Preliminary study on the use of an inhomogeneous anthropomorphic Fricke gel phantom and 3D magnetic resonance dosimetry for verification of IMRT treatment plans.
An inhomogeneous anthropomorphic phantom of the human thorax including lungs and spine was developed for verification of three-dimensional (3D) intensity-modulated radiotherapy (IMRT). The phantom and spinal cord were filled with undiluted Fricke gel, whereas the lungs were filled with a special low-density Fricke gel. Based on a computed tomography scan of the phantom, an intensity-modulated stereotactic radiotherapy plan for a bronchial carcinoma was calculated using an inverse planning system (KonRad, DKFZ Heidelberg, Germany). The plan consisted of seven beams delivered in a step and shoot technique out of 67 sub-fields. Immediately after irradiation 3D magnetic resonance (MR) imaging of the phantom was performed using a special pulse sequence for T1 relaxometry. From the MR image data maps of the longitudinal relaxation rate R1 = 1/T1 were calculated. The R1 maps were converted to dose-proportional image data and compared to planning data. Measurement and planning show good agreement in regions of standard Fricke gel with an average deviation below 5%. In regions of the low-density Fricke gel, deviations are higher due to a decreased signal-to-noise ratio in the MR measurement. In these areas also a different sensitivity of the dose response was observed as compared to standard Fricke gel. The inhomogeneous thorax phantom has proven to be a useful pre-clinical tool for 3D methodical verifications.


A systematic review of the prevalence of nutrition labels and completeness of nutrient declarations on pre-packaged foods in China.
The Chinese government launched a voluntary nutrition labelling code in 2007 and made it mandatory since 1 January 2013. This article aims to quantify the prevalence of nutrition labels and the completeness of nutrient declarations on pre-packaged foods in China and to explore the impact of the 2007 code. A systematic search of the published and grey literature was done, and a random-effects meta-analysis was used to obtain summary estimates. There were 15 surveys identified from 13 reports. For 44% (95% confidence interval: 37-51%) of the 22 636 food items, the product label provided information on one or more nutrients. There was significant heterogeneity between the surveys (I(2) = 99%, P < 0.001) raising some uncertainty about the reliability of the estimate. The heterogeneity was in part explained by differences in labelling between food categories (P < 0.001) but not by changes in the prevalence of nutrition labels over time (P = 0.36). Most pre-packaged foods in this survey had a nutrition label non-compliant with current Chinese nutrition labelling standards. The voluntary code launched in 2007 had limited impact on nutrition labelling. There is significant scope for the recently introduced mandatory labelling requirements to improve nutrition labelling in China.


Monoclonal antibodies as immunospecific probes for virus and cell surface antigen localization with the unlabeled antibody hemocyanin bridge: a review.
Hemocyanin (Hcy) from whelks, Busycon canniculatum has been developed as a visual marker for the identification of virus and cell surface antigens by the correlative techniques of fluorescence microscopy, TEM and SEM. A series of hybridomas producing monoclonal antibodies that allow the identification of type-, group-, and class-specific antigenic determinants on the major envelope glycoprotein of mouse mammary tumor virus (MMTV) gp 52 and two group-specific monoclonal antibodies to MMTV gp 36 have been developed. We used these antibodies in the unlabeled antibody Hcy bridge for immunoelectron microscopy (IEM) and found that each gp 52 antigenic determinant was expressed on virus during all stages of morphogenesis and on the infected cell surface while the gp 36 determinants were not detected. The positive labeling of gp 52 by IEM correlated well with immuno-experiments using the 125I Staph protein A plate binding assay (125IPA). The anti-gp 36 monoclonals in contrast, however, gave positive results only in the 125IPA assay. Hybridomas to murine and primate type C virion envelope proteins [gp 70 and p15(E)] have also been developed. None of the monoclonal antibodies to murine type C virus gp 70 or p15(E) gave positive labeling by IEM when tested with Rauscher murine leukemia virus but two were positive by the 125IPA assay. Monoclonal antibodies to the gp 70 of a baboon type C virus, M-7 were positive in IEM, labeling both the cell surface and viral envelope and reacted with virus in the 125IPA assay. Since monoclonal antibodies provide a much better resolution of the molecular structure and antigenic differences of viruses, interpretations of labeling results are thoroughly discussed. Methods for testing the specificity and titer of monoclonals are presented. The unlabeled antibody Hcy bridge technique and recent advances in methodology are reviewed.


Hyaluronate effect on bacterial biofilm in ENT district infections: a review.
Bacterial resistance is a growing phenomenon which led the scientific community to search for new therapeutic targets, such as biofilm. A bacterial biofilm is a surface-associated agglomerate of microorganisms embedded in a self-produced extracellular polymeric matrix made of polysaccharides, nucleic acids, and proteins. Scientific literature offers several reports on a biofilm's role in infections regarding various body districts. The presence of a bacterial biofilm is responsible for poor efficacy of antibiotic therapies along with bacterial infections in ear, nose, and throat (ENT) districts such as the oral cavity, ear, nasal cavities, and nasal sinuses. In particular, bacterial biofilms are associated with recalcitrant and symptomatically more severe forms of chronic rhinosinusitis. As of today, there are no therapeutic options for the eradication of bacterial biofilm in ENT districts. Hyaluronic acid is a glycosaminoglycan composed of glucuronic acid and N-acetylglucosamine disaccharide units. Its efficacy in treating rhinosinusitis, whether or not associated with polyposis, is well documented, as well as results from its effects on mucociliary clearance, free radical production and mucosal repair. This review's aim is to evaluate the role of bacterial biofilms and the action exerted on it by hyaluronic acid in ENT pathology, with particular attention to the rhinosinusal district. In conclusion, this paper underlines how the efficacy of hyaluronate as an anti-bacterial biofilm agent is well demonstrated by in vitro studies; it is, however, only preliminarily demonstrated by clinical studies.


[Effect of neoadjuvant chemotherapy on the results of resection of colorectal liver metastases].
Surgery is the treatment of choice in patients with colorectal liver metastases. However, only 10% to 20% of these cases are resectable. The use of neoadjuvant chemotherapy may allow surgery in patients with tumors initially considered unresectable. The aim of this study was to compare the results of liver resection due to colorectal liver metastases in patients with and without neoadjuvant chemotherapy. We studied 105 patients who underwent surgery for liver metastases from colorectal cancer. The patients were divided into two groups according to treatment: surgery in patients with initially resectable tumors (group 1) and neoadjuvant chemotherapy plus surgery (group 2) in patients with initially irresectable tumors, who were considered for surgery after response to chemotherapy. Age, sex, origin of primary tumor, time of presentation, number, maximum size and location of metastases, CEA, resection margin, postoperative morbidity and mortality, length of hospital stay, recurrence rate, survival and disease-free survival were compared between the 2 groups of patients. When group 1 was compared with group 2, statistically significant differences were observed in synchronicity (30.8% vs 77.4%), bilobarity (13.5% vs 58.5%), number and size of metastases (1 vs 3 nodules and 4 cm vs 2 cm), resectability rate (96.1% vs 81.1%), disease-free interval (25 vs 11 months) and long-term survival at 1, 3 and 5 years (93%, 67% and 36% vs 78%, 26% and 12%). However, no statistically significant differences were found in postoperative morbidity and mortality (28.8% and 0% in group 1 and 22.6% and 1.8% in group 2, respectively). Neoadjuvant chemotherapy was not associated with greater postoperative morbidity and mortality after resection of colorectal liver metastases, but long-term survival was lower in the group of patients receiving this treatment modality than in those with tumors initially considered resectable.


Increasing incidence of colon cancer in patients <50 years old: a new entity?
Colorectal cancer (CRC) is the third most common cancer type in humans, the fourth most common cause of death because of cancer, and the second most common cancer type in terms of the number of individuals living with cancer 5 years after diagnosis worldwide, almost 694,000 people die from CRC annually. As it is expected is more frequent in older patients (patients older than 70 years old than in young patients (patients younger than 40 years old). The incidence of CRC in young adults is rising the last years and this fact arises the question; is this coincidence or is young adult CRC a real epidemy. In our current commentary we try and elucidate based on current data whether disease on young individuals is a new entity.


MiR-21: A key player in glioblastoma pathogenesis.
Glioblastoma multiform (GBM) is one of common cancers worldwide which has high rate among various populations. Despite serious efforts worldwide, GBM remains a deadly disease which is associated with poor prognosis. Multiple lines evidence indicated that deregulation of a variety of cellular and molecular pathways are related with GBM pathogenesis. Among of various targets involved in GBM pathogenesis, microRNAs (miRNAs) have been emerged as targets which deregulation of them are related with various stages of GBM. These molecules are small non-coding RNAs which could affect on a variety of cellular and molecular pathways involved in GBM. It has been showed that deregulation of them are associated with initiation and progression of GBM. MiR-21 is one of important miRNAs involved in GBM pathogenesis. A large number studies indicated that this miRNA could affect on a variety of cellular and molecular pathways such as insulin-like growth factor (IGF)-binding protein-3 (IGFBP3), RECK, and TIMP3. Exosomes are one of important players in GBM pathogenesis. Among of various exosomes, exosomal miR-21 may has key roles in GBM pathogenesis. These findings indicated that miR-21 has critical roles in GBM pathogenesis and could be used as diagnostic and therapeutic biomarkers for GBM patients. Here, we summarized the roles of miR-21 and exosomal miR-21 in GBM pathogenesis. Moreover, we highlighted utilization of miR-21 as diagnostic and therapeutic biomarker for GBM patients.


