatic irradiation (50 Gy) and 66% hepatectomy. The engrafted UGT1A1-positive immortalized hepatocytes replaced approximately 80% of the host hepatocytes in 20 weeks, leading to normalization of hyperbilirubinemia. Liver histology, and serum albumin and alanine aminotransferase levels remained normal. We achieved complete cure of hyperbilirubinemia in Gunn rats by ex vivo gene therapy via genetically modified and conditionally immortalized hepatocytes.


Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: early results of a pilot study.
To report the early results of hyperfractionated craniospinal radiation therapy with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs). Thirty-nine patients with PNETs were classified as good-risk (23) or poor-risk (16), based on postoperative magnetic resonance imaging and a cytological examination of cerebrospinal fluid. All patients received hyperfractionated craniospinal radiation therapy; poor-risk patients subsequently received adjuvant chemotherapy with cisplatin, lomustine, and vincristine. The first six patients received 72 Gy to the primary tumor site and 24 Gy to the rest of the craniospinal axis. Subsequent patients received 30 Gy to the craniospinal axis. During a median of 1.9 years of follow-up (range 4 months to 3.5 years), there have been ten treatment failures in 39 patients, five in the good-risk group and five in the poor-risk group. Three failures occurred in the primary tumor site in areas that received 72 Gy; two were in poor-risk patients with residual disease after surgery; one was in a good-risk patient who had a gross total resection. Three failures occurred in the spine and craniospinal fluid of patients treated with 24 Gy. Four occurred in areas treated to 30 Gy; two of these were in areas thought to be undertreated because of treatment planning errors. Adjuvant chemotherapy was difficult to give to poor-risk patients because of poor bone marrow recovery, even with relatively low doses of lomustine (75 mg/m2). We think a dose of 24 Gy to the craniospinal axis is inappropriate because three of the six patients who received it had treatment failures outside the primary site. Whether 30 Gy is an appropriate dose for good-risk patients is still unclear. Even after a dose of 30 Gy, chemotherapy was difficult to give; this potentially limits the impact of adjuvant chemotherapy in poor-risk patients. Further follow-up is necessary to evaluate the use of hyperfractionated radiation therapy alone or with chemotherapy in patients with PNETs.


Ablation index-guided ablation with milder targets for atrial fibrillation: Comparison between high power and low power ablation.
High power-ablation index (HP-AI)-guided ablation for atrial fibrillation (AF) targeting high AIs has been implemented in European countries. However, milder AI targets are widely used in Asia. The safety and efficacy of HP-AI-guided ablation compared with those of low-power AI-guided ablation in a milder AI-targeting setting are unknown. The goal of this study was to explore the efficacy and safety of HP-AI-guided ablation in a milder AI-targeting setting. Patients who underwent pulmonary vein isolation (PVI) for AI-guided atrial fibrillation ablation in our center were enrolled and divided into 2 groups according to the ablation power used. In the HP-AI group, the ablation power was over 45 W, while the low power-AI group was ablated with <35 W power. The targeted AIs were 450-500 in the anterior wall and 350-400 in the posterior wall. The efficacy outcome was expressed as the single-procedure atrial arrhythmia-free survival between 91 days and 1 year. Safety outcomes included severe adverse events (SAEs), including symptomatic pulmonary vein (PV) stenosis, atrioesophagal fistula, cardiac tamponade, stroke, thromboembolism events, myocardial infarction, and major bleeding. A total of 134 patients were enrolled, of whom 74 underwent PVI using HP-AI, while 60 received low power-AI ablation. After a mean follow-up time of 7.4 months, 22 (16.4%) patients showed arrhythmia recurrence: 5 (6.8%) patients in the HP-AI group and 17 (28.3%) patients in the low power-AI group. The HP-AI group showed a significantly higher arrhythmia-free survival than the low power-AI group (p = 0.011). Two patients in the low power-AI group and 1 patient in the HP-AI group developed an SAE (p = NS). Compared with the low power-AI group, the HP-AI group demonstrated a higher PV first-pass isolation rate, shorter ablation time, and fewer patients with anatomical leakages and sites of unreached AI. In a milder AI setting, HP-AI ablation might result in significantly higher arrhythmia-free survival than low power-AI ablation and a similar safety profile.


Long-term survival of a female patient with primary malignant melanoma of the urethra.
Primary malignant melanoma of the female urethra comprises 0.2% of all melanomas and has poor prognosis. In the period 1972-1992, 75 cases of primary urethra carcinomas were treated at the Roswell Park Cancer Institute. Among them, only an 80-year-old woman was diagnosed with primary malignant melanoma. Despite conservative treatment, she lived for 7 years. We believe that local surgical excision can be an option for treatment in selected patients as it retains quality of life.


Severe heart failure in the setting of relatively mild mitral stenosis: the role of invasive hemodynamic assessment.
For patients with heart failure and relatively mild mitral stenosis, an exercise hemodynamic study should be considered. However, exercise intolerance is a common symptom in a variety of cardiac and noncardiac diseases, emphasizing the need for a thorough differential diagnosis in the planning and execution of these studies. This manuscript discusses two cases that illustrate the need for this comprehensive approach, the indications for balloon mitral valvuloplasty, and the recognition of diastolic dysfunction in these patients.


Comparison of depressive indices: reliability, validity, relationship to anxiety and personality and the role of age and life events.
Although a great number of depressive scales were developed during the last decades, there are only a few studies that compare them in terms of reliability and validity. The current study aimed to compare the properties of some of the most popular of these scales. The study sample included 40 depressed patients 29.65+/-9.38 years old, and 120 normal comparison subjects 27.23+/-10.62 years old. The clinical diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0. The scales compared were the CES-D, ZDRS, BDI-I, and the KSQ. The STAI, the Life Change Scale (Holms and Rahe), and the EPQ were also administered. The analysis included the comparison of psychometric properties and the use of Pearson correlation coefficient and factor analysis. The results suggested that no scale was clearly superior to the others. All scales correlated to anxiety measurements, sociodemographic variables, personality dimensions and non-specific indices. The results reported here include an appendix with algorithms that help transforming one scale score into other scales scores. These algorithms can be useful for comparison purposes in meta-analytic studies. The comparison of several depressive scales provided no impressive results on the superiority or inferiority of a specific scale in comparison to the others.


Components of heart rate variability measured during healing of acute myocardial infarction.
A high degree of heart rate (HR) variability is found in persons with normal hearts, whereas low HR variability can be found in patients with severe coronary artery disease, congestive heart failure and diabetic neuropathy. Two weeks after acute myocardial infarction, low HR variability predicted reduced long-term survival even after adjusting for clinical risk indicators, left ventricular ejection fraction, HR and ventricular arrhythmias. The present study elucidated the causes of differences in HR and HR variability between patients with low and high HR variability. In a matched-pair study, 10 patients with low HR variability (24-hour standard deviation of N-N intervals less than 50 ms) were randomly selected. For each of these 10 patients, a control patient with high HR variability (24-hour standard deviation of N-N intervals greater than or equal to 100 ms), matched for age, left ventricular ejection fraction and rales in the coronary care unit was selected. Patients who were taking either digitalis or beta-adrenergic blocking drugs were excluded. Analysis of 24-hour electrocardiograms showed that for the low HR variability group compared with the high: (1) the daytime and nighttime average HR was faster; (2) the difference between daytime and nighttime HR was less; (3) the proportion of differences greater than 50 ms between successive N-N intervals was smaller; and (4) the number of HR "spikes" per day (increase in HR greater than or equal to 10 beats/min, lasting from 3 to 15 minutes) was less.(ABSTRACT TRUNCATED AT 250 WORDS)


