Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus.
A noninvasive assessment of left ventricular (LV) diastolic performance by tissue Doppler imaging was performed in 56 patients (8 patients with atypical chest pain, 42 with coronary artery disease with a previous myocardial infarction, and 6 without a previous myocardial infarction) who underwent cardiac catheterization. Mitral annular velocity (MAV) during early ventricular diastole was obtained by M-mode color tissue Doppler imaging at the posterior corner of the mitral annulus. In each patient, the negative peak of the first derivative of LV pressure decay (peak -dP/dt) and a time constant of LV relaxation (tau) were calculated from the LV pressure waves obtained by a catheter-tip micromanometer. LV end-systolic volume index was measured from contrast left ventriculography. MAV during early diastole was significantly correlated with tau (r = -0.73, p <0.001), peak -dP/dt (r = 0.58, p <0.001), and LV end-systolic volume index (r = -0.63, p <0.001). On multivariate regression analysis with MAV during early diastole, tau and LV end-systolic volume index were selected as prime determinants (r = 0.80, p <0.001). These findings suggest that MAV during early diastole has a direct relation to LV elastic recoil as well as to LV relaxation. MAV during early diastole gives important information regarding LV behavior in late systole to early diastole where LV early diastolic performance is determined.


Development and psychometric properties of a friendly dietary function assessment scale for home-dwelling people with dementia.
Mealtime difficulties related to cognitive functioning negatively impact a patient's life during the various stages of dementia, and they typically cause a burden and stress on family caregivers. Most people with dementia live at home alone or are cared for by informal caregivers, typically their spouses or other family members. However, no suitable screening tools for home-dwelling patients with dementia have been developed, nor have measurements focused on executive and self-eating functions. This study aimed to develop and evaluate the psychometric properties of the Dietary Function Assessment Scale (DFAS) for community-dwelling persons with dementia. A mixed-method design was used to develop the instrument. Methods included a comprehensive literature review to identify the item pool and an expert panel to assess the initial item pool. We performed convenience sampling of 190 home-dwelling people with dementia for psychometrical evaluation. The psychometric properties tests included item and factor analyses, criterion-related validity testing, internal consistency reliability testing, and defining the optimal cut-off values. The study was conducted from 2018 to 2019. Items were generated based on an extensive literature review and pre-existing scales related to mealtime and executive functions in persons with dementia. The S-CVI/Ave of the DFAS was 0.89. A Principal Component factor analysis demonstrated seven items, with a two-factor structure accounting for 56.94% of the total variance. The two extracted factors were Self-eating ability and Dietary executive function. The confirmatory factor analysis indicated a good model fit. The criterion-related validity was adequate (r = -0.528, p < 0.01). The reliability of Cronbach's alpha internal consistency was 0.74, and McDonald's Omega coefficient was 0.80; the optimal cut-off value of 13 points with an AUC of 0.74 was established to determine poor dietary functioning in persons with dementia. The DFAS was simple, user-friendly, and a valid and reliable instrument to assess dietary functioning in community-dwelling persons with dementia. This short scale can be helpful for caretakers, who can use it to identify the dietary needs of home-dwelling persons with dementia and improve their care and eating experience.


Neuronal intermediate filaments in rat dorsal root ganglia: differential distribution of peripherin and neurofilament protein immunoreactivity and effect of capsaicin.
Two major neuronal populations were revealed in rat dorsal root ganglia, immunoreactive for either peripherin, or neurofilament triplet proteins (adult L2 ganglia: 66.2% and 25.6%, mainly small and large diameter cells, respectively), together with a minor, double-immunostained population (L2: 8.1%, mainly intermediate-size neurons). After capsaicin treatment, a striking expansion in the latter population was seen (L2: 22.0%) together with a significant increase in size, restricted to the same population and the (remaining) peripherin-only immunoreactive neurons. Calcitonin gene-related peptide (CGRP) immunoreactivity was revealed in neurons of all 3 groups, in both normal and capsaicin-treated rats.


Lymphocyte-tumor cell interaction in patients with head and neck cancer.
Peripheral lymphocytes from 12 patients with squamous cell carcinoma of the lead and neck were incubated with autologous tumor explants. Four of the 12 patients demonstrated lymphocyte induced tumor cytotoxicity. These lymphocytes adhered to the tumor cells and deposited a radioactive label from their surface onto tumor cells. The deposition of this label was associated with tumor death. Tissue sections from those patients who demonstrated lymphocyte cytotoxicity showed a marked plasmacytic infiltration. This was in contrast to non-responders where only a desmoplastic tissue response was observed with few inflammatory cells.


An exploratory application of machine learning methods to optimize prediction of responsiveness to digital interventions for eating disorder symptoms.
Digital interventions show promise to address eating disorder (ED) symptoms. However, response rates are variable, and the ability to predict responsiveness to digital interventions has been poor. We tested whether machine learning (ML) techniques can enhance outcome predictions from digital interventions for ED symptoms. Data were aggregated from three RCTs (n = 826) of self-guided digital interventions for EDs. Predictive models were developed for four key outcomes: uptake, adherence, drop-out, and symptom-level change. Seven ML techniques for classification were tested and compared against the generalized linear model (GLM). The seven ML methods used to predict outcomes from 36 baseline variables were poor for the three engagement outcomes (AUCs = 0.48-0.52), but adequate for symptom-level change (R2 = .15-.40). ML did not offer an added benefit to the GLM. Incorporating intervention usage pattern data improved ML prediction accuracy for drop-out (AUC = 0.75-0.93) and adherence (AUC = 0.92-0.99). Age, motivation, symptom severity, and anxiety emerged as influential outcome predictors. A limited set of routinely measured baseline variables was not sufficient to detect a performance benefit of ML over traditional approaches. The benefits of ML may emerge when numerous usage pattern variables are modeled, although this validation in larger datasets before stronger conclusions can be made.


Factor analysis models via I-divergence optimization.
Given a positive definite covariance matrix [Formula: see text] of dimension n, we approximate it with a covariance of the form [Formula: see text], where H has a prescribed number [Formula: see text] of columns and [Formula: see text] is diagonal. The quality of the approximation is gauged by the I-divergence between the zero mean normal laws with covariances [Formula: see text] and [Formula: see text], respectively. To determine a pair (H, D) that minimizes the I-divergence we construct, by lifting the minimization into a larger space, an iterative alternating minimization algorithm (AML) à la Csiszár-Tusnády. As it turns out, the proper choice of the enlarged space is crucial for optimization. The convergence of the algorithm is studied, with special attention given to the case where D is singular. The theoretical properties of the AML are compared to those of the popular EM algorithm for exploratory factor analysis. Inspired by the ECME (a Newton-Raphson variation on EM), we develop a similar variant of AML, called ACML, and in a few numerical experiments, we compare the performances of the four algorithms.


[Importance of patient's choice in the treatment of erectile dysfunction].
Erectile dysfunction (ED) affects nearly one out of two men over age 45. ED is known to alter the quality of life of patients, and to affect significantly their sexual life and relations, as well as those of their female partners. Phosphodiesterase 5 inhibitors (PDE5) inhibitors currently represent the reference treatment for ED, because of their efficacy and good tolerability. The presence of erectile disorders capable of altering considerably the life of a couple makes it necessary to find ways for patients and their partners to get more involved in the treatment choices. A "customized" solution responding to patient's needs and resulting from a decision shared with the patient and his partner will allow a better compliance and efficacy of the treatment.


Behavioral and Emotional Outcomes in Children with Congenital Heart Disease: Effects of Disease Severity, Family Life Stress, Disease-Related Chronic Stress, and Psychosocial Adaptation.
To evaluate whether effects of congenital heart disease (CHD) severity and family life stress on behavioral and emotional functioning are mediated by disease-related chronic stress and psychosocial adaptation. A cross-sectional analysis of the Pediatric Cardiac Quality of Life Inventory Testing Study was performed. Relationships between CHD severity (comprising 3 groups: mild heart disease, moderate biventricular disease, and single ventricle) and family life stress, on patient- and parent disease-related chronic stress, psychosocial adaptation, and behavioral-emotional outcomes were assessed using structural equation modeling. Patient and parent models were reported separately. There were 981 patient-parent dyads: 22% had mild heart disease, 63% biventricular, and 15% single ventricle; 19% of families reported moderate to major family life stress. Path models revealed that CHD severity and family life stress were mediated by disease-related chronic stress and psychosocial adaptation factors (R2 = 0.18-0.24 for patient outcomes and R2 = 0.33-0.34 for parent outcomes, P < .001, respectively). The effects of greater CHD severity and family life stress on behavioral-emotional outcomes were mediated by worse disease-related chronic stress and psychosocial adaptation factors. Both disease-related chronic stress and psychosocial adaptation factors may be targets for interventions to improve behavioral and emotional outcomes.


Air/liquid interfacial formation process of conductive metal-organic framework nanosheets.
The air/liquid interface is a superior platform to create nanosheets of materials by promoting spontaneous two-dimensional growth of components. Metal-organic frameworks (MOFs)-intrinsically porous crystals-with π-conjugated triphenylene-based ligands show high electrical conductivities. Forming nanosheets of such conductive MOFs should enable their use in electronic devices. Although highly conductive MOF nanosheets have been created at the air/liquid interface, direct control of their continuity, morphology, thickness, crystallinity, and orientation directly influencing device performance remains as an issue to be addressed. Here, we present detailed insights into the formation process of electrically conductive MOF nanosheets composed of 2,3,6,7,10,11-hexaiminotriphenylene (HITP) and Ni2+ ions (HITP-Ni-NS) at the air/liquid interface. The morphological and structural features of HITP-Ni-NS strongly depend on the standing time-the time without any external actions involved, but leaving the interface undisturbed after setting the ligand solution onto the metal-ion solution. We find that the fundamental features of HITP-Ni-NS are determined by the standing time with conductivity sensitively influenced by such pre-determined HITP-Ni-NS characteristics. These findings will lead towards the establishment of a rational strategy for creating MOF nanosheets at the air/liquid interface with desired properties, thereby accelerating their use in diverse potential applications.


