An evaluation of some of the methods currently available for the production of leucocyte-poor blood.
Four methods used for the production of leucocyte-poor blood were compared: liquid nitrogen recovery and washing, washing alone, the Imugard filter and the Leuko-Pak filter. Twenty units of blood were tested by each technique. Liquid nitrogen recovery and washing, and the Imugard filter removed over 95% of white cells, and 95% and 56% respectively of platelets. Washing alone was unreliable and removed on average 47% of white cells and 85% of platelets. The Leuko-Pak filter removed on average 42% of white cells and 79% of platelets.


Role of adiponectin and proinflammatory gene expression in adipose tissue chronic inflammation in women with metabolic syndrome.
The purpose of this research was to study the gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), vascular endothelial growth factor A (VEGF-A) and adiponectin (AdipoQ) genes in the visceral (omental, mesenteric) and subcutaneous adipose tissue depots in metabolic syndrome (MS). We studied 23 women with MS, with a mean age of 50.7 ± 4.5 years and mean body mass index (BMI) of 45.6 ± 9.8 kg/m(2). The control group included 10 women, with a mean age of 40.6 ± 8.7 years and normal BMI (22.3 ± 3.7 kg/m(2)). The gene expression levels in the omental (OAT), mesenteric (MAT) and subcutaneous (SAT) adipose tissues were assessed by quantitative real-time PCR. Increased gene expression levels of IL-6 and TNF-α were detected in MAT in patients with MS, compared with the control group (p < 0.05 and p < 0.005, respectively). Significant positive correlations were observed between IL-6 mRNA expression levels in OAT and the content of CD14 + cells in the peripheral blood (r = 0.55, p < 0.05), as well as between NF-κB and VEGF-A mRNA levels in OAT (r = 0.43, p < 0.05) in patients with MS. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group (p < 0.05). In addition, there were inverse correlations between AdipoQ gene levels in MAT and serum CRP levels (r = -0.63, p < 0.05), as well as between AdipoQ gene levels in MAT and serum IL-6 levels (r = -0.46, p < 0.05). These data demonstrate that proinflammatory gene expression of MAT in women with MS was increased compared with the control group. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group.


Free radical scavenging activity of Elsholtzia densa.
Medicinal plants have been used traditionally to cure a variety of diseases since ancient times. Elsholtzia densa, a rare annual herb of the Kashmir valley, was assessed for its antioxidant efficacy. Antioxidant activity of the crude extracts was evaluated using 1, 1- diphenyl-2-picryl hydrazyl free radical (DPPH), DNA sugar damage, lipid peroxidation, ferric thiocyanate (FTC) and hydrogen peroxide scavenging assays. The maximum percentage decrease of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) standard solution was recorded for the 50% ethanolic extract (90.48%). The extracts were further evaluated using the thiobarbituric acid reactive substances assay. The methanolic extract showed the highest activity (32.02%) in reducing oxidative damage to DNA. The antioxidant activity of the extracts was also determined using the linoleic acid system and the highest antioxidant activity (49.64%) was found in the 50% ethanolic extract. In the case of the FTC assay, the 50% ethanolic extract showed the highest activity (70.14%) which was comparable to that of α-tocopherol. Moreover, total phenolics concentration was found to be 62.5mg% and 77.5mg% in the cases of absolute ethanolic and 50% ethanolic extracts, respectively. These findings indicate promising antioxidant activity of crude extracts of the plant and the need for further exploration of their effective use in both modern and traditional systems of medicine.


Prevalence of Anxiety and Depression in the Iranian General Population during the COVID-19 Pandemic: A Web-Based Cross-Sectional Study.
Objective: This study aimed to determine prevalence of anxiety and depression and associated factors in the general population of Iran during the COVID-19 pandemic. Method : We conducted this web-based cross-sectional study on 5328 individuals in Iran between 17th and 29th of April 2020. Data were collected using the convenience sampling method through an anonymous online questionnaire via social media like WhatsApp and Telegram. The online survey collected data on demographic variables, COVID-19-related variables, and symptoms of anxiety and depression. Anxiety and depression were assessed using the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), respectively. Simple and multiple logistic regression analyses were performed to determine independent predictors of anxiety and depression. Results: The mean GAD-7 and PHQ-9 total scores were 7.17 (SD = 5.42) and 7.80 (SD = 6.68), respectively. Prevalence of anxiety, depression, and comorbid anxiety-depression were 30.1%, 33.4%, and 22.1%, respectively. According to the adjusted analysis, anxiety was significantly associated with female gender, being young and middle-aged, being unemployed or a housewife, having chronic diseases, spending considerable time thinking about COVID-19, having family members, friends, and/or relatives infected with COVID-19, and death of family members, relatives or friends due to COVID-19. Same results were also found for depression. Furthermore, depression was associated with being single, being resident in urban area, and having high risk individual in family. Conclusion: Prevalence of anxiety and depression were considerably higher in the general population of Iran during the COVID-19 pandemic. In addition, the findings suggest that more attention needs to be paid to vulnerable groups such as women, young/middle-aged adults, the unemployed, and people with chronic disease.


