Measurement of older adults' social networks using technologies in the context of health and social care: a scoping review protocol.
This scoping review aims to identify and map the use of technology in measuring and analyzing older adults' social networks in the context of health and social care. Research has shown that social networks impact the health and well-being of older adults. Advancements in the internet, electronic and digital devices, social media, and healthcare technology enhance our ability to collect social network and health data. These rapidly evolving technologies present opportunities to overcome limitations in social network measurement and promote improved understanding of the impact of social networks on the health and well-being of older adults. This scoping review will include studies of older adults that measured social networks using technology and were related to health or health and social care. Studies published in English from 2004 to the present will be included. Books, editorials, letters, and commentaries will be excluded. PubMed (MEDLINE), Sociological Abstracts, SocINDEX, CINAHL, and Web of Science will be searched for related articles. Gray literature will be included by searching conference abstracts via Conference Papers Index and hand-searching conference proceedings from the American Sociological Society and the Gerontological Society of America. Data will be extracted by two independent reviewers using an a priori data extraction tool. Tables and summary narratives will be used to map and synthesize existing approaches to measuring social networks using technology, the settings for measurement development or testing, and the use of approaches in discovery science, implementation science, or clinical care.


The Effect of Balance Training by Tetraks Interactive Balance System on Balance and Fall Risk in Parkinson's Patients: A Report of Four Cases.
This pilot study aimed to investigate the effect of balance training by Tetraks Interactive Balance System (TIBS) on balance and fall risk in patients with mild to moderate Parkinson's disease. Four patients with Parkinson's disease between the ages of 56 and 70 years (61.25±6.70) were applied balance training for 3 weeks by TIBS. Sociodemographic features and physical properties of the subjects were recorded. Their motor performance was evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS), balance was measured using the Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up and Go Test (TUG), and the Standing on One Leg Balance Test (SOL) and, their fall risks were evaluated by TIBS. Evaluations were performed twice, before and after treatment. Following training, Parkinson's patients showed improvements in UPDRS, TUG, BBS, FRT, SOL and fall risk. Balance training by TIBS has positive effects on balance and decreases fall risk in Parkinson's disease patients.


Pancreatic endosonographic findings and clinical correlation in Crohn's disease.
We aimed to evaluate the incidence of pancreatic alterations in Crohn's disease using endoscopic ultrasound (EUS) and to correlate the number of alterations with current clinical data. Patients diagnosed with Crohn's disease (n=51) were examined using EUS, and 11 variables were analyzed. A control group consisted of patients with no history of pancreatic disease or Crohn's disease. Patients presenting with three or more alterations underwent magnetic resonance imaging (MRI). Pancreatic function was determined using a fecal elastase assay. Two of the 51 patients (3.9%) presented with four EUS alterations, 3 (5.9%) presented with three, 11 (21.5%) presented with two, and 13 (25.5%) presented with one; in the control group, only 16% presented with one EUS alteration (p<0.001). Parenchymal abnormalities accounted for 39 of the EUS findings, and ductal abnormalities accounted for 11. Pancreatic lesions were not detected by MRI. Low fecal elastase levels were observed in 4 patients, none of whom presented with significant pancreatic alterations after undergoing EUS. Ileal involvement was predictive of the number of EUS alterations. A higher incidence of pancreatic abnormalities was found in patients with Crohn's disease than in individuals in the control group. The majority of these abnormalities are related to parenchymal alterations. In this group of patients, future studies should be conducted to determine whether such morphological abnormalities could evolve to induce exocrine or endocrine pancreatic insufficiency and, if so, identify the risk factors and determine which patients should undergo EUS.


Ouabain-induced vacuolar formation in marginal cells in the stria vascularis is dependent on perilymphatic Na(+).
In the stria vascularis (SV), it is known that the Na(+)-K(+)-ATPase is expressed abundantly and its activity in the basolateral membrane of marginal cells is high. Ouabain, an inhibitor of the Na(+)-K(+)-ATPase, causes not only a decline in the endocochlear DC potential but also acute vacuolar formation in marginal cells. We studied the ionic mechanisms underlying the ouabain-induced vacuolar formation in marginal cells using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with 1 mM ouabain dissolved in the artificial perilymph for 50 min caused many vacuoles of a wide range of sizes in the apical cytoplasm of marginal cells, the bulging of marginal cells into the scala media and strial volume increase. Removal of K(+) from the perilymph reduced the proportion of vacuoles and strial thickening, but the bulging of marginal cells remained. In contrast, the sizes of vacuoles were drastically reduced and extrusion of marginal cells into the scala media could not be observed in the absence of perilymphatic Na(+). Furthermore, the total volume of SV was obviously reduced in comparison with the control. These results indicate that perilymphatic Na(+) and K(+) are responsible for these morphological changes caused by ouabain, and that perilymphatic Na(+) plays an important role in the cellular volume regulation in SV in the presence of ouabain. It is supposed that the transport system of perilymphatic Na(+) and K(+) into marginal cells may contribute to vacuolar formation when ouabain is administered. Regarding Na(+), we hypothesize two possibilities for the perilymphatic Na(+) transporting pathway as follows. Na(+) in the perilymph could enter the endolymph via Reissner's membrane or the basilar membrane; Na(+) in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na(+)-K(+)-ATPase in the basolateral membrane. Another, less likely, possibility is that Na(+) in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na(+)-K(+)-ATPase of intermediate cells. Regarding K(+), it is expected that the K(+) recycling pathway plays a role in ouabain-induced vacuolar formation in marginal cells.


Allergic rhinitis and sinusitis in asthma: differential effects on symptoms and pulmonary function.
Allergic rhinitis and sinusitis are frequently associated with asthma. The purpose of this study was to determine the impact of self-reported allergic rhinitis and sinusitis on lower airway disease in a large cohort of participants with well-characterized asthma. A cohort study of participants in two trials of the American Lung Association-Asthma Clinical Research Centers: 2,031 asthmatics in the Safety of Inactivated Influenza Vaccine in Asthma in Adults and Children (SIIVA) trial and 488 asthmatics in the Effectiveness of Low Dose Theophylline as Add-on Treatment in Asthma (LODO) trial. At baseline, participants reported the presence of allergic rhinitis and sinusitis, and then lung function and asthma control were measured. During the trials, participants were monitored for asthma exacerbations. More than 70% of participants reported either allergic rhinitis or sinusitis. Sinusitis was more common in female patients (odds ratio, 1.46 [SIIVA]), those with gastroesophageal reflux disease (odds ratio, 2.21 [SIIVA]), and those of white race (odds ratio, 1.53 [SIIVA]). Similar associations were seen for allergic rhinitis. LODO participants with allergic rhinitis and sinusitis had increased asthma symptoms and a trend toward more sleep disturbance. Participants with allergic rhinitis had higher baseline lung function than those without allergic rhinitis measured by peak flow (91.2% vs 95.8% in the SIIVA trial). Participants with sinusitis had similar lung function to those without sinusitis. Participants with and without allergic rhinitis had similar exacerbation rates. In the LODO trial only, participants with sinusitis had increased asthma exacerbations (5.68 per patient per year vs 3.72 per patient per year). Allergic rhinitis and sinusitis are associated with more severe asthmatic symptoms and, in patients with poorly controlled asthma, more exacerbations but are not associated with low lung function.


De novo congenital melanoma: analysis of 2 cases with array comparative genomic hybridization.
Congenital melanoma is extraordinarily rare, and 3 types have been described: transplacental metastases from the mother, de novo congenital melanoma, and melanoma occurring in association with a congenital melanocytic nevus. We describe 2 reports of array comparative genomic hybridization analysis of de novo congenital melanoma. The first patient was male, and the second was female; both had a scalp lesion present at birth, which grew quickly. The scalp mass from patient 1 showed a heterogeneous, anaplastic melanocytic neoplasm with large size and depth, high mitotic rate, ulceration, and necrosis. The scalp mass from patient 2 showed a broad melanocytic neoplasm with single cell and junctional nested proliferation at the dermal-epidermal junction and cellular, confluent aggregates of highly atypical melanocytes in the dermis with high mitotic rate. Patient 1 had lung and liver metastases detected by radiologic imaging and was treated with cisplatin, vinblastine, and dacarbazine but expired at the age of 5 months. Patient 2 developed a metastasis to the right neck with similar histologic features, and pulmonary metastases were also detected by imaging. Patient 2 is currently alive at the age of 4 years. Array comparative genomic hybridization analysis of the first case revealed loss of chromosomes 3p26.3-p21.31, 5p15.33-q23.1, 11q15.5-q13.2, 14 (complete deletion), and 15q11.1-q22.31. The second case displayed gains in chromosomes 1q21.1-q44, 2p25.3-p11.1, 2q11.1-q37.3, 6p25.3-p11.1, 7p22.3-p11.2, 7q11.1-q36.3, 8p23.3-p11.1, 8q11.1-q24.3, 9p24.3-p11.2, 9q12-q34.3, 11q13.2-q13.4, 13q11-q34, 18p11.32-p11.21, 19p13.3-p11, 19q11-q13.43, 20p13-p11.1, and 20q11.21-q13.33. In both cases, the presence of multiple chromosomal aberrations corroborated the diagnosis of melanoma.


Growth, heart weight, cardiac lipid, and pathology of chickens fed soybean oil or oil extracted from different rapeseed cultivars.
A total of 384 male Single Comb White Leghorn chicks of the Hyline strain were randomized in 24 Petersime battery units of 16 birds per unit. Four replicate pens were fed either a basal (control) diet containing no added oil or a diet supplemented with 20% by weight of either soybean oil or rapeseed oil (RSO) from cultivars Tower, Candle, Regular, or R-500. Levels of crucic acid (22:1) in the RSO's ranged from .1 to 51.6%. Four birds from each unit were killed at 4, 8, 12, and 16 weeks for cardiac lipid analysis and pathology. Feeding RSO had no consistent effect on body weights, heart weights, or the heart-to-body weight ratio. Only the diet containing R-500 (51.6% 22:1) consistently increased cardiac lipid levels as measured gravimetrically. Maximum deposition of the long-chain monoenes (22:1) and eicosenoic acids (20:1) occurred in the cardiac lipids by 8 weeks, and the levels remained high throughout the 16-week trial. The relative concentration of these long-chain monoenes in the cardiac lipids was positively correlated to the dietary levels of these acids. The incidence of lesions found in heart, liver, and skeletal muscle was significantly higher in chickens fed RSO's high in 22:1 than in chickens fed control or soybean oil, and the incidence significantly correlated to the level of 22:1 in the diet. The incidence of heart and muscle lesions and sinusoidal distention in chickens fed RSO's low in 22:1 was not significantly different from that of chickens fed the control diet or soybean oil, but the incidence of hepatic necrosis was significantly higher for chickens fed RSO's low in 22:1 compared to those fed the control diet or soybean oil.


