Cerebral (31)P magnetic resonance spectroscopy and systemic acid-base balance during hypoxia in fetal sheep.
The purpose of this study was to investigate cerebral energy metabolism and acid-base homeostasis during impaired oxygen supply in fetal sheep. Systemic acid-base balance was correlated with the sequence in changes of cerebral phosphorus metabolite ratios and intracellular pH. Phosphorus magnetic resonance spectra were obtained from the brain of six fetal sheep simultaneously with repeated measurements of fetal arterial oxygen saturation and acid-base balance. Fetal hypoxia was induced by gradually reducing the oxygen supply to the anesthetized pregnant ewe to establish an intended arterial pH of 7.00 or lower. The ratio of phosphocreatine to inorganic phosphate decreased from 1.08 +/- 0.10 (SD) during the control period to 0.77 +/- 0.29 at an arterial pH between 7.20 and 7.25. The inorganic phosphate level became significantly increased at an arterial pH between 7.10 and 7.15 compared with control values. With ongoing arterial acidosis, cerebral intracellular pH decreased linearly with the arterial pH. At an arterial pH of 7.00, cerebral intracellular pH was decreased from 7.18 +/- 0.03 to 6.71 +/- 0.28, and phosphocreatine and nucleoside triphosphates levels were decreased significantly. In fetal sheep brain, cerebral oxidative phosphorylation (ratio of phosphocreatine to inorganic phosphate) is already affected at a mild arterial acidosis. At an arterial pH of 7.00 or lower, nucleoside triphosphates disappeared, which almost inevitably was followed by death in fetal sheep.


Vacuolar CBL-CIPK12 Ca(2+)-sensor-kinase complexes are required for polarized pollen tube growth.
Polarized tip growth is a fundamental process of specialized eukaryotic cells like neuronal axons, fungal hyphae, and plant root hairs and pollen tubes. In pollen tubes, a tip-focused oscillating Ca(2+) gradient governs ions fluxes, vesicle transport, and cytoskeleton dynamics to ensure proper polarized cell growth [1, 2]. While a crucial role of vacuolar Ca(2+) signaling is established for cellular movements like guard cell dynamics [3-5], its contribution to polarized growth remains to be defined. Here we identified the two closely related tonoplast-localized Ca(2+)-sensor proteins CBL2 and CBL3 as crucial regulators of vacuolar dynamics and polarized pollen tube growth. Overexpression of CBL2 or CBL3 in Arabidopsis and tobacco pollen tubes affected vacuolar morphology, pollen germination, and tube growth, but did not alter actin organization, PI(4,5)P2 distribution, or tip-focused Ca(2+) oscillations. Similarly, loss of function of each single Ca(2+) sensor and cbl2/cbl3 double mutants exhibited impaired pollen tube growth in vitro and in vivo. Both Ca(2+) sensors interacted with the kinase CIPK12, which translocated from the cytoplasm to the vacuolar membrane upon this interaction. Also, overexpression of CIPK12 induced severe vacuolar phenotypes, and loss of function of CIPK12 lead to impairment of polar growth. Remarkably, co-expression of CBL2 or CBL3 with CIPK12 resulted in a phosphorylation-dependent, massively enhanced vacuolar inflation and further disruption of polar growth. Together, these findings identify an essential role of the vacuole and vacuolar Ca(2+) signaling for polarized tip growth. We propose that a faithfully balanced activity of Ca(2+)-activated CBL2/3-CIPK12 complexes fulfills fundamental functions to enable the fast growth of pollen tubes in higher plants.


Life-history responses of Daphnia magna Straus to binary mixtures of toxic substances: pharmacological versus ecotoxicological modes of action.
Two prevailing theoretical models: concentration addition (CA) and independent action (IA), predict mixture toxicity on the basis of known toxicities of the mixture components. To date, both models have been in most occasions evaluated using unicellular in vivo responses or biochemical in vitro responses. However, when considering more complex models such as the whole organism physiology or life-history traits, the dominant ecotoxicological mode of action, based on the exposure concentrations at which various toxicological effects become operative at the level of whole organism, should be considered. Offspring production in Daphnia magna is driven by the resources acquired from food, and the number of live offspring produced by an organism is the result of two independent factors: the number of eggs produced and the percentage of eggs that survive egg development. In this study joint toxicity effects on offspring production in D. magna were tested using binary mixtures of toxic contaminants known to specifically impair food acquisition (lambda-cyhalothrin and cadmium) or to cause egg mortality during development (3,4 dichloroaniline). Tests were performed using a simplified 10-day reproduction assay initiated with gravid females. The results obtained indicate that irrespective of their primary pharmacological mode of action, the joint toxicity of cadmium and lambda-cyhalothrin was predicted by the CA model, whereas the joint toxicity of cadmium and 3,4 dichloroaniline was predicted by the IA model. Thus, the results obtained indicate that for life-history traits such as reproduction responses, the dominant ecotoxicological rather than the pharmacological mode of action should be used for predicting joint mixture effects.


Performance of Five Postharvest Storage Methods for Maize Preservation in Northern Benin.
Several postharvest technologies are currently being commercialized to help smallholder farmers in sub-Saharan Africa reduce grain storage losses. We carried out a study in Northern Benin to compare the effectiveness of five technologies being sold to protect stored grain. Maize that had been naturally infested by insects was stored in four hermetic storage technologies (SuperGrainbag™, AgroZ® bag, EVAL™, and Purdue Improved Crop Storage-PICS™ bags), an insecticide impregnated bag (ZeroFly®), and a regular polypropylene (PP) woven bag as control. Oxygen levels in hermetic bags fluctuated between 0.5 ± 0.0 (v/v) and 1.0 ± 0.3 (v/v) percent during the seven months of storage. No weight loss or insect damage was observed in grain stored in any of the hermetic storage bags after seven months. However, grain stored in ZeroFly® and PP woven bags had weight losses of 6.3% and 10.3%, respectively. These results will help farmers and development agencies when making decisions to use and/or promote storage technologies to reduce postharvest grain losses.


Deriving convincing human health ambient water quality criteria for benzo[a]pyrene and providing basis for the water quality management: The impacts of national bioaccumulation factors and probabilistic modeling.
Science-based water quality criteria are the cornerstone of water quality standards. This paper improved the methodology for the derivation of human health water quality criteria (HHWQC) and applied it for benzo[a]pyrene (BaP) to provide a scientific basis for the management of polycyclic aromatic hydrocarbons (PAHs) in surface waters. First, the national bioaccumulation factors (BAFs) for BaP were derived using field-measured BAFs and field-measured biota-sediment accumulation factors (BSAFs) across China, respectively, which results were comparable and demonstrated the reliability of the obtained national BAFs for BaP. The HHWQC for BaP derived using the probabilistic approach were 3.98-4.70 ng/L and were comparable with those derived by the deterministic approach, suggesting the accuracy of derived HHWQC for BaP. Through the probabilistic approach, the probability distributions of lifetime incremental cancer risk from BaP in water were provided and the consumption rates of aquatic products at trophic level 2 and 3 were identified as factors influencing risks of BaP significantly. The derived HHWQC for BaP in China are approximately 33-36 times higher than those in the United States because of the high national BAFs and cancer slope factor of BaP used for the United States. In addition, the recommended HHWQC for BaP conform to the situation in China and are approximately 1.5 times higher than the standard value of BaP in the current National Surface Water Quality Standard (GB 3838-2002) in China (2.80 ng/L), which will play an important role in the amendment of National Surface Water Quality Standard in the future. Approximately 36% of the studied surface freshwater in China contains BaP with levels exceeding the recommended HHWQC, suggesting the pollution of BaP in surface freshwater is severe and needs to be given more attention. This study is significant for the scientific development of HHWQC worldwide and the management of pollutants in water.


Lack of suppressive activity of human primary melanoma cells on the activation of autologous lymphocytes.
Previous studies have indicated that primary but not metastatic melanomas were able to stimulate the proliferation of autologous (Auto) peripheral blood lymphocytes (PBL) in 73% of cases. On the other hand, 57% of the metastatic melanomas were shown to be suppressive when melanoma cells (Me) were admixed with Auto-PBL stimulated with allogeneic (Allo) PBL or interleukin 2 (IL-2) at the beginning of a 6-day incubation period. Here, we report that the suppressive activity of Me is a functional characteristic associated with a particular stage of the disease. In fact, we found that none of the 11 primary tumors tested were able to inhibit the proliferative response of Auto-PBL to Allo-PBL or IL-2 at all the doses of tumor cells used. The generation of lymphocytes cytotoxic against Auto-Me or K562 was also not inhibited. Of the 11 primary tumors checked for suppression, 8 were able to stimulate Auto-PBL in a primary mixed lymphocyte tumor culture. We conclude that opposite functions, stimulation and inhibition of autologous lymphocyte responses are characteristics of primary and metastatic Me, respectively.


Meta-analysis of randomized controlled trials comparing lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair.
Lichtenstein inguinal hernia repair is associated with a low incidence of recurrence; however, the use of heavyweight mesh has been linked with chronic pain and foreign body sensation. It is hypothesized that the use of lightweight mesh may reduce these problems. This study aims to use meta-analysis to compare lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair. Information was gathered from randomized controlled trials that compared lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair. The Cochrane Library, Medline, EMBASE, trial registries, conference proceedings and reference lists were searched. Primary outcome measures were chronic pain, foreign body sensation and hernia recurrence. Secondary outcome measures were duration of surgery, mean visual analogue scale (VAS) pain scores, surgical-site infection, testicular atrophy and haematoma/seroma. The pooled Peto odds ratio (OR) was calculated for categorical data and weighted mean difference (WMD) for continuous data. Six trials with 1936 hernias were included. Lightweight mesh was associated with reduced chronic pain (OR = 0.67, 95% CI = 0.50-0.90; p < 0.01) and foreign body sensation (OR = 0.43, 95% CI = 0.21-0.93; p < 0.05). Lightweight mesh was also associated with lower VAS pain scores at 3 months after surgery (WMD = -0.35, 95% CI = -0.39 to -0.31; p < 0.0001). There were no differences in hernia recurrence (OR = 1.19, 95% CI = 0.54-2.64; p = 0.66) or other post-operative complications between the two groups. The use of lightweight mesh in Lichtenstein inguinal hernia repair is associated with less chronic pain, and foreign body sensation compared with heavyweight mesh without any difference in recurrence.


