Ureterouterine fistula post caesarean section: a case report.
Ureteric injury is usually iatrogenic in origin, in particular as a result of laparoscopic or gynaecological surgery. Of those possible complications of ureteric injury, uretero-uterine fistulae are a rarity. The most common presentation of uretero-uterine fistulae is in women who have had a caesarean section. We present the case of a 35 year old woman who presented with continuous vaginal discharge three weeks after undergoing caesarean section. Management of ureterouterine fistulae aims to conserve renal function and restore ureteral integrity. The relative rareity of such fistulae however means that there are no clear guidelines on their management. The resolution of this case and general management of uretero-uterine fistulae are discussed.


Assessing & preventing medication interactions.
The use of multiple drugs to treat medical conditions has become a common practice that significantly increases the risk of drug interactions.This article describes three types of drug interactions by clarifying how these occurrences transpire within the body. Practical strategies for preventing drug interactions are provided.


Toll-receptor 9 gene in the black tiger shrimp (Penaeus monodon) induced the activation of the TLR-NF-κB signaling pathway.
Toll receptors are important pathogen recognition receptors (PRRs) in shrimps, which play a vital role in defending against virus and bacterial challenge. In this paper, the characterization and functional analysis of a Toll9 receptor gene from Penaeus monodon was performed in HEK293T cells. Data showed that PmToll9 can activate the NF-κB promoter activities of TLR pathway, while ISRE and IFN-β promoter cannot be activated obviously in HEK293T cells using dual-luciferase reporter system. The downstream immune factors of IL-8, IκB-α, and TRAF6 were activated by PmToll9 and IL-8 showed the most significant up-regulation in expression levels, indicating the activities of NF-κB can be mediated by PmToll9. Six LRRs-deletion mutants were constructed and results showed these mutants had obvious declines in luciferase activities, among which the mutant pCMV-DeLRR4 showed the most significant decline. qPCR data indicated LRRs-deletion mutants efficiently impaired the activities of the downstream immune factors IL-8, IκB-α, and TRAF6. It demonstrates that LRRs-deletion mutants could result in the weaken abilities of PmToll9 in signaling transduction. Overexpression of PmToll9-GFP fusion protein in Hela cells revealed the primary cellular localization of PmToll9 is in the cytoplasm.


Role of additive manufacturing in medical application COVID-19 scenario: India case study.
This paper reviews how the Additive Manufacturing (AM) industry played a key role in stopping the spread of the Coronavirus by providing customized parts on-demand quickly and locally, reducing waste and eliminating the need for an extensive manufacturer. The AM technology uses digital files for the production of crucial medical parts, which has been proven essential during the COVID-19 crisis. Going ahead, the 3D printable clinical model resources described here will probably be extended in various centralized model storehouses with new inventive open-source models. Government agencies, individuals, corporations and universities are working together to quickly development of various 3D-printed products especially when established supply chains are under distress, and supply cannot keep up with demand.


Whey protein consumption following fasted exercise reduces early postprandial glycaemia in centrally obese males: a randomised controlled trial.
Acute submaximal exercise and whey protein supplementation have been reported to improve postprandial metabolic and appetite responses to a subsequent meal independently. We aimed to examine the combination of these strategies on postprandial responses to a carbohydrate-rich breakfast. Twelve centrally obese males (age 41 ± 3 years, waist circumference 123.4 ± 2.9 cm), completed three trials in a single-blind, crossover design. Participants rested for 30 min (CON) or completed 30 min low-moderate-intensity treadmill walking (51 ± 1% [Formula: see text]) followed immediately by ingestion of 20 g whey protein (EX + PRO) or placebo (EX). After 15 min, a standardised breakfast was consumed and blood, expired gas and subjective appetite were sampled postprandially. After 240 min, an ad libitum lunch meal was provided to assess energy intake. During EX + PRO, post-breakfast peak blood glucose was reduced when compared with EX and CON (EX + PRO: 7.6 ± 0.4 vs EX: 8.4 ± 0.3; CON: 8.3 ± 0.3 mmol l-1, p ≤ 0.04). Early postprandial glucose AUC0-60 min was significantly lower under EX + PRO than EX (p = 0.011), but not CON (p = 0.12). Over the full postprandial period, AUC0-240 min during EX + PRO did not differ from other trials (p > 0.05). Peak plasma insulin concentrations and AUC0-240 min were higher during EX + PRO than CON, but similar to EX. Plasma triglyceride concentrations, substrate oxidation and subjective appetite responses were similar across trials and ad libitum energy intake was not influenced by prior fasted exercise, nor its combination with whey protein supplementation (p > 0.05). Following fasted low-moderate-intensity exercise, consuming whey protein before breakfast may improve postprandial glucose excursions, without influencing appetite or subsequent energy intake, in centrally obese males. NCT02714309.


[Comparison of the effectiveness of cognitive restructuring and systematic desensitization in reducing high-stakes test anxiety].
This study aimed to compare the effectiveness of systematic desensitization (behavioral therapy and cognitive restructuring (cognitive therapy) in reducing high-stakes test anxiety. We hypothesized that cognitive restructuring would be superior to systematic desensitization in reducing the severity of the cognitive symptoms of anxiety, whereas systematic desensitization would be superior to cognitive restructuring in reducing the severity of the physiological symptoms of anxiety. The study included 50 (36 female and 14 male) high school graduates and high school seniors aged 16-22 years (mean:18.3 years) that experienced test anxiety while taking their university entrance exam. Participants were randomly assigned to the behavior therapy or cognitive therapy groups. Participants in both groups received 9 sessions of structured group therapy with the same therapist. Each participant's level of anxiety and depression, psychiatric symptoms, and dysfunctional thoughts were measured throughout the therapy process. Statistical analysis showed that there was a significant decrease in the score of each outcome measure employed in both groups. There weren't any significant differences in terms of the alleviation of the cognitive symptoms of anxiety, as measured with the Dysfunctional Attitudes Scale, or physiological symptoms, as assessed with the Beck Anxiety Inventory between the 2 groups. The 2 therapy methods resulted in statistically significant reductions in the level of test anxiety, as well as state anxiety, trait anxiety, self-reported depression, and general symptom levels. The behavioral and cognitive therapies were equally effective in reducing the severity of the cognitive and physiological components of test anxiety.


The effect of fibrinolytic inhibition in the resolution of experimental vitreous hemorrhage.
Complete inhibition of vitreous fibrinolytic activity with 4-amino-methylcyclohexane carbonic acid was associated with significantly delayed resolution of vitreous hemorrhages in rabbits. However, polyacrylamide gel electrophoresis indicated but a slight delay in the removal of the fibrin component of vitreous clots, and most of the residual vitreous opacity comprised intact red blood cells. Fibrin degradation products may act as chemotactic agents, promoting the removal of red blood cells by leukocytes; hence, their absence in treated rabbits might explain in part the delayed red blood cell clearance.


Hepatic multi-nodular focal fatty metamorphosis in acquired porphyria cutanea tarda. Sonographic, CT, and MRI features.
The authors report the sonographic, computed tomography (CT), and magnetic resonance imaging (MRI) findings in a patient with acquired porphyria cutanea tarda and hepatic multi-nodular focal fatty metamorphosis. There has only been one previous description of an association between these two conditions. The diagnosis was confirmed by histological analysis of a liver biopsy specimen. Symptomatology related to the hepatic abnormality may be due to an inflammatory reaction induced by the presence of uroporphyrin crystals in the liver. Each of the radiological techniques demonstrated unusual hepatic abnormalities and, in particular, MRI showed poorly defined areas in the liver which, on T2-weighted sequences, exhibited a hypersignal with fat saturation. Treatment of porphyria cutanea tarda led to clinical remission and resolution of radiological abnormalities.


Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies.
In this retrospective study we compared accuracy of panel reactive antibodies (PRA) with serum soluble CD30 (sCD30) contents in predicting acute rejection crisis post-renal transplant. Pre-transplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin inhibitor-based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven acute rejection (AR) episodes within first six months of the transplant. Post-transplant sera of patients with AR were tested for the presence of donor-specific HLA antibodies (DSA). Overall AR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared with those patients negative for both the tests (36% vs. 5%, p=0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% vs. 5%, p=0.04). Of the 18 patients with AR, 14 were positive for sCD30, and 13 of them (93%) developed DSA post-transplant (p=0.001). These data showed that patients positive for sCD30 contents are at high risk for the development of DSA and AR post-transplant regardless of their pre-transplant PRA.


End-of-life care for HIV-infected patients with malignancies: A questionnaire-based survey.
The number of HIV-infected patients who require palliative or end-of-life care is increasing, and the status of end-of-life care for HIV patients with malignancies is unclear. This study aimed to evaluate the end-of-life care provided to HIV patients with malignancies in Japan. National cross-sectional questionnaire-based survey. Questionnaires were delivered to the medical staff of 378 regional core hospitals/core hospitals for AIDS and 285 palliative care units in Japan. Data were collected between August and October 2013. Overall, 226 regional core hospitals/core hospitals for AIDS (59.8%) responded. A total of 55 institutions (24.3%) provided end-of-life care to HIV patients with malignancies. Regarding the place of death of the patients, 69.1% died at the institution whereas 18.2% were transferred to palliative care units. The requests of 16 (29.1%) institutions to transfer patients to palliative care units were rejected. Of the 378 palliative care units, 179 (62.8%) responded. While 13 palliative care units (4.6%) provided care to hospitalized HIV patients with malignancies, 20 (11.2%) refused to accept these patients for treatment because of a lack of experience in treating these patients and a lack of knowledge regarding HIV infection. Our findings suggest that in Japan, HIV patients with malignancies have difficulties obtaining hospitalization at a palliative care unit, which is likely due to a lack of experience among the professionals in treating such patients as well as a lack of knowledge about HIV.


Isolation, primary structure and bioactivity of schistoflrf-amide, a FMRF-amide-like neuropeptide from the locust, Schistocerca gregaria.
We have isolated a neuropeptide, related to the Phe-Met-Arg-Phe-NH2 family, from the thoracic nervous system of the locust, Schistocerca gregaria, using a purification system based on the radioimmunoassay of high pressure liquid chromatography fractions. The primary sequence of this locust peptide is Pro-Asp-Val-Asp-His-Val-Phe-Leu-Arg-Phe-NH2. The bioactivities of the native and synthetic neuropeptide are identical in both the locust heart and hindleg extensor-tibiae muscle bioassays.