Myocardial infarction during sleep deprivation in a patient with dextrocardia--a case report.
A patient with dextrocardia who suffered his first myocardial infarction after approximately 26 hours of a diagnostic sleep deprivation protocol is described. The infarction started about 3 hours after a significant improvement in mood, which persisted during and after infarction. Total sleep deprivation may be an acute risk factor for myocardial infarction.


The Relationship of Systolic Pulmonary Artery Pressure with Perioperative Mortality and Morbidity in Patients Undergoing Non-Cardiac Surgery: A Single-Center Experience.
Pulmonary hypertension (PH) is associated with adverse perioperative events in patients undergoing non-cardiac surgery. In this study, we aimed to investigate the relationship between systolic pulmonary artery pressure (sPAP), evaluated by transthoracic echocardiography (TTE) before surgery, and perioperative mortality and morbidity in patients who underwent non-cardiac surgery in our center. Of the 3425 retrospectively screened patients who underwent non-cardiac surgery, 3049 patients whose estimated sPAP values were previously determined by TTE were included in the study. Patients were classified into 3 groups according to their estimated sPAP levels. sPAP <35 mmHg formed group 1, 35-39 mmHg group 2, and ≥ 40 mmHg group 3. All demographic and perioperative data obtained from the database of our institute were compared in three groups. Of the 3049 patients enrolled in the study, 2406 (78.9%) were in group 1, 259 (8.5%) in group 2, and 384 (12.6%) in group 3. Thirty-day all-cause mortality was observed in 82 (2.7%) patients, cardiac mortality occurred in 9 patients (0.3%). In the group with sPAP ≥40 mmHg, cardiac mortality was 0.5% and all-cause mortality was 7.3%. Thirty-day all-cause mortality, acute pulmonary edema, and acute renal failure were significantly higher in group 3 than in the other groups. Cardiac mortality did not differ significantly between the groups. Age, sPAP value, and chronic obstructive pulmonary disease history were revealed as independent predictors of all-cause mortality in multivariate logistic regression analysis. In conclusion, increased sPAP is associated with adverse postoperative outcomes. The evaluation of sPAP with TTE before non-cardiac surgery in patients whose clinical features and examination findings suggest PH may contribute to preoperative risk assessment.


Fibrosis and cardiac function in obesity: a randomised controlled trial of aldosterone blockade.
As myocardial fibrosis might be an important contributor to the association of obesity with left ventricular (LV) dysfunction and heart failure, we investigated the effects of spironolactone on LV function and serological fibrosis markers (procollagen type III N-terminal propeptide (PIIINP) and procollagen type I C-terminal propeptide (PICP)) in patients with obesity and abnormal LV performance. A prospective, randomised, double-blind, placebo-controlled study. A university hospital. 113 patients (mean±SD age 58±8 years) with body mass index≥30, without any comorbidities, with impaired early diastolic mitral annular velocity, randomised to spironolactone 25 mg/day or placebo for 6 months. Echocardiographically derived indices of LV systolic (strain and strain rate) and diastolic (E velocity, tissue e' and E/e' ratio) function, myocardial reflectivity (calibrated integrated backscatter (IB)), and serum PICP and PIIINP. In the spironolactone group, significant improvements in myocardial deformation, peak early diastolic velocity (Em), E/e' and IB were noted with a simultaneous decrease in PICP and PIIINP. No corresponding alterations were found with placebo. Improvement in LV systolic function (increase in strain) was independently associated with baseline strain (β=-0.43, p<0.001), change in IB (β=0.26, p<0.02) and baseline PICP (β=0.24, p<0.04). Among the independent determinants of LV diastolic improvement were for increase in Em - baseline Em (β=-0.44, p<0.001) and baseline PICP (β=0.35, p<0.002), and for decrease in E/e' - baseline E/e' (β=-0.35, p<0.005) and change in PICP (β=0.25, p<0.04). In patients with obesity without other comorbidities, aldosterone antagonism improves LV function and myocardial acoustic properties, and reduces circulating procollagen levels. Beneficial changes in cardiac performance are independently predicted by baseline LV dysfunction and baseline disturbances, as well as treatment-induced improvements in fibrosis markers. http://www.anzctr.org.au ACTRN12609000655246.


Susceptibility to vinblastine-induced aneuploidy and preferential chromosome segregation during meiosis I in Robertsonian heterozygous mice.
Chromosome segregation at meiosis I was studied in oocytes and spermatocytes of four different Robertsonian (Rb) heterozygous mouse stocks by cytogenetic analysis of meiotic products. Two Rb heterozygotes spontaneously yielded high frequencies of unbalanced oocytes. In one case, Rb(2.18)Rma, the excess hyperploidy was mainly accounted for by nondisjunction of normal bivalents, suggesting a generalized impairment of meiotic segregation. In each stock, frequencies of hyperploid spermatocytes were either not significantly different or significantly lower than the corresponding frequencies in the oocytes. This confirmed the greater risk of segregational errors in female than in male carriers of the same Rb metacentric. The hypothesis that an error prone system of meiotic segregation, such as the trivalent configuration of single Rb heterozygous oocytes, could be hypersensitive to chemically induced malsegregation was tested by injecting Rb heterozygous females with low doses of vinblastine (VBL). An intraperitoneal injection of 0.06 or 0.09 mg/kg VBL before the first meiotic division significantly increased the spontaneous frequency of hyperploid oocytes, inducing segregational errors of both the trivalent and normal bivalents. The comparison of these data with VBL effects in B6C3F1 mice showed that single Rb heterozygous oocytes are more sensitive to VBL-induced meiotic aneuploidy than oocytes with a standard karyotype. Although segregation distortion has been repeatedly shown in the progeny of Rb heterozygous mice with a significant excess of all telocentric balanced offspring, it has never been demonstrated whether this is a primary event occurring during meiotic segregation or a consequence of selective postconceptional death. In this study, we showed that preferential segregation occurred during female meiosis in all the Rb stocks tested. When segregation distortion was analyzed separately in balanced and unbalanced oocytes, the latter did not show preferential segregation, suggesting that, when the two telocentrics segregated from each other, then the metacentric was randomly directed to the ovum or the polar body.


Impact of social interdependence on emotional well-being of medical students.
To observe the effect of social interdependence on emotional well-being in medical students. This cross-sectional study was conducted in Karachi from June 2013 to January 2014 and comprised first-year medical students of 5 private and 3 public-sector colleges. Students of both genders aged 19-24 years were included. Quantitative aspects of social and emotional wellness were evaluated using a structured questionnaire from the wellness wheel on a four-point Likert's scale (score ranging from 0 to 3). Two focus group discussions were conducted in each medical college from the qualitative aspect. Of the 736 participants, 526(71.47%) were females and 210(28.53%) were males. Males reported significantly less inclination towards exhibiting fairness, solving problems, teaching batch fellows and attending group discussion (p<0.05). They were significantly least anxious with less frequency of helping others during emotional outbursts (p<0.05). Females had higher frequency of close friends and self-improvement (p<0.05). The scores of social wellness were significantly better in females compared to males (p<0.001) while there was no significant difference in emotional wellness on the basis of gender (p>0.05). Social communication and help was highly positively correlated with self-content in students (p<0.05). The medical students of Karachi had good social and emotional well-being.


Magnitude and determinants of glaucoma in type II diabetics: A hospital based cross-sectional study in Maharashtra, India.
Glaucoma and diabetes have a common pathogenesis. We estimated the magnitude and determinants of glaucoma in adults with type II diabetes who presented to a tertiary level eye center in 2010. A cross-sectional survey. Diabetes was diagnosed by history and measurement of blood sugar levels. Glaucoma was diagnosed by assessing optic disc morphology, visual fields, and intraocular pressure. Data were collected on patient demographics, clinical characteristics of diabetes and ocular status through interviews and measurements. The prevalence of glaucoma in diabetics was estimated, and variables were analyzed for an association to glaucoma. The 95% confidence intervals (CIs) were calculated. Statistical significance was indicated by P < 0.05. The study cohort was comprised of 841 diabetics. The mean age of the cohort was 53.8 ± 10.7 years. There were 320 (38%) females. The prevalence of glaucoma was 15.6% (95% CI: 13.1-18.1). More than 75% of the diabetics had no evidence of diabetic retinopathy (DR). Half of the diabetics with glaucoma had primary open angle glaucoma. The presence of glaucoma was significantly associated to the duration of diabetes (Chi-square = 10.1, degree of freedom = 3, P = 0.001). The presence of DR was not significantly associated to the presence of glaucoma (odds ratio [OR] = 1.4 [95% CI: 0.88-1.2]). The duration of diabetes (adjusted OR = 1.03) was an independent predictor of glaucoma in at least one eye. More than one-sixth of diabetics in this study had glaucoma. Opportunistic screening for glaucoma during DR screening results in an acceptable yield of glaucoma cases.


Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma.
Extracellular vesicles (EVs) are lipid-based nanosized particles that convey biological material from donor to recipient cells. EVs play key roles in glioblastoma progression because glioblastoma stem-like cells (GSCs) release pro-oncogenic, pro-angiogenic, and pro-inflammatory EVs. However, the molecular basis of EV release remains poorly understood. Here, we report the identification of the pseudokinase MLKL, a crucial effector of cell death by necroptosis, as a regulator of the constitutive secretion of EVs in GSCs. We find that genetic, protein, and pharmacological targeting of MLKL alters intracellular trafficking and EV release, and reduces GSC expansion. Nevertheless, this function ascribed to MLKL appears independent of its role during necroptosis. In vivo, pharmacological inhibition of MLKL reduces the tumor burden and the level of plasmatic EVs. This work highlights the necroptosis-independent role of MLKL in vesicle release and suggests that interfering with EVs is a promising therapeutic option to sensitize glioblastoma cells.


