Early discharge policy of patients with acute colonic diverticulitis following initial CT scan.
Diverticulitis develops in 15-20% of individuals with diverticulosis. Severity ranges from mild to severe. Mild diverticulitis is uncomplicated confined per colonic inflammation commonly treated conservatively. Recent literature suggests it could be managed in an outpatient setup. To determine if patients with mild acute colonic diverticulitis (ACD) on early CT scan can be treated and discharged at an early time. Retrospective review of patient's charts admitted during 2005 with ACD confirmed by CT scan performed within 24 h of admission. Severity of ACD was determined according to CT classification. Forty-two (31 women, 11 men) patients included, mean age 66 years, CT severity classification: 61.9% mild, 7.1% moderate, and 31.0% severe diverticulitis. Patients with mild ACD were discharged safely, had no recurrence of their symptoms, and needed no readmission within 6 months of follow-up. Patients with mild ACD on CT scan performed within 24 h could be safely discharged and treated according to protocols of outpatient management of diverticulitis.


Alendronate sodium/vitamin D3 combination tablet versus calcitriol for osteoporosis in Chinese postmenopausal women: a 6-month, randomized, open-label, active-comparator-controlled study with a 6-month extension.
This study compares efficacy of ALN/D5600 versus that of calcitriol in osteoporotic Chinese postmenopausal women. ALN/D5600 produced greater bone mineral density (BMD) increases, greater bone turnover marker decreases, and less vitamin D insufficiency. This study provided detailed clinical information regarding ALN/D5600 treatment versus calcitriol 0.25 μg/day. The study did not evaluate fracture risk. The aim of this study is to investigate efficacy of alendronate 70 mg/vitamin D3 5600 IU combination tablets (ALN/D5600) versus calcitriol in osteoporotic Chinese postmenopausal women. This study is a 6-month, randomized, open-label, active-comparator study with 6-month extension (clinicaltrials.gov number NCT01350934) in postmenopausal women aged >55 years with osteoporosis (low bone mineral density (BMD) with/without prior fragility fracture). Patients were randomized to ALN/D5600 once weekly or calcitriol 0.25 μg daily. The primary efficacy end point of the base study was percent change from baseline in lumbar spine BMD (month 6). Hypercalcemia and hypercalciuria were safety events of special interest. A total of 219 patients (ALN/D5600 n = 111, calcitriol n = 108) were randomized. Baseline characteristics were similar, 30.3 % baseline 25-hydroxyvitamin D (25(OH)D) ≤15 ng/mL. At months 6 and 12, changes in lumbar spine BMD from baseline were 3.5 versus 1.6 % and 5.2 versus 2.3 % for ALN/D5600 versus calcitriol (between-group differences p < 0.001), respectively. Between-group differences for ALN/D5600 versus calcitriol were significant (p < 0.001) at months 6 and 12 for change from baseline in procollagen type 1 N-terminal propeptide (-59.1 versus -16.8 %, -68.1 versus -17.0 %) and serum C-telopeptides (-79.2 versus -27.2 %, -76.2 versus -24.2 %). Drug-related adverse events (AEs) and discontinuations due to drug-related AEs occurred in 15 (14.0 %) versus 8 (7.4 %) patients and 3 (2.8 %) versus 0 patients in the ALN/D5600 and calcitriol group, respectively. Hypercalciuria 12-month incidence (24-h urine Ca >300 mg) was 8.4 (ALN/D5600) versus 13.9 % (calcitriol) (p > 0.05). One patient (calcitriol) had hypercalcemia. ALN/D5600 produced greater increases in lumbar spine BMD and greater decreases in bone turnover markers versus calcitriol in osteoporotic Chinese women. It is not known whether the greater increase in BMD results in fewer fractures. ALN/D5600 was generally well tolerated in Chinese patients.


Should patients with implantable cardioverter-defibrillators be allowed to drive? Observations in 291 patients from a single center over an 11-year period.
Motor-vehicle driving restrictions for patients with implantable cardioverter-defibrillators (ICDs) vary widely throughout the world because safety concerns have never been adequately resolved in this patient population. To address this issue, we examined the driving behavior of 291 ICD patients to correlate the frequency of device therapy during driving, the occurrence of syncopal symptoms, and the incidence of traffic accidents. Fifty of the 291 patients had never driven. Of the remaining 241 patients, 171 (59%) continued driving postimplant and 70 (24%) elected to stop prior to (n = 30) or at the time of ICD implantation (n = 40). Patients were followed for a mean of 38 +/- 26 months (range < 1-124). During this period, no patients died while driving. Of 11 accidents involving 11 driving patients (6%), only 1 was caused by the driver, and none was related to syncopal symptoms or ICD therapy. Although 2 accidents (8%) occurred within 12 months postimplant, the majority (50%) took place after more than 36 months. ICD therapy was delivered in 8 patients (5%) while driving: 13% (1 episode) of the discharges occurred within the first year postimplant, 13% (1 episode) occurred between 1-2 years, and 74% (6 episodes) occurred > 2 years. None of these patients experienced syncope before or during these episodes. A multivariate analysis was unable to identify any variables that might predict increased risk of ICD therapy (with or without sudden death) while driving and consequent motor vehicle accidents. Our data suggest that such events occur only rarely.


Blood pressure and cardiovascular involvement in children with neurofibromatosis type1.
We evaluated blood pressure in a sample of patients with neurofibromatosis type 1 (NF1), using ambulatory blood pressure monitoring (ABPM), to determine whether ABPM, when compared with casual BP recordings, allowed the detection of a higher risk for hypertension. We also evaluated the correlation between BP and vascular abnormalities. We studied 69 NF1 patients (36 males and 33 females) with a mean age of 11+/-4 years, divided into group A, with 24-h mean systolic blood pressure (SBP) or diastolic blood pressure (DBP) <95th percentile, and group B, with mean SBP or DBP >95th percentile. Standard electrocardiography and M-mode, two-dimensional echocardiography were performed and all patients were in sinus rhythm. ABPM identified 11 hypertensive patients (16%); 5 had a mean SBP >95th percentile, 3 mean SBP-DBP >95th percentile, and 3 a mean DBP >95th percentile. Laboratory and other investigations to exclude secondary hypertension were normal. Cardiac abnormalities were found in 13 of the 69 patients (18.8%) with NF1. There were no significant clinical and cardiac differences between the normotensive and hypertensive group. Our data emphasize the importance of periodic ABPM in NF1 patients to diagnose hypertension early and avoid target organ damage and increased mortality.


Finite element analysis of a healthy knee joint at deep squatting for the study of tibiofemoral and patellofemoral contact.
In non-western countries, deep squatting is a daily activity, and prolonged deep squatting is common among occupational squatters. Household tasks, taking a bath, socializing, using toilets, and performing religious acts are among the activities frequently carried out while squatting by the Asian population. High knee loading is responsible for a knee injury and osteoarthritis. Finite element analysis is an effective tool to determine stresses on the knee joint. Magnetic Resonance Imaging (MRI) and Computed Tomographic (CT) images were acquired of one adult without knee injuries. The CT images were acquired at the fully extended knee and one more set of images was acquired with the knee at a deeply flexed knee position. The MRI was acquired with the fully extended knee. 3-Dimensional models of bones were created using CT and soft tissue using MRI with the help of 3D Slicer software. Kinematics and finite element analysis of the knee was performed for standing and deep squatting posture using Ansys Workbench 2022. High peak stresses were observed at deep squatting compared to standing along with the reduction in the contact area. Peak von Mises stresses on femoral cartilage, tibial cartilage, patellar cartilage, and meniscus were increased from 3.3 MPa to 19.9 MPa, 2.9 MPa to 12.4 MPa, 1.5 MPa to 16.7 MPa and 15.8 MPa to 32.8 MPa respectively during deep squatting. Posterior translation of 7.01 mm, and 12.58 mm was observed for medial and lateral femoral condyle respectively from full extension to 153° knee flexion. Increased stresses in the knee joint at deep squat posture may cause cartilage damage. A sustained deep squat posture should be avoided for healthy knee joints. More posterior translations of the medial femoral condyle at higher knee flexion angle warrant further investigation.


[Radiotherapy and radiosurgery of pituitary adenomas].
There are two principal types of treatment for pituitary adenomas: fractionated conventional radiation therapy, based on biological selectivity, and radiosurgery, which is delivered in a single dose, based on anatomic selectivity and indicated preferentially for small tumors sufficiently distant from the optic chiasm. Conventional radiation therapy is effective against secretion in 60-80% of cases and radiosurgery in 40-50%, depending on the type of secretion. Maximum antisecretory efficacy is not reached immediately: this delay is longer for conventional radiation therapy (5-10 years) than for radiosurgery (2-3 years). In both cases, antisecretory treatment must be started, while awaiting remission. Radiation therapy and radiosurgery make it possible to stabilize or diminish tumor volume in 70-100% of cases. This is especially useful in the case of an active residue after surgery for non-secreting adenoma, but the long-term side effects of radiation must be borne in mind. The principal side effect is the onset of a pituitary deficiency (in more than 50% of cases after radiation therapy, 20% after radiosurgery). The risk increases with time since treatment. Other very long-term side effects have been described with radiation therapy: radiation-induced tumors, cerebral necrosis, strokes, etc. The role of radiosurgery and radiation therapy is growing ever more limited, because of the increasing efficacy of drug treatments and the excellent surgical results of experienced teams.


Additive Manufacturing of Bioactive Poly(trimethylene carbonate)/β-Tricalcium Phosphate Composites for Bone Regeneration.
Implants of bioresorbable materials combined with osteoconductive calcium phosphate ceramics show promising results to replace and repair damaged bone tissue. Here we present additive manufacturing of patient-specific porous scaffolds of poly(trimethylene carbonate) (PTMC) including high amounts of β-tricalcium phosphate (β-TCP). Tensile testing of composite networks showed that addition of β-tricalcium phosphate reinforces the composites significantly. Three-dimensional structures containing up to 60 wt % β-TCP could be built by stereolithography. By lowering the content to 51 wt %, manufacturing of a large-sized patient-specific prototype was possible at high resolution. Closer examination revealed that the created scaffolds contained more β-TCP on the surface of the builds. Stereolithography therefore provides a manufacturing technique where the bioactive agent is directly available for creating an enhanced microenvironment for cell growth. The biocompatibility and bioresorption of PTMC coupled with the osteoconductivity of β-TCP are an important candidate to consider in additive manufacturing of bone regeneration implants.