Spontaneous rupture of the urinary bladder due to bacterial cystitis.
We report a case of spontaneous rupture of the urinary bladder (SRUB) due to bacterial cystitis in a 76-year-old woman with chief complaint of abdominal pain a day before presentation. She had fever (38.0°C), and her systolic blood pressure dropped to 70 mmHg; she was referred to our hospital, where she was admitted with a diagnosis of ileus. However, her abdominal pain worsened the following day, and abdominal CT showed free air. Emergency laparotomy was performed for suspicion of digestive tract perforation, which revealed a small hole at the dome of the urinary bladder and another at the peritoneum. Suture repair was performed. We reviewed the abdominal CT on admission and noted that the perforation of the urinary bladder was present during admission, whereas that of the peritoneum occurred the following day. SRUB is rare, and bacterial cystitis rarely causes it; thus, accurate diagnosis and proper treatment are essential.


Is a single anterolateral screw-plate fixation sufficient for the treatment of spinal fractures in the thoracolumbar junction? A biomechanical in vitro investigation.
Controversy exists about the indications, advantages and disadvantages of various surgical techniques used for anterior interbody fusion of spinal fractures in the thoracolumbar junction. The purpose of this study was to evaluate the stabilizing effect of an anterolateral and thoracoscopically implantable screw-plate system. Six human bisegmental spinal units (T12-L2) were used for the biomechanical in vitro testing procedure. Each specimen was tested in three different scenarios: (1) intact spinal segments vs (2) monosegmental (T12/L1) anterolateral fixation (macsTL, Aesculap, Germany) with an interbody bone strut graft from the iliac crest after both partial corpectomy (L1) and discectomy (T12/L1) vs (3) bisegmental anterolateral instrumentation after extended partial corpectomy (L1), and bisegmental discectomy (T12/L1 and L1/L2). Specimens were loaded with an alternating, nondestructive maximum bending moment of +/-7.5 Nm in six directions: flexion/extension, right and left lateral bending, and right and left axial rotation. Motion analysis was performed by a contact-less three-dimensional optical measuring system. Segmental stiffness of the three different scenarios was evaluated by the relative alteration of the intervertebral angles in the three main anatomical planes. With each stabilization technique, the specimens were more rigid, compared with the intact spine, for flexion/extension (sagittal plane) as well as in left and right lateral bending (frontal plane). In these planes the bisegmental instrumentation compared to the monosegmental case had an even larger stiffening effect on the specimens. In contrast to these findings, axial rotation showed a modest increase of motion after bisegmental instrumentation. To conclude, the immobilization of monosegmental fractures in the thoracolumbar junction can be secured by means of bone grafting and the implant used in this study for all three anatomical planes. After bisegmental anterolateral stabilization a sufficient reduction of the movements was registered for flexion/extension and lateral bending. However, the observed slight increase of the range of motion in the transversal plane may lead to loosening of the implant before union. Therefore, the use of an additional dorsal fixation device should be considered.


Thermal effect on structure organizations in cobalt-fullerene nanocomposition.
Effect of deposition temperature (Ts) on structure of Co-C60 nanocomposite (NC) prepared by simultaneous deposition of cobalt and fullerene on sapphire is presented. The NC structure variations with Ts increasing from room temperature (RT) to 400 degrees C have been analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM) and Raman spectroscopy. AFM and SEM show granule-like structure of the Co-C60 film. The mixture film deposited at RT includes the hills on the surface suggesting accumulation of internal stress during phase separation. Raman spectra show 25 cm(-1) downshift of Ag(2) C60 peak suggesting -Co-C60- polymerization in C60-based matrix of the NC film. Analysis of Raman spectra has revealed existence of amorphous carbon (a-C) in the NC matrix that argues C60 decomposition. The Ts increase to 200 degrees C causes the surface hills smoothing. In parallel, downshift of the Ag(2) peak decreases to 16 cm(-1) that implies more pronounced phase separation and lower -Co-C60- polymerization efficiency. Also, amount of a-C content slightly increases. Further Ts increasing to 400 degrees C changes the NC structure dramatically. AFM shows evident enlargement of the granules. According to Raman spectra the high Ts deposition yields pronounced C60 decomposition increasing the a-C content. Features of a-C Raman peak imply nucleation of graphitic islands at the NC interfaces. Abundant decomposition of C60 in the mixture film deposited at 400 degrees C is referred to cobalt catalytic effect.