Interferon signaling in ascites-associated macrophages is linked to a favorable clinical outcome in a subgroup of ovarian carcinoma patients.
Although tumor-associated macrophages (TAMs) are essential for cancer progression, connections between different clinical outcomes and transcriptional networks have not been reported. We have addressed this issue by analyzing global expression patterns of TAMs isolated from the ascites of ovarian cancer patients. TAMs isolated from different ovarian cancer patients can be stratified by coexpression or principal component analysis into subgroups with specific biological features and associated with distinct clinical outcomes. A hallmark of subgroup A is a high expression of clinically unfavorable markers, including (i) high CD163 expression, a surface receptor characteristic of an anti-inflammatory activation state, (ii) increased PCOLCE2 expression, indicative of enhanced extracellular matrix organization, and (iii) elevated ascites levels of IL-6 and IL-10, linked to the aggressiveness of ovarian cancer and immune suppression. In contrast, subgroup B TAMs are characterized by the upregulation of genes linked to immune defense mechanisms and interferon (IFN) signaling. Intriguingly, analysis of published data for 1763 ovarian cancer patients revealed a strong association of this transcriptional signature with a longer overall survival. Consistent with these results, IFNγ was able to abrogate the suppressive effect of ovarian cancer ascites on the inducibility of IL12B expression and IL-12 secretion, a key determinant of a cytotoxic immune response. The survival of ovarian cancer patients is linked to the presence of TAMs with a transcriptional signature that is characterized by a low expression of protumorigenic and immunosuppressive markers and an upregulation of genes linked to interferon signaling. The observed IFNγ-mediated restoration of the inducibility of IL-12 in the presence of ascites provides a possible explanation for the association of an interferon signaling-associated signature with a favorable clinical outcome.


3-Acetyl deoxynivalenol production in a strain ofFusarium culmorum insensitive to the fungicide difenoconazole.
The production of the mycotoxin, 3-acetyl deoxynivalenol (3-ADON), was investigated in a strain ofFusarium culmorum insensitive to the systemic fungicide, difenoconazole. On exposure to graded concentrations of the fungicide, the insensitive strain continued to synthesise 3-ADON when difenoconazole levels of 100 and 200μg/ ml media were used. In contrast, a control (sensitive) strain ceased production of 3-ADON at difenoconazole levels of 100 μg/ml. Differences between the two strains were also observed for 3-ADON production with time. Following incubation with fungicide at 0.1 μg/ ml, 3-ADON production occurred more rapidly in CS than in IS cultures. This is the first report of increased persistence and alteration of the pattern of production of a mycotoxin following the development of fungicide insensitivity in a fungal phytopathogen.


In vitro inhibitory effects of DNA topoisomerase II by fernane-type triterpenoids isolated from a Euphorbia genus.
Several kinds of naturally occurring fernane-type triterpenoids isolated from a Euphorbia genus were tested on the inhibitory effects of DNA Topoisomerases I (Topo I) and II (Topo II) activities. A-ring cleaved 3,4-seco-8 beta H-ferna-4(23),9(11)-dien-3-oic acid and its 3-hydroxyl derivative were found to be selective inhibitors of Topo II activity without the stabilization of a DNA/Topo II cleavable complex.


Long-term tract-specific white matter microstructural changes after acute stress.
Acute stress has substantial impact on white matter microstructure of people exposed to trauma. Its long-term consequence and how the brain changes from the stress remain unclear. In this study, we address this issue via diffusion tensor imaging (DTI). Twenty-two trauma-exposed individuals who did not meet post-traumatic stress disorder (PTSD) diagnostic criteria were recruited from the most affected area of Wenchuan earthquake and scanned twice (within twenty-five days and two years after the quake, respectively). Their emotional distress was evaluated with the Self-Rating Anxiety/Depression Scales (SAS/SDS) at both scans. Automatic fiber quantification was used to examine brain microstructure alterations. Correlation analyses were also conducted to investigate relationships between brain microstructure changes and symptom improvement. A group of demographically matched healthy controls (N = 22) from another project were scanned once before the quake using the same imaging protocols as used with trauma-exposed non-PTSD (TENP) participants. Two years after the earthquake, TENP individuals exhibited significantly reduced FA in the parietal portion of left superior longitudinal fasciculus and high FA in the parietal portion of left corticospinal tract. Over the follow-up, increased FA of the left uncinate fasciculus and the left corticospinal tract with parallel reduction of SAS and SDS were observed in TENP. No significant association was found between brain microstructure changes and symptom improvement. These results indicate changes in WM microstructure integrity of TENP brains parallel with symptom improvement over time after acute stress. However, the change would be a long-term process without external intervention.


ABCs or 123s? The independent contributions of literacy and numeracy skills on health task performance among older adults.
To investigate the relationship between literacy and numeracy and their association with health task performance. Older adults (n=304) completed commonly used measures of literacy and numeracy. Single factor literacy and numeracy scores were calculated and used to predict performance on an established set of health self-management tasks, including: (i) responding to spoken information; (ii) comprehension of print and (iii) multimedia information; and (iv) organizing and dosing medication. Total and sub-scale scores were calculated. Literacy and numeracy measures were highly correlated (rs=0.68; ps<0.001). In multivariable models adjusted for age, gender, race, education, and comorbidity, lower literacy (β=0.44, p<0.001) and numeracy (β=0.44, p<0.001) were independently associated with worse overall task performance and all sub-scales (literacy range, β=0.23-0.45, ps<0.001; numeracy range, β=0.31-0.41, ps<0.001). Multivariable analyses with both constructs entered explained more variance in overall health task performance compared with separate literacy and numeracy models (8.2% and 10% respectively, ps<0.001). Literacy and numeracy were highly correlated, but independent predictors of health task performance. These skill sets are complementary and both are important for health self-management. Self-management interventions may be more effective if they consider both literacy and numeracy skills rather than focusing on one specific ability.


KSR Int'l Co. v. Teleflex, Inc.: no obvious changes for the biotechnology market.
With the advent of molecular biology, genomics, and proteomics, the intersection between science and law has become increasingly significant. In addition to the ethical and legal concerns surrounding the collection, storage, and use of genomic data, patent disputes for new biotechnologies are quickly becoming part of mainstream business discussions. Under current patent law, new technologies cannot be patented if they are "obvious" changes to an existing patent. The definition of "obvious," therefore, has a huge impact on determining whether a patent is granted. For example, are modifications to microarray protocols, popular in diagnostic medicine, considered "obvious" improvements of previous products? Also, inventions that are readily apparent now may not have been obvious when discovered. Polymerase chain reaction, or PCR, is now a common component of every biologist's toolbox and seems like an obvious invention, though it clearly was not in 1983. Thus, there is also a temporal component that complicates the interpretation of an invention's obviousness. The following article discusses how a recent Supreme Court decision has altered the definition of "obviousness" in patent disputes. By examining how the obviousness standard has changed, the article illuminates how legal definitions that seem wholly unrelated to biology or medicine could still potentially have enormous effects on these fields.


Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts.
Drosophila neuroblasts divide asymmetrically by aligning their mitotic spindle with cortical cell polarity to generate distinct sibling cell types. Neuroblasts asymmetrically localize Galphai, Pins, and Mud proteins; Pins/Galphai direct cortical polarity, whereas Mud is required for spindle orientation. It is currently unknown how Galphai-Pins-Mud binding is regulated to link cortical polarity with spindle orientation. Here, we show that Pins forms a "closed" state via intramolecular GoLoco-tetratricopeptide repeat (TPR) interactions, which regulate Mud binding. Biochemical, genetic, and live imaging experiments show that Galphai binds to the first of three Pins GoLoco motifs to recruit Pins to the apical cortex without "opening" Pins or recruiting Mud. However, Galphai and Mud bind cooperatively to the Pins GoLocos 2/3 and tetratricopeptide repeat domains, respectively, thereby restricting Pins-Mud interaction to the apical cortex and fixing spindle orientation. We conclude that Pins has multiple activity states that generate cortical polarity and link it with mitotic spindle orientation.


Efficacy of cytarabine, aclarubicin and granulocyte colony-stimulating factor (CAG) regimen compared to FLAG regimen for adult patients with relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia.
In this study, we retrospectively assess the results in comparing the efficacies and toxicities of the three chemotherapy regimens: CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor (G-CSF), n=87), HD-CAG (increasing the dose of aclarubicin in CAG regimen, n=73), and FLAG (fludarabine, cytarabine and G-CSF, n=41) regimens in patients with relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph--ALL). Our study indicated that after one therapy course, the overall response (OR, complete reimssion (CR)+partial remission (PR)) rate was higher in CAG than that in FLAG regimen (55.2% vs. 31.7%, P=0.013), while the CR (50.7% vs. 26.8%, P =0.013) and OR (64.4% vs. 31.7%, P=0.001) rates in HD-CAG regimen were both higher than that in FLAG regimen. Furthermore, the results were more pronounced in the subgroup of patients with T cell and refractory Ph--ALL. There were no significant differences in CR and OR rates between the CAG and HD-CAG regimens. Meanwhile, the adverse effects of CAG regimen were less toxic than the FLAG and HD-CAG regimens. There were no statistically significant differences in overall survival rates at two years among the three groups (FLAG: 9.8%±4.6%, CAG: 11.8%±4.5%, HD-CAG: 11.1%±4.0%; P>0.05). Our preliminary results indicated that CAG and HD-CAG regimens could be more effective and safer than FLAG regimen for relapsed/refractory Ph--ALL.