A new method for cell permeabilization reveals a cytosolic protein requirement for Ca2+ -activated secretion in GH3 pituitary cells.
Ca2+ is a major regulator of exocytosis in secretory cells, however, the biochemical mechanisms underlying regulation remain to be identified. To render the secretory apparatus accessible for biochemical studies, we have developed a cell permeabilization method (cell cracking) which utilizes mechanical shear. GH3 pituitary cells subjected to cracking were permeable to macromolecules but retained a normal cytoplasmic ultrastructure including secretory granules. Incubation of the permeable cells at 30-37 degrees C with 0.1-1.0 microM Ca2+ and millimolar MgATP resulted in the release of the secretory proteins, prolactin (PRL) and a proteoglycan, but not lysosomal enzymes. Extensively washed permeable cells were incapable of releasing PRL in response to Ca2+ and MgATP addition. However, addition of cytosol was found to restore Ca2+-activated, MgATP-dependent PRL release. The cytosolic factor responsible for activity was thermolabile and protease sensitive. The protein was partially purified, and its molecular mass was estimated to be equivalent to that of a globular protein of 200-350 kDa by molecular sieve chromatography. Inhibitors of calmodulin or protein kinase C (trifluroperazine, calmidazolium, H-7) failed to inhibit Ca2+-activated PRL release, and the required cytosolic protein could not be replaced by purified calmodulin, calmodulin-dependent protein kinase II, protein kinase C, or calpactin I. Further purification and characterization of the cytosolic protein should reveal the nature of biochemical events involved in regulated secretory exocytosis.


Heart Failure and Diabetes Mellitus: Defining the Problem and Exploring the Interrelationship.
Type 2 diabetes mellitus and congestive heart failure are highly prevalent diseases with significant morbidity and mortality. These 2 diseases often occur concurrently because of shared risk factors such as coronary artery disease, and also because type 2 diabetes mellitus has direct cardiotoxic effects. Type 2 diabetes mellitus likely has a causative role in the development and prognosis of patients with heart failure. Optimal prevention and treatment of type 2 diabetes mellitus and heart failure likely involves identifying and treating their shared pathophysiologic features. Novel drug therapies, such as sodium-glucose co-transporter 2 inhibitors, offer an exciting potential to better understand the relationship between type 2 diabetes mellitus and heart failure, and may prove to have beneficial effects on cardiovascular outcomes in patients affected by these diseases.


Three-dimensional modeling of air flow and pollutant dispersion in an urban street canyon with thermal effects.
Effects of excess ground and building temperatures on airflow and dispersion of pollutants in an urban street canyon with an aspect ratio of 0.8 and a length-to-width ratio of 3 were investigated numerically. Three-dimensional governing equations of mass, momentum, energy, and species were modeled using the RNG k-epsilon turbulence model and Boussinesq approximation, which were solved using the finite volume method. Vehicle emissions were estimated from the measured traffic flow rates and modeled as banded line sources, with a street length and bandwidths equal to typical vehicle widths. Both measurements and simulations reveal that pollutant concentrations typically follow the traffic flow rate; they decline as the height increases and are higher on the leeward side than on the windward side. Three-dimensional simulations reveal that the vortex line, joining the centers of cross-sectional vortexes of the street canyon, meanders between street buildings and shifts toward the windward side when heating strength is increased. Thermal boundary layers are very thin. Entrainment of outside air increases, and pollutant concentration decreases with increasing heating condition. Also, traffic-produced turbulence enhances the turbulent kinetic energy and the mixing of temperature and admixtures in the canyon. Factors affecting the inaccuracy of the simulations are addressed.


Xenopus differentiation: VegT gets specific.
Depletion of the maternal store of the localised mRNA encoding the T-box transcription factor VegT in Xenopus embryos has recently been shown to dramatically block endoderm formation and change the normal position of the mesodermal and ectodermal germ layers.


Comparison of injuries of belted occupants among different BMI categories in frontal crashes.
Previous studies have shown that occupants with obesity are at a greater risk of fatality and serious injury than other occupants in motor vehicle crashes. To provide a more complete description of the most frequent injuries and the most frequently injured body regions for occupants with obesity. Sampled cases (n = 13,470) representing ~4.7 million adult occupants involved in frontal crashes (between 2000 and 2015) were selected from the U.S. National Automotive Sampling System-Crashworthiness Data System database. A retrospective cohort study was performed to study the effect of BMI on the risk of injury to different body regions and to identify the most frequent injuries to occupants with different BMIs. Lastly, in-depth crash analysis cases from the U.S. Crash Injury Research and Engineering Network (CIREN) database were studied to elucidate the source of the most common injuries to occupants with obesity. Occupants with obesity experienced a higher risk of upper extremity (4.79 vs 2.92%), lower extremity (8.37 vs 3.23%), and spine (1.53 vs 1.09%) injuries than other occupants. After adjusting for other variables, the risks of spinal, thoracic, and extremities injuries were found to be affected by the BMI class. Seven out of the ten most common injuries sustained by occupants with obesity were lower extremity injuries, and talus fractures were the most common overall. Direct loading through the plantar surface of the foot by the vehicle toe pan was found to be a likely cause of many of those injuries based on CIREN cases. The injuries of occupants with obesity are different than other occupants which can be attributed to their different interaction with the seat belt and vehicle interior. The findings of this study should be considered for designing restraint systems to protect occupants with obesity in car crashes.


Postoperative rehospitalization in older surgical patients: an age-stratified analysis.
Older adults comprise 40% of surgical inpatients and are at increased risk of postoperative rehospitalization. A decade ago, 30-day rehospitalizations for Medicare patients were reported as 15%, and more than 70% was attributed to medical causes. In the interim, there have been several large-scale efforts to establish best practice for older patients through surgical quality programs and national initiatives by Medicare and the National Health Service. To understand the current state of rehospitalization in the USA, we sought to report the incidence and cause of 30-day rehospitalization across surgical types by age. We performed a retrospective study utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) dataset from 2015 to 2019. Our primary exposure of interest was age. Patients were categorized into four groups: 18-49, 50-64, 65-74, and 75 + years old. Reasons for rehospitalization were evaluated using NSQIP defined causes and reported International Classification of Disease (ICD)-9 and ICD-10 codes. Our primary outcome was the incidence of unplanned 30-day rehospitalization and secondary outcome the cause for rehospitalization. Variables were summarized by age group through relative (%) and absolute (n) frequencies; chi-square tests were used to compare proportions. Since rehospitalization is a time-to-event outcome in which death is a competing event, the cumulative incidence of rehospitalization at 30 days was estimated using the procedure proposed by Gray. The same strategy was used for estimating the cumulative incidence for unplanned rehospitalizations. A total of 2,798,486 patients met inclusion criteria; 198,542 had unplanned rehospitalization (overall 7.09%). Rehospitalization by age category was 6.12, 6.99, 7.50, and 9.50% for ages 18-49, 50-64, 65-74, and 75 + , respectively. Complications related to the digestive system were the single most common cause of rehospitalization across age groups. Surgical site infection was the second most common cause, with the relative frequency decreasing with age as follows: 21.74%, 19.08%, 15.09%, and 9.44% (p < .0001). Medical causes such as circulatory or respiratory complications were more common with increasing age (2.10%, 4.43%, 6.27%, 8.86% and 3.27, 4.51, 6.07, 8.11%, respectively). We observed a decrease in overall rehospitalization for older surgical patients compared to studies a decade ago. The oldest (≥ 75) surgical patients had the highest 30-day rehospitalization rates (9.50%). The single most common reason for rehospitalization was the same across age groups and likely attributed to surgery (ileus). However, the aggregate of medical causes of rehospitalization was more common in older patients; surgical and respiratory reasons were twice as common in this group. Rehospitalization increased by age for some surgery types, e.g., lower extremity bypass, more than others, e.g., ventral hernia repair. Future investigations should focus on interventions to reduce medical complications and further decrease postoperative rehospitalization for older surgical patients undergoing high-risk procedures.