[Scarf osteotomy of hallux valgus in children and adolescents].
The aim of this study was to analyze the results of surgical treatment of hallux valgus using scarf osteotomy in children and adolescents. Twelve children and adolescents (19 feet) operated on with scarf osteotomy were reviewed retrospectively with a mean follow-up of 15 months. Clinical and radiographic results were assessed. We obtained 10 good results (asymptomatic cases), 9 poor with residual symptoms such as pain or cosmetic problems. Two populations could be identified considering the metatarsus varus and distal metatarsal angle. Those with metatarsus varus >/= 10 degrees or normal distal metatarsal angle had good results. Those without metatarsus varus had poor results. There was no disturbance of growth. Scarf osteotomy can be used in children without risk of hindering growth. Nevertheless, good results can be achieved only in cases of true metatarsus varus and normal distal metatarsal angle. In other cases, a different osteotomy of the first metatarsal would be preferable.


Quantitative analysis of gains and catch-up saccades of video-head-impulse testing by age in normal subjects.
To evaluate video-head-impulse test (vHIT) results in normal subjects, to determine the normative values of vHIT for the vestibulo-ocular reflex (VOR) and to characterise the catch-up saccades (CSs). Prospective cohort study. Tertiary care academic referral centre. Fifty healthy subjects with no history of vestibular impairment, ten each in their 20's, 30's, 40's, 50's and 60's, underwent vHITs in the lateral semicircular canal plane. vHIT gains and the incidence and amplitudes of covert and overt CSs. The mean vHIT gain was 1.02 ± 0.07, and the mean gain asymmetry was 2.39 ± 1.96%, with no significant differences among age groups. CSs were observed during 22.6% of the trials and in 49% of the ears. The incidence of CSs was not associated with age. The mean velocity of CSs was 55.5 ± 16.9°/s, and its mean interaural difference was 11.8 ± 10.7°/s. vHIT gains were consistently equal to 1.0 in all age groups (20's to 60's), suggesting that abnormal criteria for vHIT gain (e.g. 0.8) and gain asymmetry (e.g. 8%) can be used, regardless of age. CSs were observed in about half of normal ears, suggesting that VOR is a hypometric system. The amplitudes and interaural difference of CSs were also similar in all age groups, suggesting that abnormal criteria for CS amplitude (e.g. 100°/s) and interaural difference (e.g. 40°/s) can be used, regardless of age.


Fluorescence imaging of the lymph node uptake of proteins in mice after subcutaneous injection: molecular weight dependence.
To use noninvasive fluorescence imaging to investigate the influence of molecular weight (MW) of proteins on the rate of loss from a subcutaneous (SC) injection site and subsequent uptake by the draining lymph nodes in mice. Bevacizumab (149 kDa), bovine serum albumin (BSA, 66 kDa), ovalbumin (44.3 kDa) or VEGF-C156S (23 kDa), labeled with the near infrared dye IRDye 680, were injected SC into the front footpad of SKH-1 mice. Whole body non-invasive fluorescence imaging was performed to quantitate the fluorescence signal at the injection site and in axillary lymph nodes. The half-life values, describing the times for 50% loss of proteins from the injection site, were 6.81 h for bevacizumab, 2.85 h for BSA, 1.57 h for ovalbumin and 0.31 h for VEGF-C156S. The corresponding axillary lymph node exposure, represented as the area of the % dose versus time curve, was 6.27, 5.13, 4.06 and 1.54% dose ∙ h, respectively. Our results indicate that the rate of loss of proteins from a SC injection site is inversely related to MW of proteins, while lymph node exposure is proportionally related to the MW of proteins in a mouse model.


Postprandial effects of dietary protein source on metabolic responses, appetite, and arterial stiffness indices in overweight and obese men: the study protocol for a randomized crossover clinical trial.
Different dietary protein sources are supposed to have various effects on metabolic responses and arterial stiffness in the postprandial period. This study aims to assess the postprandial effects of dietary protein sources, including animal-based protein (AP) and plant-based protein (PP), as part of a high-protein breakfast on appetite response, energy metabolism, and arterial stiffness in overweight and obese men. This acute randomized crossover clinical trial will be conducted at the Persian study research center at Imam Reza Hospital, affiliated with the Mashhad University of Medical Sciences, located in the northeast of Iran. Forty-six healthy overweight, and obese men aged 18-60 years will be enrolled based on the eligibility criteria. The subjects will complete two interventions (high-protein AP and PP meals) with 1 week washout period. The primary outcome will be the acute effect of the two test meals on appetite response, energy metabolism parameters, including resting metabolism rate (RMR), diet-induced thermogenesis (DIT), and substrate oxidation (SO), and arterial stiffness indices, including pulse wave velocity (PWV) and pulse wave analysis (PWA). The secondary outcomes include changes in lipemia, glycemia, and insulinemia. The findings of this study will provide novel insight regarding the acute effects of different protein sources on energy metabolism, appetite, and arterial stiffness as a significant cardiovascular disease (CVD) risk factor. It will help dieticians develop effective and efficient meal plans to improve weight reduction and maintenance in overweight/obese individuals. Iranian Registry of Clinical Trials; code: IRCT20211230053570N1; registered on February 10, 2022.


Persistent cell contacts enable E-cadherin/HMR-1- and PAR-3-based symmetry breaking within a developing C. elegans epithelium.
Tissue-wide patterning is essential to multicellular development, requiring cells to individually generate polarity axes and coordinate them in space and time with neighbors. Using the C. elegans intestinal epithelium, we identified a patterning mechanism that is informed by cell contact lifetime asymmetry and executed via the scaffolding protein PAR-3 and the transmembrane protein E-cadherin/HMR-1. Intestinal cells break symmetry as PAR-3 and HMR-1 recruit apical determinants into punctate "local polarity complexes" (LPCs) at homotypic contacts. LPCs undergo an HMR-1-based migration to a common midline, thereby establishing tissue-wide polarity. Thus, symmetry breaking results from PAR-3-dependent intracellular polarization coupled to HMR-1-based tissue-level communication, which occurs through a non-adhesive signaling role for HMR-1. Differential lifetimes between homotypic and heterotypic cell contacts are created by neighbor exchanges and oriented divisions, patterning where LPCs perdure and thereby breaking symmetry. These cues offer a logical and likely conserved framework for how epithelia without obvious molecular asymmetries can polarize.


Effect of visual acuity on biometry prediction error after cataract surgery.
To determine the effect of visual acuity on biometry prediction error. Postgraduate teaching hospital. The study was an observational case series of the first operated eye of 2149 consecutive patients who had cataract surgery. Biometry prediction error was defined as the difference between the planned refraction determined by biometry and the spherical equivalent of the final refraction. The principal outcome measure was the percentage of eyes within +/-1.00 diopter (D) of the intended refraction. This outcome was calculated for patients with visual loss caused by cataract alone, defined as eyes with a postoperative acuity of 6/6 or better, and eyes with different levels of postoperative visual acuity. Complete data were available for 1978 eyes (92%). Of these, 1438 (73%) were within +/-1.00 D of the intended refraction. When the final corrected visual acuity was 6/6 or better, the percentage of eyes within +/-1.00 D of the predicted refraction was at least 78%. When the preoperative acuity was worse than 6/60, 74% in the counting fingers group and 69% in the hand movements group with a final corrected acuity of 6/6 or better were within +/-1.00 D. This trend bordered on statistical significance (P =.05). There was a rapid reduction in the percentage of eyes within +/-1.00 D of the intended refraction as the postoperative acuity decreased because of ocular comorbidity, with a statistically significant difference between eyes with a postoperative acuity of 6/6 or better and each group with an acuity of 6/9 or worse (P<.01). In eyes without visually significant ocular comorbidity, cataract must reduce vision to 6/60 or worse before there is an increase in biometry prediction error. In contrast, ocular comorbidity that reduces the postoperative acuity causes an early and marked increase in biometry prediction error.


Effect of chronic exposure to pendimethalin on the susceptibility of rainbow trout, Oncorhynchus mykiss L., to viral hemorrhagic septicemia virus (VHSV).
In this study, the in vivo effects of chronic pollution by the active substance (AS) pendimethalin, a dinitroaniline herbicide, on the susceptibility of rainbow trout, Oncorhynchus mykiss L., to an experimental challenge with viral hemorrhagic septicemia virus (VHSV) were assessed. After four weeks of exposure to fresh water (C group) or 500 ng L(-1) of AS (P500 group), the fish were challenged by immersion in water containing 10(4) TCID(50) mL(-1) of VHSV. While exposure to pendimethalin was maintained throughout the experiment, mortalities were recorded during the 40 days post-infection (dpi) and organs were collected from dead fish for virological examination. At the end of the experiment, anti-VHSV antibodies and the classical pathway of complement activity were assessed in trout plasma. Exposure to pendimethalin significantly affected the distribution of cumulative mortality accelerating death in fish infected by VHSV. Pendimethalin appeared to decrease the Mean Time to Death (MTD) after virus treatment from 14.9 days (C-VHSV) to 10.2 days (P500-VHSV). Nevertheless, by the end of the experiment, differences in cumulative mortality were no longer observed between the two groups, which had reached the same stage (50 percent). Furthermore, a higher concentration of the virus was recovered from the pools of organs from the P500-VHSV group than the C-VHSV group. Moreover, at 40 dpi, although no significant difference was observed in the immune response between the two groups, more fish in the P500-VHSV group had set up an immune response by secreting antibodies than in the control viral group (C-VSHV).


A Multicenter Survey of Pediatric-Neonatal Transport Teams in the United States to Assess the Impact of the Coronavirus Disease 2019 Pandemic on Staffing.
The coronavirus disease 2019 pandemic has resulted in unprecedented burnout in frontline health care providers. However, the impact of the pandemic on interfacility pediatric and neonatal transport team members has not been studied. The current study uses a survey design to document the impact of the pandemic on pediatric and neonatal transport team members with a focus on staffing and resilience promotion strategies. Data for this study came from a short cross-sectional survey distributed to members of the American Academy of Pediatrics Section on Transport Medicine. Sixty-six teams responded (around 45%). Forty-one respondents (62%) reported vacancies on their transport teams, with 35 (53.8%) reporting more vacancies during the pandemic. Forty percent of highly trained registered nurses and respiratory therapists from specialty teams left their positions for those with better compensation during the pandemic. Forty-two percent of respondents were not trained to recognize burnout, stress, or compassion fatigue. Our study shows that half of the respondents had more vacancies during the pandemic than in previous years and reported difficulty in filling those positions. We were unable to link the vacancies to the pandemic and burnout because hospitalizations and transports in the pediatric facilities decreased during the pandemic; however, we do report that coronavirus disease 2019 exposure before the vaccine was a source of stress for team members. There are opportunities to improve the identification of burnout and to foster resilience and boost retention of this highly skilled niche workforce.


