Breaking the myths of competition: a cross-sectional analysis of injuries among CrossFit trained participants.
The purpose of this study was to examine the injury rates of individuals engaged in CrossFit training and examine the risk of injury associated with competition. Cross-sectional analysis. Descriptive statistics, including injury incidence and rates, were examined for individuals reporting participation in a CrossFit sanctioned competition between 2013 and 2017. To examine the odds of being injured, we considered logistic regression models, where the primary independent measure was participation length-individual measures of interest included age, sex, body mass index, CrossFit affiliation and competition status. 3049 individuals completed the survey (60% completion rate). All competitors, regardless of competition level, had similar incidence of injury (χ2=1.1, p=0.571). For those who reported competing, our calculated injury rate was 0.21-0.54 injuries per 1000 training hours, while for those not competing, the injury rate was calculated as 0.39-1.30 injuries per 1000 training hours. Logistic regression demonstrated short length of participation in CrossFit training as the main factor associated with the odds of being injured (OR=1.82; 95% CI: 1.15 to 2.92). Additionally, training at an official CrossFit affiliate appeared to have a protective effect from injury (OR=0.85; 95% CI: 0.65, 1.10). Our findings provide evidence of the low risk of injury related to these events. Moreover, these findings support the notion that musculoskeletal injuries may be the result of poor progression plans, which may be minimised by participating in an official CrossFit affiliate.


Inflammation in the subcutaneous adipose tissue does not attenuate endothelial function in subjects with diabetes mellitus and subjects with dyslipidaemia and hypertension: A cross-sectional study.
Obesity is associated with low-grade inflammation that may be related to vascular disease. We hypothesized that inflammation in the subcutaneous adipose tissue is associated with impaired endothelium-dependent vasodilatation. We assessed endothelial function by measuring forearm vascular response to acetylcholine and determined inflammation in subcutaneous fat biopsies in 2 groups of subjects; 15 patients with type 2 diabetes mellitus (T2DM) and 19 subjects with dyslipidaemia combined with hypertension (DcH). The adipose tissue inflammation score was based on adipocyte size, influx of macrophages and presence of crown-like structures. We compared the vascular response to acetylcholine between subjects with and without adipose tissue inflammation. Patients with diabetes had clearly decreased vasodilatation compared to patients with DcH. In total, 23 of the 34 fulfilled the criteria of subcutaneous adipose tissue inflammation. However, there was no difference in vascular response to acetylcholine between the group with and without inflammation (changes in FBF from baseline 3.9 ± 0.8, 7.8 ± 1.0 and 13.6 ± 1.0 mL/dL/min compared to 4.3 ± 1.0, 7.9 ± 2.1 and 12.2 ± 2.4 mL/dL/min in response to acetylcholine 0.5, 2.0 and 8.0 μg/dL/min), nor was there a relationship between systemic hs-CRP levels and endothelial function. We confirm that subjects with T2DM have impaired endothelial function compared to age- and BMI-matched subjects with DcH. However, endothelial function did not differ between participants with or without inflammation in the subcutaneous adipose tissue. These results suggest that fat tissue inflammation, at least in the subcutaneous compartment, does not affect vascular function.


Developmental toxicity in rare minnow (Gobiocypris rarus) embryos exposed to Cu, Zn and Cd.
Using rare minnow (Gobiocypris rarus) embryos as experimental model, the developmental toxicity of Cu, Zn and Cd were investigated following exposure to 0.001-1.000mg/L for 72h, and the toxicity effects were evaluated by larval malformation rate, heart rate, pericardial area, spontaneous movements, tail length, enzyme activities and biomarker genes. Our results revealed that increased malformation rate provide a gradual dose-response relationship, and the most pronounced morphological alteration was heart and body malformations. Values of 72h EC50 with their 95 percent confidence intervals on G. rarus embryos were 0.103 (0.072-0.149)mg/L for Cu, 0.531 (0.330-1.060)mg/L for Zn, 0.219 (0.147-0.351)mg/L for Cd. Enzyme activities can be regard as a type of low-dose stimulation and high-dose inhibition. Stress and metabolism-related genes (hsp70, cyp1a and mt) were significantly up-regulated, development-related genes (wnt8a, vezf1 and mstn) were significantly down-regulated after the treatment by Cu, Zn and Cd. Overall, the present study points out Cu, Zn and Cd are highly toxic to G. rarus embryos. The information presented in this study will be helpful in fully understanding the toxicity induced by Cu, Zn and Cd in fish embryos.


Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits.
To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging. The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC). The three biomarkers demonstrated excellent inter-rater reliability (ICC >0.94, P-values < .001), very high agreement between test and retest sessions (ICC >0.98, P-values < .001), and were extremely consistent across the three scanners (ICC >0.98, P-values < .001). The three biomarker kits demonstrated very high inter-rater reliability, test-retest repeatability, and inter-scanner reproducibility, offering robust biomarkers suitable for future multi-site observational studies and clinical trials in the context of vascular cognitive impairment and dementia (VCID).


Interleukin-12 induces interferon-gamma expression and natural killer cytotoxicity in cord blood mononuclear cells.
Severe viral infection in newborns has been attributed to immaturity of the immune system including a defect in natural killer cytotoxicity (NKC) and decreased production of cytokines that are important for natural killer (NK) function. We investigated the induction of interferon (IFN)-gamma and activation of NK activity in adult and cord blood mononuclear cells (BMC) after IL-12 treatment. The levels of mRNA in these BMC were measured by Northern blot and reverse transcription-polymerase chain reactions using primers specific for IFN-gamma. The levels of IFN-gamma protein were measured by ELISA. In the absence of IL-12, only adult BMC spontaneously produced low levels of IFN-gamma. After IL-12 treatment, induction of IFN-gamma expression was detected as early as 4 h in both cord and adult BMC. Both cord and adult cells showed similar levels of IFN-gamma mRNA and protein expression in response to IL-12 at a concentration as low as 10 U/mL. In contrast, upon phorbol ester and ionomycin treatment, adult BMC produced more IFN-gamma mRNA than cord BMC. In a 51Cr release assay with human immunodeficiency-infected H9 cells as indicators, both cord and adult cells responded to IL-12 induction of NKC. Our findings demonstrate that cord BMC are capable of responding to IL-12 stimulation, competent in synthesizing IFN-gamma, and able to mount NKC. Thus, it appears that the deficiency in IFN-gamma production or NKC in cord cells is not due to an inherent defect in IL-12 response of the cord cells.


Effects of continuous positive airway pressure on diaphragmatic kinetics and breathing pattern in healthy individuals.
In this study, we investigate the changes in diaphragmatic kinetics, breathing pattern and work of breathing induced by 10 cmH2 O of continuous positive airway pressure (CPAP). We used sonography to study diaphragmatic kinetics and measured energy expenditure using indirect calorimetry in 50 healthy volunteers at 0 cmH2 O positive end expiratory pressure (ZEEP) and after application of 10 cmH2 O CPAP. In a subgroup of 14 subjects, the changes in thoracic and abdominal volumes and thoraco-abdominal asynchrony were recorded with inductive plethysmography, while accessory respiratory muscle activity was recorded with electromyography. Continuous positive airway pressure breathing induced acute lung hyperinflation of 600 mL above passive functional residual capacity. This hyperinflation induced changes in diaphragmatic kinetics and breathing pattern; diaphragmatic excursion, thickness and thickness ratio, tidal volume (Vt) and oxygen consumption (VO2) increased while respiratory rate decreased. The increase in Vt with CPAP was mainly due to rib cage contribution. Activation of the accessory inspiratory (scalene) and expiratory (transversus abdominis) muscles was recorded. The raised respiratory muscles workload induced an increase in VO2. In healthy volunteers, CPAP therapy leads to lung overdistention and recruitment of respiratory muscles. These mechanisms operate at a high energy cost.


[Cartilage chip transplantation for cartilage defects of the first metatarsophalangeal joint].
Treatment of circumscribed cartilage defects in the first metatarsophalangeal joint (MTP1) using autologous cartilage fragments. Full thickness cartilage defects (ICRS IV) or focal osteoarthritis in combination with hallux rigidus. Pre-existing ankylosis of the metatarsophalangeal joint; global osteoarthritis of the joint; advanced osteoarthritis of the sesamoidal articulation; osteonecrotic cysts in the head of the first metatarsal bone. Preparation of the metatarsophalangeal joint. Mobilization of the first metatarsal head. Harvesting of the cartilage fragments from the dorsal rim portion as part of the cheilectomy. Mincing the cartilage fragments with a 3.0 mm shaver in sterile conditions. Augmenting the cartilage fragments with autologous conditioned plasma (ACP). Preparing the defect area and creation of a "contained" defect. Replantation of the resulting minced cartilage mass into the defect of the articular surface on the first metatarsal head. Immobilization of the MTP1 for 48 h. Intensive physiotherapy for 3 months. Full weight bearing after reduced swelling. In 2020, 5 patients were treated with the method described and followed up for a period of 1 year. All patients were subjectively satisfied with the result of the operation. There were no relevant surgery-associated complications.


Morphologic and neurochemical abnormalities in the auditory brainstem of the genetically epilepsy-prone hamster (GPG/Vall).
This study was performed to evaluate whether audiogenic seizures, in a strain of genetically epilepsy-prone hamsters (GPG/Vall), might be associated with morphologic alterations in the cochlea and auditory brainstem. In addition, we used parvalbumin as a marker of neurons with high levels of activity to examine changes within neurons. Cochlear histology as well as parvalbumin immunohistochemistry were performed to assess possible abnormalities in the GPG/Vall hamster. Densitometry also was used to quantify levels of parvalbumin immunostaining within neurons and fibers in auditory nuclei. In the present study, missing outer hair cells and spiral ganglion cells were observed in the GPG/Vall hamster. In addition, an increase was noted in the size of spiral ganglion cells as well as a decrease in the volume and cell size of the cochlear nucleus (CN), the superior olivary complex nuclei (SOC), and the nuclei of the lateral lemniscus (LL) and the inferior colliculus (IC). These alterations were accompanied by an increase in levels of parvalbumin immunostaining within CN, SOC, and LL neurons, as well as within parvalbumin-immunostained fibers in the CN and IC. These data are consistent with a cascade of atrophic changes starting in the cochlea and extending along the auditory brainstem in an animal model of inherited epilepsy. Our data also show an upregulation in parvalbumin immunostaining in the neuropil of the IC that may reflect a protective mechanism to prevent cell death in the afferent sources to this nucleus.