Variation in theophylline clearance rate with time in chronic childhood asthma.
Wide theophylline clearance rate (TCR) range between different individuals has been reported, but little is known about its change with the passage of time. Optimal theophylline therapy for asthma aimed at plasma or serum levels of 10 to 20 microng/ml is now strongly recommended. Significant TCR variability with time might easily result in theophylline levels in the toxic or subtherapeutic ranges. Thirty severe asthmatics (mean age, 13 yr) received 24 hr constant intravenous infusion of 1 mg/kg/hr aminophylline USP. TCR was determined after a steady state was reached. Twelve of these patients with persisting poorly controlled asthma underwent repeat infusion for TCR determination at intervals of 1 to 8 mo (mean, 4.7 mo). When these results were compared to the initial individual TCR, the mean absolute change was 28 +/- 24% (mean +/-SD). Thus, this significant individual variation in TCR with the passage of time (p less than 0.01) requires periodic monitoring of plasma theophylline levels in severe asthma treated by optimized theophylline dosage.


Authoritarian parenting and youth depression: Results from a national study.
Depression is a prevalent illness affecting youth across the nation. The study purpose was to examine depression and authoritarian parenting among youth from 12 to 17 years of age. A secondary data analysis of the National Survey on Drug Use and Health was performed in the present study. All participants in the present study were youth (N = 17,399) nationwide. The results revealed that 80.6% of youth participants reported having five or more depressive symptoms. Parenting styles based on depression significantly differed among males, females, 12-13-year-olds, 14-15-year-olds, and 16-17-year-olds. Specifically, those who reported experiencing authoritarian parenting practices were more likely to report depressive symptoms compared to their counterparts who experienced authoritative parenting practices. Emphasizing the role of the parents and teaching positive parenting practices and authoritative parenting styles may increase success of prevention programs.


Multicystic encephalomalacia after first-trimester intrauterine fetal death in monochorionic twins.
Multicystic encephalomalacia occurs in approximately 20% of surviving cotwins after second- and third-trimester intrauterine fetal death of one twin in monochorionic pregnancies. We report a case of multicystic encephalomalacia after the demise of a cotwin in the first trimester diagnosed by magnetic resonance imaging and confirmed pathologically.


Fatty acids in green algae cultivated on a pilot-plant scale.
Fatty acids from Chlorella vulgaris, Scenedesmus obliquus var. acutus and from a mixed culture of the two strains, Melnik, were converted to methyl esters, separated by gas chromatography, and identified by means of standards. The spectrum of fatty acids included both saturated and unsaturated acids (with odd and even numbers of carbon atoms) from C12 to C22. Fatty acids C16:0, C18:0 and C20:3 were the major components in all cultures. Pure strains differed from the mixed culture in the production of C18:1, C12:0 and C19:2 acids; the first of these was present in higher amounts in pure cultures only, the latter two being found in the mixed culture. The level of lipids was lower as compared to the literature data and their extractability was affected by the manner of preparation of algae and extraction conditions.


New measures of right ventricle-pulmonary artery coupling in heart failure: An all-cause mortality echocardiographic study.
Right ventricle-pulmonary artery coupling (RVPAC) has emerged from pathophysiology to clinical interest for prognostic implication in heart failure and is commonly measured as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/SPAP). However, feasibility of SPAP is limited (down to 60% in trials, and maybe lower in clinical practice). We ought to assess the prognostic value of the TAPSE times pulmonary acceleration time (TAPSE x pACT) product and TAPSE to peak tricuspid regurgitation velocity (TAPSE/TRV) ratio as new alternative measures of RVPAC. Two-hundred patients hospitalized with heart failure were followed-up (median time of 2.7 years) and 82 died. Non survivors had significantly lower TAPSE/SPAP, TAPSE x pACT and TAPSE/TRV than survivors (0.31 vs 0.40 mm/mmHg, 130 vs 156 cm·ms, 5.0 vs 5.8 ms, respectively). Four multivariate models were performed, each one including TAPSE, TAPSE/SPAP, TAPSE x pACT or TAPSE/TRV. TAPSE/SPAP resulted the most powerful predictor of mortality (HR 0.74 per mm/mmHg increase, P < 0.001, C-Statistic 0.778), followed by TAPSE x pACT (HR 0.95 per 10 cm·ms increase, P = 0.013, C-Statistic 0.776), TAPSE/TRV (HR 0.76 per ms increase, P < 0.001, C-Statistic 0.774) and TAPSE (HR 0.91 per mm increase, P = 0.003, C-Statistic 0.769). Cutoff values of 140 cm·ms and 5.5 ms were respectively identified for TAPSE x pACT and TAPSE/TRV with receiving operating characteristic analysis for mortality. TAPSE x pACT product and TAPSE/TRV ratio are alternative measures of RVPAC for prognostic assessment in heart failure that can be applied if TAPSE/SPAP is not feasible.


C1-C2 instability with severe occipital headache in the setting of vertebral artery facet complex erosion.
An exact understanding of patient vertebral artery anatomy is essential to safely place screws at the atlanto-axial level in posterior arthrodesis. We aim to report a case of erosion of the left vertebral artery into the C1-C2 facet complex with resultant rotatory and lateral listhesis presenting with severe occipital headache. This represents a novel etiology for this diagnosis and our report illustrates technical considerations when instrumenting the C1-C2 segment. We report a case of severe occipital headache due to C1-C2 instability with resultant left C2 nerve compression in the setting of erosion of the vertebral artery into the C1-C2 facet complex. A 68-year-old woman presented with a 12-month history of progressively debilitating headache and neck pain with atlanto-axial instability. Computed tomography (CT) angiography demonstrated erosion of the left vertebral artery into the left C1-C2 facet complex. In addition, the tortuous vertebral arteries had eroded into the C2 pedicles, eliminating the possibility for posterior pedicle screw placement. The patient underwent posterior arthrodesis of C1-C2 utilizing bilateral lateral mass fixation into C1 and bilateral trans-laminar fixation into C2 with resolution of all preoperative complaints. This study constitutes the first report of a tortuous vertebral artery causing the partial destruction of a C1-C2 facet complex, as well as instability, with the clinical presentation of severe occipital headache. It hereby presents a novel etiology for both the development of C1-C2 segment instability as well as the development of occipital headache. Careful evaluation of such lesions utilizing CT angiography is important when formulating a surgical plan.


The rise in divorce rates, 1960-1974: age-specific omponents.
This paper uses vital statistics data from 15 states in the Divorce Registration Area to decompose into age-specific components the rise in the aggregate divorce rate between 1960 and 1974. While women in their twenties comprise only about 20 percent of the married population, they appear to have contributed over 60 percent of the growth in the divorce rate during the decade of the sixties,


Metabolic profile of keratoconic cornea.
To investigate the difference in metabolic profile of keratoconic and normal corneas using two different analysis methods. Keratoconic corneas were obtained from patients (aged 19-27) during transplantation surgery. Control samples were obtained from human donors (aged 61-75) 1-8 h post-mortem. The metabolic profile of tissues was investigated with high-resolution magic angle spinning (1)H nuclear magnetic resonance (NMR) spectroscopy and high performance liquid chromatography (HPLC). Nine amino acids and 20 metabolites were assigned with HPLC and NMR spectroscopy, respectively. No significant biochemical difference was revealed between keratoconic and control samples, which represent distant age groups. It suggests that development of keratoconus might be related to the accelerated ageing of the cornea. This issue warrants further studies.


Teratogenic effects of benzo[a]pyrene in developing chick embryo.
The effect of benzo[a]pyrene (BP), an established carcinogen, on developing chick embryos was investigated. The embryos were exposed in different stages of development to various doses of BP via the yolk sac route. This resulted in retarded growth, as reflected by lower embryonic body weight, reduced crown-rump length and bill length. Abnormal survivors showed remarkably twisted legs with shortening of the bones, abdominal oedema, haematomas, blisters and a short neck. These findings suggest that BP is a teratogen when injected via this route, and the 'oedema syndrome' is a possible mechanism causing teratogenic effects in developing chick embryos when treated with BP.


Intelligent attendance monitoring system with spatio-temporal human action recognition.
This paper proposes an intelligent attendance monitoring system based on spatio-temporal human action recognition, which includes human skeleton gait recognition, multi-action body silhouette recognition and face recognition. Our system solves several problems, for example, when a mask is worn to conceal the face, which leads to a decrease in recognition accuracy performance, and when a 3D face mask is used to fake an identity. The skeleton gait feature of our intelligent attendance monitoring system uses a temporal weighted K-nearest neighbours algorithm to train the recognition model and carry out identification, while the multi-action body silhouette feature uses a multiple K-nearest neighbours algorithm to train the recognition model, identify the person and vote on the outcome. Using the proposed system, which integrates skeleton gait features, action silhouette features and face features, more effective recognition can be achieved. When the system encounters a situation with feature masking, such as when an individual is wearing a mask or has changed their clothes, or when the viewing angle is masked, it can continue to deliver good recognition ability through multi-angle skeleton synthesis gait recognition. Our experimental results show that the recognition accuracy of the system is 83.33% when a specific person wears a mask and passes through a monitored area. The intelligent attendance monitoring system uses a LINE messaging API as the access control notification function and provides a responsive web platform that allows managers to perform follow-up management and monitoring.


Outcome of percutaneous drainage in patients with pancreatic necrosis having organ failure.
Percutaneous catheter drainage (PCD) is an effective way of drainage in acute pancreatitis (AP) and its role in persistent organ failure (OF) has not been studied. This study assessed the outcome of severe AP managed with PCD. We retrospectively analysed outcome of AP patients undergoing PCD for persistent OF with respect to success of PCD, etiology, severity scores, OF, imaging features and PCD parameters. Success of PCD was defined as resolution of with PCD and survived without surgical necrosectomy. Between January 2016 and May 2018, 83 patients underwent PCD for persistent OF at a mean duration of 25.59 ± 21.2 days from pain onset with successful outcome in 47 (56.6%) patients. Among PCD failures, eleven (13.25%) patients underwent surgery. Overall mortality was 31 (37.3%). On multivariate analysis, pancreatic necrosis <50% and absence of extrapancreatic infection (EPI) predicted the success of PCD. Presence of infected necrosis did not affect the outcome of PCD in organ failure. PCD improves the outcome in patients with OF even when done early irrespective of the status of infection of necrosis. Therefore, PCD may be considered early in the course of patients with OF.