Chemopreventive effect of vanadium in a rodent model of chemical hepatocarcinogenesis: reflections in oxidative DNA damage, energy-dispersive X-ray fluorescence profile and metallothionein expression.
In the present study, we investigated the antitumour efficacy of vanadium in a defined rodent model of experimental hepatocarcinogenesis. Hepatic preneoplasia was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal injection of diethylnitrosamine (DEN) (200 mg/kg body weight) followed by promotion with phenobarbital (PB). The levels of modified DNA bases 8-hydroxy-2'-deoxyguanosine (8-OHdG), a potential marker involved in the initiation of carcinogenesis, were measured by high-performance liquid chromatography, whereas tissue trace element status and expression of metallothionein (MT), a Cu-Zn metalloprotein associated with neoplastic cell growth and subsequent development of premalignant phenotype of the cell, were studied by energy-dispersive X-ray fluorescence spectrometry and enzyme-coupled immunohistochemistry, respectively. There was a significant and steady elevation of modified bases (8-OHdG) along with substantial increase in MT immunoexpression and disturbance in trace element homeostasis following DEN exposure. Supplementation of vanadium at a dose of 0.5 ppm for four consecutive weeks strictly abated the formation of 8-OHdG (P < 0.0001; 81.28%) in preneoplastic rat liver. In a long-term DEN plus PB regimen, vanadium was able to limit in situ MT expression with a concomitant decrease in MT immunoreactivity (P < 0.05). Furthermore, vanadium treatment throughout the study restored hepatic levels of essential trace elements and decreased nodular incidence (58.34%) and nodule multiplicity (P < 0.001; 66.89%) in rats treated with DEN plus PB. Taken together, the study provides evidence in support of the chemopreventive potential of vanadium in limiting neoplastic transformation during the preneoplastic stages of hepatocarcinogenesis in rats.


Quantitative methylation analysis of human papillomavirus 16L1 gene reveals potential biomarker for cervical cancer progression.
Human papillomavirus 16 is the most prevalent type found in cervical cancer worldwide, accounting for >50% of all cases. Quantitative methylation analysis of human papillomavirus 16L1 gene within 5' (CpGs 5600, 5606, 5609, 5615) and 3' (7136 and 7145) regions to determine potential biomarker for cervical cancer progression was performed in exfoliated cervical cells collected from 101 Thai women of precancerous and cancerous lesions. Intermediate to high methylation levels (>20%) were detected in HPV16 5'L1 regions especially CpG 5600 of all cancerous (100%) and 50% of CIN3 samples, whereas normal/CIN1 samples (80%) showed methylation levels <20%. Our results indicate the potential use of HPV 16L1 gene methylation at specific site as a biomarker for prognostic cervical cancer screening, however, suitable cutoff should be further evaluated in a larger sample size.


A psychometric stury of 34 patients afflicted with spasmodic torticollis.
The clinical and psychometric comparison of two group of patients, one with spasmodic torticollis, the other with operated herniated disc, showed closely related psychological profiles. The most important perturbations are found in spasmodic torticollis and seem related to the disease's chronicity. In no case was a predominant hysteric structure found. The results of these investigations on the disorder's etiology are discussed.


Precision oncology for intrahepatic cholangiocarcinoma in clinical practice.
Advanced cholangiocarcinoma has a poor prognosis. Molecular targeted approaches have been proposed for patients after progression under first-line chemotherapy treatment. Here, molecular profiling of intrahepatic cholangiocarcinoma in combination with a comprehensive umbrella concept was applied in a real-world setting. In total, 101 patients received molecular profiling and matched treatment based on interdisciplinary tumour board decisions in a tertiary care setting. Parallel DNA and RNA sequencing of formalin-fixed paraffin-embedded tumour tissue was performed using large panels. Genetic alterations were detected in 77% of patients and included gene fusions in 21 patients. The latter recurrently involved the FGFR2 and the NRG1 gene loci. The most commonly altered genes were BAP1, ARID1A, FGFR2, IDH1, CDKN2A, CDKN2B, PIK3CA, TP53, ATM, IDH2, BRAF, SMARCA4 and FGFR3. Molecular targets were detected in 59% of patients. Of these, 32% received targeted therapy. The most relevant reason for not initiating therapy was the deterioration of performance status. Patients receiving a molecular-matched therapy showed a significantly higher survival probability compared to patients receiving conventional chemotherapy only (HR: 2.059, 95% CI: 0.9817-4.320, P < 0.01). Molecular profiling can be successfully translated into clinical treatment of intrahepatic cholangiocarcinoma patients and is associated with prolonged survival of patients receiving a molecular-matched treatment.


Human monocyte heterogeneity: interleukin 1 and prostaglandin E2 production by separate subsets.
Human peripheral blood monocytes were separated into four different subpopulations by means of a discontinuous bovine serum albumin gradient. Of the least dense population, 7% were present in fraction A, 11% in fraction B, 28% in fraction C and of the most dense, 34% were in fraction D. The rest (17%) of the recovered cells sedimented as a pellet, of which 95% were dead. The monocytes of fraction D (= greater than or equal to 1.075 kg/l) were major interleukin 1 (IL 1) producers and their presence enhanced immunoglobulin synthesis in vitro. Fraction C (= greater than or equal to 1.070 kg/l) were the major prostaglandin E2 (PGE2) producers and demonstrated suppressor activity on in vitro IgG and IgM synthesis. Fractions A and B had minimal production of either IL 1 or PGE2 and lesser effects on the IgG and IgM synthesis. These data demonstrate functional heterogeneity of peripheral blood monocytes with respect to production of both IL 1 and PGE2 as well as accessory cells for immunoglobulin synthesis.


Treatment of mandibular grade III furcation involvement using platelet-rich fibrin and allogenic graft with 12-month follow-up - A case report.
Furcation involvement (FI) in multi-rooted teeth is challenging for proper oral hygiene, clinical treatment, and leads to poor prognosis. Traditional treatment modalities often result in sacrificing periodontal bone. Multiple regenerative approaches have been attempted to treat furcation defects, but complete regeneration of the periodontal apparatus in grade III furcation has not been reported. Platelet rich fibrin (PRF) shows great potential in enhancing tissue regeneration, angiogenesis, and prevention of infection. This case report introduces a treatment combining allogenic bone grafts with PRF to treat mandibular grade III furcation lesions with a one-year follow-up. Two patients presented with grade III FIs of the mandibular first molars, with intrabony defects requiring guided tooth regeneration (GTR). PRF was collected from each patient to serve as biologics, by mixing with allogenic bone graft, and packed into the furcation and intrabony defects. The PRF membranes were also used for space maintenance. The twelve-month postoperative follow-up demonstrated quicker tissue healing, significant pocket reduction, clinical attachment gain, as well as radiographic bone fill in both cases. Successful periodontal regeneration of grade III furcation defects can be achieved by using PRF in combination with bone allograft.


Short-Term Tibial Baseplate Fracture After Total Knee Arthroplasty in the Absence of Osteolysis and Implant Loosening: A Case Report.
The patient is a 62-year-old man with early tibial baseplate failure involving fracture and subsidence of the posteromedial metal implant, only 3 years after primary total knee replacement. Although this mode of failure is frequently observed secondary to polyethylene wear and osteolysis, this case was likely because of suboptimal tibial baseplate size and positioning with lack of cortical support that underwent accelerated fatigue, given the high activity level of the patient. This case demonstrates rare sequelae of inadequate tibial coverage and cortical structural support of the baseplate. Tibial coverage is influenced by implant sizing, implant positioning, and variations in patient anthropometrics.


A classification of feline calicivirus isolates based on plaque morphology.
Isolates of feline calicivirus (FCV) can be divided into four groups according to plaque size under an agar overlay. All isolates classified as minute plaque, along with certain other isolates, are sensitive to inhibitors present in agar.


Functional Dependence and Mortality in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).
Patients receiving long-term dialysis have among the highest mortality and hospitalization rates. In the nonrenal literature, functional dependence is recognized as a contributor to subsequent disability, recurrent hospitalization, and increased mortality. A higher burden of functional dependence with progressive worsening of kidney function has been observed in several studies, suggesting that functional dependence may contribute to both morbidity and mortality in dialysis patients. Prospective cohort study. 7,226 hemodialysis patients from 12 countries in the DOPPS (Dialysis Outcomes and Practice Patterns Study) phase 4 (2009-2011) with self-reported data for functional status. Patients' ability to perform 13 basic and instrumental activities of daily living was summarized to create an overall functional status score (range, 1.25 [most dependent] to 13 [functionally independent]). Cox regression was used to estimate the association between functional status and all-cause mortality, adjusting for several demographic and clinical risk factors for mortality. Median follow-up was 17.2 months. The proportion of patients who could perform each activity of daily living task without assistance ranged from 97% (eating) to 47% (doing housework). 36% of patients could perform all 13 tasks without assistance (functional status = 13), and 14% of patients had high functional dependence (functional status < 8). Functionally independent patients were younger and had many indicators of better health status, including higher quality of life. Compared with functionally independent patients, the adjusted HR for mortality was 2.37 (95% CI, 1.92-2.94) for patients with functional status < 8. Possible nonresponse bias and residual confounding. We found a high burden of functional dependence across all age groups and across all DOPPS countries. When adjusting for several known mortality risk factors, including age, access type, cachexia, and multimorbidity, functional dependence was a strong consistent predictor of mortality.


Cyclosporine A inhibits relaxation but does not induce vasoconstriction in human subcutaneous resistance vessels.
The effects of cyclosporine on the functional characteristics of human subcutaneous resistance vessels were investigated. Resistance vessels were obtained from normal subjects undergoing routine surgery. Incubation with cyclosporine did not alter the resting tone of the vessels, but decreased the maximum contractile response and the sensitivity of the vessels to stimulation with exogenous noradrenaline and potassium. Cyclosporine decreased the rate of spontaneous relaxation and inhibited endothelium-dependent relaxation as assessed by the response to acetylcholine. Paradoxically, endothelium-independent relaxation as assessed by the response to sodium nitroprusside was augmented. Hypertension induced by cyclosporine may, in part, be explained by a reduction in relaxation of peripheral resistance vessels.