Measurement of pubic symphysis width in different birthing positions using ultrasound.
Studies have shown that some vertical birthing positions, such as squatting and standing, may influence labour and childbirth. However, a rigorous biomechanical understanding of how different positions affect a woman's pelvis during labour is currently lacking. It was hypothesized that the position of pubic bones is affected in different positions, and thus the pubic symphysis width changes. Therefore, we measured pubic symphysis width on eleven women in their seventh to ninth months of pregnancy in different positions through three-dimensional (3D) reconstruction of pubic symphysis ultrasound images. Positions studies included those used in clinics like supine and lithotomy positions, in addition to squatting and standing, which are recommended by midwives. The results showed that the average superior and inferior pubic symphysis widths in lithotomy, squatting and standing positions were approximately 1 mm larger than those in the supine position. However, no significant difference between lithotomy, squatting and standing positions was found. The results were consistent with those of two comparable studies. A significant difference was only found between standing and squatting, standing and lithotomy in the rotation angle about the medio-lateral axis. The results suggest that positions with thigh hyperflexion and gravity effect make a difference in pubic symphysis width and might have a positive effect in childbirth. However, due to the small sample size, no definite conclusion can be drawn.


Facilitating treatment initiation and reproductive care postpartum to prevent substance-exposed pregnancies: A randomized bayesian pilot trial.
For non-treatment-seeking women who use substances during pregnancy, immediately postpartum may be an optimum time for intervention. Our study tested a novel, brief, hospital-initiated, adaptive motivational interviewing plus acceptance and commitment therapy (MIACT) intervention to facilitate treatment initiation and reproductive planning postpartum among mothers who used substances during pregnancy. Mothers (N = 64) with an infant admitted to a neonatal intensive care unit were enrolled if they or their infant tested positive for an illicit substance at delivery or had a documented positive drug screen during pregnancy. A parallel group, randomized controlled design assigned participants to MIACT or conventional care (CC), with assessments at week 2 and 4 during treatment and follow-up at 2 and 6 months post treatment. Bayesian generalized linear modeling was used to evaluate outcomes as a function of treatment. Results indicated that during treatment the MIACT group demonstrated an 84% probability of benefit relative to CC with regard to initiating treatment (RR=1.5), however the effect was not seen at follow-up. MIACT was also associated with an increased probability of attending a postpartum obstetrics visit (RR=1.4), and receiving contraception during treatment and at both follow-ups, with posterior probabilities of 96% or higher and relative risks ranging from 1.5 to 5.1 at varying timepoints. Substance use rates for the MIACT versus CC were higher at follow-up. Brief, hospital-initiated interventions can assist postpartum mothers who use substances to enter treatment and obtain contraception in order to reduce future substance-exposed pregnancies.


The upregulation of osteoblast marker genes in mesenchymal stem cells prove the osteoinductivity of hydroxyapatite/tricalcium phosphate biomaterial.
Calcium phosphate (Ca-P), mainly concerning hydroxyapatite (HA), is the main inorganic component of the body's hard tissue. It is acknowledged that Ca-P biomaterial not only has osteoconduction but also can form bone bonding to host bone, making an ideal tissue-engineering scaffold. However, whether Ca-P biomaterial possesses osteoinductivity is still debated. The present study was performed to explore the expression level of osteoblast maker genes in human mesenchymal stem cells (hMSCs) grown on a Ca-P biomaterial. hMSCs were cultured on the HA/tricalcium phosphate-(TCP) double-phase ceramic. After coculture for 5, 10, 15, or 20 days, the cells were digested for isolation of total RNA. Fluorescence quantitative polymerase chain reaction was used to detect the relative mRNA levels of Runx2, collagen type I, osteopontin, and osteocalcin, all of which are the marker genes for osteoblasts. The mg63 cell was recruited as the reference and un-cocultured hMSCs as the negative controls. Alkaline phosphatase (ALP) activity in the cells was also examined after culture for 10 or 20 days. Our results showed that the expression levels of all four genes continued to rise during the first 10 days. Then, both collagen type I and Runx2 decreased. In contrast, osteocalcin mRNA reached its maximum at day 15 and osteopontin mRNA kept increasing throughout the whole experimental period. Additionally, ALP activity increased in a time-dependent manner. The up-regulation of all four osteoblast marker genes in hMSCs grown on Ca-P biomaterial suggested that HA/TCP biomaterials possess osteoinductivity on hMSCs, cells a mechanism that requires further investigation.


Impact of metformin therapy on health-related quality of life outcomes in tuberculosis patients with diabetes mellitus in India: A prospective study.
To assess the impact of metformin use on health-related quality of life (HRQoL) in tuberculosis (TB) patients who are presented with type 2 diabetes mellitus (T2DM). In this community-based prospective study, TB patients attending Hakeem Abdul Hameed Centenary Hospital, New Delhi (India) and had comorbidity of T2DM between April 2018 and July 2019 were enrolled. Patients were divided into metformin users and metformin non-users on the basis of the presence of metformin in their routine as antidiabetic drug(s). HRQoL was determined using a validated TB-specific tool (Dhingra and Rajpal-12 scale ie, DR-12) consists of symptom and socio-psychological and exercise adaptation domains. The HRQoL scores were compared at pretreatment (1st visit), end of intensive phase (2nd visit) and end of treatment (3rd visit) between the two groups. A total of 120 patients were enrolled, of which 24 were excluded as they did not respond at follow-up visits. Among the metformin users (n = 48) the mean age of patients was 47.56 years and 62.50% was males. Among the metformin non-users (n = 48), the mean age of patients was 49.02 years and 54.10% was males. The baseline characteristics were similar in both groups except for the substance used history (P = .025), literacy level (P = .048) and BMI (P = .028). Metformin users demonstrated significant improvement in symptom scores (2nd visit: P < .001; 3rd visit: P = .001) and socio-psychological and exercise adaptation scores (2nd visit: P < .0001; 3rd visit: P < .0001) as compared with metformin non-users at 2nd visit and 3rd visit. Overall, scores were also found to be significantly improved in metformin users (2nd visit: P < .001; 3rd visit: P = .001). Metformin therapy exerted favourable effects on HRQoL in patients with TB and T2DM and can be recommended as an adjuvant antitubercular drug in TB patients with co-morbidity of T2DM, unless contraindicated.


Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates cytokinesis, and its expression correlates with the prognosis of renal cell carcinoma.
Hypoxia plays a crucial role in many pathophysiological conditions, including cancer biology, and hypoxia-inducible factor (HIF) regulates transcriptional responses under hypoxia. To elucidate the cellular responses to hypoxia, we performed chromatin immunoprecipitation with deep sequencing in combination with microarray analysis and identified HIF-1 targets. We focused on one of the novel targets, sperm-associated antigen 4 (SPAG4), whose function was unknown. SPAG4, an HIF-1-specific target, is up-regulated in various cultured cells under hypoxia. Examination of SPAG4 expression using a tissue microarray consisting of 190 human renal cell carcinoma (RCC) samples revealed that SPAG4 is an independent prognostic factor of cancer-specific mortality. Live-cell imaging revealed localization of SPAG4 at the intercellular bridge in telophase. We also studied cells in which SPAG4 was knocked down. Hypoxia enhances tetraploidy, which disturbs cell proliferation, and knockdown of SPAG4 increased tetraploid formation and decreased cell proliferation under both normoxic and hypoxic conditions. Studies using deletion mutants of SPAG4 also suggested the involvement of SPAG4 in cytokinesis. Microarray analysis confirmed dysregulation of cytokinesis-related genes by knockdown of SPAG4. In conclusion, SPAG4 is an independent prognostic factor in RCC and plays a crucial role in cytokinesis to defend against hypoxia-induced tetraploid formation. This defensive mechanism may promote survival of cancer cells under hypoxic conditions, thus leading to poor prognosis.


Effects of the xanthine oxidase inhibitor allopurinol on the renal clearance of nitroimidazoles.
We have investigated the effects of the xanthine oxidase inhibitor allopurinol on the pharmacokinetics of nitroimidazoles in mice and dogs. Studies in mice showed that at a dose of 32 mg/kg given 30-60 min before, allopurinol had little or no effect on the clearance of misonidazole (MISO) or of the more lipophilic analogue Ro 07-0913, but did increase the blood concentrations of the hydrophilic dealkylation product desmethylmisonidazole (DEMIS). In addition, the clearances of administered DEMIS and the even more hydrophilic analogue SR-2508 were markedly reduced. This dose of allopurinol also caused a considerable fall in the clearances of 51Cr-EDTA and 125I-iodohippurate, normally used to measure glomerular filtration rate and effective renal plasma flow respectively. These data are consistent with a model in which allopurinol inhibits the renal clearance of hydrophilic nitroimidazoles. This leads to an increase in the acute toxicity of DEMIS and, to a lesser extent, of MISO. However, lower doses of allopurinol did not change the pharmacokinetics of MISO or DEMIS. A five-day pretreatment regimen (32 mg/kg/day) followed by a 66-76 hr recovery period was also without effect, thus demonstrating that the inhibition was reversible. Investigations in the dog showed that oral doses of 10-20 mg/kg allopurinol caused no change in the clearance of either 51Cr-EDTA or DEMIS.


Sudden Death Risk Assessment in Hypertrophic Cardiomyopathy Across the Lifespan: Reconciling the American and European Approaches.
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease. Since the modern description of HCM more than seven decades ago, great focus has been placed on preventing its most catastrophic complication: sudden cardiac death (SCD). Implantable cardioverter-defibrillators (ICD) have been recognized to provide effective prophylactic therapy. Over the years, two leading societies, the European Society of Cardiology (ESC) and the American Heart Association/American College of Cardiology (AHA/ACC), have proposed risk stratification models to assess SCD in adults. European guidelines rely on a risk calculator, the HCM Risk-SCD, while American guidelines propose a stand-alone risk factor approach. Recently, risk prediction models were also developed in the pediatric population. This article reviews the latest recommendations on the risk stratification of SCD in HCM and summarises current indications for ICD use.