Implicit and explicit self-schema in active deluded, remitted deluded, and depressed patients.
The main objective of this study was to analyze the hypothesis that patients with persecutory delusions would show a depressive-type self-concept when assessed with implicit measures of self-schema (i.e., a free recall test of self-relevant adjectives) but would show a normal self-concept when assessed with explicit measures (i.e., a self-concept questionnaire and a task requiring endorsement of self-relevant adjectives). The sample consisted of 136 participants (40 acute deluded participants, 25 remitted deluded participants, 35 depressed patients and 36 normal controls). Our results revealed that both groups of deluded participants showed no significant discrepancy between explicit and implicit measures of self-concept. These findings do not support the hypothesis of an implicit negative cognitive schema in persecutory deluded participants.


Reciprocal changes in center and surrounding S potentials of fish retina in response to dopamine.
Effects of dopamine (DA) were examined on the intracellularly recorded potential from horizontal cells in the fish (Eugerres plumieri) rentina. DA (100 micron in the perfusate) augmented the center S potential in a response to a spot illumination and attenuated the surrounding S potential to an annular light by approximately 40%. These reciprocal changes in the S potentials were associated with a slight depolarization (2.5 mV) of the horizontal cell, and were reversible in 10-15 min. The results indicate that DA at this concentration does not affect directly the synaptic transmission from photoreceptors to horizontal cells, while it appears to interfere selectively with the lateral propagation of an S potential. The effects of DA observed may represent an aspect of function of DA-containing interplexiform cells in the retina.


Highly Active Thermophilic L-Asparaginase from Melioribacter roseus Represents a Novel Large Group of Type II Bacterial L-Asparaginases from Chlorobi-Ignavibacteriae-Bacteroidetes Clade.
L-asparaginase (L-ASNase) is a biotechnologically relevant enzyme for the pharmaceutical, biosensor and food industries. Efforts to discover new promising L-ASNases for different fields of biotechnology have turned this group of enzymes into a growing family with amazing diversity. Here, we report that thermophile Melioribacter roseus from Ignavibacteriae of the Bacteroidetes/Chlorobi group possesses two L-ASNases-bacterial type II (MrAII) and plant-type (MrAIII). The current study is focused on a novel L-ASNase MrAII that was expressed in Escherichia coli, purified and characterized. The enzyme is optimally active at 70 °C and pH 9.3, with a high L-asparaginase activity of 1530 U/mg and L-glutaminase activity ~19% of the activity compared with L-asparagine. The kinetic parameters KM and Vmax for the enzyme were 1.4 mM and 5573 µM/min, respectively. The change in MrAII activity was not significant in the presence of 10 mM Ni2+, Mg2+ or EDTA, but increased with the addition of Cu2+ and Ca2+ by 56% and 77%, respectively, and was completely inhibited by Zn2+, Fe3+ or urea solutions 2-8 M. MrAII displays differential cytotoxic activity: cancer cell lines K562, Jurkat, LnCap, and SCOV-3 were more sensitive to MrAII treatment, compared with normal cells. MrAII represents the first described enzyme of a large group of uncharacterized counterparts from the Chlorobi-Ignavibacteriae-Bacteroidetes clade.


Subjective well-being, but not subjective mental functioning shows positive associations with neuropsychological performance in schizophrenia-spectrum disorders.
To assess the association of subjective quality of life as measured by the Subjective Well-being under Neuroleptic Treatment questionnaire (SWN-K) with neuropsychological functioning; to address interactions with the SWN-K domain mental functioning as a measure of subjective cognitive dysfunction; and to examine the interaction of subjective well-being and psychopathology ratings. Forty-five patients diagnosed with schizophrenia spectrum disorder (SSD) were assessed regarding subjective well-being (SWN-K), neuropsychological impairment, and psychopathology (Brief Psychiatric Rating Scale; BPRS). After controlling for multiple comparisons, SWN-K total score showed significant positive correlations with concentration/attention (r=.498), working memory (r=.537), verbal memory (r=.522), and global cognition (r=.459). No correlations of SWN mental functioning and neuropsychological impairment remained significant after Bonferroni correction. Correlations between SWN-K subscales and neuropsychological functioning were generally positive, indicating higher subjective well-being in patients with better neurocognition. In multivariate analyses, global cognition was a significant predictor (p=.011), accounting for 19.7% of SWN total score variance. Adding BPRS total score as predictor (p=.054) explained an additional 6.9% of SWN-K variance. Linear regression analyses with SWN-K mental functioning as dependent variable did not yield statistically significant models. Subjective well-being and objective neuropsychological functioning show only moderate associations and can be seen as largely independent parameters. In particular, subjective mental functioning cannot serve as a proxy for objective neuropsychological testing.


Oral leukoplakia and the long-term risk of upper gastrointestinal cancer deaths in the Linxian dysplasia population.
To investigate oral leukoplakia (OL) and risk of upper gastrointestinal (UGI) cancer deaths in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. A total of 3318 subjects with esophageal squamous dysplasia enrolled on 1 May 1985, and were followed up until 30 September 2015. Participants with OL at baseline were treated as an exposed group, while the remainder was selected as a control group. All subjects were followed monthly and reviewed quarterly by the Linxian Cancer Registry. Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During the 30-year follow-up, a total of 902 UGI cancer deaths occurred, including 541 esophageal squamous cell carcinoma (ESCC) related, 284 gastric cardia carcinoma (GCC) related, and 77 gastric noncardia carcinoma (GNCC) related deaths. Relative to subjects without OL, the long-term risk of ESCC mortality in participants with OL increased by 26.1% (HR = 1.26, 95% CI: 1.05-1.52). In the subgroup analyses, adverse effects of OL on ESCC mortality were observed especially in younger subjects (HR = 1.48, 95% CI: 1.11-1.97), females (HR = 1.44, 95% CI: 1.11-1.89), non-smokers (HR = 1.44, 95% CI: 1.15-1.81), nondrinkers (HR = 1.28, 95% CI: 1.04-1.57), and individuals with a family history of cancer (HR = 1.37, 95% CI: 1.05-1.79). No associations were observed between OL and risk of GCC and GNCC mortality. OL may increase the long-term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non-smokers, and subjects with a family cancer history. Future studies are needed to explore the potentially etiological mechanism.


Comparison of mineral metabolites as risk factors for adverse clinical outcomes in CKD.
Patients with chronic kidney disease are at increased risk for progressing to end-stage renal disease, developing cardiovascular disease, and dying prematurely. Recent evidence has suggested that disordered mineral metabolism, which includes hyperphosphatemia, secondary hyperparathyroidism, vitamin D deficiency, and fibroblast growth factor 23 excess, may contribute to the high rates of adverse outcomes in this population. However, marked within-subject variability for some of these biochemical parameters exists, potentially detracting from the utility of certain metabolites as prognostic tools. This review summarizes the available data on the epidemiology of phosphate, parathyroid hormone, vitamin D, and fibroblast growth factor 23, and their relationships with adverse clinical outcomes in chronic kidney disease, compares the performance of each as a biomarker of risk and introduces recent insights into the pathophysiology behind some of the observed relationships.


RNA sequencing to characterize transcriptional changes of sexual maturation and mating in the female oriental fruit fly Bactrocera dorsalis.
Female reproductive potential plays a significant role in the survival and stability of species, and sexual maturation and mating processes are crucial. However, our knowledge of the reproductive genes involved in sexual maturation and mating has been largely limited to model organisms. The oriental fruit fly Bactrocera dorsalis is a highly invasive agricultural pest, known to cause major economic losses; thus, it is of great value to understand the transcriptional changes involved in sexual maturation and mating processes as well as the related genes. Here, we used a high-throughput sequencing method to identify multiple genes potentially involved in sexual maturation and mating in female B. dorsalis. We sequenced 39,999 unique genes with an average length of 883 bp. In total, 3264 differentially expressed genes (DEGs) were detected between mature virgin and immature Bactrocera dorsalis libraries, whereas only 83 DEGs were identified between flies that had mated or were mature virgins. These DEGs were functionally annotated using the GO and KEGG pathway annotation tools. Results showed that the main GO terms associated with the DEGs from the mature virgin vs. immature groups were primarily assigned to the metabolic and developmental processes, which we focused on, whereas those from the mated vs. mature virgin group largely belonged to the response to stimulus and immune system processes. Additionally, we identified multiple DEGs during sexual maturation that are involved in reproduction, and expression pattern analysis revealed that the majority DEGs detected were highly enriched in those linked to the ovaries or fat bodies. Several mating responsive genes differentially expressed after mating were also identified, and all antimicrobial peptides detected were highly enriched in fat body and significantly up-regulated approximately 2- to 10-fold at 24 h after mating. This study supplied female reproductive genes involved in sexual maturation and the post-mating response in B. dorsalis, based on RNA-seq. Our data will facilitate molecular research related to reproduction and provide abundant target genes for effective control of this agricultural pest.


Primary hepatocellular carcinoma and hepatitis B virus infection in Korea.
Serological evidence of hepatitis B virus (HBV) infection and serum alphafetoprotein (AFP) were assayed in sera from 112 Korean patients with primary hepatocellular carcinoma (PHC) and from 63 age- and sex-matched controls. Serological evidence of HBV infection was found in 100% of PHC patients and in 97% of controls. The majority of PHC patients (87%) were positive for hepatitis B surface antigen (HBsAg). In contrast, only 14% of control individuals were positive for HBsAg, but 82% were positive for antibody to HBsAg (anti-HBs). Hepatitis B e antigen (HBeAg) was detected in a high percentage (38%) of HBsAg-positive PHC patients, but in none of the nine HBsAg-positive control individuals. Serum AFP was detectable in 83% of PHC patients but in only one of 63 controls (1.5%). These results document that HBV infection may be the major factor in the development of PHC in this country.


Papillary muscle insertion directly into the anterior mitral leaflet in hypertrophic cardiomyopathy, its identification and cause of outflow obstruction by cardiac magnetic resonance imaging, and its surgical management.
This case presents an uncommon but important mechanism of muscular left ventricular outflow obstruction in hypertrophic cardiomyopathy due to anomalous and direct papillary muscle insertion into the anterior mitral leaflet, a finding reliably identified clinically by cardiac magnetic resonance imaging. The identification of this left ventricular outflow tract morphology is important before invasive ventricular septal reduction therapy because it dictates a specific surgical strategy. These findings further support the role of cardiac magnetic resonance imaging in the early evaluation of hypertrophic cardiomyopathy patients.