Effect of exogenous insulin on glucose kinetics in rats with noninsulin-dependent diabetes.
Noninsulin-dependent diabetes (NIDD) was induced in adult female rats by neonatal administration of streptozotocin. Despite elevated basal plasma glucose values in the postabsorptive state (196 +/- 16 mg/100 mL as compared to 118 +/- 7 in the controls), the glucose disappearance rate measured after the intravenous glucose load was not significantly lower in the diabetic than in control rats. In contrast, in vivo glucose-induced insulin release was drastically reduced, thus suggesting that endogenous insulin was more effective on the target tissues of the diabetic rats. Glucose kinetics (glucose production, utilization, and clearance) in response to intravenous insulin injection were studied in anesthetized postabsorptive diabetic and control female rats using [6-3H] glucose. With a maximal dose of insulin (0.5 U/kg body weight) no difference in blood glucose-lowering effect of insulin was found between the 2 groups. With 2 submaximal insulin doses (0.15 and 0.3 U/kg body weight), glucose production was inhibited more rapidly and more efficiently in diabetic rats than in control rats: 2 minutes after the 0.15 U/kg insulin injection, endogenous glucose production fell by 79 +/- 5% in the diabetics while being unchanged in the controls and the maximal decrease of glucose production after the same insulin injection was significantly greater in the diabetic rats (79 +/- 5% at 2 minutes) compared to the controls (33 +/- 4% at 6 min). The rise of glucose clearance in response to insulin was not significantly different in the 2 groups. These findings are discussed in view of the increased insulin clearance rate in these diabetic females.(ABSTRACT TRUNCATED AT 250 WORDS)


Repeated remissions of Cushing's disease due to recurrent infarctions of an ACTH-producing pituitary macroadenoma.
Infarction of prolactin-secreting or growth hormone-secreting pituitary adenomas is not unusual. However, Infarction of ACTH-secreting adenomas has rarely been reported. Cyclical course of Cushing's syndrome alternating with adrenal insufficiency due to recurrent infarction of an ACTH-secreting pituitary adenoma has not been reported. We report here a 20-year-old lady who presented with florid signs of Cushing's syndrome but was found to have adrenal insufficiency on biochemical evaluation. Magnetic resonance imaging (MRI) of the pituitary gland showed that she had infarction of an ACTH-secreting macroadenoma. Over the next 6 years, her disease ran a cyclical course characterized by periods of hypercortisolism alternating with adrenal insufficiency due to repeated episodes of infarctions of the ACTH-secreting pituitary macroadenoma with corresponding changes in the pituitary adenoma on serial MRIs. The case alerts clinicians to this possibility when a patient presents with clinical picture of Cushing's syndrome but has adrenal insufficiency on biochemical testing. It also suggests that silent or subclinical infarction of pituitary adenomas is not uncommon and is probably under diagnosed.


Effect of cross-fostering on neonatal sodium balance and adult blood pressure in the spontaneously hypertensive rat.
1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams' milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 +/- 2.0 to 15.2 +/- 1.2 mmol/L; SHR 31.9 +/- 2.5 to 18.2 +/- 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P < 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P < 0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4-15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 +/- 3.6 vs 59.7 +/- 2.6 mumol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 +/- 7.0 mumol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 +/- 6.4 vs 200.1 +/- 9.5 mumol/g bodyweight, respectively; P < 0.05) or SHRX pups (200.0 +/- 18.0 mumol/g bodyweight; P < 0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure.


Chromosome-level genomes of two armyworms, Mythimna separata and Mythimna loreyi, provide insights into the biosynthesis and reception of sex pheromones.
Mythimna separata and Mythimna loreyi are global pests of gramineous cereals, heavily controlled with synthetic insecticides. Here, we generated two high-quality chromosome-level genome assemblies for M. separata (688 Mb) and M. loreyi (683 Mb). Our analysis identified Z and W chromosomes, with few genes and abundant transposable elements (TEs) found on the W chromosome. We also observed a recent explosion of long interspersed nuclear elements (LINEs), which contributed to the larger genomes of Mythimna. The two armyworms diverged ~10.5 MYA, with only three chromosomes have intrachromosomal rearrangements. Additionally, we observed a tandem repeat expansion of α-amylase genes in Mythimna, which may promote the digestion of carbohydrates and exacerbate their damage to crops. Furthermore, we inferred the sex pheromone biosynthesis pathway for M. separata, M. loreyi and Spodoptera frugiperda. We discovered that M. loreyi and S. frugiperda synthesized the same major constituents of sex pheromones through different pathways. Specifically, the double bonds in the dominant sex pheromone components of S. frugiperda were generated by Δ9- and Δ11-desaturase, while they were generated by Δ11-desaturase and chain-shortening reactions in M. loreyi. We also identified pheromone receptor (PR) genes and inferred their corresponding components. These findings provide a better understanding of sex pheromone communication and promote the development of a new pest control strategy involving pheromone traps, which are more effective and environmentally friendly than current strategies.


Gas exchange of Agropyron desertorum: diurnal patterns and responses to water vapor gradient and temperature.
The response of leaf gas exchange to environmental variables were measured at different levels of drought stress for Agropyron desertorum, a naturalized perennial bunchgrass of the semiarid shrub steppes of western North America. Leaf conductance (stomatal plus boundary layer) was more sensitive to changes in water vapor gradient than to changes in leaf temperature. Assimilation was sensitive to both temperature and vapor gradient, and also appeared to be affected by conductance and high transpiration rates. The magnitudes of both assimilation and conductance decreased with increased drought conditions. Diurnal patterns of gas exchange were measured during 3 growing seasons. For a typical spring day with moderate leaf temperature and vapor gradient, diurnal patterns were similar for plants at different levels of soil water availability. Assimilation was relatively constant during most of the day, but conductance decreased during the afternoon. Total daily carbon gain was decreased to a lesser extent than daily water loss as soil water was depleted. Consequently, the ratio of daily carbon gain to daily water loss, i.e. daily water use efficiency, increased with decreased soil water content for diurnals under spring conditions. Diurnal patterns of assimilation for a typical summer day with high leaf temperature and vapor gradient differend from those for a spring day. An afternoon decrease in assimilation was typical during a summer day. Daily carbon gain, water use, and water use efficiency for summer diurnals decreased only under severe drought conditions. Almost complete recovery of assimilation and conductance occurred if leaf microclimate was ameliorated during the afternoon of either spring or summer diurnals. Thus, conditions responsible for a midday depression in assimilation during a single day did not have persistent effects on leaf gas exchange. Daily carbon gain of a typical summer day was restricted by leaf microclimate during the afternoon, but daily water use efficiency was not relatively increased by the amelioration of leaf microclimate.


Current concepts and future directions in neoadjuvant chemotherapy of breast cancer.
Preoperative administration of chemotherapy is a widespread treatment approach in early stage breast cancer whenever chemotherapy is indicated in principle. In addition, neoadjuvant treatment is today regarded as the preferred way of delivering systemic therapy in triple-negative and HER2-positive breast cancer. While preoperative chemotherapy allows for disease downstaging and increases breast conservation rates, achieving pathologic complete remission (pCR) is usually regarded as the most pertinent aim as pCR predicts for improved long-term outcome in high-risk breast cancer subtypes. A multitude of clinical trials therefore have focused on strategies to increase pCR rates. This short review summarizes outcomes of selected studies investigating the addition of further chemotherapeutic drugs or biologically targeted agents to standard regimens and provides an overview of novel strategies currently under clinical evaluation.


Larval habitats and species diversity of mosquitoes (Diptera: Culicidae) in West Azerbaijan Province, Northwestern Iran.
The characteristics of a larval habitat is an important factor which affects the breeding pattern and population growth of mosquitoes Information about the larval habitat characteristics and pupal productivity can be utilized for the surveillance of the level of population growth, species diversity, and preferred breeding sites of mosquitoes, which are important aspects of integrated vector control. In the present study, mosquito larvae were collected from 22 natural habitats in five counties of the West Azerbaijan Province in the Northwest of Iran during May-November 2018. Physicochemical characteristics of the habitats were investigated. These included alkalinity, chloride (Cl) content, water temperature (°C), turbidity (NTU), Total Dissolved Solids (TDS) (ppm), Electrical Conductivity (EC) (μS/cm), and acidity (pH). The index of affinity between the collected species was calculated using Fager & McGowan test. A total of 2715 specimens were collected and identified. Seven different species belonging to four genera were identified in our study sites. The species included, Culex pipiens Linnaeus 1758, Culex theileri Theobald 1903, Culex mimeticus Noé 1899, Culex modestus Ficalbi 1947, Culiseta longiareolata Macquart 1838, Anopheles maculipennis Meigen 1818complex, and Aedes caspius Pallas 1771. There was a significant difference in chloride content and water temperature preferences among the different species (P < 0.05). Also, there was no significant difference in pH, Alkalinity, Turbidity, TDS, and EC preferences among the different species (P > 0.05). The affinity between the pair of species Cx. mimeticus/Cs. longiareolata was 0.526. There was no affinity between other pairs of species or the affinity was very weak. The physicochemical and biological characteristics of mosquito larval habitats play an important role in zoning of areas suitable for breeding and distribution. Surveillance of these characteristics can provide valuable information for entomological monitoring of mosquito vectors and for designing targeted control programs. Also, further studies should be undertaken in a wider geographical area, taking into account the complex characteristics of the physicochemical and ecological factors of the study area and their interaction with various mosquito species.


Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat prostate.
The benign hyperplasia of the prostate is a manifestation of aging, involving the accumulation, within the gland, of dihydrotestosterone, the probable mediator of the hyperplasia. Binding studies were performed on the cytosolic androgenic receptor of the rat prostate using [3H]methyltrienolone as a ligand. The binding of [3H]methyltrienolone at 5 nM, was inhibited by various drugs, such as methyltrienolone and cyproterone acetate. Permixon, a liposterolic extract of the plant, Serenoa Repens B, inhibits competitively the binding to the cytosolic receptor of the rat prostate. Various vegetable and mineral oils, the plant steroid: beta sitosterol and the antiprostatic drug: Tadenan, were all found to be inactive. The antiprostatic activity of Permixon shown in animal studies and controlled clinical trials, may thus result from a direct action at the cytosolic receptor.


Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation.
The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.


Hemodynamic measurements in a sheep model with a hollow fiber artificial kidney containing modified cellulose.
HFAK-RC caused pronounced leukopenia, increase in TXB2 levels in plasma and hemodynamic pressure changes as a reflection of complement activation during EC in sheep. In contrast no increase in TXB2 levels and no changes in hemodynamics are observed with HFAK-MC. The leukopenia and granulocytopenia in the latter is much less pronounced and probably reflects the phenomenon "frustrated phagocytosis".


[The effect of treatment expectations on pruritus and skin pain].
Patients' expectations in terms of the benefit of a treatment are key determinants of placebo responses and can affect the development and course of medical conditions as well as the efficacy and tolerability of active medical treatment. The mechanisms mediating these placebo and nocebo effects have been best described in the field of experimental pain and placebo analgesia. However, also in dermatology experimental and clinical studies demonstrate that different skin symptoms such as itch, skin pain and dermatologic diseases can be modulated by patients' expectations. The aim of this review is to provide a current overview of the empirical evidence for the effects of patients' expectations in the field of dermatology with a focus on different skin symptoms such as itch and pain. Finally, the relevance of this topic for physicians who treat patients with dermatologic symptoms is discussed. The article is a narrative review. Steadily growing evidence from experimental and clinical studies in healthy volunteers and dermatologic patients suggests that patients' positive treatment expectations can reduce skin disease symptoms and enhance treatment efficacy, while negative treatment expectations can induce a nocebo effect associated with increased symptomatology. Patients' prior treatment experiences as well as the quality and quantity of doctor-patient communication play a central role in shaping treatment expectations. Techniques aimed at maximizing positive expectation effects in patients should be implemented in daily clinical routine.


Glutamine dependency of human skin fibroblasts: modulation by hexoses.
The combined effects of carbohydrates and glutamine were investigated in diploid strains of normal human skin fibroblasts cultured for 21 days under eight different culture conditions: hexose-free medium or medium containing D-glucose, D-galactose, or D-fructose, with or without added glutamine. Cell growth, hexose consumption, lactate production, intracellular glycogen content and extracellular amino acid levels were measured every third to fourth day. In the presence of glutamine, cells reached a higher saturation density in fructose medium than in glucose or galactose medium but per cell consumption of fructose and galactose was much less than that of glucose. Consumption of all three carbohydrates per unit cell growth exhibited three distinct phases: Days 1-3, 3-10, and 10-20, respectively. In the absence of glutamine the rate of cell growth was not altered in glucose or galactose medium, but slowed down considerably in fructose medium. Glutamine deprivation also led to changes in hexose consumption. In hexose-free media the cell growth rate at first was very slow, but rose after 2 or 3 weeks of culture. The levels of extracellular nonessential amino acids varied according to medium and growth phase. One of the most exciting findings was that human fibroblasts are able to maintain a slight excess of glutamine in all media not supplemented with glutamine and, more surprisingly, to synthesize it in a medium containing galactose and glutamine.


Relationship between ACE gene polymorphism and ischemic chronic heart failure in Turkish population.
Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with the development of left ventricular hypertrophy, myocardial infarction, and remodeling. However, little is known about its role in ischemic chronic heart failure (CHF). We investigated the relationship between ACE gene I/D polymorphism and ischemic CHF and its influence on exercise capacity. ACE gene I/D polymorphism was analyzed in 209 Turkish patients with coronary artery disease (CAD) undergoing coronary angiography. ACE genotype distributions were examined in 84 consecutive patients with ischemic CHF, functional capacity class II-IV to New York Heart Association and left ventricular ejection fraction (LVEF) < 40% and 125 consecutive patients with stable angina pectoris and LVEF > or = 40%. Furthermore the results of the cardiopulmonary exercise testing (CPX) in each ACE genotype were compared in medically treated ischemic CHF patients (n = 84). ACE genotype distributions were similar between the patients with and without symptomatic CHF in CAD. The odds ratios were 0.95 for D homozygotes (p > 0.05) and 0.98 for the D allele (p > 0.05). In patients with ischemic CHF the differences in CPX findings were statistically not significant in ACE D/D, I/D and I/I genotypes (peak oxygen consumptions 13.7 +/- 4.6; 14.6 +/- 5.1 and 14.5 +/- 5.0 ml/kg/min, respectively (p >0.05). In this study population, there was no evidence that ACE gene I/D polymorphism plays a role in the development of CHF in CAD or any influence on exercise capacity in treated patients with ischemic CHF.


Cardiorespiratory Fitness, Body Fatness, and Submaximal Systolic Blood Pressure Among Young Adult Women.
We examined the independent and combined associations of cardiorespiratory fitness (CRF), body fat (BF) percentage (BF%), and body mass index (BMI) with submaximal systolic blood pressure (SSBP) among young adult women. Analyses included a sample of 211 normotensive women with a BMI between 20 and 35 kg/m(2); BF% was calculated using total BF measured from dual X-ray absorptiometry, CRF was assessed using a graded exercise test, and SSBP was measured at each stage. There was a significant direct association of SSBP with BF% and BMI, whereas an inverse association between SSBP and CRF when adjusted for the covariates. There was no significant association between SSBP and BF% across the stages 1-3 with a borderline significant association at stage 4 when further adjusted for CRF, whereas no association at any of the stages when adjusted for BMI. A borderline significant association between SSBP and BMI was found at stage 1 and significant association at stages 2-4 when additionally adjusted for CRF, whereas the association disappeared at stages 1-2 when adjusted for BF%. The inverse association between SSBP and CRF was eliminated at stages 3-4 when further adjusted for BF% with borderline significant association at stages 1-2. The associations remained significant at the stages 1-2 but not at stages 3-4 after adjusting for BMI. CRF, BF%, and BMI seem to have critical roles in determining SSBP with CRF and BF% being more potent at lower intensity exercise, whereas BMI was more strongly associated at higher intensity exercise.


Safety and Outcome of Decompressive Hemicraniectomy After Recombinant Tissue Plasminogen Activator Thrombolysis for Acute Ischemic Stroke: A Systematic Review.
Decompressive hemicraniectomy (DH) is widely recommended as a surgical treatment for intractable increased intracranial pressure after malignant cerebral infarction. Many patients given recombinant tissue plasminogen activator (rtPA) develop cerebral edema after reperfusion or failed recanalization. However, the safety and efficacy of DH after rtPA administration remain largely unknown. A systematic review was performed using PubMed, Embase, Scopus, Cochrane, and HERDIN. Studies were eligible if they included patients who underwent DH after intravenous thrombolysis for acute ischemic stroke. Unweighted odds ratio (OR) for mortality (primary outcome) and good functional outcome defined as modified Rankin Scale score 0-3 or Glasgow Outcome Scale score 4-5 at 3-6 months (secondary outcome) were compared between the DH + rtPA group and DH alone group. Four studies with a total of 98 patients undergoing DH + rtPA were compared with 110 patients undergoing DH alone without previous thrombolysis. Age, vascular risk factors, and cause of stroke were comparable between the 2 groups. Pooled analysis showed that mortality and functional outcomes were not statistically different between the DH + rtPA and DH alone groups (OR, 0.56, P = 0.07 and OR, 0.83, P = 0.30, respectively). Likewise, both minor and major hemorrhagic rates were similar between the 2 groups (37.76% vs. 27.27%; P = 0.053). DH for malignant cerebral infarction after intravenous rtPA administration is a viable treatment option, with a comparable mortality and functional outcome to those who had DH without previous thrombolysis.


Profiling the DNA methylation patterns of imprinted genes in abnormal semen samples by next-generation bisulfite sequencing.
Changes in DNA methylation modifications have been associated with male infertility. With the development of assisted reproductive technologies (ARTs), abnormal DNA methylation in sperm, especially in imprinted genes, may impact the health of offspring and requires an in-depth study. In this study, we collected abnormal human semen samples, including asthenospermic, oligospermic, oligoasthenospermic and deformed sperm, and investigated the methylation of imprinted genes by reduced representation bisulfite sequencing (RRBS) and bisulfite amplicon sequencing on the Illumina platform. The differentially methylated regions (DMRs) of imprinted genes, including H19, GNAS, MEG8 and SNRPN, were different in the abnormal semen groups. MEG8 DMR methylation in the asthenospermic group was significantly increased. Furthermore, higher methylation levels of MEG8, GNAS and SNRPN DMR in the oligospermic and oligoasthenospermic groups and a decrease in the H19 DMR methylation level in the oligospermic group were observed. However, the methylation levels of these regions varied greatly among the different semen samples and among individual sperm within the same semen sample. The SNP rs2525883 genotype in the H19 DMR affected DNA methylation. Moreover, DNA methylation levels differed in the abnormal semen groups in the non-imprinted genomic regions, including repetitive sequence DNA transposons and long/short interspersed nuclear elements (LINEs and SINEs). Our study established that imprinted gene DMRs, such as H19, GNAS, SNRPN and MEG8, were differentially methylated in the abnormal semen groups with obvious inter- and intra-sample heterogeneities. These results suggest that special attention needs to be paid to possible epigenetic risks during reproduction.