Correction: Flavin-adenine-dinucleotide gold complex nanoparticles: chemical modeling design, physico-chemical assessment and perspectives in nanomedicine.
[This corrects the article DOI: 10.1039/D1NA00444A.].


The effect of lateral ankle sprain on dorsiflexion range of motion, posterior talar glide, and joint laxity.
Retrospective study. Assess range of motion, posterior talar glide, and residual joint laxity following ankle sprain in a population of athletes who have returned to unrestricted activity. Lateral ankle sprains occur frequently in athletic populations and the reinjury rate may be as high as 80%. In an effort to better understand risk factors for reinjury, the sequelae to injury in a sample of college athletes were assessed. Twelve athletes with a history of lateral ankle sprain within the last 6 months and who had returned to sport participation were tested. Only athletes who reported never injuring the contralateral ankle were included. The injured and uninjured ankles of subjects were compared for measures of joint laxity, ankle dorsiflexion range of motion, and posterior talar glide. Friedman's test of rank order was used to analyze the laxity measures and a MANOVA was used to assess the dorsiflexion and posterior talar glide measures. Laxity was significantly greater at the talocrural and subtalar joints of the injured ankles. There were no significant differences in any of the ankle dorsiflexion measurements between injured and uninjured ankles, but posterior talar glide was significantly reduced in injured ankles as compared to uninjured ankles. In our sample of subjects, residual ligamentous laxity was commonly found following lateral ankle sprain. Dorsiflexion range of motion was restored in the population studied despite evidence of restricted posterior glide of the talocrural joint. Although restoration of physiological range of motion was achieved, residual joint dysfunction persisted. Further research is warranted to elucidate the role of altered arthrokinematics after lateral ankle sprain.


Salt-induced electrical epithelial responses of the frog (Rana catesbeiana) tongue and their relation to gustatory nerve activity in vivo.
Stimulation of the frog tongue with various salts produced changes in epithelial potential of the tongue, accompanied by changes in gustatory nerve activity. Both changes varied similarly according to the stimulus. The results indicate that cation transport in the lingual epithelium is involved in gustation.


Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals.
Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Voxelwise regression models tested the cross-sectional association between [18F]fluorodeoxyglucose ([18F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [18F]FDG in amyloid positive (Aβ+) and negative (Aβ-) subjects. Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [18F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [18F]FDG-NfL were confined to cognitively impaired Aβ+ individuals. These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.


Advanced bioscience and AI: debugging the future of life.
Scientific advancements lead us towards a future in which Homo sapiens may no longer be the only sapient being. The societal and legal challenges of this potentiality are immense, and it will require traditionally disparate branches of science to recognise their similarities in order to address them effectively.


Treatment of complex stenoses involving renal artery bifurcations with use of drug-eluting stents.
Percutaneous angioplasty with stent placement is effective for the treatment of renal artery stenosis (RAS). RAS involving the bifurcation is technically challenging because of possible occlusion of a renal artery branch after stent implantation. The present report describes experiences in four patients with stenosis involving the renal artery bifurcation treated with drug-eluting stents (DESs). DESs were used instead of bare stents because of their potential advantage of lower restenosis rates. There was no evidence of restenosis on ultrasonography, with stable renal function and blood pressure at a median follow-up of 13 months.


Monoaminergic and GABAergic terminations in phrenic nucleus of rat identified by immunohistochemical labeling.
The termination patterns of axons in the phrenic nucleus immunoreactive to synthetic enzymes for catecholamines and for serotonin and GABA were studied in rats. Spinal cord tissue in which phrenic motoneurons were retrogradely labeled with horseradish peroxidase was incubated with antisera against dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, 5-hydroxytryptamine, and GABA to identify presumptive terminations of monoaminergic and GABAergic neurons onto identified phrenic motoneurons. In the C3 to C5 spinal cord, 5-hydroxytryptamine-, dopamine beta-hydroxylase- and GABA-like positive terminals with varicosities formed a dense network, with presumptive synaptic contacts on dendrites and somas of phrenic motoneurons. A similar pattern of terminations was also observed in adjacent (non-respiratory muscle) motoneuron pools. There were fewer phenylethanolamine-N-methyltransferase-positive terminal arborizations in the cervical spinal cord compared to thoracic spinal cord; phenylethanolamine-N-methyltransferase terminals were not seen in the vicinity of phrenic motoneurons. These results suggest that phrenic motoneuronal activity is influenced by multiple supraspinal inputs utilizing different neurotransmitters. These transmitters also mediate inputs to other (nearby) spinal motoneurons and thus are not unique for signal transmission to phrenic motoneurons.


Generation of an internal matrix in mature avian erythrocyte nuclei during reactivation in cytoplasts.
When fused with mouse L-cell cytoplasts, chick erythrocyte nuclei enlarge, take up proteins from the host cytoplasm, and recommence RNA synthesis. We found that during this transition the erythrocyte nuclei gain an internal nuclear matrix, thus providing a novel approach to questions concerning the nature of the salt-resistant intranuclear skeleton. A new method for preparation and examination of the nuclear matrix in situ is also described.


Fatal bleeding from a laceration of superficial temporal artery: A rare case.
We report a case of a 34-year-old drunken male, who was found dead in his apartment. On scene inspection, the deceased body was found in the sitting position on a chair, and a massive arterial blood pattern was observed at the scene. First responders and the coroner visited the scene considered this case as a criminally suspicious due to arterial blood pattern on walls and excessive blood pool at the scene. At autopsy, a laceration was present on the left side of the scalp with an underlying transection of the left superficial temporalis artery. Subsequent histological examination of the arterial section established its transection and cellular response to injury. After careful perusal of CCTV camera footages, pre-autopsy CT, macroscopic examination of injury, histological examination of the transected artery, and toxicological analysis report, cause of death was given as exsanguination due to laceration of a superficial temporal artery following blunt force head trauma. The manner of death was accidental. Although it is not uncommon to see deaths of alcoholics following scalp trauma, the peculiarity of this case lies in the fact that no evidence of fatal accidental superficial temporal artery has ever been reported in the forensic literature. We also suggest that a thorough analysis of history, circumstances, and histologic examination, even of a transacted artery can provide medicolegal relevant data.


Ultrastructural studies on erythropoiesis in the avian thymus. I. Description of cell types.
Thymus lobes from three species of birds, Quelea quelea, Passer domesticus and Sturnus vulgaris, have been examined ultrastructurally. The component cell types are compared with their counterparts in mammalian thymus glands, and found to be similar. Greater differences between small, intermediate and enlarged lobes of one species than exist between species. Developing erythroid cells are present in most enlarging and some enlarged glands. They appear to be developing at the expense of lymphoid cells in some birds. The origin of these cells is discussed. Cells that are possible candidates for the production of some thymic hormones are also described.


Synthesis and structure-activity relationship studies of substituted isoquinoline analogs as antitumor agent.
A number of substituted isoquinolin-1-ones, possible bioisosteres of the 5-aryl substituted 2,3-dihydroimidazo[2,1-a]isoquinolines, were synthesized and tested for their antitumor activity against five different human tumor cell lines. O-(3-hydroxypropyl) substituted compound (15) exhibited the best antitumor activity which is 3-5 times better than 5-[4'-(piperidinomethyl) phenyl]-2,3-dihydroimidazo[2,1-a]isoquinoline (1).


PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR.
Specific cellular functions mediated by GPCRs are often associated with signalling through a particular G protein or β-arrestin. Here, we examine signalling through a GPCR, protease-activated receptor 2 (PAR2), in a high-grade serous ovarian cancer cell line (OV90). Human ovarian cancer tissues (n = 1,200) and nine human ovarian cancer cell lines were assessed for PAR2 expression. PAR2 signalling mechanisms leading to cell migration and invasion were dissected using cellular assays, western blots, CRISPR-Cas9 gene knockouts, pharmacological inhibitors of PAR2 and downstream signalling proteins in OV90 cancer cells. PAR2 was significantly overexpressed in clinical ovarian cancer tissues and in OV90 ovarian cancer cells. PAR2 agonists, an endogenous protease (trypsin) and a synthetic peptide (2f-LIGRL-NH2 ), induced migration and invasion of OV90 ovarian cancer cells through activating a combination of Gαq/11 , Gα12/13 and β-arrestin1/2, but not Gαs or Gαi . This novel cooperative rather than parallel signalling resulted in downstream serial activation of Src kinases, then transactivation of epidermal growth factor receptor (EGFR), followed by downstream MEK-ERK1/2-FOS/MYC/STAT3-COX2 signalling. Either a PAR2 antagonist (I-191), CRISPR-Cas9 gene knockouts (PAR2 or Gα proteins or β-arrestin1/2), or inhibitors of each downstream protein attenuated human ovarian cancer cell motility. This study highlights a novel shared signalling cascade, requiring each of Gαq/11 , Gα12/13 and β-arrestin1/2 for PAR2-induced ovarian cancer cell migration and invasion. This mechanism controlling a cellular function is unusual in not being linked to a specific individual G protein or β-arrestin-mediated signalling pathway.


Identifying patient and physician characteristics that affect compliance with antihypertensive medications.
Compliance with antihypertensive medications is essential to the clinical management of hypertension. Poor compliance with antihypertensive medications has often been associated with treatment failure and disease progression. To identify patient and prescriber characteristics that may influence compliance with antihypertensive medications. We used pharmacy records within the Veterans Health Administration, a database which included 1292 patients and 656 physicians over a 2-year time period from April 1, 1996, to April 1, 1998. The level of compliance with antihypertensive medications was assessed using a measure developed for this purpose within the Administration. Three separate ordinary least squares regression models were conducted to ascertain the effects of patient and physician characteristics on compliance. Despite the importance of compliance in the clinical management of hypertension, poor compliance with antihypertensive drug treatment was still widespread. Patients who were younger and less active in their treatment decisions tended to be less compliant (P < 0.05 and 0.05, respectively). Health care providers who were older, residents in speciality care, and physicians (as compared with non-physicians) had patients who were also less likely to be compliant (P < 0.01, 0.01, and 0.05, respectively). These findings suggest that in order to increase the effectiveness of medical care for hypertension, it is important to improve compliance with antihypertensive agents.


