Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective.
The direct impact and sequelae of infections in children and adults result in significant morbidity and mortality especially when they involve the central (CNS) or peripheral nervous system (PNS). The historical understanding of the pathophysiology has been mostly focused on the direct impact of the various pathogens through neural tissue invasion. However, with the better understanding of neuroimmunology, there is a rapidly growing realization of the contribution of the innate and adaptive host immune responses in the pathogenesis of many CNS and PNS diseases. The balance between the protective and pathologic sequelae of immunity is fragile and can easily be tipped towards harm for the host. The matter of immune privilege and surveillance of the CNS/PNS compartments and the role of the blood-brain barrier (BBB) and blood nerve barrier (BNB) makes this even more complex. Our understanding of the pathogenesis of many post-infectious manifestations of various microbial agents remains elusive, especially in the diverse African setting. Our exploration and better understanding of the neuroimmunology of some of the infectious diseases that we encounter in the continent will go a long way into helping us to improve their management and therefore lessen the burden. Africa is diverse and uniquely poised because of the mix of the classic, well described, autoimmune disease entities and the specifically "tropical" conditions. This review explores the current understanding of some of the para- and post-infectious autoimmune manifestations of CNS and PNS diseases in the African context. We highlight the clinical presentations, diagnosis and treatment of these neurological disorders and underscore the knowledge gaps and perspectives for future research using disease models of conditions that we see in the continent, some of which are not uniquely African and, where relevant, include discussion of the proposed mechanisms underlying pathogen-induced autoimmunity. This review covers the following conditions as models and highlight those in which a relationship with COVID-19 infection has been reported: a) Acute Necrotizing Encephalopathy; b) Measles-associated encephalopathies; c) Human Immunodeficiency Virus (HIV) neuroimmune disorders, and particularly the difficulties associated with classical post-infectious autoimmune disorders such as the Guillain-Barré syndrome in the context of HIV and other infections. Finally, we describe NMDA-R encephalitis, which can be post-HSV encephalitis, summarise other antibody-mediated CNS diseases and describe myasthenia gravis as the classic antibody-mediated disease but with special features in Africa.


Couple-based interventions in the treatment of adult anorexia nervosa: A brief case example of UCAN.
Adult anorexia nervosa (AN) is a serious and often fatal illness that significantly erodes quality of life for both the patient and loved ones. Treatment of adults with AN has focused largely on individual therapy, with recent findings suggesting that improvement is limited and dropout rates are high. In an effort to improve treatment response, we developed a couple-based intervention, Uniting Couples in the treatment of Anorexia Nervosa (UCAN) as an adjunct treatment to standard multidisciplinary care. UCAN leverages the support of a partner and the relationship in treatment by decreasing avoidance around AN, teaching the couple how to effectively address the eating disorder, and helping to foster a more satisfying relationship. This paper presents a case study of a couple who completed UCAN, "Laura and Steve," including their experiences in treatment and outcome measures at pretest, posttest, and 3-month follow-up. Laura showed clinically significant change on the Restraint subscale of the Eating Disorders Examination at follow-up, and both partners showed clinically significant improvements in relationship satisfaction, as well as on self-reported and observed communication. Both partners reported very high satisfaction with the treatment. A discussion of therapists' experiences in delivering UCAN is provided, including common challenges for therapists with primarily a couple therapy or an individual CBT for eating disorders background, as well as important factors for therapists to consider in order to optimally leverage the benefits of including partners in treatment for AN. (PsycINFO Database Record


[Subtotal Stomach-Preserving Pancreaticoduodenectomy for Large Laterally Spreading Early Duodenal Cancer-A Case Report].
A 76-year-old man came to our hospital for a close examination after an abnormal finding during a medical checkup. Upper gastrointestinal endoscopy revealed a circumferential flat lesion with irregularity in the second to third portions of the duodenum. Biopsy diagnosed papillary adenocarcinoma. Contrast-enhanced CT of the abdomen showed no evidence of lymph node enlargement and distant metastasis. Endoscopic depth of the lesion was estimated to be intramucosal carcinoma, but it was approximately 60 mm in size, circumferential, and located near the papilla Vater. Therefore, endoscopic resection was deemed difficult. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Postoperative pathological examination revealed type 0-Ⅱa, tub1>pap, pTis, Ly0, V0, 80×50 mm, BD1, Ex0, Pn0, pPM0, pDM0, pN0, pStage 0. There has been no recurrence since then. Lateral spreading duodenal carcinoma is a rare disease, and endoscopic resection, local resection, and pancreaticoduodenectomy have been reported as treatment options. We report a case of resection of a large lateral spreading duodenal carcinoma with a review of the literature.


Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series.
Sorafenib and hepatic arterial infusion chemotherapy (HAIC) are both indicated for unresectable hepatocellular carcinoma (HCC). In this study, we compared the efficacy and safety of HAIC to that of sorafenib in elderly patients with HCC. Eligible patients included those aged ≥70 years, with histologically or clinically confirmed advanced HCC. A total of 12 patients received sorafenib (800 mg per day) and 8 patients received HAIC with 5-fluorouracil (300 mg/m2 on days 1-5 and 8-12) with or without cisplatin (20 mg/m2 on days 1 and 8), with interferon-α (3 times per week for 4 weeks). The response rate was significantly higher in patients treated with HAIC (37.5%) compared to that in patients treated with sorafenib (no response). The median overall survival (18.6 and 11.7 months) and progression-free survival (4.0 and 5.0 months) were similar between the sorafenib and HAIC groups, respectively. In the sorafenib group, 58.3% of the patients discontinued treatment compared to none in the HAIC group. The most frequent adverse event leading to discontinuation of sorafenib was anorexia. Similar to sorafenib, HAIC appears to be a feasible treatment and may also have the advantage of an adequate safety profile for elderly patients with advanced HCC. Further study of HAIC in a larger population of elderly patients is required to assess its potential as an alternative to sorafenib for HCC.


Controlled clinical trial addressing teeth whitening with hydrogen peroxide in adolescents: a 12-month follow-up.
To evaluate the colorimetric change in incisors and canines of adolescents aged 12 to 20 years submitted to at-home whitening and to evaluate satisfaction, sensitivity and discomfort during the procedures through a questionnaire. Thirty adolescents were randomly assigned to the following groups: 1) 6.0% hydrogen peroxide (White Class with calcium - FGM); 2) 7.5% hydrogen peroxide (White Class with calcium - FGM); 3) 10% hydrogen peroxide (Oral B 3D White - Oral-B); 4) Control group - placebo. Assessments were performed prior to treatment as well as at 7, 30, 180 and 360 days after treatment. Friedman's ANOVA was used to analyze color. The Kruskal-Wallis test followed by Dunn's post hoc test was used to compare the groups at the different evaluation times. Answers on the questionnaires were ranked, and non-parametrical tests were employed. The groups were compared in each period using the Kruskal-Wallis test followed by the Student-Newman-Keuls test. Categorical data were analyzed using Fisher's exact test, and the Wilcoxon test was used for the analysis of different periods. P-values were corrected using the Hyan-Holm step-down Bonferroni procedure. Clinicaltrials.gov: NCT01998386. Similar results were obtained one month after treatment with both tooth whitening gels and whitening strips. Patients were partially satisfied with the treatment after the first and second weeks and would recommend it. All products demonstrated color stability after 12 months of follow-up. The bleaching procedure was efficient, and the patients could perceive its result. Further investigations are needed to determine the effects of bleaching on young teeth.


Ultrasound-Guided Regional Anesthesia for Pediatric Burn Reconstructive Surgery: A Prospective Study.
Pediatric patients face multiple reconstructive surgeries to reestablish function and aesthetics postburn injury. Often, the site of the harvested graft for these reconstructions is reported to be the most painful part of the procedure and a common reason for deferring these reconstructive procedures. This study in pediatric burn patients undergoing reconstructive procedures examined the analgesia response to local anesthetic infiltration versus either a single ultrasound-guided regional nerve block of the lateral femoral cutaneous nerve (LFCN) or a fascia iliaca compartment block with catheter placement and continuous infusion. Nineteen patients were randomized to one of three groups (infiltration, single-shot nerve block, or compartment block with catheter) and received intraoperative analgesia intervention. Postoperatively, visual analog scale pain scores were recorded-for pain at the donor site-every 4 hours while awake-for 48 hours. This nonparametric data was analyzed using a two-way ANOVA, Friedman's test, and Kruskal-Wallis test, with significance determined at P < 0.05. The analysis demonstrated that the patients in the regional anesthesia groups were significantly more comfortable over the 48 hour hospital course than the patients in the control group. The patients receiving a single-shot block of the LFCN were more comfortable on postoperative day (POD) 0 while the catheter patients were more comfortable on POD 1 and POD 2. There was not a statistically significant difference in opioid requirements in any group. Regional anesthetic block of the LFCN, with or without catheter placement, provides an improved postoperative experience for the pediatric patient undergoing reconstructive surgery with lateral/anterolateral skin graft versus local anesthesia infiltration of donor site. For optimal comfort throughout the postoperative period, an ultrasound-guided block with continuous catheter may be beneficial.


Aza-dicyclopenta[a,g]naphthalenes: controllable seesaw-like emissive behavior and narrowband AIEgens.
Molecular motions significantly influence the emissive behavior and properties of organic fluorescent molecules. However, achieving controllable emission remains a major challenge for fluorophores. In the case of aggregation-induced emission luminogens (AIEgens), the desired properties of aggregated emission and narrowband spectrum demand molecular motion patterns that inherently oppose each other. A nitrogen-containing dicyclopenta[a,g]naphthalene scaffold was discovered as a controllable luminogenic structure through a highly efficient one-step intermolecular cascade reaction. By carefully balancing molecular motions and introducing additional nitrogen atoms into the skeleton, pyrrole-conjugated dicyclopenta[a,g]naphthalenes with aggregation-caused quenching (ACQ) could be transformed into dual-state emission luminogens (DSEgens). This transformation was achieved by incorporating an additional weak H-bond "lock." Furthermore, the DSEgens could be converted into AIEgens with an exciting narrow full-width-at-half-maximum (FWHM, <50 nm) by methylation. This unprecedented discovery is attributed to the contribution of the weak H-bond "lock," which overcomes the limitations of broad band emission in AIEgens caused by restrictions of intramolecular motion. Specific organelle probes were developed by replacing the methyl group of the onium product with different positioning groups. This study emphasizes the delicate balance of molecular motions in controlling luminescence and demonstrates a successful approach to designing organic luminogens with controllable emission and narrowband AIEgens.