An archaeal trkA homolog near dnaK and dnaJ.
The first trkA gene homolog in the phylogenetic domain Archaea is reported. The gene is located near the dnaK-dnaJ gene cluster in the genome of Methanosarcina mazei S-6, and encodes a protein homologous to the only other TrkA known, i.e., that of the bacterium Escherichia coli, involved in K+ transport. This finding supports an essential, evolutionarily early, and conserved role for this gene in cell survival and adaptation.


Modeling VOC adsorption in lab- and industrial-scale fluidized bed adsorbers: Effect of operating parameters and heel build-up.
Scale-up and optimization of fluidized beds are challenging due to the difficulty in accounting for the interrelated effect of various phenomena, which are typically described by empirical and/or semi-empirical equations. In this study, a two-phase model was introduced to simulate the adsorption of VOCs on beaded activated carbon (BAC) in a lab-scale fluidized bed adsorber. The model assumes the presence of a bubble phase free from adsorbent particles, and an emulsion phase composed of the adsorbent particles and interstitial gas. The versatility of the proposed model was then evaluated using data from an industrial scale adsorber with different operating conditions, adsorbent properties, and bed geometry. The response of the model to the operating conditions (adsorbent feed rate, air flow rate and initial concentration) showed better agreement with the experimental lab-scale data when the emulsion gas in two-phase model was considered in plug flow than in perfectly-mixed flow (R2 = 0.96 compared to 0.91). To simulate the performance of BACs with different service lifetimes (degree of exhaustion as a result of heel developed inside their pores), the main characteristics of the BACs (pore diameter, porosity, and adsorption capacity) were first correlated to their apparent densities. The model could accurately predict the experimental lab-scale VOC concentrations in each stage (R2 = 0.92) as well as overall removal efficiencies (R2 = 0.99) for BACs ranging from virgin to fully-spent. Finally, the model was used to predict the performance of an industrial-scale fluidized bed adsorber for VOC removal at different operating conditions and apparent densities. Predicted and measured VOC removal efficiencies were in good agreement (R2 = 0.94). Although the model was verified for adsorption of VOCs on BAC, the modeling approach presented in this study could be used for describing adsorption in different adsorbate-adsorbent systems in multistage counter-current fluidized bed adsorbers.


Binding of plasma membrane glycoproteins to the cytoskeleton during patching and capping is consistent with an entropy-enhancement model.
Concentrations of concanavalin A that induced patching and capping of cell surface receptors on Dictyostelium discoideum also induce binding of the receptors to the cortical cytoskeleton, which was isolated by density-gradient centrifugation. The receptors were solubilized by deoxycholate, purified by affinity chromatography, and used to determine whether the receptors bound directly to the cytoskeletal protein, actin. As the concentration of actin was increased, many of the receptors became bound to purified filamentous rabbit muscle actin, even in the absence of concanavalin A. As in the ligation-induced binding of receptors to the cortical cytoskeleton in cells, concanavalin A induced much stronger binding of the purified receptors to filamentous actin. The results were consistent with a previously stated hypothesis that induction of receptor binding to the cytoskeleton during their patching and capping is driven by clustering the receptors, which reduces their translational entropy and by doing so enhances their avidity for the cytoskeleton.


Considerations towards the better integration of epidemiology into quantitative risk assessment.
Environmental epidemiology has proven critical to study various associations between environmental exposures and adverse human health effects. However, there is a perception that it often does not sufficiently inform quantitative risk assessment. To help address this concern, in 2017, the Health and Environmental Sciences Institute initiated a project engaging the epidemiology, exposure science, and risk assessment communities with tripartite representation from government agencies, industry, and academia, in a dialogue on the use of environmental epidemiology for quantitative risk assessment and public health decision making. As part of this project, four meetings attended by experts in epidemiology, exposure science, toxicology, statistics, and risk assessment, as well as one additional meeting engaging funding agencies, were organized to explore incentives and barriers to realizing the full potential of epidemiological data in quantitative risk assessment. A set of questions was shared with workshop participants prior to the meetings, and two case studies were used to support the discussion. Five key ideas emerged from these meetings as areas of desired improvement to ensure that human data can more consistently become an integral part of quantitative risk assessment: 1) reducing confirmation and publication bias, 2) increasing communication with funding agencies to raise awareness of research needs, 3) developing alternative funding channels targeted to support quantitative risk assessment, 4) making data available for reuse and analysis, and 5) developing cross-disciplinary and cross-sectoral interactions, collaborations, and training. We explored and integrated these themes into a roadmap illustrating the need for a multi-stakeholder effort to ensure that epidemiological data can fully contribute to the quantitative evaluation of human health risks, and to build confidence in a reliable decision-making process that leverages the totality of scientific evidence.


An integration of the DSM-III and ICD-8 by global severity assessments for measuring multidimensional outcomes in general hospital psychiatry.
A multiaxial classification system has been developed in which three ICD-8 derived axes of psychiatric syndromes, personality disorders and somatic syndromes, and two DSM-III axes of psychosocial stressors and social functioning have been included. Global assessment scales were annexed the three ICD-8 axes. This DSM-III/ICD-8 system was used for registration of 880 consequetively admitted psychiatric patients in a general hospital setting. The results showed that six psychiatric syndromes (substance use disorders, schizophrenia, manic-depressive psychosis, reactive psychosis, neurosis, and adjustment reactions) were responsible for 80% of the diagnostic variance. Of these syndromes, manic-depressive psychosis had the highest improvement rate both concerning symptoms and social functioning. Manic-depressive psychosis had also the lowest coefficient of variation in the stay in hospital indicating a high degree of homogeneity in accordance to the diagnose-related group system. However, patients within the categories of reactive psychosis and neurosis who received antidepressants also had a low coefficient of variation, although the neurotics were significantly more depressed than the manic-depressives at discharge from hospital.


Follicular viability and histological assessment after cryopreservation of whole sheep ovaries with vascular pedicle by vitrification.
To evaluate a cryopreservation technique by vitrification of whole ovaries with their vascular pedicle in sheep, by using two cryoprotectant solutions. Animal study. Fertility clinic in a university teaching hospital. Five to 6-month-old ewes. Whole sheep ovaries with their vascular pedicles were collected at the slaughterhouse and prepared for cryoprotectant toxicity tests and freezing procedures. Follicle viability assessment by trypan blue test and histological examination of ovary and vessel structure. No statistically significant difference in follicle viability or normal primordial follicle rates were observed between ovaries exposed or nonexposed to cryoprotectant solutions. Nor was any statistically significant difference observed before and after vitrification with the two cryoprotectant solutions. The decrease in the number of primordial follicles was smaller when frozen-thawed ovaries were treated with VS4 solution containing dimethyl sulfoxide, formamide, and propylene glycol. There were fewer nuclear anomalies and general follicular anomalies with the VS4 solution. Pedicle fractures occurred in most ovaries during thawing (11/15). Cryopreservation of whole ovary by vitrification appears a promising technique in reproductive medicine. The best histologic results were obtained with the VS4 cryoprotectant. Further studies are required to overcome vitrified ovarian vessel fracture.


Neonatal non-contact respiratory monitoring based on real-time infrared thermography.
Monitoring of vital parameters is an important topic in neonatal daily care. Progress in computational intelligence and medical sensors has facilitated the development of smart bedside monitors that can integrate multiple parameters into a single monitoring system. This paper describes non-contact monitoring of neonatal vital signals based on infrared thermography as a new biomedical engineering application. One signal of clinical interest is the spontaneous respiration rate of the neonate. It will be shown that the respiration rate of neonates can be monitored based on analysis of the anterior naris (nostrils) temperature profile associated with the inspiration and expiration phases successively. The aim of this study is to develop and investigate a new non-contact respiration monitoring modality for neonatal intensive care unit (NICU) using infrared thermography imaging. This development includes subsequent image processing (region of interest (ROI) detection) and optimization. Moreover, it includes further optimization of this non-contact respiration monitoring to be considered as physiological measurement inside NICU wards. Continuous wavelet transformation based on Debauches wavelet function was applied to detect the breathing signal within an image stream. Respiration was successfully monitored based on a 0.3°C to 0.5°C temperature difference between the inspiration and expiration phases. Although this method has been applied to adults before, this is the first time it was used in a newborn infant population inside the neonatal intensive care unit (NICU). The promising results suggest to include this technology into advanced NICU monitors.


Labetalol in controlled hypotension: administration of labetalol when adequate hypotension is difficult to achieve.
A study of controlled hypotension was undertaken in 50 major surgical patients using labetalol, a drug with both alpha- and beta-adrenoceptor blocking activity. The patients were such that difficulty in achieving controlled hypotension could be anticipated: the young, the anxious and those for whom halothane was contraindicated. The administration of labetalol quickly induced hypotension which was controlled easily and was rapidly antagonized.


Research to inform the strategic management of supply in pressure area care.
The NHS spends an estimated 45 million Pounds each year on products and services directly relating to the prevention and management of pressure sores. The role of the NHS Purchasing and Supply Agency (one of two successor bodies to NHS Supplies) at the most fundamental level is to ensure that the NHS secures maximum value from that expenditure. However, the Agency is also expected to establish and implement an overall framework for the management of purchasing and supply in the NHS--and one that increasingly takes into account the key government themes of efficiency and quality of care. This paper is in two parts. Part A describes the rationale for a more strategic approach to the management of supply at the macro level, and illustrates how the broad principles are being applied to pressure area care. Part B outlines how qualitative research has been used to inform the development of a 'supply strategy' in this field, and discusses the main outputs of this study. The research found significant differences in trusts' approaches to pressure area care, depending on the type, size and specialty of trust and the experiences and views of individuals. The level and profile of expenditure on pressure relieving equipment was similarly diverse. Rental arrangements were favoured over capital purchase in most of the trusts visited, although many had a mixed economy. Common themes were continuity of care, the importance of prevention, value for money and the need for an holistic approach.