Comparative Genetic Structure of Cannabis sativa Including Federally Produced, Wild Collected, and Cultivated Samples.
Currently in the United States, the sole licensed facility to cultivate Cannabis sativa L. for research purposes is the University of Mississippi, which is funded by the National Institute on Drug Abuse (NIDA). Studies researching Cannabis flower consumption rely on NIDA-supplied "research grade marijuana." Previous research found that cannabinoid levels of NIDA-supplied Cannabis do not align with commercially available Cannabis. We sought to investigate the genetic identity of Cannabis supplied by NIDA relative to common categories within the species. This is the first genetic study to include "research grade marijuana" from NIDA. Samples (49) were assigned as Wild Hemp (feral; 6) and Cultivated Hemp (3), NIDA (2), CBD drug type (3), and high THC drug type subdivided into Sativa (11), Hybrid (14), and Indica (10). Ten microsatellites targeting neutral non-coding regions were used. Clustering and genetic distance analyses support a division between hemp and drug-type Cannabis. All hemp samples clustered genetically, but no clear distinction of Sativa, Hybrid, and Indica subcategories within retail marijuana samples was found. Interestingly, the two analyzed "research grade marijuana" samples obtained from NIDA were genetically distinct from most drug-type Cannabis available from retail dispensaries. Although the sample size was small, "research grade marijuana" provided for research is genetically distinct from most retail drug-type Cannabis that patients and patrons are consuming.


Trajectory encoding in the hippocampus and entorhinal cortex.
We recorded from single neurons in the hippocampus and entorhinal cortex (EC) of rats to investigate the role of these structures in navigation and memory representation. Our results revealed two novel phenomena: first, many cells in CA1 and the EC fired at significantly different rates when the animal was in the same position depending on where the animal had come from or where it was going. Second, cells in deep layers of the EC, the targets of hippocampal outputs, appeared to represent the similarities between locations on spatially distinct trajectories through the environment. Our findings suggest that the hippocampus represents the animal's position in the context of a trajectory through space and that the EC represents regularities across different trajectories that could allow for generalization across experiences.


Comparison of the effects of Ca2+ and those of Mg2+ and La3+ on endplate currents in mouse interosseus muscles.
Acetylcholine-induced currents were measured in dissociated muscle fibres from the mouse interosseus. Fast and slow desensitization could be distinguished, the latter ending in a steady-state current. The time constants of the two phases of current decrease and the steady-state current were decreased when the superfusing solution contained di- or trivalent cations in addition to the 0.2 mM Mg2+ present in the control solution. When Ca2+, Mg2+ or La3+ was added at the time at which the current had settled to a near steady-state, there was a fall of current, the time course of which was much faster than that during desensitization. The amplitude and the time course of current change were nearly the same for Ca2+ and Mg2+, showing that the effect was not specific for any particular cation. No evidence of intracellular action of the cations was found. The [ACh]-current relationship was shifted to a higher [ACh] by raising [Mg2+] or [La3+]. Recovery of the ability to react to ACh was slowed by increasing [La3+], but the initial recovery of fast and slow time constants of desensitization was not much changed. Recovery was impeded by the presence of a low (conditioning) [ACh]; this effect was enhanced by La3+. It was concluded that the effects of polyvalent cations are similar to those of non-specific blockers.


Rhinoviruses: kinetics of ultraviolet inactivation and effects of UV and heat on immunogenicity.
The kinetics of ultraviolet inactivation for two human rhinoviruses and poliovirus were compared. No major differences in the rates of ultraviolet inactivation were detectable. All viral preparations inactivated by ultraviolet irradiation induced neutralizing antibody in guinea pigs. In contrast, when guinea pigs were immunized with a heat inactivated rhinovirus preparation, little or no neutralizing antibody was elicited. Immune electron microscopy of the heated rhinovirus preparations revealed the presence of particles resembling empty capsids. These results suggest that rhinoviruses and enteroviruses are affected in a similar manner when subjected to ultraviolet or heat inactivation.


Left side approach for aortic valve replacement in patient with dextrocardia and situs inversus totalis.
Aortic valve replacement in patients with dextrocardia and situs inversus totalis is technically challenging due to anatomical considerations. Modifications of the cannulation strategy and operative tool sets are helpful. We report a 47-year-old man who had dextrocardia with situs inversus totalis with severe aortic regurgitation. Our approach was precisely planned depending on the clear anatomy outlined by preoperative contrast-enhanced computed tomography of the chest. We used a surgical approach in which the main surgeon was standing on the left side of the patient. Left sided approach provided excellent exposure for aortic valve replacement in this case scenario.


Editorial Commentary: Feeling the Pressure! A Biomechanical Analysis of All-Inside and Inside-Out Knee Meniscus Repair.
A biomechanical, time-zero comparison found that both No. 2-0 UltraBraid inside-out sutures and FasT-Fix 360 all-inside devices used to repair a displaced bucket handle knee meniscus tear increased the contact area in deeper flexion angles (at 45°-60°) and reduced the peak contact pressure (at 45°-90°). No significance difference was observed between the inside-out and all-inside repair techniques.


Related Gunmen Paddock Committed Murder-Suicide in 1888 and in 2017.
Genealogical and periodical research reveals that two distantly related gunmen surnamed Paddock, a retired dentist-anesthetist and a retired accountant, committed murder-suicide in 1888 and in 2017, respectively.


The depolarising action of capsaicin on rat isolated sciatic nerve.
The effect of capsaicin on the isolated sciatic nerve of rat was studied by extracellular recording of membrane polarisation. Capsaicin depolarised the sciatic nerve, but desensitization occurred rapidly upon repeated administration. Several other neuroactive substances, including substance P, were inactive. The depolarisation was reduced in nerves depleted of unmyelinated fibres by neonatal capsaicin treatment, suggesting that it occurs mainly in C-fibres. This depolarising action of capsaicin could explain the irritant and acute antinociceptive properties of capsaicin.


New Report on Malpractice Claims Highlights Risks for Nurses.
Failing to adequately monitor patients heads the list of nursing-related errors.


Frequency of Otitis Media with Effusion in recurrent upper respiratory tract infection in children.
To determine the frequency of Otitis Media with Effusion (OME) in children with recurrent upper respiratory tract infections. A descriptive study. Combined Military Hospital, Gujranwala, from September 2003 to September 2005. Children of either gender suffering from more than 2 episodes of upper respiratory tract infection in the last 12 weeks were studied. The inclusion criteria were mild intermittent ear pain, fullness or "popping" of the ear drum; poor response to normal speech, inattentiveness, behavioural changes; irritability, sleep disturbances; balance problems and poor school performance. Diagnosis of OME was confirmed by pneumatic otoscopy while tuning-fork tests, tympanometry, pure tone audiometry were used as adjunct investigations. Results were described in percentage and 95% confidence interval was determined. Out of the 350 referred cases, pneumatic otoscopy by otolaryngologists diagnosed OME in 147 (42%, 95% CI=37.9-47.1). Out of these, 112 (76%) had retracted tympanic membrane, 25 (17%) had bulging of tympanic membrane and 10/147 (6.08%) cases showed dullness of tympanic membrane with no additional features. Tympanometry confirmed fluid behind the tympanic membrane in 145/147 (98.6%) cases. Tuning-fork tests showed negative Rinne's test in 122 (83%). Pure tone audiometry diagnosed deafness in 138/147 (93.8%) cases. OME with hearing loss is common in children having recurrent upper respiratory tract infection and nonspecific ear-related symptoms.


The sigma-receptor antagonist BD-1063 decreases ethanol intake and reinforcement in animal models of excessive drinking.
Sigma-Receptors (SigRs) have been implicated in behavioral and appetitive effects of psychostimulants and may also modulate the motivating properties of ethanol. This study tested the hypothesis that SigRs modulate ethanol reinforcement and contribute to excessive ethanol intake. The effects of subcutaneous treatment with the potent, selective Sig-1R antagonist BD-1063 on operant ethanol self-administration were studied in two models of excessive drinking-Sardinian alcohol-preferring (sP) rats and acutely withdrawn ethanol-dependent Wistar rats-and compared to ethanol self-administration in nondependent Wistar controls. To assess the specificity of action, the effects of BD-1063 on self-administration of an equally reinforcing saccharin solution were determined in Wistar and sP rats. Gene expression of Sig-1R in reward-related brain areas implicated in ethanol reinforcement was compared between ethanol-naive sP and Wistar rats and withdrawn ethanol-dependent Wistar rats. BD-1063 dose dependently reduced ethanol self-administration in sP rats (3.3-11 mg/kg) and withdrawn, dependent Wistar rats (4-11 mg/kg) at doses that did not modify mean ethanol self-administration in nondependent Wistar controls. BD-1063 did not reduce concurrent water self-administration and did not comparably suppress saccharin self-administration, suggesting selectivity of action. BD-1063 also reduced the breakpoints of sP rats to work for ethanol under a progressive-ratio reinforcement schedule. Ethanol-naive sP rats and 24-h withdrawn, dependent Wistar rats showed reduced Sig-1R mRNA expression in the nucleus accumbens. The results suggest that SigR systems may contribute to innate or ethanol-induced increases in susceptibility to self-administer high ethanol levels, identifying a potential neuroadaptive mechanism contributing to excessive drinking and a therapeutic target for alcohol abuse and dependence.


The 2015 Resuscitation Council of Asia (RCA) guidelines on adult basic life support for lay rescuers.
This paper introduces adult basic life support (BLS) guidelines for lay rescuers of the resuscitation council of Asia (RCA) developed for the first time. The RCA BLS guidelines for lay rescuers have been established by expert consensus among BLS Guidelines Taskforce of the RCA on the basis of the 2015 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science with Treatment Recommendations. The RCA recommends compression-only CPR for lay rescuers and emphasizes high-quality CPR with chest compression depth of approximately 5cm and chest compression rate of 100-120min(-1). Role of emergency medical dispatchers in helping lay rescuers recognize cardiac arrest and perform CPR is also emphasized. The RCA guidelines will contribute to help Asian countries establish and implement their own CPR guidelines in the context of their domestic circumstances.