[Transcultural aspects of depression].
For many decades it was assumed that depressive disorders are mainly a problem of Western societies. However, a World Bank report published in 1993 revealed that Major Depression is already the fifth leading contributor to the Global Burden of Disease (GBD) among women in developmentally disadvantaged countries. The core symptoms of depression are disorders of affect, conduct and somatic complaints. In Western societies, the key symptom of depression is regarded to be a disorder of affect. However, in other cultural settings, different symptoms may be more central for depression. Nowadays mental health specialists have regular contact with patients from different cultural backgrounds. In order to achieve optimal results in diagnosing and treating mental disorders, it is important to consider the cultural background of a patient and her or his explanatory model of the disease. Transcultural psychiatry and psychotherapy aims at developing culture-sensitive concepts for treatment and mental health services and tries to increase insight in culture-related psychopathology and epidemiology.


Preclinical Evidence for the Effectiveness of Mesenchymal Stromal Cells for Diabetic Cardiomyopathy: A Systematic Review and Meta-analysis.
Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus that endangers human health. DCM results in cardiac dysfunction, which eventually progresses to heart failure. Mesenchymal stromal cells (MSCs), a type of multipotent stem cell, have shown promising therapeutic effects in various cardiovascular diseases and diabetic complications in preclinical studies due to their immunomodulatory and regenerative abilities. However, there is still a lack of evidence to summarize the effectiveness of MSCs in the treatment of DCM. Therefore, a meta-analysis and systematic review are warranted to evaluate the therapeutic potential of MSCs for DCM in preclinical studies. A comprehensive literature search in English or Chinese was conducted in PubMed, EMBASE, web of Science, Cochrane Library, and China National Knowledge Internet from inception to June 30, 2022. The summarized outcomes included echocardiography, morphology, and pathology. Data were independently extracted and analyzed by two authors. The software we adopted was Review Manager5.4.1. This systematic review was written in compliance with PRISMA 2020 and the review protocol was registered on PROSPERO, registration no. CRD42022350032. We included 20 studies in our meta-analysis to examine the efficacy of MSCs in the treatment of DCM. The MSC-treated group showed a statistically significant effect on left ventricular ejection fraction (WMD=12.61, 95% CI 4.32 to 20.90, P=0.003) and short axis fractional shortening (WMD=6.84, 95% CI 4.09 to 9.59, P < 0.00001). The overall effects on the ratio of early to late diastolic mitral annular velocity, left ventricular end-diastolic pressure, maximum positive pressure development, maximum negative pressure development, left ventricular relaxation time constant, heart weight to body weight ratio, fibrosis area, and arteriole density were analyzed, suggesting that MSCs represent an effective therapy for the treatment of DCM. Our results suggest a therapeutic role for MSCs in the treatment of DCM, and these results provide support for the use of MSCs in clinical trials of patients with DCM.


Characterization of Lactococcus lactis response to ampicillin and ciprofloxacin using surface-enhanced Raman spectroscopy.
Decades of antibiotic use or misuse has resulted in antibiotic resistance in lactic acid bacteria, a group of common culture starters and probiotic microorganisms. This has urged researchers to study how lactic acid bacteria respond to antibiotics, so as to have a better strategy to identify and predict the antibiotic-resistant bacteria. This study aimed to characterize the biochemical profiles of Lactococcus lactis responding to antibiotics using surface-enhanced Raman spectroscopy (SERS). Lactococcus lactis exposed to antibiotics was mixed with 50-nm gold nanoparticles for subsequent SERS measurements. The SERS spectra analyzed by principal component analysis showed no significant change after 30 min of antibiotic treatment, whereas distinct changes were clearly observed after 60 and 90 min of antibiotic treatment. Different antibiotics induced different spectral changes, and these changes revealed the detailed biochemical information of cellular responses. This study demonstrates that the SERS method developed not only senses the changes in the bacterial cell wall, but also reveals details of the biochemical profiles, which help us to understand how lactic acid bacteria respond to antibiotics, as well as to set a base for the detection of antibiotic susceptibility of bacteria by SERS.


Pharmacodynamic analysis of recombinant human erythropoietin effect on reticulocyte production rate and age distribution in healthy subjects.
To evaluate the effect of recombinant human erythropoietin (rHuEPO) on the reticulocyte production rate and age distribution in healthy subjects. Extensive pharmacokinetic and pharmacodynamic data collected from 88 subjects who received a single subcutaneous dose of rHuEPO (dose range 20-160 kIU) were analysed. Four nonlinear mixed-effects models were evaluated to describe the time course of the percentage of reticulocytes and their age distribution in relation to rHuEPO pharmacokinetics. Model A accounted for stimulation of the production of progenitor cells in bone marrow, and model B implemented shortening of differentiation and maturation times of early progenitors in bone marrow. Model C was the combination of models A and B, and model D was the combination of model A with an increase in the maturation times of the circulating reticulocytes. Model evaluation was performed using goodness-of-fit plots, a nonparametric bootstrap and a posterior predictive check. Model D was selected as the best model, and evidenced accurate and precise estimation of model parameters and prediction of the time course of the percentage of reticulocytes. At baseline, the estimated circulating reticulocyte maturation time was 2.6 days, whereas the lifespan of the precursors in the bone marrow was about 5 days. The rHuEPO potency for the stimulatory effect (7.61 IU/L) was higher than that for the increase in reticulocyte maturation times (56.3 IU/L). There was a significant 1- to 2-day lag time in the reticulocyte response. The effect of rHuEPO on the reticulocyte age distribution consisted of a transient increase in the reticulocyte maturation time from baseline up to 6-7 days, occurring 1 day after administration. The dose-dependent amplitude of the changes in the age distribution lasted for 12-14 days. The model-predicted peak increase in the reticulocyte release rate ranged from 140% to 160% of the baseline value and was maximal on days 7-8 following rHuEPO administration. A semiphysiological model quantifying the effect of rHuEPO on the reticulocyte production rate and age distribution was developed. The validated model predicts that rHuEPO increases the reticulocyte production rate and modifies the reticulocyte age distribution in a dose-dependent manner.


An antibody to the Drosophila period protein recognizes circadian pacemaker neurons in Aplysia and Bulla.
The molecular mechanisms of the pacemakers underlying circadian rhythms are not well understood. One molecule that presumably functions in the circadian clock of Drosophila is the product of the period (per) gene, which dramatically affects biological rhythms when mutated. An antibody specific for the per protein labels putative circadian pacemaker neurons and fibers in eyes of two marine gastropods, Aplysia and Bulla. As was found for the Drosophila per protein, there is a daily rhythm in the levels of the per-like antigen in Aplysia eyes. Thus, certain molecular features of the per protein, as well as aspects of the temporal regulation of its expression, may be conserved in circadian pacemakers of widely divergent species.


Malaria and urbanization in central Africa: the example of Brazzaville. Part IV. Parasitological and serological surveys in urban and surrounding rural areas.
Five schools were chosen in different districts of Brazzaville where the intensity of malaria transmission, determined in a previous study, is representative of the very varied conditions observed in this town in relation to urbanization. The parasitological and serological results found in schoolchildren are analysed according to the level of transmission to which they are exposed, and compared with the results of a longitudinal survey carried out in the rural area of the Brazzaville region. In the urban area malaria prevalences in schoolchildren aged from 5 to 9 years and from 10 to 14 years vary considerably according to the districts. They are, respectively, 78.9% and 84% in Massina, 58.8% and 71.7% in Talangai, 32.3% and 46.9% in Bacongo and 5.6% and 12.6% in Moungali. In Poto-Poto, no positive thick films were found in a representative sample of 62 schoolchildren aged 6 and 7 years who have always lived in this district, and the malaria prevalence is only 6.9% in schoolchildren aged 14 and 15. In the rural area, the malaria prevalence is 76.4% in schoolchildren aged 5 to 9 and 82% in those aged from 10 to 14. According to standard immunofluorescent technique, 63% of children aged 6 and 7 years living since birth in the central part of the Poto-Poto and Moungali districts have no detectable antibodies. In the rural area, all children over 4 years of age are seropositive. These results show that the decrease in vectorial density which accompanies urbanization has considerable parasitological repercussions.(ABSTRACT TRUNCATED AT 250 WORDS)


Biology of ticks.
Ticks are among the most significant blood-sucking arthropods worldwide. They transmit various pathogens that can cause disease and death in people, domesticated animals, and wildlife. Ticks have several morphologic features and physiologic mechanisms that facilitate host selection, ingestion of vertebrate blood, mating, survival, and reproduction. Although the natural history of ticks varies considerably among species, these arthropods are well-adapted to survive in tropical, temperate, and even subarctic habitats. Key factors, including the reversion of agricultural lands to forests and a close association between people and ticks, have greatly increased the risk of tick bite and human disease.


Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose.
LTRPC2 is a cation channel recently reported to be activated by adenosine diphosphate-ribose (ADP-ribose) and NAD. Since ADP-ribose can be formed from NAD and NAD is elevated during oxidative stress, we studied whole cell currents and increases in the intercellular free calcium concentration ([Ca(2+)](i)) in long transient receptor potential channel 2 (LTRPC2)-transfected HEK 293 cells after stimulation with hydrogen peroxide (H(2)O(2)). Cation currents carried by monovalent cations and Ca(2+) were induced by H(2)O(2) (5 mm in the bath solution) as well as by intracellular ADP-ribose (0.3 mm in the pipette solution) but not by NAD (1 mm). H(2)O(2)-induced currents developed slowly after a characteristic delay of 3-6 min and receded after wash-out of H(2)O(2). [Ca(2+)](i) was rapidly increased by H(2)O(2) in LTRPC2-transfected cells as well as in control cells; however, in LTRPC2-transfected cells, H(2)O(2) evoked a second delayed rise in [Ca(2+)](i). A splice variant of LTRPC2 with a deletion in the C terminus (amino acids 1292-1325) was identified in neutrophil granulocytes. This variant was stimulated by H(2)O(2) as the wild type. However, it did not respond to ADP-ribose. We conclude that activation of LTRPC2 by H(2)O(2) is independent of ADP-ribose and that LTRPC2 may mediate the influx of Na(+) and Ca(2+) during oxidative stress, such as the respiratory burst in granulocytes.