Influence of counterions on micellization of tetramethylammonium perfluorononanoic carboxylate in 1-butyl-3-methylimidazolium ionic liquid.
The influence of counterions on micellization of perfluorononanoic carboxylate ammonium salts in water and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF(4)) solutions was investigated by surface tension and (19)F NMR measurements and freeze-fracture transmission electron microscopy (FF-TEM) observations. Changes in the counterions of the fluorocarbon surfactants have different effects on the two solvents. With the increase of counterion volume, the critical micelle concentration (cmc) value of relevant fluorinated surfactant decreases in aqueous solutions. This is because the counterions with larger size, such as (+)N(CH(3))(4), can be little hydrated, which can screen the electrostatic repulsion of the headgroups of the fluorocarbon surfactant and thus facilitate micelle formation. However, the fluorocarbon surfactants can dissolve and form micelles in [bmim]BF(4) only when they provide with largest counterion such as (+)N(CH(3))(4). This is because the counterion, (+)N(CH(3))(4), disperses the charge of the cations, which could weaken the electrostatic interaction between the ion pair of the surfactant, leading to a higher degree of counterion binding. The thermodynamic parameters estimated from the temperature dependence of the cmc values tell us that the micelle formation for tetramethylammonium perfluorononanoic carboxylate (C(8)F(17)COON(CH(3))(4), PFNT) in ionic liquids (ILs) is an entropy-driven process at low temperature but an enthalpy-driven process at high temperature. The driving force of the micellization for fluorocarbon surfactants in [bmim]BF(4) is the solvophobic effect, due to the hydrophobic and oleophobic properties of fluorocarbon chains.


Effects of varied vocal intensity on ventilation and energy expenditure in women and men.
This study was completed to determine how ventilatory responses change by means of speech reading at three different sound pressure levels (SPL) as compared to quiet breathing prior to each task. The energy required to alter SPL was also studied and compared to energy expenditures during a quiet breathing condition. Twenty-four adults (12 women, 12 men) were studied while reading a standard passage at low, comfortable, and high SPLs for 7 minutes with quiet breathing periods between each task to achieve respiratory steady state and serve as a control to which the reading tasks were compared. The last 2 minutes of exhaled air for all speaking and quiet breathing tasks were collected using a Hans Rudolph mouth breathing face mask. A Sensor Medics Vmax 29 series diagnostic instrument system measured all ventilatory responses and energy expenditures. Volume and timing alterations in ventilation were characterized by measuring tidal volume (V[T]), inspiratory time (T[I]), inspiratory flow rate (V[T]/T[I]), and expiratory time (T[E]). Average ventilation, energy expenditure, and adequacy of ventilation were measured using minute ventilation (V[E]), oxygen consumption (VO2), carbon dioxide production (VCO2), and partial pressure of end-tidal carbon dioxide (end-tidal PET[CO2]). Results indicated volume, timing, ventilation, and energy expenditure values remained closest to quiet breathing values for the comfortable SPL. Volume, ventilation, and energy expenditure were significantly greater for the high SPL and lower for the low SPL, compared to the baseline steady state, indicating that the low SPL causes a ventilatory deficit that was found to be paid back at the end of the speech task during the quiet breathing period. These results demonstrate that an individual's comfortable SPL is the least energy-requiring way to speech breathe. As SPL rises above or below comfortable SPL, speech breathing requires more energy.


Changes in lung permeability after chronic pulmonary artery obstruction.
We have shown that left pulmonary artery ligation (LPAL) in mice causes a prompt angiogenic response, with new systemic vessels from intercostal arteries penetrating the pleura within 6 days. Because angiogenic vessels in other organs have been shown to exhibit increased permeability, we studied vascular permeability (Evans blue dye extravasation, lung wet weight-to-dry weight ratio, and lavaged protein) in naive C57BL/6 mice and 4 h, and 14 and 21 days after LPAL (4-6 mice/time point). We also measured radiolabel clearance as an index of functional perfusion after LPAL. Tracer clearance from the left lung was maximal by 6 days after LPAL and not different from right lungs. Thus a functional vasculature is established before 6 days of LPAL that results in normal tracer clearance. By 21 days after LPAL, Evans blue-albumin was significantly increased in the left lung relative to both 4 h (no vasculature) and 14 days after LPAL. Only after 21 days of LPAL was left lung wet weight-to-dry weight ratio significantly different from naive lungs. Additionally, lavaged protein was significantly increased both 4 h and 21 days after LPAL relative to control mice. Thus, using three different methods, results consistently demonstrated increased permeability to protein and water 21 days after LPAL. Although changes in surface area of perfusion might affect the interpretation of these results, blood flow measured with labeled microspheres indicated no change in left lung perfusion between 14 and 21 days of LPAL. Thus the lung vasculature, remodeled as a consequence of chronic pulmonary artery obstruction, demonstrates increased water and protein permeability.


Biofortification of Sodium Selenate Improves Dietary Mineral Contents and Antioxidant Capacity of Culinary Herb Microgreens.
Selenium biofortification of plants has been suggested as a method of enhancing dietary selenium intake to prevent deficiency and chronic disease in humans, while avoiding toxic levels of intake. Popular herbs such as basil (Ocimum basilicum L.), cilantro (Coriandrum sativum L.), and scallions (Allium fistulosum L.) present an opportunity for biofortification as these plants are used for added flavors to meals and are available as microgreens, young plants with increasing popularity in the consumer marketplace. In this study, basil, cilantro, and scallion microgreens were biofortified with sodium selenate under hydroponic conditions at various selenium concentrations to investigate the effects on yield, selenium content, other mineral contents (i.e., sodium, potassium, calcium, magnesium, phosphorus, copper, zinc, iron, manganese, sulfur, and boron), total phenol content, and antioxidant capacity [oxygen radical absorbance capacity (ORAC)]. The results showed that the selenium content increased significantly at all concentrations, with scallions demonstrating the largest increase. The effects on other minerals varied among herb species. Antioxidant capacity and total phenol content increased in all herbs at the highest selenium treatments, but basil and scallions demonstrated a decreased crop yield. Overall, these biofortified culinary herb microgreens are an ideal functional food for enhancing selenium, other dietary minerals, and antioxidants to benefit human health.


Preovulatory follicular events in sheep.
To investigate the number, size and fate of the follicles greater than 2 mm in diameter involved in the differentiation of the preovulatory follicle in-vivo monitoring of growth and regression of individual follicles was performed at different times after a PG-induced follicular phase. In Exp. 1, the 3 largest follicles of each ovary were labelled with ink in the peripheral stroma at 0, 4, 8, 12, 24 or 48 h after a PG injection. At a second laparotomy, it was assessed which follicles had ovulated. In Exp. 2, a similar procedure was applied in 12 ewes which underwent repeated laparotomies at 6, 30 and 54 h after PG and after ovulation. At all times, there was a huge variability in the size at the time of ink labelling of the follicles that finally ovulated ('ovulatory' follicles). A single measurement of follicle size is therefore a poor prediction of the ovulatory follicles. However, a significant reduction in the proportion of non-ovulatory follicles within the size range of ovulatory follicles occurred at 12-24 h after PG, together with a change in follicle hierarchy at 8-24 h after PG. The results of repeated laparotomies showed that only 60% of follicles greater than 2 mm at 6 h after PG had grown by 30 h. Selection occurred between 30 and 54 h after PG as indicated by a significant drop in the number of growing follicles to a level at 54 h that equalled the ovulation rate. The growth rate of the ovulatory follicles was 1.4 and 0.4 mm per day between 6 and 30 h and 30 and 54 h after PG respectively. The shrinkage rate of non-ovulatory follicles was 1.6 mm/day.


Three-layer flow membrane system on a microchip for investigation of molecular transport.
A stable three-layer flow system, water/organic solvent/water, has been successfully applied for the first time in a microchannel to get rapid transport through an organic liquid membrane. In the continuous laminar flow region, the analyte (methyl red) was rapidly extracted across the microchannel from the donor to the acceptor phase through the organic solvent phase (cyclohexane). Thermal lens microscopy was used to monitor the process. The thickness of the organic phase, sandwiched by the two aqueous phases, was approximately 64 microm, and it was considered as a thin liquid organic membrane. Permeability studies showed the effects of molecular diffusion, layer thickness, and organic solvent-water partition coefficient on the molecular transport. In the microchip, complete equilibration was achieved in several seconds, in contrast to a conventionally used apparatus, where it takes tens of minutes. The thickness of the organic and aqueous boundary layers was defined as equal to the microchannel dimensions, and the organic solvent-water partition coefficient was determined on a microchip using the liquid/liquid extraction system. Experimental data on molecular transport across the organic membrane were in agreement with the calculated permeability based on the three-compartment water/organic solvent/water model. This kind of experiment can be performed only in a microspace, and the system can be considered as a potential biological membrane for future in vitro study of drug transport.


[Multidrug resistance protein (MRP)].
Two different integral glycoproteins, the 170 kD P-glycoprotein(P-gp) and the 190 kD multidrug resistance protein (MRP), are involved in the acquisition of multidrug resistance phenotypes in cancer cells. These two proteins belong to the ATP-binding cassette (ABC) superfamily but their primary structures are quite dissimilar, sharing only approximately 15% amino acid identity. Nevertheless, MRP and P-gp confer resistance to a similar profile of chemotherapeutic agents. These two proteins seem to play a similar role in the acquirement of multidrug resistance. However, it has recently been demonstrated that MRP can specifically transport the cysteinyl leukotriene, LTC4, and some other glutathione conjugates, suggesting that MRP had a function different from P-gp. This review summarizes the current data on the structural and functional characteristics of MRP, its ability to confer multidrug resistance and its clinical relevance in drug resistant malignant disease.