Regulation of pre-B cell proliferation in bone marrow: immunofluorescence stathmokinetic studies of cytoplasmic mu chain-bearing cells in anti-IgM-treated mice, hematologically deficient mutant mice and mice given sheep red blood cells.
To identify factors influencing the in vivo proliferate activity of bone marrow pre-B cells, the metaphase-blocking drug, vincristine sulfate, was injected into (a) mice depleted of B lymphocytes by treatment with anti-mouse IgM antibodies from birth; (b) hematologically deficient W/Wv and Sl/Sld mutants, and (c) mice injected with a foreign agent, sheep red blood cells (SRBC). Subsequently, a quantitative measure of pre-B cell proliferation was provided by examining marrow cells by immunofluorescence labeling for the absolute number of pre-B cells, identified by the presence of cytoplasmic mu chains (c mu) without surface mu (s mu), which had been arrested in metaphase. In anti-IgM-treated mice, some changes were observed in the size of the large pre-B cell population and in the incidence of mitotic cells after vincristine administration, but the overall production rate of pre-B cells did not differ from that in controls given normal rabbit serum. Pre-B cell kinetics in W/Wv and Sl/Sld mice also generally resembled those in homozygous controls. In contrast, after SRBC injection, there was an increase in the rate at which large pre-B cells entered mitosis. Thus, the proliferation of c mu + s mu- bone marrow pre-B cells shows no evidence of feedback control from the mature B lymphocyte pool, as indicated by lack of stimulation of pre-B cell production in anti-IgM-treated mice, and is independent of the hemopoietic defects of W/Wv or Sl/Sld mutants. On the other hand, the increased bone marrow pre-B cell proliferation after SRBC injection demonstrates that the magnitude of B cell genesis in the bone marrow can be influenced by extrinsic agents and thus may be influenced by environmental stimuli.


Feasibility and safety of laparoscopic resection for gastric GISTs larger than 5 cm: Results from a prospective study.
The role of laparoscopic resection for large gastric gastrointestinal stromal tumors (GISTs), particularly those >5 cm, remains under debate due the possibility of intraoperative tumor rupture. To determine the feasibility and safety of the laparoscopic approach in the treatment of large gastric GISTs, a prospective study was performed between March 2011 and March 2014. Intraoperative tumor rupture was studied as the primary outcome. Secondary outcomes were the conversion rate, surgical duration, estimated blood loss, time to tolerate fluid and solid diets, length of post-operative hospital stay and recurrence rate at the end of the follow-up. A total of 16 patients were included in this study, with a tumor size of 7.04±1.53 cm (range, 5.2-10.8 cm). No intraoperative tumor rupture occurred. The median duration of surgery was 88.1±31.9 min, with an estimated blood loss volume of 37.1±18.7 ml. No patient required a blood transfusion. The mean time until the start of oral intake for fluid and solid diets was 1.1±0.6 and 2.5±0.9 days, respectively. The median length of post-operative hospital stay was 5.4±5.8 days. The follow-up period for all patients was 16.9±11.2 months (range, 2-38 months). No local or distant recurrence was observed. The study indicates that laparoscopic resection for large gastric GISTs is feasible and safe. Laparoscopic surgery should be considered as the standard approach in all cases, irrespective of tumor size or location.


Essential roles of mGluR1 and inhibitory synaptic transmission in NMDA-independent long-term potentiation in the spinal trigeminal interpolaris.
Patterns of synaptic activity determine synaptic strengthening or weakening that is typically represented as long-term potentiation (LTP) and long-term depression (LTD), respectively. In the present study, we aim to test whether a conditioning stimulation of the spinal trigeminal subnucleus caudalis (Vc) induces LTP at excitatory synapses in the subnucleus interpolaris (Vi) and to characterize the LTP. Generally, a presynaptic high-frequency stimulation (HFS) protocol can induce LTP at excitatory synapses in the brain, including the spinal cord. Therefore, LTP in the Vi was induced by the HFS (3 tetani at 100 Hz) of Vc in the horizontal brainstem slices. By pretreating slices with antagonists for NMDA receptors, metabotropic glutamate receptor subtype 1 or 5 (mGluR1 or 5), GABAA receptors, glycine receptors and Ca(2+) chelator, the LTP was characterized. The HFS reliably but slowly induced LTP of excitatory synaptic transmission in the Vi. This LTP was not dependent on NMDA receptor activation; however, it did require the activation of mGluR1, but not mGluR5, and an intracellular Ca(2+) rise. Interestingly, this LTP induction required inhibitory synaptic transmission mediated by GABAA and glycine receptors, and coincided with the slow development of LTD at GABAergic synapses. The GABAergic LTD was mediated by mGluR1 and the intracellular Ca(2+) rise. These data suggest that the modulation of GABAergic synaptic transmission by conditioning synaptic activity contributes to the induction and expression of LTP at excitatory synapses in the Vi.


Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome.
People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs). Cohort study. Event-based and dose-response Emax models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease-modifying treatments that reduced decline by 35% or 75%. Seventy-five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50-200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years. Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose-response models could help tailor future RCTs.


Phase I study of beta-alanyl-melphalan as a potent anticancer drug.
The dipeptide beta-alanyl-melphalan was synthesized and tested for its potential anticancer activity. It is shown to possess considerable toxicity toward Ehrlich ascites tumor cells and 3T3 mouse embryo cells in in vitro toxicity assays and is a potent anticancer agent when used in vivo in traditional phase I chemotherapy assays. The potential role for small peptide transport mechanisms in transportation of anticancer agents is discussed.


CSF sTREM2 in neurological diseases: a two-sample Mendelian randomization study.
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been described as a biomarker for microglial activation, which were observed increased in a variety of neurological disorders. Our objective was to explore whether genetically determined CSF sTREM2 levels are causally associated with different neurological diseases by conducting a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms significantly associated with CSF sTREM2 levels were selected as instrumental variables to estimate the causal effects on clinically common neurological diseases, including stroke, Alzheimer's diseases, Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and epilepsy and their subtypes. Summary-level statistics of both exposure and outcomes were applied in an MR framework. Genetically predicted per 1 pg/dL increase of CSF sTREM2 levels was associated with higher risk of multiple sclerosis (OR = 1.038, 95%CI = 1.014-1.064, p = 0.002). Null association was found in risk of other included neurological disorders. These findings provide support for a potential causal relationship between elevated CSF sTREM2 levels and higher risk of multiple sclerosis.


In vitro evaluation of various quinolone antibacterial agents against veterinary mycoplasmas and porcine respiratory bacterial pathogens.
The in vitro activities of 12 quinolones and four antibiotics were determined against 15 veterinary mycoplasmal species and four species of bacteria commonly involved in respiratory infections in pigs. The newer quinolones were markedly more active in vitro against a wide range of mycoplasmas than nalidixic acid and the earlier quinolones. Against Mycoplasma hyopneumoniae ciprofloxacin was the most active quinolone with a geometric mean minimal inhibitory concentration (MIC) against 16 strains of 0.01 microgram ml-1 compared with 0.04 microgram ml-1 for tiamulin, 0.06 microgram ml-1 for tylosin, 0.17 microgram ml-1 for oxytetracycline and 0.23 microgram ml-1 for gentamicin. M hyosynoviae was less sensitive to the quinolones with mean MICs of 0.6 microgram ml-1 for ofloxacin and 0.7 microgram ml-1 for ciprofloxacin compared with 0.034 microgram ml-1, or less, for tiamulin. Norfloxacin and its 6-chloro analogue were both mycoplasmacidal in vitro at five or 10 times their MICs against M hyopneumoniae UCD4. Tiamulin was mycoplasmastatic. The quinolones were also active against porcine Bordetella bronchiseptica and Pasteurella multocida strains and Haemophilus species. Ciprofloxacin was the most active quinolone with mean MICs of 0.58 microgram ml-1 against B bronchiseptica (nine strains), 0.026 microgram ml-1 against P multocida (five strains) and 0.01 microgram ml-1, or less, against Haemophilus pleuropneumoniae (nine strains) and H parasuis (two strains) compared with mean MICs of from 0.5 microgram ml-1 to 64 micrograms ml-1, or more, for the antibiotics. This combination of excellent mycoplasmacidal activity against M hyopneumoniae and good antibacterial activity, suggests that the quinolones have great potential for treating respiratory infections in pigs, including enzootic pneumonia.


Laparoscopic adjustable gastric banding: initial Tasmanian experience.
The laparoscopic adjustable gastric band (LAGB) is a minimally invasive, adjustable and reversible bariatric procedure. The present paper reports an initial 2 year experience at Royal Hobart Hospital, Tasmania. Between February 1999 and June 2001, 207 patients underwent LAGB insertion (176 female, 31 male). The mean age was 43 years (range: 16-74 years). Mean preoperative weight was 125 kg (range: 83-210 kg) and mean body mass index (BMI) was 45.9 (range: 32.6-67.0). The Bioenterics LAGB (Inamed, Chullora, NSW, Australia) was used in all cases. The average follow up was 17 months (range: 3-24 months). Three patients were lost to follow up (1.5%). The average weight loss was 12.4 kg at 3 months, 25.3 kg at 1 year and 34.8 kg at 2 years. The average BMI was reduced from 45.9 preoperatively to 41.3 at 3 months, 36.9 at 1 year and 33.5 at 2 years. Reoperation for band slippage occurred in 24 patients (11%), and the injection reservoir required changes in 22 patients (11%). There were three perforations while inserting the LAGB, two non-fatal pulmonary emboli (1%) and two cases of deep vein thrombosis (1%). There has been no mortality. Laparoscopic adjustable gastric banding is a safe and effective method of achieving significant (P < 0.0001) weight reduction in the morbidly obese.


Regulatory T cells, inflammation, and endoplasmic reticulum stress in women with defective endometrial receptivity.
To investigate immunologic parameters and endoplasmic reticulum (ER) stress associated with unexplained infertility. Case-control study. Academic center. Women with no fertility problems (FS) (n = 13), women with recurrent miscarriage (RM) (n = 15) and women with repeated in vitro fertilization failure (RIF) (n = 15). Endometrial biopsy and collection of peripheral blood during the midsecretory phase of menstrual cycle. Leptin, resistin, soluble tumor necrosis factor receptor (sTNF-R), myeloperoxidase (MPO), soluble intercellular adhesion molecule 1 (sICAM-1), and interleukin 22 (IL-22) concentration in peripheral blood, endometrial CD3(+), CD4(+), CD5(+), CD8(+), and FoxP3(+) T lymphocytes, and endometrial expression of HSPA5, a specific marker of ER stress. We found an increase of proinflammatory molecules such as resistin, leptin, and IL-22 in both RM and RIF patients; sTNF-R and MPO only in RIF patients when compared with the FS women. We also found in endometria of infertile women a statistically significant increase of CD3(+), CD4(+), CD8(+) in both RM and RIF patients and CD5(+) in RM patients when compared with FS women. This was paralleled by a statistically significant reduction of infiltrating FoxP3(+) regulatory T cells. Finally, endometrial HSPA5 expression levels were statistically significantly up-regulated in both RM and RIF patients. Women with RM and RIF showed an increase of circulating proinflammatory cytokines, altered endometrial T lymphocytes subsets, and signs of endometrial ER stress.