Dual role of the metalloprotease FtsH in biogenesis of the DrrAB drug transporter.
This study provides the first direct evidence for the dual role of the metalloprotease FtsH in membrane protein biogenesis. Using the physiological substrate DrrAB, it is shown that FtsH is not only responsible for proteolysis of unassembled DrrB protein but also plays a much broader role in biogenesis of the DrrAB complex. Previous studies showed that the stable expression of DrrB in the membrane depends on simultaneous expression of DrrA. Here we show that DrrB is proteolyzed by FtsH when it is expressed alone. Moreover, DrrA and DrrB proteins expressed together in a temperature-sensitive ftsH mutant strain of Escherichia coli were found to be nonfunctional due to their incorrect assembly. Simultaneous expression of wild-type FtsH in trans resulted in normal doxorubicin efflux. Strikingly, doxorubicin efflux could be restored in mutant cells irrespective of whether FtsH was expressed simultaneously with DrrAB or expressed after these proteins had already accumulated in an inactive conformation, thus providing crucial evidence for the ability of FtsH to refold the misassembled proteins. Complementation experiments also showed that the catalytic AAA domain of FtsH contains a chaperone-like activity, however, unlike wild-type FtsH, it was unable to restore function. Our results therefore show for the first time that FtsH contains the protease as well as refolding functions, and both the AAA and the proteolytic domains of FtsH are required for each of these activities.


Transcriptome analysis of Ophiocordyceps sinensis before and after infection of Thitarodes larvae.
Ophiocordyceps sinensis, also referred to as the Chinese caterpillar fungus, is a rare entomopathogenic fungus found in the Qinghai-Tibetan Plateau that is used as a traditional Chinese medicine. O. sinensis parasitizes the larvae of the ghost moth Thitarodes. Characterization of the transcriptome of O. sinensis before and after host infection may provide novel insight into the process by which the fungus interacts with Thitarodes and may help researchers understand how to sustain this valuable resource. In this study, we performed RNA-sequencing (RNA-seq) using Illumina HiSeqTM 2000 technology to generate gene expression profiles of two developmental stages of O. sinensis. Thread-like hyphae before infection and yeast-like hyphal bodies after infection of host larvae were collected for transcriptome analysis. We found that 1640 genes were differentially expressed (q-value < 0.05), of which 818 were upregulated (49.878 %) and 822 were downregulated (50.122 %). Gene ontology (GO) analysis revealed that the differentially expressed genes (DEGs) were especially enriched in terms associated with Biological Process and Molecular Function. Several genes encoding transporter and permease proteins, three glycoside hydrolases, two mycotoxin-related proteins, an antigen protein, and an allergen were identified as being significantly up- or downregulated. Collectively, our findings provide a novel resource for understanding O. sinensis during two critical developmental stages, and offer the opportunity to further investigate the functional mechanisms underlying these stage-specific molecular differences.


Study on oxidation activity of Ce-Mn-K composite oxides on diesel soot.
As an effective method, diesel particulate filter (DPF) technology has a great contribution in reducing soot emissions from diesel engines. To achieve passive regeneration of DPF at low temperatures, K-doped Ce0.5Mn0.5O2 catalysts were synthesized using sol-gel method. The effect of K-doped catalysts-Kz-Ce0.5Mn0.5O2-on the oxidation of soot had been studied by thermogravimetric analysis, and the corresponding catalytic properties were evaluated based on X-ray diffraction (XRD), hydrogen temperature programmed reduction (H2-TPR), O2 temperature programmed desorption (O2-TPD) Raman spectroscopy (Raman), Brunauer-Emmett-Teller (BET) and Fourier-Transform-Infrared (FTIR).The results showed that K doping facilitated the oxidation of diesel particulate matter, which was indicated by the entire mass loss curve shifting to lower temperatures. K0.2-Ce0.5Mn0.5O2 showed the best performance among the series of K-doped catalysts. Compared with the findings for Ce0.5Mn0.5O2, the ignition temperature of soot oxidation (Ti) had been lowered by 28 ℃, and the maximum peak combustion temperature (Tm) of the dry soot decreased by 61 °C. Furthermore, compared with the Ce0.5Mn0.5O2-catalyzed reaction, K doping led to a lower activation energy and significantly improved pre-exponential factor. The minimum reaction activation energy of 27.46 kJ/mol was exhibited by K0.2-Ce0.5Mn0.5O2.


Peroxisome proliferator-activated receptor gamma coactivator-1α/HSF1 axis effectively alleviates lipopolysaccharide-induced acute lung injury via suppressing oxidative stress and inflammatory response.
Acute lung injury (ALI) interferes with lung function by causing pulmonary inflammation and oxidative stress. Suppressing intracellular reactive oxygen species (ROS) may block intracellular inflammation. Thus, the purpose of the current study was to investigate the roles of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α)/HSF1 axis in an lipopolysaccharide (LPS)-induced ALI murine model and in RAW264.7 macrophages. In the LPS-administrated mouse model, the addition of PGC1α obviously ameliorated secretion of pro-inflammatory mediators tumor necrosis factor-α and Interleukin 6 as well as MCP-1 expression triggered by LPS stimulation, accompanied with reduced infiltration of inflammatory cells. Meanwhile, introduction of PGC1α strongly diminished the expression of cyclooxygenase-2 and inducible nitric oxide synthase as well as their products PGE2 and NO. In addition, administering PGC1α also dramatically alleviated LPS-triggered oxidative stress, as reflected by a reduction of ROS production, and also reduced malondialdehyde and O 2 content, concomitant with enhancement of superoxide dismutase, catalase, and glutathione peroxidase. Similarly, PGC1α effectively ameliorated LPS-induced inflammation response and oxidative stress, as exemplified by reduced pro-inflammatory cytokines and ROS production in LPS-induced RAW264.7 macrophages. Interestingly, PGC1α modulated the expression of HSF1 and the transcriptional activity of X-linked inhibitor of apoptosis (XIAP)-associated factor 1, whereas silencing of HSF1 abolished these effects. More importantly, deletion of HSF1 impeded the anti-inflammatory and anti-oxidant effects of PGC1α in LPS-induced macrophages. Taken together, PGC1α/HSF1 axis have an anti-oxidant and anti-inflammatory effects, indicating that PGC1α/HSF1 may protect against LPS-induced ALI, and thus may be a promising therapy to treat ALI.


The risk of polypharmacy and potentially inappropriate drugs in residential care dementia patients: tips from the PharE study.
The aims of the present study, conducted in two regions of Italy, Calabria and Piedmont, were to assess the use of inappropriate drugs according to the Beers Criteria and to study the possible drug-drug interactions. Data were obtained retrospectively from 972 residential care patients between 2016 and 2018. Mean age was 82.4 ± 8.4 years, with a prevalence of women (64.8%). Activities of daily living, instrumental activities of daily living, Mini-Mental State Examination, Cumulative Illness Rating Scale, Neuropsychiatric Inventory Scale and number and kind of drugs were recorded. A classification of potential inappropriate drugs was made according to the Beers criteria. Data were collected through an Excel file able to gather the main information. In the case of suspected adverse event, Naranjo Scale was applied. The study of possible drug-drug interactions was made by Micromedex 2.0. Functional and cognitive impairments, comorbidities and number of drugs were assessed. The bivariate relationship between number of drugs and glomerular filtration rate assessed by CKD-EPI showed that the higher was the number of drugs used, the worst was kidney function assessment (p = 0.0001). The most frequent inappropriate drugs were anticholinergic drugs, tricyclics antidepressants, long-half-life benzodiazepines, antipsychotics and proton pump inhibitors. These data are very interesting and show the need for an accurate choice of drugs in elderly people and for starting a wise deprescribing procedure.


Editorial Commentary: Meniscal Root Avulsion Repair Outcomes Are at the Level of a Salvage Procedure.
Indications for meniscal root avulsion repair require refinement because current results show failure or extrusion in more than one-third of patients, and long-term follow-up is required before concluding that saving the meniscus results in osteoarthritis prevention.


Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain.
All attempts at treating strokes by pharmacologically reducing the human brain's vulnerability to ischaemia have failed, leaving stroke as a leading cause of death, disability and massive socioeconomic loss worldwide. Over decades, research has failed to translate over 1,000 experimental treatments from discovery in cells and rodents to use in humans, a scientific crisis that gave rise to the prevailing belief that pharmacological neuroprotection is not feasible or practicable in higher-order brains. To provide a strategy for advancing stroke therapy, we used higher-order gyrencephalic non-human primates, which bear genetic, anatomical and behavioural similarities to humans and tested neuroprotection by PSD-95 inhibitors--promising compounds that uncouple postsynaptic density protein PSD-95 from neurotoxic signalling pathways. Here we show that stroke damage can be prevented in non-human primates in which a PSD-95 inhibitor is administered after stroke onset in clinically relevant situations. This treatment reduced infarct volumes as gauged by magnetic resonance imaging and histology, preserved the capacity of ischaemic cells to maintain gene transcription in genome-wide screens of ischaemic brain tissue, and significantly preserved neurological function in neurobehavioural assays. The degree of tissue neuroprotection by magnetic resonance imaging corresponded strongly to the preservation of neurological function, supporting the intuitive but unproven dictum that integrity of brain tissue can reflect functional outcome. Our findings establish that tissue neuroprotection and improved functional outcome after stroke is unequivocally achievable in gyrencephalic non-human primates treated with PSD-95 inhibitors. Efforts must ensue to translate these findings to humans.


New DNA diagnostic system for detection of factor V Leiden.
Use was made of allele-specific PCR to develop a highly effective DNA diagnostic system for detection of the factor V Leiden mutation in exon 10 of human factor V gene. The allele-specific primers contain a 3'-OH end nucleotide, which matches a mutant or wild-type nucleotide of the template DNA (A-allele and G-allele, respectively) and also one mismatched nucleotide near the 3'-end. The universal primers have an internal mismatch with the mutant nucleotide of the template DNA and another mismatched nucleotide at 3'-OH end. The A-allele-specific primer enables the preferential amplification of both the homozygous and heterozygous mutant alleles. The extension of the G-allele-specific primer or the universal one is inhibited in the presence of the homozygous factor V Leiden. The developed assay system allowed us to detect five patients, who are heterozygous for factor V Leiden among the 48 patients with deep venous thrombosis and pulmonary thromboembolism.


Tricarboxylic acid cycle of glia in the in vivo human brain.
In the brain, acetate is exclusively oxidized by glia. To determine the contribution of glial metabolism to the tricarboxylic acid cycle (TCA), 1-(13)C-acetate was infused in six studies in three normal adult subjects and -one epileptic receiving valproic acid for seizure control. Ten grams of 99% 1-(13)C labeled acetate were infused intravenously as a 3.3% w/v solution over 60 min, during which in vivo 13C MR spectra of the brain were acquired. As expected, 13C label rapidly enriched cerebral bicarbonate, glutamate and glutamine C5. The mean rate of acetate oxidation calculated from steady-state 13C enrichment of bicarbonate in fasted normal subjects was 0.13 +/- 0.03 micromol/g/min (n=4), approximately 20% of the total cerebral TCA cycle rate.