New fluorescent method for the histochemical detection of tripeptidyl peptidase I using glycyl-l-prolyl-l-met-2-anthraquinonyl hydrazide as substrate.
A new substrate for tripeptidyl peptidase I (TPP I; E.C.18.104.22.168)-Gly-L-Pro-L-Met-2-anthraquinonyl hydrazide (Gly-Pro-Met-2-AH) is synthesized and used for the fluorescent histochemical detection of the enzyme. The enzyme liberates low soluble 2-anthraquinonylhydrazine, which-couples quickly with 3-nitrobenzaldehyde (3-NBA) yielding a highly fluorescent water-insoluble hydrazone--3-nitrobenzylidene-2-anthraquinonylhydrazone. The latter compound is localized precisely at sites of enzymatic activity and marks them with a very bright and stable orange-red fluorescence after excitation with conventional monochromatic andlaser green light (lambda(exc)=520-580 nm). The new technique is used successfully for the visualization of the enzyme in tissue sections of different rat organs - and represent the first fluorescent histochemical method for that peptidase.


Combination of early constraint-induced movement therapy and fasudil enhances motor recovery after ischemic stroke in rats.
Constraint-induced movement therapy (CIMT) is a promising technique for the recovery of upper extremity movement in chronic stroke patients. However, the effectiveness of its use in acute ischemia has not been confirmed. Myelin-associated inhibitors, which have upregulated functions in tissues affected by acute focal infarction, limit axonal regeneration via activation of the Rho-Rho-associated protein kinase (ROCK) pathway. The present study examined whether early CIMT combined with the ROCK inhibitor fasudil promotes motor recovery after acute ischemic stroke. Rats were trained to perform the skilled-reach test and then subjected to middle cerebral artery occlusion (MCAO), producing a stroke affecting the preferred forelimb. Rats were assigned to one of four groups (N = 6/group): (nontreated) Control, CIMT, Fasudil, or CIMT+fasudil. CIMT and/or intraperitoneal infusion of fasudil were initiated 1 day postMCAO. Skilled reach and foot fault test data were collected once before and repeatedly over 4 weeks after the operation. Infarct volumes were calculated. All four groups showed similar forelimb impairment before treatment. The performance of CIMT alone group was similar to that of controls on both tests. Fasudil alone facilitated recovery in the foot-fault test, but not in the skilled-reach test. Rats in the CIMT+fasudil group demonstrated enhanced recovery in both tests, including better performance over time than the Fasudil group on the foot-fault test. Infarct size did not differ significantly between the groups. Early CIMT promotes motor recovery after acute ischemic stroke when it is administered with fasudil pharmacotherapy, but not without it.


Adjusting sample size for anticipated dropouts in clinical trials.
Statistical models for calculating sample sizes for controlled clinical trials often fail to take into account the negative impact that dropouts have on the power of intent-to-treat analyses. Empirically defined dropout correction coefficients are proposed to adjust sample sizes for endpoint analysis of variance (ANOVA) and analysis of covariance (ANCOVA) that have been initially calculated assuming complete data. The implications of type of analysis (change-score ANOVA or ANCOVA), correlational structure of the repeated measurements (compound symmetry or autoregressive), and percentage of dropouts (20% or 30%) are considered, together with other less influential design and data parameters. We recommend the use of ANCOVA to correct for baseline differences and for time-in-study if there is a nonspecific change across time. Given a realistic autoregressive (order 1) correlational structure for the repeated measurements and a proposed endpoint ANCOVA, the empirical results support the common practice of increasing calculated sample size by the anticipated number of dropouts. The previous rationale has been to retain a requisite number of "completers" on which to base statistical inferences. We believe the present results provide the first documentation of the relevance of that strategy for intent-to-treat analyses in which the incomplete data for dropouts must be included. Based on comparative power analyses, the strategy also seems appropriate for maintaining the power of mixed-model regression analyses, simple regression on a normalized time scale, and analyses of trends fitted to imputed scores for dropouts.


Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity.
Besides its function in lymphoid cells, which has been addressed by numerous studies, the paracaspase MALT1 also plays an important role in innate cells downstream of pattern recognition receptors. Best studied are the Dectin-1 and Dectin-2 members of the C-type lectin-like receptor family that induce a SYK- and CARD9-dependent signaling cascade leading to NF-κB activation, in a MALT1-dependent manner. By contrast, Toll-like receptors (TLR), such as TLR-4, propagate NF-κB activation but signal via an MYD88/IRAK-dependent cascade. Nonetheless, whether MALT1 might contribute to TLR-4 signaling has remained unclear. Recent evidence with MLT-827, a potent and selective inhibitor of MALT1 paracaspase activity, indicates that TNF- production downstream of TLR-4 in human myeloid cells is independent of MALT1, as opposed to TNF- production downstream of Dectin-1, which is MALT1 dependent. Here, we addressed the selective involvement of MALT1 in pattern recognition sensing further, using a variety of human and mouse cellular preparations, and stimulation of Dectin-1, MINCLE or TLR-4 pathways. We also provided additional insights by exploring cytokines beyond TNF-, and by comparing MLT-827 to a SYK inhibitor (Cpd11) and to an IKK inhibitor (AFN700). Collectively, the data provided further evidence for the MALT1-dependency of C-type lectin-like receptor -signaling by contrast to TLR-signaling.


Normalized light reactions in mycosis fungoides patients after complete remission of skin lesions.
Eleven mycosis fungoides patients were phototested on apparently normal skin before treatment with mechlorethamine, topically in 8 patients and with methoxsypsoralen followed by longwave ultraviolet light (PUVA) in 3 patients. Abnormal photosensitivity to UVB was seen before treatment in 4, to UVA in 4, and to visible light in one patient. The abnormal photosensitivity to all wavelength regions was normalized after complete remission of the cutaneous lesions. Two of the PUVA-treated patients demonstrated that special care should be taken during the initial phase of this treatment because of the light sensitivity, especially on lesional skin.


Endothelin-1 induces lysyl oxidase expression in pulmonary artery smooth muscle cells.
The increase in thickening of the arterial wall of pulmonary arterial hypertension (PAH) includes cellular proliferation as well as matrix deposition and interrupted internal elastic lamina (IEL) consisting of a thick homogeneous sheet of elastin. Little is, although, known about the detail of IEL formation in PAH. Endothelin-1 is overexpressed in pulmonary arterioles of PAH. We aimed to examine the expression of genes contributing to IEL formation in pulmonary artery smooth muscle cells (PASMCs) especially focused on lysyl oxidase (LOx), an exreacellular matrix enzyme that catalyzes the cross-linking of collagens or elastin. We quantified mRNA expressions of genes contributing to IEL formation including LOx in PASMCs using real-time quantitative polymerase chain reaction. We stimulated human PASMCs with endothelin-1 with prostacyclin or trapidil. Endothelin-1 significantly increased LOx expression. Prostacyclin and trapidil restored endothelin-1-induced LOx expression to the basal level. Endothelin-1 increased LOx expression strongly in PASMCs from PAH patients compared to those from controls. Trapidil reduced LOx expression only in PASMCs from PAH patients. Overexpressed endothelin-1 in PAH patients can increase expression of LOx and agitate cross-linking of elastin and collagen, resulting in ectopic deposition of these in the vascular media.


[Refractive defects of the eye in descendents of a rural population in western Moravia].
The results from longitudinal follow-up of the incidence of refractive eye errors in a population from rural region have contributed to the characteristics of the regional gene pool. Generation born within 1950-1964 (Generation I.) was compared with that born within 1980-1994 (Generation II.). At the same time, a long-term follow-up has demonstrated changes in the quantity of phenotypes in absolute number (values of morbidity: generation I.--all types of refractive errors: urban population men 104/1000, women 132/1000. Rural population men 119/1000, women 135/1000. Generation II.: urban men 132/1000, women 169/1000, rural men 124/1000, women 136/1000. The difference in morbidity between women and men in the Ist and IInd generations, both urban and rural, has not changed. A more pronounced difference can be seen in urban population, namely at myopia in both generations (myopia urban population: generation I. men 40.8%, women 59.2%, generation II. men 43.9%, women 56.1%, myopia rural population: generation I.: men 44.2%, women 55.8%, generation II.: men 47.2%, women 52.8%. Hyperopia urban population: generation I., men 46.7%, women 53.3%, generation II. men 47.3%, women 52.7%. The incidence of astigmatism has shown constant ratio 1:1 both between men and women, and urban and rural populations. These changes were demonstrated most markedly in urban population, but these deviations are caused by emigration from rural to urban districts, especially from a hinterland. 10% of IInd generation (1980-1994) are relatives of Ist generation (1950-1964) only.


PSKH1 affects proliferation and invasion of osteosarcoma cells via the p38/MAPK signaling pathway.
Malignant osteosarcoma (OS) is a tumor of bone and soft tissue that metastasizes early and has a high mortality rate. Protein serine kinase H1 (PSKH1), an autophosphorylating human protein serine kinase, controls the trafficking of serine/arginine-rich domain, with downstream effects on mRNA processing. It is also associated with tumor progression. However, how this protein contributes to OS progression and metastasis is unknown. The present study evaluated the potential effect of PSKH1 on proliferation of human OS cells. OS cell lines were used in Cell Counting Kit-8, colony formation, wound-healing and Transwell assays, to investigate cellular processes such as proliferation, migration and invasion and underlying molecular mechanisms. Expression of PSKH1 in OS tissue was significantly greater than in adjacent non-malignant tissue. PSKH1 knockdown inhibited the proliferation, migration and invasion of OS cells. Conversely, PSKH1 overexpression promoted proliferation of OS cells. PSKH1 upregulated phosphorylated-p38 in OS cells. Moreover, the p38 MAPK inhibitor SB203580 effectively blocked the tumor-promoting action of PSKH1. Furthermore, PSKH1 knockdown inhibited tumor growth and metastasis in vivo. In conclusion, these findings suggested that PSKH1 promoted OS proliferation, migration and invasion. Thus, PSKH1 may serve an oncogenic role in the development of human OS.