Role of the dysmorphologic evaluation in the child with developmental delay.
This article focuses on the dysmorphologic evaluation of the child who has developmental delay or cognitive impairment. Attention is focused on minor anomalies, because those are often considered to be the dysmorphic features that are the component manifestations of a particular syndrome. This article provides a brief discussion of craniofacial, skin, and limb anomalies (which are more likely to be noted not only by clinicians but also by allied health workers) and notes which features are particularly helpful clues to common syndromes, metabolic disorders, or autism syndromes.


Antiviral activity of tiazofurine against barley stripe mosaic virus.
Tiazofurine (2-beta-D-ribofuranosylthiazole-4-carboxamide) was found to inhibit replication of barley stripe mosaic virus (BSMV) in barley and wheat plants. Treatment with this nucleoside analogue delayed and inhibited symptom development and suppressed virus multiplication. The most effective concentration applied twice as a foliar spray 3 h and one day after inoculation, was 10(-3) M. Decreased virus multiplication was obtained without marked phytotoxicity. Three weeks after treatment the antiviral effect declined.


Effects of p-chloroamphetamine and 5,7-dihydroxytryptamine on the sexual behavior of gonadectomized male and female rats.
Treatment with the 5-HT neurotoxins p-chloroamphetamine (PCA, 2 X 10 mg/kg) or 5,7-dihydroxytryptamine (5,7-DHT, 2 X 6 microgram intracerebrally) stimulated the display of all aspects of sexual behavior, including ejaculations, by castrated male rats in the absence of testosterone (T) treatment and increased the behavioral sensitivity to a low level of T stimulation. The reduction of the (3H) 5-HT uptake after PCA treatment was more pronounced in the cortex than in the hypothalamus. 5,7-DHT treatment reduced the (3H) 5-HT uptake in the septum, hippocampus, amygdala, hypothalamus and cortex but the behavioral effects produced by the 5,7-DHT treatment could not be correlated to the biochemical effects in any of these brain areas. Since the behavioral effect of PCA appears to be stronger than that of 5,7-DHT, the 5-HT neurotoxins may exert their effect on sexual behavior in forebrain structures rather than in the hypothalamus. PCA treatment had a very small effect on mounting behavior but 5,7-DHT treatment stimulated the display of mounts and intromission patterns by ovariectomized female rats given no hormone treatment. Neither PCA nor 5,7-DHT had any effect on lordosis behavior tested before and after treatment with estradiol benzoate alone or in combination with progesterone. The observations support the conclusion that 5-HT is involved in the control by T of sexual behavior in male rats, but argue against a role of 5-HT in the neural control of lordosis behavior.


A new microdrive for extracellular recording of single neurons using fine wires.
We have developed a new microdrive for fine-wire electrode recording of extracellular neuronal potentials. The new microdrive has advantages of durability of construction as well as enhanced precision and stability of electrode movement, and can be easily assembled with common laboratory tools.


Regulation of indole-3-acetic acid biosynthesis and consequences of auxin production deficiency in Serratia plymuthica.
Indole-3-acetic acid (IAA) is emerging as a key intra- and inter-kingdom signal molecule that modulates a wide range of processes of importance during plant-microorganism interaction. However, the mechanisms by which IAA carries out its functions in bacteria as well as the regulatory processes by which bacteria modulate auxin production are largely unknown. Here, we found that IAA synthesis deficiency results in important global transcriptional changes in the broad-range antibiotic-producing rhizobacterium Serratia plymuthica A153. Most pronounced transcriptional changes were observed in various gene clusters for aromatic acid metabolism, including auxin catabolism. To delve into the corresponding molecular mechanisms, different regulatory proteins were biochemically characterized. Among them, a TyrR orthologue was essential for IAA production through the activation of the ipdc gene encoding a key enzyme for IAA biosynthesis. We showed that TyrR specifically recognizes different aromatic amino acids which, in turn, alters the interactions of TyrR with the ipdc promoter. Screening of mutants defective in various transcriptional and post-transcriptional regulators allowed the identification of additional regulators of IAA production, including PigP and quorum sensing-related genes. Advancing our knowledge on the mechanisms that control the IAA biosynthesis in beneficial phytobacteria is of biotechnological interest for improving agricultural productivity and sustainable agricultural development.


Does hepatitis C virus infection contribute to hepatocellular carcinoma in Hong Kong?
Hong Kong has a high incidence of hepatocellular carcinoma (HCC) and, because it is an endemic area for hepatitis B virus (HBV) infection, the etiologic association between HCC and HBV infection is reported to be as high as 80%. Hepatitis C virus (HCV) recently was shown to be a possible pathogenetic agent for HCC in a number of countries. To assess the relative importance of these two viruses in HCC in Hong Kong, a retrospective study of 424 Chinese patients with HCC was performed. Three hundred forty-one (80.3%) patients were found to be carriers of hepatitis B surface antigen (HBsAg). Hepatitis C antibodies (anti-HCV) were detected in 31 patients (7.3%). Fifteen patients with positive findings for anti-HCV had concurrent HBV infection, 11 had serologic evidence of previous HBV infection, and only 5 patients had anti-HCV marker alone. Patients with positive findings for anti-HCV were older than those with HBsAg (mean ages, 60 and 53 years, respectively). A higher preponderance of male patients was found in the HBsAg-positive group; the male to female ratio was 11:1, compared with 7:1 among patients with anti-HCV. Anti-HCV was detected in 0.64% of 175 age-matched and sex-matched controls. These data indicate a possible causal role of HCV infection in HCC, but it is of relatively minor epidemiologic significance in Hong Kong, where HBV infection is overwhelming.


[Experimental investigations of the content of glycogen in the adrenal gland of the rat after application of dexamethasone, ACTH and a combination of both (author's transl)].
The influence of dexamethasone, ACTH and the combination of both on the glycogen content of the rat adrenal gland was studied. Dexamethasone induces a transient increase of the adrenal glycogen content in a time and dose-dependent manner. The application of ACTH has no effect on the glycogen content. Surprisingly, the increase of the glycogen content induced by dexamethasone is completely blocked by the simultaneous application of ACTH.


Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized primarily at the apical or luminal surfaces of epithelial cells that line the airway, gut, and exocrine glands; it is well established that CFTR plays a pivotal role in cholera toxin (CTX)-induced secretory diarrhea. Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in blood and foods, has been reported to play a vital role in a variety of conditions involving gastrointestinal wound repair, apoptosis, inflammatory bowel disease, and diarrhea. Here we show, for the first time, that type 2 LPA receptors (LPA2) are expressed at the apical surface of intestinal epithelial cells, where they form a macromolecular complex with Na+/H+ exchanger regulatory factor-2 and CFTR through a PSD95/Dlg/ZO-1-based interaction. LPA inhibited CFTR-dependent iodide efflux through LPA2-mediated Gi pathway, and LPA inhibited CFTR-mediated short-circuit currents in a compartmentalized fashion. CFTR-dependent intestinal fluid secretion induced by CTX in mice was reduced substantially by LPA administration; disruption of this complex using a cell-permeant LPA2-specific peptide reversed LPA2-mediated inhibition. Thus, LPA-rich foods may represent an alternative method of treating certain forms of diarrhea.


Quaternary substituted PDE IV inhibitors II: the synthesis and in vitro evaluation of a novel series of gamma-lactams.
This communication describes the synthesis and in vitro evaluation of a novel potent series of phosphodiesterase type (IV) (PDE IV) inhibitors. Several of the quaternary substituted lactams presented possess low nanomolar IC50's for PDE IV inhibition.


Assembling novel Cd(II) complexes with multidentate nitrogen donor ligands obtained in situ from the system: zerovalent copper, cadmium oxide, 1-hydroxymethyl-3,5-dimethylpyrazole and ammonium thiocyanate.
A novel 3D coordination polymer [Cd2(L(1))(2)(SCN)(4)(MeOH)(2)](n) (1) and monomeric [Cd(NCS)(2)L(2)] (2) (L(1) = urotropine, L(2) = tris(1-(3,5-dimethylpyrazolylmethyl))amine) have been prepared in a one-pot synthesis using 1-hydroxymethyl-3,5-dimethylpyrazole as the starting ligand. The most prominent feature is the formation in situ of the organic compounds: urotropine and scorpionate-tripodal ligands.


Embryonic versus adult myocardium: adenine nucleotide degradation during ischemia.
Neonatal myocardium demonstrates better recovery from ischemia than does adult tissue. We tested the hypothesis that developmental differences in adenine nucleotide degradation might facilitate recovery by quantitating depletion of high-energy phosphates in nine-day-old embryonic (n = 9) and 15-month-old adult (n = 14) chicken hearts at 15-, 30-, 45-, and 60-minute intervals of normothermic ischemia in vitro. Nucleotides adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate and nucleosides adenosine, inosine, hypoxanthine, and xanthine were determined by high-performance liquid chromatography. Several observations in metabolite degradative response to ischemia were noted. The embryonic myocardium maintained higher adenosine triphosphate and adenosine monophosphate levels over the course of the investigation than did mature myocardium. Moreover, the adult group showed an increase in diffusible nucleoside pool metabolites. Relative immaturity of enzymes responsible for nucleotide degradation may facilitate postischemic recovery by preserving nondiffusible high-energy phosphate precursors to participate in salvage resynthesis of adenosine triphosphate.


Ethnobotany, ethnopharmacology, and phytochemistry of traditional medicinal plants used in the management of symptoms of tuberculosis in East Africa: a systematic review.
Many studies on the treatment of tuberculosis (TB) using herbal medicines have been undertaken in recent decades in East Africa. The details, however, are highly fragmented. The purpose of this study was to provide a comprehensive overview of the reported medicinal plants used to manage TB symptoms, and to analyze scientific reports on their effectiveness and safety. A comprehensive literature search was performed in the major electronic databases regarding medicinal plants used in the management of TB in East Africa. A total of 44 reports were retrieved, and data were collected on various aspects of the medicinal plants such as botanical name, family, local names, part(s) used, method of preparation, efficacy, toxicity, and phytochemistry. The data were summarized into percentages and frequencies which were presented as tables and graphs. A total of 195 species of plants belonging to 68 families and 144 genera were identified. Most encountered species were from Fabaceae (42.6%), Lamiaceae (19.1%), Asteraceae (16.2%), and Euphorbiaceae (14.7%) families. Only 36 medicinal plants (18.5%) have been screened for antimycobacterial activity. Out of these, 31 (86.1%) were reported to be bioactive with minimum inhibitory concentrations ranging from 47 to 12,500 μg/ml. Most tested plant extracts were found to have acceptable acute toxicity profiles with cytotoxic concentrations on normal mammalian cells greater than 200 μg/ml. The most commonly reported phytochemicals were flavonoids, terpenoids, alkaloids, saponins, cardiac glycosides, and phenols. Only Tetradenia riparia, Warburgia ugandensis, and Zanthoxylum leprieurii have further undergone isolation and characterization of the pure bioactive compounds. East Africa has a rich diversity of medicinal plants that have been reported to be effective in the management of symptoms of TB. More validation studies are required to promote the discovery of antimycobacterial drugs and to provide evidence for standardization of herbal medicine use.