Simultaneous ultrastructural demonstration of multiple peptides in endocrine cells by a novel immunocytochemical method.
Current immunocytochemical techniques detect all antibodies that react with tissue. Unfortunately, some of these antibodies may react with antigens other than those intended. Such problems are minimised by using sets of antibodies detecting different regions of the desired antigen. However, as immunocytochemical methods can now detect very low antibody concentrations, the purity of antisera is critical. Furthermore, although antisers may be purified by affinity chromatography, difficulties in recovering high-avidity antibodies cause most affinity-purified antisera to be enriched in low-avidity antibodies, which may be dislodged during staining. We have therefore developed, and describe here, a new ultrastructural post-embedding staining technique, based on the divalency of IgG molecules and using antigen-coated colloidal gold granules. Previously, colloidal gold-labelled antibodies have been used for post-embedding staining. Unlike our gold-labelled antigen detection (GLAD) technique, however, these methods do not differentiate between specific and nonspecific antibodies. The GLAD method detects only specific antibodies and does not select against high-avidity antibodies, and in this it resembles the radioimmunocytochemical method. However, the GLAD method differs from the latter in that it is useful for ultrastructural studies, does not require autoradiography and allows simultaneous detection of multiple antigens. Moreover, specific activity compared with background may be quantitated.


Coordinate regulation and synergistic actions of BMP4, SHH and FGF8 in the rostral prosencephalon regulate morphogenesis of the telencephalic and optic vesicles.
We investigated the roles of bare morphogenetic protein (BMP), sonic hedgehog (SHH) and fibroblast growth factor (FGF)-expressing signaling centers in regulating the patterned outgrowth of the telencephalic and optic vesicles. Implantation of BMP4 beads in the anterior neuropore of stage 10 chicken embryos repressed FGF8 and SHH expression. Similarly, loss of SHH expression in Shh mutant mice leads to increased BMP signaling and loss of Fgf8 expression in the prosencephalon. Increased BMP signaling and loss of FGF and SHH expression was correlated with decreased proliferation, increased cell death, and hypoplasia of the telencephalic and optic vesicles. However, decreased BMP signaling, through ectopic expression of Noggin, a BMP-binding protein, also caused decreased proliferation and hypoplasia of the telencephalic and optic vesicles, but with maintenance of Fgf8 and Shh expression, and no detectable increase in cell death. These results suggest that optimal growth requires a balance of BMP, FGF8 and SHH signaling. We suggest that the juxtaposition of Fgf8, Bmp4 and Shh expression domains generate patterning centers that coordinate the growth of the telencephalic and optic vesicles, similar to how Fgf8, Bmp4 and Shh regulate growth of the limb bud. Furthermore, these patterning centers regulate regional specification within the forebrain and eye, as exemplified by the regulation of Emx2 expression by different levels of BMP signaling. In summary, we present evidence that there is cross-regulation between BMP-, FGF- and SHH-expressing signaling centers in the prosencephalon which regulate morphogenesis of, and regional specification within, the telencephalic and optic vesicles.


Salt-induced modulation in growth, photosynthesis and antioxidant system in two varieties of Brassica juncea.
The present study was carried out to examine salt-induced modulation in growth, photosynthetic characteristics and antioxidant system in two cultivars of Brassica juncea Czern and Coss varieties (Varuna and RH-30). The surface sterilized seeds of these varieties were sown in the soil amended with different levels (2.8, 4.2 or 5.6 dsm(-1)) of sodium chloride under a simple randomized block design. The salt treatment significantly decreased growth, net photosynthetic rate and its related attributes, chlorophyll fluorescence, SPAD value of chlorophyll, leaf carbonic anhydrase activity and leaf water potential, whereas electrolyte leakage, proline content, and activity of catalase, peroxidase and superoxide dismutase enzymes increased in both the varieties at 30 d stage of growth. The variety Varuna was found more resistant than RH-30 to the salt stress and possessed higher values for growth, photosynthetic attributes and antioxidant enzymes. Out of the graded concentrations (2.8, 4.2 or 5.6 dsm(-1)) of sodium chloride, 2.8 sm(-1) was least toxic and 5.6 dsm(-1) was most harmful. The variation in the responses of these two varieties to salt stress is attributed to their differential photosynthetic traits, SPAD chlorophyll value and antioxidant capacity, which can be used as potential markers for screening mustard plants for salt tolerance.


Congenital toxoplasmic retinochoroiditis in the mouse--the use of the peroxidase anti-peroxidase method to demonstrate Toxoplasma antigen.
The peroxidase anti-peroxidase immunocytochemical staining method has been used to demonstrate Toxoplasma antigen within paraffin-embedded sections of the eyes of mice congenitally infected with Toxoplasma. Intact Toxoplasma tissue cysts were demonstrated within the retina but in no other ocular structure. No endozoites and no extra-cystic antigens were detected by this technique within any of the eyes examined. The possible implications of these findings in relation to the pathogenesis of toxoplasmic retinochoroiditis are discussed.


Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis.
The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca2+ level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca2+ and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1α. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca2+ homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages.


Spoilage bacteria in canned foods. I. Flat sour spoilage bacteria in canned asparagus and the thermal death time.
Bacillus stearothermophilus was found to be a cause of spoilage of asparagus canned in Taiwan. The F(250) and Z values of the isolates were 14.2 min and 17.8 F (-7.9 C), respectively.


Prospects of a new antistaphylococcal drug batumin revealed by molecular docking and analysis of the complete genome sequence of the batumin-producer Pseudomonas batumici UCM B-321.
Meticillin-resistant Staphylococcus aureus (MRSA) is a serious public health threat causing outbreaks of clinical infection around the world. Mupirocin is a promising anti-MRSA drug, however mupirocin-resistant strains of S. aureus are emerging at an increasing rate. The newly discovered antibiotic batumin may contribute to anti-MRSA therapy. The objective of this work was to identify possible molecular targets for batumin as well as mechanisms of its antistaphylococcal activity using computational molecular docking and by analysing the complete genome sequence of the batumin-producer Pseudomonas batumici UCM B-321. It was found that batumin acted very similarly to mupirocin by inhibiting aminoacyl tRNA synthetases. A previous hypothesis considering the trans-enoyl-CoA reductase FabI as a prime molecular target of batumin was rejected. However, indirect inhibition of fatty acid biosynthesis in sensitive bacteria does take place as a part of stringent response repression triggered by accumulation of uncharged tRNA molecules. Paralogues of diverse leucine-tRNA synthetases in the genome of P. batumici indicated that this protein might be the prime target of batumin. A batumin biosynthesis operon comprising 28 genes was found to be acquired through horizontal gene transfer. It was hypothesised that, in contrast to mupirocin, batumin could inhibit a broader range of aminoacyl tRNA synthetases and that acquired resistance to mupirocin might not endow S. aureus strains with resistance against batumin.


Inulin improves the egg production performance and affects the cecum microbiota of laying hens.
Egg production performance, egg quality, nutrient digestibility, and microbial composition as affected by dietary inulin supplementation were evaluated in laying hens. A total of 300 laying hens were divided into 5 groups and fed diets containing inulin at levels of 0 (control), 5, 10, 15 and 20 g/kg, respectively. The results showed that the 15 g/kg inulin supplementation level improved average egg weight by 2.54%, egg mass by 5.76%, and laying rate by 3.09%, and decreased the feed conversion ratio by 3.61% compared to those of the control during feeding weeks 1 to 8. Dietary inulin supplementation improved eggshell thickness, nutrient digestibility and cecum Bacteroidales_S24-7_ group abundance in the laying hens. In conclusion, dietary inulin supplementation, particularly at the level of 15 g/kg, improved the egg production performance and eggshell thickness of laying hens, mainly due to increased nutrient digestibility and selective modulations of the cecum microbial communities.


Laser in situ keratomileusis in patients with a history of ocular herpes.
To report the outcomes of laser in situ keratomileusis (LASIK) in patients with a history of ocular herpes simplex virus (HSV) or herpes zoster ophthalmicus (HZO). Clínica Baviera, Instituto Oftalmológico Europeo, Madrid, Spain. In this retrospective case series, the records of eyes with a history of ocular herpes that had LASIK from 2003 through 2005 were reviewed. The main outcome measure was postoperative recurrence of ocular herpes. Forty-nine eyes (48 patients) with a history of ocular herpes (HSV keratitis, 28 eyes; HSV eyelid lesions, 17 eyes; HZO, 4 eyes) were identified. All LASIK procedures were uneventful. Herpetic disease was inactive at the time of surgery in all eyes and for more than 1 year in 31 eyes. Perioperative antiviral systemic prophylaxis was used in 13 patients with a history of HSV keratitis. No eye developed reactivation of herpetic keratitis during the follow-up (range 1 to 28 months). Laser in situ keratomileusis was safe in patients with a history of ocular herpes; no recurrences occurred during the follow-up period. However, candidates should be selected with caution and surgery performed only in eyes in which the herpes has been inactive for 1 year before surgery, without stromal disease, and with regular topography and pachymetry maps and normal corneal sensitivity. The most reasonable clinical strategy is perioperative systemic antiviral prophylaxis.


A new approach to analyze the dynamic strength of eggs.
The mechanical behavior of eggshell was determined in terms of average rupture force and corresponding deformation. For the experiment, we selected goose eggs (Anser anser f. domestica). Samples of eggs were compressed along their x-axis and z-axis. The effect of the loading orientation can be described in terms of the eggshell contour curvature. Two different experimental methods were used: compression between two plates (loading rates up to 5 mm/s) and the Hopkinson split pressure bar technique. This second method enables achieving loading rates up to about 17 m/s. The response of goose eggs to this high loading rate was characterized also by simultaneous measurement of the eggshell surface displacements using a laser vibrometer and by the measurement of both circumferential and meridian strains.


Advanced radiation treatment planning and delivery approaches for treatment of lung cancer.
Great technologic progress has been made in the last decade in the radiation treatment of lung cancer. In particular, the widespread use of 3D conformal therapy has the potential to escalate the dose to the tumor while sparing dose to normal tissue. Current technology, however, has yet to impact local control and survival. It could be hypothesized that this is due to geographic misses because of poor target definition, movement of the tumor due to respiration, and dose/ fractionation levels. Several emerging technologies that are described in this article have the potential to address these problems, with results expected in the near future. The technical delivery of radiation has not reached its limit.