Molecular Footprints on Osmoregulation-Related Genes Associated with Freshwater Colonization by Cetaceans and Sirenians.
The genetic basis underlying adaptive physiological mechanisms has been extensively explored in mammals after colonizing the seas. However, independent lineages of aquatic mammals exhibit complex patterns of secondary colonization in freshwater environments. This change in habitat represents new osmotic challenges, and additional changes in key systems, such as the osmoregulatory system, are expected. Here, we studied the selective regime on coding and regulatory regions of 20 genes related to the osmoregulation system in strict aquatic mammals from independent evolutionary lineages, cetaceans, and sirenians, with representatives in marine and freshwater aquatic environments. We identified positive selection signals in genes encoding the protein vasopressin (AVP) in mammalian lineages with secondary colonization in the fluvial environment and in aquaporins for lineages inhabiting the marine and fluvial environments. A greater number of sites with positive selection signals were found for the dolphin species compared to the Amazonian manatee. Only the AQP5 and AVP genes showed selection signals in more than one independent lineage of these mammals. Furthermore, the vasopressin gene tree indicates greater similarity in river dolphin sequences despite the independence of their lineages based on the species tree. Patterns of distribution and enrichment of Transcription Factors in the promoter regions of target genes were analyzed and appear to be phylogenetically conserved among sister species. We found accelerated evolution signs in genes ACE, AQP1, AQP5, AQP7, AVP, NPP4, and NPR1 for the fluvial mammals. Together, these results allow a greater understanding of the molecular bases of the evolution of genes responsible for osmotic control in aquatic mammals.


Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy.
Epilepsy is one of the oldest neurological conditions known to humankind. It is known that oxidative stress and generation of reactive oxygen species are a cause and consequence of epileptic seizures. Although recent years have seen tremendous progress in the molecular biology and metabolism of selenium, we still know little about the cell type-specific and temporal pattern of selenium and its derivatives in the brain of epileptic humans and experimental animals. It has been suggested that some antiepileptic drug therapies such as valproic acid, deplete the total body selenium level and selenium-dependent glutathione peroxidase (GSH-Px) activity although therapy with a new epileptic drug, topiramate, activated GSH-Px activity in epileptic animals and humans. An observation of lower blood or tissue selenium level and GSH-Px activity in epileptic patients and animals compared to controls in recent publications may support the proposed crucial role of selenium level and GSH-Px activity in the pathogenesis of epilepsy. Selenium is incorporated into an interesting class of molecules known as selenoproteins that contain the modified amino acid, selenocysteine. There are signs of selenium and selenoprotein deficiency in the pathogenesis of epilepsy. In conclusion, there is convincing evidence for the proposed crucial role of selenium and deficiency of GSH-Px enzyme activity in epilepsy pathogenesis. Blood GSH-Px activities could be a reliable indicator of selenium deficiency in patients with epilepsy.


Etiology, Clinical, Radiological, and Microbiological Profile of Patients with Non-cystic Fibrosis Bronchiectasis at a Tertiary Care Hospital of Pakistan.
Objectives To identify the etiology of non-cystic fibrosis bronchiectasis (NCFB), to assess the clinical presentation, radiological findings, and microbiological profile of patients presenting with a diagnosis of bronchiectasis in a tertiary care center of Pakistan. Methods This was a prospective observational cohort study where patients with a diagnosis of bronchiectasis proven by high-resolution computed tomography (HRCT) were evaluated for etiology, clinical characteristics, microbiology, radiology, spirometric profile, and in-hospital outcomes. Results During the study period, 196 patients were diagnosed with NCFB. The majority of the patients were men 76.5% (n = 150) and 83.6% (n = 163) of the total patients were younger than 60 years of age. The majority of these patients (58.7%, n = 111) had a duration of symptoms between 5-10 years. The etiology of bronchiectasis was identified in 92.9% of cases. Post-infectious bronchiectasis was the most common cause (67.8%, n = 133), followed by chronic obstructive pulmonary disease (COPD) (9.2%, n = 18), and allergic bronchopulmonary aspergillosis (ABPA) (7.1%, n = 14). Among the post infectious causes, a history of TB was present in 85% (n = 114/133) of patients. Obstructive impairment was the most common spirometric pattern, observed in 68.9% (n = 135) of patients. Pseudomonas aeruginosa was the most commonly isolated organism (36.2%, n = 71). Hemoptysis was the most frequent complication found in 20.9% of patients (n = 41). Out of these 196 patients, 94.4% (n = 185) received medical management and were discharged from the hospital. Respiratory failure was significantly associated with the Pseudomonas group as compared to non-pseudomonas group [(n = 21 (29%) vs n = 18 (14.4%) p = 0.01]. During hospitalization seven patients (3.6%) were died because of respiratory failure. Conclusions Post TB bronchiectasis was the leading cause of non-cystic fibrosis (CF) bronchiectasis in this cohort, with Pseudomonas was the commonest pathogen isolated from the respiratory specimen, which was significantly associated with respiratory failure. On spirometry, obstructive impairment was found in the majority of patients and hemoptysis was the most frequent complication.


Multiple giant prostatic urethral stones with an ureteral stone in a young patient.
Giant prostatic urethral stones have been reported as a very rare entity, and the etiology of these stones is not clear. We report a case of a 40-year-old man with giant multiple prostatic urethral stones whereby the entire gland was replaced, and a big ureteral stone presented with voiding difficulty and recurrent urinary tract infections. In the literature, to our knowledge, this is the youngest case wherein giant prostatic urethral stones coexisted with a big ureteral stone. Many different-sized stones were observed endoscopically, some protruding into the urethra, and some filling different cavities on the prostate. Following cystoscopy, multiple giant prostatic stones weighing a total of 151 g were removed by the open retropubic route. We treated the big ureteral stone endoscopically.


Parental Acceptability of COVID-19 Vaccination for Children Under the Age of 18 Years: Cross-Sectional Online Survey.
It is expected that COVID-19 vaccines will become available in China by the end of 2020. Vaccinating children against COVID-19 would contribute to the control of the pandemic and the recovery of the global economy. For children under the age of 18 years, parents are usually the decision makers regarding their children's vaccination. The goal of this study was to investigate parental acceptability of free COVID-19 vaccination for children under the age of 18 years in China. This is a secondary analysis of a cross-sectional, closed online survey among 2053 factory workers in Shenzhen, China, implemented from September 1 to 7, 2020. Participants of the online survey were full-time employees aged 18 years or over who had resumed work in factories in Shenzhen. Factory workers in Shenzhen are required to receive physical examinations once a year. Eligible workers attending six designated physical examination sites were invited to complete an online survey. This study was based on a subsample of those who had at least one child under the age of 18 years (N=1052). After being briefed that COVID-19 vaccines developed by China are likely to be available by the end of 2020, participants were asked about their likelihood of having their children under the age of 18 years take up free COVID-19 vaccination provided by the government, if it existed. Multivariate logistic regression models were fitted to examine the associations of perceptions related to COVID-19 vaccination based on the theory of planned behavior (TPB) and exposure to information related to COVID-19 through social media with parental acceptability, after controlling for significant background characteristics. The prevalence of parents' acceptability of COVID-19 vaccination for their children was 72.6% (764/1052). After adjusting for significant background characteristics, positive attitudes toward COVID-19 vaccination (adjusted odds ratio [AOR] 1.70, 95% CI 1.50-1.91), the perception that a family member would support them in having their children take up COVID-19 vaccination (ie, perceived subjective norm) (AOR 4.18, 95% CI 3.21-5.43), and perceived behavioral control to have the children take up COVID-19 vaccination (AOR 1.84, 95% CI 1.49-2.26) were associated with higher parental acceptability of COVID-19 vaccination. Regarding social media influence, higher exposure to positive information related to COVID-19 vaccination was associated with higher parental acceptability of COVID-19 vaccination (AOR 1.35, 95% CI 1.17-1.56). Higher exposure to negative information related to COVID-19 vaccination was negatively associated with the dependent variable (AOR 0.85, 95% CI 0.74-0.99). Parents' acceptability of COVID-19 vaccination for their children under 18 years of age was high in China. The TPB is a useful framework to guide the development of future campaigns promoting COVID-19 vaccination targeting parents. Transparency in communicating about the vaccine development process and vaccine safety testing is important. Public health authorities should also address misinformation in a timely manner.


Large genomic differences between the morphologically indistinguishable diplomonads Spironucleus barkhanus and Spironucleus salmonicida.
Microbial eukaryotes show large variations in genome structure and content between lineages, indicating extensive flexibility over evolutionary timescales. Here we address the tempo and mode of such changes within diplomonads, flagellated protists with two nuclei found in oxygen-poor environments. Approximately 5,000 expressed sequence tag (EST) sequences were generated from the fish commensal Spironucleus barkhanus and compared to sequences from the morphologically indistinguishable fish parasite Spironucleus salmonicida, and other diplomonads. The ESTs were complemented with sequence variation studies in selected genes and genome size determinations. Many genes detected in S. barkhanus and S. salmonicida are absent in the human parasite Giardia intestinalis, the most intensively studied diplomonad. For example, these fish diplomonads show an extended metabolic repertoire and are able to incorporate selenocysteine into proteins. The codon usage is altered in S. barkhanus compared to S. salmonicida. Sequence variations were found between individual S. barkhanus ESTs for many, but not all, protein coding genes. Conversely, no allelic variation was found in a previous genome survey of S. salmonicida. This difference was confirmed by sequencing of genomic DNA. Up to five alleles were identified for the cloned S. barkhanus genes, and at least nineteen highly expressed S. barkhanus genes are represented by more than four alleles in the EST dataset. This could be explained by the presence of a non-clonal S. barkhanus population in the culture, by a ploidy above four, or by duplications of parts of the genome. Indeed, genome size estimations using flow cytometry indicated similar haploid genome sizes in S. salmonicida and G. intestinalis (approximately 12 Mb), whereas the S. barkhanus genome is larger (approximately 18 Mb). This study indicates extensive divergent genome evolution within diplomonads. Genomic traits such as codon usage, frequency of allelic sequence variation, and genome size have changed considerably between S. barkhanus and S. salmonicida. These observations suggest that large genomic differences may accumulate in morphologically indistinguishable eukaryotic microbes.