Psychosocial causes of duodenal ulcer.
The evidence that duodenal ulcer is a psychosomatic disorder is reviewed. A variety of both experimental stressors and differing states of emotional arousal (anxiety and anger in particular) are associated with increased acid and pepsin secretion. Furthermore, chronic life stressors predispose to duodenal ulcer, presumably by way of symptomatic anxiety or depression, while poor social support may comprise another risk factor. Subjects with high levels of trait anxiety or neuroticism are more prone to stress-induced anxiety and its physiological consequences. There is minimal acceptable evidence to support more specific personality-related theories, including Type A behaviour, alexithymia or the earlier psycho-analytic theories of Alexander. Nonetheless, it is concluded that Alexander's inclusion of duodenal ulcer as one of a handful of classic psychosomatic disorders has been confirmed. Since some 40% of duodenal ulcer patients relapse in the first year after medical treatment, there may be some role for psychological treatments (especially in the domain of stress/anxiety management) for those patients who relapse and have co-existing high state or trait anxiety or exposure to chronic stressors.


Defective calcium absorption in the proximal small intestine in chronic renal failure: effect of dihydrotachysterol.
Intestinal absorption of calcium was evaluated in 6 uraemic patients and in 7 control subjects by a two isotope technique exploring absorption in the four hours following ingestion of the dose. In the first two hours, calcium absorption in the patients was markedly lower than normal and was corrected by 6-10 day administration of dihydrotachysterol, 0.66 mg per day. The administration of 0.33 mg per day proved less effective. The data indicate the existence of impaired intestinal calcium absorption in chronic renal failure and reversal of the defect after DHT administration. The method of investigation appears to be a valid procedure for the study of calcium malabsorption of CRF and in the evaluation of the effect of vitamin D metabolities and analogs.


KCa 2.2 (KCNN2): A physiologically and therapeutically important potassium channel.
One group of the K+ ion channels, the small-conductance Ca2+ -activated potassium channels (KCa 2.x, also known as SK channels family), is widely expressed in neurons as well as the heart, endothelial cells, etc. They are named small-conductance Ca2+ -activated potassium channels (SK channels) due to their comparatively low single-channel conductance of about ~10 pS. These channels are insensitive to changes in membrane potential and are activated solely by rises in the intracellular Ca2+ . According to the phylogenic research done on the KCa 2.x channels family, there are three channels' subtypes: KCa 2.1, KCa 2.2, and KCa 2.3, which are encoded by KCNN1, KCNN2, and KCNN3 genes, respectively. The KCa 2.x channels regulate neuronal excitability and responsiveness to synaptic input patterns. KCa 2.x channels inhibit excitatory postsynaptic potentials (EPSPs) in neuronal dendrites and contribute to the medium afterhyperpolarization (mAHP) that follows the action potential bursts. Multiple brain regions, including the hippocampus, express the KCa 2.2 channel encoded by the KCNN2 gene on chromosome 5. Of particular interest, rat cerebellar Purkinje cells express KCa 2.2 channels, which are crucial for various cellular processes during development and maturation. Patients with a loss-of-function of KCNN2 mutations typically exhibit extrapyramidal symptoms, cerebellar ataxia, motor and language developmental delays, and intellectual disabilities. Studies have revealed that autosomal dominant neurodevelopmental movement disorders resembling rodent symptoms are caused by heterozygous loss-of-function mutations, which are most likely to induce KCNN2 haploinsufficiency. The KCa 2.2 channel is a promising drug target for spinocerebellar ataxias (SCAs). SCAs exhibit the dysregulation of firing in cerebellar Purkinje cells which is one of the first signs of pathology. Thus, selective KCa 2.2 modulators are promising potential therapeutics for SCAs.


Molecular dynamics simulations of linear and cyclic amphiphilic polymers in aqueous and organic environments.
We have studied the conformational changes of two novel amphiphilic homopolymers in water and toluene relevant to delivery applications using molecular dynamics simulations supplemented with enhanced sampling techniques. The individual homopolymer repeating units are amphiphilic with a hydrophobic dodecyl chain and a hydrophilic tetra(ethylene glycol) chain attached via ether linkages to each repeating unit of the polymer backbone. Two polymer topologies were examined: one cyclic and one an exact linear analog. Here we show that these polymers exhibit highly dynamic conformations with the side arm orientations driven by the solvent polarity. In water these polymers exhibit a compact conformation with the hydrophobic arms retracted toward the backbone core, whereas in toluene the hydrophobic arms extended into the solvent. Different from the hydrophobic arms, the hydrophilic ethylene glycol chain orientations and backbone conformations are largely unperturbed by the solvent polarity. Probing the polymer microenvironment in different solvents to examine solute uptake supports the hypothesis that these polymers can selectively encapsulate/release guest molecules depending on the solvent polarity, highlighting the potential of these polymers as drug delivery vehicles.


The dose-response effect in routinely delivered psychological therapies: A systematic review.
The dose-response effect refers to the relationship between the dose (e.g., length, frequency) of treatment and the subsequent probability of improvement. This systematic review aimed to synthesize the literature on the dose-response effect in routine psychological therapies delivered to adult patients with mental health problems. Twenty-six studies were eligible for inclusion. Different methodological approaches have been used to examine the dose-response effect; including survival analysis, multilevel modelling and descriptive cluster analyses. Replicated and consistent support was found for a curvilinear (log-linear or cubic) relationship between treatment length and outcomes, with few exceptions such as eating disorders and severe psychiatric populations. Optimal doses of psychotherapy in routine settings range between 4 and 26 sessions (4-6 for low intensity guided self-help) and vary according to setting, clinical population and outcome measures. Weekly therapy appears to accelerate the rate of improvement compared to less frequent schedules. Most of the reviewed evidence is from university counselling centres and outpatient psychotherapy clinics for common mental health problems. There is scarce and inconclusive evidence in clinical samples with chronic and severe mental disorders.


Multimodal Disentangled Variational Autoencoder With Game Theoretic Interpretability for Glioma Grading.
Effective fusion of multimodal magnetic resonance imaging (MRI) is of great significance to boost the accuracy of glioma grading thanks to the complementary information provided by different imaging modalities. However, how to extract the common and distinctive information from MRI to achieve complementarity is still an open problem in information fusion research. In this study, we propose a deep neural network model termed as multimodal disentangled variational autoencoder (MMD-VAE) for glioma grading based on radiomics features extracted from preoperative multimodal MRI images. Specifically, the radiomics features are quantized and extracted from the region of interest for each modality. Then, the latent representations of variational autoencoder for these features are disentangled into common and distinctive representations to obtain the shared and complementary data among modalities. Afterwards, cross-modality reconstruction loss and common-distinctive loss are designed to ensure the effectiveness of the disentangled representations. Finally, the disentangled common and distinctive representations are fused to predict the glioma grades, and SHapley Additive exPlanations (SHAP) is adopted to quantitatively interpret and analyze the contribution of the important features to grading. Experimental results on two benchmark datasets demonstrate that the proposed MMD-VAE model achieves encouraging predictive performance (AUC:0.9939) on a public dataset, and good generalization performance (AUC:0.9611) on a cross-institutional private dataset. These quantitative results and interpretations may help radiologists understand gliomas better and make better treatment decisions for improving clinical outcomes.


An impenetrable barrier to ultrarelativistic electrons in the Van Allen radiation belts.
Early observations indicated that the Earth's Van Allen radiation belts could be separated into an inner zone dominated by high-energy protons and an outer zone dominated by high-energy electrons. Subsequent studies showed that electrons of moderate energy (less than about one megaelectronvolt) often populate both zones, with a deep 'slot' region largely devoid of particles between them. There is a region of dense cold plasma around the Earth known as the plasmasphere, the outer boundary of which is called the plasmapause. The two-belt radiation structure was explained as arising from strong electron interactions with plasmaspheric hiss just inside the plasmapause boundary, with the inner edge of the outer radiation zone corresponding to the minimum plasmapause location. Recent observations have revealed unexpected radiation belt morphology, especially at ultrarelativistic kinetic energies (more than five megaelectronvolts). Here we analyse an extended data set that reveals an exceedingly sharp inner boundary for the ultrarelativistic electrons. Additional, concurrently measured data reveal that this barrier to inward electron radial transport does not arise because of a physical boundary within the Earth's intrinsic magnetic field, and that inward radial diffusion is unlikely to be inhibited by scattering by electromagnetic transmitter wave fields. Rather, we suggest that exceptionally slow natural inward radial diffusion combined with weak, but persistent, wave-particle pitch angle scattering deep inside the Earth's plasmasphere can combine to create an almost impenetrable barrier through which the most energetic Van Allen belt electrons cannot migrate.