Improvement of water recovery from phosphate sludge at the M'Dhilla Mine, Tunisia.
In Tunisia, phosphate beneficiation from ores by the Gafsa Phosphate Company (GPC) is a water-intensive process that generates large amounts of sludge. Responsible mining minimizes water use and prioritizes its recycling and reuse to limit the impact on water resources. Recovery of water from the phosphate sludge (PS) using the densification with adapted flocculants-a low-energy consuming process-is plausible for efficient management of water resources. The objective of this study was to improve low-cost water recovery from PS produced at the M'Dhilla Mine plant operated by GPC in Tunisia. Representative samples of PS were first collected and characterized for physicochemical and mineralogical properties. To maximize water recovery, densification based on flocculation was then performed using two different flocculants (Slim Floc vs Flomin 905) with different doses (0.1 g/L vs 0.3 g/L), consumption (100-1200 g per ton of dry sludge g/tds), sludge concentration (50 g/L vs 60 g/L), and settling time (15-1200 s). Results showed that PS particles were fine-grained and contained carbonates, silicates, and significant residual fluorapatite (59%) that could be valorized. Up to 91% of water was recovered using anionic flocculant Flomin 905. These findings show an improvement of 24% relative to the current water recovery at M'Dhilla plant (66%) while using a flocculant dose three times lower than the conventional flocculent Sim Floc (0.1 g/L vs 0.3 g/L). The best sludge settlement conditions were obtained with 0.1 g/L Flomin 905 at 600 g/tds and 10 min of settling time. The densification process using Flomin 905 proved efficient in maximizing water recovery (91%) with a consumption of flocculant that could be decreased by up to 70% annually in comparison with Slim Floc, thus decreasing treatment costs by 63%. Results will help to prevent exhaustion of groundwater resources and limit land exploitation while decreasing the volume of settling ponds.


Terpenoid traceability of commercial sheep cheeses produced in mountain and valley farms: From pasture to mature cheeses.
Mountain cheeses are characterized by their strong link to the territory and are testimonial of the cultural heritage. However, there is a lack of traceability and authenticity indicators for most mountain cheeses produced in Europe even though their terroir value is demanded by cheese-makers, consumers and regulatory bodies. The present study investigated the potential and reliability of terpenoids as traceable compounds in Idiazabal PDO cheeses made with raw milk from commercial sheep flocks grazed on lowlands or mountain grasslands. Terpenoids were analysed in individual pasture plants and ripened cheeses. Ingested diets were estimated by microscopic examination of plant residues in sheep faeces, and terpenoid composition of pastures and sheep diets were calculated from isolated plant species analysis. About 100 individual terpenoids were detected in botanical species collected from pastures and 40 compounds in mature cheeses. Important differences were found in the abundance of terpenoids identified in lowland and highland pastures mainly depending on the botanical family and the contribution of each botanical species to both type of grasslands. Estimated sheep diet composition of lowland and highland flocks was different and, in consequence, ingested terpenoids calculated from the estimated diet composition and individual plant terpene analysis were different. The multivariate approach provided robustness in the terpenoid traceability from pasture to cheese selecting individual terpenoids, particularly sesquiterpenoids such as γ-cadinene and aromadendrene, which strongly contributed to discriminate between mountain and valley cheeses. These results can help regulatory bodies to implement effective traceability and authentication procedures to identify mountain cheeses and to protect added-value dairy products.


A Meta-Analysis of Ring Annuloplasty Versus Combined Ring Annuloplasty and Subvalvular Repair for Moderate-to-Severe Functional Mitral Regurgitation.
A ring annuloplasty (Ring) for moderate-to-severe functional mitral regurgitation (MR) is associated with suboptimal outcomes, and adjunctive subvalvular repair techniques (Ring + Subvalvular) have been advocated to improve repair durability. However, the outcomes of this strategy are not clearly defined. A systematic review was performed to identify studies that compared a Ring versus Ring + Subvalvular repair for the treatment of moderate-to-severe functional MR. A meta-analysis was conducted on clinical outcomes and echocardiographic measures of follow-up MR and left ventricular reverse remodeling. Risk ratio (RR) and mean difference (MD) were calculated by the Mantel-Haenszel and Inverse Variance methods under a fixed or random effects model, as appropriate. Seven non-randomized studies were identified, with a total of 531 patients (Ring = 301, Ring + Subvalvular = 230). At follow-up (range 30-47 months), a Ring + Subvalvular repair was associated with a lower mortality (RR = 0.59, 95%confidence interval [CI] 0.37-0.94, p = 0.03), greater freedom from moderate or greater MR (RR = 0.44, 95%CI 0.27-0.72, p = 0.001), and improved left ventricular end-diastolic diameter (MD = -3.49 mm, 95%CI -5.45 to -1.53, p = 0.0005) and New York Heart Association functional class (MD = -0.25, 95%CI -0.42 to -0.08, p = 0.004). A trend toward a reduced risk of reoperation for recurrent MR was noted with a combined Ring + Subvalvular repair (RR = 0.28, 95%CI 0.06-1.22, p = 0.09). Finally, a Ring + Subvalvular repair did not impact operative mortality or follow-up left ventricular ejection fraction. A combined Ring + Subvalvular repair for moderate-to-severe functional MR can be safely performed, and may improve mid-term outcomes, as compared with Ring alone.


Lamin disassembly kinetics: a cell-free system with extracts from mitotic HeLa cells.
We describe a cell-free system in which a postribosomal supernatant from metaphase HeLa cells induces prophase-like changes in permeabilized HeLa cell populations as evidenced by the nuclear lamin disassembly and chromatin condensation. We have attempted to characterize the cell-free system with permeabilized HeLa cells. First, by extracting lamins with agents known to disrupt the noncovalent interactions in the supramolecular lamin aggregate in interphase using polyclonal and a newly established monoclonal anti-lamin Ab 2E3, uniform extraction of lamins was achieved with urea and deoxycholate whereas the cation Mg2+ and 2-mercaptoethanol had little effect on the disassembly of interphase lamins. Second, cytoplasmic extract from mitotic HeLa cells, synchronized by a nitrous oxide metaphase arrest, was tested. It had a differential effect on interphase lamin depolymerization. Nuclei in G1 phase of the cell cycle were more resistant against the mitotic extracts than cells in S and G2 phase. The results are discussed in terms of a possible inactivation of mitotic extracts by factors present in nuclei in early interphase.


New ways to impact primary palliative care practices using online continuing education.
Healthcare professionals trained in palliative care (PC) improve satisfaction and decrease healthcare overutilization for patients with serious illness and their families. A continuing education (CE) series on primary PC aligned to the National Clinical Practice Guidelines for Quality PC was developed by local, interdisciplinary experts for a target audience of rural, primary care healthcare professionals. The modules were accessed on an online learning management system platform. The study objectives were to assess differences in participants' knowledge, competence, performance, and ability to improve patient care as well as commitment to change practice after taking each of the CE modules. To achieve these objectives, a descriptive design was used with a convenience sample of healthcare professionals who registered for the CE series and completed at least one module. Participants completed demographic questions and an evaluation survey after completing each module. So far, 158 healthcare professionals have registered for the series with the majority being nurses and social workers. Although the professionals reported having extensive healthcare experience, they did not report having the same level of PC experience. The professionals represent nine different states. All the CE modules increased teamwork skills for most participants. The CE modules on cultural aspects and self-care had the biggest influence on participants' ability to improve patient outcomes. Cultural aspects, care of the actively dying, and advance care planning had the greatest impact on participants' knowledge, competence, and performance. The primary PC education series improved self-reported skills in teamwork, practice habits, and meeting goals of healthcare professionals from a variety of disciplines and settings. These enhanced primary PC skills will improve the incorporation of PC into a variety of practice settings, by multiple disciplines to enhance access to PC outside of, and potentially referrals to, specialty PC programs.Palliative care (PC) is an emerging field of healthcare aimed at positively affecting patients living with serious illness and their families. An important factor that influences a health professional's successful delivery of PC may be their knowledge, experiences, and confidence. PC training provided to healthcare professionals improves patients' and healthcare professionals' satisfaction and reduces healthcare expenditures through cost savings and cost avoidance.1,2.


A review of recently described genetic alterations in central nervous system tumors.
Advances in molecular profiling of central nervous system tumors have enabled the development of classification schemes with improved diagnostic and prognostic accuracy. As such, the 2016 World Health Organization Classification of Tumors of the Central Nervous System (WHO 2016) introduced a paradigm shift in the diagnosis of brain tumors. For instance, integrated assessment incorporating both histologic features and genetic alterations was introduced into the diagnostic framework of gliomas. IDH1/2 mutation status now represents the most important initial stratifier of diffuse gliomas in adults, although rarer subtypes within the IDH-wildtype category continue to be elucidated. Medulloblastomas and other embryonal neoplasms were also genetically defined and segregated based on molecular subtypes, and 1 molecular subtype of ependymoma was added. In this review, we summarize the rapidly evolving spectrum of recurrent genetic alterations described in central nervous system tumor entities since the publication of the WHO 2016.


Low-dose immunosuppression in a rat hind-limb transplantation model.
Composite tissue allografts (CTAs) offer an alternative to conventional reconstructive methods. However, the toxicity of the drugs that are required to prevent rejection has prevented its widespread clinical application. The purpose of this study was to determine whether a low-dose, corticosteroid-free combination regimen of tacrolimus and mycophenolate mofetil (MMF) would prevent rejection in a rat hind-limb model, with minimal toxic side effects. Three groups were used in this study. In group I, Wistar Furth (WF) rats received a syngeneic WF hind-limb. In groups II and III, WF rats received an ACI hind-limb. The latter were treated with tacrolimus-MMF. Assessment for rejection, flow cytometry, and mixed lymphocyte reactions was performed. Biopsies were taken regularly and at the time of killing. Combination therapy with low-dose tacrolimus-MMF effectively prolonged CTA survival indefinitely, with minimal side effects. Toxicity associated with immunosuppressive drugs can be avoided in a low-dose combination corticosteroid-free regimen.