The successful hearing aid user.
Improvements and modifications in design, construction, evaluation, and application procedures with the wearable hearing aid have brought the benefits of successful hearing aid use to an ever increasing proportion of the hearing impaired population. Many of today's successful hearing aid users would have been regarded at one time as extremely poor risks for hearing aid use. As a consequence, many of the prognostic principles developed as guidelines in advising for or against hearing aid trial are no longer true and should be discarded. Every person who experiences difficulties related to a permanent hearing impairment, no matter how slight or severe hearing loss, should have access to aural rehabilitation, including the use of wearable amplication.


The MOMANT study, a caregiver support programme with activities at home for people with dementia: a study protocol of a randomised controlled trial.
Because of the expected increase in the number of people with dementia, and the associated social and economic costs, there is an urgent need to develop effective and cost-effective care for people with dementia and their caregivers. The intervention proposed here combines two approaches to caregiver support that have shown to be effective in empowering caregivers, i.e., multiple components for caregiver support and actively engaging caregivers to involve the person with dementia in activities at home. The aim is to investigate whether the intervention is effective in improving quality of life in the caregiver and the person with dementia. A further aim will be to investigate whether this intervention can improve caregivers' feeling of competence, experience of caregiving, and mood. The study design is a pragmatic, cluster randomised controlled trial with cost-effectiveness analysis. The study participants are informal caregivers and home-living persons with dementia for whom they care, recruited in various regions in the Netherlands. The trial will compare outcomes in two groups of participants: 85 dyads who receive the intervention, and 85 dyads who receive care as usual. The intervention is a caregiver support training that is manual based and consists of 6 group sessions over 2 months. Training takes place in small groups of caregivers led by a health care professional presented at dementia day care centres. Randomisation occurs at the level of the day care centre. Participants are assessed on the outcome measures at baseline, prior to the intervention, and at 3 and 6 months after baseline. The study will provide insight into effectiveness and cost-effectiveness of an intervention that has not previously been evaluated or implemented in the Netherlands. The intervention potentially adds to the effective support options for informal caregivers of people with dementia without greatly increasing the workload for health- or social care professionals. The trial is registered at the Dutch Trial Register at NTR6643 ; August 22nd, 2017.


Surveillance technology for HIV-1 subtype C in Ethiopia: an env-based NASBA molecular beacon assay to discriminate between subcluster C and C'.
Forty-nine samples with known C2V3 sequences were used for the evaluation of an env-based molecular beacon assay to distinguish between the two genetic subclusters C and C' which characterize the HIV-1 epidemic in Ethiopia. Two subcluster C and two subcluster C' beacons targeting two different loci in the C2V3 region were developed. Using a three beacon-based (2C and 1C'=C prime), isothermal amplification assay, concordance with DNA sequencing was achieved for 43 (87.8%) samples. Sensitivity was 81.8% and specificity 97.4% for subcluster C beacons. For the subcluster C' beacon, a sensitivity of 97% and a specificity of 87.5% was achieved. Five samples were ambiguous by sequencing of which two samples were subcluster C' by the beacon assay and one subcluster C. Two of the samples remained ambiguous with different beacon-pair combinations as well. From samples with a clear C or C' phylogeny by sequencing, three were undetected by the first-line beacon genotyping assay. Genotype ambiguity was resolved in the three samples using beacon pair combinations restricted to each targeted locus. The beacons were evaluated further in a panel including all HIV-1 subtypes. Four of five subtype C isolates were identified correctly, and no cross-reactivity was observed with other subtypes.


[Modelling the impact of vaccination on the epidemiology of varicella zoster virus].
The soon to come the availability of a combined MMR-varicella vaccine has re-stimulated the debate around universal infant vaccination against varicella. In France, the incidence of varicella is estimated at about 700,000 cases per year, with approximately 3500 hospitalisations and 15-25 deaths, the latter mainly occurring in those over 15years. Vaccination would certainly decrease the overall incidence of the disease but concerns about vaccination leading to a shift in the average age at infection followed by an increase in incidence of severe cases and congenital varicella, still remain. In order to provide support for decision-making, a dynamic mathematical model of varicella virus transmission was used to predict the effect of different vaccination strategies and coverages on the epidemiology of varicella and zoster. A deterministic realistic age-structured model was adapted to the French situation. Epidemiological parameters were estimated from literature or surveillance data. Various vaccine coverages and vaccination strategies were investigated. A sensitivity analysis of varicella incidence predictions was performed to test the impact of changes in the vaccine parameters and age-specific mixing patterns. The model confirms that the overall incidence and morbidity of varicella would likely be reduced by mass vaccination of 12-month-old children. Whatever the coverage and the vaccine strategy, the vaccination will cause a shift in age distribution with, for vaccination coverage up to at least 80% in the base-case analysis, an increased morbidity among adults and pregnant women. However, the total number of deaths and hospitalisations from varicella is predicted to remain below that expected without vaccination. The model is very sensitive to the matrix of contacts used and to the parameters describing vaccine effectiveness. Zoster incidence will increase over a number of decades followed by a decline to below prevaccination levels. Mass varicella vaccination, in France, will result in an overall reduction of varicella incidence but will cause a shift in age distribution with an increase in adult cases. Due to the uncertainties in key parameters values, the exact magnitude of this shift is difficult to assess.


Osteochondral autograft transplantation for isolated patellofemoral osteoarthritis.
The purpose of this retrospective study was to evaluate clinical outcomes of osteochondral autograft transplantation (OAT) for isolated patellofemoral (PF) osteoarthritis (OA). OAT was performed in seven patients (six men, one woman; mean age, 61.1years) with isolated PF OA. The mean duration of follow up was 46.9months (range, 24-84months). Clinical outcomes were evaluated preoperatively and postoperatively according to the International Knee Documentation Committee (IKDC) objective score and the knee scoring system of the Japanese Orthopaedic Association (JOA) score. The International Cartilage Repair Society (ICRS) score was recorded in three cases that underwent second-look arthroscopies postoperatively. For morphological evaluation, the Kellgren and Lawrence (KL) classification and the modified magnetic resonance observation of cartilage repair tissue (MOCART) score were used. The mean IKDC and JOA scores were both significantly improved. The percentage of normal and nearly normal on the IKDC score was increased from 28.6% (2/7) to 85.7% (6/7) (P=0.05). The mean JOA score was improved from 80.0 (range, 65.0-85.0) to 95.0 (range, 90.0-100) (P=0.0008). The mean ICRS scores were 10.3 (nearly normal) in the three cases that underwent second-look arthroscopies postoperatively. Regarding KL classification, the grade was unchanged in five cases (two cases in grade 1, three cases in grade 2) and improved in two cases (from grade 3 to 2, from grade 4 to 3). The mean modified MOCART score was 67.9 (range, 60.0-75) at 12-month follow up. There were no complications, and satisfaction was obtained in all cases. The study design was case series: level IV. All clinical scores improved significantly postoperatively. Osteochondral plugs were transplanted perpendicular to the articular surface to obtain good congruity of the repaired articular surface. In this way, OAT is an effective procedure to prevent progression of isolated PF OA.


Fixation preference test: reliability for the detection of amblyopia in patients with strabismus and interexaminer agreement.
The purpose of this study was to analyze the reliability of the fixation preference test (FPT) in the detection of amblyopia, and to determine interexaminer agreement. Eighty patients whose visual acuity could be tested objectively and had a horizontal misalignment of more than 10 prism diopters were enrolled. The best corrected visual acuity (BCVA) and orthoptic findings were all recorded. Non-preferred eye in primary position and fixation preference grade were assessed independently by two masked experienced examiners. The primary outcome measures were reliability of FPT in terms of its correlation with BCVA and interexaminer agreement. There was no significant correlation between fixation preference grades and interocular visual acuity difference as well as the type and amount of deviation, the presence of fusion, stereopsis, anisometropia, and previous strabismus surgery for none of the examiners (p > 0.05 for all). Sensitivity was 52.0% for examiner 1 and 54.0% for examiner 2 while specificity was 50.0 and 46.7%, respectively. Interexaminer agreement was 76.7% (p < 0.001) for all patients. FPT is widely used in children particularly when the visual acuity cannot be determined in an objective manner. The test may not be accurate and reliable in the detection of amblyopia and also in predicting the visual acuity difference between both eyes, even though it was found to show a high degree of agreement between examiners. In conclusion, it should be kept in mind that the reliability of FPT may be limited and the results should be interpreted with caution and be supported by other tests.


Systemic taxotere chemotherapy for metastatic tumor pleurisy in cats with spontaneous breast cancer.
Systemic and intrapleural chemotherapy for metastatic tumor pleurisy was carried out in cats with breast carcinoma. The animals (n=18) were divided into 2 groups. Cats of the systemic chemotherapy group received 3-6 courses of taxotere (30 mg/m(2); n=7) or 3 courses of taxotere (20 mg/m(2)) in combination with doxorubicin (20 mg/m(2)at 21-day intervals (n=5) during the adjuvant period of therapy for metastatic tumor pleurisy. Objective effect was attained in 10 (84.6%) cats: partial remission in 3 (25%) and complete remission in 7 (58.3%, p>0.05) cats. Metastatic pleurisy progressed in 2 (16.7%) cats. The median time to progression reached 1.79 months, median lifespan 2.8 months. The animals of intrapleural chemotherapy group (n=6) received 1-4 courses of cyclophosphamide (250 mg/m(2)) at 1-week interval during the adjuvant period without therapy for malignant pleurisy. Malignant pleurisy progressed in all cats. The median time to progression was equal to median lifespan (0.6 months). The therapy for malignant pleurisy in cats with breast cancer is regarded as the second-line chemotherapy with taxotere preferable as a monotherapy or in combination with doxorubicin.


Response function of NaI(Tl) detectors and multiple backscattering of gamma rays in aluminium.
The response function, converting the observed pulse-height distribution of a NaI(Tl) detector to a true photon spectrum, is obtained experimentally with the help of an inverse matrix approach. The energy of gamma-ray photons continuously decreases as the number of scatterings increases in a sample having finite dimensions when one deals with the depth of the sample. The present experiments are undertaken to study the effect of target thickness on intensity distribution of gamma photons multiply backscattered from an aluminium target. A NaI(Tl) gamma-ray detector detects the photons backscattered from the aluminium target. The subtraction of analytically estimated singly scattered distribution from the observed intensity distribution (originating from interactions of primary gamma-ray photons with the target) results in multiply backscattered events. We observe that for each incident gamma photon energy, the number of multiply backscattered photons increases with increase in target thickness and then saturates at a particular target thickness called the saturation thickness (depth). Saturation thickness for multiply backscattering of gamma photons is found to decrease with increase in energy of incident gamma-ray photons.