Lanthanum carbonate is an effective hypophosphatemic agent for hemodialysis patients intolerant of other phosphate binders.
Lanthanum carbonate (LC) is a noncalcium-containing phosphate binder of proven utility in treating hyperphosphatemia in dialysis patients, and displays a good tolerability profile. This study addressed whether this tolerability profile could result in improved phosphate control in patients intolerant of other phosphate binders, and who remain hyperphosphatemic despite intensive dietary advice and adequate dialysis provision. This 18-month study, from a large urban hemodialysis unit, studied 55 patients identified by the multidisciplinary team as fulfilling the following criteria: persistent hyperphosphatemia; intolerance of, or admitted nonadherence to, prescribed phosphate binders (either calcium-based or sevelamer); and provision of adequate dialysis (urea reduction ratio, >65%). LC was substituted for existing phosphate binders, and results were compared between baseline and 3 months after the initiation of LC. A significant fall in phosphate level from 2.28+/-0.55mmol/L to 1.89+/-0.45mmol/L (7.06+/-1.70mg/dL to 5.85+/-1.39mg/dL) was evident 3 months after the medication switch (P < .001). This fall was associated with a significant increase in the number of patients achieving United Kingdom Renal Association guidelines for serum phosphate level (17% to 48%; P=.001). Mean phosphate-binder pill burden fell significantly by 3 months after the initiation of LC, from 7.8+/-3.4 tablets daily to 3.6+/-2.3 tablets daily. A small but significant increase also occurred in serum bicarbonate levels, from 23.3+/-2.2mmol/L (23.3+/-2.2 mEq/L) at baseline to 23.9+/-2.5mmol/L (23.9+/-2.5 mEq/L) at 3 months (P=.03). This was observed despite a prescribed reduction in dialysate bicarbonate concentration across the population (P=.03). This study demonstrated the utility of LC in hemodialysis patients intolerant of alternative phosphate binders, and suggests an advantage of this agent in this patient group.


[Studies of potassium channel in pulmonary artery smooth muscle cells derived from renal hypertensive rat].
To investigate the differences of membrane capacitance, membrane current, current density and I-V curves between smooth muscle cells isolated from RHR and NTR pulmonary arteries. Under antiseptic conditions, the left renal artery was exposed through a retroperitoneal flank incision and carefully dissected free of the left renal vein. A silver clip with an internal diameter of 0.2-0.3 mm was placed around the left renal artery, resulting in partial occlusion of renal perfusion. SBP was observed by tail blood pressure. Whole cell recordings were made from smooth muscle cells freshly isolated from pulmonary arteries derived from RHR or NTR. The average membrane capacitance was (3.43 +/- 1.16) pF, decreased by 31.1%; membrane current was (0.54 +/- 0.26) nA, decreased by 68.2%; current density was (180 +/- 90) pA/pF, decreased by 48.6%; membrane potential was (-26.96 +/- 7.23) mV, decreased by 2.5%, all compared with that of NTR respectively. Iptakalim hydrochloride at the concentration of 0.1-100 micromol/L can significantly increased NTR potassium currents. Iptakalim hydrochloride 1-100 micromol/L can significantly increased RHR potassium currents. Membrane capacitance, membrane current, membrane potential were decreased, I-V curves were shift downward, compared with that of NTR. Iptakalim hydrochloride might significantly increase NTR and RHR potassium currents.


Evaluation of topical polyinosinic acid-polycytidylic acid in treatment of localized herpes zoster in children with cancer: a randomized, double-blind controlled study.
Twenty-four children with cancer and localized herpes zoster were randomized to receive either topical polyinosinic acid-polycytidylic acid [poly(I:C)] or a saline placebo. Solutions containing 1.0 or 2.5 mg of drug per ml were applied to the lesions every 3 h, seven times a day for 7 consecutive days. Serial, standardized color photographs were used to evaluate the progression of lesions and maximum percentage of dermatome involvement. In patients receiving poly(I:C), the median days of new lesions after therapy was 2.0 days as opposed to 3.5 days in placebo-treated patients. This difference was not statistically significant. Moreover, the total median days of lesions and percentage of dermatome involvement were similar in both groups, as were complications. Neither the concentration nor the total dose of drug was related to the outcome of infection. We conclude that topical poly(I:C), as used in this study, was of no benefit in treatment of localized herpes zoster.


Mastocytosis and Hymenoptera allergy.
Mastocytosis is a rare disease with associations with anaphylactic reactions to Hymenoptera stings. The purpose of this review is to examine these associations with regard to prevalence, diagnosis, treatment and prognosis in the insect-venom-allergic population. Systemic mastocytosis is overrepresented in the Hymenoptera-allergic population and is associated with an increased risk of more-severe reactions following field stings or sting challenges, lack of sensitization to venoms by skin test or radioallergosorbent test, increased side effects to venom immunotherapy, reduced efficacy of venom immunotherapy and treatment failures. Serum tryptase determinations are a simple and reliable screening procedure for systemic mastocytosis. Patients with elevated values should be referred to specialized centers for confirmatory diagnosis including bone marrow histology. The diagnosis of systemic mastocytosis should be considered in Hymenoptera-allergic patients showing any of the management problems associated with this disease. Patients with mastocytosis and Hymenoptera allergy require special attention, mainly because of reduced safety and efficacy of venom immunotherapy. Whether or not venom immunotherapy is given, such patients should continue to carry an Epipen indefinitely.


The efficacy of abatacept in Japanese patients with rheumatoid arthritis: 104 weeks radiographic and clinical results in clinical practice.
We aimed to assess the efficacy of abatacept in Japanese patients with rheumatoid arthritis (RA) in clinical practice. We examined 92 patients who received abatacept for 104 weeks. Analysis of radiographic efficacy was conducted using van der Heijde-modified total Sharp score (mTSS). Disease activity score was assessed using disease activity score in 28 joints (DAS28) and simplified disease activity index (SDAI) by last observation carried forward. The change in mTSS was 0.61 at 52 weeks and 0.27 at 52-104 weeks. Structural remission occurred in 64.9% at 52 weeks and 76.6% at 104 weeks. The significant risk factors for joint damage progression at 52 weeks were prednisolone use, baseline C-reactive protein level (CRP), and erythrocyte sedimentation rate (ESR), as well as average DAS28-CRP and DAS28-ESR scores, SDAI, CRP, ESR, and matrix metalloproteinase-3 (MMP-3) levels. The clinical remission rates were 47.8% by DAS28-CRP, 39.1% by DAS28-ESR, and 30.4% by SDAI at 52 weeks, were 59.8% by DAS28-CRP, 48.9% by DAS28-ESR, and 43.5% by SDAI at 104 weeks. This study suggested efficacy of abatacept treatment in Japanese patient with RA for 104 weeks in daily clinical practice. Abatacept lead to suppress joint destruction for 104 weeks.


Left atrial appendage occlusion: A better alternative to anticoagulation?
Non-valvular atrial fibrillation is associated with a significantly increased risk of embolic stroke due to blood clot forming predominantly in the left atrial appendage (LAA). Preventive measures to avoid embolic events are permanent administration of anticoagulants or surgical closure of the LAA. Various clinical trials provide evidence about safety, effectiveness and therapeutic success of LAA occlusion using various cardiac occluder devices. The use of such implants for interventional closure of the LAA is likely to become a valuable alternative for stroke prevention, especially in patients with contraindication for oral anticoagulation as safety, clinical benefit and cost-effectiveness of LAA occlusion has recently been demonstrated.


A study on the anisole-water complex by molecular beam-electronic spectroscopy and molecular mechanics calculations.
An experimental and theoretical study is made on the anisole-water complex. It is the first van der Waals complex studied by high resolution electronic spectroscopy in which the water is seen acting as an acid. Vibronically and rotationally resolved electronic spectroscopy experiments and molecular mechanics calculations are used to elucidate the structure of the complex in the ground and first electronic excited state. Some internal dynamics in the system is revealed by high resolution spectroscopy.


Theory of radon exhalation into accumulators placed at the soil-atmosphere interface.
A theoretical analysis is provided for the phenomenon of radon diffusion into cylindrical accumulators (inverted cups), which are commonly used for the measurement of radon exhalation rates from the earth's surface. Analytical solutions to the diffusion equations in the soil and the cup spaces are obtained by a two-dimensional (2-D) analysis that takes into account the perturbation in the horizontal and vertical radon concentration profiles brought about by the presence of the cup. The mixed nature of the boundary conditions at the soil surface and the cup-soil interface is handled by dual integral equation techniques. The treatment includes steady-state and time-dependent situations with and without ventilation. Formulae are derived for the effective time constant of radon build-up in the cup and for the back diffusion correction factors in different experimental situations. It is found that the effective time constant of radon build-up is much larger than the radon decay constant and it increases for smaller cups. The back diffusion correction factors to be employed in one-time measurement methods also increase as the cup dimensions decrease. The present work provides an analytical basis of an earlier numerical treatment for the growth curve analysis of the same problem. Although the results are based on the assumptions of somewhat ideal nature for mathematical tractability, they provide upper bound estimates of the phenomenon of back diffusion. Some practical applications of the results for extracting diffusion length of radon in materials are also suggested.


Characteristics and distribution of somatosensory evoked potentials in the subthalamic region.
The aim of the present study is to evaluate the topographical distribution of somatosensory evoked potentials (SSEPs) in the subthalamic area, including the zona incerta (ZI). Determination of this distribution may help in the correct placement of deep brain stimulation (DBS) leads. Intraoperative SSEPs were recorded from contacts of DBS electrodes at 221 sites in 41 patients: three patients with essential tremor and 38 with Parkinson disease who underwent implantation of DBS electrodes for the relief of severe tremor or parkinsonism. Two distinct SSEPs were recorded in the subthalamic area. One was a monophasic positive wave with a mean latency of 15.8 +/- 0.9 msec, which the authors designated subthalamic P16. Using both cephalic and noncephalic references, subthalamic P16 was only recorded in the ventral part of the ZI (mean 6.6 +/- 1.3 mm posterior to the midcommissure point, 4.8 +/- 1.2 mm inferior to the anterior commissure-posterior commissure line, and 9.7 +/- 0.6 mm lateral to the midline). When bipolar recordings were made, the traces showed a phase reversal at the caudal part of the ZI. The second potential is a positive-negative SSEP recorded throughout the entire subthalamic area. The mean latencies of the initial positive peak and the major negative peak were 13.6 +/- 1.1 msec and 16.4 +/- 1.1 msec, respectively. Several small notches were superimposed on the peaks, and their amplitudes were largest at the contact close to the medial lemniscus. The results indicate that intraoperative SSEPs from DBS electrodes are helpful in refining stereotactic targets in the thalamus and subthalamic areas.