Immediate impact of Mindfulness-Based Cognitive Therapy (MBCT) among women with breast cancer: a systematic review and meta-analysis.
Mindfulness-based cognitive therapy (MBCT) may have positive physiological and psychological benefits for breast cancer survivors. However, few studies involved a combination of the relevant literatures to confirm the effects. Our study included randomized controlled trials (RCTs) and non-RCTs comparing interventions of MBCT and control protocols for alleviation of symptoms among breast cancer survivors. We calculated pooled mean differences (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) by using random effects models to estimate summary effect sizes. Thirteen trials with 20-245 participants were considered in our studies; for the meta-analysis, 11 of these studies were eligible for assessment. The pooled meta-analysis results revealed that at the end of the MBCT intervention, participants' anxiety (SMD, - 0.70; 95% CI, - 1.26 to - 0.13; I2 = 69%), pain (SMD, - 0.64; 95% CI, - 0.92 to - 0.37; I2 = 0%), and depression (SMD, - 0.65; 95% CI, - 1.14 to - 0.17; I2 = 75%) levels significantly decreased, and their mindfulness (MD, 8.83; 95% CI, 3.88 to 13.78; I2 = 68%) levels significantly increased. The MBCT may be associated with improved pain, anxiety, depression, and mindfulness. However, the quantitative analysis pointed to an inconclusive result due to moderate to high levels of heterogeneity among indicator of anxiety, depression, and mindfulness. Future work requires more studies to better elucidate the clinical significance of this possible association. The results suggest that MBCT is highly beneficial as an intervention for patients who have received treatment for breast cancer.


[A case of lithium intoxication at therapeutic lithium dosage due to additional diuretic therapy (author's transl)].
A case is presented of lithium intoxication with therapeutic doses of lithium, owing to the additional administration of a sodium-excreting diuretic. Since the patient was receiving neuroleptic therapy at the same time, intoxication symptoms at the onset were falsely attributed to neuroleptic extrapyramidal effects. The possible effects of widely-used diuretics in conjunction with lithium therapy are presented. The combination of both therapeutic substances is possible, but calls for extreme caution and strict control of medication, diet and serum lithium levels.


[Hereditary epidermolysis bullosa in school children and adolescents. Clinical picture and interdisciplinary management].
Hereditary epidermolysis bullosa (EB) represents a clinically heterogeneous group of congenital blistering disorders requiring multiprofessional care. EB is associated with a broad spectrum of potentially severe complications often reaching their full extent during school age and adolescence. This review aims at summarizing cutaneous manifestations of EB as well as extracutaneous complications of this complex disease and their interdisciplinary management.


Does adding hydroxychloroquine to empiric treatment improve the live birth rate in refractory obstetrical antiphospholipid syndrome? A systematic review.
The current standard prevention of obstetric complications in patients with antiphospholipid antibody syndrome (APS) is the use of combination low-dose aspirin and low molecular weight heparin. However, 20-30% of women still experience refractory obstetrical APS. Hydroxychloroquine (HCQ) is an immunomodulatory agent that has been shown in laboratory studies to decrease thrombosis risk, support placentation, and minimize the destructive effects of antiphospholipid antibodies. The objective of this study was to evaluate the risk of pregnancy loss upon treatment with HCQ among women with refractory obstetrical APS. A systematic review was conducted according to PRISMA guidelines. Studies that evaluated the use of HCQ during pregnancy in women with primary APS were included. The primary outcomes of interest were live birth and pregnancy losses after treatment with HCQ. Twelve studies met inclusion criteria. Three retrospective cohort studies demonstrated improved live birth rate, and four studies demonstrated a reduction in pregnancy loss rate. Two case reports also demonstrated a benefit in the use of HCQ compared to previous obstetrical outcomes. Our findings suggest a significant benefit of HCQ in addition to aspirin and heparin for patients with APS to mitigate the risk of antiphospholipid antibody mediated obstetrical complications. Randomized controlled trials with standardized patient selection criteria need to be conducted to corroborate these findings.


Unmasking right ventricular-arterial uncoupling during fluid challenge in pulmonary hypertension.
Patients with pulmonary hypertension (PH) frequently show preserved right ventricular (RV) function at rest. However, volume challenge may uncover pending RV dysfunction. We aimed to assess the physiological and prognostic impact of RV-pulmonary arterial (RV-PA) uncoupling during volume challenge in patients with precapillary PH. We prospectively assessed 32 patients with PH (pulmonary arterial hypertension, n = 27; inoperable chronic thromboembolic disease, n = 5) and 4 controls using invasive pressure-volume (PV) catheterization. PV loops were recorded during preload reduction (balloon occlusion of inferior vena cava; baseline) and acute volume loading (200 ml saline in 20 s). Contractility (multi-beat end-systolic elastance [Ees]), arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were obtained at baseline and at maximum volume loading (MVL). Median [interquartile range] time to MVL was 19 [18-22] s. Ees/Ea significantly declined from baseline (0.89 [0.69-1.23]) to MVL (0.16 [0.12-0.34]; p < 0.001) in patients with PH but remained stable in controls (baseline: 1.08 [0.94-1.80]; MVL: 1.01 [0.80-2.49]; p = 0.715). The same pattern was observed for Ees, while Ea remained unchanged. The percent decline of RV-PA coupling (ΔEes/Ea) during fluid challenge was significantly associated with pulmonary resting hemodynamics, RV ejection fraction (RVEF), and RV end-diastolic volume. Kaplan-Meier analysis revealed that patients with PH who had a smaller ΔEes/Ea (<-65%) had a significantly better prognosis (log-rank p = 0.0389). In multivariate Cox regression analysis, clinical worsening was predicted by ΔEes/Ea (hazard ratio: 0.96 [95% confidence interval: 0.93-1.00]) and RVEF (hazard ratio: 0.95 [95% confidence interval: 0.92-0.98]). Assessment of PV loops during fluid challenge uncovers exhausted RV coupling reserve with severely reduced contractility in PH. RV-PA uncoupling during volume challenge can be predicted by pulmonary resting hemodynamics and RVEF. RV-PA uncoupling during fluid challenge and RVEF (as a noninvasive correlate) are predictors of clinical worsening. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868 (January 19, 2018).


Immunocytochemical detection of luteinizing hormone in epididymis of mature mouse.
Luteinizing hormone (LH) binds to the Leydig cells of several mammalian species where it stimulates steroidogenesis, protein synthesis and protein phosphorylation. In the present study, standard immunoperoxidase (PAP) and avidin-biotin complex (ABC) techniques were used to detect the binding of endogenous and exogenous LH to the epididymis of the mature mouse. Throughout the epididymal duct, a positive reaction for peroxidase, indicating LH binding, occurred in the Golgi area of principal cells. In segment 1, positive reactions were also visualized in the perinuclear area and in the region located between the Golgi area and the apical surface of the principal cells (supra-Golgi area). In the corpus and cauda epididymidis, scattered entire principal cells were also positive. Throughout the epididymal duct, the reactions indicating the binding of exogenous LH were more intense than those of endogenous LH. The significance of LH binding to the epididymis is uncertain but LH may perform the same functions in epididymal principal cells as it does in Leydig cells.


3D Modeling and Advanced Visualization of the Pediatric Brain, Neck, and Spine.
The ready availability of advanced visualization tools on picture archiving and communication systems workstations or even standard laptops through server-based or cloud-based solutions has enabled greater adoption of these techniques. We describe how radiologists can tailor imaging techniques for optimal 3D reconstructions provide a brief overview of the standard and newer "on-screen" techniques. We describe the process of creating 3D printed models for surgical simulation and education, with examples from the authors' institution and the existing literature. Finally, the review highlights current uses and potential future use cases for virtual reality and augmented reality applications in a pediatric neuroimaging setting.


Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis.
T cell activation is regulated by inhibitory molecules such as PD-1 and CTLA-4, whose expression may be affected by gene polymorphisms. Increased T cell activation is present in patients with ANCA-associated vasculitis (AAV). We investigated two single-nucleotide polymorphisms (SNPs) in PDCD1 and five polymorphisms in CTLA4 in 102 patients with AAV and 188 healthy controls (HC). The distributions of the PD-1.3 and PD-1.5 SNPs, and the distributions of the CTLA4 promoter polymorphisms -1722T/C, -1661A/G, -318 C/T, and the (AT)(n) microsatellite in the 3'-untranslated region of CTLA4, did not differ between patients and HC. However, the +49 G allele was significantly more often present in patients with AAV. Furthermore, the co-occurrence of the PD-1.5 T allele with CTLA4 +49 AA homozygosity (i.e., the absence of a G allele) was less often present in patients compared to HC. These genetic polymorphisms may lead to hyperreactivity of T cells and thus may contribute to the pathogenesis of AAV.


Opioid analgesics.
Opioids are useful and potent drugs for the management of pain in small animal patients. They have a wide therapeutic index and can be given by a number of different routes. Some of these techniques (e.g., epidural and intraarticular) allow for the production of profound analgesia in a localized area of the body while limiting the dose and the side effects, and others provide a noninvasive method for the delivery of continuous analgesia (e.g., transdermal administration).


Pre- and Postseason Dynamic Ultrasound Evaluation of the Pitching Elbow.
To use ultrasound imaging to document changes over time (i.e., preseason v postseason) in the pitching elbow of high school baseball pitchers. Twenty-two high school pitchers were prospectively followed. Pitchers were evaluated after a 2-month period of relative arm rest via preseason physical exams, dynamic ultrasound imaging of their throwing elbow, and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) assessment. Players were reevaluated within 1 week of their last game. Dynamic ultrasound images were then randomized, blinded to testing time point, and evaluated by 2 fellowship-trained musculoskeletal radiologists. Average pitcher age was 16.9 years. Average pitches thrown was 456.5, maximum velocity 77.7 mph, games pitched 7.3, and days off between starts 6.6. From preseason to postseason, there were significant increases in ulnar collateral ligament (UCL) thickness (P = .02), ulnar nerve cross-sectional area (P = .001), UCL substance heterogeneity (P = .001), and QuickDASH scores (P = .03). In addition, there was a nonsignificant increase in loaded ulnohumeral joint space (P = .10). No pitchers had loose bodies on preseason exam, while 3 demonstrated loose bodies postseason. The increase in UCL thickness was significantly associated with the number of bullpen sessions per week (P = .01). The increase in ulnar nerve cross-sectional area was significantly associated with the number of pitches (P = .04), innings pitched (P = .01), and games pitched (P = .04). The stresses placed on the elbow during only one season of pitching create adaptive changes to multiple structures about the elbow including UCL heterogeneity and thickening, increased ulnohumeral joint space laxity, and enlarged ulnar nerve cross-sectional area. Level II prospective observational study.