The trustworthiness of the cumulative knowledge in industrial/organizational psychology: The current state of affairs and a path forward.
The goal of industrial/organizational (IO) psychology, is to build and organize trustworthy knowledge about people-related phenomena in the workplace. Unfortunately, as with other scientific disciplines, our discipline may be experiencing a "crisis of confidence" stemming from the lack of reproducibility and replicability of many of our field's research findings, which would suggest that much of our research may be untrustworthy. If a scientific discipline's research is deemed untrustworthy, it can have dire consequences, including the withdraw of funding for future research. In this focal article, we review the current state of reproducibility and replicability in IO psychology and related fields. As part of this review, we discuss factors that make it less likely that research findings will be trustworthy, including the prevalence of scientific misconduct, questionable research practices (QRPs), and errors. We then identify some root causes of these issues and provide several potential remedies. In particular, we highlight the need for improved research methods and statistics training as well as a re-alignment of the incentive structure in academia. To accomplish this, we advocate for changes in the reward structure, improvements to the peer review process, and the implementation of open science practices. Overall, addressing the current "crisis of confidence" in IO psychology requires individual researchers, academic institutions, and publishers to embrace system-wide change.


Proteomic and phosphoproteomic analysis of cellular responses in medaka fish (Oryzias latipes) following oral gavage with microcystin-LR.
Chronic and subchronic toxicity resulting from exposure to microcystins (MCs) receives increasing attention due to the risk of bioaccumulation of these toxins by aquatic animals, including fish. The mechanisms of action of MCs that target the liver, involve modifications of protein phosphorylation resulting from phosphatases 1 and 2A inhibition. Therefore, studying phosphoprotein modifications by using a specific phosphoprotein stain Pro-Q Diamond in fish liver contaminated with MC-leucine-arginine (MC-LR), the most toxic MC, should help dissecting disturbed signaling and metabolic networks. We have recently used this technology to identify several proteins that are modulated either in expression or phosphorylation in the liver of medaka following short-term exposure to MC-LR by balneation. In the present study, we have decided to use an alternative way of introducing the toxin into fish; that is by gavage (force-feeding). This was first achieved using tritiated MC-LR and allowed us to quantify the quantity of toxin incorporated into fish and to demonstrate that the toxin is mainly accumulated in liver. Afterwards a proteomics study limited to liver cytosolic proteins of contaminated animals showed that several proteins were up or down regulated either in quantity or in phosphorylation or both. Some of them had been previously detected as modified in balneation experiments but new molecules were identified as involved in signal transduction pathways activated by the toxin. In addition, in the conditions used (5 microg toxin/g body weight) anatomopathological studies supported a process of apoptonecrosis established after 24h, which was suggested to proceed by the evolution of some of the proteins after 2h contamination.


Orbital dirofilariasis.
To warn the ophthalmologist to consider orbital dirofilariasis in the differential diagnosis of inflammatory masses of the orbit. Two cases with non-specific swelling and pain of the orbit who had a initial diagnosis of "inflammatory pseudotumor of the orbit". These are two new cases of orbital dirofilariasis. In the ophthalmic literature, the highest incidence of ocular dirofilariasis is reported in Italy. Since both these patients had no history of travel in endemic areas of Dirofilaria, this parasitic infection is presumably not rare in Italy and is probably underdiagnosed.


Investigation of the gut microbiome of Apis cerana honeybees from Vietnam.
In this study, the gut microbiome of healthy adult honeybees, Apis cerana, was investigated by sequencing the V3 - V4 region in 16S rRNA gene using Illumina Miseq platform. The total of 37,853 reads for 16S rRNA gene were obtained and 30,121 (79.6%) reads were valid with 25,291 (84.0%) reads that were classified into 116 species belonging to four major phyla. The relative abundances of the bacterial isolates in honeybee samples were phylum Proteobacteria (70.7%), Actinobacteria (10.7%), Firmicutes (10.3%), and Bacteroidetes (8.4%), respectively. Lactic acid bacteria comprised 18.95% with 10 groups including Bifidobacterium asteroides, B. indicum, Fructobacillus fructosus, Lactobacillus apinorum, L. apis, L. helsingborgensis, L. kimbladii, L. kullabergensis, and L. kunkeei. The presence of beneficial bacteria in the gut highlighted their role in the honeybee and suggested that they can be promising candidates for the development of probiotics for health improvement, infection control and disease management of honeybees.


Bioactive molecules from protists: Perspectives in biotechnology.
For hundreds of years, mankind has benefited from the natural metabolic processes of microorganisms to obtain basic products such as fermented foods and alcoholic beverages. More recently, microorganisms have been exploited for the production of antibiotics, vitamins and enzymes to be used in medicine and chemical industries. Additionally, several modern drugs, including those for cancer therapy, are natural products or their derivatives. Protists are a still underexplored source of natural products potentially of interest for biotechnological and biomedical applications. This paper focuses on some examples of bioactive molecules from protists and associated bacteria and their possible use in biotechnology.


Supracervical and total abdominal hysterectomy trends in New York State: 1990-1996.
To describe practice trends for total abdominal hysterectomy (TAH) and supracervical abdominal hysterectomy (SCH) in New York State and to identify fiscal features associated with these two operations, all inpatient discharges for TAH and SCH performed for benign indications from 1990 to 1996 were reviewed using the Statewide Planning and Resource Cooperative System, a centralized data reporting system. For each year examined, the number of TAHs and SCHs performed, the procedure rates adjusted for the total New York State female population, and the per diem charge (calculated from mean institutional charge as a function of average length of stay) were evaluated. While the TAH rate declined in New York State, from 34.0 in 1990 to 28.4 in 1996 (P = .01), the SCH rate increased nearly five-fold during the same period, from 0.62 to 3.07 (P = .0003). Patients tended to be discharged later following SCH than for TAH, although by 1996, the LOS for both operations was equivalent. The per diem institutional charge for SCH was consistently higher than for TAH in each year studied. The changes in charge and relative frequency of TAH and SCH in New York State invite further study to describe these trends more fully.


Marginal donor liver versus standard donor liver: A single-center observational study.
The effectiveness and safety of marginal donor livers remain controversial. This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation (LT). This study included 199 liver donors (including 16 split donors) and 206 liver recipients from January 1, 2018 to January 27, 2020, with case follow-up until July 31, 2021. Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers. Indices of liver and kidney functions, complications, and survival curves of the two groups were compared. Compared with the standard donor group, the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation (P < 0.05); there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels after LT (all P > 0.05); there was no significant difference in the incidence of complications after LT (P > 0.05); there was also no significant difference in the survival curve (P = 0.335). There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups. The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.


In silico mutagenesis-based designing of oncogenic SHP2 peptide to inhibit cancer progression.
Cancer is among the top causes of death, accounting for an estimated 9.6 million deaths in 2018, it appeared that approximately 500,000 people die from cancer in the United States alone annually. The SHP2 plays a major role in regulation of cell growth, proliferation, and differentiation, and functional upregulation of this enzyme is linked to oncogenesis and developmental disorders. SHP2 activity has been linked to several cancer types for which no drugs are currently available. In our study, we aimed to design peptide inhibitors against the SHP2 mutant. The crystal structure of the human Src SH2-PQpYEEIPI peptide mutant was downloaded from the protein databank. We generated several peptides from the native wild peptide using an in silico mutagenesis method, which showed that changes (P302W, Y304F, E306Q, and Q303A) might boost the peptide's affinity for binding to SHP2. Furthermore, the dynamical stability and binding affinities of the mutated peptide were confirmed using Molecular dynamics simulation and Molecular Mechanics with Generalized Born and Surface Area Solvation free energy calculations. The proposed substitution greatly enhanced the binding affinity at the residue level, according to a study that decomposed energy into its component residues. Our proposed peptide may prevent the spread of cancer by inhibiting SHP2, according to our detailed analyses of binding affinities.