Nationwide Incidence of Infantile Cataract Surgery and Risk of Secondary Glaucoma in a Population-based Birth Cohort.
To determine the nationwide birth cohort incidence of infantile cataract (IC) surgery and the risk of secondary glaucoma in a Korean population. A population-based, retrospective cohort study. We accessed the Korean National Health Claims database to identify patients with IC who were diagnosed before 1 year of age and who underwent IC surgery among all Koreans born between 2008 and 2018 (n = 9,593,003). We estimated IC surgery incidence in a birth cohort. The incidence rates of post-IC surgery glaucoma were estimated per 100 person-years, based on the Poisson distribution. The risk factors for post-IC surgery glaucoma, including ophthalmic and systemic comorbidities, were analyzed by multivariable logistic regression analysis. During the 11-year study period, 692 patients underwent IC surgery. The annual birth cohort incidence of IC surgery in the general population ranged from 5.10 to 9.29 cases per 100,000 individuals. Among patients who had been followed up for longer than 1 year (n = 650), 92 (14.2%) developed glaucoma, and its incidence rate was 2.29 (95% confidence interval, 1.86-2.80) per 100 person-years. The mean time from IC surgery to glaucoma development was 4.7 ± 3.5 years. No factors were identified as being associated with post-IC surgery glaucoma risk other than primary or secondary intraocular lens implantation, which reduces the risk (all P < .05). In patients without primary intraocular lens implantation, the risk of glaucoma increased steeply during the first 2 years after IC surgery. This study identified the birth cohort incidence of IC surgery and secondary glaucoma risk in individuals of East Asian ethnicity. These estimates may help to better understand the epidemiologic features and clinical courses of patients with IC.


COVID-19 challenges and WASH in informal settlements: Integrated action supported by the sustainable development goals.
•COVID-19 has exposed service gaps in Water, Sanitation and Hygiene (WASH) in informal settlments in cities.•The vulnerability of informal settlements to COVID-19 is not accidental, but a result of the type of cities that were built.•The Sustainable Development Goals provide a framework for integrated actions in WASH benefitting other sectors.•Partnerships for interventions must consider scalar dynamics with different responses taken at different governance levels.


The metabolic syndrome is associated with advanced vascular damage in patients with coronary heart disease, stroke, peripheral arterial disease or abdominal aortic aneurysm.
The metabolic syndrome is associated with an increased risk of cardiovascular disease in patients without a cardiovascular history. We investigated whether the metabolic syndrome is related to the extent of vascular damage in patients with various manifestations of vascular disease. The study population of this cross-sectional survey consisted of 502 patients recently diagnosed with coronary heart disease (CHD), 236 with stroke, 218 with peripheral arterial disease (PAD) and 89 with abdominal aortic aneurysm (AAA). Metabolic syndrome was diagnosed according to Adult Treatment Panel III criteria. Carotid Intima Media Thickness (IMT), Ankle Brachial Pressure Index (ABPI) and albuminuria were used as non-invasive markers of vascular damage and adjusted for age and sex if appropriate. The prevalence of the metabolic syndrome in the study population was 45%. In PAD patients this was 57%; in CHD patients 40%, in stroke patients 43% and in AAA patients 45%. Patients with the metabolic syndrome had an increased mean IMT (0.98 vs 0.92mm, P-value <0.01), more often a decreased ABPI (14% vs 10%, P-value 0.06) and increased prevalence of albuminuria (20% vs 15%, P-value 0.03) compared to patients without this syndrome. An increase in the number of components of the metabolic syndrome was associated with an increase in mean IMT (P-value for trend <0.001), lower ABPI (P-value for trend <0.01) and higher prevalence albuminuria (P-value for trend <0.01). In patients with manifest vascular disease the presence of the metabolic syndrome is associated with advanced vascular damage.


Anteroposterior dynamic balance reactions to circular movement of the visual field without ocular pursuit.
It has been hypothesised that during natural vision, retinal image motion and eye motion information exert antagonistic effects on balance that cancel each other out. In a previous study, we found that pursuit movements of the eye unaccompanied by background slip on the retina induced strong, stereotyped anteroposterior sway in dynamic balance. In the present work, we investigated the influence of background retinal image slip alone on anteroposterior dynamic balance. We expected that retinal slip without ocular pursuit would induce large anteroposterior sway. Circular slip without rotation of the whole visual field image on the retina was obtained using a rotating prism. In this study, carried out on monocular vision, eye movement was prevented by fixating a stationary target seen through a small aperture in the prism. Anteroposterior dynamic balance conditions were elicited by a rocking platform. Strong, stereotyped anteroposterior sway accompanied by a visual illusion of target motion was observed. The induced sway was synchronised to the stimulus and led to a significant disturbance of balance. The similarity in magnitude of the effects of both retinal image motion studied here and eye motion information obtained previously, and their opposing phases, strongly support the initial hypothesis that the antagonistic effects of the two sources of information provided by normal ocular pursuit could interact in an additive algebraic mode.


On-line mass spectrometric investigation of the peroxidase-catalysed oxidation of uric acid.
The enzymatic and electrochemical oxidation pathways of uric acid were determined on-line with thermospray-tandem mass spectrometry. Products and intermediates formed as a result of electrooxidation were monitored as the electrode potential was varied. Electrochemical results served as a model for the enzymatic studies. In fact, electrochemical studies were essential for elucidating the structures of intermediates because of the high conversion efficiencies in electrooxidation. Products and intermediates formed as a result of enzymatic oxidation of uric acid were monitored as the reaction time was varied. When the enzymatic oxidation of uric acid with peroxidase and H2O2 was studied, the same intermediates and products were observed as in the electrochemical oxidation. The tandem mass spectrometric results provide convincing evidence that the primary intermediate produced during both the enzymatic and electrochemical oxidation of uric acid has a quinonoid diimine structure. The primary intermediate can follow three distinct reaction pathways to produce the identified final products. The final enzymatic and electrochemical oxidation products observed in these studies were urea, CO2, alloxan, alloxan monohydrate, allantoin, 5-hydroxyhydantoin-5-carboxamide and parabanic acid.


Acute effects of low-level laser therapy (660 nm) on oxidative stress levels in diabetic rats with skin wounds.
Laser therapy influences oxidative stress parameters such as the activity of antioxidant enzymes and the production of reactive oxygen species. To analyze the effects of low-level laser therapy on oxidative stress in diabetics rats with skin wounds. Thirty-six animals were divided into 4 groups: NDNI: non-diabetic rats with cutaneous wounds that not received laser therapy; NDI: non-diabetic rats with cutaneous wounds that received laser therapy; DNI: diabetic rats with skin wounds who did not undergo laser therapy; DI: rats with diabetes insipidus and cutaneous wounds and received laser therapy. The animals were treated with LLLT (660 nm, 100 mW, 6 J/cm, spot size 0.028 cm). On the day of killing the animals, tissue-wrapped cutaneous wounds were collected and immediately frozen, centrifuged, and stored to analyze malondialdehyde (MDA) levels. Significant difference was observed within the groups of MDA levels (ANOVA, p = 0.0001). Tukey's post-hoc test showed significantly lower values of MDA in irradiated tissues, both in diabetic and non-diabetic rats. ANOVA of the diabetic group revealed a significant difference (p < 0.01) when all groups, except NDI and DI, were compared. LLLT was effective in decreasing MDA levels in acute surgical wounds in diabetic rats.


Cyclic AMP regulate adenovirus mediated inducible nitric oxide synthase expression and CMV promoter activity in cultured hepatocytes.
We examined effects of cyclic AMP on adenovirus mediated inducible nitric oxide synthase expression in primary rat hepatocytes. In AdCMV-hiNOS infected hepatocytes, dbcAMP at a concentration of 1-100 microM inhibited nitrite and nitrate accumulation, iNOS protein and iNOS mRNA expression. At a concentration of 1-5mM, dbcAMP increased iNOS activity and expression. Both the inhibitory and stimulatory effects of cAMP on adenovirus mediated iNOS expression were dose dependent. This dual effect of cAMP on iNOS activity and expression can be accounted by its effect on CMV promoter activity since dbcAMP significantly inhibited CMV promoter activity in hepatocytes at low concentration and induced it at high concentration. We concluded that dbcAMP can regulate adenovirus-mediated human iNOS expression in primary hepatocytes by the mechanisms regulating the CMV promoter used in the adenovirus vector.


Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom.
A cytotoxin NN-32 (6.7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay. NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis. Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell. Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities.


[Diagnostic approach and optimal treatment of aortic valve stenosis].
The slow progression of valvular aortic stenosis enables the left ventricular myocardium to adapt itself to the increasing afterload. When myocardial adaption is exhausted, surgical intervention is urgent, the prognosis, however, is already limited. To quantify the hemodynamic severity of aortic stenosis, transaortic pressure gradients (dp) measured by Doppler echocardiography or hemodynamically are inappropriate, because dp is significantly dependent on the transaortic flow volume. In severe aortic stenosis, despite constant narrowing of the aortic valve area, the reduced stroke volume results in decreasing transaortic pressure gradients. With aortic valve resistance or transaortic pressure loss (PL)--the quotient of pressure gradient and stroke volume--the hemodynamic severity of aortic stenosis can be described accurately. If PL is known, a decompensated aortic stenosis (PL > 1 mm Hg/ml) may be differentiated from myocardial failure of another etiology and a concomitant left ventricular outflow tract obstruction. With respect to medical therapy, the prevention of bacterial endocarditis and thromboembolic complications is important. Knowing the potential danger of syncopies and ventricular arrhythmias during exercise with increasing severity of aortic stenosis, patients have to be informed about their limited functional capacity. The occurrence of typical symptoms during the natural history of chronic aortic stenosis (e.g. dizziness, syncopes, angina pectoris, arrhythmias) manifestation of ST-T-alterations or silent myocardial ischemias and demonstration of an inadequate myocardial adaptation to the chronic pressure overload in asymptomatic patients are accepted indications for a surgical intervention. If the indication for surgery remains uncertain, stress tests (e.g. radionuclidventriculography) may be performed to demonstrate an exhausted myocardial adaptation. If the PL and the severity of aortic valve/anulus calcification is known, the progression of a chronic aortic stenosis can be estimated. This might be important, if a cardiosurgical intervention has to be performed for other indications and aortic stenosis is co-existent but does not require an intervention at that time. For prognostic reasons myocardial decompensation due to aortic stenosis is an indication for an urgent surgical intervention. Attempts for medical recompensation or bridging strategies (e.g. balloon valvotomy) worsens the prognosis significantly.