[Advantages of using robotic Da Vinci system for unilateral adrenalectomy: early results].
The goal of this study was to report the early results of unilateral transperitoneal adrenalectomy using robotic Da Vinci system, and to compare them to the results of the laparoscopic standard adrenalectomy. Prospective study included all patients operated on for unilateral laparoscopic or robotic adrenalectomy from November 2000 to November 2002. Twenty-eight patients underwent unilateral adrenalectomy using either standard laparoscopy (14 patients) or robotic Da Vinci system (14 patients). Mean duration of robotic adrenalectomy seemed to be longer than standard laparoscopy (111 vs. 83 min; P = 0.057). This tendency decreased while surgeons' experience was increasing. Mean duration of operating room activity was similar for both types of surgery. Peroperative events without conversion, conversion rate (7%), drainage, morbidity (21%), duration of hospitalisation were similar for both types of surgery. Duration of standard laparoscopic adrenalectomy was positively correlated to patients body mass index. This correlation was absent in patients operated on by robotic Da Vinci system. This preliminary study found no objective data demonstrating that robotic Da Vinci system was superior to standard laparoscopic approach for unilateral adrenalectomy. However, we think that it is necessary to continue further evaluation of this system to demonstrate its possible superiority.


Teaching medical communication skills: a call for greater uniformity.
Evidence suggests that strategies used in teaching communication skills vary widely among, and within, medical education programs. Such variance also exists in the amount of emphasis placed on specific communication skills. This study examines the degree of variability among medical faculty in identifying opportunities for teaching communication skills. Sixty-seven medical faculty (physicians and behavioral scientists) reviewed a videotaped interview of a clinician with a standardized patient. Using a transcript of the interview, participants identified moments in the tape they believed warranted an instructional intervention to reinforce or modify the clinician's communication skills. Items identified by the participants were compared to items identified by a panel of experts. Frequencies and ANOVAs were used to report on consistency and on consistency as a function of faculty experience and educational background. Faculty demonstrated marked differences in identifying teachable moments across all six communication categories: (1) rapport building, (2) agenda setting, (3) information management, (4) active listening for the patient's perspective, (5) responding to emotion, and(6) skills in reaching common ground. Of 67 respondents, 29.6% identified none of the opportunities to teach rapport building, while only 31% identified all opportunities; 32.8% identified none of the information management opportunities, 26.9% identified all; 77.6% failed to identify the agenda-setting opportunity, 22% did identify the opportunity; 25.4% identified none of the active listening opportunities, 9% identified all; 57.6% identified none of the responding to emotion opportunities, 18% identified all; 35.8% did not identify the opportunity for reaching common ground, 64% did identify the opportunity. Our findings demonstrate that faculty who teach communications vary widely in the issues that they identify and about which they chose to teach. Recommendations are made for further research in this area.


Patient engagement to enhance recovery for children undergoing surgery.
For over 20 years enhanced recovery protocols (ERPs) have been used to decrease the physiologic stress and inflammation of surgery using evidence-based principles. ERPs include optimizing patient preparation, creating less trauma using minimally invasive anesthetic and surgical techniques, and regular audit of outcomes. A critical aspect of ERPs is patient engagement in all phases of care, which facilitates effective team function and focused oversight of patient flow through the system. Counseling extends beyond traditional review of surgical risks and benefits, by creating clear daily patient goals, establishing pain management plans, optimizing nutrition, and defining criteria for discharge. The patient and family are provided written and visual media resources to review. This counseling and education clearly outlines the bidirectional expectations, ensures preparedness, and empowers the patient and family by explaining the logic surrounding many of the ERP interventions. The patient and family are, in turn, activated as key stakeholders in the process and have a shared vision with the healthcare team. Most patients enjoy being considered partners and agents in their own healthcare. ERPs facilitate an optimal surgical experience that can improve patient satisfaction, outcomes, and value.


Non-canonical dimerization of the androgen receptor and other nuclear receptors: implications for human disease.
Nuclear receptors are transcription factors that play critical roles in development, homeostasis and metabolism in all multicellular organisms. An important family of nuclear receptors comprises those members that respond to steroid hormones, and which is subdivided in turn into estrogen receptor (ER) isoforms α and β (NR3A1 and A2, respectively), and a second subfamily of so-called oxosteroid receptors. The latter includes the androgen receptor (AR/NR3C4), the glucocorticoid receptor (GR/NR3C1), the mineralocorticoid receptor (MR/NR3C2) and the progesterone receptor (PR/NR3C3). Here we review recent advances in our understanding of the structure-and-function relationship of steroid nuclear receptors and discuss their implications for the etiology of human diseases. We focus in particular on the role played by AR dysregulation in both prostate cancer (PCa) and androgen insensitivity syndromes (AIS), but also discuss conditions linked to mutations of the GR gene as well as those in a non-steroidal receptor, the thyroid hormone receptor (TR). Finally, we explore how these recent results might be exploited for the development of novel and selective therapeutic strategies.