Primary Cutaneous Mucormycosis: A Necrotising Soft Tissue Infection with Poor Prognosis.
Cutaneous mucormycosis is an unusual fungal infection that continues to occur. It needs aggressive surgical debridement and timely administration of antifungals due to its high fatality rate. High clinical suspicion on the part of a surgeon is required to prevent the same. We present two cases of cutaneous mucormycosis in which the patients succumbed to death, highlighting the seriousness of the condition. One patient had a lower leg ulcer and was diabetic, and the other patient had a gluteal abscess following an intramuscular injection. Tissue samples grew Rhizopus arrhizus and Apophysomyces sp., respectively. Both patients were treated with amphotericin B, and extensive debridement was performed. Cutaneous mucormycosis can be reported in immunocompetent people, and there is a need for early recognition of the entity as a differential diagnosis of any nonhealing necrotic ulcer. Proper training and education of technical and clinical staff should be done at peripheral primary and secondary care centres so as not to miss out on cases of mucormycosis and for better prognosis in a cutaneous variety of mucormycosis in surgical patients.


To publish and perish: A Faustian bargain or a Hobson's choice.
As a matter of career choice, doctors have to choose between becoming an 'academic' or a 'practitioner.' To conduct research and publish articles in scientific journals is compulsory for the academic professional and mostly optional for the latter. The Medical Council of India has revised the eligibility qualifications for medical teachers over the past decade, and has now come out with regulations for streamlining the process of promotion by focusing on scientific papers, apart from clarifying on required experience and qualifications. 'Predatory publishers' are proliferating across the world, exploiting the reach of the Internet, and are enticing naïve professionals to publish their research work with them. The pitfalls of paid publishing in such journals may tarnish upcoming careers if doctors are not cautious. For a price, there are many publishers who will process articles without even rudimentary peer review; and for the sake of padding up of the resume, this Faustian bargain may eventually prove detrimental to authors, and thus with their professional credibility at stake, may prove to be a Hobson's choice. It is suggested for authors to make a wise choice and a correct decision when selecting a journal to submit their manuscripts.


Assessing performance of ZCTA-level and Census Tract-level social and environmental risk factors in a model predicting hospital events.
Predictive analytics are used in primary care to efficiently direct health care resources to high-risk patients to prevent unnecessary health care utilization and improve health. Social determinants of health (SDOH) are important features in these models, but they are poorly measured in administrative claims data. Area-level SDOH can be proxies for unavailable individual-level indicators, but the extent to which the granularity of risk factors impacts predictive models is unclear. We examined whether increasing the granularity of area-based SDOH features from ZIP code tabulation area (ZCTA) to Census Tract strengthened an existing clinical prediction model for avoidable hospitalizations (AH events) in Maryland Medicare fee-for-service beneficiaries. We created a person-month dataset for 465,749 beneficiaries (59.4% female; 69.8% White; 22.7% Black) with 144 features indexing medical history and demographics using Medicare claims (September 2018 through July 2021). Claims data were linked with 37 SDOH features associated with AH events from 11 publicly-available sources (e.g., American Community Survey) based on the beneficiaries' ZCTA and Census Tract of residence. Individual AH risk was estimated using six discrete time survival models with different combinations of demographic, condition/utilization, and SDOH features. Each model used stepwise variable selection to retain only meaningful predictors. We compared model fit, predictive performance, and interpretation across models. Results showed that increasing the granularity of area-based risk factors did not dramatically improve model fit or predictive performance. However, it did affect model interpretation by altering which SDOH features were retained during variable selection. Further, the inclusion of SDOH at either granularity level meaningfully reduced the risk that was attributed to demographic predictors (e.g., race, dual-eligibility for Medicaid). Differences in interpretation are critical given that this model is used by primary care staff to inform the allocation of care management resources, including those available to address drivers of health beyond the bounds of traditional health care.


ExCAPE-DB: an integrated large scale dataset facilitating Big Data analysis in chemogenomics.
Chemogenomics data generally refers to the activity data of chemical compounds on an array of protein targets and represents an important source of information for building in silico target prediction models. The increasing volume of chemogenomics data offers exciting opportunities to build models based on Big Data. Preparing a high quality data set is a vital step in realizing this goal and this work aims to compile such a comprehensive chemogenomics dataset. This dataset comprises over 70 million SAR data points from publicly available databases (PubChem and ChEMBL) including structure, target information and activity annotations. Our aspiration is to create a useful chemogenomics resource reflecting industry-scale data not only for building predictive models of in silico polypharmacology and off-target effects but also for the validation of cheminformatics approaches in general.


Development of fast dissolving polymer-based microneedles for delivery of an antigenic melanoma cell membrane.
Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM. Two polymers were tested for the fabrication of MNs: poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) and hyaluronic acid (HA). The incorporation of CM in MNs was achieved through coating of the MNs using a multi-step layering procedure or the micromolding technique. The CM loading and its stabilization were improved by adding sugars (sucrose and trehalose) and a surfactant (Poloxamer 188), respectively. In an ex vivo experiment, both PMVE-MA and HA showed fast dissolutions (<30 s) after insertion into porcine skin. However, HA-MN showed better mechanical properties, namely improved resistance to fracture when submitted to a compression force. Overall, a B16F10 melanoma CM-dissolving MN system was efficiently developed as a promising device suggesting further studies in immunotherapy and melanoma applications.


Effect of crotamine, a toxin of South American rattlesnake venom, on the sodium channel of murine skeletal muscle.
1 Crotamine (0.5 mug/ml) augmented the single twitch response of the rat and mouse isolated diaphragm to direct stimulation and prolonged the time course of contraction. At higher doses (10 to 50 mug/ml), contracture was observed with spontaneous fibrillation.2 The resting membrane potential of diaphragm was rapidly depolarized to about -50 mV within 5 minutes. No increase of depolarization occurred on prolongation of the incubation time or increase of crotamine concentration from 0.5 mug/ml to 50 mug/ml. The effect was not reversed by washing.3 Tetrodotoxin, low Na(+) (12 mM), Ca(2+) (10 mM) and procaine (1 mM) prevented the crotamine-depolarization. However, depolarization resumed when crotamine and the antagonists were removed.4 Low Cl(-) (8.5 mM) and pretreatment with ouabain enhanced depolarization by crotamine.5 High K(+) (25 to 50 mM) prevented the further depolarization by crotamine and the membrane potential was restored to normal on washout of crotamine with normal Tyrode solution.6 Effective membrane resistance was decreased by about 50% by crotamine.7(24)Na-influx of the rat diaphragm was increased by crotamine. (42)K-influx was slightly increased if tetrodotoxin was also present but was decreased in the absence of tetrodotoxin.8 No effect on the miniature and evoked endplate potential of the rat diaphragm was observed. Skeletal muscles from frog and chick were not affected.9 It is inferred that crotamine acts on a molecule regulating the Na(+) - permeability of the Na(+) channel of murine muscles. It is proposed that extracellular K(+) depresses the permeability of the Na(+) channel by acting on the same regulator molecule.