Cytotoxicity of D-penicillamine in association with several heavy metals against cultured rabbit articular chondrocytes.
The potentiation or antagonistic effects of Cu, Hg, Pb and Cd salts in the presence of a long-acting anti-rheumatic drug, D-penicillamine (D.P.) were studied on cultured chondrocytes. CuSO(4) (10(-4)M), HgCl(2) (10(-5)M), Pb(CH(3)COO)(2) (10(-3)M) and D.P. (10(-3)M) when used alone caused a small decrease in cell proliferation. The addition of D.P. with Cu, Hg or Pb salts resulted in a marked increase in the extent of growth inhibition. In contrast, CdCl(2) (10(-5)M) produced an important growth inhibitory effect, and D.P. antagonized CdCl(2) action. The CuSO(4) D.P. toxicity was probably due to production of H(2)O(2) in situ. To verify this hypothesis, catalase, responsible for H(2)O(2) metabolism was used, and was found to partially reverse the inhibitory effect of CuSO(4)-D.P.


[The role of nitric oxide in the pathogenesis of portal hypertension].
To investigate the role of nitric oxide in the pathogenesis of portal hypertension. We measured the portal venous pressure of 75 patients via a catheter and detected the levels of plasma endotoxin and NO(2)(-)/NO(3)(-). The mean levels of plasma endotoxin and NO(2)(-)/NO(3)(-) (0.249 +/- 0.112 Eu/ml and 55.9 +/- 26.2 micromol/L) in portal hypertensive patients were significantly higher than those in the controls, and the highest values were observed in the portal venous blood. The mean portal venous pressure of the portal hypertensive patients was 35.5 +/- 4.4 cm H(2)O and was positively correlated with the levels of NO(2)(-)/NO(3)(-) (n = 25, r = 0.55, P < 0.01). Positive correlation existed between them during the postoperative period (r = 0.57, P < 0.05). There was a negative correlation between the levels of albumin and NO(2)(-)/NO(3)(-) (n = 75, r = -0.35, P < 0.01), and the mean levels of NO(2)(-)/NO(3)(-) were 72.4 +/- 20.3 micromol/L in the patients with ascites, much higher than those (50.3 +/- 21.0 micromol/L) without ascites. The levels of plasma endotoxin and nitric oxide were elevated in patients with portal hypertension, and NO might play an important role in the abnormal elevation of portal venous pressure and the damage to liver function.


Quantitative and temporal approach to utilising electronic medical records from general practices in mental health prediction.
This study proposes a framework for mining temporal patterns from Electronic Medical Records. A new scoring scheme based on the Wilson interval is provided to obtain frequent and predictive patterns, as well as to accelerate the mining process by reducing the number of patterns mined. This is combined with a case study using data from general practices in the Netherlands to identify children at risk of suffering from mental disorders. To develop an accurate model, feature engineering methods such as one hot encoding and frequency transformation are proposed, and the pattern selection is tailored to this type of clinical data. Six machine learning models are trained on five age groups, with XGBoost achieving the highest AUC values (0.75-0.79) with sensitivity and specificity above 0.7 and 0.6 respectively. An improvement is demonstrated by the models learning from patterns in addition to non-temporal features.


The distal fibular perforating axial flap for lateral malleolus coverage: an anatomical description and surgical technique.
Skin closure disorders in ankle surgery are a recurrent problem not only in traumatology but also in elective surgery. The aim of the study was to describe the anatomical basis of the fasciocutaneous vascularization of the lateral malleolus region to develop a posterior cover flap for the region. We dissected ten fresh frozen specimens after arterial injection of an Indian ink preparation and individualized the perforating arteries. Their positions and diameters were collated. Then, the surgical technique was clinically applied for two different cases by transferring the fasciocutaneous flap posterior to the lateral malleolus to cover a loss of skin substance. There were in average 5 fibular perforators over the last 100 mm of the fibula. The average diameter of the first two perforating arteries was 0.6 ± 0.12 mm and 0.9 ± 0.25 mm, respectively, and the consistency of the latter makes it possible to produce a skin flap with anterior translation. This is an axial flap. Two patients were operated on using this technique. There was no necrosis of the posterior fibular flap and healing was achieved by the third post-operative week. This study showed the presence of fibular perforating arteries with a high reproducibility of their dissection. This anatomical description served as the basis for the description of a new distal fibular perforating flap.


Anti-allergic activity of glycyrrhizic acid on IgE-mediated allergic reaction by regulation of allergy-related immune cells.
Glycyrrhizic acid (GA), the major bioactive triterpene glycoside of glycyrrhiza, has been shown to possess a wide range of pharmacological properties, including anti-inflammatory and anti-viral properties. However, few studies have examined the anti-allergic activity and exact mechanism of action of GA. In the present work, the anti-allergic activity and possible mechanisms of action of GA on an immunoglobulin (Ig) E-mediated allergic reaction has been studied using three models of allergic reaction in vivo and in vitro. Active systemic allergic reaction in Balb/c mice showed that GA can suppress the increased level of IL-4 to restore the immune balance of TH1/TH2 cells in a dose-dependent manner. Additionally, GA attenuated significantly the B cells producing allergen-specific IgE and IgG1 partly because of the low levels of TH2 cytokines. Both passive cutaneous anaphylaxis in vivo and an RBL-2H3 cell-based immunological assay in vitro indicated that GA acted as a "mast cell stabilizer", as it inhibited mast cell degranulation and decreased vascular permeability by inhibiting the expression of Orai1, STIM1 and TRPC1, which blocked extracellular Ca2+ influxes. The current study suggests that GA may serve as an effective anti-allergic agent derived from food for the prevention and treatment of IgE-mediated allergic reaction.


New developments in medical-surgical treatment of acute myocardial infarction.
Selective intracoronary thrombolysis with streptokinase was successful in 72 of 84 (86%) patients admitted to the hospital with definitive signs of acute transmural myocardial infarction due to complete occlusion of either the left anterior descending coronary artery, the right coronary artery, or the circumflex artery. The average time between onset of acute symptoms and medically induced reperfusion was 241 +/- 90 minutes (SD). Reperfusion resulted in prompt relief of pain, regression of cardiogenic shock, and normalization of electrocardiograms. Follow-up treatment was either medical or surgical. The 32 medically treated patients had a high reocclusion rate, with 6 fatal (19%) and 9 nonfatal (28%) reinfarctions. In order to the reduce the risk of reinfarction, additional simultaneous transluminal balloon angioplasty was done in a recent series of patients with stenoses accessible to this technique. The best early and long-term results were achieved in 17 patients who underwent coronary artery bypass grafting within three days after successful thrombolysis. There was no operative mortality, and subsequent bleeding has not been a problem. It is concluded that early operation is the treatment of choice in all patients suitable for such intervention who have undergone successful intracoronary thrombolysis within 4 hours after onset of acute myocardial infarction. Late coronary bypass operation should be reserved for symptomatic patients who have definitive signs of infarction in spite of successful thrombolysis.


High concentrations of NaCl induce cell swelling leading to senescence in human cells.
Cell swelling and retardation in DNA replication are always observed in senescent cells. When DNA replication is slowed down with RNA and protein syntheses unchanged in proliferating cells, it causes a phenomenon known as unbalanced growth. The purpose of this study is to assess the role of cell swelling in unbalanced growth in terms of senescence and investigate the mechanism underlying this phenomenon. We tried to induce cell swelling with minimum damage to cells in this study. We perturbed the osmoregulatory functions to induce cell swelling under hypotonic and hypertonic conditions in normal human fibroblasts. Addition of excess NaCl was found to induce significant cell and nuclear swelling in dose- and time-dependent manners. Excess NaCl immediately retarded DNA replication, accumulated cells at G1 phase of the cell cycle, and eventually deprived division potential of the cells. Such cells showed typical senescent cell shape followed by expression of the typical senescence-associated genes. Excess NaCl also activated ERK1/2, p38, and JNK of the mitogen activated protein kinase family. Addition of U0126, an inhibitor of ERK1/2, prevented appearance of senescent features induced by excess NaCl. These results suggest that hypertonic conditions induce cell swelling due to unbalanced growth, thereby leading to cellular senescence.


Feline testicular ultrasonogram differentiates pre vs. postpubertal and normal vs. disrupted spermatogenesis.
The aims of this study were: to ultrasonograhically describe and compare testicular parenchyma echogenicity and heterogeneity using digital image analysis in: I) prepubertal (PREP), peripubertal (PERI) and mature (MAT) cats; II) Normal and abnormal mature felids. Secondary, the relationships between histomorphological and ultrasonographic attributes of the testes were also determined. I) Fourteen, PREP, PERI and MAT male cats were ultrasonographically examined and then castrated. II) Seven adult cats were ultrasonographically examined before and after a GnRH antagonist administration and then castrated. All the testes were grossly and histomorphometrically assessed. In the frozen digital images of the longitudinal ultrasound sections, 3 regions of interest (ROI, 1 mm2) were selected. Within each ROI the echogenicity and the heterogeneity of the testicular parenchyma were digitally analyzed. In experiment I, testicular volume (0.15 ± 0.0 vs. 0.49 ± 0.1 vs. 1.65 ± 0.1; P < 0.01) and gonadosomatic index (0.04 ± 0.0 vs. 0.05 ± 0.0 vs. 0.08 ± 0.0; P < 0.01), echogenicity (56.54 ± 0.75 vs. 81.87 ± 5.88 vs.94.67 ± 3.62; P < 0.01) and heterogeneity (10.2420 ± 1.3740 vs.13.65 ± 0.65 vs. 14.67 ± 1.49; P < 0.01) augmented throughout PRE, PERI, and MAT. In experiment II, testicular volume (1.00 ± 0.09 vs. 0.85 ± 0.09; P < 0.05), echogenicity (87.74 ± 1.53 vs. 83.32 ± 1.54; P 0.01) but not heterogeneity (14.09 ± 0.26 vs. 14.19 ± 0.29; P > 0.05) decreased in the post GnRH antagonist abnormal testes. For both experiments, testicular volume, seminiferous tubular diameter, percentage of spermatids as the most mature cell type, and luminal/intertubular ratio were highly correlated (P < 0.01) with their echotextural attributes. Computer-assisted image analysis of B mode ultrasonogram appears as a good indicator of pubertal development and mild alterations of spermatogenesis in felids.