A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation.
The suppressor of Hairy wing (su(Hw)) protein inhibits the function of transcriptional enhancers located distally from the promoter with respect to the location of su(Hw)-binding sites. This polarity is due to the ability of the su(Hw)-binding region to form a chromatin insulator. Mutations in modifier of mdg4 (mod(mdg4)) enhance the effect of su(Hw) by inhibiting the function of enhancers located on both sides of the su(Hw)-binding region. This inhibition results in a variegated expression pattern, and mutations in mod(mdg4) act as classical enhancers of position-effect variegation. The mod(mdg4) and su(Hw) proteins interact with each other. The mod(mdg4) protein controls the nature of the repressive effect of su(Hw): in the absence of mod(mdg4) protein, su(Hw) exerts a bidirectional silencing effect, whereas in the presence of mod(mdg4), the silencing effect is transformed into unidirectional repression.


Immune Checkpoint Inhibitor-induced Pancreatitis with Pancreatic Enlargement Mimicking Autoimmune Pancreatitis: A Case Report and Review of the Literature.
A 61-year-old woman was administered 35 cycles of pembrolizumab for the treatment of recurrent endometrial cancer, achieving a complete response. She presented with asymptomatic pancreatic enlargement and elevated hepatobiliary enzymes, but amylase and lipase levels were within the normal ranges. Intrapancreatic bile duct stenosis due to pancreatic enlargement was present, mimicking autoimmune pancreatitis on computed tomography performed before the onset of clinical manifestations. A histological examination of a biopsy specimen showed lymphocyte and plasma cell infiltration with dense fibrosis in the stroma. The patient was successfully treated with oral prednisolone. There were no manifestations of recurrent pancreatitis after tapering the prednisolone dose.


Endoscopic cubital tunnel release: a systematic review.
Theoretical advantages of endoscopic cubital tunnel release are the short incision, lower risk of nerve damage, reduced manipulation of the nerve and possible faster recovery. We systematically searched Medline (PubMed), Web of Science and Scopus databases using the following keywords: 'endoscopic ulnar nerve', 'endoscopic cubital nerve', 'endoscopic ulnar compression' and 'endoscopic ulnar neuropathy'. Twenty-one studies were included in this review. The quality of the studies was assessed using the Coleman Methodological Score. Endoscopic release is effective for cubital tunnel entrapment and allows adequate visualization of the site of entrapment. There is a negative association between the severity of the compression and reported outcomes. Injury to the medial branch of the antebrachial cutaneous nerve is less frequent thanks to the limited dissection. The most frequent complication is the development of a hematoma. It is unclear whether ulnar nerve instability is a contraindication to simple decompression. The shorter time to return to work and the cosmetic appearance of the scar can be considered advantages of the endoscopic technique. There is a need to perform randomized clinical trials with common and validated scoring system with a longer duration of follow-up. The literature pertinent to endoscopic cubital tunnel release is lacking in the evaluation of the learning curve. Further investigations are necessary to assess the role of ulnar nerve instability.


Less invasive stabilisation system (LISS) for the treatment of periprosthetic femoral fractures: a 3-year follow-up.
Recent publications have reported encouraging results with a locked plating system in the management of periprosthetic femoral fractures. However, data on mid- or long-term functional outcome is not available. Here we report on the mid-term functional outcome of 16 patients with a periprosthetic femoral fracture following total hip arthroplasty managed with the LISS-system at a 3-year follow-up. Functional outcome was measured using the Harris Hip score and the Karnofsky activity index. The Harris Hip score and the Karnofsky activity index averaged 79.5 points and 81%, respectively. There were a total of two major complications due to screw pullout representing a complication rate of 13%. This series suggests that the management of periprosthetic femoral fractures with the LIS-System results in a good mid-term functional outcome.


Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli.
Four cases are described in which spindle-shaped, yellow-brown bodies were seen in the mesenteric lymph nodes of patients with melanosis coli. A comparison of the staining reactions and ultrastructural appearances of the spindle bodies and melanosis pigment suggest that they are related within the broad group of lipofuscins and that the spindle bodies are formed as a result of coalescence of lysosomes containing the pigment.


A rapid procedure for the enrichment of undenaturated, antigenically active herpes simplex virus glycoproteins.
The usefulness of lentil lectin affinity chromatography for the rapid enrichment of HSV glycoproteins in an undenatured state for both research and clinical purposes was investigated. In order to compare the lentil lectin-binding characteristics and immunologic specificities of undenatured HSV-1 and HSV-2 glycoproteins, [35S]methionine-labelled extracts of virus-infected HEp-2 cells were subjected to lentil lectin affinity chromatography. Individual HSV-1 and HSV-2 glycoproteins in bound and unbound fractions were identified using monoclonal antibodies. With the exception of a portion of pgD and gD, all major viral glycoprotein species (gA, gB, gC, gD, gE and gF) and their glycosylated processive intermediates bound to lentil lectin indicating that all possess predominantly mannosyl and/or glucosyl carbohydrate moieties. Although the unbound pgD and gD species were glycosylated, no gD and only a portion of pgD bound to lentil lectin when reapplied to the column indicating that these subspecies possess alterations in factors required for efficient lectin binding. Immunoprecipitation of undenatured lectin-bound glycoproteins from infected cells using HSV-1 and HSV-2-specific rabbit and human antisera confirmed previous findings that the predominant type-specific glycoproteins of HSV-1 and HSV-2 are gC and gE/gF, respectively.


Microbial degradation of poly(D-3-hydroxybutyrate) by a new thermophilic streptomyces isolate.
A new thermophilic microorganism capable of degrading poly(D-3-hydroxybutyrate) (PHB) was isolated from soil. A phylogenetic analysis based on 16S rDNA sequences indicated that the new isolate belongs to genus Streptomyces. PHB film and powder were completely degraded after 6 and 3 d cultivation, respectively at 50 degrees C. Scanning micrographs showed adherence of the microbial cells to the entire film surface, indicating that biodegradation occurs by colonization of the PHB surface. The film was degraded both by microbial attack and by the action of an extracellular enzyme secreted by the microorganism. The strain can also degrade poly(ethylene succinate), poly(ester carbonate), polycaprolactone and poly(butylene succinate), but to a lesser extent.


A new bi-radical species formed during the photochemical degradation of synthetic musk tonalide in water: Study of in-situ laser flash photolysis and validation of synthesized standard sample.
The ubiquitous presence of synthetic musks is causing serious concern due to the species produced from their transformation and environmental impacts. In this study, tonalide was selected as a representative synthetic musk to evaluate the transformation mechanism and pathway in water under ultraviolet (UV) irradiation. The results showed that tonalide could undergo rapid photochemical degradation through a new pivotal bi-radical, which acts as the initial active species. The bi-radicals with a typical absorption peak at 340 nm was observed by in-situ laser flash photolysis technology, and the absolute decay rate constant was obtained as 3.61 ± 0.01 × 109 M-1 s-1 with the life-time of 83.3 ns. The photochemical degradation by-products of tonalide were also identified by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and the precise structures of key by-products have been validated by our preparative synthesized standard samples confirmed by nuclear magnetic resonance. Thus, the mechanism of tonalide photochemical degradation, continuous photoenolization of the bi-radicals and followed cycloaddition reaction with O2, was proposed as the predominant pathway. The main degradation by-product, photoenol which has a higher bioconcentration than that of tonalide, was found to form from the bi-radicals photoenolization. This study is the first work to propose a new bi-radical as the photoenol precursors during photochemical degradation of tonalide in water.


A randomized clinical trial for the effect of static stretching and strengthening exercise on pelvic tilt angle in LBP patients.
Stretching and strengthening exercises are commonly used to improve muscle shortness of the hamstring as any tension in this muscle can have an effect on the pelvic posture. Thus, the aim of this study was to evaluate the effects of two methods of improving short hamstring on the angle of pelvic tilt in LBP sufferers. Forty-five low back pain patients aged 19-59 years with hamstring tightness participated in this clinical trial. The patients were categorized randomly into three groups: 1- static stretching, 2-strengthening exercise and 3-control group. The two intervention groups received physical therapy and special exercise program thrice a week in a total of 12 sessions, while the control group received only conventional physical therapy. Before and after the treatment implementation, the pelvic tilt and straight leg raising (SLR) degree were assessed for each group. After 12 sessions of treatment, the ANCOVA models indicated non-significant differences in pelvic tilt angle and SLR score changes (p > 0.05), among the three groups. In addition, no statistically significant correlation was observed between the pelvic tilt and SLR test [except for the strengthening exercise group (Pearson correlation coefficient = -0.54, P < 0.05)]. In LBP sufferers, both static stretching and strengthening of hamstring muscle in its lengthened position caused elongation and extensibility in the hamstring muscle and increased SLR test score, but did not change pelvic tilt angle.


["Possessedness" and exorcism in the year 1976 (author's transl)].
A 23 year-old woman died as a result of deficient food and liquid intake as well as of physical exhaustion brought about by an unchecked pathological displacement impulse. Finally pneumonia developed in a typical manner. During the previous 9 months exorcism had been carried out a total of 60 to 70 times, the last time being on the eve of her death, to "expel demons" and to heal the "possessed". Summarized the medical diagnosis of "possession" was: Parnoid-hallucinatory psychosis with epilepsy in the background of special psycho-social factors. During the time of influence by the priests who carried out the exorcism all medical treatment was denied. This, it was pointed out by the participants, occurred at the express wish of the "possessed" and also due to the conviction that medical aid would be ineffective. This fateful development took place in a milieu of belief in demons fostered by the priests and uncritical rejection of medico-scientific treatment methods. According to the results of the hearing of witnesses during the now legally valid proceedings ending with the exorcists and the deceased's parents being convicted for accidental homicide a doctor probably also participated in what happend in a reprehensible manner.