Bedside measurement of systolic and diastolic time intervals using the stethometer.
Using a modified electronic stethoscope, a simple visual method has been developed for bedside estimation of systolic and diastolic intervals. This has been applied to the measurement of S1-S2, LVET, and 2-OS as well as the intervals produced by prosthetic valve sounds.


Incidence and predictors of neuropathic pain following breast surgery.
Neuropathic pain (NPP) following breast surgery extends morbidity in the postoperative period. The incidence and etiology of postoperative NPP remains unclear and under-reported in literature. This study aims to define the incidence of neuropathic pain following breast surgery and to identify patient characteristics that are predictors for developing postoperative NPP. Consecutive female patients undergoing breast resection surgery over a 5-year period (2008-2012) with 1-year minimum follow-up were included in this single-center study. Retrospective chart review was performed to identify patient specific characteristics including the development of post-operative NPP. Data was analyzed using univariate and multivariate logistic regression. A total of 470 patients were identified for study inclusion. The incidence of postoperative NPP was 14.7 % (69 of 470). Significant predictors for the development of postoperative NPP in the univariate analyses included history of diabetes mellitus, diabetic neuropathy, or fibromyalgia, concomitant axillary surgery, axillary node dissection, and taxane-based chemotherapy regimen. Multivariate analysis identified African American race [odds ratio (OR) = 1.78; 95 % CI = 1.01-3.17; p = 0.05), history of diabetes mellitus (OR = 1.98; 95 % CI = 1.0-3.74; p = 0.01) or fibromyalgia (OR = 2.75; 95 % CI = 1.13-6.69; p = 0.03), and taxane-based chemotherapy regimen (OR = 2.85; 95 % CI = 1.23-6.58; p = 0.01) as being independently associated with the development of postoperative NPP. NPP is a significant risk following breast surgery. African American race, history of either diabetes mellitus or fibromyalgia, and treatment with taxane-based chemotherapy regimens are all associated with an increased risk of NPP.


Selective BH3 mimetics synergize with BET inhibition to induce mitochondrial apoptosis in rhabdomyosarcoma cells.
BH3 mimetics are promising novel anticancer therapeutics. By selectively inhibiting BCL-2, BCL-xL, or MCL-1 (i.e. ABT-199, A-1331852, S63845) they shift the balance of pro- and anti-apoptotic proteins in favor of apoptosis. As Bromodomain and Extra Terminal (BET) protein inhibitors promote pro-apoptotic rebalancing, we evaluated the potential of the BET inhibitor JQ1 in combination with ABT-199, A-1331852 or S63845 in rhabdomyosarcoma (RMS) cells. The strongest synergistic interaction was identified for JQ1/A-1331852 and JQ1/S63845 co-treatment, which reduced cell viability and long-term clonogenic survival. Mechanistic studies revealed that JQ1 upregulated BIM and NOXA accompanied by downregulation of BCL-xL, promoting pro-apoptotic rebalancing of BCL-2 proteins. JQ1/A-1331852 and JQ1/S63845 co-treatment enhanced this pro-apoptotic rebalancing and triggered BAK- and BAX-dependent apoptosis since a) genetic silencing of BIM, BAK or BAX, b) inhibition of caspase activity with zVAD.fmk and c) overexpression of BCL-2 all rescued JQ1/A-1331852- and JQ1/S63845-induced cell death. Interestingly, NOXA played a different role in both treatments, as genetic silencing of NOXA significantly rescued from JQ1/A-1331852-mediated apoptosis but not from JQ1/S63845-mediated apoptosis. In summary, JQ1/A-1331852 and JQ1/S63845 co-treatment represent new promising therapeutic strategies to synergistically trigger mitochondrial apoptosis in RMS.


Occupational Risk of Low-Level Blast Exposure and TBI-Related Medical Diagnoses: A Population-Based Epidemiological Investigation (2005-2015).
Because traumatic brain injury (TBI)-most often caused by exposure to high-level blast (HLB)-is a leading cause of medical evacuations of deployed U.S. service members in recent conflicts, researchers seek to identify risk factors for TBI. Previous research using self-reported data has identified low-level blast (LLB) as one such risk factor and suggests an association with susceptibility to and symptoms associated with TBI. This article presents a population-based study of all branches of military service that examines the association between occupational risk for LLB and both clinically diagnosed TBIs-from concussions to severe and penetrating TBIs-and conditions commonly comorbid with concussion. Using archival medical and career records from >2 million service members between 2005-2015, this work demonstrates that occupational risk of LLB is associated with any TBI, mild TBI, moderate TBI, cognitive problems, communication problems, hearing problems, headaches, any behavioral health condition, anxiety, drug abuse/dependence, alcohol abuse/dependence, delirium/dementia, posttraumatic stress disorder, post-concussive syndrome, tinnitus, fatigue, and migraines. Understanding the full scope of the effects of LLB on service members will help ensure the health and readiness of service members and may influence both military policy and clinical practice guidelines for blast-induced injuries.


Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures.
Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats.


Combined effects of four SNPs within goat PRLR gene on milk production traits.
Xinong Saanen (SN, n=323) and Guanzhong (GZ, n=197) goat breeds were used to detect single nucleotide polymorphisms (SNPs) in the coding regions with their intron-exon boundaries of prolactin receptor (PRLR) gene by DNA sequencing, primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Four novel SNPs (g.40452T>C, g.40471G>A, g.61677G>A and g.61865G>A) were identified. The g.61677G>A and g.61865G>A SNPs caused amino acid variations p.Ser485Asn and p.Val548Met, respectively. Both g.40452T>C and g.40471G>A loci were closely linked in SN and GZ goat breeds (r(2)>0.33). In addition, there was also a close linkage between g.61677G>A and g.61865G>A loci in both goat breeds. Statistical results indicated that the g.40452T>C, g.61677G>A and g.61865G>A SNPs were significantly associated with milk production traits in SN and GZ breeds. Further analysis revealed that combinative genotype C1 (TTAAGGGG) was better than the others for milk yield in SN and GZ goat breeds. These results are consistent with the regulatory function of PRLR in mammary gland development, milk secretion, and expression of milk protein genes, and extend the spectrum of genetic variation of the caprine PRLR gene, which might contribute to goat genetic resources and breeding.


Direct rapid quality assurance analysis of complex matrix materials: A chemometrics enabled energy dispersive X-ray fluorescence and scattering spectrometry application.
Compared to energy dispersive X-ray fluorescence (EDXRF) that is limited to analysis of elements (Z ≥ 13) via fluorescence and which is hardly direct, energy dispersive X-ray fluorescence and scattering (EDXRFS) spectrometry exploits additionally, scatter radiation to quantify both low- and heavy-Z elements as well as predict various material properties. The goal of this work was to demonstrate proof-of-concept for chemometrics-enabled EDXRFS spectrometry utilizing a weak sample excitation source towards rapid quality assurance (QA) analysis of complex matrix materials. A109Cd source was used to analyse three types of polymer powders - polypropylene (PP), low density polyethene (LDPE) and high density polyethene (HDPE) moulded as ∼ 2.5 g (∅ = 2.5 cm) pellets; and both actual as well as simulate lubricating oils spiked with trace additive metals B, Na, Ca, Mg, Fe and Zn and subjected to thermal degradation between 100 °C and 400 °C for 24 h. EDXRFS combined with principal components analysis (PCA) and soft independent modelling of class analogy (SIMCA) accurately identified polypropylene as well as differentiated it from both low density polyethene (LDPE) and high density polyethene (HDPE). LDPE and HDPE were fairly discriminated on the basis of density. In the second application partial least squares (PLS) modelling successfully determined the viscosity of lubricating oils utilizing the combination of the scatter peak and the Zn fluorescence signature, as well as correlated the lubricating oils viscosity to their thermal degradation. The reported method is applicable in industrial quality assurance due to its non-destructivity and speed.