[Conisation in stage Ia cervix cancer].
Between 1975 and 1988, a total of 78 patients suffering from cervical cancer stage Ia were treated by conisation based on a positive smear. According to FIGO, these 78 patients consisted of 53 (67.9%) stage Ia1 and 25 (32.1%) stage Ia2 cases. Complete removal of the tumour by conisation was achieved in 51 patients. In 23 cases (29.5%) the margin of resection was reached by a carcinoma in situ, in 4 cases (5.1%) invasive carcinoma was found. Conisation was not followed by further surgery in 10/51 patients with complete tumour removal. One patient (1/23) with incomplete removal underwent surgery elsewhere. In the other 67/78 patients following hysterectomy, the pathologist diagnosed three cases of cervical cancer, 11 cases of carcinoma in situ and 53 cases (67.9%) without pathological findings. Carcinoma in situ after hysterectomy was found in only 2 cases (4.9%) with primarily free resection margins of the conus. Among the 27 patients with carcinoma in situ or invasive carcinoma reaching the conus margin, 9 cases of carcinoma in situ and 3 invasive carcinomas were diagnosed histologically after hysterectomy and one patient underwent surgery elsewhere. In this study, the value of conisation as single therapy of cervical cancer stage Ia1 and stage Ia2 with good prognosis (depth of infiltration of < 3 mm and no invasion of blood vessels) is discussed and the importance of thorough and exact histological examination is emphasised.


Effects of ambient temperature and exposure to 2450-MHz microwave radiation on evaporative heat loss in the mouse.
Whole-body evaporative heat loss was measured as whole-body evaporative water loss in mice during a 90-min exposure to 2450-MHz microwave radiation at an ambient temperature of 20 degrees C and in non-exposed mice maintained at ambient temperatures of 20, 25, 30, 33, and 35 degrees C. The ambient-temperature threshold for increasing evaporative water loss was between 30 and 33 degrees C. A specific absorption rate of microwave radiation in excess of 29 W/kg was required to produce an increase in heat loss. For absorption rates ranging from 29 to 44 W/kg, the mouse dissipated 65% of the total absorbed heat by water evaporation; the remainder was dissipated passively. The data collected in the mouse may be extrapolated to larger species, such as man, but only by an exponential relationship. Using this relationship, it was shown that a threshold specific absorption rate of 29 W/kg in a 0.033-kg mouse was equivalent to approximately 0.25 W/kg in a 70-kg human.


Ang II and Ang IV: unraveling the mechanism of action on synaptic plasticity, memory, and epilepsy.
The central angiotensin system plays a crucial role in cardiovascular regulation. More recently, angiotensin peptides have been implicated in stress, anxiety, depression, cognition, and epilepsy. Angiotensin II (Ang II) exerts its actions through AT(1) and AT(2) receptors, while most actions of its metabolite Ang IV were believed to be independent of AT(1) or AT(2) receptor activation. A specific binding site with high affinity for Ang IV was discovered and denominated "AT(4) receptor". The beneficiary effects of AT(4) ligands in animal models for cognitive impairment and epileptic seizures initiated the search for their mechanism of action. This proved to be a challenging task, and after 20 years of research, the nature of the "AT(4) receptor" remains controversial. Insulin-regulated aminopeptidase (IRAP) was first identified as the high-affinity binding site for AT(4) ligands. Recently, the hepatocyte growth factor receptor c-MET was also proposed as a receptor for AT(4) ligands. The present review focuses on the effects of Ang II and Ang IV on synaptic transmission and plasticity, learning, memory, and epileptic seizure activity. Possible interactions of Ang IV with the classical AT(1) and AT(2) receptor subtypes are evaluated, and other potential mechanisms by which AT(4) ligands may exert their effects are discussed. Identification of these mechanisms may provide a valuable target in the development in novel drugs for the treatment of cognitive disorders and epilepsy.


Illness beliefs and alexithymia in headache patients.
Research regarding psychological factors in head pain have generally focused upon personality traits and psychopathology. The role of illness beliefs offers another method of elucidating perceptions, attitudes and convictions towards a somatic complaint. One hundred patients, evaluated for head pain at a neurology clinic, were administered the illness Behavior Questionnaire (IBQ) to delineate illness beliefs; the illness Effects Questionnaire (IEQ) to quantify the disruptive aspects of head pain; and the Toronto Alexithymia Scale (TAS) to assess the subjects propensity to somatize as well as the ability to identify and report emotions. The data found no difference between subjects diagnosed with migraine syndrome and those with tension head pain in the IBQ dimensions, the TAS or in reported levels of anxiety or depression. However, chronicity of symptoms was associated with increased irritability. The clinical implications of the findings suggest that patients with head pain are psychologically distressed but often possess alexithymic characteristics that make insightful associations difficult.


Efficacy of enoximone in the management of refractory low-output states following cardiac surgery.
Fifteen consecutive patients with post-cardiac surgery low-output states refractory to catecholamine inotropic support and intra-aortic balloon counter-pulsation (seven patients), were given enoximone (MDL 17,043, a phosphodiesterase inhibitor), 1 to 2 mg/kg, as a slow intravenous bolus injection, followed by a continuous infusion of 3 to 10 microg/kg/min. Enoximone resulted in a marked improvement in clinical and hemodynamic conditions. Despite the severity of their initial status, all the patients survived their acute circulatory failure and all but two were discharged from the hospital. Hemodynamic improvement was observed as early as 15 minutes after the drug administration and reflected the previously reported inotropic and vasodilatory properties of enoximone. No serious adverse effects were observed. Enoximone thus appears safe and effective in the management of post-cardiac surgery low-output states. Its effects are additive to those of high-dose catecholamines.