Classification and analysis of corn steep liquor by UPLC/Q-TOF MS and HPLC.
Corn steep liquor (CSL), an important raw material with high nutritional value, serves as a nitrogen source in the fermentation industry. The CSL quality directly affects the yield and quality of fermentation products. In this work, a fingerprinting technique was used to identify the potential markers of CSL. Forty-two CSL samples from different manufacturers were profiled by ultra-performance liquid chromatography with tandem quadrupole time-of-flight mass spectrometry. Sixteen compounds, almost all of which were amino acids and their derivatives, were considered as the potential markers. Then, o-phthalaldehyde-9-fluorenylmethyl chloroformate precolumn derivatization by high-performance liquid chromatography was performed to identify the free amino acids in CSL. Principal component analysis (PCA) was used to distinguish among the samples from different manufacturers. The results demonstrated that the fingerprinting technique combined with PCA analysis was a powerful tool for determining the CSL quality.


Endometrial gene expression differences in women with coronavirus disease 2019.
To study the potential effect of coronavirus disease (COVID-19) on the endometrial transcriptome of affected, symptomatic women for the detection of altered gene expression. Pilot study of the endometrial transcriptomes of women manifesting COVID-19 compared with those of women without COVID-19 undergoing hysteroscopic procedures for benign gynecologic disorders using RNA sequencing. Hospital and university laboratories. Women with (n = 14) and without a COVID-19 (n = 10) diagnosis based on a nasopharyngeal swab analysis using quantitative reverse-transcription polymerase chain reaction. The endometrium of the patients with COVID-19 had previously been tested for severe acute respiratory syndrome coronavirus 2 infection, revealing the absence of the virus in this tissue. Endometrial biopsy sample collection. Endometrial gene expression and functional analysis of symptomatic patients with COVID-19 vs. individuals without the infection. The systemic disease COVID-19 altered endometrial gene expression in 75% of the women, with the patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, and BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, and IRF4) (false discovery rate<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in the endometria of the patients with COVID-19, including up-regulation in pathways involved in the development of immune responses to viruses and cytokine inflammation, reflecting elicitation of a COVID-19 response pathway. Coronavirus disease 2019 affects endometrial gene expression despite the absence of severe acute respiratory syndrome coronavirus 2 RNA in endometrial tissues.


Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents.
Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.


PEG conjugated VEGF siRNA for anti-angiogenic gene therapy.
A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.


Leaf orientation and the response of the xanthophyll cycle to incident light.
Leaves from two species, Euonymus kiautschovicus and Arctostaphylos uva-ursi, with a variety of different orientations and exposures, were examined in the field with regard to the xanthophyll cycle (the interconversion of three carotenoids in the chloroplast thylakoid membranes). East-, south-, and west-facing leaves of E. kiautschovicus were sampled throughout the day and all exhibited a pronounced and progressive conversion of violaxanthin to zeaxanthin, followed by a reconversion of zeaxanthin to violaxanthin later in the day. Maximal levels of zeaxanthin and minimal levels of violaxanthin were observed at the time when each leaf (orientation) received the maximum incident light, which was in the morning in east-facing, midday in southfacing, and in the afternoon in west-facing leaves. A very slight degree of hysteresis in the removal of zeaxanthin compared to its formation with regard to incident light was observed. Leaves with a broader range of orientations were sampled from A. uva-ursi prior to sunrise and at midday. All of the examined pigments (carotenoids and chlorophylls) increased somewhat per unit leaf area with increasing total daily photon receipt. The sum of the carotenoids involved in the xanthophyll cycle, violaxanthin + antheraxanthin + zeaxanthin, increased more strongly with increasing growth light than any other pigment. In addition, the amounts of zeaxanthin present at midday also increased markedly with increasing total daily photon receipt. The percentage of the xanthophyll cycle that was converted to zeaxanthin (and antheraxanthin) at peak irradiance was very large (approximately 80%) in the leaves of both E. kiautschovicus and A. uva-ursi. The daily changes in the components of the xanthophyll cycle that paralleled the daily changes in incident light in the leaves of E. kiautschovicus, and the increasing levels of the xanthophyll cycle components with total daily photon receipt in the leaves of A. uva-ursi, are both consistent with the involvement of zeaxanthin (i.e. the xanthophyll cycle) in the photoprotection of the photosynthetic apparatus against damage due to excessive light.


Identification of neomycin B-binding site in T box antiterminator model RNA.
The T box transcription antitermination mechanism regulates the expression of unique genes in many Gram-positive bacteria by responding, in a magnesium-dependent manner, to uncharged cognate tRNA base pairing with an antiterminator RNA element and other regions of the 5'-untranslated region. Model T box antiterminator RNA is known to bind aminoglycosides, ligands that typically bind RNA in divalent metal ion-binding sites. In this study, enzymatic footprinting and spectroscopic assays were used to identify and characterize the binding site of neomycin B to an antiterminator model RNA. Neomycin B binds the antiterminator bulge nucleotides in an electrostatic-dependent manner and displaces 3-4 monovalent cations, indicating that the antiterminator likely contains a divalent metal ion-binding site. Neomycin B facilitates rather than inhibits tRNA binding indicating that bulge-targeted inhibitors that bind the antiterminator via non-electrostatic interactions may be the more optimal candidates for antiterminator-targeted ligand design.


Tosylation of alcohols: an effective strategy for the functional group transformation of organic derivatives of polyoxometalates.
Recently, the organic functionalization of polyoxometalates (POMs) has drawn increasing interest, and an easy and effective route to achieve organic derivatives is of great importance. Herein, the first reported synthesis of a tosyl ester derivative of the polyoxometalate (Bu4N)2[V6O13{(OCH2)3CCH2SO3C7H4}2]·2.5CH3CN (compound 1) was performed by using DMAP as an activating reagent and triethylamine as an HCl scavenger. The tosyl ester was transformed into an azide or halide group by using sodium azide or sodium bromide, respectively, as the nucleophilic agent. Two derivatives of POMs, (Bu4N)2[V6O13{(OCH2)3CCH2N3}2]·4CH3CN (compound 2) and (Bu4N)2[V6O13{(OCH2)3CCH2Br}2] (compound 3), were easily obtained. All the compounds were structurally and compositionally characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy, NMR spectroscopy, ESI-MS, UV-Vis spectroscopy and TGA. This work provides a new route for the functional group transformation of organic derivatives of polyoxometalates.


MAIT cell-directed therapy of Mycobacterium tuberculosis infection.
Mucosal-associated invariant T (MAIT) cells are potential targets of vaccination and host-directed therapeutics for tuberculosis, but the role of MAIT cells during Mycobacterium tuberculosis (Mtb) infection in vivo is not well understood. Here we find that following Mtb infection MAIT cells mount minimal responses, and MAIT cell-deficient MR1-/- mice display normal survival. Preinfection expansion of MAIT cells through 5-OP-RU vaccination fails to protect against subsequent Mtb challenge. In fact, 5-OP-RU vaccination delays Mtb-specific CD4 T cell priming in lung-draining lymph nodes, and conversely MR1 deficiency or blockade accelerates T cell priming. The MAIT cell-mediated delay in T cell priming is partly dependent on TGF-β. Surprisingly, 5-OP-RU treatment during chronic infection drives MAIT cell expansion and an IL-17A-dependent reduction in bacterial loads. Thus, during early infection MAIT cells directly contribute to the notoriously slow priming of CD4 T cells, but later during infection MAIT cell stimulation may be an effective host-directed therapy for tuberculosis.


Changes in activities of superoxide dismutase, nitric oxide synthase, glutathione-dependent enzymes and the incidence of apoptosis in sheep corpus luteum during the estrous cycle.
Anti-oxidative enzymes play a role in protecting cells from oxidative stress-induced cell death. The present study was conducted to evaluate whether the anti-oxidant and pro-oxidant enzymatic capacities of the sheep corpus luteum (CL) are correlated with steroidogenic and structural status of the gland during the estrous cycle. Steroidogenic activity, apoptosis and superoxide dismutase (SOD1 and SOD2), nitric oxide synthase (NOS), glutathione peroxidase (GPX), glutathione reductase (GSR) and glutathione S-transferase (GST) activities were determined in the CL at specific developmental stages of the luteal phase. The intensity of apoptotic DNA fragmentation, characteristic of physiological cell death, was much greater in CL at late luteal phase than at early and mid-luteal phase, concomitantly with the diminution in the plasma progesterone concentrations from mid-to late luteal phase. SOD1 and GPX activities increased from early to mid-luteal phase, and increased further at late luteal phase. SOD2 and GST activities were not different between early and mid-luteal phase, but increased at late luteal phase. GSR activity was not different between any luteal phase examined. NOS activity decreased from early to mid- and late luteal phase. These results show that the activities of SOD1, SOD2, NOS, GPX, GSR and GST in the sheep CL are subject to major changes during the estrous cycle, and that the anti-oxidant and pro-oxidant enzymatic capacities of luteal cells are not correlated with cell steroidogenic status and integrity during the late luteal phase.


Gold nanorods-based multicolor immunosensor for visual detection of enterovirus 71 infection.
Based on the etching of gold nanorods (GNRs) and enzyme-linked immunosorbent assay (ELISA), a multicolor immunosensor for visual detection of enterovirus 71 infection is proposed. Once the immunocomplex is formed, the horseradish peroxidase bound to the ELISA plate oxidizes 3,3',5,5'-tetramethylbenzidine (TMB) into TMB2+ in the presence of hydrogen peroxide. Subsequently, TMB2+ quantitatively etches GNRs to the short GNRs, leading to a blue shift of longitudinal localized surface plasmon resonance and corresponding color responses. This change is used to develop two types of cut-off standards, which respond to the human anti-enterovirus at a concentration of 71 IgM antibody. The method has been validated with clinical serum samples and showed high sensitivity and specificity . This visual immunosensor has an important application value for point-of-care detection of EV71, especially in areas lacking detection equipment. Graphical abstract.