"Eating for outsiders": cancer causation discourse among the Iñupiat of Arctic Alaska.
Cancer is the leading cause of death among Alaska Natives. Although cancer mortality rates are widely studied, as well as high-risk behaviours in relation to site-specific tumors, little is known about Alaska Native understandings of cancer. This study explores how Iñupiat living in northwest Alaska conceptualize the etiology, transmission and prevention of cancer. Long-term ethnographic research. Qualitative research was conducted in northwest Alaska over the course of 30 months, including 8 months accompanying an Iñupiaq family on their seasonal rounds to hunting and fishing camps. In addition, open-ended interviews were conducted with 50 Iñupiaq men and women, and the life histories of 3 Iñupiaq healers were recorded. Iñupiat spoke of cancer as a germ-induced condition that emerged from the "outside." Routes of infection include the ingestion of contaminated food and water, as well as inhalation or injection of outside agents. "Bad-blood" was considered a precursor to, and product of, cancer. Iñupiaq discourse about cancer prevention focused on consuming foods that strengthened the blood, including meat harvested from the country. Educational efforts that focused on lowering risk by eating diets low in meat and fat and high in fruit and vegetables were rejected as an assault from outsiders on their hunting way of life. The development of meaningful cancer prevention and early detection programs must be sensitive not only to cultural conceptions of disease but also to relations of power in which recommendations and policies are constituted and asserted.


Microbial Composition and Diversity Patterns in Deep Hyperthermal Aquifers from the Western Plain of Romania.
A limited number of studies have investigated the biodiversity in deep continental hyperthermal aquifers and its influencing factors. Here, we present the first description of microbial communities inhabiting the Pannonian and Triassic hyperthermal aquifers from the Western Plain of Romania, the first one being considered a deposit of "fossilized waters," while the latter is embedded in the hydrological cycle due to natural refilling. The 11 investigated drillings have an open interval between 952 and 3432 m below the surface, with collected water temperatures ranging between 47 and 104 °C, these being the first microbial communities characterized in deep continental water deposits with outflow temperatures exceeding 80 °C. The abundances of bacterial 16S rRNA genes varied from approximately 105-106 mL-1 in the Pannonian to about 102-104 mL-1 in the Triassic aquifer. A 16S rRNA gene metabarcoding analysis revealed distinct microbial communities in the two water deposits, especially in the rare taxa composition. The Pannonian aquifer was dominated by the bacterial genera Hydrogenophilus and Thermodesulfobacterium, together with archaeal methanogens from the Methanosaeta and Methanothermobacter groups. Firmicutes was prevalent in the Triassic deposit with a large number of OTUs affiliated to Thermoanaerobacteriaceae, Thermacetogenium, and Desulfotomaculum. Species richness, evenness, and phylogenetic diversity increased alongside with the abundance of mesophiles, their presence in the Triassic aquifer being most probably caused by the refilling with large quantities of meteoric water in the Carpathian Mountains. Altogether, our results show that the particular physico-cheminal characteristics of each aquifer, together with the water refilling possibilities, seem to determine the microbial community structure.


Evidence-Based Interventions to Improve Quality of Life for Individuals with Dementia.
Individuals with cognitive impairment, their family members, and their care providers have all identified "quality of life" as a central goal in the treatment of dementia. In this article, we identify factors that influence quality of life for individuals with cognitive impairment, review evidence-based psychosocial interventions that improve quality of life for community-residing individuals with dementia, and describe innovative ongoing randomized clinical trials designed to improve or maintain quality of life for individuals with mild to moderate memory problems.


State estimation for jumping recurrent neural networks with discrete and distributed delays.
This paper is concerned with the state estimation problem for a class of Markovian neural networks with discrete and distributed time-delays. The neural networks have a finite number of modes, and the modes may jump from one to another according to a Markov chain. The main purpose is to estimate the neuron states, through available output measurements, such that for all admissible time-delays, the dynamics of the estimation error is globally asymptotically stable in the mean square. An effective linear matrix inequality approach is developed to solve the neuron state estimation problem. Both the existence conditions and the explicit characterization of the desired estimator are derived. Furthermore, it is shown that the traditional stability analysis issue for delayed neural networks with Markovian jumping parameters can be included as a special case of our main results. Finally, numerical examples are given to illustrate the applicability of the proposed design method.


Intra-muscular ketorolac administered as a supplemental analgesic for removal of impacted third molar teeth: a prospective study.
Post-operative pain follows dentalveolar oral surgery. Ketorolac is a potent non-steroidal analgesic with moderate anti-inflammatory effects. The purpose of this study was to test whether a single supplementary dose of ketorolac reduced post-operative pain experienced by patients having third molar teeth removed. A prospective double-blind trial utilizing 30mg of ketorolac and a standard anaesthetic and surgical technique was performed on 65 female patients having impacted third molar teeth removed. Assessment was made by means of a patient questionnaire and visual analogue pain scales and subjected to statistical analysis. There was a statistically significant difference confirming improved pain relief for patients receiving ketorolac 30mg at the early postoperative stage (two hours) but at later time intervals (four and six hours) there was no significant difference. Seventy two per cent of patients found ketorolac to be a satisfactory analgesic for postoperative pain. There were minimal side effects. A single supplemental dose of ketorolac 30mg provides improved pain relief in the immediate post-operative phase following the removal of third molar teeth. Oral ketorolac can be recommended as a oral analgesic for post-operative pain, with minimal side effects.


The role of MicroRNA as a potential diagnostic and prognostic biomarker for cerebral aneurysms.
To identify the dysregulated functional miRNAs, miRNA-16, miRNA-143, and miRNA-200 as potential biomarkers of cerebral aneurysms(CAs) to aid in diagnosis and prognosis. This is a prospective case-control study conducted among patients with CA. All patients' computed tomography angiography (CTA) and interventional angiogram were assessed and studied. The miRNAs were isolated and quantified from peripheral blood samples and the expression profiling was done using TaqMan chemistry on Real-Time PCR. A total of 37 samples were included. Three cases had double aneurysms and 10 cases presented with aneurysmal rupture. miRNA-16, miRNA-143, and miRNA-200 were upregulated with an absolute fold-change of >8 in the CA group in comparison to controls (p<0.05). miRNA-200 showed double expression in patients with single aneurysm. A statically significant increase was observed in the expression of miRNA-143 in patients who had an aneurysmal rupture with p<0.05. Diabetic patients showed an obvious increase in miRNA-200 (13.03 folds) and miRNA-16 (26.82 folds) expression. Also, there was a notable elevation in miRNA-16, miRNA-143, and miRNA-200 in patients who had hypertension in comparison to those who did not. miRNA-16, miRNA-143, and miRNA-200 showed statically significant higher expression among cases with cerebral aneurysms in comparison to controls. Thus, these preliminary results of miRNAs biomarkers are promising future tool to be used for aneurysmal screening.


Primary Cystic Lesions of the Retrorectal Space: MRI Evaluation and Clinical Assessment.
The purpose of this study was to assess the a priori chance that primary cystic lesions of the retrorectal space are malignant and to investigate MRI characteristics that indicate malignancy. Patients referred to a center for colorectal surgery were recruited from 2000 to 2014. Lesions were proven by clinical assessment and histopathology. MRI was performed at 1.5 T with examinations evaluated by two radiologists. Interobserver agreement was assessed (Cohen kappa) and differences between malignant and benign lesions calculated (Fisher exact test). Twenty-eight patients (22 women, six men; age range, 18-70 years) with 31 lesions were included. Lesions were categorized as tailgut cysts (n = 16, 52%), teratomas (n = 9, 29%), lesions of colorectal origin (n = 4, 13%), or neurogenic lesions (n = 2, 6%). Five patients (18%) had malignant lesions. Colorectal lesions had the highest percentage of malignancy (3/4, 75%). A solid tissue component was found in all five (100%) malignant lesions and two (8%) of the benign lesions, which were both teratomas (p < 0.05). Sensitivity and specificity for malignancy according to the presence of a solid tissue component was 100% (5/5) and 92% (24/26). For unilocularity, multilocularity, debris, septa, and wall thickening, differences were not significant. Interobserver agreement was excellent (κ = 1) for all characteristics except debris (κ = 0.795). The majority of retrorectal cystic lesions are benign. The presence of a solid tissue component should raise suspicion for malignancy.


Experimental Realization of Type-II Dirac Fermions in a PdTe_{2} Superconductor.
A Dirac fermion in a topological Dirac semimetal is a quadruple-degenerate quasiparticle state with a relativistic linear dispersion. Breaking either time-reversal or inversion symmetry turns this system into a Weyl semimetal that hosts double-degenerate Weyl fermion states with opposite chiralities. These two kinds of quasiparticles, although described by a relativistic Dirac equation, do not necessarily obey Lorentz invariance, allowing the existence of so-called type-II fermions. The recent theoretical discovery of type-II Weyl fermions evokes the prediction of type-II Dirac fermions in PtSe_{2}-type transition metal dichalcogenides, expecting experimental confirmation. Here, we report an experimental realization of type-II Dirac fermions in PdTe_{2} by angle-resolved photoemission spectroscopy combined with ab initio band calculations. Our experimental finding shows the first example that has both superconductivity and type-II Dirac fermions, which turns the topological material research into a new phase.


Meal frequency and incidence of type 2 diabetes: a prospective study.
Dietary habits play an important role in the development of obesity and type 2 diabetes. However, evidence on association between diet frequency and type 2 diabetes was limited and inconclusive. We aimed to examine the association between meal frequency and risk of type 2 diabetes. The cohort study used data from China Health and Retirement Longitudinal Study of 8874 community-dwelling people aged over 45 years. Participants were classified as eating two meals per day, three meals per day and four meals per day. Multiple Poisson regression models were used to examine risk of 4-year incident type 2 diabetes among people who ate more or less than three meals per day compared with people who ate three meals per day. We documented 706 type 2 diabetes cases during follow-up. After adjustment for known risk factors for type 2 diabetes, except for BMI, participants who ate four meals per day were at a lower risk of type 2 diabetes than those who ate three meals per day (relative risk(RR) = 0·73 (0·58, 0·92)). After further adjustment for baseline BMI, the association was slightly attenuated but remained statistically significant (RR = 0·76 (0·60, 0·97)). Subgroup analysis showed that the fully adjusted RR of type 2 diabetes for people eating four meals per day were 0·66 (0·48, 0·91) and 0·93 (0·65, 1·34) among those had a BMI < 25 and ≥ 25 kg/m2, respectively. Eating four meals per day, compared with eating three meals per day was associated with lower risk of developing type 2 diabetes in a Chinese population, particularly in those with a BMI < 25 kg/m2.