Common variants in CACNA1C and MDD susceptibility: A comprehensive meta-analysis.
Major depressive disorder (MDD) is one of the most common psychiatric disorders with a relatively high heritability (35-40%). Though rs1006737 in the CACNA1C gene showed significant association with MDD in a British large-scale candidate association study, most of the replication analyses with relatively small sample size reported negative association. Moreover, this locus has never been identified in previous genome-wide association studies (GWAS) for MDD. Here, we conducted a comprehensive meta-analysis of the association between CACNA1C variants and MDD risk by combining all published data. Genetic data from one European GWAS and five individual follow-up studies, which include up to 12,629 patients of MDD and 28,653 controls, that is, the largest sample size on CACNA1C to date, were collected. Rs1006737 showed significant association with MDD in the fixed-effect model (Z = 2.56, P = 0.011, OR = 1.08, 95%CI = 1.04-1.12) and the association remained after reanalyzing the data according to ethnicity. We additionally analyzed other 25 SNPs, genotyped in only one replication study, across the CACNA1C locus, and found that two SNPs, rs4765905 (P = 0.041, OR = 1.05, 95%CI 1.00-1.09) and rs4765937 (P = 0.025, OR = 1.05, 95%CI 1.01-1.09) showed nominal association with MDD, while rs2239073 (P = 0.002, OR = 1.07, 95%CI 1.02-1.11) exhibited significant association with MDD, which survived from multiple corrections. Our study provides support for positive association between CACNA1C and MDD; however, the current data suggest the necessity of replication analyses in a larger-scale sample. © 2016 Wiley Periodicals, Inc.


Processes and outcomes in prevention-focused time-limited groups for girls.
Processes and outcomes in 8-week prevention-focused, school-based groups for preadolescent girls were assessed in a naturalistic study. Specifically, whether such groups would facilitate their social-emotional development and whether affiliative processes in the groups were related to outcome were explored. In addition to expecting the groups to be effective, it was hypothesized that affiliative processes would be directly related to outcome and, more particularly, that increased positive affiliative feelings from the group toward the individual would be more predictive of positive treatment outcome than increased positive feelings from the individual toward the group. While findings did not support these hypotheses linking process to outcome, ancillary analyses revealed that different patterns of affiliation over time (i.e., U-shape pattern versus inverted U-shape pattern) distinguished the high- versus low-outcome participants, respectively.


[Shuxuening injection combined with routine therapy in treating patients with active ulcerative colitis: an analysis of efficacy ].
To observe the therapeutic effect and relevant mechanism of shuxuening Injection (SI) in treating patients with active ulcerative colitis (UC). Totally 91 patients with active UC were randomly assigned to 2 groups, 44 in the control group and 47 in the treatment group. Patients in the control group received routine treatment, while patients in the treatment group additionally received intravenous injection of SI (15 mL), twice daily for 14 days in total. Colonoscopy was performed before and after treatment. The therapeutic effect was assessed by Mayo scoring system and the grading of activities evaluated by Baron endoscope. Serum levels of IL-6 and TNF-α were detected by ELISA. The activity of SOD was detected by xanthine oxidase method. The content of MDA was detected by thiobarbituricacid (TBA). Besides, 20 healthy subjects were recruited as the healthy control group. Totally 82 patients completed the study (40 in the control group and 42 in the treatment group). There was no statistical difference in serum levels of IL-6, TNF-α, SOD, MDA, the Mayo score and endoscope grading between the two groups before treatment (P >0. 05). Compared with the healthy control group, serum levels of IL-6, TNF-α, MDA significantly increased (P <0.01), and the serum SOD level decreased (P < 0. 05) in the treatment grup and the control group before treatment. Compared with before treatment in the same group, serum levels of IL-6, TNF-α, MDA, the Mayo score and endoscope grading all decreased in the treatment group and the control group after treatment (P <0. 01, P <0. 05). Compared with the control group after treatment, serum levels of IL-6, TNF-α, MDA, the Mayo score and endoscope grading all decreased (P <0.01, P <0.05), the serum SOD level increased (P <0.05) in the treatment group after treatment. The serum SOD level was obviously negative correlated with serum levels of IL-6, TNF-a, Mayo score, and endoscope score (r = -0. 621, -0.638, -0. 509, -0.787, P <0.01). The serum MDA level was obviously positive correlated with serum levels of IL-6, TNF-α, Mayo score, and endoscope score (r =0.711, 0. 882, 0. 525, 0. 639, P <0.01). SI could improve inflammatory injury and clinical symptoms of patients with active UC, and its mechanism might be associated with antioxidant and scavenging oxygen free radicals.


Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: a role for GH in early embryogenesis?
The results of this study challenge the widely held view that growth hormone (GH) acts only during the postnatal period. RNA phenotyping shows transcripts for the GH receptor and GH-binding protein in mouse preimplantation embryos of all stages from fertilized eggs (day 1) to blastocysts (day 4). An antibody specific to the cytoplasmic region of the GH receptor revealed receptor protein expression, first in two-cell embryos, the stage of activation of the embryonic genome (day 2), and in all subsequent stages. In cleavage-stage embryos this immunoreactivity was localized mainly to the nucleus, but clear evidence of membrane labeling was apparent in blastocysts. GH receptor immunoreactivity was also observed in cumulus cells associated with unfertilized oocytes but not in the unfertilized oocytes. The blastocyst receptor was demonstrated to be functional, exhibiting the classic bell-shaped dose-response curves for GH stimulation of both 3-O-methyl glucose transport and protein synthesis. Maximal stimulation of 40-50% was seen for both responses at less than 1 ng/ml recombinant GH, suggesting a role for maternal GH. However mRNA transcripts for GH were also detected from the morula stage (day 3) by using reverse transcription-PCR, and GH immunoreactivity was seen in blastocysts. These observations raise the possibility of a paracrine/autocrine GH loop regulating embryonic development in its earliest stages.


Bronchioloalveolar lavage in the diagnosis of CMV pneumonitis in lung transplant recipients: an immunocytochemical study.
Cytomegalovirus (CMV) pneumonitis is a common opportunistic infection in lung transplant recipients. Its diagnosis usually rests on the identification of viral inclusions in lung parenchyma obtained by transbronchial biopsy, or by examination of the cytologic material obtained by bronchioloalveolar lavage (BAL). To determine whether the use of immunocytochemistry (ICC) increases the sensitivity of cytology in the diagnosis of CMV pneumonitis, we retrospectively selected 17 cases in which transbronchial biopsy and BAL were performed simultaneously, and had positive histology with negative cytology. Five negative controls were selected. The 22 slides were decolorized and restained with ICC for CMV. Of the 17 slides, nine (53%) showed cells with positive nuclear staining. All controls were negative. These results were then correlated with the number of infected cells present in the biopsy tissue, and the location of the cells (interstitial vs. intraalveolar). A good correlation was found between positive cytology and intraalveolar location of infected cells, and no correlation was seen between number of infected cells in the biopsy and the positive cytology. In summary, although histologic evaluation of lung parenchyma obtained by transbronchial biopsy is more sensitive for diagnosis of CMV pneumonitis, the sensitivity of the cytologic evaluation of BAL material can be increased by the use of ICC. The likelihood of positive ICC seems to be related to the presence of infected cells in the alveolar space rather than to the number of infected cells.


Using the Idexx SediVue Dx to predict the need for urine bacteriologic culture in cats.
We analyzed urine samples from 191 cats for bacteriuria with an automated urine sediment analyzer (Idexx SediVue Dx), combined with image review by an observer, and compared to bacteriologic culture results. Sixty-nine samples were unambiguously assigned to be free of bacteria by the instrument and the observer, and no bacterial growth was detected. Twenty-seven samples were unambiguously assigned to have bacteriuria; 24 of these 27 samples were culture-positive. For these samples, bacteriuria was predicted with a sensitivity of 100% and a specificity of 96%. A clear assignment was not possible for 95 samples, 81 of which were culture-negative. Specificity dropped to 45% when all samples were considered. Using the automated leukocyte count to predict bacteriuria, sensitivity was 82% and specificity was 75%. Automated sediment analysis is faster and less observer-dependent than sediment analysis under a microscope, but accurate detection of bacteriuria remains difficult in a large proportion of samples. Bacteriuria was significantly associated with leukocyte count; the leukocyte count was >5/high power field in 82% of culture-positive samples.


Effects of High and Low Salt Concentrations in Electrolytes at Lithium-Metal Anode Surfaces Using DFT-ReaxFF Hybrid Molecular Dynamics Method.
Due to creating a passivated solid electrolyte interphase (SEI), high concentration (HC) electrolytes demonstrate peculiar physicochemical properties and outstanding electrochemical performance. However, the structures of such SEI remains far from clear. In this work, a hybrid ab initio and reactive molecular dynamics (HAIR) scheme is employed to investigate the concentration effect of SEI formation by simulating the reductive degradation reactions of lithium bis(fluorosulfonyl)imide (LiFSI) in 1,3 dioxalane (DOL) electrolytes at concentrations of 1 M, 4 M, and 10 M. The efficient HAIR scheme allows the simulations to reach 1 ns to predict electrolytes' deep products at different concentrations. The simulation findings show that the most critical distinction between HC and its low concentration (LC) analogue is that anion decomposition in HC is much more incomplete when only S-F breaking is observed. These insights are important for the future development of advanced electrolytes by rational design of electrolytes.