The hormone-binding unit of luteinizing hormone receptor.
Rat ovarian luteinizing hormone/human choriogonadotropin binding sites were labelled with 125I-choriogonadotropin in vivo, and the resulting 125I-choriogonadotropin-receptor complexes were solubilized by Triton X-100 and purified by use of antibodies to choriogonadotropin immobilized to agarose. The purified 125I-choriogonadotropin-receptor complex was treated with glutaraldehyde to crosslink radiolabelled hormone to the receptor. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the crosslinked product revealed a labelled Mr 130 000 major band in addition to the hormone and its alpha-subunit, indicating that a single receptor component was linked to the hormone. Unoccupied binding sites for luteinizing hormone were also solubilized by Triton X-100 from pseudopregnant rat ovaries, and attached to choriogonadotropin-agarose. The agarose gel was washed, and eluted with 0.1 M-sodium acetate, pH 4. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the pH 4 eluate revealed an Mr 90 000 major band which was abolished when ovaries presaturated with choriogonadotropin were used as starting material. These observations suggest that the hormone-binding component of the luteinizing hormone receptor is a polypeptide of Mr 90 000. This polypeptide was isolated and labelled with Na 125I. The labelled polypeptide showed a single band on sucrose density gradient centrifugation and on gel filtration on agarose.


Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice.
We evaluated the therapeutic effect and fate of high doses of human umbilical cord Wharton jelly cells (hUCWJCs) after IP administration to streptozotocin (STZ)-induced diabetic mice. Type 1 diabetes (T1D) was induced in Kunming mice via IP injection of STZ. hUCWJCs were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). Diabetic animals with sustained hyperglycemia for at least 2 weeks were administered 1 × 107 Dil-hUCWJCs via intraperitoneal injection. Insulin, glucagon and PDX-1 were detected by immunofluorescence with confocal microscopy. Serum mouse and human C-peptide was assayed in blood collected via intracardiac puncture. Specific β-cell differentiation markers and human DNA were assessed using qPCR performed with 200 ng of target DNA. hUCWJCs migrated to the STZ-damaged organs and contributed to lower blood glucose levels in 30% of the treated mice. Confocal microscopy revealed the presence of resident insulin-positive cells in the liver and kidneys. hUCWJC-treated mice with restored hyperglycemia also showed increased serum mouse C-peptide levels. The qPCR results, particularly in the liver, revealed that after transplantation hUCWJCs upregulated genes of endocrine precursors but failed to express endocrine stage markers. Mice with restored hyperglycemia had reduced urinary volume and lacked glomerular hypertrophy, exhibiting a morphology resembling that of normal glomeruli. Moreover, we also verified that one of the possible mechanisms by which hUCWJCs exert immunosuppressive effects is through down-regulation of the cell surface receptor HLA-1. We confirmed the potential of IP administration of hUCWJCs and the capability of these cells to migrate to damaged tissues and promote insulin secretion from non-pancreatic local cells and to improve renal damage. These findings confer unique therapeutic properties to hUCWJCs, suggesting a promising future in the treatment of diabetes mellitus.


The influence of maca (Lepidium meyenii) on antioxidant status, lipid and glucose metabolism in rat.
This work focused on the effect of Maca on lipid, anti-oxidative, and glucose parameters in hereditary hypertriglyceridemic (HHTg) rat. Maca (1%) was administred to rats as a part of a high-sucrose diet (HSD) for 2 weeks. Rosiglitazone (0.02%) was used as a positive control. Maca significantly decreased the levels of VLDL (very low density lipoproteins), LDL (low density lipoproteins), and total cholesterol, and also the level of TAG (triacylglycerols) in the plasma, VLDL, and liver. Maca, as well as rosiglitazone, significantly improved glucose tolerance, as the decrease of AUC (area under the curve) of glucose showed, and lowered levels of glucose in blood. The activity of SOD (superoxide dismutase) in the liver, the GPX (glutathione peroxidase) in the blood, and the level of GSH (glutathione) in liver increased in all cases significantly. Results demonstrate that maca seems to be promising for a positive influence on chronic human diseases (characterized by atherogenous lipoprotein profile, aggravated antioxidative status, and impaired glucose tolerance), and their prevention.


Origins of eukaryotic excitability.
All living cells interact dynamically with a constantly changing world. Eukaryotes, in particular, evolved radically new ways to sense and react to their environment. These advances enabled new and more complex forms of cellular behaviour in eukaryotes, including directional movement, active feeding, mating, and responses to predation. But what are the key events and innovations during eukaryogenesis that made all of this possible? Here we describe the ancestral repertoire of eukaryotic excitability and discuss five major cellular innovations that enabled its evolutionary origin. The innovations include a vastly expanded repertoire of ion channels, the emergence of cilia and pseudopodia, endomembranes as intracellular capacitors, a flexible plasma membrane and the relocation of chemiosmotic ATP synthesis to mitochondria, which liberated the plasma membrane for more complex electrical signalling involved in sensing and reacting. We conjecture that together with an increase in cell size, these new forms of excitability greatly amplified the degrees of freedom associated with cellular responses, allowing eukaryotes to vastly outperform prokaryotes in terms of both speed and accuracy. This comprehensive new perspective on the evolution of excitability enriches our view of eukaryogenesis and emphasizes behaviour and sensing as major contributors to the success of eukaryotes. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.


Characterization of human-induced pluripotent stem cells carrying homozygous RB1 gene deletion.
Retinoblastoma is an infant cancer that results from loss of RB1 expression in both alleles. The RB1 gene was the first reported cancer suppressor gene; however, the mechanism by which RB1 loss causes cancer in the retina has not yet been clarified. Human-induced pluripotent stem cells (iPSCs) provide an ideal tool for mechanistic research regarding retinoblastoma. However, because RB1 is a tumor suppressor, loss of both alleles of RB1 in human iPS cells may affect the phenotype of the cells. To examine this possibility, we established human iPSCs with deletions in both alleles of RB1 by CRISPR/Cas9 technique to characterize the associated phenotype. We first examined the expression of RB1 transcripts by RT-qPCR, and RB1 transcripts were expressed in immature hiPSCs and then the expression levels of RB1 transcripts consistently increased during retinal organoid differentiation in human iPSCs. Expression levels of immature markers including SSEA4, OCT3/4 and NANOG were indistinguishable between control iPSCs and RB1 knockout iPSCs. Proliferative activity was also unaffected by homozygous RB1 deletion. Taken together, we showed that homozygous deletion of RB1 did not affect the maturation and proliferation statuses of human iPSCs.


Reliability analysis of the 3-min all-out exercise test for cycle ergometry.
The 3-min all-out exercise test (3 MT) is purported to estimate critical power (CP) and anaerobic work capacity (W') and serve as an exercise mode for measuring maximum oxygen uptake (VO(2max)). Reliability analysis of the 3 MT has been confined to CP, not W', and verification of "true" VO(2max)was exclusive to a graded exercise test (GXT). We conducted a reliability analysis of the 3 MT and compared VO(2max)values from the 3 MT with a GXT and an exhaustive square-wave verification bout. Upon completion of a custom GXT and square-wave verification protocol, 11 subjects of various aerobic powers completed two 3 MTs (separate visits). CP, W', average power during 150 s from the 3 MT, and VO(2max)values were assessed using typical error (TE), coefficient of variation (CV), and intraclass correlation (α). CP (W) (trial 1 = 206 ± 47, trial 2 = 206 ± 42) did not differ between 3 MT trials (P = 0.37) and was reliable (TE = 15 W, CV = 7%, α = 0.93). W' was less reliable (TE = 2864 J, CV = 28%, α = 0.76) but did not alter power-duration estimates from the two 3 MTs (P > 0.05). Variability for VO(2max)(TE (mL·kg(-1)·min(-1)) between the GXT and the verification bout (1.16) was more consistent than the first (2.03) or second (2.69) 3 MT. The 3 MT yields reliable estimates of CP and consistent estimates of the power-duration relationship. Power for 150 s, in comparison with W', is a more reliable metric of short-term power performance. The square-wave protocol is recommended over the 3 MT for verifying true VO(2max).


A polymer-dependent increase in phosphorylation of beta-tubulin accompanies differentiation of a mouse neuroblastoma cell line.
We have examined the phosphorylation of cellular microtubule proteins during differentiation and neurite outgrowth in N115 mouse neuroblastoma cells. N115 differentiation, induced by serum withdrawal, is accompanied by a fourfold increase in phosphorylation of a 54,000-mol-wt protein identified as a specific isoform of beta-tubulin by SDS PAGE, two-dimensional isoelectric focusing/SDS PAGE, and immunoprecipitation with a specific monoclonal antiserum. Isoelectric focusing/SDS PAGE of [35S]methionine-labeled cell extracts revealed that the phosphorylated isoform of beta-tubulin, termed beta 2, is one of three isoforms detected in differentiated N115 cells, and is diminished in amounts in the undifferentiated cells. Taxol, a drug which promotes microtubule assembly, stimulates phosphorylation of beta-tubulin in both differentiated and undifferentiated N115 cells. In contrast, treatment of differentiated cells with either colcemid or nocodazole causes a rapid decrease in beta-tubulin phosphorylation. Thus, the phosphorylation of beta-tubulin in N115 cells is coupled to the levels of cellular microtubules. The observed increase in beta-tubulin phosphorylation during differentiation then reflects developmental regulation of microtubule assembly during neurite outgrowth, rather than developmental regulation of a tubulin kinase activity.


Effect of ethylene on flower abscission: a survey.
The effect of ethylene on flower abscission was investigated in monocotyledons and eudicotyledons, in about 300 species from 50 families. In all species studied except Cymbidium, flower abscission was highly sensitive to ethylene. Flower fall was not consistent among the species in any family studied. It also showed no relationship with petal senescence or abscission, nor with petal colour changes or flower closure. Results suggest that flower abscission is generally mediated by endogenous ethylene, but that some exceptional ethylene-insensitive abscission occurs in the Orchidaceae.