Effect of a two-base insertion mutation of the TP53 gene on expression of p53 protein in canine histiocytic sarcoma cells.
To examine effects of a common mutation (2-base insertion in exon 5) of the TP53 gene on biological function of p53 protein in canine histiocytic sarcoma cells. Canine histiocytic tumor cell lines DH82 with deletion of TP53 and CHS-3 with the wild-type TP53 and canine wild-type and mutant TP53 fragments. Wild-type or mutant TP53 with a polyprotein peptide tag at the N-terminus was transduced into DH82 and CHS-3 cells. Expression of p53 protein, changes in function as a transcription factor, and susceptibility to doxorubicin and nimustine were compared. Transduced p53 protein was detected in wild-type TP53-transduced DH82 and CHS-3 cells, whereas expression was not detected in mutant TP53-transduced cells. There were significant increases in expression of target genes of p53 protein, including p21 and MDM2, in wild-type TP53-transduced cells, compared with results for native and mock-transfected cells, but not in mutant TP53-transduced cells. There was no significant difference in drug susceptibilities among native and derivative cells of CHS-3. However, cell viabilities of wild-type TP53-transduced DH82 cells incubated with doxorubicin were significantly lower than viabilities of native, mock-transfected, and AT insertion mutation-TP53-transduced DH82 cells; susceptibility to nimustine did not differ significantly among cells. Expression of p53 protein and its function as a transcription factor were lost after addition of a 2-base insertion in the TP53 gene in canine histiocytic tumor cells. Additional studies are needed to investigate the clinical relevance of this mutation in histiocytic sarcomas of dogs.


Transradial approach (left vs right) and procedural times during percutaneous coronary procedures: TALENT study.
most of the studies assessing transradial approach for coronary angiography (CA) have been performed through right radial approach (RRA). Our aim was to evaluate the safety and efficacy of left radial approach (LRA) compared with RRA for coronary procedures. from January 2009 to December 2009, in 2 hospitals, 1,540 patients were randomized to RRA (770 patients) or LRA (770 patients) for percutaneous coronary procedures. The primary end point was fluoroscopy time for CA and for percutaneous coronary intervention (PCI) evaluated independently. Prespecified subgroup analyses according to patient age and operator experience were planned. in 1,467 patients (732 RRA and 735 LRA), a CA (diagnostic group) was performed, and in 688 (344 each for RRA and LRA), a PCI. In the diagnostic group, LRA was associated with significantly lower fluoroscopy time (149 seconds, interquartile range [IQR] 95-270 seconds) and dose area product fluoroscopy (10.7 Gy cm(2), IQR 6-20.5 Gy cm(2)) compared with the RRA (168 seconds, IQR 110-277 seconds, P = .0025 and 12.1 Gy cm(2), IQR 7-23.8 Gy cm(2), P = .004, respectively). In the PCI group, there were no significant differences in fluoroscopy time (614 seconds, IQR 367-1,087 seconds for LRA and 695 seconds, IQR 415-1,235 seconds, P = .087 for RRA) and dose area product fluoroscopy (53.7 Gy cm(2), IQR 29-101 Gy cm(2) for LRA and 63.1 Gy cm(2), IQR 31-119 Gy cm(2), P = .17 for RRA). According to subgroup analyses, the differences between LRA and RRA were confined to older patients (≥ 70 years old) and to operators in training. left radial approach for coronary diagnostic procedures is associated with lower fluoroscopy time and radiation dose adsorbed by patients compared with the RRA, particularly in older patients and for operators in training.


Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals.
Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals. To validate our model, two compounds (quercetin and genistein), known to have anti-inflammatory effects on vasculatures, were selected. We found that both quercetin and genistein were ineffective at suppressing inflammatory activation by interleukin-1β owing to limited metabolic activity of hPSC-ECs. Conversely, hPSC-HEPs demonstrated metabolic capacity to break down both nutraceuticals into primary and secondary metabolites. When hPSC-HEPs were cocultured with hPSC-ECs to permit paracrine interactions, the continuous turnover of metabolites mitigated interleukin-1β stimulation on hPSC-ECs. We observed significant reductions in inflammatory gene expressions, nuclear translocation of nuclear factor κB, and interleukin-8 production. Thus, integration of hPSC-HEPs could accurately reproduce systemic effects involved in drug metabolism in vivo to unravel beneficial constituents in nutraceuticals. This physiologically relevant endothelial-hepatic platform would be a great resource in predicting the efficacy of complex nutraceuticals and mechanistic interrogation of vascular-targeting candidate compounds. Stem Cells Translational Medicine 2017;6:851-863.


Homelessness at diagnosis is associated with death among people with HIV in a population-based study of a US city.
San Francisco, California, has experienced a 44% reduction in new HIV diagnoses since 2013 supported by its 'Getting to Zero' initiative; however, the age-adjusted mortality rate in people with HIV (PWH) has not decreased. We sought to identify factors associated with death among PWH in San Francisco. Population-based incidence-density case-control study. Among PWH in the San Francisco HIV surveillance registry, a random sample of 48 decedents from 1 July 2016 to 31 May 2017 were each matched to two to three controls who were alive at the date of death (108 controls matched on age and time since diagnosis). Covariates included demographics, substance use, housing status, medical conditions, and care indicators from the study population. We used matched-pair conditional logistic regression to examine factors associated with mortality. Of the 156 PWH in the study, 14% were African-American, 14% Latino, and 8% female sex. In adjusted analysis, factors associated with higher odds of death included: homelessness at HIV diagnosis [adjusted odds ratio (AOR) = 27.4; 95% confidence interval (CI) = 3.0-552.1], prior-year IDU (AOR = 10.2; 95% CI = 1.7-128.5), prior-year tobacco use (AOR = 7.2; 95% CI = 1.7-46.9), being off antiretroviral therapy at any point in the prior year (AOR = 6.8; 95% CI = 1.1-71.4), and being unpartnered vs. married/partnered (AOR = 4.7; 95% CI = 1.3-22.0). People homeless at HIV diagnosis had 27-fold higher odds of death compared with those with housing; substance use and retention on antiretroviral therapy in the prior year are other important intervenable factors. New strategies to address these barriers, and continued investment in supportive housing and substance use treatment, are needed.


A reliable witness: dual-chamber pacemaker prolonged intracardiac recordings of a resuscitated cardiac arrest episode.
We report the case of a patient with a previously implanted pacemaker, who suffered cardiac arrest due to ventricular fibrillation requiring cardiopulmonary resuscitation (CPR) manoeuvres and electrical cardioversion to restore sinus rhythm. Analysis of the pacemaker's stored electrograms showed the arrhythmia progression from monomorphic ventricular tachycardia to ventricular fibrillation and the electrophysiological effects of CPR manoeuvres and epinephrine administration before successful cardioversion.


Using PICO Methodology to Answer Questions About Smoking in COPD Patients.
The ALAT and SEPAR Treatment and Control of Smoking Groups have collaborated in the preparation of this document which attempts to answer, by way of PICO methodology, different questions on health interventions for helping COPD patients to stop smoking. The main recommendations are: (i)moderate-quality evidence and strong recommendation for performing spirometry in COPD patients and in smokers with a high risk of developing the disease, as a motivational tool (particularly for showing evidence of lung age), a diagnostic tool, and for active case-finding; (ii)high-quality evidence and strong recommendation for using intensive dedicated behavioral counselling and drug treatment for helping COPD patients to stop smoking; (iii)high-quality evidence and strong recommendation for initiating interventions for helping COPD patients to stop smoking during hospitalization with improvement when the intervention is prolonged after discharge, and (iv)high-quality evidence and strong recommendation for funding treatment of smoking in COPD patients, in view of the impact on health and health economics.


Ultrasonic sensing of temperature of liquids using inexpensive narrowband piezoelectric transducers.
We investigated the possibility of substantially reducing the cost of minimally invasive ultrasonic non-destructive evaluation (NDE) of liquids, in particular, temperature sensing, using inexpensive narrowband transducers. Although designed for operation in air, ultrasonic transducers enclosed in an aluminum case could be submerged in water and were found to be suitable for this application; however, their responses changed substantially when submerged. The test cell developed was complemented by an amplifier to operate as an oscillator and some other support electronics to supervise the sensor's operation. The sensor was tested in temperatures ranging from 26 to 32°C at a nominal central frequency of 330 kHz and showed a sensitivity of around 280 Hz/K.


Differences in the interaction of histamine H2 receptor antagonists and tricyclic antidepressants with adenylate cyclase from guinea pig gastric mucosa.
The interaction of adenylate cyclase with histamine H2 receptor agents and with tricyclic antidepressants was studied in guinea pig gastric mucosal membranes. The H2 receptor antagonist tiotidine acted as a competitive inhibitor of histamine-stimulated adenylate cyclase. The tricyclic antidepressants imipramine and amitryptyline were also competitive inhibitors. The dissociation constant of imipramine was the same whether histamine or dimaprit was used to activate the enzyme. In membrane preparations that had been stored frozen, there was a marked increase in the concentration of histamine or dimaprit required to cause half-maximal enzyme stimulation, and the dissociation constants of some classical H2 receptor antagonists were greatly increased. In contrast, the dissociation constants of the antidepressants were either unchanged or decreased. These results suggest that antidepressants are potent blockers of H2 receptors in gastric mucosal membranes, but there are differences between antidepressants and classical H2 receptor antagonists in their interaction with H2 receptors.