The RNA-binding protein RBPMS2 regulates development of gastrointestinal smooth muscle.
Gastrointestinal development requires regulated differentiation of visceral smooth muscle cells (SMCs) and their contractile activities; alterations in these processes might lead to gastrointestinal neuromuscular disorders. Gastrointestinal SMC development and remodeling involves post-transcriptional modification of messenger RNA. We investigated the function of the RNA-binding protein for multiple splicing 2 (RBPMS2) during normal development of visceral smooth muscle in chicken and expression of its transcript in human pathophysiological conditions. We used avian replication-competent retroviral misexpression approaches to analyze the function of RBPMS2 in vivo and in primary cultures of chicken SMCs. We analyzed levels of RBPMS2 transcripts in colon samples from pediatric patients with Hirschsprung's disease and patients with chronic pseudo obstruction syndrome (CIPO) with megacystis. RBPMS2 was expressed strongly during the early stage of visceral SMC development and quickly down-regulated in differentiated and mature SMCs. Misexpression of RBPMS2 in differentiated visceral SMCs induced their dedifferentiation and reduced their contractility by up-regulating expression of Noggin, which reduced activity of bone morphogenetic protein. Visceral smooth muscles from pediatric patients with CIPO expressed high levels of RBPMS2 transcripts, compared with smooth muscle from patients without this disorder. Expression of RBPMS2 is present in visceral SMC precursors. Sustained expression of RBPMS2 inhibits the expression of markers of SMC differentiation by inhibiting bone morphogenetic protein activity, and stimulates SMC proliferation. RBPMS2 transcripts are up-regulated in patients with CIPO; alterations in RBPMS2 function might be involved in digestive motility disorders, particularly those characterized by the presence of muscular lesions (visceral myopathies).


The effect of prolonged ethanol administration and its withdrawal on catecholamine turnover in the rat brain.
Dopamine (DA) and noradrenaline (NA) levels and their turnover were determined in the rat brain after seven weeks of oral administration of ethanol and five or ten days after its withdrawal. No changes in DA and NA levels were found. Elevation of 14C-DA and 14C-NA accumulation and acceleration of 3H-DA disappearance were shown after prolonged ethanol administration. The effect of ethanol on NA turnover was much smaller than that on DA turnover. Five days after ethanol withdrawal no changes were found in DA and NA turnover. Five days later DA turnover was slightly slower than that in the control animals.


A Qualitative View of Homecare Support Workers on Unmet Health Needs of People with Dependency.
Longevity and population growth generate an increase in the number of people with dependency, who require homecare assistance to meet their health needs. Homecare support workers provide this care in Spain, and they may have unique insights into the unmet health needs of those receiving homecare assistance. The aim of this study was to determine the unmet health needs of people with dependency based on the perspective of homecare support workers. Qualitative exploratory-descriptive study. Through convenience sampling, homecare support workers from a Spanish province were selected, following inclusion and exclusion criteria. Four focus groups, transcription and thematic analyses were performed using Atlas.ti. Coding triangulation was carried out, applying criteria for scientific rigour. The six themes obtained were classified into the material, psychoemotional, socioeconomical and psychosocial needs of people with dependency from the point of view of homecare support workers, along with the contributions of improvements and the need of these professionals for continuous training. People with dependency need complex technical assistance, materials, psychological attention due to their situation, and more effective assessments of their health and disability status. Homecare support workers perceive themselves to be essential in these assessments. They ask for psychological assistance, due to the emotional burden of their work, and believe this help would contribute to improving the quality of their service. Homecare support workers perceive that they are capable of performing their job, although they believe that some delegated activities are beyond their levels of competency.


Assessment of Thrombotic Risk in Atrial Fibrillation with Ultrasound Molecular Imaging of P-Selectin.
Molecular imaging of inflammatory mediators in atria may contribute to thrombotic risk assessment of atrial fibrillation (AF). We investigated the feasibility of ultrasound molecular imaging (UMI) targeted to P-selectin to assess thrombotic risk in AF. Rat AF models were established with rapid atrial pacing. Microbubbles targeted to P-selectin were injected into the rats, followed by left atrial (LA) UMI examination. Furthermore, P-selectin, platelets (PLTs), fibrin and tissue factor (TF) of LA were detected by histopathology and scanning electron microscopy. Plasma levels of P-selectin, thrombin-antithrombin complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2) were measured by enzyme-linked immunosorbent assay. The data showed that P-selectin in LA was correlated with PLT, fibrin and TF (r = 0.735, p < 0.05; r = 0.827, p < 0.05; r = 0.785, p < 0.05, respectively). The plasma level of P-selectin was correlated with the expression of TAT and F1 + 2 (r = 0.866, p < 0.05; r = 0.916, p < 0.05, respectively). The contrast video intensity of adhered microbubbles targeted to P-selectin was correlated with the levels of P-selectin, PLT and fibrin in LA (r = 0.768, p < 0.05; r = 0.798, p < 0.05; r = 0.745, p < 0.05, respectively). In conclusion, P-selectin may serve as a biomarker for thrombotic risk in AF and can be quantified by UMI to assess thrombotic risk.


Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.
The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.


Measurement system for respiratory water vapor and temperature dynamics.
An instrumentation system has been developed to simultaneously measure water vapor and temperature at the same point within respiratory airways during breathing. A mass spectrometer was used to analyze gas continuously sampled through a modified inlet catheter. At the tip of the catheter, gas temperature is sensed by a microbead thermistor. Adequate water vapor dynamics is achieved by a two-step procedure. First, the tip of the sampling catheter is constricted to reduce the catheter's internal pressure and thereby prevent condensation and evaporation. Second, the water vapor signal from the mass spectrometer is compensated electronically to improve its transient response. As part of the evaluation of the system, water vapor and gas temperature were measured in the oropharynx of human subjects.


Identification of the amino acids inserted during suppression of CFTR nonsense mutations and determination of their functional consequences.
In-frame premature termination codons (PTCs) account for ∼11% of all disease-associated mutations. PTC suppression therapy utilizes small molecules that suppress translation termination at a PTC to restore synthesis of a full-length protein. PTC suppression is mediated by the base pairing of a near-cognate aminoacyl-tRNA with a PTC and subsequently, the amino acid becomes incorporated into the nascent polypeptide at the site of the PTC. However, little is known about the identity of the amino acid(s) inserted at a PTC during this process in mammalian cells, or how the surrounding sequence context influences amino acid incorporation. Here, we determined the amino acids inserted at the cystic fibrosis transmembrane conductance regulator (CFTR) W1282X PTC (a UGA codon) in the context of its three upstream and downstream CFTR codons during G418-mediated suppression. We found that leucine, cysteine and tryptophan are inserted during W1282X suppression. Interestingly, these amino acids (and their proportions) are significantly different from those recently identified following G418-mediated suppression of the CFTR G542X UGA mutation. These results demonstrate for the first time that local mRNA sequence context plays a key role in near-cognate aminoacyl-tRNA selection during PTC suppression. We also found that some variant CFTR proteins generated by PTC suppression exhibit reduced maturation and activity, indicating the complexity of nonsense suppression therapy. However, both a CFTR corrector and potentiator enhanced activity of protein variants generated by G418-mediated suppression. These results suggest that PTC suppression in combination with CFTR modulators may be beneficial for the treatment of CF patients with PTCs.


Cavity-Assisted Single-Mode and Two-Mode Spin-Squeezed States via Phase-Locked Atom-Photon Coupling.
We propose a scheme to realize the two-axis countertwisting spin-squeezing Hamiltonian inside an optical cavity with the aid of phase-locked atom-photon coupling. By careful analysis and extensive simulation, we demonstrate that our scheme is robust against dissipation caused by cavity loss and atomic spontaneous emission, and it can achieve significantly higher squeezing than one-axis twisting. We further show how our idea can be extended to generate two-mode spin-squeezed states in two coupled cavities. Because of its easy implementation and high tunability, our scheme is experimentally realizable with current technologies.


Drug candidates in clinical trials for Alzheimer's disease.
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation. The lowered concentrations of acetylcholine (ACh) in AD result in a progressive and significant loss of cognitive and behavioral function. Current AD medications, memantine and acetylcholinesterase inhibitors (AChEIs) alleviate some of these symptoms by enhancing cholinergic signaling, but they are not curative. Since 2003, no new drugs have been approved for the treatment of AD. This article focuses on the current research in clinical trials targeting the neuropathological findings of AD including acetylcholine response, glutamate transmission, Aβ clearance, tau protein deposits, and neuroinflammation. These investigations include acetylcholinesterase inhibitors, agonists and antagonists of neurotransmitter receptors, β-secretase (BACE) or γ-secretase inhibitors, vaccines or antibodies targeting Aβ clearance or tau protein, as well as anti-inflammation compounds. Ongoing Phase III clinical trials via passive immunotherapy against Aβ peptides (crenezumab, gantenerumab, and aducanumab) seem to be promising. Using small molecules blocking 5-HT6 serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials. We here systemically review the findings from recent clinical trials to provide a comprehensive review of novel therapeutic compounds in the treatment and prevention of AD.


All voices matter in experience design: A commitment to action in engaging patient and family voice.
This article intends to frame the broader concept of experience design and the engagement of patient and family voice, reinforcing how truly aligned healthcare professionals are not only on the value of this work but also in understanding the benefits of it. When addressing the idea of design, it is important to look at the broadest possible construct and consider the engagement of patient and family voices in healthcare operational efforts, not as passive advisors but as active participants in data gathering, providing input, and with actual decision-making. The article offers engagement is not just part of process, facility, or experience design but must be part of the decisions made in how organizations in healthcare today are built, led, and sustained, fundamentally reinforcing our opportunity in healthcare is to focus on overall experience with purpose and intention. This commitment is what will lead to the outcomes all ultimately hope to achieve.


[Education and life long learning].
In this article the term "lifelong learning" is discussed in detail from a pedagogic perspective. Lifelong learning is seen as an integral part of "competence" and of mastering different developmental tasks in old age. Moreover, it is seen as a component of "education". Education comprises not only the acquisition of knowledge, but is understood to develop strategies and competence for coping with tasks and crises. This is illustrated in discussing theoretical models of critical life events and developmental tasks.