Detection of a novel point mutation causing haemophilia A by PCR/direct sequencing of ectopically-transcribed factor VIII mRNA.
Specifically-primed reverse transcripts of lymphocyte-derived factor VIII (FVIII) mRNA were successfully amplified by means of the polymerase chain reaction (PCR) thus further extending the phenomenon of ectopic ("illegitimate") transcription of tissue-specific genes. The diagnostic potential of a basal rate of transcription in non-expressing tissues was then demonstrated by the detection of a novel point mutation in the FVIII gene causing haemophilia A by PCR/direct sequencing of ectopically transcribed mRNA derived from patient lymphocytes.


Intramedullary Well-differentiated Osteosarcoma: Imaging and Pathologic Findings in 17 Patients.
Intramedullary well-differentiated osteosarcoma (IMWDOS) is rare and may easily be misdiagnosed. This study aimed at investigating the clinical, imaging, and pathological features of IMWDOS for correct diagnosis. Seventeen patients with IMWDOS were enrolled, and their clinical, imaging, and pathological data were analyzed. Total 13 males and 4 females aged 19-55 years (mean 36. 1) were selected. The lesion was located at long bones in 16 patients and the second region of the acetabulum in one patient. Except for three patients with limited areas of lesions, all the other patients had a wide distribution of tumor, and the lesion in long bones involved the metaphysis area with possible extension towards the diaphysis. In imaging, the lesion usually had an unclear boundary with the destruction of bone cortex, uneven thickness of the bone cortex, thick and coarse trabecula in the lesion, but few periosteal reactions and soft tissue masses. The lesion was histologically composed of spindle cells with slight atypia. Follow-up was performed 2-101 months (mean 31.9m) in 14 cases, 10 years in one case, and 26 years in the remaining two. At follow-up, 12 patients (12/17 or 70.6%) who had a complete resection, including amputation (n=2), wide excision (n=8), and endoprosthetic replacement (n=2), showed no recurrence or metastasis. Among five patients who underwent curettage, three (3/17 or 17.6%) had recurrent lesions, leading to death in two of them, and the third one died during post-operation chemotherapy. Intramedullary well-differentiated osteosarcoma tends to occur at the metaphysis of long bones, especially at the distal femur. Histological, clinical, and imaging findings lack specific characteristics and should be examined collectively to reach a correct diagnosis. The prognosis of patients with complete lesion resection is good, while incomplete lesion curettage or resection will lead to recurrence and transformation into a highly malignant tumor.


Outgrowth and directional specificity of fibers from embryonic retinal transplants in the chick optic tectum.
Retinal pieces taken from known positions of 6-day chick embryos were vitally labeled with the fluorescent dye Rhodamine-B-isothiocyanate (RITC). They were then transferred onto the surfaces of optic tecta following early bilateral removal of the embryo's optic vesicles. One to 5 days after transplantation the tecta were fixed and transplants that issued fibers were examined on tectal whole-mounts or were sectioned and viewed with a fluorescence microscope. Retinal fibers growing out from transplants on day E6 tecta showed a capacity for changing their initial outgrowth directions and for reorienting themselves towards their specific retinotopic projection area. Frequently, changes in growth direction appeared in a right-angled pattern. The capacity for turning was strongest for fibers of nasal retinal origin, less strong for fibers of temporal origin, and occurred rarely but unquantifiably in the case of fibers of ventral retinal origin. Fibers of all investigated retinal quadrants were found to reach their corresponding projection areas and to arborize there, that is, fibers of nasal retinal transplants in the posterior tectum, of temporal transplants in the anterior tectum, and of ventral transplants in the dorsal tectum. Furthermore, once in their target region, the fibers left the outer layer of the tectum and turned, again in right angles, to invade deeper layers. Capacity of fibers to turn towards their projection area was not observed for fibers issued from transplants placed on the tectum later than day E8. We suggest that there is a specific guidance of retinal axons on the tectum.


Hormonal activation of the cGMP-inhibited low-Km cyclic AMP phosphodiesterase of rat adipocytes from different sites: influence of ovariectomy.
Hormonal activation of the cGMP-inhibited low Km cyclic AMP phosphodiesterase isoenzyme (cGI.PDE) by effectors, acting either through the cAMP-independent (insulin) or through cAMP-dependent (isoproterenol, forskolin ACTH and 8Br-cAMP) mechanisms, were compared in parametrial (PM) and femoral subcutaneous (SC) adipocytes from sham-operated (SHAM) and ovariectomized (OVX) rats. In SHAM rats, the basal cGI.PDE activity was 50% higher in PM than in SC adipocytes. In OVX rats, the cGi.PDE activatory responses to all the effectors tested remained unchanged in SC, but were completely suppressed in PM adipocytes. The mechanism underlying these defective cGI.PDE activatory responses to cAMP-dependent effectors observed in PM adipocytes after OVX seems to involve protein kinase A, since a decreased activation of cGI.PDE by protein kinase A was also found in these cells. Treatment of OVX rats with both estradiol and progesterone reversed the defective cAMP-dependent activation of cGI.PDE, but not the refractoriness of this isoenzyme to insulin activation. Taken together with previous observations from this laboratory on the fat cell adenylate cyclase system (Lacasa et al. (1991) Endocrinology 128, 747-753), these results: (a) demonstrate that the influence of the ovarian status on the key enzymes controlling cAMP metabolism in fat cells depends on the anatomical origin of these cells, and; (b) provide a biochemical explanation to the insensitivity of the SC adipocyte lipolytic system to ovarian hormones.


The use of prosthetics in pelvic reconstructive surgery.
With an ageing population, increasing numbers of women are presenting with pelvic floor disorders. The lifetime risk of undergoing prolapse or incontinence surgery in the USA is 1 in 11. With a recognized reoperation rate exceeding 30% for prolapse surgery, attempts are being made to improve our primary surgical outcomes. The introduction of synthetic and biological prostheses have been proposed to reduce recurrence rates whilst maintaining vaginal capacity and coital function. The role of synthetic prostheses is well established for use in continence surgery in the form of midurethral slings and for abdominal sacrocolpopexy to correct vault prolapse. However, postoperative morbidity-specifically the risk of mesh erosion-has limited their use for vaginal prolapse surgery. Biological prostheses have been introduced to offer an alternative for use in these repairs. While these grafts largely obviate the problem of erosion there are concerns regarding longevity, and only short-term outcome data are currently available. The role of prosthetics in pelvic floor surgery is an evolving and controversial field. Current and future research should be directed at evaluating the safety and efficacy of specific products and comparison of subjective and objective outcome parameters to standard surgical techniques for pelvic organ prolapse.


Updates on new monogenic inborn errors of immunity.
Inborn errors of immunity (IEI), also referred to as primary immunodeficiencies (PID), are disorders that, for the most part, result from mutations in genes involved in immune host defense and immune regulation. Thanks to the increased availability of high-throughput DNA sequencing and the improvement in genomic data interpretation, the number of newly identified genes associated with IEI has exponentially increased over the last decade. We reviewed four recently described monogenic IEI and discussed the clinical and immunologic features of these new conditions.


[Comparison of mortality of lung cancer resections in France to other European countries].
France is characterized by the dispersion of its technical surgical platforms, and it seemed interesting for us to obtain information on quality of care compared to other European countries, which often have different organizations and practices. The objective of the study was to compare the 30-day mortality of patients operated on for bronchial cancer in France with that of other European countries. We conducted a literature review on practices in different European countries. The terms used for the selection were: lung cancer surgery, 30-day mortality in different hospitals in European countries. We selected 9 articles corresponding to 9 European countries. The correlation coefficient between the number of lung resections per year and the population of the country was 0.967. The linear regression model between number of annual lung resections and population showed that except for Great Britain, most of the countries were close to the linear regression line. Germany and France had a mortality rate of 2.887% and 2.937% respectively, whereas the average is 2.13%. Following sensitivity analysis, the mortality rates for Germany and France remained higher than the average. France is among the European countries with the highest postoperative mortality rates. These results should induce surgical teams to adopt quality-of-care measures focusing on outcome analysis.


The Construction of Binary Phase Electrolyte Interface for Highly Stable Zinc Anodes.
Metal zinc is a promising anode candidate of aqueous zinc-ion batteries due to high theoretical capacity, low cost, and high safety. However, it often suffers from hydrogen evolution reaction (HER), dendrite growth, and formation of by-products. Herein, a triethyl phosphate (TEP)/H2 O binary phase electrolyte (BPE) interface is developed by introducing TEP-based electrolyte-wetted hydrophobic polypropylene (PP) separator onto the Zn anode surface. The equilibrium of the BPE interface depends on the comparable surface tensions of H2 O-based and TEP-based electrolytes on hydrophobic PP separator surfaces. The BPE interface induces Zn2+ solvation structure conversion from [Zn(H2 O)x ]2+ to [Zn(TEP)n (H2 O)y ]2+ , where most solvated H2 O molecules are removed. In [Zn(TEP)n (H2 O)y ]2+ , the residual H2 O molecules can be further constrained by the formation of H bonds between TEP and H2 O molecules. Consequently, the ionization of solvated H2 O molecules is effectively suppressed, and HER and by-products are effectively restricted on Zn anode surfaces in BPE. As a result, Zn anodes exhibit a high Coulombic efficiency of 99.12% and superior cycling performance of 6000 h, which is much higher than the case in single-phase aqueous electrolytes. To illustrate the feasibility of BPE in full cells, the Zn/Alx V2 O5 batteries are assembled based on the BPE and exhibited enhanced cycling performance.


Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana.
HIV infection is associated with increased risk of renal dysfunction, including tubular dysfunction (TD) related to antiretroviral therapy (ART). Tenofovir disoproxil fumarate (TDF) is becoming available for ART in sub-Saharan Africa, although data on its long-term safety there is limited. We aimed to study the prevalence of HIV-associated renal dysfunction in Ghana and explore associations between proteinuria or TD and potential risk factors, including TDF use. A single-centre cross-sectional observational study of patients taking ART was undertaken. Creatinine clearance (CrCl) was calculated and proteinuria detected with dipsticks. Spot urinary albumin and protein:creatinine ratios (uACR/uPCR) were measured and further evidence of TD (defined as having two or more characteristic features) sought. Logistic regression analysis identified factors associated with proteinuria or TD. In 330 patients, of whom 101 were taking TDF (median 20 months), the prevalence of CrCl < 60 ml/min/1.73 m(2), dipstick proteinuria and TD was 7 %, 37 % and 15 %. Factors associated with proteinuria were baseline CD4-count [aOR 0.86/100 cell increment (95 % CI, 0.74-0.99)] and TDF use [aOR 2.74 (95 % CI, 1.38-5.43)]. The only factor associated with TD was TDF use [aOR 3.43 (95 % CI, 1.10-10.69)]. In a subset with uPCR measurements, uPCRs were significantly higher in patients taking TDF than those on other drugs (10.8 vs. 5.7 mg/mmol, p < 0.001), and urinary albuin:protein ratios significantly lower (0.24 vs. 0.58, p < 0.001). Both proteinuria and TD are common and associated with TDF use in Ghana. Further longitudinal studies to determine whether proteinuria, TD or TDF use are linked to progressive decline in renal function or other adverse outcomes are needed in Africa.


Passenger-surface microbiome interactions in the subway of Mexico City.
Interaction between hands and the environment permits the interchange of microorganisms. The Mexico City subway is used daily by millions of passengers that get in contact with its surfaces. In this study, we used 16S rRNA gene sequencing to characterize the microbiomes of frequently touched surfaces and compare regular and women-only wagons. We also explored the effect of surface cleaning on microbial resettling. Finally, we studied passenger behavior and characterized microbial changes after traveling. Most passengers (99%), showed some type of surface interaction during a wagon trip, mostly with the hands (92%). We found microbiome differences associated with surfaces, probably reflecting diverse surface materials and usage frequency. The platform floor was the most bacterial diverse surface, while the stair handrail and pole were the least diverse ones. After pole cleaning, the resettling of microbial diversity was fast (5-30 minutes); however, it did not resemble the initial composition. After traveling, passengers significantly increased their hand microbial diversity and converged to a similar microbial composition among passengers. Additionally, passenger hand microbiomes resembled subway surfaces in diversity. However, microbial fingerprints were preserved within passengers after traveling.


Skin infections in pregnancy.
A wide array of infectious diseases can occur in pregnancy. Their acquisition, clinical presentation, and course during gestation may be altered due to an impairment of the maternal cellular immunity. Some infectious diseases can lead to serious consequences for the mother or the offspring, including congenital malformations. This review describes in detail the clinical presentation, course, management, and associated maternal and fetal risks of selected viral (varicella-zoster virus infections, condylomata acuminata), fungal (candida vulvovaginitis), bacterial (Lyme borreliosis), and parasitic (scabies) infections. The treatment options are critically reviewed. First-line therapies include acyclovir and varicella-zoster virus immunoglobulin for varicella-zoster virus infections, surgical modalities for genital warts, topical clotrimazole and oral fluconazole for Candida vulvovaginitis, amoxicillin and cefuroxime for Lyme borreliosis, and permethrin for scabies. A synopsis of maternal and fetal risks of other important infections is also included.


Sirolimus in pediatric patients: results in the first 6 months post-renal transplant.
We report our experience with sirolimus in children during the first 6 months after renal transplantation. From July 2000 to January 2004, 66 children received 33 deceased donor and 33 living donor transplants. Maintenance immunosuppression included sirolimus 3 mg/m(2) in addition to prednisone and tacrolimus or cyclosporine. Patient survival was 100% and graft survival was 65 of 66. Seven children experienced acute rejection episodes. All were reversible with increased doses of corticosteroid. One case of graft failure was caused by ischemic renal injury. Adverse events included Epstein-Barr viremia (8 patients) with three cases of post-transplant lymphoproliferative disease (PTLD), cytomegalovirus viremia (4 patients), poor wound healing (4 patients), pneumonitis (3 patients), nephrotic syndrome (3 patients), perinephric abscess (1 patient) and insulin-dependant diabetes (2 patients). Sirolimus was discontinued in 13 children for adverse events predominantly for wound dehiscence and pneumonitis. Cholesterol levels >200 mg/dL were observed in 33 children. Thrombocytopenia (platelet count <140 000) was not observed. We concluded that early outcomes with sirolimus were acceptable with 98% graft survival and 11% incidence of acute rejection. Medication was discontinued in 20% for adverse events which included poor wound healing and non-infectious pneumonitis. Infections with cytomegalovirus and Epstein-Barr virus, and PTLD were also significant early complications. Therefore, a sirolimus-based regimen that is combined with both an interleukin-2 receptor antibody and a calcineurin inhibitor may be excessive immunosuppression for pediatric renal transplant recipients.


Obesity, Hypovitaminosis D, and COVID-19: the Bermuda Triangle in Public Health.
The COVID-19 pandemic has challenged public health to a significant extent by markedly increasing morbidity and mortality. Evidence suggests that obesity and hypovitaminosis D constitute important risk factors for SARS-CoV-2 infection, severity of disease, and poor outcomes. Due to their high prevalence globally, obesity and hypovitaminosis D are considered pandemics. This review presents current epidemiologic and genetic data linking obesity, hypovitaminosis D, and COVID-19, highlighting the importance of the convergence of three pandemics and their impact on public health. We also briefly summarize potential mechanisms that could explain these links. Epidemiologic data have shown that obesity is an independent risk factor for COVID-19, severe disease and death, and genetic evidence has suggested a causal association between obesity-related traits and COVID-19 susceptibility and severity. Additionally, obesity is independently associated with hypovitaminosis D, which is highly prevalent in subjects with obesity. Hypovitaminosis D is independently associated with a higher risk for COVID-19, severity, hospitalization, infectious complications, acute respiratory distress syndrome, and poor outcomes. However, genome-wide association studies have not revealed any causal association between vitamin D levels and the risk for COVID-19, while there is no robust evidence for a beneficial role of vitamin D supplementation in the prevention and treatment of COVID-19. In the context of the ongoing COVID-19 pandemic, the epidemiologic impact of obesity and hypovitaminosis D is emphasized. Efforts to increase public awareness and reinforce preventive and therapeutic measures against obesity and hypovitaminosis D are strongly required.


Scanning electron microscope study of the rabbit anterior chamber angle.
The three-dimensional fine structure and the collagenous framework of the anterior chamber angle (chamber angle) of albino rabbits, which does not posses a Schlemm's canal, were examined, with or without NaOH maceration, by scanning electron microscopy. The chamber angle is ill defined because the deep ciliary cleft appears parceled by iris pillars. The collagenous framework of the pectinate ligaments and iris pillars arising from the iris root join to the collagen bundles of the trabecular sheet, and the surface of the ciliary cleft is covered by an endothelial cell layer that screens the trabecular meshwork. Round openings are apparent in the recesses of the ciliary cleft, with junctions between more superficial or deeper trabecular sheets resulting in direct communication between adjacent trabecular spaces. Openings of the angular aqueous plexus/sinus in place of Schlemm's canal were seen on the inner surface of the corneosclera after removing the trabecular meshwork. The framework of the trabecular sheet is basically formed of circumferentially arranged flat collagen bundles and reticularly diverged narrow collagen bundles extending from them. There is no shift between collagen bundles of the trabecular meshwork and the corneosclera, suggesting a frail connection between the two tissues.


Volatile organic compounds of Schenella pityophilus.
Volatile organic compounds of Schenella pityophilus have been identified via solid-phase microextraction-gas chromatography-mass spectrometry analysis. Ten compounds have been identified, in which 3-methylthio-1-propene was the most significant component. Some other components were previously identified in Tuber aestivum and Tuber melanosporum.


Computer vision syndrome prevalence according to individual and video display terminal exposure characteristics in Spanish university students.
To estimate the prevalence of computer vision syndrome (CVS) in university students and its relationship with sociodemographic and optical correction factors and exposure to video display terminal (VDT). This cross-sectional study included 244 Spanish university students who responded to an anamnesis, a VDT exposure questionnaire and the Computer Vision Syndrome Questionnaire (CVS-Q© ). A descriptive analysis was performed and the prevalence of CVS was calculated. Logistic regression models were used to measure the association between CVS and the variables studied. The mean age was 20.7 years (SD = 2.1), 57% were women, 78.3% used VDTs ≥ 2 hours/day to study. The prevalence of CVS was 76.6%, and the most frequent symptoms were headache and itching. In the crude analysis, being a woman, using glasses daily and to study, and a longer VDT use to study and in total were associated with a higher prevalence of CVS; while in the older group, the prevalence was lower. In the multivariate model, VDT use to study was associated with a greater probability of CVS (aOR: 3.43; 95%CI: 1.03-11.42), and being between 22 and 29 years was associated with a lower probability of it (aOR: 0.36; 95%CI: 0.15-0.89). CVS has a high prevalence amongst Spanish university students. The most affected are the younger ones and those who use VDTs for longer hours to study. It is essential to continue investigating the influence of the type of tasks conducted with VDTs on CVS and thus to establish the preventive measures to reduce this syndrome.


Efficacy and safety of erenumab in migraine prevention: evidences from direct and indirect comparisons.
To date, it remains challenging for clinicians to make informed decisions about which dosage of erenumab is more effective for treating adult patients with migraine. Thus, we sought to examine the safety and efficacy of different doses of erenumab in this group of patients. We searched several databases from inception to May 31, 2021, irrespective of language. We included only RCTs that compared erenumab 70 mg, erenumab 140 mg, and placebo in migraine patients. The primary efficacy outcome was change in monthly migraine days (MMDs). The primary safety outcome was defined as treatment-emergent adverse events (TEAEs). We reported relative risks (RRs) with 95% credible intervals (CrIs) from the analysis. Overall, eight trials comprising 4281 participants were included in this study. Network meta-analysis showed that both erenumab 70 mg (MD: - 1.43, 95% CrI: - 1.71 to - 1.16) and erenumab 140 mg (MD: - 1.78, 95% CrI: - 2.21 to - 1.45) were associated with decreased MMDs. Also, erenumab 140 mg was associated with significantly lower MMDs than erenumab 70 mg (MD: - 0.34, 95% CrI: - 0.68 to - 0.01). In terms of primary safety outcome, neither erenumab 70 mg (RR: 0.98, 95% CrI: 0.92 to 1.05) nor erenumab 140 mg (RR: 0.99, 95% CrI: 0.91 to 1.07) was associated with increased risk of TEAEs. The results from this study suggested erenumab 140 mg might provide better efficacy than 70 mg among adult patients with migraine, without increasing TEAEs. Future elaborated RCTs with a larger number of participants are warranted to validate these discoveries.