Effects of combined abiotic stresses on nutrient content of European wheat and implications for nutritional security under climate change.
Climate change is causing problems for agriculture, but the effect of combined abiotic stresses on crop nutritional quality is not clear. Here we studied the effect of 10 combinations of climatic conditions (temperature, CO2, O3 and drought) under controlled growth chamber conditions on the grain yield, protein, and mineral content of 3 wheat varieties. Results show that wheat plants under O3 exposure alone concentrated + 15 to + 31% more grain N, Fe, Mg, Mn P and Zn, reduced K by - 5%, and C did not change. Ozone in the presence of elevated CO2 and higher temperature enhanced the content of Fe, Mn, P and Zn by 2-18%. Water-limited chronic O3 exposure resulted in + 9 to + 46% higher concentrations of all the minerals, except K. The effect of climate abiotic factors could increase the ability of wheat to meet adult daily dietary requirements by + 6% to + 12% for protein, Zn and Fe, but decrease those of Mg, Mn and P by - 3% to - 6%, and K by - 62%. The role of wheat in future nutrition security is discussed.


Acute Surgical Management of the Burn Patient.
Burn management has developed over time to encompass care that includes more than just survival but also quality of life and successful reintegration into society. Identification of burns that require timely operative intervention supports the goals of excellent functional and aesthetic outcomes in burn survivors. Appropriate patient optimization, detailed preoperative planning, and intraoperative communication are keys to success.


Growth fraction and cycle duration of hepatocytes in the three-week-old rat.
The proliferation of hepatocytes in the liver of 3-week-old rats has been investigated by autoradiographic methods. This investigation is a continuation of earlier work on the same topic (Schultze & Maurer, 1972; 1973). 21 days after birth, 102 rats received a single injection of 3H-TdR. The percentage of labelled mitoses was then determined 1 hr later and at various times throughout the interval up to 12 days after application of 3H-TdR. In agreement with earlier work, a first peak of labelled mitoses was found 7 hr after 3H-TdR injection. The area under the peak indicates an S phase duration of 8 hr. In addition a second very broad peak of labelled mitoses was found between 2 and 12 days after pulse labelling. The analysis of the results leads to the conclusion that the hepatocytes of the 3-week-old rat have a growth fraction close to 1 and a doubling time of 6-7 days. This is at variance with earlier results of Post, Huang & Hoffman (1963) and Grisham (1969) who had derived a value of 21.5 hr for the duration of the cell cycle and a value of only 0.1-0.2 for the growth fraction of the hepatocytes.


Urinary Tract Infection in Infants <1 Month of Age: Demographic, Clinical, and Microbiological Characteristics.
This cross-sectional study was conducted on 232 infants aged <1 month with proven UTI admitted to three major teaching hospitals for the period 2010-2018 to assess clinical, demographic, and laboratory findings of urinary tract infection in this age group. All information was extracted from the medical records. Urinary tract infection was defined as ≥ 50,000 colony-forming units per milliliter of a single uropathogen isolated from a catheterized or suprapubic aspiration or greater than 100,000 colony-forming units per milliliter from a midstream, clean-catch sample. The most common pathogen isolated was E. coli (78.4%), followed by Enterobacter and Klebsiella, accounting for 12.1 and 4.7% respectively. The main presenting clinical manifestation was jaundice, which was found in 54.7% of cases; it was followed by restlessness (45.6%) and fever (40%). During infancy, the signs and symptoms of UTI are often nonspecific and although urine culture is a gold standard diagnostic tool specimen collection is challenging and urine contamination is common in children, therefore it makes the diagnosis difficult. UTI in infants may indicate underlying genitourinary abnormalities; therefore, appropriate diagnosis and immediate initiation of antibiotic therapy are crucial to decrease long-term complications like renal scarring. According to our study, the most common clinical features were jaundice, restlessness, and fever, therefore it is suggested that urine culture should be performed for all infants presenting with these signs and symptoms.


The auditory midbrain of a marsupial: the brush-tailed possum (Trichosurus vulpecula).
A microelectrode survey was made of the midbrain auditory nuclei of the brushtailed possum (Trichosurus vulpecula), a common Australian marsupial. Information was sought on the tuning characteristics of individual neurones, tonotopic organization and mechanisms of sound localization. It was felt that such information would be of use in future studies of the development and evolution of mammalian hearing. Twelve possums were anaesthetized with ketamine and chloralose-urethane, and recordings were made of extracellular unit discharges in the inferior colliculus during monaural and binaural tonal stimulation. The inferior colliculus of the possum consists of a central nucleus - a darkly stained, densely packed group of cells - flanked laterally by an external nucleus with a lower density of paler cells. Tonotopic organization was demonstrated by discretelytuned elements in the central nucleus, but was not observed in the external nucleus. In the latter region broad and irregular tuning was commonly seen. Most units in both divisions were influenced by binaural stimuli, with patterns of binaural interaction similar to those observed in the cat inferior colliculus. Cells influenced by changes in the interaural time and intensity difference were commonly observed, but only a subclass of these were suited in sensitivity for sound localization. In general, the midbrain auditory system of the possum was similar in unit discharge characteristics and organization to those of the eutherian mammals commonly studied.


Community oncology research award winners use awards to enhance quality of their practices.
The 2009 Community Oncology Research Award (CORA) winners say they plan to improve practice research management, increase minority participation in clinical trials, improve communication, and invest in staff training and certification.


Severe thermal hand burns--factors affecting prognosis.
This paper presents the results of the analysis of clinical data from a series of 132 thermally injured patients with 214 burned hands. The objective was to identify the factors affecting the pathogenesis of postburn hand deformities. The study indicates that deep burns have the worst prognosis and that circumferential burns are always followed by secondary sequelae. The incidence of secondary hand deformity rises sharply when the burn affects more than 25 per cent of the total body surface area (TBSA). Given the same physical therapy programme, early tangential excision and immediate grafting yield better results than conservative treatment. The results underline the role of patient motivation in maximal hand rehabilitation.


Micro X-ray diffraction study of superelastic nickel-titanium orthodontic wires at different temperatures and stresses.
The phase transformation behavior in three commercial nickel-titanium orthodontic wires having different transformation temperatures was studied by micro X-ray diffraction (micro-XRD). Micro-XRD spectra were obtained at three different included bending angles (135 degrees, 146 degrees and 157 degrees) and three different temperatures (25 degrees C, 37 degrees C and 60 degrees C). The regions analyzed by micro-XRD were within the separate areas of a given wire specimen that experienced only tensile or compressive strain. The intensity ratio (M002/A110) between the 002 peak for martensitic NiTi and the 110 peak for austenitic NiTi was employed as the index to the proportions of the martensite and austenite phases. The ratio of martensite to austenite increased in all three nickel-titanium wires with decreasing included bending angle (greater permanent bending deformation), and was lower within the compression area for all wires at all bending angles than within the tension area. Micro-XRD provides an effective method for quantitative evaluation of the proportions of these two phases in nickel-titanium orthodontic wires, even though considerable preferred crystallographic orientation exists because of the wire drawing process.


The association of maternal and neonatal thrombocytopenia in high-risk pregnancies.
In this study of 136 women with pre-eclampsia, eclampsia, placenta previa, or abruptio placentae, 21 mothers were noted to have thrombocytopenia. Seventeen of the 21 were in the pre-eclampsia group. Of the 21 thrombocytopenic mothers, nine were associated with thrombocytopenia in the children, seven children had normal platelet counts, and five had no counts performed. Eight of the nine thrombocytopenic neonates were associated with pre-eclampsia in the mother, and five of these were not believed to have disseminated intravascular coagulation as the etiology of the platelet defect. The results suggest that thrombocytopenia is common in high-risk pregnancies in both the mother and the baby. However, the etiology of the platelet defect cannot be easily explained on the basis of a hypercoagulable state.


The domain-specificity of serial order working memory.
Making a turn while driving is simple: turn on the indicator, check for cars, then turn. Two types of information are required to perform this sequence of events: information about the items (e.g., the correct indicator), and the serial order of those items (e.g., checking before turning rather than vice-versa). Previous research has found distinct working memory capacities (WMCs) for item and serial order information in both verbal and nonverbal domains. The current study investigates whether the serial order WMC is shared for sequences from different content domains. One hundred and fifty-three participants performed sequence matching tasks with verbal (letters and words) and nonverbal (locations and arrows) stimuli. The accuracy of detecting mismatched item-identity and serial order information in sequences was used to operationalize item and order WMC. Using structural equation modeling analyses, we directly compared models that included either domain-specific or domain-general serial order WMC latent variables, finding that models with domain-specific serial order WMC latent variables for verbal and nonverbal materials fit the data better than models with domain-general latent variables. The findings support the hypothesis that there are separate capacities for serial order working memory depending on the type of material being ordered.


An analysis of the indications for cesarean section in a teaching hospital in China.
Cesarean delivery rates have increased remarkably worldwide. The indications for this increase are not fully understood and there may be regional, ethnic or health system differences in quoted indications which may explain, at least in part, the observed changes. In 2008 China was cited as having one of the highest rates of cesarean delivery in the world, but there was no accurate information about the indications for the high rate. This study sought to provide some information about the high cesarean section rate in China. Data on all births in a university teaching hospital in northern China serving a general obstetric population, excluding premature births, were collected from the hospital database from January 2009 to September 2012. All indications on the mode of delivery were analyzed for live births. There were 5267 births and the cesarean delivery rate was 41.4% in the study period. There was no significant trend in the cesarean delivery rate from 2009 to 2012. Fetal indications contributed most to the rate. More than 50% of all cesarean deliveries were due to nuchal cord, previous cesarean delivery, fetal distress and malpresentation. The rate of cesarean delivery on maternal request was 9.07%. Smaller contributions to the indications for cesarean delivery came from cephalopelvic disproportion, preeclampsia, prolonged labor, uterine rupture and other obstetric conditions. The data show increased fetal or maternal risk assessments are the main indications for cesarean delivery rather than cesarean delivery on maternal request in China.


Uncloaking lncRNA-meditated gene expression as a potential regulator of CMS in cotton (Gossypium hirsutum L.).
Cytoplasmic male sterility is a well-proven mechanism for cotton hybrid production. Long non-coding RNAs belong to a class of transcriptional regulators that function in multiple biological processes. The cDNA libraries from the flower buds of the cotton CGMS, it's restorer (Rf) and maintainer lines were sequenced using high throughput NGS technique. A total of 1531 lncRNAs showed significant differential expression patterns between these three lines. Functional analysis of the co-expression network of lncRNA-mRNA using gene ontology vouchsafes that, lncRNAs play a crucial role in cytoplasmic male sterility and fertility restoration through pollen development, INO80 complex, development of anther wall tapetum, chromatin remodeling, and histone modification. Additionally, 94 lncRNAs were identified as putative precursors of 49 miRNAs. qRT-PCR affirms the concordance of expression pattern to RNA-seq data. These findings divulge the lncRNA driven miRNA-mediated regulation of gene expression profiling superintended for a better understanding of the CMS mechanisms of cotton.