Clinical significance of prognostic nutritional index in renal cell carcinomas.
Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study. The prognostic correlation between PNI and overall survival (OS) and recurrence-free survival (RFS) was analyzed respectively using Kaplan-Meier method and univariate and multivariate Cox model. Studies about the association between pretreatment or preoperative PNI and prognosis of RCC were systemically reviewed and a meta-analysis method was performed to further evaluate the pooled prognostic value of PNI in RCC.267 (38.47%) RCC patients had low PNI according to the cut off value (49.08). Low PNI was associated with poor OS (P < .001) and RFS (P < .001), respectively. In the multivariate Cox analysis, PNI was identified to be an independent prognostic factor for OS (hazard ratio [HR] = 2.13, 95%CI: 1.25-3.62, P = .005). Compared to other nutritional indexes, this risk correlation of PNI is better than that of geriatric nutritional risk index (GNRI; HR = 1.19; P = .531), while is no better than that of neutrophil-lymphocyte ratio (NLR; 1/HR = 2.56; P < .001) and platelet-lymphocyte ratio (PLR; 1/HR = 2.85; P < .001) respectively. Meanwhile, additional 4785 patients from 6 studies were included into pooled analysis. For RCC patients who underwent surgery, low preoperative PNI was significantly associated with worse OS (pooled HR = 1.57, 95%CI: 1.37-1.80, P < .001) and worse RFS (pooled HR = 1.69, 95%CI: 1.45-1.96, P < .001). Furthermore, low PNI (<41-51) was also significantly associated with poor OS (HR = 1.78, 95%CI: 1.26-2.53 P < .05) and poor RFS (HR = 2.03, 95%CI: 1.40-2.95, P < .05) in advanced cases treated with targeted therapies.The present evidences show that PNI is an independent prognostic factor in RCC. Low PNI is significant associated with poor prognosis of RCC patients.


beta-Phenylethylamines and the isoquinoline alkaloids.
This review covers beta-phenylethylamines and isoquinoline alkaloids derived from them, including further products of oxidation, condensation with formaldehyde and rearrangement, some of which do not contain as isoquinoline system, together with napthylisoquinoline alkaloids, which have a different biogenetic origin. The occurrence of the alkaloids with the structures of new bases, together with their reactions and syntheses, are reported. The literature from July 2003 to June 2004 is reviewed, with 145 references cited.


Pesticide exposure in dwellings near bulb growing fields in The Netherlands: an explorative study.
An explorative field study was conducted to assess residential exposure to pesticides, regularly applied in bulb farming. House dust floor samples were taken from homes of bulb farmers (n = 12) and from homes in close proximity to a bulb field (i.e. non-farmers) (n = 15). Samples were analysed for 7 pesticides used by bulb growers in the sampling period. Of these pesticides, chloropropham, flutolanil and vinchlozolin could be detected in non-farmers homes. All pesticides were detected in farmers' homes, except metamitron. Median concentrations for chloropropham were significantly higher in farmers' homes (0.05 vs. 0.20 microg/m(2), p = 0.03). Logistic regression analyses showed that the odds for detecting pesticides were higher in farmers' compared to non-farmers' homes and remained higher after correction for potential confounders. Results showed no significant effect of proximity of a residence to a bulb field for median concentrations of pesticides; however, logistic regression analysis showed a borderline statistically significant effect for detecting chloropropham above the detection limit (OR = 10, p = 0.08). These findings demonstrate that, as expected, risk of exposure is higher for bulb farmers than for non-farmers. They also indicate that exposure to pesticides is not limited to bulb farmers only, and this warrants further investigation.


Cell-intrinsic effects of non-MHC NOD genes on dendritic cell generation in vivo.
Genes outside the MHC create a general susceptibility to autoimmunity in non-obese diabetic (NOD) mice. Here we describe marked differences in dendritic cell generation in vivo, caused by non-MHC NOD genes. Analyses of splenic dendritic cells from the autoimmunity-prone NOD.H-2(k) mice revealed a relative over-representation of the CD8 alpha(-) subsets, in contrast to the level of these subsets observed in the autoimmunity-resistant B10.H-2(k) congenic strain or other H-2(k) strains. The imbalance towards CD8 alpha(-) dendritic cells was selectively manifested by NOD.H-2(k)-derived cells in radiation chimeras reconstituted with equal mixtures of NOD.H-2(k) and B10.H-2(k) bone marrow cells. In addition to the cell-intrinsic imbalance in dendritic cell subsets, the myeloid lineage overall was intrinsically altered by NOD genes, as this lineage was disproportionately derived from the NOD.H-2(k) donor in mixed chimeras. These results identify a striking effect of non-MHC NOD genes upon the balance of dendritic cell subsets that may contribute to the generalized defects in self-tolerance in the NOD strain.