Vicinal dithiol-disulfide distribution in the Escherichia coli mannitol specific carrier enzyme IImtl.
Escherichia coli mannitol specific EII in membrane vesicles can be inhibited by the action of the oxidizable substrate-reduced phenazine methosulfate (PMS) in a manner similar to E. coli enzyme IIGlc [Robillard, G. T., & Konings, W. (1981) Biochemistry 20, 5025-5032]. The fact that reduced PMS and various oxidizing agents protect the enzyme from inactivation by the sulfhydryl reagents N-ethylmaleimide and bromopyruvate suggests that the active form possesses a dithiol which can be protected by conversion to a disulfide. The sulfhydryl-disulfide distribution has been examined in purified EIImtl by labeling studies with N-[1-14C]ethylmaleimide ( [14C]NEM). EIImtl can be alkylated at three positions per peptide chain. When alkylation takes place in 8 M urea, only two positions are labeled. The third position becomes labeled in urea only after treatment with DTT, suggesting that the native enzyme is composed of two subunits linked by a disulfide bridge. The remaining two sulfhydryl groups per peptide chain appear to undergo changes in oxidation state as indicated by the following results. (1) Treatment of the active enzyme with NEM leads to complete inactivation and incorporation of 1 mol of [14C]NEM per peptide chain. Oxidizing agents protect the activity and prevent labeling presumably by forming a disulfide. (2) Phosphorylating the enzyme (one phosphoryl group per peptide chain) fully protects the activity, but 1 mol of NEM per peptide chain is still incorporated. Subsequent dephosphorylation by adding mannitol causes a second mole of [14C]NEM to be incorporated and results in complete inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunoaffinity purification: basic principles and operational considerations.
Immunoaffinity purification has become an important technique in biotechnology. In this review the basic principles of immunoaffinity separations are described with respect to the stages of operation and potential application. The most commonly used support materials, activation procedures, and coupling chemistries are compared to one another for suitability in various applications. Individual operational steps for fixed bed immunoadsorbents including loading, washing, elution and regeneration are described in terms of both theory and practice. Factors influencing adsorbent stability are identified, and alternative operation and configuration strategies are discussed in light of their application to immunoaffinity systems.


Visualization of MG53-mediated cell membrane repair using in vivo and in vitro systems.
Repair of acute injury to the cell membrane is an elemental process of normal cellular physiology, and defective membrane repair has been linked to many degenerative human diseases. The recent discovery of MG53 as a key component of the membrane resealing machinery allows for a better molecular understanding of the basic biology of tissue repair, as well as for potential translational applications in regenerative medicine. Here we detail the experimental protocols for exploring the in vivo function of MG53 in repair of muscle injury using treadmill exercise protocols on mouse models, for testing the ex vivo membrane repair capacity by measuring dye entry into isolated muscle fibers, and for monitoring the dynamic process of MG53-mediated vesicle trafficking and cell membrane repair in cultured cells using live cell confocal microscopy.


Volumetric uncertainty in radiotherapy.
The technologies available to identify anatomical structures (including radiotherapy target and normal tissue 'volumes'), and to deliver dose accurately to these volumes, have improved significantly in the past decade. However, the ability of clinicians to identify volumes accurately and consistently in patients still suffers from uncertainties that arise from human error, inadequate training, lack of consensus on the derivation of volumes and inadequate characterisation of the accuracy and specificity of imaging technologies. Inadequate volume definition of a target can result in treatment failure and, consequently, disease progression; excessive volume may also lead to unnecessary patient injury. This is a serious problem in routine clinical care. In the context of large multi-centre clinical trials, uncertainty and inconsistency in tissue-volume reporting will be carried through to the analysis of treatment effect on outcome, which will subsequently influence the treatment of future patients. Strategies need to be set in place to ensure that the abilities and consistency of clinicians in defining volumes are aligned with the ability of new technologies to present volumetric information. This review seeks to define the concept of volumetric uncertainty and propose a conceptual model that has these errors evaluated and responded to separately. Specifically, we will explore the major causes, consequences of, and possible remediation of volumetric uncertainty, from the point of view of a multidisciplinary radiotherapy clinical environment.


VCAP-AMP-VECP as a preferable induction chemotherapy in transplant-eligible patients with aggressive adult T-cell leukemia-lymphoma: a propensity score analysis.
A dose-intensified multi-agent chemotherapy regimen called VCAP-AMP-VECP was investigated in Japan as front-line therapy for patients with adult T-cell leukemia-lymphoma (ATL). Although a prospective randomized controlled study showed that VCAP-AMP-VECP was superior to CHOP, the trial was rather small and no subsequent studies confirmed the benefit of VCAP-AMP-VECP over CHOP. We conducted a retrospective analysis of transplant-eligible patients with ATL who received only VCAP-AMP-VECP or CHOP, incorporating inverse probability of treatment weighting (IPTW) using propensity scoring. Overall, 947 and 513 patients were treated with VCAP-AMP-VECP and CHOP, respectively. The median follow-up of surviving patients was 1006 days. The crude probabilities of 2-year overall survival (OS) for patients in the VCAP-AMP-VECP and CHOP groups were 31.2% and 24.6%, respectively (P < 0.001). Stratified by risk group according to the modified ATL-prognostic index score at diagnosis, the crude probabilities of 2-year OS in the VCAP-AMP-VECP and CHOP groups were 39.8 and 45.0% in the low-risk group (P = 0.69), 32.2 and 21.6% in the intermediate-risk group (P < 0.001), and 17.2 and 6.2% in the high-risk group (P = 0.005). Our current analysis suggests that VCAP-AMP-VECP regimen is a preferable front-line therapy in patients with aggressive ATL in intermediate- and high-risk groups.


Subtalar instability.
Subtalar instability is a confusing yet important condition in patients with lateral ankle instability. The author will explore subtalar kinematics, and how they are closely related to the joint stability of the subtalar joint, both with respect to its intrinsic ligaments and its extrinsic ligaments. As subtalar instability is difficult to diagnose, this article will provide readers with a better understanding of its clinical presentation. Discussions will also include useful radiographic modalities and the most recent evidence regarding their accuracy. The last section discusses surgical options and what the readers need to know in order to make a decision.


Perioperative breast MRI is not associated with lower locoregional recurrence rates in DCIS patients treated with or without radiation.
For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT). A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis. There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79-1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78-2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86). We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.


The pharmacology of stuttering: a critical review.
The author critically examines the limited world literature on pharmacologic treatments of stuttering. The literature on stuttering and drugs was identified by means of two computer-assisted searches. A great variety of pharmacologic agents have been used to treat stuttering, reflecting the many theories about the origin and nature of the disorder. In some instances new hypotheses about the nature of stuttering have followed the chance discovery of agents having some efficacy. Few studies have used adequate experimental designs. Promising avenues of research, both for the treatment of stuttering and for exploring its nature, include the use of calcium channel blocking agents and cholinergic drugs.


Injury to the immature carpus.
Traumatic injury to the immature carpus is infrequent because of the sequence of carpal ossification, the resiliency of surrounding ligaments, and the vulnerability of the radius to fracture. Diagnosis requires careful palpation and suspicion, particularly in younger children. Treatment should consider the healing, growth, and modeling potential of the carpus.


International radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting.
This study explored international radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting (RINV). Radiation oncology trainees who were members of the national radiation oncology associations of the USA, Canada, Netherlands, Australia, New Zealand, France, Spain and Singapore completed a Web-based survey. Respondents estimated the risks of nausea and vomiting associated with six standardised radiotherapy-only clinical case vignettes modelled after international anti-emetic guidelines and then committed to prophylactic, rescue or no therapy as an initial management approach for each case. One hundred and seventy-six trainees from 11 countries responded. Only 28 % were aware of any anti-emetic guideline. In general, risk estimates and management approaches for the high-risk and minimal risk cases varied less and were more in line with guideline standards than were estimates and approaches for the moderate- and low-risk cases. Prophylactic therapy was the most common approach for the high-risk and a moderate-risk case (83 and 71 % of respondents respectively), while rescue therapy was the most common approach for a second moderate-risk case (69 %), two low-risk cases (69 and 76 %) and a minimal risk case (68 %). A serotonin receptor antagonist was the most commonly recommended prophylactic agent. On multivariate analysis, a higher estimated risk of nausea predicted for recommending prophylactic therapy, and a lower estimated risk of nausea predicted for recommending rescue therapy. Radiation oncology trainee risk estimates and recommended management approaches for RINV clinical case vignettes varied and matched guideline standards more often for high-risk and minimal risk cases than for moderate- and low-risk cases. Risk estimates of nausea specifically were strong predictors of management decisions.


Statistical factorial analysis approach for parameter calibration on material nonlinearity of intervertebral disc finite element model.
In the biomechanics field, material parameters calibration is significant for finite element (FE) model to ensure a legit estimation of biomechanical response. Determining an appropriate combination of calibration factors is challenging as each constitutive component responds differently. This study proposes a statistical factorial analysis approach using L16(45) orthogonal array to evaluate material nonlinearity and applicable calibration factor of the intervertebral disc FE model in pure moment. The calibrated model exhibits improved agreement to the experimental findings for all directions. Appropriate combination of calibration parameter reduces the estimation gap to the experimental findings, ensuring agreeable biomechanical responses.


Effects of cholecystokinin, caerulein and pentagastrin on arterial blood pressure and plasma renin activity in rats.
Effects of cholecystokinin (CCK-33), caerulein (CER) and pentagastrin (PG) on arterial blood pressure and plasma renin activity (PRA) were studied in rats. The results showed that CCK-33 (106.25, 212.5 and 425.0 pmoles/kg i.v.) increased systolic and diastolic blood pressure and decreased PRA. CER used at doses: 0.37, 1.85 and 3.7 nmoles/kg (i.v.) did not change systolic blood pressure. CER administered at the higher doses slightly decreased diastolic blood pressure, evoked bradycardia and increased PRA. PG used at doses of 0.13, 1.3 and 13.0 nmoles/kg (i.v.) and the peptide given at the highest dose (13.0 nmoles/kg, i.v.) slightly increased arterial blood pressure. PG administered at all doses did not change PRA. This research shows that in spite of similarity in biochemical structure of CCK-33, CER, PG there are differences in effects of the studied peptides on arterial blood pressure and PRA. The correlation between an influence of CCK-33, CER and PG on arterial blood pressure and PRA was also observed.