First-trimester maternal serum progesterone in aneuploid pregnancies.
First-trimester maternal serum screening for Down syndrome (DS) can be improved by the use of additional serum markers. We examined whether progesterone (P), synthesized by placenta, might be a first-trimester maternal serum marker for fetal DS. P was quantified in first-trimester maternal serum from 42 DS, six trisomy 18 and two trisomy 13 pregnancies and 115 controls. Log-regression of P versus gestational age in days was used to convert P concentrations into multiples of the median (MoM). The P concentrations in controls increased with gestational age (p = 9.5 x 10(-7)). The log10MoM P distribution in DS pregnancies was not significantly different from that in controls. However, from day 58-67, the log10MoM P was elevated in DS pregnancies (n = 10) with a mean (SD) of 0.1040 (0.0956), compared to a mean (SD) of - 0.0109 (0.1661) in controls (n = 24) (p = 0.05). Five out of six trisomy 18 and both trisomy 13 pregnancies had a P MoM < 1. P is not a useful marker for DS in first trimester, except perhaps in a narrow gestational age window from day 58 to 67. P is a trisomy 18/13 marker.


Mycobiota composition and changes across pregnancy in patients with gestational diabetes mellitus (GDM).
The gut mycobiota has never been studied either during pregnancy or in patients with gestational diabetes (GDM). This study aimed to analyze the fecal mycobiota of GDM patients during the second (T2) and third (T3) trimester of pregnancy and to compare it with the mycobiota of pregnant normoglycemic women (controls). Forty-one GDM patients and 121 normoglycemic women were studied. GDM mycobiota was composed almost exclusively by the Ascomycota phylum; Basidiomicota accounted for 43% of the relative frequency of the controls. Kluyveromyces (p < 0.001), Metschnikowia (p < 0.001), and Pichia (p < 0.001) showed a significantly higher frequency in GDM patients, while Saccharomyces (p = 0.019), were more prevalent in controls. From T2 to T3, a reduction in fungal alpha diversity was found in GDM patients, with an increase of the relative frequency of Candida, and the reduction of some pro-inflammatory taxa. Many associations between fungi and foods and nutrients were detected. Finally, several fungi and bacteria showed competition or co-occurrence. Patients with GDM showed a predominance of fungal taxa with potential inflammatory effects when compared to normoglycemic pregnant women, with a marked shift in their mycobiota during pregnancy, and complex bacteria-fungi interactions.


Phase 2 reentry in man.
Ventricular extrasystoles are characterized by a fixed coupling interval to the last QRST complex preceding it. We hypothesized that this QRST complex differed from QRST complexes of other sinus beats not followed by ventricular extrasystoles. Further, we investigated whether phase 2 reentry, demonstrated in animal experiments to initiate ventricular extrasystoles, ventricular tachycardia, and ventricular fibrillation, also plays a role in humans. We examined 18 patients with ventricular extrasystoles and/or ventricular tachycardia by signal averaging of the ECG (group A) or by single-beat analysis of intracardiac electrograms (group B). Group A consisted of six patients without structural heart disease and one patient with the Brugada syndrome. Six of the seven patients had right ventricular outflow tract ventricular extrasystoles. Group B consisted of 11 patients undergoing radiofrequency ablation. Eight of the 11 patients had right ventricular outflow tract extrasystoles. In six of the seven patients in group A, we demonstrated significant ST-elevation and/or T-wave changes in the sinus beat preceding ventricular extrasystoles compared with the second last sinus beat in one or more of the three orthogonal leads X, Y, and Z. In 9 of the 11 patients in group B, single-beat analysis of unipolar and bipolar electrograms recorded close to successful ablation sites demonstrated similar changes, that is, ST-elevation (median peak voltage gradient 150 muV, range 0-1,700) and T-wave changes in the sinus beat prior to ventricular ectopy. In addition, J-point elevation was demonstrated in several cases. In total, significant changes were demonstrated in 15 of the 18 patients studied (83%). J-point elevation, ST-elevation, and T-wave changes documented in the last sinus beat prior to ventricular extrasystoles are in agreement with phase 2 reentry, suggesting that this may be the responsible mechanism for ventricular extrasystoles and ventricular tachycardia/fibrillation. The phenomenon has been demonstrated in only animal experiments to date.


d-Cycloserine reverses scopolamine-induced object and place memory deficits in a spontaneous recognition paradigm in rats.
d-Cycloserine (DCS) is a partial agonist of the glutamatergic N-methyl-d-aspartate (NMDA) receptor-associated glycine site, and it prevents the amnesic effects of the muscarinic receptor antagonist scopolamine in various memory tests in rodents. In the present study, we tested the hypothesis that DCS has anti-amnesic effects in scopolamine-induced deficits using spontaneous object recognition and place recognition tests. In both tests, scopolamine (0.5 mg/kg, i.p.) was systemically administered 60 min prior to testing, while DCS (7.5, 15, 30 mg/kg, i.p.) was administered 30 min before testing, which consisted of a sample phase (5 min), a delay interval (15 min) and a test phase (2 min). DCS treatment reversed scopolamine-induced deficits in discriminatory behavior during the test phase. However, DCS did not affect decreased object exploration itself or increased thigmotaxis in the open-field arena induced by scopolamine. These results support our hypothesis and suggest differential contributions of glutamatergic-cholinergic system interactions to recognition memory and non-mnemonic exploratory behaviors.


A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia Aging Study.
This study prospectively describes the relationships between alcohol intake and subsequent cognitive performance among participants in the Honolulu Heart Program (HHP). Alcohol intake was assessed at Exam III of the HHP, and cognitive performance was measured approximately 18 years later with the Cognitive Abilities Screening Instrument (CASI). Complete information was available for 3556 participants, aged 71 to 93 years at follow-up. In multivariate analyses, the relationship between drinking and later cognitive performance appeared nonlinear, as nondrinkers and heavy drinkers (more than 60 ounces of alcohol per month) had the lowest CASI scores and the highest risks of poor and intermediate CASI outcomes. Compared with nondrinkers, the risk of a poor CASI score was lowered by 22% to 40% among men who consumed 1-60 ounces of alcohol per month. We report a positive association between moderate alcohol intake among middle-aged men and subsequent cognitive performance in later life. However, it is possible that the health risks associated with drinking outweight any potential benefits for many elderly persons.


LC-MS/MS-based quantification of tryptophan, kynurenine, and kynurenic acid in human placental, fetal membranes, and umbilical cord samples.
Tryptophan breakdown metabolites formed along the kynurenine pathway play a significant role in pregnancy and fetal development. To understand their involvement, it is crucial to quantify the levels of tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA) in relevant biological samples such as the placenta, fetal membranes, and umbilical cord. This study used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine TRP, KYN, and KYNA levels. The LC-MS/MS method was optimized for high sensitivity and specificity, demonstrating good reproducibility with a precision of < 10% CV and an accuracy of 85-115%. The lower limit of quantification for both TRP and KYN was 0.5 µg/ml, while for KYNA, it was 0.5 ng/mL. The method exhibited linearity within the examined range of concentrations in the homogenate, ranging from 0.5 to 30 µg/ml for TRP and KYN and from 0.5 to 25 ng/ml for KYNA. Using this method, we found significant differences in the concentrations of these substances in investigated maternal-fetal compartments. Placenta samples exhibited higher KYN and lower KYNA concentrations than the umbilical cord and fetal membrane, indicating a potentially important role for kynurenines in late pregnancy. Collectively, this finding may facilitate further research and provide inside into the involvement of the kynurenine pathway of TRP metabolism in fetal development.


The gene for mouse epidermal filaggrin precursor. Its partial characterization, expression, and sequence of a repeating filaggrin unit.
Filaggrin is an important keratin intermediate filament-associated protein of terminally differentiated mammalian epidermis. Its aberrant expression has been implicated in a number of keratinizing disorders. We have isolated and sequenced a cDNA clone to mouse filaggrin, of 1.479 kilobase pairs, which represents less than 10% of the full-length mRNA estimated by Northern blot analysis to be 17 kilobases long. The cDNA clone delineates a 744-base pair repeat. This encodes a protein of 248 amino acids or 26,330 Da, which is almost identical to the known properties of mouse filaggrin in size, amino acid composition, and charge. Total mouse genomic DNA and the filaggrin gene isolated from a cosmid library were found to contain a super-stoichiometric repeat of the same size. These data support the hypothesis (Haydock, P.V., and Dale, B.A. (1986) J. Biol. Chem. 261, 12520-12525) that filaggrin is initially synthesized as a polyprotein precursor containing many tandem copies. However, our data suggest that the repeating filaggrin units of the precursor are not separated by "large linker" peptides as suggested by these authors. In situ hybridization was used to show that the filaggrin precursor mRNA is located precisely over the granular layer of the epidermis, indicating that expression of this gene is regulated at the transcriptional level as for the differentiation-specific keratin 1 protein. These probes will now permit detailed studies on the regulation of expression of the filaggrin gene.


Melanosis of the dentate nucleus: fine structure and histochemistry.
Ultrastructural and histochemical studies were done on a rare case of primary melanosis of the dentate nucleus. The coexistence of extraneuronal neuromelanin and glial lipofuscin in that region was observed and the interconvertability of these two pigments is suggested.


Distressing perineal and vaginal pain in prepubescent girls: an aetiology.
To propose an aetiology and treatment for distressing perineal and vaginal pain in a paediatric female population. Between 1997 and 2011, we saw 24 prepubertal girls (mean age of seven years, 11 months) with distressing vaginal pain, both before and after we suspected that pinworms (Enterobius vermicularis) were the cause. Prior to 2005, two of six girls had resolution of their symptoms, one of whom had repeated courses of mebendazole. After 2005, when pinworms were discovered in one patient, treatment with mebendazole 100 mg weekly for three weeks resolved symptoms in 18 girls. Three girls had a recurrence of symptoms within 2-4 months, and repeat treatment with mebendazole was successful. Pinworms should be considered when prepubertal girls present with distressing perineal or vaginal pain, and treatment with weekly mebendazole should be offered.