A curriculum for the ideal orthopaedic residency. Academic Orthopaedic Society.
The Academic Orthopaedic Society met in April 1994 to discuss manpower issues in orthopaedics. The members developed an approach using the Delphi system to define and obtain consensus on the characteristics of the ideal residency. Six categories of educational attributes were included: General; Clinical Management; Skills and Technical Aspects; Rehabilitation; Basic Science and Research; and Educational Environment. The following year a questionnaire was sent to more than 125 programs in an attempt to have residents and staff anonymously self score their residencies according to the standards defined by the Delphi panels. The results obtained from the 745 responders from 73 programs validate effectively the characteristics of the ideal program and also show the variation among the programs.


Potentially fatal paracetamol overdose and successful treatment with 3 days of intravenous N-acetylcysteine regime--a case report.
Paracetamol overdose is the most common drug overdose worldwide. To our knowledge, the maximum number of paracetamol tablets ingested reported in the literature is 45 g. We describe a 21-year-old patient who acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to 1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors for paracetamol overdose in our patient included massive paracetamol ingestion (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189 U/L). She was treated with a 3-day modified regimen of intravenous N-acetylcysteine. The liver function tests and the prothrombin time remained normal over the second and third day of admission and the patient was discharged without complications on the fifth day. From this experience we feel that in very severe paracetamol poisoning, a modified regime of intravenous N- acetylcysteine for 3 days is safe and efficacious.


LLC-PK1 cysts: a model for the study of epithelial polarity.
In the present work, we have taken advantage of the properties of two recently isolated clonal subpopulations of the pig kidney-derived LLC-PK1 cell line to study aspects of the establishment of epithelial polarity. When grown in suspension, LLC-PK1/D + Sc cells reaggregated within a few hours and, during the following days of culture, formed free-floating, hollow spheres or cysts, lined by a monolayer of polarized cells. In contrast, LLC-PK1/D- cells were unable to develop such polarized structures even upon prolonged culture in suspension. The polarity of the LLC-PK1/D + Sc cells lining the cysts was inverted compared to that in intact renal tubules, the microvilli-rich "apical" pole being oriented toward the external medium. However, upon embedding these preformed cysts in collagen gels, a reversal of polarity was observed within hours, the microvilli-rich pole now facing the cyst cavity. Thus, in the same clonally derived cell population, cell-to-cell contact and interaction with the extracellular matrix differentially affect the orientation of cellular polarity. The LLC-PK1/D + Sc cysts provide a suitable in vitro model system for further study of the sequential events by which extracellular matrix components induce an appropriately oriented polarization. In addition, the comparison between LLC-PK1/D + Sc and D- cells, which differ in their ability to polarize in response to cell-to-cell contact, should help define some of the cellular determinants involved in epithelial organization.


Individual and COVID-19-Specific Indicators of Compliance with Mask Use and Social Distancing: The Importance of Norms, Perceived Effectiveness, and State Response.
COVID-19 is a global pandemic that has resulted in widespread negative outcomes. Face masks and social distancing have been used to minimize its spread. Understanding who will engage in protective behaviors is crucial for continued response to the pandemic. We aimed to evaluate factors that are indicative of mask use and social distancing among current and former college students prior to vaccine access. Participants (N = 490; 67% female; 60% White) were current and former U.S. undergraduate college students. Perceived effectiveness and descriptive norms regarding COVID-19 safety measures, COVID-19-related news watching and seeking, state response timing to stay-at-home mandates, impulsivity-like traits, affect (mood), and demographic variables were assessed. Results found that greater perceived effectiveness indicated increased personal compliance within and across behaviors. Greater norms related to compliance within behaviors (e.g., indoor norms related to indoor compliance). Increased perceived stress, anxiety, and negative affect indicated greater compliance. More positive affect was associated with less compliance. Being non-White, compared to White (p < 0.001), and female, compared to male (p < 0.001), were associated with greater compliance. Overall, early implementation of stay-at-home orders, exposure to COVID-19-related news, and increased perceived effectiveness are crucial for health safety behavior compliance. Findings are important for informing response to health crises, including COVID-19.


Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis. Anti-α-gal antibodies identified α-gal in the salivary glands of both Am. americanum and Ix. scapularis, while Am. maculatum and De. variabilis appeared to lack the carbohydrate. PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands. Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks. Am. americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal. N-linked glycan analysis revealed that Am. americanum and Ix. scapularis have α-gal in their saliva and salivary glands, but Am. maculatum contains no detectable quantity. Consistent with the glycan analysis, salivary samples from Am. americanum and Ix. scapularis stimulated activation of basophils primed with plasma from α-gal allergic subjects. Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.


Complete Genome Sequence of Bacillus subtilis Strain WB800N, an Extracellular Protease-Deficient Derivative of Strain 168.
Bacillus subtilis WB800N is a genetically engineered variant of B. subtilis 168, such that all extracellular proteases are disrupted, which enables WB800N to be widely used for the expression of secretory proteins. Here, we report the 4.2-Mb complete genome sequence of WB800N and present all of the disrupted gene structure.


Evaluation of the ray-casting analytical algorithm for pencil beam scanning proton therapy.
For pencil beam scanned (PBS) proton therapy, analytical dose calculation engines are still typically used for the optimisation process, and often for the final evaluation of the plan. Recently however, the suitability of analytical calculations for planning PBS treatments has been questioned. Conceptually, the two main approaches for these analytical dose calculations are the ray-casting (RC) and the pencil-beam (PB) method. In this study, we compare dose distributions and dosimetric indices, calculated on both the clinical dose calculation grid and as a function of dose grid resolution, to Monte Carlo (MC) calculations. The analysis is done using a comprehensive set of clinical plans which represent a wide choice of treatment sites. When analysing dose difference histograms for relative treatment plans, pencil beam calculations with double grid resolution perform best, with on average 97.7%/91.9% (RC), 97.9%/92.7% (RC, double grid resolution), 97.6%/91.0% (PB) and 98.6%/94.0% (PB, double grid resolution) of voxels agreeing within ±5%/± 3% between the analytical and the MC calculations. Even though these point-to-point dose comparison shows differences between analytical and MC calculations, for all algorithms, clinically relevant dosimetric indices agree within ±4% for the PTV and within ±5% for critical organs. While the clinical agreement depends on the treatment site, there is no substantial difference of indices between the different algorithms. The pencil-beam approach however comes at a higher computational cost than the ray-casting calculation. In conclusion, we would recommend using the ray-casting algorithm for fast dose optimization and subsequently combine it with one MC calculation to scale the absolute dose and assure the quality of the treatment plan.


Evaluating physical functioning in critical care: considerations for clinical practice and research.
The evaluation of physical functioning is valuable in the intensive care unit (ICU) to help inform patient recovery after critical illness, to identify patients who may require rehabilitation interventions, and to monitor responsiveness to such interventions. This viewpoint article discusses: (1) the concept of physical functioning with reference to the World Health Organization International Classification of Functioning, Disability and Health; (2) the importance of measuring physical functioning in the ICU; and (3) methods for evaluating physical functioning in the ICU. Recommendations for clinical practice and research are made, along with discussion of future directions.


Map1lc3b and Sqstm1 Modulated Autophagy for Tumorigenesis and Prognosis in Certain Subsites of Oral Squamous Cell Carcinoma.
Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1(SQSTM1) are widely used proteins to evaluate autophagy in tumor tissues. However, the role of MAP1LC3B and SQSTM1 in OSCC is not fully understood, particularly in certain subsites. With a tissue microarray comprised of 498 OSCC patients, including 181 BMSCC, 244 TSCC, and 73 LSCC patients, we found that the expression levels of MAP1LC3B and cytoplasmic SQSTM1 were elevated in the tumor tissues of three subsites compared with those in adjacent normal tissues. MAP1LC3B was associated with a poor prognosis only in TSCC. SQSTM1 was associated with poor differentiation in three subsites, while the association with lymph node invasion was only observed in BMSCC. Interestingly, MAP1LC3B was positively correlated with SQSTM1 in the tumor tissues of BMSCC, whereas it showed no correlation with SQSTM1 in adjacent normal tissue. The coexpression of higher MAP1LC3B and SQSTM1 demonstrated a significantly worse disease-specific survival (DSS) and disease-free survival (DFS) in patients with BMSCC and LSCC, but not TSCC. The knockdown of MAP1LC3B and SQSTM1 reduced autophagy, cell proliferation, invasion and tumorspheres of BMSCC cells. Additionally, silencing both MAP1LC3B and SQSTM1 enhanced the cytotoxic effects of paclitaxel in the tumorspheres of BMSCC cells. Taken together, MAP1LC3B and SQSTM1 might modulate autophagy to facilitate tumorigenesis and chemoresistance in OSCC, particularly in BMSCC.


Migration as a risk and a livelihood strategy: HIV across the life course of migrant families in India.
Migrant workers are understood to be vulnerable to HIV. However, little is known about the experience of migration-based households following HIV infection. This qualitative study examined the migration-HIV relationship beyond the point of infection, looking at how it affects livelihood choices, household relationships and the economic viability of migrant families. We conducted semi-structured interviews with 33 HIV-positive migrant men and women recruited from an anti-retroviral therapy (ART) centre in north India. Following infection among the migrant men, contact with free, public-sector HIV services was often made late, after the development of debilitating symptoms, abandonment of migrant work and return to native villages. After enrolment at the ART centre participants' health eventually stabilised but they now faced serious economic debt, an inflexible treatment regimen and reduced physical strength. Insecure migrant job markets, monthly drug collection and discriminatory employment policies impeded future migration plans. HIV-positive wives of migrants occupied an insecure position in the rural marital household that depended on their husbands' health and presence of children. The migration-HIV relationship continued to shape the life course of migrant families beyond the point of infection, often exposing them again to the economic insecurity that migration had helped to overcome, threatening their long-term survival.