Effectively control negative thermal expansion of single-phase ferroelectrics of PbTiO3-(Bi,La)FeO3 over a giant range.
Control of negative thermal expansion is a fundamentally interesting topic in the negative thermal expansion materials in order for the future applications. However, it is a challenge to control the negative thermal expansion in individual pure materials over a large scale. Here, we report an effective way to control the coefficient of thermal expansion from a giant negative to a near zero thermal expansion by means of adjusting the spontaneous volume ferroelectrostriction (SVFS) in the system of PbTiO3-(Bi,La)FeO3 ferroelectrics. The adjustable range of thermal expansion contains most negative thermal expansion materials. The abnormal property of negative or zero thermal expansion previously observed in ferroelectrics is well understood according to the present new concept of spontaneous volume ferroelectrostriction. The present studies could be useful to control of thermal expansion of ferroelectrics, and could be extended to multiferroic materials whose properties of both ferroelectricity and magnetism are coupled with thermal expansion.


Efficacy and Safety of Pleurodesis Using Platelet-Rich Plasma and Fibrin Glue in Management of Postoperative Chylothorax After Esophagectomy.
Chylothorax is by definition a collection of lymphatic fluids in the pleural cavity because of leakage from main thoracic duct or its tributaries. It is an uncommon but serious postoperative complication in esophageal cancer patients. There is no standard therapeutic algorithm for chylothorax because no prospective or randomized trials have yet been performed to evaluate the available treatment options. The aim of this study was to evaluate the efficacy of pleurodesis with a combination of platelet-rich plasma (PRP) and fibrin glue to the treatment of chylothorax after trans-hiatal esophagectomy. We randomly allocated 52 consecutive esophageal cancer patients with postoperative chylothorax who did not respond to conservative management to either PRP fibrin glue pleurodesis or surgical thoracic duct ligation. 26 patients in each group were treated with PRP fibrin glue pleurodesis or surgical thoracic duct ligation in order to control chylothorax. Perioperative data, including success rate and complications of both interventions, were analyzed. Two groups were similar in terms of patients' demographics and tumor characteristics. All 26 patients in pleurodesis group (100%) and 20 patients in surgery group (76.9%) were successfully treated (p = 0.009). Seven patients (26.92%) in pleurodesis group required a second application of PRP fibrin glue after a week. The mean length of hospital stay was 53.50 ± 16.662 days in surgery group and 36.04 ± 8.224 days in pleurodesis group (p < 0.001). Although mortality rate in surgery group was higher than pleurodesis group, it was not statistically significant (p = 0.1621). There was no significant difference in complications between two groups either. No serious side effect occurred with PRP fibrin glue application. In conclusion, pleurodesis using PRP and fibrin glue for chylothorax after trans-hiatal esophagectomy was associated with significantly increased success rate, decreased ICU stay, decreased overall hospital stay, and decreased mortality compared with surgical thoracic duct ligation. No patient after PRFG required additional intervention including surgery. Thus, given the improved outcomes with PRFG pleurodesis, this technique may be considered in all patients with postoperative chylothorax after or during conservative management and before proceeding to more invasive interventions.


The positivity principle: do positive instructors improve learning from video lectures?
The positivity principle states that people learn better from instructors who display positive emotions rather than negative emotions. In two experiments, students viewed a short video lecture on a statistics topic in which an instructor stood next to a series of slides as she lectured and then they took either an immediate test (Experiment 1) or a delayed test (Experiment 2). In a between-subjects design, students saw an instructor who used her voice, body movement, gesture, facial expression, and eye gaze to display one of four emotions while lecturing: happy (positive/active), content (positive/passive), frustrated (negative/active), or bored (negative/passive). First, learners were able to recognize the emotional tone of the instructor in an instructional video lecture, particularly by more strongly rating a positive instructor as displaying positive emotions and a negative instructor as displaying negative emotions (in Experiments 1 and 2). Second, concerning building a social connection during learning, learners rated a positive instructor as more likely to facilitate learning, more credible, and more engaging than a negative instructor (in Experiments 1 and 2). Third, concerning cognitive engagement during learning, learners reported paying more attention during learning for a positive instructor than a negative instructor (in Experiments 1 and 2). Finally, concerning learning outcome, learners who had a positive instructor scored higher than learners who had a negative instructor on a delayed posttest (Experiment 2) but not an immediate posttest (Experiment 1). Overall, there is evidence for the positivity principle and the cognitive-affective model of e-learning from which it is derived.


Plants in space.
Virtually all scenarios for the long-term habitation of spacecraft and other extraterrestrial structures involve plants as important parts of the contained environment that would support humans. Recent experiments have identified several effects of spaceflight on plants that will need to be more fully understood before plant-based life support can become a reality. The International Space Station (ISS) is the focus for the newest phase of space-based research, which should solve some of the mysteries of how spaceflight affects plant growth. Research carried out on the ISS and in the proposed terrestrial facility for Advanced Life Support testing will bring the requirements for establishing extraterrestrial plant-based life support systems into clearer focus.


Immunohistochemical expression of TWIST in oral squamous cell carcinoma and its correlation with clinicopathologic factors.
TWIST is a transcription factor that plays a key role in the development of primary tumor to metastatic stage of cancer. It is an inhibitor of E-cadherin in epithelial-to-mesenchymal transformation process (epithelial-mesenchymal transition). Few studies are available on the use of TWIST as a goal in molecular-targeted therapy. The aim of this study was to evaluate of TWIST expression in oral squamous cell carcinoma (OSCC) and its correlation with clinicopathologic factors. In this cross-sectional study, immunohistochemical staining was for TWIST performed on 30 paraffin-embedded blocks of OSCC. Furthermore, thirty paraffin-embedded blocks of normal oral mucosa with minimum inflammation from the clinical and histopathologic aspects were selected. Staining intensity and percentage of stained cells from nuclear and cytoplasmic aspects were ranked in epithelial cells. TWIST expression and correlation with clinicopathologic factors were analyzed using Cox regression and Chi-square tests. TWIST expression in OSCC was significantly increased compared to oral normal mucosa. Nuclear expression of TWIST in OSCC was significantly associated with clinical stage (P = 0.01) and lymph node metastasis (P = 0.007). Cytoplasmic expression of TWIST in OSCC was not associated with any clinicopathological factors. The results support the role of TWIST in carcinogenesis, development of OSCC, and its metastasis to lymph nodes.


Fetal ovarian cysts: prenatal diagnosis and management. Report of two cases and review of literature.
The Authors report two cases of antenatally diagnosed fetal ovarian cysts. In the first case the cysts underwent spontaneous resolution. In the second case the newborn was submitted to adnexectomy for cyst torsion. A review of the literature is reported.


A ω-mercaptoundecylphosphonic acid chemically modified gold electrode for uranium determination in waters in presence of organic matter.
A chemically modified electrode (CME) on a gold surface assembled with a ω-phosphonic acid terminated thiol was investigated for its capability to complex uranyl ions. The electrode, characterized by electrochemical techniques, demonstrated to be effective for the determination of uranyl at sub-μgL(-1) level by differential pulse adsorptive stripping voltammetry (DPAdSV) in environmental waters, also in presence of humic matter and other potential chelating agents. The accuracy of the measurements was investigated employing as model probes ligands of different complexing capability (humic acids and EDTA).