Separation of gliadin at pH 3.1 in a polyacrylamide gel suitable for blotting procedures.
A polyacrylamide gel electrophoresis system for the separation of gliadin at acidic pH is described. The gel is cast at neutral pH with polymerization in 20 min. Equilibration of the gel to pH 3.1 takes place during the electrophoresis. The gel is highly uniform with good mechanical properties and therefore suitable for blotting procedures.


Advancing edema detection: Harnessing the power of machine learning and near infrared spectroscopy for cerebral and cerebellar edema assessment.
Edema, characterized by brain swelling, is a common response observed in various brain injuries. Timely detection of edema is crucial to mitigate the associated risks and improve patient care. This study evaluates the efficacy of CEREBO®, a non-invasive machine learning-powered near-infrared spectroscopy (mNIRS) based device, in detecting edema. The study was conducted on 234 participants with suspected head injuries who underwent simultaneous CEREBO® scans and CT head scans. The results of the study showed that CEREBO® effectively identified edematous lobes, achieving a sensitivity of 95.7%, specificity of 97%, and accuracy of 96.9% for cases with intracranial hemorrhage (ICH). Additionally, for cases without ICH, the device exhibited a sensitivity of 100%, specificity of 97.2%, and accuracy of 97.2%. Two cases were reported where CEREBO® failed to detect edematous ICH. The study highlights the potential of CEREBO® as a valuable tool for early detection of pre-symptomatic edema and ICH, enabling timely interventions and improved patient care. The findings support the reliability of near-infrared spectroscopy as a diagnostic modality for edema.


Oxidation of polyaromatic hydrocarbons in systems containing water miscible organic solvents by the lignin peroxidase of Gleophyllum striatum MTCC-1117.
Lignin peroxidase has been purified to homogeneity using a process of concentration by ultrafiltration and anion exchange chromatography on diethylaminoethyl (DEAE) cellulose from the liquid culture filtrate of the brown rot fungi Gleophyllum striatum MTCC-1117. The molecular mass of the purified enzyme is 43 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The K(m) values for the enzyme using veratryl alcohol, hydrogen peroxide and n-propanol were 66 microM, 82 microM and 476 microM, respectively. The pH and temperature optima of the enzyme were 2.8 and 25 degrees C, respectively. The enzyme is completely inhibited by 20% of the water miscible organic solvents acetone dioxane, diethylether, acetonitrile and dimethylformamide. The lignin peroxidase oxidizes polycyclic aromatic hydrocarbons pyrene, acenaphthene, anthracene, dibenothiophene and 9-methyl anthracene.


Double-blind randomised crossover trial comparing isosorbide dinitrate cream and oral sustained-release tablets in patients with angina pectoris.
Percutaneous isosorbide dinitrate cream and sustained-release tablets were compared in a double-blind randomised crossover trial in 28 patients with coronary artery disease and chronic stable angina pectoris. Twenty-two patients completed the trial. Both preparations significantly increased the mean exercise time to the onset of angina (P less than 0.001) and to termination of exercise (P less than 0.001) compared to the pre-treatment period. There were no significant differences between the cream and tablets with respect to frequency of anginal attacks, glyceryl trinitrate consumption, heart rate and ST segment depression at the onset of angina, ST segment depression at maximal exercise and the double product of heart rate and systolic blood pressure at maximal exercise. Equal numbers of patients expressed preference for cream and tablets. We conclude that in this group of patients isosorbide dinitrate sustained-release tablets have no clinical advantage over isosorbide dinitrate cream which, may, therefore, be of particular value for those patients with angina pectoris who dislike taking tablets or who prefer this form of nitrate preparation.


Plant uncoupling protein in mitochondria from aged-dehydrated slices of Jerusalem artichoke tubers becomes sensitive to superoxide and to hydrogen peroxide without increase in protein level.
We investigated the occurrence of the plant Uncoupling Protein (UCP) in mitochondria isolated from both fresh (f-JAM) and aged-dehydrated (a-d-JAM) slices of Jerusalem artichoke tubers (Helianthus tuberosus L.). The presence of UCP was shown by immunological analysis and its function was investigated by measuring the decrease of the mitochondrial membrane potential due to linoleic acid (LA) and its inhibition by purine nucleotides under conditions in which the adenine nucleotide translocator (ANT) was inhibited by atractyloside (Atr). f-JAM and a-d-JAM had the same protein content, but differed from one another with respect to purine nucleotide inhibition, substrate specificity, and sensitivity to ROS. Hydrogen peroxide and superoxide anion, generated in situ by xanthine plus xanthine oxidase, caused a significant increase in the UCP function in a-d-JAM, but not in f-JAM. This occurred in a manner sensitive to ATP, but not to Atr, thus showing that ANT has no role in the process. The dependence of the rate of membrane potential decrease on increasing LA concentrations, either in the absence or the presence of ROS, showed a sigmoidal saturation both in f-JAM and a-d-JAM. However, addition of ROS in a-d-JAM resulted in about 40% increase of the Vmax value, with no change in the K0.5 (about 20 microM), whereas in f-JAM no effect on either the Vmax or K0.5 (about 28 microM) was found. Furthermore, a decreased ROS production as a result of LA addition was found in both f-JAM and a-d-JAM, the effect being more marked in a-d-JAM.


A Highly Selective and Sensitive Peptide-Based Fluorescent Ratio Sensor for Ag.
A fluorescence ratio sensor based on dansyl-peptide, Dansyl-Glu-Cys-Glu-Glu-Trp-NH2 (D-P5), was efficiently synthesized by Fmoc solid phase peptide synthesis. The sensor exhibits high selectivity and sensitivity for Ag+ over 16 metal ions in 100 mM sodium perchlorate and 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer solution by fluorescence resonance energy transfer. The 1:1 binding stoichiometry of the sensor and Ag+ is measured by fluorescence ratio response and the job's plot. The dissociation constant of the sensor with Ag+ was calculated to be 6.4 × 10-9 M, which indicates that the sensor has an effective binding affinity for Ag+. In addition, the limit of detection of the sensor for Ag+ was determined to be 80 nM, which also indicates that the sensor has a high sensitivity to Ag+. Result showed that the sensor is an excellent Ag+ sensor under neutral condition. Furthermore, this sensor displays good practicality for Ag+ detection in river water samples without performing tedious sample pretreatment, as well as for silver chloride detection.


Strengthening primary care: The Veneto Region's model of the Integrated Medical Group.
This paper aims to illustrate the development of the Veneto Region's (Italy) new primary care model and to report on the preliminary results. Achieving integrated management and continuity of care are the two main aims of the Veneto Region's health planning legislation for 2012-2016. Under this framework, and to meet new emerging population needs, it has become necessary to adopt a new primary care model that embraces multi-professional teams. In response the Veneto Region has developed the Integrated Medical Group (IMG), launched in 2016. The Integrated Medical Group is an innovative model at both the regional and national level and represents a key element of the health care system. It targets several goals: it provides more effective care than in the past; guarantees services within the region while optimizing the use of resources, through integrated patient care and its accompanying care pathways; it builds dialogue between hospitals and community based primary care services; develops relationships of trust between doctors and patients, pursuing shared team goals and enhances the different skills and roles of their constituent members. Regional legislation sets challenging objectives, stating that by the end 2017, 60% of all GPs in the region should conduct their activities as part of an IMG, with a further target of 80% by the end 2018.


Early-spring gas exchange and uptake of deuterium-labelled water in the poikilohydric fernPolypodium virginianum.
This study was carried out to determine if the desiccation-tolerant fernPolypodium virgimanum L. ecologically resembles lower plants by absorbing atmospheric water through its fronds and actively growing in early spring when the soil along cliff edges is still frozen. Three times between February and April, 1991,P. virginianum clonal mats were treated with deuterium-labelled water. Following each application, fronds were collected over several days and analyzed for the presence of deuterium. Two treatment groups plus a control were used: fronds were sprayed directly while covering the soil, or the roots were watered while protecting the fronds. The control mats were left untreated. Soil, air, and frond temperatures, plus photosynthesis and frond conductance were monitored throughout the study period. At subfreezing temperatures in February, no labelled water was taken up from the soil and no photosynthesis took place. Small amounts of label were absorbed from the soil in March during freeze-thaw cycles when rates of photosynthesis and stomatal conductance were both low. Large amounts of label were taken up from the soil in April when the soil was fully thawed and gas exchange was at normal seasonal levels. Label was not absorbed directly through the fronds when the plants were actively growing. Despite the desiccation tolerance ofP. virginianum, the timing and patterns of its water uptake and gas exchange in early spring resemble those found in higher vascular plants, not poikilohydric lower plants.


[Policy decisions from a societal perspective: local or national evaluation of health related quality of life not necessary].
Research among a sample of the Dutch population has shown that different relative values are assigned to some of the five sub-domains of the 'Euro-Quality of life, five dimensions' (EQ-5D) questionnaire when compared to the current English values. These findings might be interpreted as proof that the resulting 'tariffs' should also differ across countries. Conversely, one could argue that the current Oxford tariffs are simply inadequate. Clearly, decisions for individual patients should be based on the individual's preferences. However, policy decisions taken from a societal perspective should be based on a global value system. It would seem that a single Western European tariff would be preferable to a whole range of national tariffs.


A novel, simple, validated and reproducible instrument for assessing provocation threshold levels in patients with symptomatic dermographism.
Symptomatic dermographism is a common urticarial condition. There is a need for an objective method to determine the provocation threshold for patients, in order to facilitate individualized diagnosis and treatment. To compare the dermal responses evoked by a new type of dermographometer (FricTest) with those evoked by a spring-loaded dermographometer (the Dermographic tester). Dermal provocation was performed in 30 patients with symptomatic dermographism and 30 healthy controls. The FricTest consists of six tips of varying length, which are stroked over the skin, while the Dermographic tester has a single tip. The widths and volumes of the resulting weals were measured. Both instruments were similar in their ability to produce dermal responses. The weal widths of 1 and 3 mm induced by the FricTest were used as the provocation thresholds to distinguish between patients and controls, and to indicate the different levels of severity within the patient group. The FricTest was easy to use and produced an objective response. This simple and inexpensive instrument could be used to individualize diagnosis and treatment of patients with symptomatic dermographism, allowing for better personalized management.