Transanal endoscopic microsurgery: long-term experience, indication expansion, and technical improvements.
This study aimed to review the authors' 16-year experience with transanal endoscopic microsurgery (TEM). Mortality, morbidity, recurrence rate, and functional outcome were assessed. New indications and technical improvements are presented. From November 1991 to August 2008, 123 patients (72 men and 51 women; median age, 68 years; range, 21-91 years) underwent TEM for excision of 105 adenomas with low- or high-grade dysplasia, 9 invasive adenocarcinomas (5 curative and 4 palliative resections), 2 neuroendocrine tumors, and 2 extramucosal lesions. Five additional patients had excisional biopsies, allowing staging after previous endoscopic resection. Most of the resections were full-thickness rectal resections using electrocautery or, more recently, the Harmonic scalpel. The latest mucosectomies were performed using the endoscopic submucosal dissection (ESD) technique. In addition, nontumoral indications included pelvic abscess (7 patients) and rectal strictures, which were either anastomotic or chemical. Pelvic abscesses were drained transrectally, whereas rectal stenoses were treated by strictureplasty. Foreign object retrieval and collagen plug placement for anal fistulas were performed using TEM in three patients. No mortality occurred. One intraoperative rectal perforation required conversion to laparotomy. The postoperative complications included one pneumoperitoneum, which was treated medically, and one rectal perforation requiring Hartmann's procedure. In the polyp subgroup, six patients (6/91, 7%) experienced local recurrence. Pelvic abscesses were successfully treated, and stenosis did not recur after strictureplasty. Anorectal manometry showed functional alterations without significant clinical impact. The findings showed TEM to be a safe and effective procedure for local excision of rectal lesions with a low recurrence rate and minimal consequences in terms of anorectal function. In addition, TEM proved to be feasible and effective for pelvic abscess drainage and rectal stenosis treatment. New technologies such as the Harmonic scalpel and ESD increase the precision already offered by this approach.


Experimental datasets on properties of river sand as an aggregate in replacement of crushed rock for interlocking stones production.
The data explored the assessment of the quality of river sand as an aggregate in replacement of crushed stones which are widely used by majority of manufacturers in production of interlocking stones. Experimental tests carried out on river sand and crushed rock as aggregates include: Grain size distribution, Specific gravity, moisture content determination and Bulk density to determine the quality behavior parameters and (compressive strength) to determine the strength parameters. The data of the experiments are presented in Tables and Bar charts.


Sponge-Associated Bacteria Produce Non-cytotoxic Melanin Which Protects Animal Cells from Photo-Toxicity.
Melanin is a photo-protective polymer found in many organisms. Our research shows that the bacteria associated with darkly pigmented sponges (Haliclona pigmentifera, Sigmadocia pumila, Fasciospongia cavernosa, Spongia officinalis, and Callyspongia diffusa) secrete non-cytotoxic melanin, with antioxidant activity that protects animal cells from photo-toxicity. Out of 156 bacterial strains screened, 22 produced melanin and these melanin-producing bacteria (MPB) were identified as Vibrio spp., Providencia sp., Bacillus sp., Shewanella sp., Staphylococcus sp., Planococcus sp., Salinococcus sp., and Glutamicibacter sp. Maximum melanin production was exhibited by Vibrio alginolyticus Marine Microbial Reference Facility (MMRF) 534 (50 mg ml-1), followed by two isolates of Vibrio harveyi MMRF 535 (40 mg ml-1) and MMRF 546 (30 mg ml-1). Using pathway inhibition assay and FT-IR spectral analysis, we identified the melanin secreted into the culture medium of MPB as 1,8-dihydroxynaphthalene-melanin. The bacterial melanin was non-cytotoxic to mouse fibroblast L929 cells and brine shrimps up to a concentration of 200 and 500 ppm, respectively. Bacterial melanin showed antioxidant activity at very low concentration (IC50-9.0 ppm) and at 50 ppm, melanin protected L929 cells from UV-induced intracellular reactive oxygen stress. Our study proposes sponge-associated bacteria as a potential source of non-cytotoxic melanin with antioxidant potentials.


Evaluation of the Balloon Analogue Risk Task (BART) as a predictor of adolescent real-world risk-taking behaviours.
The Balloon Analogue Risk Task (BART) was administered to a sample of 26 high school-aged adolescents to test the utility of the BART as a behavioural measure of risk-taking propensity. Data indicate that riskyness on the BART was related to self-reported engagement in real-world risk-taking behaviours. These data replicate and uniquely extend past research to an adolescent sample, suggesting that the BART may be a useful addition to self-report batteries for the assessment of risk-taking behaviours in adolescents.


Methylphenidate increases thought disorder in recent onset schizophrenics, but not in normal controls.
The effects of apomorphine and methylphenidate on thought disorder, as measured by the Thought Disorder Index, in schizophrenic patients and in normal controls were evaluated. Methylphenidate, but not apomorphine, increased thought disorder in patients. Neither drug significantly increased thought disorder in controls.


Prenatal HIV screening in a tertiary care centre.
Strategies are available to reduce maternal-fetal transmission of HIV and depend on adequate prenatal screening. At present, a significant proportion of Canadian pregnant women remain unscreened. We reviewed our screening practices before and after the implementation of a departmental policy on universal counselling for HIV screening and the distribution of a patient educational brochure developed at our centre (interventions). Charts of all new antenatal patients seen during February-April in 1996 (n = 186) and 1998 (n = 212) were reviewed. Maternal demographics and evidence of HIV counselling and screening were collected and analyzed. Following our interventions, HIV counselling and screening rates increased from 13% to 72%. Patient acceptance of testing was high. The majority of missed opportunities for HIV testing were patients transferred urgently from other institutions. HIV counselling and screening can be improved by implementation of local strategies. We have demonstrated the feasibility of this approach in a tertiary care unit.


Costimulation improves the killing capability of T cells redirected to tumor cells expressing low levels of CD33: description of a novel modular targeting system.
Owing to their clinical success, there is growing interest in novel bispecific antibodies (bsAbs) for retargeting of T cells to tumor cells including for the treatment of acute myeloid leukemia (AML). One potential target for retargeting of T cells to AML blasts is the surface molecule CD33. Here we describe a novel modular targeting platform that consists of a universal effector module (EM) and individual target modules (TMs). Both modules can form an immune complex via a peptide epitope. The resulting targeting complex can functionally replace a conventional bsAb. By fusion of a costimulatory domain (for example, the extracellular CD137 ligand domain) to the TM, the targeting complex can even provide a costimulatory signal to the redirected T cells at their side of interaction with the tumor cell. Furthermore, we observed that an efficient killing of tumor cells expressing low levels of the tumor target CD33 becomes critical at low effector-to-target cell ratios but can be improved by costimulation via CD137 using our novel targeting system.


Development and validation of a script concordance test to assess biosciences clinical reasoning skills: A cross-sectional study of 1st year undergraduate nursing students.
Developing evaluative measures that assess clinical reasoning remains a major challenge for nursing education. A thorough understanding of biosciences underpins much of nursing practice and is essential to allow nurses to reason effectively. A gap in clinical reasoning can lead to unintended harm. The Script Concordance test holds promise as a measure of clinical reasoning in the context of uncertainty, situations common in nursing practice. The aim of this study is to develop and validate a test for first year undergraduate nursing students that will evaluate how bioscience knowledge is used to clinically reason. An international team, teaching biosciences to undergraduate nurses constructed a test integrating common clinical cases with a series of related test items: diagnostic, investigative and treatment. An expert panel (n = 10) took the test and commented on authenticity/ambiguities/omissions etc. This step is crucial for validity and for scoring of the student test. The test was administered to 47 first year undergraduate nursing students from the author sites. Students rated educational aspects of the tool both quantitatively and qualitatively. Statistical and content analyses inform the findings. Results indicate that the test is reliable and valid, differentiating between experts and students. Students demonstrated an ability to identify relevant data, link this to their bioscience content and predict outcomes (mean score = 50.78 ± 8.89). However, they lacked confidence in their answers when the scenarios appeared incomplete to them. Nursing practice is dependent on a thorough understanding of biosciences and the ability to clinically reason. Script concordance tests can be used to promote both competencies. This method of evaluation goes further than probing factual knowledge. It also explores capacities of data interpretation, critical analysis, and clinical reasoning. Evaluating bioscience knowledge and real-world situations encountered in practice is a unique strength of this test.


Utility of cell block preparation in diagnosis of paediatric abdominal neoplasms.
Paediatric abdominal neoplasms are fairly common. Fine needle aspiration cytology (FNAC) is used for the initial evaluation of paediatric abdominal neoplasms. However, sometimes FNA interpretation can be difficult on limited material, owing to tumour heterogeneity and overlapping features. Therefore, we attempted to obtain additional information using cell block (CB) preparation from residual aspiration material along with immunohistochemistry (IHC) to enhance the diagnostic accuracy. To evaluate the correlation between CB preparation and FNAC in diagnosis of paediatric abdominal tumours with the help of an extended panel of IHC markers and to highlight some of the diagnostic difficulties. A total of 113 cases of paediatric abdominal masses were studied. In addition to routine FNA smears, CBs were prepared from the residual material for IHC analysis as considered appropriate. This study included a total of 113 children with abdominal masses. Histopathology following surgical resection was available in 53 cases. Histology was taken as gold standard to measure the diagnostic accuracy with reference to sensitivity (Sn), specificity (Sp), positive predictive value and negative predictive value. The Sn of FNA alone was 87.5% and Sp was 97.78%. The Sn and Sp increased with use of CB alone and were 100% and 97.78% respectively. The highest Sn and Sp were observed when CB was combined with IHC where both the values were 100%. CB with IHC is a useful adjunct to the routine FNA smears that further contributes to enhance the accuracy of the cytopathological diagnosis and is useful for choosing pre-operative chemotherapeutic regimen.


Inhibition of HMGB1 involved in the protective of salidroside on liver injury in diabetes mice.
High mobility group box 1 (HMGB1) is a nuclear protein that is released on injury triggers inflammation. This study aims to elucidate the effects of salidroside on diabetes-induced liver inflammation. The levels of glucose, inflammatory cytokines and hepatic functional parameters in serum and liver of type 2 diabetic db/db mice were examined. Immunohistochemistry, immunofluorescence and western blot tests were performed to determine the mechanisms underlying the action. Palmitic acid (PA) or HMGB1-stimulated was adopted as an in vitro cell model. Salidroside treatment improved glucose tolerance, lipid profiles while decreased the production of inflammatory cytokines. It also reduced the levels of serum biochemical markers. In addition, salidroside inhibited HMGB1 signaling pathway in db/db mice. In the salidroside treatment significantly inhibited PA or HMGB1 induced inflammatory signaling pathway, too. HMGB1 inhibitors and HMGB1 knockdown both hindered PA-induced HMGB1 signaling pathway, showing the same effect as salidroside. Salidroside treatment significantly alleviates insulin resistance, hyperglycemia and hepatic inflammation in db/db mice, and also showed beneficial to PA-stimulated. Salidroside proves to control hyperglycemia and hepatic inflammation via inhibiting HMGB1/RAGE/NF-κB and HMGB1/TLR4/NLRP3 signaling pathways.