Maximin 9, a novel free thiol containing antimicrobial peptide with antimycoplasma activity from frog Bombina maxima.
Amphibian skin is a rich resource of antimicrobial peptides, like maximins and maximin Hs from frog Bombina maxima. Novel cDNA clones encoding a precursor protein, which comprises a novel maximin peptide (maximin 9) and reported maximin H3, were isolated from two constructed skin cDNA libraries of B. maxima. The predicted primary structure of maximin 9 is GIGRKFLGGVKTTFRCGVKDFASKHLY-NH2. A surprising substitution is at position 16, with a free cysteine in maximin 9 rather than usual conserved glycine in other reported maximins. Maximin 9, the homodimer form and its Cys16 to Gly16 mutant were synthesized and their antimicrobial activities were evaluated. Unlike previously reported maximin 3, the tested bacterial and fungal strains were resistant to maximin 9, its homodimer and the Cys16 to Gly16 mutant (with MICs>100 microM). On the other hand, interestingly, while eight clinical Mollicutes strains were generally resistant to maximin 9 homodimer and its Cys16 to Gly16 mutant, most of them are sensitive to maximin 9 at a peptide concentration of 30 microM, especially in the presence of dithiothreitol. These results indicate that the presence of a reactive Cys residue in maximin 9 is important for its antimycoplasma activity. The diversity of antimicrobial peptide cDNA structures encountered in B. maxima skin cDNA libraries and the antimicrobial specificity differences of the peptides may reflect well the species' adaptation to the unique microbial environments.


Correlation between clinical and brain computed tomography findings of stroke patients: A cross-sectional study.
In developing countries, the burden of stroke is growing and causing significant morbidity and disability with high mortality rates. Neuroimaging plays a crucial role in differentiating ischemic stroke from an intracerebral hemorrhage, as well as entities other than stroke. This study sought to determine the correlation between the clinical and brain CT scan findings of stroke patients attending three hospitals in Kampala, Uganda. This was a cross-sectional study of clinically suspected stroke patients who were sent for brain CT scan at three selected hospitals in Kampala, Uganda. All brain CT scans of patients with suspected stroke were evaluated and the Alberta stroke program early CT score (ASPECTS) was used for middle cerebral artery (MCA) strokes. Univariate analysis was used to describe the clinico-demographic and brain CT features of stroke and summarized them as percentages. Bivariate and multivariate analysis were used to determine the adjusted odds ratios as a measure of association with a 95% confidence interval (CI). Of the 270 study participants, 141 (52.2%) were male. 162 (60%) had CT findings of stroke, and 90 (33.3%) had normal brain CT findings. Eighteen (6.7%) had other CT findings like tumor, dural hemorrhage, epidermoid cyst, and others. Ischemic stroke, hemorrhagic stroke, and subarachnoid hemorrhage accounted for 124 (45.9%), 34 (12.6%), and 4 (1.5%) respectively. Limb weakness (55.2%), headache (41.1%), and loss of consciousness (39.3%) were associated with stroke findings on CT. Among the acute ischemic strokes, 30 (73.2%) had a worse (0-7) ASPECT score. Those aged ≥65 years were associated with a worse ASPECTS [AOR: 22.01, (95% CI: 1.58-306.09) p = 0.021]. More than a third of patients with a clinical diagnosis of stroke had either no CT features of stroke or had other findings. The most commonly affected vascular territory was left MCA. Old age was strongly associated with having the worst ASPECTS score.


Cervical Cancer Screening among HIV-Positive Women in Nigeria: An Assessment of Use and Willingness to Pay in the Absence of Donor Support.
The sustainability of donor-supported cervical cancer screening for HIV-positive women in underresourced setting is a concern. The authors aimed to determine the willingness of HIV-positive women for out-of-pocket payment for the cancer screening, if necessary. Questionnaires were administered to 400 HIV-positive women at the Adult HIV clinic, University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria. In all 11 (2.8%) respondents were aware of Pap smear, but only 1 (9.1%) of them had used it. After cervical cancer screening counseling, 378 (94.5%) respondents were willing to pay for Pap smear, irrespective of the cost. This willingness showed no trend across marital or educational groups. Younger age of respondents was not associated with willingness to pay for Pap smear (odds ratio = 1.24; confidence interval 95%: 0.52, 2.94). Willingness to pay for Pap smear by HIV-positive women in Enugu, Nigeria, is high. This has implication for the program sustainability.


[Risk factors for in-transit metastasis in patients with cutaneous melanoma].
In-transit metastases have been associated with the presence of various negative prognostic factors in patients with cutaneous melanoma. It has recently been suggested that sentinel lymph node biopsy (SLNB) may lead to an increase in the incidence of this particular type of metastasis. In this study, we analyzed risk factors for the appearance of in-transit metastasis and its potential association with the use of SLNB. A prospective study was undertaken in a cohort of 404 patients with cutaneous melanoma seen in the melanoma unit of Hospital San Cecilio in Granada, Spain. Statistical analysis was performed with SPSS 15.0 and Epidat 3.1 using the χ(2) and Fisher exact tests. Out of 93 (23%) patients with recurrence at any time, 28 (6.9%) had in-transit metastases. The occurrence of in-transit metastasis was associated with age greater than 50 years, greater Breslow depth and Clark level, the presence of ulceration, positive SLNB, and the presence of other types of recurrence (local recurrence, lymph node metastasis, or distant metastasis). There was no relationship between surgical treatment or performing SLNB and the presence of in-transit metastasis. The risk factors for in-transit metastasis are the same as those for any type of recurrence and coincide with factors linked to poor prognosis. Given that in-transit metastases are much more common in patients with positive SLNB, while the technique itself is not linked to their occurrence, these findings suggest that the appearance of in-transit metastasis is linked to biological characteristics of the tumor cells rather than an influence of the surgical technique.


Functions and Biosynthesis of O-Acetylated Sialic Acids.
Sialic acids have a pivotal functional impact in many biological interactions such as virus attachment, cellular adhesion, regulation of proliferation, and apoptosis. A common modification of sialic acids is O-acetylation. O-Acetylated sialic acids occur in bacteria and parasites and are also receptor determinants for a number of viruses. Moreover, they have important functions in embryogenesis, development, and immunological processes. O-Acetylated sialic acids represent cancer markers, as shown for acute lymphoblastic leukemia, and they are known to play significant roles in the regulation of ganglioside-mediated apoptosis. Expression of O-acetylated sialoglycans is regulated by sialic acid-specific O-acetyltransferases and O-acetylesterases. Recent developments in the identification of the enigmatic sialic acid-specific O-acetyltransferase are discussed.


[The state of energy metabolism in the rat liver after a single acute hemorrhage].
A system of adenine nucleotides and redox state of liver cells as well as activities of dehydrogenases of the tricarbonic acid cycle and of cytochrome oxidase in liver cell homogenates were not altered after an acute single hemorrhage in rats even though the process run into the step of circulation decompensation (AP 40 mm Hg).


Policies to restrict secondhand smoke exposure: American College of Preventive Medicine Position Statement.
Secondhand smoke (SHS) exposure poses serious health risks for all nonsmokers, especially children and pregnant women. SHS is estimated to contribute to heart attacks in nonsmokers and nearly 53,800 deaths in the U.S. annually. A literature review of English-language articles was performed using PubMed, organizational websites, and pertinent review articles. Over the past 25 years, smokefree policies have protected nearly half the U.S. population from the adverse health effects of SHS. Smokefree policies have been shown to improve health outcomes with no consequences to local businesses. As of April 2013, a total of 24 states and 561 municipalities and territories, including the District of Columbia, New York City, Puerto Rico, and the U.S. Virgin Islands, have established laws that require nonhospitality workplaces, restaurants, and bars to be 100% smokefree. Four other states-Florida, Indiana, Louisiana, and Nevada-have smokefree laws that cover restaurants but provide an exemption for stand-alone bars. At least 14 states have no smokefree laws. This paper describes the benefits of policies that reduce SHS and concludes with recommendations for future directions. The American College of Preventive Medicine (ACPM) recommends expanded clean indoor air policies for workplaces, stand-alone bars, restaurants, and multi-use family housing such as apartment buildings. ACPM recommends clean air policies for all university campuses, secondary school campuses, primary schools, child care centers, and city landmarks to further shift social norms and protect the health of children, adolescents, and adults. ACPM recommends closing existing gaps in clean indoor air policies.