Artificial neural network analysis of data from multiple in vitro assays for prediction of skin sensitization potency of chemicals.
In order to develop in vitro risk assessment systems for skin sensitization, it is important to predict a threshold from the murine local lymph node assay (LLNA). We first confirmed that the combination of the human Cell Line Activation Test (h-CLAT) and the SH test improved the accuracy and sensitivity of prediction of LLNA data compared with each individual test. Next, we assessed the mutual correlations among maximum amount of change of cell-surface thiols (MAC value) in the SH test, CV75 value (concentration giving 75% cell viability) in a cytotoxicity assay, EC150 and EC200 values (thresholds concentrations of CD86 and CD54 expression, respectively) in h-CLAT and published LLNA thresholds of 64 chemicals. Based on the results, we selected MAC value and the minimum of CV75, EC150 (CD86) and EC200 (CD54) as descriptors for the input layer of an artificial neural network (ANN) system. The ANN-predicted values were well correlated with reported LLNA thresholds. We also found a correlation between the SH test and the peptide-binding assay used to evaluate hapten-protein complex formation. Thus, this model, which we designate as the "iSENS ver. 1", may be useful for risk assessment of skin sensitization potential of chemicals from in vitro test data.


Polymeric Backbone Eutectogel Electrolytes for High-Energy Lithium-Ion Batteries.
This work introduces a polymeric backbone eutectogel (P-ETG) hybrid solid-state electrolyte with an N-isopropylacrylamide (NIPAM) backbone for high-energy lithium-ion batteries (LIBs). The NIPAM-based P-ETG is (electro)chemically compatible with commercially relevant positive electrode materials such as the nickel-rich layered oxide LiNi0.6Mn0.2Co0.2O2 (NMC622). The chemical compatibility was demonstrated through (physico)chemical characterization methods. The nonexistence (within detection limits) of interfacial reactions between the electrolyte and the positive electrode, the unchanged bulk crystallographic composition, and the absence of transition metal ions leaching from the positive electrode in contact with the electrolyte were demonstrated by Fourier transform infrared spectroscopy, powder X-ray diffraction, and elemental analysis, respectively. Moreover, the NIPAM-based P-ETG demonstrates a wide electrochemical stability window (1.5-5.0 V vs Li+/Li) and a reasonably high ionic conductivity at room temperature (0.82 mS cm-1). The electrochemical compatibility of a high-potential NMC622-containing positive electrode and the P-ETG is further demonstrated in Li|P-ETG|NMC622 cells, which deliver a discharge capacity of 134, 110, and 97 mAh g-1 at C/5, C/2, and 1C, respectively, after 90 cycles. The Coulombic efficiency is >95% at C/5, C/2, and 1C. Hence, gaining scientific insights into the compatibility of the electrolytes with positive electrode materials that are relevant to the commercial market, like NMC622, is important because this requires going beyond the electrolyte design itself, which is essential to their practical applications.


Examining the Impact of Alcohol Labels on Awareness and Knowledge of National Drinking Guidelines: A Real-World Study in Yukon, Canada.
Alcohol labels are one strategy for communicating health information to consumers. This study tested the extent to which consumers recalled alcohol labels with national drinking guidelines and examined the impact of labels on awareness and knowledge of the guidelines. A quasi-experimental study was conducted in two jurisdictions in northern Canada examining the impact of labels on the following outcomes: unprompted and prompted recall of the drinking guideline label message, awareness of the drinking guidelines, and knowledge of the daily and weekly recommended drink limits. The intervention site applied labels with national drinking guidelines, a cancer warning, and standard drink information to alcohol containers in its liquor store, whereas the comparison site did not apply these labels. In total, 2,049 cohort participants in both sites were recruited to complete surveys before and at two time points after the intervention. Changes in outcomes were examined using generalized estimating equations. After the intervention, unprompted and prompted recall of the drinking guideline label message increased more in the intervention versus comparison site (adjusted odds ratio [AOR] = 10.8, 95% CI [0.9, 127.6]; AOR = 7.0, 95% CI [3.3, 14.9], respectively). Awareness of the drinking guidelines increased 2.9 times more in the intervention versus comparison site (AOR = 2.9, 95% CI [2.0, 4.3]). In addition, knowledge of the daily and weekly drink limits increased 1.5 and 1.4 times more in the intervention versus comparison site, respectively (daily: AOR = 1.5, 95% CI [1.0, 2.1]; weekly: AOR = 1.4, 95% CI [1.0, 2.0]). Enhanced alcohol labels get noticed and may be an effective population-level strategy for increasing awareness and knowledge of national drinking guidelines.


Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial.
Thirty-eight women, aged 25-65 yr, with androgen deficiency due to hypopituitarism were treated with oral dehydroepiandrosterone (DHEA; 30 mg/d if <45 yr of age and 20 mg if > or =45 yr of age) for 6 months in a randomized, placebo-controlled, double blind study, followed by a 6-month open treatment period. The administration of DHEA raised the serum levels of DHEAS to normal age-related reference ranges and increased androstenedione and T to subnormal levels. Androgen effects on skin and/or pubic and/or axillary hair were observed in 84% (32 of 38) of the women after all received 6 months of DHEA treatment. No such effects were observed after the placebo treatment. These effects after 6 months were correlated with the serum levels of DHEAS (r = 0.37; P = 0.03), androstenedione (r = 0.42; P = 0.01), and T (r = 0.37; P = 0.03). The percentages of partners who reported improved alertness, stamina, and initiative by their spouses were 70%, 64%, and 55%, respectively, in the DHEA group and 11%, 6%, and 11%, respectively, in the placebo group (P < 0.05). According to the partners, sexual relations tended to improve compared with placebo (P = 0.06). After 6 months of treatment, increased sexual interest or activity was reported by 50% of the women taking 30 mg DHEA, by none taking 20 mg DHEA, and by two women taking placebo (P = NS). Compared with levels after placebo administration, high density lipoprotein cholesterol and apolipoprotein A-1 levels decreased after DHEA. Serum concentrations of IGF-I, serum markers of bone metabolism, and bone density did not change. In conclusion, oral administration of a low dose of DHEA to adult hypopituitary women induced androgen effects on skin and axillary and pubic hair as well as changes in behavior, with only minor effects on metabolism.


Total synthesis of (-)-apratoxin A, 34-epimer, and its oxazoline analogue.
A concise and convergent total synthesis of the highly cytotoxic marine natural product apratoxin A is accomplished by an 18-step linear sequence. The high sensitivity of the thiazoline, bearing an adjacent beta-hydroxyl group at the C35-position, results in the assembly process requiring the inclusion of appropriate protecting groups and the careful optimization of all individual transformations. In the synthesis of 3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid (Dtena), the three reagent-controlled asymmetric reactions enables us to introduce four chiral carbon centers in a dihydroxylated fatty acid moiety. Formation of the hindered ester and sterically-unfavorable N-methylamide bonds were successfully demonstrated. The thiazoline in apratoxin A was constructed by Tf(2)O and Ph(3)PO-mediated dehydrative cyclization, and final macrocyclization was achieved between N-methylisoleucine and proline residues. Moreover, an oxazoline analogue and a C34 epimer of apratoxin A have also been elaborated in a similar approach. This synthetic route would enable assembly of other analogues differing in stereocenters of Dtena and their amino acids.


Lower Back Injuries in National Collegiate Athletic Association Football Players: A 5-Season Epidemiological Study.
Low back injuries are common in collegiate football players and can frequently lead to persistent pain, reinjuries, and time lost from participation. To describe the epidemiology of back injuries in National Collegiate Athletic Association (NCAA) football players during the 2009/2010 through 2013/2014 academic years utilizing the NCAA Injury Surveillance Program (ISP) database. Descriptive epidemiology study. A convenience sample of NCAA varsity football teams was utilized to determine the rates and patterns of back injuries as well as to generate national injury estimates. The rates and distribution of back injuries were identified within the context of mechanism of injury, injury chronicity, and time lost from sport. Injury rates were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). Incidence rate ratios were calculated to compare the rates of injury between season, event type, mechanism of injury, injury chronicity, and time lost from sport. Nationally, there were 267 low back injuries reported in the database. These were used to estimate 7076 back injuries over the 5-year period, approximately 82% of which were new injuries. The injuries occurred at a rate of 2.70 per 10,000 AEs. Overall, injuries were 3.12 times more likely to occur in competitions than in practices. Athletes were 4.67 times more likely to sustain a back injury during the preseason compared with the postseason but were 1.41 times more likely to sustain a low back injury during the preseason compared with the regular season. Both contact and noncontact were reported equally as the mechanism of injury (37.8% and 38.3%, respectively), and unspecified low back pain was the most common injury (64.2%). Only 1.6% of patients required surgery for their injury, and the majority of athletes (59.6%) returned to play within 24 hours. There was a relatively high rate of lumbar back injuries at the collegiate level (2.70/10,000 AEs), the majority of which were new injuries. About 18% of reported injuries were reinjuries. Although very few required surgery, a careful examination and work-up should be conducted to evaluate each injury. Regimented physical therapy and reconditioning programs are recommended to avert reinjuries.


Cow hair allergen concentrations in dairy farms with automatic and conventional milking systems: From stable to bedroom.
Bovine hair and dander are considered to be a notable risk factor for sensitization and allergic symptoms in occupationally exposed cattle farmers due to various IgE binding proteins. Farmers are suspected not only to be exposed during their work inside the stables but also inside their homes as allergens could be transferred via hair and clothes resulting in continued bovine allergen exposure in private areas. In recent years a new sensitive sandwich ELISA (enzyme linked immunosorbent assay) test has been developed to measure the cow hair allergen (CHA) concentration in dust. The aim of the present study was to determine the CHA concentration in airborne and settled dust samples in stables and private rooms of dairy cattle farms with automatic milking systems (AM) and conventional milking systems (CM), also with respect to questionnaire data on farming characteristics. For this purpose different sampling techniques were applied, and results and practicability of the techniques were compared. Dust sampling was performed in the stable, computer room (only AM), changing room, living room and bedroom (mattress) of 12 dairy farms with automatic milking systems (AM group) and eight dairy farms with conventional milking systems (CM group). Altogether, 90 samples were taken by ALK filter dust collectors from all locations, while 32 samples were collected by an ion charging device (ICD) and 24 samples by an electronic dust fall collector (EDC) in computer rooms (AM) and/or changing and living rooms (not stables). The dust samples were extracted and analyzed for CHA content with a sandwich ELISA. At all investigated locations, CHA concentrations were above the limit of detection (LOD) of 0.1 ng/ml dust extract. The median CHA concentrations in dust collected by ALK filters ranged from 63 to 7154 μg/g dust in AM farms and from 121 to 5627 μg/g dust in CM farms with a steep concentration gradient from stables to bedrooms. ICD sampling revealed median CHA contents of 112 μg/g airborne dust in the computer rooms of the AM farms and median CHA loads of 5.6 μg/g (AM farms) and 19.8 μg/g (CM farms) in the living rooms. Passive dust sampling by EDC was performed only at two locations in the AM group resulting in median CHA values of 116 μg/m(2) (computer room) and 55.0 μg/m(2) (changing room). Except for the stable samples the median CHA load was lower in AM farms compared to CM farms. The CHA contents of ALK filter samples were significantly correlated in most locations. Differences between the farming types were not significant. Although allergen transfer to the private area of the farmers has been found and results from several locations were correlated, differences in CHA concentrations were not significant with respect to questionnaire data such as the wearing of stable clothes in living room, free access of pets to stable and home, frequency of hair washing. All sampling techniques seem to being practicable for simple and effective CHA measurement.