Morphological changes of the rete system in the ovaries of adult bat, Scotophilus heathi, during breeding cycle.
The present study describes a well developed rete ovarii in the ovary of the adult Indian vespertilionid bat, Scotophilus heathi, and supports the role of the rete system in early follicular growth in the ovary. A close contacts between the rete tubules and follicles have been found at the beginning of the follicular growth in the mature ovary. Ultrastructural features of connecting rete cells indicate the active protein synthesis, while those of intraovarian rete cells suggest their role in transportation of secretory materials.


Cardiac surgery unmasks latent hypoparathyroidism in a child with the 22q11.2 deletion syndrome.
The 22q11.2 deletion syndrome is a developmental field defect of the third and fourth pharyngeal pouches characterized by a spectrum of thymic and parathyroid gland abnormalities and conotruncal cardiac defects. Latent hypoparathyroidism, defined as normocalcaemia at rest but reduced ability to secrete parathyroid hormone (PTH) in response to pharmacologically evoked hypocalcaemia, is found in 30-50% of people with this syndrome. Its natural history is unknown. We describe a 1.5 year-old girl with tetralogy of Fallot, normal calcium metabolism and few facial dysmorphic features who developed transient hypoparathyroidism in the postoperative period, which lasted months and waxed and waned during this observation period. The clinical picture led us to the diagnosis of 22q11.2 deletion syndrome.


Complications of percutaneous femoral vein catheterizations for hemodialysis.
Five life threatening complications of percutaneous femoral vein catheterization for hemodialysis (Shaldon Technique) are presented. They occurred over a period of five years during which 700 uneventful catheterizations were carried out. In three instances femoroiliac vein thrombosis occurred, and on one occasion this was complicated by pulmonary embolism. In two other instances perforation of the inferior vena cava occurred with profuse bleeding. These complications can be aboided by early removal of the catheters after dialysis and by cautiously manipulating the wireguide when resistance or obstruction is encountered during insertion.


A comparison of activity demands between trial matches and in-season matches across multiple teams and seasons in semi-professional, male rugby league players.
Trial matches are frequently used for team preparation in rugby league competitions, making it essential to understand the demands experienced to assess their specificity to actual competition. Consequently, this study aimed to compare the activity demands between pre-season trial matches and early in-season rugby league matches. Following a repeated-measures observational design, 39 semi-professional, male rugby league players from two clubs were monitored using microsensors during two trial matches and the first two in-season matches across two consecutive seasons. Total distance, average speed, peak speed, absolute and relative high-speed running (HSR; > 18 km · h-1) and low-speed running (LSR; < 18 km · h-1) distance, as well as absolute and relative impacts, accelerations (total and high-intensity > 3 m · s-2), and decelerations (total and high-intensity < -3 m · s-2) were measured. Linear mixed models and Cohen's d effect sizes were used to compare variables between match types. Playing duration was greater for in-season matches (p < 0.001, d = 0.64). Likewise, higher (p < 0.001, d = 0.45-0.70) activity volumes were evident during in-season matches indicated via total distance, HSR distance, LSR distance, total accelerations, high-intensity accelerations, total decelerations, and high-intensity decelerations. Regarding activity intensities, a higher average speed (p = 0.008, d = 0.31) and relative LSR distance (p = 0.005, d = 0.31) only were encountered during in-season matches. Despite players completing less volume, the average activity intensities and impact demands were mostly similar between trial and early in-season matches. These findings indicate trial matches might impose suitable activity stimuli to assist players in preparing for early in-season activity intensities.


Transient intubation for surfactant administration in the treatment of respiratory distress syndrome in extremely premature infants.
To investigate the effectiveness of transient intubation for surfactant administration and extubated to nasal continuous positive pressure (INSURE) for treatment of respiratory distress syndrome (RDS) and to identify the factors associated with INSURE failure in extremely premature infants. Eighty-four infants with gestational age less than 28 weeks treated with surfactant administration for RDS for 8 years were included. Perinatal and neonatal characteristics were retrospectively reviewed, and major pulmonary outcomes such as duration of mechanical ventilation (MV) and bronchopulmonary dysplasia (BPD) plus death at 36-week postmenstrual age (PMA) were compared between INSURE (n=48) and prolonged MV groups (n=36). The factors associated with INSURE failure were determined. Duration of MV and the occurrence of BPD at 36-week PMA were significantly lower in INSURE group than in prolonged MV group (P<0.05), but BPD plus death at 36-week PMA was not significantly different between the 2 groups. In a multivariate analysis, a reduced duration of MV was only significantly associated with INSURE (P=0.001). During the study period, duration of MV significantly decreased over time with an increasing rate of INSURE application (P<0.05), and BPD plus death at 36-week PMA also tended to decrease over time. A low arterial-alveolar oxygen tension ratio (a/APO2 ratio) was a significant predictor for INSURE failure (P=0.001). INSURE was the noninvasive ventilation strategy in the treatment of RDS to reduce MV duration in extremely premature infants with gestational age less than 28 weeks.