Health-related quality of life after thoracoscopic sympathectomy for palmar hyperhidrosis.
Palmar hyperhidrosis is a benign functional disorder regarded as a psychological and social handicap. Improvement of the quality of life is a major goal of treatment. However, little attention has been given to quality of life after thoracoscopic sympathectomy, which is the first line of treatment for palmar hyperhidrosis. This study investigated the impact of thoracoscopic sympathectomy on subjective health-related quality of life (HRQoL) and psychological properties. Forty patients who underwent thoracoscopic sympathectomy were followed up for 6 months. The HRQoL measures were the Medical Outcomes Study Short Form 36 (SF-36), the Spielberger State Trait Anxiety Inventory (STAI), and the Zung Self-Rating Depression Scale (SDS). Patients were administered these questionnaires before procedure and then again at 1, 3, and 6 months after sympathectomy. A comparison between the current sample and Japanese normative data for the SF-36 showed mild impairment of HRQoL before sympathectomy. However, it also showed significant improvement of the social functioning domain after sympathectomy. While there was worsening of the bodily pain and role physical domains 1 month after sympathectomy, both domains recovered in 3 months. The results of STAI showed significant improvement of both trait and state anxiety after sympathectomy. However, the results of SDS showed patients remained neurotic. This study is the first to show the pattern of impairment in health status and therapeutic impact in palmar hyperhidrosis patients. Hyperhidrosis is associated with impaired HRQoL. It was also demonstrated that thoracoscopic sympathectomy is safe, minimally invasive, and improves HRQoL, even if compensatory hyperhidrosis occurs.


Antibodies to oxidized LDL/beta2-glycoprotein I in antiphospholipid syndrome patients with venous and arterial thromboembolism.
It has been reported that IgG to oxidized LDL/beta2-glycoprotein I (oxLDL/beta2GPI) complexes are associated with arterial thromboembolism (TE) in patients with antiphospholipid syndrome (APS). How these antibodies behave in arterial as compared to venous TE in APS is unknown. The aim of the present study was to evaluate the association of IgG anti-oxLDL/beta2GPI with clinical manifestations in category I APS patients. Fifty-seven APS patients with triple positivity (Lupus Anticoagulant (LAC), anti cardiolipin (aCL) and anti-beta2-glycoprotein I (abeta2GPI) antibodies), 28 with arterial and 29 with venous thromboembolism, were included in the study. There were no differences in the dRVVT ratio, IgG/IgM aCL and IgG/IgM abeta2GPI titers in the two patient groups. There were no differences in the IgG (78.5 U+/-59.8 vs. 112.2 U+/-92.3) and IgM (16.3 U+/-15.9 vs. 21.1 U+/-14.3) anti-oxLDL/beta2GPI mean values. A significant correlation was found between IgG anti-oxLDL/beta2GPI and IgG anti-beta2GPI titers in the whole group of APS patients. Patients in the arterial group were older and had more risk factors for atherosclerosis. Data from this study do not support the hypothesis that IgG anti-oxLDL/beta2GPI are specifically associated to arterial TE in Category I APS patients.


Transmission Potential of Human Monkeypox in Mass Gatherings.
Since May 2022, a large number of monkeypox cases have been reported in Europe, the United States, and other nonendemic settings. Taking into account the strict measures implemented due to the coronavirus disease 2019 pandemic and the desire of people to reclaim what is perceived as lost time, mass gatherings this summer were highly attended. Based on data for the secondary attack rate among unvaccinated contacts from endemic countries, we estimate that, on average, >1 secondary case is anticipated per infectious person if he/she has a high number of group contacts (>30) or >8 close contacts. Although the role of group contacts in mass gatherings is uncertain (less likely to involve physical contact, shorter duration), close contacts associated with the event (eg, intimate/sexual contact with other attendees) might be the amplifying event. Enforcing awareness, early recognition, and engaging affected populations in the monkeypox response are important to control transmission.


Awareness, knowledge, and factors that influenced the uptake of screening tests for prostate cancer among men aged 40 and older in Ido-Ekiti, Ekiti State, Nigeria.
Despite being the second most common and deadliest cancer in males, prostate cancer could go unnoticed in the early stages. Prevention programs have been set in place to help in the early detection and reduction of mortality rates in developed countries. The aim of this study was to determine awareness, knowledge, and the uptake of prostate cancer screening tests. Another objective was to identify the factors that determine the uptake of prostate cancer screening among men living in Ido-Ekiti. A cross-sectional study was conducted among males aged 40 and above living in Ido-Ekiti in Ido-Osi local government area, Ekiti State, Nigeria. The sample size of 380 respondents was obtained using Leslie Fisher's formula. The study revealed that the majority of the correspondents are aware of prostate cancer (57.9%). More than two-thirds of the respondents have poor knowledge of prostate cancer and the screening test (74.4%), with a median knowledge score of 30%. The uptake of prostate cancer screening tests was very low among the respondents (18.2%). Despite the high level of awareness of prostate cancer disease among the respondents, the majority have poor knowledge of the disease and the screening test. There was a low uptake of prostate cancer screening tests among the respondents.


A study on how using an interactive multimedia e-book improves teachers' ability to teach evidence-based medicine depending on their seniority.
Teaching evidence-based medicine (EBM) is not an easy task. The role of the electronic book (e-book) is a useful supplement to traditional methods for improving skills. Our aim is to use an interactive e-book or PowerPoint to evaluate instructors' teaching effects on EBM. Our study group was introduced to learning EBM using an interactive e-book available on the Internet, while the control group used a PowerPoint presentation. We adopted the Modified Fresno test to assess EBM skills both before and after their learning. EBM teaching sessions via e-book or PowerPoint were 20-30 min long, followed by students' feedback. We adopted Student's t-test to compare teachers' evaluation of their EBM skills prior to the class and the students' assessment of the teachers' instruction. We also adopted repeated measures ANCOVA to compare teachers' evaluation of their EBM skills using the Fresno test both before and after the class. We observed no difference regarding EBM skills between the two groups prior to their experimental learning, which was assessed by the Modified Fresno test. After learning, physicians in the study group ranked higher in choosing a case to explain which kind of research design was used for the study type of the question and explaining their choice (P = 0.024) as assessed by the post-test to pre-test Fresno test. Teaching effect was better in the e-book group than in the control group for the items, "I am satisfied with this lesson," "The teaching was of high quality," "This was a good teaching method," and "It aroused my interest in EBM." However, no differences were observed between the two groups in physicians who had more than 10 years' experience. The use of interactive e-books in clinical teaching can enhance a teacher's EBM skills, though not in more senior physicians. This may suggest that teaching methodology and activities differ for teachers' varying years of experience.


A comparison of deaf, normal, and brain damaged adults on a tachistoscopic task.
Printed words and letters, pictures of signed words, and pictures of finger-spelled letters were presented tachistoscopically to deaf, normal, and brain-damaged adults. The findings suggest that (1) the deaf show no cerebral asymmetry for any of the material but found identification of the stimuli very difficult unless a forced-choice recognition procedure was used or the exposure time was very long; (2) both the normal and the brain-damaged groups show left hemisphere superiority for printed material but no cerebral specialization for signed material; (3) the left-right hemisphere difference is more marked in the brain-damaged group regardless of which hemisphere showed most damage. This may be explained, at least in some cases, by impaired transfer across the corpus callosum.


The ABC transporter gene family of Caenorhabditis elegans has implications for the evolutionary dynamics of multidrug resistance in eukaryotes.
Many drugs of natural origin are hydrophobic and can pass through cell membranes. Hydrophobic molecules must be susceptible to active efflux systems if they are to be maintained at lower concentrations in cells than in their environment. Multi-drug resistance (MDR), often mediated by intrinsic membrane proteins that couple energy to drug efflux, provides this function. All eukaryotic genomes encode several gene families capable of encoding MDR functions, among which the ABC transporters are the largest. The number of candidate MDR genes means that study of the drug-resistance properties of an organism cannot be effectively carried out without taking a genomic perspective. We have annotated sequences for all 60 ABC transporters from the Caenorhabditis elegans genome, and performed a phylogenetic analysis of these along with the 49 human, 30 yeast, and 57 fly ABC transporters currently available in GenBank. Classification according to a unified nomenclature is presented. Comparison between genomes reveals much gene duplication and loss, and surprisingly little orthology among analogous genes. Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times. ABC transporter evolution fits a pattern expected from a process termed 'dynamic-coherence'. This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life. Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication.


Hydrogen sulfide poisoning: clarification of some controversial issues.
Hydrogen sulfide is a toxic gas about which much has been written. We discuss here several issues we believe would benefit from further clarification. We conclude that: 1) Certain neurotoxic effects of exposure are probably due to a direct toxic effect on the brain, while others are almost certainly a result of hypoxia secondary to H2S-induced respiratory insufficiency; 2) pulmonary edema is a common consequence of poisoning and there is suggestive evidence of hyperactive airway responses in some individuals following brief H2S-induced unconsciousness (knockdown); 3) criteria for acceptable community levels are very different than those governing occupational standards; 4) urinary thiosulfate determinations can be useful for monitoring occupational exposure; and 5) determination of sulfide ion concentrations in blood or major organs can be useful in corroborating a diagnosis of fatal H2S toxicity, but there are many pitfalls in collecting, storing, and analyzing tissue and fluid samples.