Translucency of dental porcelains.
The translucency of comparable shades of five dental porcelains was determined. Both direct transmittance and total transmittance were measured at wavelengths of 400-700 nm. For 1 mm of porcelain, the values for direct transmittance were low and averaged 0.13 percent, whereas the values for total transmittance averaged 26.8 percent. Transmittance increased with increasing incident wavelength. These results indicated a high degree of light scattering.


Synchronization in an array of output-coupled Boolean networks with time delay.
This brief presents an analytical study of synchronization in an array of coupled deterministic Boolean networks (BNs) with time delay. Two kinds of models are considered. In one model, the outputs contain time delay, while in another one, the outputs do not. One restriction in this brief is that the state delay and output delay are restricted to be equal. By referring to the algebraic representations of logical dynamics and using the techniques of semitensor product of matrices, some necessary and sufficient conditions are derived for the synchronization of delay-coupled BNs. Examples including a practical epigenetic example are given for illustration.


Quality of Antimalarial Drugs in East Africa: A Systematic Review.
The use of poor quality drugs will have multiple consequences with an extended hazard of growing drug-resistant strains. The review aimed to provide the quality status of antimalarial drugs in East Africa. PubMed, Scopus, Web of Science, and Google Scholar were searched from September 5 to September 12, 2021. The review included articles available as original research targeted at evaluating the quality of antimalarial drugs. For inclusion, data on at least one of the following quality control parameters were required: packaging and labeling, hardness, friability, weight variation/uniformity of weight, disintegration, dissolution, and assay/percentage purity. Mendeley citation manager version 1.19.4 was used to avoid duplication and organize references, and titles and abstracts were primarily used for screening. The sample collection site, drug name, and the quality control parameters tested were retrieved from the selected studies. Totally, 300 antimalarial drug samples from Ethiopia, Kenya and Tanzania were included in this review. No antimalarial drug tested failed the identification and disintegration test. However, 15.93% (36/226), 5.00% (15/300), and 1.90% (3/158) of antimalarial samples failed the dissolution, assay and mass uniformity test, respectively. Moreover, amodiaquine and sulfadoxine/pyrimethamine samples failed dissolution and assay tests. In addition, amodiaquine samples failed the mass uniformity test. However, artemether/lumefantrine and quinine passed all quality control parameters tested. Overall, 19.67% (59/300) of antimalarial drug samples did not meet at least one quality control parameter. And the higher faller rate was reported for sulfadoxine/pyrimethamine accounting for 52.86% (37/70). An unneglected amount of antimalarial drug failed to meet at least one quality control parameter. Strengthening pharmaceutical management systems, including post-marketing surveillance, and providing the resources required for medication quality assurance, are recommended.


Intermolecular interactions in AST zeolites through 14N NMR and DFT calculations.
The structure of the silica AST zeolites (octadecasil) synthesized in fluoride medium using tetramethylammonium (TMA) as the organic structure-directing agent has been reinvestigated using 14N NMR quadrupolar parameters and DFT calculations. The value of the experimental 14N quadrupolar coupling constant (CQ = 27 kHz) is larger than expected for a TMA cation possessing a high degree of motion. The analysis of a DFT-optimized octadecasil cluster along with the comparison between measured and calculated 14N NMR parameters demonstrate the presence of weak C-H...O hydrogen bonds between the TMA in the [46612] cages and the silica skeleton. These intermolecular interactions can be related to the presence of Si...F tetrel bonds within the [46] cages. These new results provide additional information with regard to the formation mechanisms and structure of the octadecasil zeolites.


The many faces of FcγRI: implications for therapeutic antibody function.
Fcγ receptor I (FcγRI or CD64) is the sole human Fc receptor with high affinity for monovalent IgG. While it contains an immunoreceptor tyrosine-based activation motif in its cytoplasmic domain, binding of FcγRI can result in a complex array of activating and inhibitory outcomes. For instance, binding of monomeric IgG provides a low-intensity tonic signal through FcγRI that is necessary for full interferon γ receptor signaling in the same cell. Interaction of FcγRI with larger high-avidity complexes can result in phagocytosis, the generation of reactive oxygen species, as well as the synthesis and release of inflammatory cytokines. However, numerous reports also document potent anti-inflammatory effects brought about by FcγRI engagement with immune complexes such as the inhibition of IFNγ and TLR4 signaling, and secretion of interleukin-10. This has led to conflicting hypotheses regarding the function of FcγRI, especially with regard to its role in the efficacy of several therapeutic monoclonal antibodies. While many of these issues are still unclear, continued characterization of the regulation and context dependence of FcγRI function, as well as the molecular mechanisms responsible for these various outcomes, will improve our understanding of FcγRI biology as well as the therapeutic strategies designed to harness or constrain its actions.


Jak2 mutation-positive polycythemia vera presenting as central retinal artery occlusion.
To report the case of a 49-year-old man who presented with profound visual loss in his right eye because of a central retinal artery occlusion, accompanied by a stroke in the ipsilateral middle cerebral artery with left upper extremity sequelae. The patient underwent a comprehensive ophthalmologic examination, fluorescein angiography, thorough neuroophthalmology evaluation, including magnetic resonance imaging and magnetic resonance angiography, 12-lead electrocardiogram, transesophageal echocardiogram, bilateral carotid artery Doppler, Holter monitoring, comprehensive laboratory testing, bone marrow biopsy, and genetic testing. Despite an initially normal hematocrit, the etiology of the central retinal artery occlusion and that of the nearly concomitant stroke in the right medial cerebral artery territory was confirmed by bone marrow biopsy to be polycythemia vera (positive JAK2 mutation). Patient received treatment with aspirin, serial phlebotomies, and hydroxyurea, demonstrating a slight improvement in vision and substantial normalization of neurologic and hematological status. At the time of this report, 2 years later, patient remains stable. Central retinal artery occlusion, a disease with a frequently devastating visual outcome, is often not an "isolated" ocular occurrence. In the absence of an obvious local trigger, a thorough work-up is always warranted, especially in younger patients, as the ocular pathology oftentimes may herald severe cerebro-cardiovascular events.


Intraocular pressure measurement over amniotic membrane patch in human subjects.
To investigate the accuracy of intraocular pressure (IOP) measurement over amniotic membrane patching on human ocular surface using Tono-Pen tonometry. The IOP of 28 normal eyes in 14 volunteers (mean age, 27.6 years; range, 25-34) was measured by a handy applanation tonometer and the Tono-Pen XL. Then, a single layer of amniotic membrane (approximately 50 microm) was placed onto the corneal surface of the volunteers and the IOP was again measured using the Tono-Pen XL. The average IOP using handy applanation tonometry and the Tono-Pen was 14.3 +/- 2.1 and 14.3 +/- 2.4 mm Hg, respectively. In the presence of amniotic membrane, the average IOP was not significantly overestimated (14.7 +/- 2.6 mm Hg). The bias between handy applanation tonometry or the Tono-Pen XL without amniotic membrane and the Tono-Pen XL with amniotic membrane was only -0.40 and -0.18 mm Hg, respectively. The Tono-Pen XL is accurate and useful for IOP monitoring even in eyes with amniotic membrane patching.


Posterior circulation stroke: animal models and mechanism of disease.
Posterior circulation stroke refers to the vascular occlusion or bleeding, arising from the vertebrobasilar vasculature of the brain. Clinical studies show that individuals who experience posterior circulation stroke will develop significant brain injury, neurologic dysfunction, or death. Yet the therapeutic needs of this patient subpopulation remain largely unknown. Thus understanding the causative factors and the pathogenesis of brain damage is important, if posterior circulation stroke is to be prevented or treated. Appropriate animal models are necessary to achieve this understanding. This paper critically integrates the neurovascular and pathophysiological features gleaned from posterior circulation stroke animal models into clinical correlations.


Single-Molecule Narrow-Field Microscopy of Protein-DNA Binding Dynamics in Glucose Signal Transduction of Live Yeast Cells.
Single-molecule narrow-field microscopy is a versatile tool to investigate a diverse range of protein dynamics in live cells and has been extensively used in bacteria. Here, we describe how these methods can be extended to larger eukaryotic, yeast cells, which contain subcellular compartments. We describe how to obtain single-molecule microscopy data but also how to analyze these data to track and obtain the stoichiometry of molecular complexes diffusing in the cell. We chose glucose mediated signal transduction of live yeast cells as the system to demonstrate these single-molecule techniques as transcriptional regulation is fundamentally a single-molecule problem-a single repressor protein binding a single binding site in the genome can dramatically alter behavior at the whole cell and population level.