Vibrational multiconfiguration self-consistent field theory: implementation and test calculations.
A state-specific vibrational multiconfiguration self-consistent field (VMCSCF) approach based on a multimode expansion of the potential energy surface is presented for the accurate calculation of anharmonic vibrational spectra. As a special case of this general approach vibrational complete active space self-consistent field calculations will be discussed. The latter method shows better convergence than the general VMCSCF approach and must be considered the preferred choice within the multiconfigurational framework. Benchmark calculations are provided for a small set of test molecules.


[Effect of brachytherapy and teletherapy on treatment results in primary vaginal cancer].
From 1971 to 1977 99 cases of primary carcinoma of the vagina were treated at the Radiotherapy Department of the I. University Clinic for Gynecology and Obstetrics in Vienna. Radiotherapy was adapted individually as far as possible due to the different localisations and extensions of this tumor and to the vicinity of bladder and rectum, two very radiation-sensitive organs. Basically a three-phased scheme of treatment was intended: primarily a focal irradiation of the tumor by plaque-application, then combined intra-uterine and intra-vaginal radium insertion, followed by a vaginal cylinder. Thus the vaginal tissue is charged with about 32 Gy in a depth of 0,5 cm, the tumor itself with about 100 Gy. Percutaneous telecobalt irradiation was applied additionally following the method prescribed for carcinoma of the cervix uteri. A vulvo-perineal irradiation field was applied supplementarily , if the tumor was localised in the lower third of the vagina. 5-year overall remission rate amounted to 32% for the years 1971 to 1977; hence it was somewhat lower than for the total time observed (1950 to 1977), which was 39,8%. This could be explained by the sharp increase of very old patients and of progressed stages. For separate stages, the following 5-year healing rates were observed: stage I: 78%; stage II: 48%; stage III: 24% and stage IV: 19%. Recto-vaginal or vesico-vaginal fistulas occurred in 8% of the cases; less severe complications, such as cystitis or proctitis, were found in 41 and 43%, respectively. The effect of percutaneous telecobalt irradiation on the healing rate was marked in progressed cases, especially. Only 1 patient of 15 (7%), who were not treated by teletherapy, reached 5-year remission , as compared to 14 of 52 (27%), who received teletherapy. Stages I and II did not show a comparable difference. Intrauterine brachytherapy was of more importance for remission rate in early stages: 11 of 16 (69%) patients with stages I and II, who were treated with intrauterine curietherapy, survived 5 years or more; of those who did not have intrauterine insertion, only 6 of 15 (40%) reached 5-year remission . For stages III and IV, intrauterine curietherapy did not markedly change the healing rate.


Design, Synthesis and Fungicidal Activity of Ester Derivatives of 4-(3,4-Dichloroisothiazole) 7-Hydroxy Coumarin.
The development of new fungicides is vital for safeguarding crops and ensuring sustainable agriculture. Building on our previous finding that 4-(3,4-dichloroisothiazole)-7-hydroxy coumarins can be used as fungicidal leads, 44 novel coumarin ester derivatives were designed and synthesized to evaluate whether esterification could enhance their fungicidal activity. In vitro fungicidal bioassays indicated that compound 2ai displayed good activity against Alternaria solani, Botrytis cinereal, Cercospora arachidicola, Physalospora piricola and Sclerotinia sclerotiorum, with an EC50 value ranging from 2.90 to 5.56 μg/mL, comparable to the lead compound 1a, with its EC50 value ranging from 1.92 to 9.37 μg/mL. In vivo bioassays demonstrated that compounds 1a, 2ar and 2bg showed comparable, excellent efficacy against Pseudoperonospora cubensis at a dose of 25 µg/mL. Our research shows that the esterification of 4-(3,4-dichloroisothiazole) 7-hydroxycoumarins results in a fungicidal activity equivalent to that of its lead compounds. Furthermore, our density functional theory (DFT) calculations and 3D-QSAR modeling provide a rational explanation of the structure-activity relationship and offer valuable insights to guide further molecular design.


Tissue localization of threonine oxidation in pigs.
Two experiments were designed to determine the tissue distribution of threonine oxidation through the threonine dehydrogenase (EC 220.127.116.11) pathway in pigs. The first experiment was conducted on eleven Piétrain x Large White piglets. The piglets were slaughtered at 5, 12 or 20 kg after 1 h of infusion with L-[U-14C]threonine (55 kBq/kg) mixed with unlabelled threonine (100 mg/kg). In the second experiment, four Piétrain x Large White and four large White piglets (10 kg body weight) were infused with L-[1-13C]threonine (50 mg/kg) mixed with 50 mg/kg unlabelled threonine for 1 h, then killed for tissue sampling. In the two experiments, threonine dehydrogenase specific activity and threonine and glycine specific radioactivities and enrichments were measured in several tissues and in plasma. The higher level of labelling of threonine in the pancreas than in the liver suggested either a lower protein degradation rate or a faster rate of threonine transport in the liver than in the pancreas. Threonine dehydrogenase activity was found only in the liver and the pancreas. Whereas liver and pancreas threonine dehydrogenase specific activities were similar, glycine specific radioactivity and enrichment were 12- to 14-fold higher in the pancreas than in the liver. This is probably the consequence of a higher production rate of glycine from sources other than threonine (protein degradation, de novo synthesis from serine) in the liver than in the pancreas. Our results showed that Large White pigs could oxidize more threonine than Piétrain x Large White pigs. This could be related to the difference in growth performance and dietary N efficiency for protein deposition between these two genotypes.