Relationship of brain morphine levels to analgesic activity in acutely treated mice and rats and in pellet implanted mice.
The relationship of brain morphine concentration, determined fluorometrically, to tail-flick activity was investigated after acute and chronic morphine treatment of mice and acute treatment of rats. Brain morphine levels were quantitatively related to the analgesic effect on acute administration, with levels of 100 and 140 ng/g of tissue corresponding to the ED50 in mice and rats, respectively. Over a 90-minute time course after acute s.c. injection, the analgesic effect of morphine in the tail-flick test lagged slightly behind morphine brain level in both species. In mice implanted s.c. with morphine pellets, significant analgesia and appreciable morphine brain levels appeared as early as 20 to 30 minutes after implantation. Increased brain morphine corresponded to increased analgesia at 1 and 4 hours after implantation. Tolerance was evident by 24 hours after implantation and was maximal at 72 hours. Brain morphine remained elevated up to 144 hours after implantation even though substantial encapsulation of the pellet occurred within 72 hours. If pellets were removed at 72 hours, brain morphine declined to control levels with 6 hours, but significant tolerance persisted for at least 24 hours after pellet removal. These results demonstrate that morphine is absorbed from the pellet up to 6 days after implantation and that the decreased analgesic activity observed in the latter times is due to tolerance to the narcotic and not to a decrease in absorption from the pellet.


[Hormonal-metabolic and immune status in recurrent laryngeal papillomatosis in children].
Clinical, biochemical and immunological findings in 12 children with recurrent laryngeal papillomatosis evidence for defects in hormonal--metabolic and immune profiles in terms of depressed sympathoadrenal, adrenocortical functions and secondary immunodeficiency. To correct the above disorders it is advisable to practice immunocorrective therapy and drugs (prospidin) stimulating adrenal function.


Expanding the Spectrum of Movement Disorders Associated With C9orf72 Hexanucleotide Expansions.
Hexanucleotide repeat expansions (HREs) in C9orf72 are a major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We aimed to determine the frequency and phenomenology of movement disorders (MD) in carriers of HRE in C9orf72 through a retrospective review of patients' medical records. We retrospectively reviewed the clinical records of patients carrying a C9orf72 HRE in the pathogenic range and compared the characteristics of patients with and without MD. Seventeen of 40 patients with a C9orf72 HRE had a documented MD. In 6 of 17, MD were the presenting symptom, and in 2 of 17, MD were the sole manifestation of the disease. FTD was present in 13 of 17 patients, ALS in 5 of 17 patients, and 2 of 17 patients did not develop FTD or ALS. Thirteen of 17 patients had more than one MD. The most common MD were parkinsonism and tremor (resembling essential tremor syndrome), each one present in 11 of 17 patients. Distal, stimulus-sensitive upper limbs myoclonus was present in 6 of 17 patients and cervical dystonia in 5 of 17 patients. Chorea was present in 5 of 17 patients, 4 of whom showed marked orofacial dyskinesias. The most frequent MD combination was tremor and parkinsonism, observed in 8 of 17 patients, 5 of whom also had myoclonus. C9orf72 patients without MD had shorter follow-up times and higher proportion of ALS, although these results did not survive the correction for multiple comparisons. MD are frequent in C9orf72. They may precede signs of ALS or FTD, or even be present in isolation. Parkinsonism, tremor, and myoclonus are most commonly observed.


CAD/CAM guided surgery in implant dentistry. A review of software packages and step-by-step protocols for planning surgical guides.
Three-dimensional radiographic imaging for dental implant treatment planning is gaining widespread interest and popularity. However, application of the data from 30 imaging can be a complex and daunting process initially. The purpose of this article is to describe features of three software packages and the respective computerized guided surgical templates (GST) fabricated from them. A step-by-step method of interpreting and ordering a GST to simplify the process of the surgical planning and implant placement is discussed.


Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial meningitis.
CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC-chemokine that specifically acts on neutrophils. To obtain insight into the extent of local presence and action of CXCL5 during bacterial meningitis, we measured its concentrations in cerebrospinal fluid (CSF) of patients with culture-proven bacterial meningitis (n=14), aseptic meningitis (n=6), and controls (n=32) and compared these results with levels of other CXC-chemokines, CXCL8- (interleukin-8) and CXCL1-related oncogene (growth-related oncogene (GRO)-alpha). Patients with bacterial meningitis had profoundly elevated CSF concentrations of all three chemokines. CXCL5 was not detectable in patients with aseptic meningitis or control subjects. CSF from patients with bacterial meningitis exerted chemotactic activity towards neutrophils, which was partially inhibited by neutralizing antibodies against CXCL5 and CXCL8, but not CXCL1. CSF from controls exerted minor chemotactic activity, which could be strongly enhanced by the addition of recombinant CXCL5, CXCL8 or CXCL1. During bacterial meningitis, CXCL5 is elevated in CSF, where it is involved in the recruitment of neutrophils to the central nervous system.


Osteoarthritis in cynomolgus macaques. III: Effects of age, gender, and subchondral bone thickness on the severity of disease.
Knee joints from cynomolgus monkeys of both genders and a wide range of ages were examined to characterize further the natural history of osteoarthritis (OA) in these animals. The objectives of this study were to characterize better the subchondral bone changes previously noted in this disease, to determine whether the severity of OA in these animals is affected by age or weight, and to determine whether males and females are affected similarly. As had been seen in previous studies, the medial tibial plateau was the most severely affected site. The thickness of the subchondral plate in the medial tibial plateau increased with increasing severity of articular cartilage lesions in both males and females; however, in monkeys with subchondral plate thicknesses less than 400 microns, articular cartilage lesions were essentially absent. Subchondral plate thickness increased with increasing weight in both genders, but females had a higher subchondral plate thickness than males for a given body weight. There was no correlation between bone volume in the proximal tibial epiphysis and articular cartilage lesions of OA. The prevalence and severity of OA in the medial tibial plateau increased with increasing age, but were not affected by gender or weight. Although there was no correlation between articular cartilage lesions and body mass index or weight, the waist/hip circumference ratio and severity of articular cartilage lesions were correlated in the female monkeys. This work provides evidence that thickening of the subchondral bone plate may be more important than the volume of epiphyseal/metaphyseal cancellous bone in determining the biomechanical stresses in the joint and in influencing the development of articular cartilage lesions.


LCMR1 interacts with DEK to suppress apoptosis in lung cancer cells.
To win the war against lung cancer, the molecular mechanisms underlying its oncogenesis and metastasis must be identified in order to develop novel diagnosis and treatment strategies. We previously identified a novel gene, namely lung cancer metastasis related protein 1 (LCMR1; GenBank accession no. AY148462), which was demonstrated to be overexpressed in non‑small‑cell lung cancer. LCMR1 expression was significantly associated with clinical stage. To further understand the mechanism of LCMR1 in lung cancer, the present study screened a cDNA library from the lung cancer cell line 95D for proteins interacting with LCMR1 by yeast two‑hybrid assay, and the protein DEK was identified. Co‑immunoprecipitation and glutathione S‑transferase pull‑down assays were performed to confirm the interaction between LCMR1 and DEK in vivo and in vitro. The results demonstrated that the interaction was mediated primarily by the N‑terminal region of DEK, suggesting that LCMR1 may be involved in the regulation of cell apoptosis. Using RNA interference, DEK and LCMR1 were demonstrated to cooperate in the inhibition of apoptosis in lung cancer cells, and this effect was associated with the induced myeloid leukemia protein cell differentiation protein 1 pathway. The present findings suggest that LCMR1 might serve as a potential molecular target for lung cancer therapy.


Toxicity of CuO nanoparticles to yeast Saccharomyces cerevisiae BY4741 wild-type and its nine isogenic single-gene deletion mutants.
A suite of eight tentatively oxidative stress response-deficient Saccharomyces cerevisiae BY4741 single-gene mutants (sod1Δ, sod2Δ, yap1Δ, cta1Δ, ctt1Δ, gsh1Δ, glr1Δ, and ccs1Δ) and one copper-vulnerable mutant (cup2Δ) was used to elucidate weather the toxicity of CuO nanoparticles to S. cerevisiae is mediated by oxidative stress (OS). Specifically, sensitivity profiles of mutants' phenotypes and wild-type (wt) upon exposure to nano-CuO were compared. As controls, CuSO4 (solubility), bulk-CuO (size), H2O2, and menadione (OS) were used. Growth inhibition of wt and mutant strains was studied in rich YPD medium and cell viability in deionized water (DI). Dissolved Cu-ions were quantified by recombinant metal-sensing bacteria and chemical analysis. To wt strain nano-CuO was 32-fold more toxic than bulk-CuO: 24-h IC50 4.8 and 155 mg/L in DI and 643 and >20000 mg/L in YPD, respectively. In toxicant-free YPD medium, all mutants had practically similar growth patterns as wt. However, the mutant strains sod1Δ, sod2Δ, ccs1Δ, and yap1Δ showed up to 12-fold elevated sensitivity toward OS standard chemicals menadione and H2O2 but not to nano-CuO, indicating that CuO nanoparticles exerted toxicity to yeast cells via different mechanisms. The most vulnerable strain to all studied Cu compounds was the copper stress response-deficient strain cup2Δ (∼16-fold difference with wt), indicating that the toxic effect of CuO (nano)particles proceeds via dissolved Cu-ions. The dissolved copper solely explained the toxicity of nano-CuO in DI but not in YPD. Assumingly, in YPD nano-CuO acquired a coating of peptides/proteins and sorbed onto the yeast's outer surface, resulting in their increased solubility in the close vicinity of yeast cells and increased uptake of Cu-ions that was not registered by the assays used for the analysis of dissolved Cu-ions in the test medium. Lastly, as yeast retained its viability in DI even by 24th hour of incubation, the profiling of the acute basal toxicity of chemicals toward yeasts may be conducted in DI.