Association between Gut Microbiota and Digestive System Cancers: A Bidirectional Two-Sample Mendelian Randomization Study.
Accumulating evidence indicates that gut microbiota closely correlates with the tumorigenesis of digestive system cancers (DSCs). However, whether the causality between gut microbiota and DSCs exists is unknown. Genome-wide association study (GWAS) summary statistics for gut microbiota and DSCs and the bidirectional two-sample Mendelian randomization (MR) analysis were utilized to assess the causality between gut microbiota and DSCs. Sensitivity analyses were performed to evaluate the robustness of our results. We found that the genus Eggerthella (OR = 0.464, 95%CI: 0.27 to 0.796, p = 0.005) was negatively associated with the risk of gastric cancer. The genetically predicted genus Lachnospiraceae FCS020 group (OR = 0.607, 95%CI: 0.439 to 0.84, p = 0.003) correlated with a lower risk of colorectal cancer, and genus Turicibacter (OR = 0.271, 95%CI: 0.109 to 0.676, p = 0.005) was a protective factor for liver cancer. In the reverse MR, DSCs regulated the relative abundance of specific strains of gut microbiota. We comprehensively screened the association between gut microbiota and DSCs using a bidirectional two-sample MR analysis and identified the causality between several microbial taxa and DSCs. Our discoveries are beneficial for the development of novel microbial markers and microbiota-modifying therapeutics for DSC patients.


Does root respiration in Australian rainforest tree seedlings acclimate to experimental warming?
Plant respiration can acclimate to changing environmental conditions and vary between species as well as biome types, although belowground respiration responses to ongoing climate warming are not well understood. Understanding the thermal acclimation capacity of root respiration (Rroot) in relation to increasing temperatures is therefore critical in elucidating a key uncertainty in plant function in response to warming. However, the degree of temperature acclimation of Rroot in rainforest trees and how root chemical and morphological traits are related to acclimation is unknown. Here we investigated the extent to which respiration of fine roots (≤2 mm) of four tropical and four warm-temperate rainforest tree seedlings differed in response to warmer growth temperatures (control and +6 °C), including temperature sensitivity (Q10) and the degree of acclimation of Rroot. Regardless of biome type, we found no consistent pattern in the short-term temperature responses of Rroot to elevated growth temperature: a significant reduction in the temperature response of Rroot to +6 °C treatment was only observed for a tropical species, Cryptocarya mackinnoniana, whereas the other seven species had either some stimulation or no alteration. Across species, Rroot was positively correlated with root tissue nitrogen concentration (mg g-1), while Q10 was positively correlated with root tissue density (g cm-3). Warming increased root tissue density by 20.8% but did not alter root nitrogen across species. We conclude that thermal acclimation capacity of Rroot to warming is species-specific and suggest that root tissue density is a useful predictor of Rroot and its thermal responses in rainforest tree seedlings.


Postexercise hypotension and heart rate variability response after water- and land-based high-intensity interval exercise in prehypertensive obese men.
A randomized crossover trial was carried out in prehypertensive obese men to compare postexercise hypotension and heart rate variability (HRV) following water-based and land-based high-intensity interval exercises (HIIEs). Nine prehypertensive obese participants, aged 23.6± 2.4 years, were randomly assigned to one of three interventions: no-exercise control, HIIE with immersion up to the chest, or HIIE on dry land. In the evenings of three separate days, participants performed either of the interventions. Matched with exercise volume, both HIIEs composed of 5 repetitions of 30-sec sprints at maximum effort followed by a 4-min rest. Ambulatory blood pressure and HRV were measured before the interventions and over the 24-hr following period. Both HIIEs resulted in significant reductions of average 24-hr mean arterial pressure (-6.7 mmHg). Notably, the water-based HIIE resulted in a significantly higher reduction of 24-hr systolic blood pressure (SBP) (-9 mmHg) than the land-based HIIE, particularly at night, in addition to a significantly longer duration of postexercise hypotension. Finally, the water-based HIIE was more effective at restoring HRV during recovery. Our findings demonstrated postexercise hypotension following the HIIEs, particularly the water-based HIIE. During recovery, the water-based HIIE was remarkably effective at restoring HRV. These findings indicate that water-based HIIE is more effective at reducing SBP and requires less recovery time than land-based HIIE in prehypertensive obese men.


Differentially expressed genes in visceral or subcutaneous adipose tissue of obese men and women.
There is growing evidence that the distribution of adipose tissue in the body is of importance in the development of metabolic complications of obesity, such as diabetes, hypertension, and hyperlipidemia. The aim of this study was to identify differentially expressed genes in subcutaneous and omental human adipose tissue in obese men, using a subtractive hybridization strategy. From the obtained set of differentially expressed transcripts, we also aimed to identify genes that have a sex-specific pattern of expression in omental or subcutaneous adipose tissue. Representational difference analysis (RDA) was performed on cDNA from subcutaneous and omental fat tissue from a man with extreme abdominal obesity. Forty-four putatively differentially expressed genes were identified. The obtained RDA products were spotted onto glass slides to screen for differential expression in other obese patients by using a microarray hybridization procedure. Five genes were confirmed to be differentially expressed in subcutaneous or omental adipose tissue from male or female obese patients. One gene was detected only in males and was found to be upregulated in subcutaneous tissue. The findings extend previous knowledge that different fat depots have differential gene expression and indicate that sex differences exist in adipose gene expression patterns.


Pseudotumours and insignificant tumours in US and CT examinations of the adrenal glands.
Pseudotumours encountered in US and CT examinations of the adrenal glands over 2 years are reviewed. 12 pseudotumours were detected in US, 1 in the right adrenal gland and 11 in the left, while 2 pseudotumours were seen in the CT. The former were due to splenic lobulation in 4 patients, accessory spleens in 4, splenic cyst in one, renal cysts in 2 and the bowel contents in one, and the latter to the stomach and an accessory spleen (both of these CT examinations were technically unsuccessful). The 7 benign, non-functioning adenomas detected in CT and causing problems of differential diagnosis were also collected over the same period. A comparison of the US findings for 30 malignant adrenal tumours and the above pseudotumours revealed no essential differences, nor did a comparison of the benign non-functioning adenomas and small malignant adrenal tumours.


Emotion lateralisation: developments throughout the lifespan.
There is a great amount of research on hemispheric lateralisation for processing emotions and on the recognition of emotions across the lifespan. However, few researchers have explored the links between these two measures. This paper highlights how trends in these two research areas inform our understanding of how lateralisation for emotion processing may influence emotion recognition performance throughout the lifespan, including if the development of emotion lateralisation is a response to our environmental experiences of learning (experience dependent) or a result of having specific experiences at a particular time (experience expectant). The development of emotion lateralisation across the lifespan (infancy through to late adulthood) is explored with reference to past research and through the integration of the novel research offered within this special issue of Laterality. We also explore what we can learn from atypical populations. We propose that researchers need to focus on three key avenues of future research (longitudinal research, investigating the role of hormones, and research that explores the evolution of laterality) all which will provide greater insight into the development of laterality and how this may be associated with emotion processing.


[Research into new methods for diagnosing, treating and preventing tuberculosis].
Tuberculosis control requires improved diagnostics, drugs, and vaccines. Their development is facilitated by progress in immunology, molecular biology, and genomics. In addition to sputum smear and culture, amplification techniques can already be used to diagnose tuberculosis and antigen-detection tests for this purpose are being developed. Molecular typing and DNA microarrays provide new insights in the natural history and transmission of tuberculosis. In addition to established drugs such as rifampicin, isoniazid, pyrazinamide, and ethambutol, a limited number of new drugs have been discovered such as rifampicin derivates and fluorochinolones. Improved screening techniques and insights from genomics may lead to new drugs being discovered. Factors hampering the development and evaluation of new vaccines include problems with extrapolation from animal models, incomplete natural immunity, and limited knowledge about protective immunity. However, new candidate vaccines are being developed and will be tested on humans in the near future.


A case of Bartonellosis presenting as a puzzling multisystem disorder complicated by nosocomial COVID-19 infection.
The most commonly considered infection with a Bartonella species is cat-scratch disease caused by Bartonella henselae Here, we discuss a unique case of a 60-year-old man who presented with Bartonella infection complicated by nosocomial COVID-19. He was admitted with a history of chest pain, persistent fever, rash and influenza-like symptoms. Positive Bartonella serology confirmed diagnosis and the patient developed complications of pericardial effusion in addition to COVID-19 infection, requiring non-invasive ventilation and admission to the intensive care unit. We discuss his symptoms, investigations, treatment and outcomes, while also highlighting the challenges of assessing patients presenting with fever of unknown origin during the COVID-19 pandemic.


Framing the futures of animal-free dairy: Using focus groups to explore early-adopter perceptions of the precision fermentation process.
This paper reports on the findings from a series of virtual focus groups that explored consumer perceptions of animal-free dairy (AFD), an emerging type of animal product alternative produced using the tools of synthetic biology and precision fermentation. Focus group participants came from an international sample of potential "early adopters." To stimulate conversation, participants were presented with a series of visual "moodboards" that framed key arguments both in favor of and in opposition to AFD. Three primary thematic clusters emerged from the discussion. The first focused on issues of "process, safety, and regulation," centered on the general reaction of participants to the concept of AFD, their primary concerns, key questions, and the assurances they would need in order to support its advancement. The second focused on issues of "consumer preferences and priorities," highlighted by the often complicated, and sometimes outright contradictory, stated consumer interests of the participants. The third focused on issues of "food technology and the future," wherein participants expressed broader views on the role of food technology in society, generally speaking, and the potential futures of AFD, specifically. The general consensus among participants was a cautious openness to the idea of AFD. Outright opposition to the concept was rare, but so too was unabashed enthusiasm. Instead, respondents had a number of questions about the nature of the technological process, its overall safety and regulatory standards, its potential contributions to individual health and climate change mitigation, as well as its organoleptic qualities and price to consumers. Among the positive frames, claims about animal welfare were deemed the most pertinent and convincing. Among the negative frames, concerns about messing with nature and creating potential health risks to individuals were seen as the strongest arguments against AFD. The findings suggest that the key to AFD's future as a viable market option will depend in large part on the extent to which it can clearly demonstrate that it is preferable to conventional dairy or its plant-based competitors, particularly in the arena of taste, but also across considerations of health and safety, nutrition, environmental effects, and animal well-being.