Unlimited volumes of laboratory data: a confusing and diagnostically deceptive product of modern technology.
The large volumes of laboratory data currently available in clinical practice can lead to erroneous conclusions. Our current statistical interpretation of these data is univariate (one variable at a time) and often not age- and sex-corrected. Using an optimal technique of multivariate analysis, a SMAC profile of 19 tests performed on normal subjects resulted in over a 500% improvement in defining the reference range. Using physiologic subsets of the SMAC profile for patients, improvements in interpretation of between 100% and 300% are possible. Results indicate a serious clinical problem that will require modification of laboratory reports using modern technology as an adjunct for diagnostic medicine.


A curious gunshot injury.
The case of a victim of an unusual gunshot injury is described. The man had been 'knee-capped' and on arrival at hospital was found to have two bullets and a cartridge casing in the knee joint. These had entered through one entrance wound. A ballistic report describes how the incident occurred.


Characterization of the various forms of the Reelin protein in the cerebrospinal fluid of normal subjects and in neurological diseases.
Reelin is a large extracellular glycoprotein that is defective in reeler mutant mice and plays a well-established role during brain development in human as well as rodents. In the adult brain, Reelin is expressed in a subset of GABAergic interneurons. Its role in disease states is not clearly defined, although it is implicated in autism and psychoses such as schizophrenia. In this report, we show that Reelin immunoreactive proteins can be detected in the human cerebrospinal fluid (CSF) with monoclonal antibodies directed against the N- and C-terminal regions of the protein. In CSF, Reelin is present as different products due to processing at two main sites; preservation at -20 degrees C increases processing further. CSF Reelin originates from the brain tissue and not from plasma. The protein was detected in comparable concentrations in children and adults, and the signal varied largely from subject to subject with no obvious correlation with age or neurological disease state.


The fine structure of epidermal lines on arms and head of postembryonic Sepia officinalis and Loligo vulgaris (Mollusca, Cephalopoda).
The structure and cell types of the epidermal lines that are found on the surface of the head and arms of Sepia officinalis and Loligo vulgaris, were investigated by light- and transmission electron microscopy. The lines consist of ciliated cells and non-ciliated, accessory cells. The axon of the ciliated cell and the ultrastructure of the latter indicate that this element is sensory; therefore, the epidermal lines of cephalopods may be regarded as a type of sensory organ.


A fully implantable stimulator with wireless power and data transmission for experimental use in epidural spinal cord stimulation.
Epidural spinal cord stimulation (ESCS) combined with partial weight bearing therapy (PWBT) has been reported to facilitate recovery of functional walking for individuals after chronic incomplete spinal cord injury. This paper describes a low cost, fully implantable, advanced ESCS stimulator that can be manufactured in a research laboratory for use in small animals. The system is composed of four main parts: an external personal digital assistant (PDA), an external controller, an implantable pulse generator (IPG), lead extension and electrode. The PDA allows the experimenter to program the stimulation parameters through a user-friendly graphical interface. The external controller placed on the rat back communicates with PDA via RF telemetry. The IPG generates the biphasic charge-balanced voltage-regulated pulses, which are delivered to the bipolar electrode by the lead extension to achieve chronic ESCS in freely moving rats. A RF carrier from the Class-E amplifier in the external controller provides both data and power for the implanted circuitry through a closely coupled inductive link. The IPG is hermetically packaged using a silicon elastomer and measures 22 mm × 23 mm × 7 mm with a mass of ~3.78 g.


Occupational exposure to veterinary antibiotics: Pharmacokinetics of enrofloxacin in humans after dermal, inhalation and oral uptake - A clinical study.
Occupational exposure to veterinary antibiotics in hen houses at poultry feeding farms was demonstrated by biomonitoring campaigns in the past. The objective of this study was to investigate pharmacokinetics of three uptake routes: dermal, oral and inhaled. In an open-label cross-over study, six healthy volunteers were exposed to single occupational relevant doses of enrofloxacin. Plasma and urine samples were analysed for enrofloxacin and ciprofloxacin. Physiologically based pharmacokinetic (PBPK) modelling based on bioanalysis data showed underestimation for the elimination rate in comparison to experimental data pointing towards a lack of sufficient ADME information and limitations of available physico-chemical properties of the parent drug. The data obtained in this study indicate that oral uptake with its various sources, e.g. airborne enrofloxacin, direct hand-mouth contact, is the major source for occupational exposure to enrofloxacin in hen houses. Dermal exposure was considered negligible.


Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model.
Cyclic alveolar recruitment/derecruitment (R/D) is an important mechanism of ventilator-associated lung injury. In experimental models this process can be measured with high temporal resolution by detection of respiratory-dependent oscillations of the paO2 (ΔpaO2). A previous study showed that end-expiratory collapse can be prevented by an increased respiratory rate in saline-lavaged rabbits. The current study compares the effects of increased positive end-expiratory pressure (PEEP) versus an individually titrated respiratory rate (RRind) on intra-tidal amplitude of Δ paO2 and on average paO2 in saline-lavaged pigs. Acute lung injury was induced by bronchoalveolar lavage in 16 anaesthetized pigs. R/D was induced and measured by a fast-responding intra-aortic probe measuring paO2. Ventilatory interventions (RRind (n=8) versus extrinsic PEEP (n=8)) were applied for 30 minutes to reduce Δ paO2. Haemodynamics, spirometry and Δ paO2 were monitored and the Ventilation/Perfusion distributions were assessed by multiple inert gas elimination. The main endpoints average and Δ paO2 following the interventions were analysed by Mann-Whitney-U-Test and Bonferroni's correction. The secondary parameters were tested in an explorative manner. Both interventions reduced Δ paO2. In the RRind group, ΔpaO2 was significantly smaller (P<0.001). The average paO2 continuously decreased following RRind and was significantly higher in the PEEP group (P<0.001). A sustained difference of the ventilation/perfusion distribution and shunt fractions confirms these findings. The RRind application required less vasopressor administration. Different recruitment kinetics were found compared to previous small animal models and these differences were primarily determined by kinetics of end-expiratory collapse. In this porcine model, respiratory rate and increased PEEP were both effective in reducing the amplitude of paO2 oscillations. In contrast to a recent study in a small animal model, however, increased respiratory rate did not maintain end-expiratory recruitment and ultimately resulted in reduced average paO2 and increased shunt fraction.


An electroaffinity labelling platform for chemoproteomic-based target identification.
Target identification involves deconvoluting the protein target of a pharmacologically active, small-molecule ligand, a process that is critical for early drug discovery yet technically challenging. Photoaffinity labelling strategies have become the benchmark for small-molecule target deconvolution, but covalent protein capture requires the use of high-energy ultraviolet light, which can complicate downstream target identification. Thus, there is a strong demand for alternative technologies that allow for controlled activation of chemical probes to covalently label their protein target. Here we introduce an electroaffinity labelling platform that leverages the use of a small, redox-active diazetidinone functional group to enable chemoproteomic-based target identification of pharmacophores within live cell environments. The underlying discovery to enable this platform is that the diazetidinone can be electrochemically oxidized to reveal a reactive intermediate useful for covalent modification of proteins. This work demonstrates the electrochemical platform to be a functional tool for drug-target identification.


Comparison of Nd:YAG laser (532 nm green) vs diode laser (810 nm) photocoagulation in the treatment of retinopathy of prematurity: an evaluation in terms of complications.
To compare the anterior and posterior segment complications of diode (810 nm) laser photocoagulation (LPC) and Nd:YAG (532 nm green) LPC in the treatment of retinopathy of prematurity (ROP). The 84 eyes of 43 patients treated with diode LPC (group 1) and 58 eyes of 31 patients treated with Nd:YAG LPC (group 2) for ROP in our clinic were enrolled in the study. Medical records of all patients were investigated retrospectively. The patients in each group were examined in terms of birth weights, gestational weeks, stage of retinopathy, number of lasers pots, laser parameters, and anterior and posterior complications of LPC. The mean birth weeks of group 1 patients were postmenstrual 27.7 ± 2.5 (23-33), while the mean birth weights were 1006.0 ± 334.5 (540-1980) grams. The mean birth weeks of group 2 patients were postmenstrual 27.4 ± 2.6 (23-33), while the mean birth weights were 1073.8 ± 329.2 (480-1720) grams. The mean numbers of laser spots were 1036.0 ± 515.2 (430-2410) in group 1 per eye, while the mean numbers of laser spots were 1085.4 ± 526.0 (445-2530) in group 2 per eye (p ≥ 0.05). Additional laser application was performed in four eyes (4.8%) in group 1 and four eyes (6.9%) in group 2. Four eyes (4.8%) treated with diode LPC and one eye (1.7%) treated with Nd:YAG laser developed retinal detachment. Two eyes of a patient (3.4%) applied Nd:YAG LPC developed cataract. Cataract may develop when Nd:YAG laser is used; however, posterior segment complications may be more likely to appear with the use of diode laser in these cases.


Relationship between waist circumference, visceral fat and metabolic syndrome in a Congolese community: further research is still to be undertaken.
The criteria of positivity of waist circumference to define the metabolic syndrome as currently recommended for the population of sub-Saharan Africa do not take into account specific ethnic or regional variation. The predictive value of different values of waist circumference compared with visceral fat as determined by OMRON BF510 body composition in 360 indigenous patients from Bukavu city between June 1, 2010 and May 30, 2011 was studied. The prevalence was higher in women for enlarged waist circumference according to the pathological IDF or NCEP/ATP III threshold (p<0.0001) contrasting with lower rates for pathological accumulation of visceral fat in men (p=0.0001). The highest values for sensitivity and specificity were obtained for a threshold value of 95 cm for men (sensitivity=72.4%, specificity=91.1%, area under the curve (99% CI)=0.899 (0.833 to 0.965)) and 99 cm in women (sensitivity=75.0%, specificity=78.3%, AUC (99% CI)=0.844 (0.777 to 0.911)). This test also showed an independent effect on the probability of accumulation of visceral fat (Odd adjusted OR=5.0 (99% CI: 2.1 to 11.7), p<0.0001). The threshold value for pathological waist circumference currently used for black African populations may overpredict abdominal fat excess in women. Further studies are needed to provide adequate cutoffs in sub-Saharan populations.