Analysis and Clustering of Upper Limb Motion during the Hand Dexterity Pegboard Test using Inertial Sensor Systems.
Maintaining hand and upper limb mobility is important from the viewpoint of freedom in daily life and high performance in work. Few studies on the mobility and dexterity of the upper limb have focused on detailed hand and finger movements. Therefore, we measured the motion of the upper limbs during a general hand dexterity pegboard test using inertial sensor systems and our previous measuring method. To clarify the characteristics of each purpose of motion, we divided the peg-in-hole motion in the pegboard test into its three sections, focusing on two sections: the pinch section, and the carry and insert section. In addition, the obtained joint angles were grouped into arm group and finger group, and singular value decomposition was performed for each joint group in each section. By clustering the decomposition results across five subjects' multiple right and left arm tests, and averaging the singular vectors in the same cluster, the joint distributions and combinations could be clarified. In addition, by recalculating joint angles from averaged SVD results and applying them to the rigid link model, we obtained motion animation with characteristics that made it possible to more clearly understand the requirements for greater dexterity. These results suggested high dexterity motion characteristics in the pinch section, and the carry and insert section of the pegboard test.


[Cancer as a microevolutionary process affecting telomere structure and dynamics: the contribution of telomeres to cancer].
Telomeres play fundamental roles in genome stability, nuclear architecture and chromosome pairing during meiosis. They shorten at every cell division and may be re-elongated or not depending on the presence of the dedicated enzyme, telomerase. Since in most human somatic cells telomerase is not expressed, shortening of telomeres during development and aging is the rule. Short telomeres being, under physiological conditions, incompatible with extended cell proliferation, telomere length defines the proliferation potential of a cell and operates as a mechanism to prevent uncontrolled cell growth. Conversely, in cells in which proliferation checkpoints have been abolished, shortening of telomeres causes chromosomes to fuse and to initiate cycles of breakage-fusion-bridge thus becoming a strong driving force for genome instability. In vitro, transformed cells with highly unstable genomes because of severe telomere shortening accumulate deleterious genetic changes and die (crisis). At the same time, random genetic or epigenetic changes may allow cells to acquire a telomere maintenance mechanism (as well as other tumor phenotypes) and to become immortal. Although telomere shortening and other types of telomere dysfunction probably contribute to the genome instability detected in early tumors in vivo, the direct contributions of dysfunctional telomeres to the acquisition of tumor phenotypes in humans remain largely unspecified.


The deficit is not a well-defined measure of fiscal policy.
Notwithstanding its widespread use, the government's deficit is not a well-defined measure of fiscal policy from the perspective of neoclassical economics; the equations of neoclassical models do not define the deficit. Rather than being a fundamental economic concept, the deficit is an arbitrary cash flow accounting construct with no necessary relation to the true stance of fiscal policy. Although the deficit is supposed to indicate how the burden of paying for the government's consumption is spread across different generations, actual changes in the measured deficit in the United States have had little if any relation to changes in the burden imposed by the government on different generations. The deficit's lack of definition is illustrated with a simple model, and the potential for misreading fiscal policy is discussed with U.S. fiscal policy in the 1980s as an example. In this article, creation of present value generational accounts are called for that would properly measure the intergenerational stance of fiscal policy.


Micafungin twice-a-week for prophylaxis of invasive Aspergillus infections in children with acute lymphoblastic leukaemia: a controlled cohort study.
Invasive Aspergillus infections during the early phase of childhood acute lymphoblastic leukemia (ALL) treatment come with morbidity and mortality. The interaction with vincristine hampers first-line azole prophylaxis. We describe the efficacy of an alternative twice-a-week micafungin regimen for Aspergillus prophylaxis. Newly diagnosed paediatric patients with ALL treated according to the ALL-11 protocol received micafungin twice-a-week (9 mg/kg/dose [max. 300 mg]) during the induction course (first 35 days of treatment) as part of routine care. A historical control cohort without Aspergillus prophylaxis was used. During the first consolidation course (day 36-79), standard itraconazole prophylaxis was used in both groups. The percentage of proven/probable Aspergillus infections during the induction/first consolidation course was compared between the cohorts. The cumulative incidence of proven/probable Aspergillus infections was estimated using a competing risk model. For safety evaluation, liver laboratory chemistry values were analysed. A total of 169 and 643 paediatric patients with ALL were treated in the micafungin cohort (median age: 4 years [range 1-17]) and historical cohort (median age: 5 years [range 1-17]). The percentage of proven/probable Aspergillus infections was 1∙2% (2/169) in the micafungin cohort versus 5∙8% (37/643) in the historical cohort (p=0.013; Fisher's exact test). The differences in estimated cumulative incidence were assessed (p=0∙014; Gray's test). Although significantly higher ALT/AST values were reported in the micafungin cohort, no clinically relevant side effects were observed. Twice-a-week micafungin prophylaxis during the induction course significantly reduced the occurrence of proven/probable Aspergillus infections in the early phase of childhood ALL treatment.


Thalamic deep brain stimulation for tremor in Parkinson disease, essential tremor, and dystonia.
To report on the long-term outcomes of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) in Parkinson disease (PD), essential tremor (ET), and dystonic tremor. One hundred fifty-nine patients with PD, ET, and dystonia underwent VIM DBS due to refractory tremor at the Grenoble University Hospital. The primary outcome was a change in the tremor scores at 1 year after surgery and at the latest follow-up (21 years). Secondary outcomes included the relationship between tremor score reduction over time and the active contact position. Tremor scores (Unified Parkinson's Disease Rating Scale-III, items 20 and 21; Fahn, Tolosa, Marin Tremor Rating Scale) and the coordinates of the active contacts were recorded. Ninety-eight patients were included. Patients with PD and ET had sustained improvement in tremor with VIM stimulation (mean improvement, 70% and 66% at 1 year; 63% and 48% beyond 10 years, respectively; p < 0.05). There was no significant loss of stimulation benefit over time (p > 0.05). Patients with dystonia exhibited a moderate response at 1-year follow-up (41% tremor improvement, p = 0.027), which was not sustained after 5 years (30% improvement, p = 0.109). The more dorsal active contacts' coordinates in the right lead were related to a better outcome 1 year after surgery (p = 0.029). During the whole follow-up, forty-eight patients (49%) experienced minor side effects, whereas 2 (2.0%) had serious events (brain hemorrhage and infection). VIM DBS is an effective long-term (beyond 10 years) treatment for tremor in PD and ET. Effects on dystonic tremor were modest and transient. This provides Class IV evidence. It is an observational study.


High-resolution computed tomography temporal bone imaging in achondroplasia.
Achondroplasia is a genetic condition caused by disordered endochondral ossification, which leads to rhizomelic dwarfism and midfacial hypoplasia. Additionally, several morphologic changes in the temporal bone are thought to at least partially contribute to hearing loss in these patients. We present a patient with achondroplasia who presented with hearing loss and was referred to radiology for temporal bone imaging. High-resolution computed tomography of temporal bones demonstrated several interesting morphological abnormalities characteristic of achondroplasia.


Validation of the circulating monocyte being representative of the cholesterol-loaded macrophage: biomediator activity.
Inflammation is pivotal to atherosclerosis. The monocyte-macrophage, a crucial cell in atherogenesis, is present during all stages of atherosclerosis. However, there is a paucity of data comparing circulating monocytes to cholesterol-laden macrophages (foam cells), with regard to their atherogenic properties, especially in subjects with established risk factors such as hyperlipidemia. To determine whether the circulating blood monocyte is representative of the cholesterol-loaded macrophage with regard to its proatherogenicity in healthy controls and hyperlipidemic patients. Fasting blood was drawn from 32 subjects (n = 16 controls and n = 16 hyperlipidemic patients), and peripheral blood monocytes were obtained. Also, macrophages were cultured and loaded with acetyl low-density lipoprotein on day 10. Day 1 peripheral blood monocytes and day 11 cholesterol-loaded macrophages were assessed for release of superoxide anion and cytokines (interleukin 1, interleukin 6, tumor necrosis factor alpha); surface expression of CD11b, VLA-4, and CD40; and adhesion to human endothelium. Monocyte and cholesterol-loaded macrophage superoxide anion release, cytokines, and adhesion of monocytes to human endothelium were significantly increased in hyperlipidemic patients compared with controls. Furthermore, following cholesterol loading, there were no significant differences in monocyte versus cholesterol-loaded macrophage activity (P = .71). Also, CD14 and CD11b surface expression on monocytes was significantly increased in hyperlipidemic patients as compared with controls. The magnitude of change in the monocytes versus cholesterol-loaded macrophages was similar. From these studies, we can conclude that the monocyte, which is readily accessible, is an appropriate cell to study for modulation of proatherogenic activity, especially with regard to genomic and proteomic analyses/ microarrays.


Locally asymptotically rank-based procedures for testing autoregressive moving average dependence.
The problem of testing a given autoregressive moving average (ARMA) model (in which the density of the generating white noise is unspecified) against other ARMA models is considered. A distribution-free asymptotically most powerful test, based on a generalized linear serial rank statistic, is provided against contiguous ARMA alternatives with specified coefficients. In the case in which the ARMA model in the alternative has unspecified coefficients, the asymptotic sufficiency (in the sense of Hájek) of a finite-dimensional vector of rank statistics is established. This asymptotic sufficiency is used to derive an asymptotically maximin most powerful test, based on a generalized quadratic serial rank statistic. The asymptotically maximin optimal test statistic can be interpreted as a rank-based, weighted version of the classical Box-Pierce portmanteau statistic, to which it reduces, in some particular problems, under gaussian assumptions.


Postnatal BDNF expression profiles in prefrontal cortex and hippocampus of a rat schizophrenia model induced by MK-801 administration.
Neonatal blockade of N-methyl-D-aspartic acid (NMDA) receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF) expression profiles in different regions and correlation with "schizophrenia-like" behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND) 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC) were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.