Evolution of a unique seed maturity pattern in Croton bonplandianum Baill strengthens ant-plant mutualism for seed dispersal.
The female flowers of Croton bonplandianum bear nectar glands which become active during fruit maturation and attain peak activity just prior to the splitting of fruits. This temporal specificity of nectar gland activity is shown to facilitate seed dispersal by ants, which are attracted to the plant only during the fruit maturation period. The nectar glands establish a "nectar influence zone" with a radius of 60 cm around the plant within which seed dispersal by ants is effective. Seed dispersal by ants is facilitated only if the seeds are placed within this nectar influence zone. This is accomplished by an intriguing evolutionary shift in the maturation pattern of the fruits. Unlike the usual acropetal development, fruit maturation in Croton is temporally asymmetrical, with the fruits nearer the parental axis maturing early. This unique pattern of fruit development together with the polychasial branching system leads to a concentration of seeds within the nectar influence zone and enhances seed dispersal by ants. The proximate factors responsible for this asynchronous fruit maturity were investigated.


Impact of metabolic syndrome on the outcome of patients with stable coronary artery disease: 2-year follow-up of the MASS II study.
We characterized the impact of the metabolic syndrome (MetS) and its components on cardiovascular adverse events in patients with symptomatic chronic multivessel coronary artery disease, which have been followed prospectively for 2 years. Patients enrolled in the MASS II study were evaluated for each component of the MetS, as well as the full syndrome. The criteria for MetS were fulfilled in 52% of patients. The presence of MetS (P<0.05), glucose intolerance (P=0.007), and diabetes (P=0.04) was associated with an increased mortality in our studied population. Moreover, despite a clear tendency for each of its components to increase the mortality risk, only the presence of the MetS significantly increased the risk of mortality among nondiabetic study participants in a multivariate model (P=0.03, relative risk 3.5, 95% confidence interval 1.1-6). Finally, MetS was still associated with increased mortality even after adjustment for diabetes status. These results indicate a strong and consistent relationship of the MetS with mortality in patients with stable coronary artery disease. Although glucose homeostasis seems to be the major force driving the increased risk of MetS, the operational diagnosis of MetS still has information for stratifying patients when diabetes information is taken into account.


The detuning factor in the dynamics of interlimb rhythmic coordination.
Dynamical models of two coupled biological oscillators interpret the detuning term as an arithmetic difference between the uncoupled frequencies, delta omega = (omega 1-omega 2). This delta omega interpretation of detuning was addressed in four experiments in which human subjects oscillated pendulums in their right and left hands in 1:1 frequency locking in antiphase (Experiments 1-3) or inphase (Experiment 4). Differences between the uncoupled frequencies were manipulated through differences in the equivalent simple pendulum lengths, and the effects of this manipulation on the detuning of relative phase from pi or O and the standard deviation of relative phase SD phi were measured. In Experiment 1, the same values of omega i were satisfied by several different physical configurations. The experiment confirmed that the detuning term is related strictly to the uncoupled frequencies rather than to other physical characteristics of the oscillators. Experiments 2, 3 and 4 showed, however, that the particular dependency of fixed point drift and SD phi on delta omega depends on the particulars of omega 1 and omega 2. With variations in delta omega brought about by different omega 1 and omega 2 that always formed a constant ratio, fixed point drift related inversely to delta omega, and SD phi varied with delta omega in ways that depended on the magnitude of the constant ratio. These outcomes do not conform to expectations from models of coordination dynamics that interpret detuning as (omega 1-omega 2).


Volume replacement is associated with a diminished osmolar effect of mannitol in patients with acute brain injury.
Animal experiments recently demonstrated that replacing urinary loses with crystalloid diminishes the therapeutic effect of mannitol by reducing the increase in osmolality. We aimed to investigate whether this effect is similarly seen in in brain-injured patients by studying the association between total body fluid balance (TBB) and the osmolar response to mannitol. We performed a retrospective cohort study of adult patients with acute brain injury between 2015 and 2021 who received ≥ 2 doses of mannitol within 8 hours and no intercurrent concentrated saline solution. We analyzed the association between the change in TBB (∆TBB) and change in osmolality (∆Osm) before and after mannitol in a linear model, both as univariate and after adjustment for common confounding factors. Of 6,145 patients who received mannitol, 155 patients met inclusion criteria (mean age 60 ± 17 years, 48% male, 83% white). The mean total mannitol dose was 2 ± 0.5 g/kg and the mean change in plasma osmolality was 7.9 ± 7.1 mOsm/kg. Each 1 L increase in ∆TBB was associated with a change of -1.1 mOsm/L in ∆Osm (95% CI [-2.2, -0.02], p = 0.045). The magnitude of association was similar to that of total mannitol dose and remained consistent in an adjusted model and after excluding outliers. In patients with acute brain injury, a positive TBB is associated with a diminished mannitol-induced increase in plasma osmolality. Future prospective studies are needed to confirm these findings and their influence on the therapeutic effect of mannitol.


Therapeutic outcome of 6198 interferon-naïve Egyptian patients with chronic hepatitis C: a real-life experience and lessons to be learned in DAAs' era.
Antiviral therapy for HCV infection has been validated in randomized controlled clinical trials, but its value in the real world is less well studied. There is relatively little data on real-world responses to interferon-based therapies for patients with genotype 4 infection. We aimed to examine experience with large-scale access to antiviral therapy in chronic HCV in a real-life clinical setting in Egypt. Detailed pretreatment data of 6198 IFN-naïve chronic HCV patients who had received PEG-IFN/RBV therapy at Cairo-Fatemic Hospital, Egypt, between 2009 and 2012 were obtained from the HCV database. At week 12, 95.7% of patients had undetectable HCV RNA, and by week 24 and 48, breakthrough was 6% and 4%, respectively. However, 43.7% of patients discontinued treatment prematurely, and intent to treat end of treatment response was 44.6% (79.3% per protocol). Sustai-ned response data were available from only 1281 patients and was 84.9%. Haematological abnormalities were comparable in patients who did or did not comply with therapy. This is the first real-world, large-scale experience of antiviral therapy in chronic HCV in Egypt. Suboptimal response in HCV predominantly genotype 4 was mainly driven by noncompliance as well as gaps in the healthcare system leading to treatment discontinuation. These results need to be considered in the era of all oral antiviral regimes.


Serial electropharmacologic studies in patients with ischemic heart disease and sustained ventricular tachyarrhythmias: when is drug testing sufficient?
Serial testing of antiarrhythmic drugs by programmed electrical stimulation can be costly in time, expense and risk. The purpose of this study was to evaluate the results of serial electropharmacologic tests for similarities that might obviate the need for protracted drug testing. Serial electropharmacologic testing was performed in 283 patients with coronary artery disease and clinical sustained ventricular tachycardia (VT) or fibrillation (VF). Drug tests were defined as concordant if sustained VT or VF could be consistently induced, or failed to be consistently induced during all such trials in a given patient. The following drugs were included for testing: procainamide, quinidine and disopyramide (class IA); phenytoin, mexiletine and tocainide (class IB); and flecainide and encainide (class IC). All patients were serially tested with > or = 2 (mean and median, 3) antiarrhythmic agents regardless of results from drug-free testing or initial acute drug testing. Overall, the results of serial drug trials directed by programmed stimulation were concordant in more than two thirds of patients. Concordance was comparably high whether patients were serially tested with drugs within the same antiarrhythmic class, or with drugs from differing classes, and was not related to patients' clinical or electrophysiologic characteristics. Protracted serial electropharmacologic testing does not appear necessary for predicting successful or unsuccessful antiarrhythmic drug therapy in survivors of clinical VT or VF. Single drug testing can identify most patients whose arrhythmia will or will not respond to medications.


24-hour shear bond strength of metal orthodontic brackets bonded to porcelain using various adhesion promoters.
Clinically, orthodontists are often faced with the difficulties of bonding to porcelain crowns, veneers, or bridges. Traditional methods of dealing with this are often time-consuming and generally esthetically unacceptable to patients. Current interest involves the use of organosilane primers with or without NTG-GMA and BPDM resins to aid in chemically bonding porcelain with traditional orthodontic adhesives. This study compared the bond strength of three types of adhesion promoters: Ormco Porcelain Primer (OR) (Ormco Corp., Glendora, Calif.), All-Bond2 (AB2) (Bisco Dental Products, Inc., Itasca, Ill.), and Scotchprime Ceramic Primer (SP) (3M, St. Paul, Minn.) with two orthodontic adhesives: Phase II (Reliance, Inc., Itasca, Ill.) and Rely-a-bond (Reliance, Inc., Itasca, Ill.). Eighty ceramometal samples were fabricated and hydrated for 1 week in distilled water before bonding. Next, the samples were etched with 2.5 % HF acid for 90 seconds, rinsed and upper central incisor metal orthodontic brackets were bonded with the various primers and adhesives. After 24 hours they were sheared off with an MTS machine at at rate of 0.5 mm/min, and the bond strength was measured. The mean shear bond strengths (MPa) with Phase II were as follows; Control 0.44 (sigma = 0.22), AB2 8.40 (sigma = 3.61), OR 13.31 (sigma = 5.79), SP 13.53 (sigma = 3.34). With Rely-a-bond, the shear bond strengths were Control 0.41 (sigma = 0.67), AB2 4.34 (sigma = 1.88), OR 9.73 (sigma = 4.58), and SP 12.40 (sigma = 3.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Drug uptake and ribonucleotide profiles of blast-enriched and blast-depleted human bone marrow cell populations.
A density cut method was used to prepare two subpopulations of bone marrow cells which were enriched (BE) and depleted (BD) respectively of blast cells. Marrow aspirates were obtained from 32 patients, 26 of whom had acute leukaemia. The uptake of a variety of chemotherapeutic agents by these two subpopulations and the acid-soluble ribonucleotide profiles of the populations were compared and significant differences were found in drug uptake by BE and BD subpopulations. For some drugs such as cytosine arabinoside, uptake was greatest by the BE cells, while for 5-azacytidine the BD subpopulation took up the greatest amount of the drug. The preparation of the BE subpopulation also permitted the recognition of several patients with acute leukaemia whose blast cells possess nondetectable levels of ATP, UTP, and GTP components in their acid-soluble fractions. The studies presented demonstrate the necessity of using purified cell populations when characterizing the drug uptake patterns and the soluble ribonucleotide profiles of the leukaemic cells. A simple method for enriching bone marrow aspirates for leukaemic cells is also presented.