TRPA1 Mechanoreceptors Mediate the IL-6 Response to a Single PD Dwell in the Rat.
The development of modern, biocompatible peritoneal dialysis (PD) fluids has not entirely eliminated the local pro-inflammatory effects of PD fluid administration. The present study was performed in order to establish the importance of known signaling pathways connected to mechano-, osmo- and chemo-sensors of the transient receptor potential (TRP) family for the acute inflammatory response to PD. Rats were exposed to a single 4-hour dwell of lactate-buffered, 2.5% glucose, filter-sterilized PD fluid through an implanted PD catheter. In some groups, the PD dwell was preceded by intravenous administration of blockers of TRPV1 (BCTC), TRPA1 (HC030031), or neurokinin 1 (NK1) (Spantide II) receptors. Cytokine messenger ribonucleic acid (mRNA) expressions were quantified in tissue biopsies (real-time polymerase chain reaction [qPCR]), and cytokine concentrations were quantified in dialysate samples by enzyme-linked immunosorbent assay (ELISA). Tissue expressions of TRPV1, TRPA1, and NK1 were evaluated immuno-histochemically. The PD dwell induced peritoneal synthesis of Il1b, Tnf, and Il6 and a secretion of interleukin-6 (IL-6) into the dialysate. The catheter implantation already induced the transcription of Il1b and Tnf but did not significantly affect Il6 transcription. The Il6 response to the PD dwell could be virtually eliminated by blocking TRPA1 but was not affected by TRPV1 blockade. Blocking the substance P receptor, NK1, produced an insignificant trend towards Il6 inhibition. TRPA1 and NK1 showed a stronger immuno-reactivity than TRPV1 on cells of the peritoneal tissue. The results show that IL-6 synthesis and secretion were connected to acute PD fluid exposure, and this response was triggered by TRPA1 receptors, possibly located to non-neuronal cells.


The ParE2-PaaA2 toxin-antitoxin complex from Escherichia coli O157 forms a heterodocecamer in solution and in the crystal.
Escherichia coli O157 paaR2-paaA2-parE2 constitutes a unique three-component toxin-antitoxin (TA) module encoding a toxin (ParE2) related to the classic parDE family but with an unrelated antitoxin called PaaA2. The complex between PaaA2 and ParE2 was purified and characterized by analytical gel filtration, dynamic light scattering and small-angle X-ray scattering. It consists of a particle with a radius of gyration of 3.95 nm and is likely to form a heterododecamer. Crystals of the ParE2-PaaA2 complex diffract to 3.8 Å resolution and belong to space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 142.9, c = 87.5 Å. The asymmetric unit is consistent with a particle of around 125 kDa, which is compatible with the solution data. Therefore, the ParE2-PaaA2 complex is the largest toxin-antitoxin complex identified to date and its quaternary arrangement is likely to be of biological significance.


Biomechanical effects of screws of different materials on vertebra-pediculoplasty: a finite element study.
Background: The effects of cannulated screws made of polyetheretherketone (PEEK) on the biomechanical properties of the vertebral body during vertebra-pediculoplasty remain unclear. This study aimed to investigate whether PEEK screws have the potential to replace titanium alloy screws. Methods: The surgical model of two different materials of screws was constructed using the finite element method. The biomechanical effects of the two models on the vertebral body under different working conditions were compared. Results: ① The peak von Mises stress of PEEK screws was significantly lower than that of titanium screws, with a reduction ranging from 52% to 80%. ② The von Mises stress values for the injured T12 spine were similar for both materials. Additionally, the segmental range of motion and intervertebral disc pressure showed no significant difference between the two materials. Conclusion: PEEK screws demonstrated advantages over titanium screws and may serve as a viable alternative for screw materials in vertebra-pediculoplasty.


Fetal yawning.
Fetal neurobehavioral patterns have been considered as indicators of nervous system development. Moreover, the capacity of 4-dimensional sonography to evaluate complex facial expressions allows recognition of common behaviors with which one can appreciate the prenatal functional development of the central nervous system. Using yawning as an example, we review this interpretation on the basis of knowledge derived from phylogeny and ontogeny. As a flip-flop switch, the reciprocal interactions between sleep- and wake-promoting brain regions allow the emergence of distinct states of arousal. By its ontogenic links with REM sleep, yawning appears to be a behavior which causes arousal reinforcement through the powerful stretching and the neuromuscular connections induced. Yawning indicates a harmonious progress in the development of both the brainstem and the peripheral neuromuscular function, testifying to the induction of an ultradian rhythm of vigilance. The lack of fetal yawn, frequently associated with lack of swallowing (associated or not with retrognathia), may be a key to predicting brainstem dysfunction after birth.


Treatment of obstructed defecation.
Obstructed defecation is a common problem that adversely affects the quality of life for many patients. Known causes of obstructed defecation include pelvic dyssynergy, rectocele, rectal intussusception, enterocele, pelvic organ prolapse, and overt rectal prolapse. Management of this condition requires an understanding of urinary, defecatory, and sexual function to achieve an optimal outcome. The goal of surgical treatment is to restore the various pelvic organs to their appropriate anatomic positions. However, there is a poor correlation between anatomic and functional results. As the pelvis contains many structures, a pelvic support or function defect frequently affects other pelvic organs. Optimal outcomes can only be achieved by selecting appropriate treatment modalities that address all of the components of a patient's problem.


EFNS guideline on mild traumatic brain injury: report of an EFNS task force.
In 1999, a Task Force on Mild Traumatic Brain Injury (MTBI) was set up under the auspices of the European Federation of Neurological Societies. Its aim was to propose an acceptable uniform nomenclature for MTBI and definition of MTBI, and to develop a set of rules to guide initial management with respect to ancillary investigations, hospital admission, observation and follow-up.


[Urogenital bilharziasis: imaging diagnosis].
Urogenital bilharziasis is a well-known disease that seldom is encountered in western countries. Therefore, bilharziasis usually only is considered after tuberculosis, the main differential diagnosis, has been excluded. Using this case, we will discuss the value of different imaging techniques (especially that of CT combined with transrectal US) for diagnosing bilharziasis and review specific criteria to more easily distinguish both pathologies.


Genetic and epidemiological studies on electrolyte transport systems in hypertension.
In recent years several different tests of cations in human cells have been studied to detect and to define possible roles in the development of essential hypertension. The goal of this report is to summarize what has been learned in genetic and epidemiological studies of human populations. The seven tests reviewed in greatest detail include sodium-lithium countertransport, intraerythrocytic sodium, sodium (or lithium)-potassium cotransport, lithium leak, sodium-potassium ATPase pump, sodium pump sites (ouabain binding), and circulating sodium pump inhibitor ('digoxin-like factor' in some studies). Countertransport, intraerythrocytic sodium and cotransport consistently show different values in hypertensives compared to normotensives and even in normotensives with a positive family history of hypertension when compared to controls without a positive family history. Thorough genetic studies have been carried out only for sodium-lithium countertransport and intraerythrocytic sodium. Both of these tests are highly heritable with a combination of both polygenic and major gene effects. Cotransport, leak, and pump sites also seem to be quite significantly heritable whereas the ATPase pump activity and the circulating pump inhibitor seem to be largely determined by nongenetic factors. Some of the most dramatic changes in these tests have been observed during pregnancy. Significant increases are seen in countertransport, cotransport, ouabain binding sites, and digoxin-like factor. Oral contraceptives also seem to affect at least cotransport. Plasma triglyceride level and body weight are some of the strongest correlates of countertransport, cotransport, and lithium leak. Cotransport increases with higher dietary sodium intake and decreases with the use of the diuretic medication. In the current developmental stage these tests have several significant limitations. In most population studies there is a considerable overlap of test values between persons with high and normal blood pressure. There are substantial variations in the methods used by different laboratories for the same tests. They are expensive, complex and usually must be done on fresh cells. There are conflicts between the results of several different reported studies that could be due to the way in which their subjects were selected, the effects of medications or other uncontrolled variables, or even due to the differences in laboratory methodologies.(ABSTRACT TRUNCATED AT 400 WORDS)


Treatment of a Lisfranc Injury in a 7-Year-Old Boy: Case Report and Surgical Technique.
This is a case of a 7-year-old boy with a Lisfranc injury identified on weight-bearing films who was treated successfully with closed reduction with a clamp and smooth pin fixation. This patient returned to sports without pain or radiographic signs of arthritis at 1 year. Lisfranc fractures and ligamentous injuries are rare and can occur in skeletally immature children. They have high potential for long-term disability if not properly diagnosed and treated. Although there is no consensus on optimal management of pediatric Lisfranc injuries, restoration of an anatomic Lisfranc joint with smooth pins and immobilization for 6 weeks is a viable treatment option.


An elderly patient with depression and a suicide attempt during the COVID-19 pandemic: a case report.
Elderly individuals are among the age groups with the highest risk of suicide. The coronavirus (COVID-19) pandemic forced isolation and resulted in an increased risk of depression, hopelessness, and perceived burdensomeness among the elderly, thereby increasing the risk of suicide. This is a case report of an elderly single retired school principal with obsessive-compulsive personality traits who developed depression with psychotic symptoms after being isolated following the movement control order (MCO) during the COVID-19 pandemic. The social isolation led to feelings of loneliness and hopelessness. The patient's depressive symptoms worsened after he developed physical illnesses, such as eye floaters, that affected his daily activities. This caused him to have suicidal ideation to the extent that he attempted suicide by ingesting 90 mL of pesticide. Two weeks prior to the attempt, he updated his will and asked his friend to keep it. After the suicide attempt, he vomited and had diarrhea and epigastric pain. He called his friend, who brought him to the hospital emergency room (ER). He was resuscitated and subsequently admitted to the intensive care unit (ICU). After being medically stabilized, he was transferred to the psychiatric ward, where further treatment was administered for his depression. His depressive symptoms and suicidal ideation improved after he was administered antidepressants and psychotherapy. The impact of the COVID pandemic has led to a surge in mental health issues such as anxiety and depression. The elderly are among the highest-risk groups of individuals to contract or die of COVID-19 infection, and they are also the most likely to develop mental health issues related to the pandemic. Furthermore, the risk of death by suicide is highest in this age group due to physical illness, social isolation, and the lack of a support system. This case also highlights the need for awareness of suicidal ideation screening among non-medical healthcare professionals and religious organizations to avoid the treatment gap. It is essential to enhance suicide risk assessment and management among the elderly after the COVID-19 pandemic.