Stem cell-derived exosomes in the treatment of acute myocardial infarction in preclinical animal models: a meta-analysis of randomized controlled trials.
Exosomes (EXOs) derived from stem cells have become a potential new treatment for acute myocardial infarction (AMI). However, their impact is still not fully understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EXOs on AMI in preclinical animal models. We searched PubMed, EMBASE, and the Web of Science from September 1, 1980 to September 1, 2021, to retrieve the studies reporting the therapeutic effects of EXOs on AMI animal models. Secondary endpoints include the fractional shortening (FS), infarct size (IS), fibrosis area (FA), the TNF-α, IL-6 and IL-10 levels, the apoptosis rate and the number of autophagic vesicles. Two authors independently screened the articles based on inclusion and exclusion criteria. All statistical analyses were conducted using Stata14.0. Ten studies satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of LVEF (WMD = 3.67%; 95% CI 2.28-5.07%; P = 0.000), FS (WMD = 3.69%; 95% CI 2.06-5.33%; P = 0.000), IS (WMD = -4.52%, 95% CI - 7.14 to - 1.9%; P = 0.001), and FA (WMD = -7.04%, 95% CI - 8.74 to - 5.34%; P = 0.000), TNF-α (WMD = -3.09, 95% CI - 5.47 to - 0.72; P = 0.011), TL-6 (WMD = -6.34, 95% CI - 11.2 to - 1.49; P < 0.01), TL-10 (WMD = 6.37, 95% CI 1.53-11.21; P = 0.01), the apoptosis rate (WMD = -8.23, 95% CI - 15.29 to - 1.17; P = 0.000), and the number of autophagic vesicles (WMD = -4.52, 95% CI - 7.43 to - 1.62; P = 0.000). Subgroup analysis showed that the EXOs were derived from HMSCs. Subgroup analysis showed that the EXOs derived from HMSCs, and that exosome therapy immediately after myocardial infarction can better improve the LVEF. EXOs therapy has the potential to improve cardiac function, fibrogenesis, and inflammatory response, as well as reducing cell apoptosis and autophagy in preclinical AMI animal models. This can inform future human clinical trials of EXOs.


Biophysical and biochemical aspects of antifreeze proteins: Using computational tools to extract atomistic information.
Antifreeze proteins (AFPs) are the key biomolecules that protect species from extreme climatic conditions. Studies of AFPs, which are based on recognition of ice plane and structural motifs, have provided vital information that point towards the mechanism responsible for executing antifreeze activity. Importantly, the use of experimental techniques has revealed key information for AFPs, but the exact microscopic details are still not well understood, which limits the application and design of novel antifreeze agents. The present review focuses on the importance of computational tools for investigating (i) molecular properties, (ii) structure-function relationships, and (iii) AFP-ice interactions at atomistic levels. In this context, important details pertaining to the methodological approaches used in molecular dynamics studies of AFPs are also discussed. It is hoped that the information presented herein is helpful for enriching our knowledge of antifreeze properties, which can potentially pave the way for the successful design of novel antifreeze biomolecular agents.


Studies on the formation of N6-hydroxylysine in cell-free extracts of Aerobacter aerogenes 62-1.
We have investigated conditions optimal for the conversion of L-lysine to its N6-hydroxy derivative by partially purified cell-free extracts of Aerobacter aerogenes 62-1. The enzyme system was highly specific to L-lysine: the D-isomer and, the N2- or N6-derivatives of lysine, and alpha-amino acids were not hydroxylated. Most of the latter compounds had little effect onthe hydroxylation of L-lysine. However, -l-glutamic acid and L-glutamine enhanced the hydroxylation, with half-maximal activation achieved at 100 micrometers concentration of the effector. The Km values for pyruvate and L-(+)-lactate (compounds known to stimulate N-hydroxylysine formation) were found to be approx. 100 micrometers. The data show that N-hydroxylation of the amino acid precedes acylation in the biosynthesis of hydroxamic acid in A. aerogenes 62-1.


Correction: Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration.
[This corrects the article DOI: 10.1371/journal.pone.0161720.].


Open resection of osteoid osteoma guided by a gamma-probe.
Osteoid osteoma is the third most common type of bone tumour. Radiofrequency ablation and other percutaneous procedures are the treatment of choice. However, in some sites these methods are difficult or dangerous. Our objective of this study was to evaluate whether open resection and intraoperative nidus detection with a hand-held gamma probe is an efficient method for treating this type of tumour. Fifty-three patients with osteoid osteomas were submitted to surgical treatment. The first group (gamma group) consisted of 34 patients submitted to open nidus resection guided by a hand-held gamma probe. The control group consisted of 19 patients operated on by conventional technique. In the postoperative period, histopathology, imaging studies, and clinical outcome were evaluated. The gamma group patients were followed up for an average 26.2 months; the control group patients were followed up for an average 38 months. There was no difference with regard to pain relief and histopathology findings between the two groups. However, in the postoperative imaging studies, there was significantly less nidus present in the gamma group (p = 0.01).The gamma probe helped to locate the osteoid osteoma nidus more precisely, as demonstrated by the postoperative imaging studies.


Peracetic acid-ionic liquid pretreatment to enhance enzymatic saccharification of lignocellulosic biomass.
To enhance enzymatic saccharification of pine biomass, the pretreatment reagents peracetic acid (PAA) and ionic liquid (IL) were validated in single reagent pretreatments or combination pretreatments with different sequences. In a 1h saccharification, 5-25% cellulose conversion was obtained from the single pretreatment of PAA or IL. In contrast, a marked enhancement in conversion rates was achieved by PAA-IL combination pretreatments (45-70%). The PAA followed by IL (PAA+IL) pretreatment sequence was the most effective for preparing an enzymatic digestible regenerated biomass with 250-fold higher glucose formation rates than untreated biomass and 2- to 12-fold higher than single pretreatments with PAA or IL alone. Structural analysis confirmed that this pretreatment resulted in biomass with highly porous structural fibers associated with the reduction of lignin content and acetyl groups. Using the PAA+IL sequence, biomass loading in the pretreatment step can be increased from 5% to 15% without significant decrease in cellulose conversion.


Red cell distribution width for prognosis in patients with pulmonary embolism: A systematic review and meta-analysis.
Patients with pulmonary embolism (PE) have a higher red cell distribution width (RDW), which may complicate the interpretation of the prognosis of PE. We aim to evaluate the diagnostic utility of the RDW in patients with PE. Eligible studies were identified by searching PubMed and EMBASE from inception to December 23, 2018. The data were pooled using Stata 12 to evaluate the prognostic value. The sources of heterogeneity were detected. For the analysis of prognosis, 7 studies with 2146 patients were included, with median RDW values ranging from 13.4% to 15.7% and a median cut-off point of 18.27%. A total of 247 patients (11.5% mortality) among the 2146 participants died. Overall, RDW was positively associated with the prognosis of PE in the overall analysis (HR = 1.19, 95% CI = 1.10-1.29, I2 = 73.4%; P = 0.000). Subgroup analyses by study design, sex and follow-up time indicated that they were not sources of heterogeneity. An elevated RDW has the potential to be a biomarker for prognosis in PE patients.