Integrated care in patients with schizophrenia: results of trials published between 2011 and 2013 focusing on effectiveness and efficiency.
Overview on integrated care trials focusing on effectiveness and efficiency published from 2011 to 2013. Eight randomized controlled trials (RCTs) and 21 non-RCT studies were published from 2011 to 2013. Studies differed in several methodological aspects such as study population, psychotherapeutic approaches used, outcome parameters, follow-up times, fidelities, and implementation of the integrated care model and the nation-specific healthcare context with different control conditions. This makes it difficult to draw firm conclusions. Most studies demonstrated relevant improvements regarding symptoms (P=0.001) and functioning (P=0.01), quality of life (P=0.01), adherence (P<.05) and patient's satisfaction (P=0.01), and reduction of caregiver's stress (P<0.05). Mean total costs were favoring or at least equalizing costs but with positive effects found on subjective health favoring integrated care models. There is an increasing interest in the effectiveness and efficiency of integrated care models in patients with mental disorders, specifically in those with severe and persistent mental illness. To increase generalizability, future trials should exactly describe rationales and content of integrated care model and control conditions.


Impairment of cardiac function in hypertensive patients with Type 2 diabetes: a LIFE study.
Type 2 diabetic patients with hypertension have an increased left ventricular (LV) mass and impaired cardiac function compared to hypertensive patients without diabetes. However, it is unknown if the impaired cardiac function can be explained solely by LV hypertrophy, or is independently related to diabetes. The aim of the present study was to compare LV function between diabetic and non-diabetic hypertensive patients with electrocardiographic LV hypertrophy. In 937 patients participating in the LIFE echocardiographic substudy, all echocardiograms were centrally evaluated by a core reading centre measuring LV mass, systolic and diastolic LV function. Known diabetes was present in 105 patients. Left ventricular mass was similar in diabetic and non-diabetic patients. Endocardial systolic LV function, estimated by LV ejection fraction, was reduced and indices of midwall systolic LV function were impaired in the diabetic patients. Diastolic LV filling pattern was impaired and arterial stiffness, measured by pulse pressure/stroke index, was increased in diabetic patients. Systolic and diastolic LV function in hypertensive patients with electrocardiographic LV hypertrophy and diabetes are impaired independent of LV mass, most likely reflecting the adverse effects of diabetes per se.


Enhancer of zeste homolog 2 activates wnt signaling through downregulating CXXC finger protein 4.
Through silencing tumor suppressor genes, epigenetic changes can activate signaling pathways important to cancer development. In this report, we found an epigenetic contribution to the aberrant activation of wnt signaling in human gastric cancer. CXXC4 (CXXC finger protein 4) was identified as a novel target of EZH2 (enhancer of zeste homolog 2), and EZH2 promotes the activation of wnt signaling by downregulating CXXC4 expression. CXXC4 inhibits the growth of gastric cancer cells both in vitro and in vivo through inactivating wnt signaling. In contrast, depletion of CXXC4 activates wnt signaling and promotes the anchorage-independent growth of nontumor gastric epithelial cells. CXXC4 is downregulated in gastric carcinoma tissues and its downregulation is associated with poor outcome of gastric cancer patients (hazard ratio: 5.053, P < 0.05). Through its binding to dishevelled (Dvl), CXXC4 stabilizes the destruction complex of β-catenin to inhibit wnt signaling. Two critical amino acid residues in CXXC4, K161 and T162 were found to be important to its binding to Dvl and the growth inhibitory effect of CXXC4. In summary, EZH2 promotes the activation of wnt signaling in gastric carcinogenesis through the downregulation of CXXC4 expression. CXXC4 is a novel potential tumor suppressor directly regulated by EZH2, and its expression is a significant prognosis factor for patients with early stages of gastric cancer.


Effects of (-) -epigallocatechin gallate in liver of an animal model of combined (physical and mental) fatigue.
Fatigue can be classified as physical and mental depending on the cause. However, in our daily lives, combined fatigue, which is the combination of physical and mental fatigue, is most often experienced. In this study, the effects of (-)-epigallocatechin gallate (EGCg) on combined fatigue were assessed. To produce an animal model of combined fatigue, rats were kept in a cage filled with water to a height of 1.5 cm for 5 d. To evaluate the extent of fatigue, the rats swam with a load of steel rings that weighed approximately 8% of their body weight and were attached to their tails. Fatigued rats treated with EGCg (50 or 100 mg/kg intraperitoneally [not for 25 mg/kg]) for 5 d could swim longer than fatigued animals given saline. Although levels of thiobarbituric acid-reactive substances in the plasma, brain, and skeletal muscle were not different between control and fatigued rats, thiobarbituric acid-reactive substance levels were higher in livers of fatigued animals than in livers of control animals. Oral intake of EGCg (50 or 100 mg/kg) for 5 d significantly decreased thiobarbituric acid-reactive substance levels in livers of fatigued animals. These results suggest that EGCg (50 or 100 mg/kg) is effective for attenuating fatigue. EGCg given orally appears to have an antioxidant effect on the oxidatively damaged liver of fatigued animals.


Evaluation and Treatment of Constipation in the Geriatric Population.
Chronic constipation affects one-third of the US population and occurs disproportionately in the elderly and female individuals, increasing in older individuals who are institutionalized. This condition has a significant impact on health care costs and quality of life. Clinicians need to consider primary as well as secondary causes of constipation in elderly individuals because the cause is often multifactorial. Diagnostic algorithms should eliminate red-flag symptoms that may indicate a malignancy but also consider pelvic floor dysfunction, which is more common in this age group. An appropriate treatment plan is tailored to the severity of the patient's symptoms.


An insight into the potentially old-wonder molecule-quercetin: the perspectives in foresee.
Use of phyto-medicine and digitalization of phyto-compounds has been fallen enthralling field of science in recent years. Quercetin, a flavonoid with brilliant citron yellow pigment, is typically found in fruits and leafy vegetables in reasonable amount. Quercetin's potentials as an antioxidant, immune-modulator, antiinflammatory, anti-cancer, and others have been the subject of interest in this review. Although, profiling the insights in to the molecular characterization of quercetin with various targets provided the loop-holes in understanding the knowledge for the aforementioned mechanisms, still necessitates research globally to unearth it completely. Thus, the available science on the synthesis and significant role played by the old molecule - quercetin which does wonders even now have been vividly explained in the present review to benefit the scientific community.


Apoptotic DNA fragments in serum of patients with muscle invasive bladder cancer: a prognostic entity.
Patients with malignancies often possess increased concentrations of cell-free serum DNA. In this study, we investigated serum DNA levels in each 45 patients with bladder cancer (BCA) undergoing radical cystectomy and with benign prostate hyperplasia. A quantitative real-time PCR was used to amplify a 124 bp (PTGS2; mostly apoptotic origin) and a 271 bp (Reprimo; mostly necrotic origin) DNA fragment. Changes in the origin of DNA fragments were specified as the Apoptosis Index (AI, ratio of 124 bp/271 bp fragments). Small and large fragments were increased (p<0.001 and p=0.041) in BCA patients. The AI increase suggests that DNA fragmentation was mostly (p<0.001) caused by apoptosis. High levels of small DNA fragments distinguished between BCA and BPH with high sensitivity (96%) and moderate specificity (62%). DNA levels and the AI were not correlated with clinicopathological parameters. However, an increased AI was correlated with BCA-specific mortality in a multivariate analysis (p=0.011) indicating that the AI is an independent prognostic factor. Thus, cell-free DNA seems to be a useful prognostic marker in patients with BCA.


Enhanced cellular fibronectin accumulation in chondrocytes treated with vitamin A.
Chick sternal chondrocytes cultured at high cell density lack fibronectin as a surface protein, while vitamin A-treated chondrocytes contain it as the major cell surface protein. We investigated the mechanism of fibronectin accumulation under these conditions. Control chondrocytes synthesized nearly as much fibronectin as vitamin A-treated chondrocytes, but it was secreted primarily into culture medium. Althought the fibronectin of control chondrocytes was of a slightly lower apparent molecular weight than the fibronectin synthesized by the treated cells, it bound as effectively to the cell layer of both normal and treated cells. In contrast, the vitamin A-treated cultures were 2.7 fold more effective in binding fibronectin synthesized by either control or treated cells. Thus in chondrocytes, vitamin A appears to regulate the cellular accumulation of fibronectin by increasing the ability of the cell layer to bind fibronectin rather than by altering its synthesis or its adhesivity for the cell layer.


A novel, conserved and possibly functional motif "WHWGHTW" in mitochondrial transcription across Bilateria.
The animal mitogenomes which undergone a reductive evolution has an obvious loss of coding capacity compared to their known closest relatives, but it has not yet been fully investigated why and how the intergenic regions do not encode protein and have no known functions, are stably maintained, replicated, and transmitted by the genome. These relatively small intergenic regions may not be under neutral evolution and they may have functional and/or regulatory roles that have yet to be identified. Here, the distribution pattern, sequence content and location of a novel sequence motif of 'WWWGHTW' were bioinformatically investigated and characterised by constructing a sampling mitogenome dataset of 1889 species from 14 phyla representing the clade of Bilateria. This motif is reverse complementary of the previously described DmTTF binding sequence and found in the nd4L- (X) -trnT gene cluster. This cluster commonly exhibits a strand displacement region and an intergenic region among the bilaterian superphylums, particularly in Ecdysozoa. This motif may be accepted as a substrate providing binding sites for the specific interaction with transcription factors because of (i) its reverse complementarity of previously described DmTTF binding sequence, and (ii) the possession of G and T nucleotides in the fourth and sixth positions, (iii) the bias on T and G nucleotides instead of C and A in the degenerated positions. This suggestion is also supported by the presence of a strand displacement region in the nd4L- (X) -trnT gene cluster, particularly in Ecdysozoa consisting of the most rearranged mitogenomes among the bilaterian superphylums.