Dorsomedial diencephalic involvement in the juvenile play of rats.
Lesions of either the dorsomedial thalamus (DMT) or the parafascicular region of the thalamus (PFA) reduced rough-and-tumble social play in juvenile rats, as measured by frequency of pinning. Pinning was reduced by 33% in pups with DMT lesions and by 73% in pups with PFA lesions. Although PFA lesions had minimal effects on average pin durations, DMT pups had pins that were, on average, 105% longer than those of controls. Lesions of the PFA, but not DMT, also reduced play solicitation behaviors. Pups with PFA lesions were also insensitive to the play modulating effects of both naloxone and morphine. DMT pups were sensitive to the facilitatory effects of morphine, but naloxone was without effect in these animals. Control studies designed to evaluate general behavioral competence showed that the observed lesion effects were relatively specific to play.


The normal distribution in scaling subjective stimulus differences: less "normal" than we think?
The Gaussian, or "normal," distribution is routinely used to model distributions of subjective quantities. This practice rests on a trust in the central limit theorem, yet this theorem does not cover the case of a mixture of Gaussian distributions with different standard deviations, which yields a distribution that is heavier tailed than the Gaussian. In psychophysical judgment experiments, this may result, for example, from fluctuating or interindividually varying attention. Two candidates for describing this commonly encountered type of distribution are the logistic distribution and the t distribution with a small number of degrees of freedom. In reanalyses of experimental data on three-category loudness comparisons, as well as in a Monte Carlo simulation, t(4) was found to model the underlying mixed inter- and intraindividual distribution of subjective loudness differences quite satisfactorily.


Small bowel feces sign in association with occlusive mesenteric ischemia.
Small bowel feces sign (SBFS) is a computed tomography (CT) finding that appears as fecal like material in dilated small bowel loops. This sign is usually seen in association with gradually progressive small bowel obstruction. We present a case of occlusive mesenteric ischemia in which the SBFS appeared on CT scan early on in the course of the disease. We put forward a suggested alternative mechanism to the appearance of this sign in association with mesenteric ischemia. The SBFS might have the potential to serve as an early sign of mesenteric ischemia on CT scan.


REtrospective Multicenter INdian Study of Derivo Embolization Device (REMIND): Periprocedural Safety.
The treatment of aneurysms with characteristics such as complex morphology, fusiform, blister-like, wide neck, or large size has been revolutionized with the introduction of flow diverters. Though flow diverters have several advantages over coiling, they also have certain important disadvantages such as the lack of immediate protection against rupture, the risk of ischemic stroke, the need for antiplatelet therapy, and long latency for complete effect. The Derivo Embolization Device (DED) is a second-generation self-expanding device that is claimed to be less thrombogenic than conventional devices. We retrospectively evaluated the periprocedural safety and risks associated with the DED across 5 centers in India. This is a multicentric, retrospective, observational study of DED, conducted at 5 high volume endovascular therapy centers in India from May 2018 to June 2020. Periprocedural demographic, clinical, and angiographic data were collected from a retrospective review of patient charts. A total of 96 patients, including 56 (58.3%) females, aged between 16-80 years (60±12.7 years) harboring 106 aneurysms were studied. Seven (7.3%) were noted to harbor multiple aneurysms: 6 had 3 aneurysms each, while 1 patient had 5 aneurysms. The following aneurysm characteristics were noted: average size, 9.8±8.2 mm; average neck size, 6.9±8.5 mm; wide-necked (>4 mm), 63 (59.4%); giant (>25 mm), 8 (7.5%); and anterior circulation location, 98 (92.5%). Eighteen (17%) of these were ruptured. Additional balloon angioplasty was performed in 5 (5.2%) patients. Intraprocedural problems were encountered in 3 (3.1%), of which only 1 had clinical implications, the device fish-mouthing with stent thrombosis resulting in a malignant middle cerebral artery territory infarction. The modified Rankin scale at 3 months was worse in 1 patient. DED is a newer generation flow diverter stent with a low periprocedural complication rate.


Trend in health-related physical fitness for Chinese male first-year college students: 2013-2019.
Physical fitness is a health indicator contributing to the prevention of non-communicable diseases that threaten public health. Studies across a number of global populations indicate that physical fitness is generally declining. This study investigated the trend in physical fitness of Chinese male first-year college students from 2013 to 2019 to offer critical information for fostering individual and public health. This study used archival data and a natural experiment design capturing 4 years of data prior to implementation of the Healthy China 2030 initiative and 3 years following. Physical fitness tests were based on the Chinese national student physical fitness standards for males including body mass index, vital capacity, standing-long-jump, sit-and-reach, pull-ups, 50 m sprint, and 1,000 m run. Because the physical fitness tests set different standards for males and females, female data will be reported separately. Data from a total of 3,185 Chinese male first-year college students from a private university in Hebei Province of China were included in the study. A one-way multivariate analysis of variance was used for analyzing the research data. The results indicated an overall significant difference in health-related physical fitness of Chinese male first-year college students, with scores on health indicators generally declining from 2013 to 2019. Despite improvement on some fitness variables in some years, performance on virtually all indicators was diminished compared to baseline years. These findings can contribute to the existing global literature in the field of public health showing general declines in physical fitness. Chinese universities have the opportunity to support Healthy China 2030 goals and cultivate individuals' physical fitness by offering physical education course that encourage college students to participate in moderate-to-vigorous-intensity physical activities in order to support physical fitness development.


Tissue-Specific Regulation of CFTR Gene Expression.
More than 2000 variations are described within the CFTR (Cystic Fibrosis Transmembrane Regulator) gene and related to large clinical issues from cystic fibrosis to mono-organ diseases. Although these CFTR-associated diseases have been well documented, a large phenotype spectrum is observed and correlations between phenotypes and genotypes are still not well established. To address this issue, we present several regulatory elements that can modulate CFTR gene expression in a tissue-specific manner. Among them, cis-regulatory elements act through chromatin loopings and take part in three-dimensional structured organization. With tissue-specific transcription factors, they form chromatin modules and can regulate gene expression. Alterations of specific regulations can impact and modulate disease expressions. Understanding all those mechanisms highlights the need to expand research outside the gene to enhance our knowledge.


Lymphocytosis and lymphadenopathy in a dog arising from two distinct lymphoid neoplasms.
A 10-year-old intact male Golden Retriever was presented to The Ohio State University Veterinary Medical Center for acute, non-painful facial swelling of the right mandibular region. On physical examination, the right mandibular swelling was found to represent marked lymphadenopathy of the submandibular lymph node. At this time, marked lymphadenopathy of the prescapular and popliteal lymph nodes was also appreciated. The CBC showed a moderate leukocytosis (38.4 × 109 cells/L, reference interval [RI] 4.8-13.9 × 109 cells/L) characterized by a moderate lymphocytosis (28.4 × 109 cells/L, RI 1.0-4.6 × 109 cells/L). Evaluation of peripheral blood and enlarged prescapular and popliteal lymph nodes revealed two morphologically different populations of homogeneous lymphocytes, with the lymphocyte population in the lymph nodes being distinct from that in the blood smear. Flow cytometry of peripheral blood revealed CD45-, CD5+, CD4-, CD8-, variably CD21+ neoplastic lymphocytes compatible with T-zone lymphocytes due to the absence of CD45 expression. Flow cytometry of the lymph node aspirate indicated a distinct population of CD21+ lymphocytes consistent with a B-cell phenotype along with a smaller proportion of the T-zone lymphocytes observed in the blood confirming the presence of two distinct populations of neoplastic lymphocytes, one involving T cells, and the other involving B cells.


Association of Genetic Polymorphisms of TGF-β1, HMOX1, and APOL1 With CKD in Nigerian Patients With and Without HIV.
Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor β1 (TGF-β1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection. Case-control study. West African adults including 217 HIV-infected patients with CKD (HIV+/CKD+ group), 595 HIV-infected patients without CKD (HIV+/CKD- group), 269 with CKD and no HIV infection (HIV-/CKD+ group), and 114 with neither CKD nor HIV (HIV-/CKD- group). The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV. CKD. Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders. Minor allele frequencies for TGF-β1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-β1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals. The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. APOL1 polymorphisms were highly prevalent in this population and among adult patients infected with HIV and were associated with increased CKD risk. The TGF-β1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD.


Stakeholders' perspectives about the impact of training and sensitization of traditional and spiritual healers on mental health and illness: A qualitative evaluation in Ghana.
Prayer camps and traditional healers have emerged recently as alternative sources of mental health care in Ghana. To increase their knowledge and collaboration between formal and informal mental health care providers, training and sensitization was organized for them. This study aimed at assessing beneficiaries' views about the impact of this intervention. We adopted narrative approach to qualitative enquiry using purposive sampling strategy to recruit formal and informal mental health care providers in Ghana for an in-depth interview. We analyzed the data thematically using QSR NVivo 12. Participants enhanced their knowledge about mental health and illness. They reported increased collaboration between formal and informal health care providers. Community psychiatric nurses (CPNs) give injections to patients instead of chaining and using shackles as was initially practiced. There are also regular visits by CPNs to traditional and spiritual healers to discuss the care of the mentally ill patients in their facilities. There has been an increased collaboration among healers of mental illness resulting in quick recovery of patients who seek care at traditional and spiritual healers. There is also abolition of chaining and using of shackles by these healers, with increasing respect for the human rights of patients.


A new snake species of the genus Gonyosoma Wagler, 1828 (Serpentes: Colubridae) from Hainan Island, China.
A new species of the genus Gonyosoma Wagler, 1828 is described herein based on six specimens from the Diaoluoshan Mountains, Hainan Island, Hainan Province, China. The new species, Gonyosoma hainanensesp. nov., is most similar to its continental sister species, Gonyosoma boulengeri (Mocquard, 1897). Both taxa have a scaled protrusion on the anterior portion of the rostrum, distinct from other congeners. However, Gonyosoma hainanensesp. nov. can be distinguished from G. boulengeri by two significant morphological characters: (1) black orbital stripe absent in adults (vs. present in G. boulengeri); and (2) two loreals (vs. one loreal in G. boulengeri). The new species is also genetically divergent and forms a unique clade from its sister species and all other congeners based on sequences of the mitochondrial gene cytochrome b (cyt b).