A proposed mechanism for the production of skeletalmotor positioning movements by the basal ganglia.
A programming function for the Basal Ganglia is suggested by implicating them in the production of positioning movements during directed skeletalmotor movements. The Association Cortex (especially the Prefrontal) sends a signal which is an internal representation of the desired end position of a movement to the Caudate. The Sensorimotor Cortex sends feedback from the commands for the primary movement to the Putamen, this representing the end position to be attained by the primary movement. These two signals are integrated in the Lateral Pallidal Segment producing a signal coding the magnitude and possibly the timing of positioning movements. This signal is sent to the Subthalamic Nucleus, which distributes it to the two main output areas of the Basal Ganglia and hence to affect motor and postural pathways.


Phylogeography of endemic Xantus' hummingbird (Hylocharis xantusii) shows a different history of vicariance in the Baja California Peninsula.
Studies of phylogeographic patterns provide insight into the processes driving lineage divergence in a particular region. To identify the processes that caused phylogeographic breaks, it is necessary to use historical information and a set of appropriate molecular data to explain current patterns. To understand the influence of geological or ecological processes on the phylogeography of the only species of hummingbird endemic to the Baja California Peninsula, Hylocharis xantusii, mitochondrial DNA sequences of three concatenated genes (Cyt-b, COI and ND2; 2297bp in total) in 100 individuals were analyzed. The spatial analyses of genetic variation showed phylogeographic structure consisting of a north, central and south regions. According to estimated divergence times, two vicariant events are supported, permanent separation of the peninsula and formation of the Gulf of California at 5mya and temporary isolation of the southern region at the Isthmus of La Paz at 3mya. The temporal frame of genetic differentiation of intraspecific haplotypes indicates that 90% of haplotypes diverged within the last 500,000years, with a population expansion 80,000years ago. Only four haplotypes diverged ∼2.2 my and occurred in the south (Hxan_36, 38 and 45), and north (Hxan_45 and 56) regions; only haplotype 45 is shared between south and north populations. These regions also have the most recent haplotypes from 12,500 to 16,200years ago, and together with high levels of genetic diversity, we suggest two refuge areas, the Northern and Southern regions. Our results indicate that the phylogeographic pattern first results from vicariance processes, then is followed by historical and recent climate fluctuations that influenced conditions on the peninsula, and it is also related to oases distribution. This study presents the first investigation of phylogeography of the peninsular' endemic Xantus' hummingbird.


Multicentre observational study of adults with asthma exacerbations: who are the frequent users of the emergency department in Japan?
Emergency department (ED) visits for asthma exacerbation reflect a failure of longitudinal asthma management. However, little is known about the characteristics of patients with frequent ED visits (≥2 visits in a 1-year period). We aimed to characterise the adult patients who frequently presented to the ED for asthma exacerbation in Japan. A multicentre chart review study of 23 EDs across Japan. Adults aged 18-54 years who presented to the ED with asthma exacerbation from 2009 to 2011. Frequency of ED visits for asthma exacerbation in a 1-year period, including the index ED visit. Of the 1002 eligible patients, 218 (22%) had frequent ED visits, accounting for 48% of total ED visits for asthma exacerbation in the 1-year period. Specifically, 12% had 2 ED visits and 10% had ≥3 visits. In these patients, guideline-recommended chronic management was suboptimal. For example, among patients with ≥3 ED visits, only 63% were treated with inhaled corticosteroids and 49% were current smokers. In a multinomial logistic regression model, markers of chronic asthma severity (history of hospitalisation for asthma and use of inhaled corticosteroids) were significantly associated with a higher frequency of ED visits (both p<0.05). This multicentre study in Japan demonstrated that many patients are frequent ED users for asthma exacerbation. We also found that their asthma control management is suboptimal, most likely contributing to worse chronic severity and more frequent ED visits. Further dissemination and adoption of evidence-based guidelines are required to reduce asthma morbidity in this high-risk population.


A multi-family cluster of COVID-19 associated with asymptomatic and pre-symptomatic transmission in Jixi City, Heilongjiang, China, 2020.
We investigated a multi-family cluster of 22 cases in Jixi, where pre-symptomatic and asymptomatic transmission resulted in at least 41% of household infections of SARS-CoV-2. Our study illustrates the challenge of controlling COVID-19 due to the presence of asymptomatic and pre-symptomatic transmission even when extensive testing and contact tracing are conducted.


Correction to: Frequent genetic aberrations in the cell cycle related genes in mucosal melanoma indicate the potential for targeted therapy.
Following publication of the original article [1], the authors reported errors in Figures 2, 3 and Figure 3 'continued'.


Glycosylation of onconase increases its conformational stability and toxicity for cancer cells.
Onconase (ONC) is currently in Phase III clinical trials as a cancer chemotherapeutic agent. Despite the finding that ONC contains an N-linked glycosylation site (-N69-V70-T71-), only the non-glycosylated form of the protein has been identified to date. We employed the Pichia pastoris expression system to produce recombinant glycosylated ONC (gONC) protein. Approximately 10 mg of ONC protein was secreted per liter of culture media, of which about 80% was glycosylated at N69. CD spectroscopic analyses revealed that the secondary structure of gONC is identical to that of ONC. We found that gONC contains a high-mannose core structure. Importantly, glycosylation of ONC at N69 greatly increased its toxicity for K-562 cancer cells. Specifically, the IC50 value of gONC was 50-fold lower than that of ONC. Glycosylation increased both the Tm of ONC and its resistance to proteinase K, suggesting that the elevated cytotoxicity of gONC is related to higher conformational stability.


Creating a virtual slide map from sputum smear images for region-of-interest localisation in automated microscopy.
We address the location of regions-of-interest in previously scanned sputum smear slides requiring re-examination in automated microscopy for tuberculosis (TB) detection. We focus on the core component of microscope auto-positioning, which is to find a point of reference, position and orientation, on the slide so that it can be used to automatically bring desired fields to the field-of-view of the microscope. We use virtual slide maps together with geometric hashing to localise a query image, which then acts as the point of reference. The true positive rate achieved by the algorithm was above 88% even for noisy query images captured at slide orientations up to 26°. The image registration error, computed as the average mean square error, was less than 14 pixel² (corresponding to 1.02 μm²). The algorithm is inherently robust to changes in slide orientation and placement and showed high tolerance to illumination changes and robustness to noise.


Draft Genome Sequences of Eight Isolates of Beauveria bassiana of Neotropical Origin.
Beauveria bassiana, a well-known entomopathogenic fungus, has a worldwide distribution; however, genomes of isolates from the Neotropical region are scarce. Here, we report the draft genome sequences of eight B. bassiana isolates from Costa Rica, Puerto Rico, and Honduras.


Transient ischemic attack and minor stroke as "surgeons affairs": a narrative review.
The scope of this paper is to review the subtypes of transient ischemic attack (TIA) and minor stroke (mS) in which a surgical treatment is needed, discussing the importance and the timing of a multidisciplinary approach, in order to achieve an optimized management and prevent major strokes or other critical complications. The keywords "transient ischemic attack," "minor stroke," "surgical treatment," "vascular surgery," "heart surgery," "neurosurgery," and "multidisciplinary" were searched using MEDLINE, EMBASE, and Scopus. Relevant search results were discussed by the authors for references inclusion. Notwithstanding that best medical therapy is usually the first choice for the most part of cases, there are specific but recurrent etiologies that must be properly recognized because of a potential surgical approach, even in urgency. In fact, symptomatic carotid stenosis, or particular cases of hemodynamic cerebrovascular events, should be promptly referred to vascular surgeon, since increasing evidences highlighted a benefit from an early artery revascularization. In addition, beyond arrhythmic causes, cardioembolic events due to bacterial endocarditis and atrial myxoma should be quickly diagnosed, possibly in emergency department, because they are a presumptive urgency for heart surgery. In addition to the above-mentioned conditions, in patients suffering from vertebrobasilar TIA or mS, clinicians should keep in mind the Bow Hunter disease, because surgical artery decompression can represent the only suitable treatment in selected cases. TIA and mS require a multidisciplinary in order to discuss therapeutic options, comparing risks and benefits and determining the best timing for an optimized management.


Optimal classifier feedback improves cost-benefit but not base-rate decision criterion learning in perceptual categorization.
Unequal payoffs engender separate reward- and accuracy-maximizing decision criteria; unequal base rates do not. When payoffs are unequal, observers place greater emphasis on accuracy than is optimal. This study compares objective classifier (the objectively correct response) with optimal classifier feedback (the optimal classifier's response) when payoffs or base rates are unequal. It provides a critical test of Maddox and Bohil's (1998) competition between reward and accuracy maximization (COBRA) hypothesis, comparing it with a competition between reward and probability matching (COBRM) and a competition between reward and equal response frequencies (COBRE) hypothesis. The COBRA prediction that optimal classifier feedback leads to better decision criterion leaning relative to objective classifier feedback when payoffs are unequal, but not when base rates are unequal, was supported. Model-based analyses suggested that the weight placed on accuracy was reduced for optimal classifier feedback relative to objective classifier feedback. In addition, delayed feedback affected learning of the reward-maximizing decision criterion.


Histopathological growth patterns and positive margins after resection of colorectal liver metastases.
Histopathological growth patterns (HGPs) of colorectal liver metastases (CRLM) may be an expression of biological tumour behaviour impacting the risk of positive resection margins. The current study aimed to investigate whether the non-desmoplastic growth pattern (non-dHGP) is associated with a higher risk of positive resection margins after resection of CRLM. All patients treated surgically for CRLM between January 2000 and March 2015 at the Erasmus MC Cancer Institute and between January 2000 and December 2012 at the Memorial Sloan Kettering Cancer Center were considered for inclusion. Of all patients (n = 1302) included for analysis, 13% (n = 170) had positive resection margins. Factors independently associated with positive resection margins were the non-dHGP (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.11-2.87, p = 0.016) and a greater number of CRLM (OR: 1.15, 95% CI: 1.08-1.23 p < 0.001). Both positive resection margins (HR: 1.41, 95% CI: 1.13-1.76, p = 0.002) and non-dHGP (HR: 1.57, 95% CI: 1.26-1.95, p < 0.001) were independently associated with worse overall survival. Patients with non-dHGP are at higher risk of positive resection margins. Despite this association, both positive resection margins and non-dHGP are independent prognostic indicators of worse overall survival.