Transcriptional changes in Crassostrea gigas oyster spat following a parental exposure to the herbicide diuron.
The Pacific oyster Crassostrea gigas is the main oyster species produced in the world, and a key coastal economic resource in France. High mortalities affect Pacific oysters since 2008 in France and Europe. Their origins have been attributed to a combination of biotic and abiotic factors, underlining the importance of environment quality. The impact of water pollution has been pointed out and one of the pollutants, the genotoxic herbicide diuron, occurs at high concentrations all along the French coasts. Previous work has revealed that a parental exposure to diuron had a strong impact on hatching rates and offspring development even if spats were not exposed to diuron themselves. In this study, we explored for the first time the transcriptional changes occurring in oyster spats (non exposed) originating from genitors exposed to an environmentally relevant concentration of diuron during gametogenesis using the RNAseq methodology. We identified a transcriptomic remodeling revealing an effect of the herbicide. Different molecular pathways involved in energy production, translation and cell proliferation are particularly disturbed. This analysis revealed modulated candidate genes putatively involved in response to oxidative stress and mitochondrial damage in offspring of genitors exposed to diuron. Complementary measures of the activity of enzymes involved in these latter processes corroborate the results obtained at the transcriptomic level. In addition, our results suggested an increase in energy production and mitotic activity in 5-month-spats from diuron-exposed genitors. These results could correspond to a "catch-up growth" phenomenon allowing the spats from diuron-exposed genitors, which displayed a growth delay at 3 months, to gain a normal size when they reach the age of 6 months. These results indicate that exposure to a concentration of diuron that is frequently encountered in the field during the oyster's gametogenesis stage can impact the next generation and may result in fitness disturbance.


[In vitro stimulation of specific antileukemia T-cell response by dendritic cells derived from CD14+ acute monocytic leukemia cells].
Dendritic cells (DCs) or DC-like cells had been successfully induced in vitro from leukemia cells, which may provide a promising immunotherapeutic protocol for leukemia. This study was designed to investigate the efficiency of in vitro generation of dendritic cells from CD14+ acute myelomonocytic (M4) or monocytic (M5) leukemia cells and their ability of stimulating specific antileukemia T-cell response. Bone marrow mononuclear cells (BMMNCs) were isolated from 5 M4/M5 leukemia patients with high CD14 expression, and then divided into 3 groups: adherent leukemia cells, nonadherent blasts, and total unfractioned blasts. CD14 expression of the 3 groups was evaluated by flow cytometry (FCM). When cultured with or without granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) for 7-10 days, monocytic leukemia cell-derived dendritic cells (Mo-LDCs) were identified through morphologic observation and immunophenotype analysis using FCM. The immune function of Mo-LDCs was detected through allogeneic mixed lymphocyte reaction (Allo-MLR) and cytotoxicity assay of antileukemia cytotoxic T lymphocytes (CTLs). The leukemic origin of Mo-LDCs was confirmed by chromosomal karyotype analysis combined with the aberrant expression of myeloid antigens. The amount of CD14+ cells, which could differentiate into CD83+ mature DCs under induction of the cytokine combination, was higher in adherent leukemia cells than in nonadherent blasts and total unfractioned blasts. Regarding each 3 cell groups of the same patient or the unfractioned blasts of various patients, initial CD14 expression was positively related to the yield of CD83+ DCs after induction (r = 0.967, P = 0.007). Mo-LDCs exhibited typical morphology and phenotype as mature DCs, induced potent proliferation of homogeneous T cells in Allo-MLR, stimulated the expansion of leukemia-specific CTLs, and continued to possess the cytogenetic abnormalities of the original leukemia, as well as the aberrant expression of myeloid antigens. In M4/M5 subtype of AML, CD14+ cells could differentiate into immune-competent Mo-LDCs under the induction of the cytokine combination. CD14 expression level may predict the DCs differentiation ability of monocytic leukemia. Mo-LDCs, which possess the classical phenotype and function of DCs, as well as the abnormal leukemic antigens, may be useful for the immunotherapy of M4/M5 AML.


[Chronic hypophosphatemic osteopathy (author's transl)].
The process of chronic hypophosphatemic vitamin D-resistant rickets--observation of two cases. With the male patient--our first case--the disease was sporadic and had not been recognized for a long time. In his early adulthood it manifested itself as Umbauzonen (pseudofractures) in the larger context of active osteomalacia. It was possible to observe the pseudofractures before and while the patient was treated with drugs. High doses of vitamin D 3 and dosage of phosphate mitigated the complains although with respect to the radiological, scintigraphic, humoral and histological findings there was only slow improvement or no improvement at all.--The patient's daughter is affected by the disease as well. In her case the pathological signs of her bones became better when treated with vitamin D 3.


Structures of thrombin retro-inhibited with SEL2711 and SEL2770 as they relate to factor Xa binding.
Most thrombin active-site inhibitors form a short antiparallel beta-strand with residues Ser214-Gly216. However, the Selectide Corp. inhibitors SEL2711 and SEL2770 bind to thrombin in a retro fashion, making a parallel beta-strand with Ser214-Gly216 similar to other retro-binding inhibitors. The crystallographic structures of thrombin-hirugen complexed with SEL2711 and SEL2770, which are isostructural with the binary thrombin-hirugen complex, have been determined and refined in the 9.0-2.1 A resolution range to final R values of 16.5 and 16.7%, respectively. The structures of the SEL2711 and SEL2770 complexes contain 131 and 104 water molecules, respectively, both of which correspond to occupancies of greater than 0.5. The L-4-amidinophenylalanyl residues of SEL2711 and SEL2770 are fixed at the S1 specificity site, utilizing favorable ionic and hydrogen-bonding interactions between the N atoms of the amidino group and the side-chain O atoms of Asp189. The Glu192 residue of thrombin adopts an extended conformation, which allows the L-cyclohexylglycyl residue in the P2 retro-binding position of the inhibitors to occupy a similar site to the P3 aspartate in thrombin platelet-receptor peptides bound to thrombin. The N-terminal acetyl group of both inhibitors is located in the S2 subsite, while the L-3-pyridyl-(3-methyl)-alanyl of SEL2711 and the L-(N,N-dimethyl)lysine of SEL2770 occupy the S3 D-Phe subsite of D-PheProArg chloromethyl ketone (PPACK) in the thrombin-PPACK complex. The two C-terminal residues of SEL2711 (leucine and proline) point into the solvent and have no electron density in the thrombin complex. Those of SEL2770 are also positioned into the solvent, but surprisingly produce weak electron density with high B values (<B> = 50 A2). Since the Selectide inhibitors are about 10(4) times more specific for factor Xa, modeling retro-binding to the latter suggests that the selectivity can be a consequence of interactions of the inhibitors in the S3-S4 binding subsites of factor Xa.


Gender disparities in HIV infection among persons who inject drugs in Central Asia: a systematic review and meta-analysis.
Disparities in HIV infection, with females having higher rates of HIV infection than males, have been noted among persons who inject drugs (PWID) in many countries. We examined male/female HIV disparities among PWID in Central Asia and compared these disparities with patterns worldwide. A systematic review and meta-analyses were conducted for studies reporting HIV prevalence by gender among PWID. To be included in the analyses, reports had to contain (1) samples of PWID from Central Asia, (2) HIV data based on laboratory testing, (3) HIV prevalence reported for males and females, and (4) samples that were not recruited on the basis of HIV status. Data were abstracted from 11 studies in 5 countries in Central Asia: China, Kazakhstan, Russia, Tajikistan, and Uzbekistan; the total sample size was 12,225. The mean weighted OR for HIV prevalence among females to males was 0.913 (95% CI 0.07, 1.26), with high heterogeneity among studies (I(2)=70.0%) and a possible publication bias among studies with small sample sizes (Eggers test=-1.81, 95% CI -5.18, 0.54). The non-significant higher HIV prevalence among male PWID in Central Asia contrasts with the worldwide findings which show slightly higher HIV prevalence among female PWID. This may reflect the relative recency of the HIV epidemics in Central Asia. The findings also suggest there may be factors that protect female PWID from HIV in some settings. Further examination of transmission dynamics in Central Asia is necessary to better understand the HIV epidemic among PWID.


[Effect of ethylenediamine derivatives on Na+, K+-ATPase and K+-p-nitrophenyl phosphatase activity of brain enzyme preparations].
The activity of Na+, K+-ATPase preparations was studied as affected by ethonium and its analogs. Ethonium is found to be able of producing a strong inhibitory effect on the Na+, K+-ATPase and K+-n-nitrophenyl phospnatase activities (I50 = 2.5.10(-5) and 6.5.10(-5) M, respectively). The inhibition is irreversible under experimental conditions and is reduced when the concentration of protein and sodium ions in the incubation medium rises. A dependence is found between the inhibitory effect of the analogs and the length of their hydrocarbon radical (the inhibition maximum corresponds to bisquarternary ammonium compound with the hydrocarbon radical consisting of 10 links) and some kinetic characteristics of this effect are studied. It is supposed that the mechanism of the inhibitory effect is due to the ethonim binding by the hydrocarbon radical in the preparation hydrophobic zone, the electrostatic interaction being not excluded.


Rapamycin promotes hematoma resorption and enhances endothelial cell function by suppressing the mTOR/STAT3 signaling in chronic subdural hematoma.
Chronic subdural hematoma (CSDH) remains a neurosurgical condition and a healthy burden especially in elderly patients. This study focuses on the functions of rapamycin and its related molecular mechanisms in CSDH management. A rat model of CSDH was induced, which developed significant hematoma on day 5 after operation. The rats were treated with rapamycin or atorvastatin, a drug with known effect on hematoma alleviation, or treated with rapamycin and atorvastatin in combination. The atorvastatin or rapamycin treatment reduced the hematoma development, blood-brain barrier permeability, neurological dysfunction in CSDH rats, and the combination treatment showed more pronounced effects. Human brain microvascular endothelial cells hCMEC/D3 were stimulated by hematoma samples to mimic a CSDH condition in vitro. The drug treatments elevated the cell junction-related factors and reduced the pro-inflammatory cytokines both in rat hematoma tissues and in hCMEC/D3 cells. Rapamycin suppressed the mTOR and STAT3 signaling pathways. Overexpression of mTOR or the STAT3 agonist suppressed the alleviating effects of rapamycin on CSDH. In summary, this study demonstrates that rapamycin promotes hematoma resorption and enhances endothelial cell function by suppressing the mTOR/STAT3 signaling.


Cerebral venous sinus thrombosis at high altitude.
Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening medical condition. We describe a case of a 47-year-old woman who presented with headache, speech defects, and visual disturbances, and was later diagnosed with cerebral venous sinus thrombosis. The article describes a possible risk of such thrombotic events with exposure to high altitude environment in patients with coagulation defects such as Factor V Leiden mutation. Besides, such neurological conditions can occur independent of altitude illness and need to be recognized as their management differs.