Solvent fractions of selected Ethiopian medicinal plants used in traditional breast cancer treatment inhibit cancer stem cells in a breast cancer cell line.
The incidence and mortality of breast cancer in women is increasing worldwide. Breast cancer contains a subpopulation of cells known as cancer stem cells (CSCs). The CSCs are believed to be responsible for chemotherapeutic resistance and are also involved in tumor initiation, progression, evolution, and metastasis to distant sites. The present study aimed to investigate the anti-CSC potential of selected Ethiopian medicinal plants traditionally used for breast cancer treatment. The solvent fractions of three medicinal plants (the ethyl acetate fraction of Vernonia leopoldi, the aqueous fraction of Sideroxylon oxyacanthum, and the chloroform fraction of Clematis simensis) resulting from the methanolic crude extracts were selected based on their previously demonstrated cytotoxic effects on breast cancer cell lines. The effect of these solvent fractions on the status of the cancer stem cell subpopulation of the JIMT-1 cell line was assessed by flow cytometric evaluation of the proportion of aldehyde dehydrogenase positive cells and by measuring colony forming efficiency in a serum-free soft agar assay after treatment. Effects on cell migration using a wound healing assay and on tumor necrosis factor-α-induced translocation of nuclear factor-kappa B to the cell nucleus were also investigated. The solvent fractions showed a dose-dependent reduction in the aldehyde dehydrogenase positive subpopulation of JIMT-1 cells. The chloroform fraction of C. simensis (80 μg/mL) completely blocked colony formation of JIMT-1 cells. The wound healing assay showed that all fractions significantly reduced cell migration. The ethyl acetate fraction of V. leopoldi (0.87 μg/mL) significantly inhibited tumor necrosis factor-α-induced nuclear factor-kappa B translocation to the nucleus. The solvent fractions of the medicinal plants showed desirable activities against breast cancer stem cells in the JIMT-1 cell line, which warrants further studies.


Dependence of ghost on the incident light angle into dichroic mirror.
The dichroic mirror (DM) is a key component in microscope. We found a ghost in the reflection channel of a dual-channel fluorescence microscope and studied the relationship between the ghost and the incidence angle θ into the DM. The DM emission surface reflection generated ghost if the θ is not 45 ° . We analyzed the distance and intensity relationship between the ghost and the primary image, which is θ -dependent and was demonstrated by imaging live cells and a stage micrometer. The ghost can be eliminated by placing the DM between objective and tube lens, but not between tube lens and detector, ensuring that the incident light into the DM is approximately parallel. Furthermore, the transmitted light of the DM is shifted towards a longer wavelength with increasing θ . Collectively, microscopists must carefully optimize the θ when designing a microscope to avoid the ghost.


Antagonization by cycloheximide of ethyl methanesulfonate-induced 6-thioguanine-resistant mutation and sister-chromatid exchanges.
We studied the effect of cycloheximide (CH) on the induction of mutation and sister-chromatid exchanges (SCEs) in ethyl methanesulfonate (EMS)-treated Chinese hamster cells. At 10(-6)M, CH strongly antagonized the induction of mutation and SCEs and cell survival increased. This suggests that protein synthesis is essential for the induction of mutation as well as SCEs. Results of experiments in which CH treatment preceded or followed exposure to mutagens were similar with respect to the response curves obtained for mutation and SCEs.


Hybrid combinatorial remanufacturing strategy for medical equipment in the pandemic.
The COVID-19 pandemic hit the medical supply chain, creating a serious shortage of medical equipment. To meet the urgent demand, one realistic way is to collect abandoned medical equipment and then remanufacture, where the disassembled modules are shared with all stock-keeping units (SKUs) to improve utilization. However, in an emergency, the equipment should be processed sequentially and immediately, which means the decision is short-sighted with limited information. We propose a hybrid combinatorial remanufacturing (HCR) strategy and develop two reinforcement learning frameworks based on Q-learning and double deep Q network to find the optimal recovery option. In the frameworks, we transform HCR problem into a maze exploration game and propose a rule of descending epsilon-greedy selection on reweighted valid actions (DeSoRVA) and Espertate knowledge dictionary to combine the cost-minimizing objective with human judgment and the global state of the problem. A real-time environment is further implemented where the quality status of the in-transit equipment is unknown. Numerical studies show that our algorithms can learn to save cost, and the larger scale of the problem is, the more cost-down can be achieved. Moreover, the sophisticated knowledge refined by Espertate is effective and robust, which can handle remanufacturing problems at different scales corresponding to the volatility of the pandemic.


Hybrid Assistive Limb® for sporadic inclusion body myositis: A case series.
We evaluated the efficacy of rehabilitation therapy with Hybrid Assistive Limb® (HAL; hereafter HAL therapy) in three patients diagnosed with sporadic inclusion body myositis (sIBM) who were hospitalized to undergo HAL therapy. Among them, one patient participated in eight courses and the other two in two courses of HAL therapy between 2017 and 2020. We determined the mean rate of improvement in two-minute walking distance and 6 m walking speed at the time of hospital discharge. After HAL therapy, we confirmed the patients' desire to continue the use of HAL. In one patient, we observed improvements of 146.0% and 120.0% in two-minute walk and 6 m walking speed, respectively, after the first course of HAL therapy; these values are 133.7% and 130% after the eighth course of HAL therapy. These values exceeded 90% in the other two patients after the second course of HAL therapy. HAL therapy maintained both quantity and quality of ambulation and showed positive psychological effects on patient conditions because it reduces exercise load and facilitates safety. While HAL therapy might be effective in maintaining and improving ambulation in patients with sIBM, we should consider to discontinue HAL therapy as it increased risk of falling.


On predatory fungi feeding on free-living amoebae harbouring yeast-like endoparasites.
Amoebae of the genus Vannella isolated from an ornamental fish aquarium were found to be infected with fungi. Upon plate culture, amoeba-trapping hyphal filaments were developed, and the amoeba trophozoites were found to harbour yeast-like parasites in their cytoplasm. Transfection of hyphae to a laboratory strain of Vannella resulted in the formation of conidia indicating the possible presence of zygomycetes of the genus Acaulopage, while efforts to culture the endoparasite remained unsuccessful. Biomolecular analysis based on rDNA revealed the presence of two distinct types of fungi, confirming the filamentous form as Acaulopage sp. (Zoopagomycota, Zoopagales) and identifying the yeast-like endoparasite as Cladosporium sp. (Ascomycota, Cladosporiales). To our knowledge, this is the first report of amoebae infected with Cladosporium.


A multivariate analysis of prognostic factors in early stage Hodgkin's disease.
A multivariate analysis of the prognostic factors was carried out with a Cox model on 1,139 patients with clinical Stage I + II Hodgkin's disease included in three controlled clinical trials. The following indicators had been prospectively registered: age, sex, systemic symptoms, erythrocyte sedimentation rate (ESR), number and sites of involved lymph node areas, histologic type, clinical stage, pattern of presentation, results of staging laparotomy when performed, as well as the date and type of treatment. A linear logistic analysis showed that most of the indicators are interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The two main prognostic indicators for relapse-free survival are systemic symptoms and/or ESR and number of involved areas. The only significant factor for survival after relapse is age. Sex has a small but significant influence on relapse-free survival. The relative influence of each indicator varies with the type of treatment and these variations may help in understanding the biologic significance of the indicators.


Intussusception secondary to squamous carcinoma of the lung.
This report describes unusual radiologic and pathologic findings in a patient with multiple small bowel metastases from squamous cell carcinoma of the lung. The diagnostic work-up revealed a large, pleural-based, right lung mass, a large left adrenal mass, two ulcerated small bowel masses, and a unique giant peduncular mass that caused intermittent intussusception. A pertinent review of the literature is presented.


Time Series Analysis of the Acute Effect of Atmospheric Fine Particulate Matter on Hospitalization for Heart Failure in Lanzhou, China.
The purpose of this study was to investigate the correlation between environmental PM 2.5 and heart failure (HF) hospitalization in Lanzhou, China. The correlation between atmospheric PM 2.5 and HF hospitalization was evaluated using a distributed lag nonlinear model. During the study period, 16,122 HF patients were hospitalized. The average concentration of PM 2.5 is 45.24 μg/m 3 . PM 2.5 was positively correlated with HF hospitalization with single lag (lag0) and cumulative lag (lag01, lag02, lag03). The maximum lag effect is estimated to occur in lag03, and with the PM 2.5 concentration increasing by 10 μg/m 3 , HF hospitalization risk increased by 1.023 (95% confidence interval, 1.006-1.039). The risk of hospitalization for HF in the male group, the age group 65 years or older, and the cold season was statistically significant and more positively correlated. PM 2.5 exposure increases the risk of HF admission in Lanzhou.


Synthesis of [1,2,4]triazolo[1,5-a]pyrazines as adenosine A2A receptor antagonists.
Potent and selective antagonists of the adenosine A2A receptor often contain a nitrogen-rich fused-ring heterocyclic core. Replacement of the core with an isomeric ring system has previously been shown to improve target affinity, selectivity, and in vivo activity. This paper describes the preparation, by a novel route, of A2A receptor antagonists containing the [1,2,4]triazolo[1,5-a]pyrazine nucleus, which is isomeric with the [1,2,4]triazolo[1,5-c]pyrimidine core of a series of known A2A antagonists with in vivo activity in animal models of Parkinson's disease.


The treatment of sleep disorders with melatonin.
Fifteen children (most of whom were neurologically multiply disabled) with severe, chronic sleep disorders were treated with 2 to 10mg of oral melatonin, given at bedtime. Nine had fragmented sleep patterns, three had delayed sleep onset and three others had non-specific sleep disturbance of unclear aetiology; all had failed to respond to conventional management. Nine patients had ocular or cortical visual impairment. The health, behavioural and social benefits of treatment were significant, and there were no adverse side-effects. While the response was not always complete, the study clearly showed that melatonin has an important role in the treatment of certain types of chronic sleep disorders.