Job Satisfaction and Perceived Structural Support in Remote Working Conditions-The Role of a Sense of Community at Work.
Changes in work assets due to the COVID-19 pandemic posed several challenges to employees' well-being, especially in the light of the changes in the work organization, such as remote working and the massive use of IT. According to the literature on the role of technologies at work, the organization's ability to support remote working is a valuable protective factor. At the same time, social distancing due to the pandemic forced employees to use a new relational asset. This, in turn, can shed new light on how the sense of connection and belonging to an organization impacts remote working experiences. This paper will test the mediational effect of structural support and sense of community at work in the link between job demands and job satisfaction in a sample of remote workers. The study involved 635 participants aged 21 to 70 (mean = 46.7, SD = 11; females = 61%). Among them, 33% had remote working experiences before the first Italian lockdown (March 2020). The research protocol included scales from the COPSOQ-III (job demands, sense of community, job satisfaction) and a questionnaire to evaluate the structural support related to the remote working asset. Results from a structural equation model showed a partial mediating effect of sense of community, but not of structural support, in the link between job demands and job satisfaction (χ2(22) = 76.918, p = 0.00, CFI = 0.966, TLI = 0.944, RMSEA = 0.063 (90% CI = 0.048-0.078, p = 0.079), SRMR = 0.044). The role of such associations for future technology-based work assets is detailed in the discussion.


Hypoxia blunts angiogenic signaling and upregulates the antioxidant system in elephant seal endothelial cells.
Elephant seals experience extreme hypoxemia during diving bouts. Similar depletions in oxygen availability characterize pathologies including myocardial infarction and ischemic stroke in humans, but seals manage these repeated episodes without injury. However, the real-time assessment of the molecular changes underlying protection against hypoxic injury in seals remains restricted by their at-sea inaccessibility. Hence, we developed a proliferative arterial endothelial cell culture system to assess the molecular response to prolonged hypoxia. Seal and human cells exposed to 1% O 2 for up to 6 h demonstrated differential responses to both acute and prolonged hypoxia. Seal cells decouple stabilization of the hypoxia-sensitive transcriptional regulator HIF-1α from angiogenic signaling at both the transcriptional and cellular level. Rapid upregulation of genes involved in the glutathione (GSH) metabolism pathway supported maintenance of GSH pools and increases in intracellular succinate in seal but not human cells during hypoxia exposure. High maximal and spare respiratory capacity in seal cells after hypoxia exposure occurred in concert with increasing mitochondrial branch length and independent from major changes in extracellular acidification rate, suggesting seal cells recover oxidative metabolism without significant glycolytic dependency after hypoxia exposure. In sum, our studies show that in contrast to human cells, seal cells adapt to hypoxia exposure by dampening angiogenic signaling, increasing antioxidant protection, and maintaining mitochondrial morphological integrity and function.


[A case of breast cancer with a chondrosarcomatous appearance].
A case of a breast tumor which showed the appearance of invasive ductal carcinoma and chondrosarcoma is reported. The patient was a 36-year-old female. Simple mastectomy and lymph node dissection were performed for the tumor. Local recurrence and metastases to the contralateral breast, lymph nodes, subcutaneous tissue, and bones arose after the operation. She died of the disease 2 years and 3 months after the operation. It is thought that this tumor had formed as a result of metaplasia of the carcinomatous tissue, since a histological transition between the carcinoma and sarcoma was demonstrated.


Safety of gadoversetamide in patients with acute and chronic myocardial infarction.
To assess the safety data from two large, multicenter, phase 2 trials on the use of gadoversetamide (OptiMARK, Tyco Healthcare/Mallinckrodt, St. Louis, MO) as a contrast agent in delayed hyperenhancement magnetic resonance imaging (DE-MRI) in patients with acute and chronic myocardial infarction (MI). The study population from both trials comprised 577 patients who were randomly assigned to one of four dose groups (0.05, 0.1, 0.2, or 0.3 mmol/kg) before undergoing DE-MRI. Safety evaluations included physical and electrocardiographic (ECG) examinations. Vital signs, laboratory values, adverse events (AE), and serious adverse events (SAE) were monitored before and after contrast administration. Of the 577 patients who received gadoversetamide, 124 (21.5%) reported a total of 164 AEs; most were mild (139 AEs; 84.8%) or moderate (25 AEs; 15.2%). ECG-related changes were the most frequent AE. Site investigators judged only eight AEs as likely related to gadoversetamide and only two of the eight as clinically relevant. Further evaluation suggested neither AE was related to gadoversetamide. Two SAEs were reported, but none was judged related to gadoversetamide by the site investigators. Gadoversetamide is safe for use in patients with acute or chronic MI up to a dose of 0.3 mmol/kg.


Identifying factors affecting willingness to participate in floating population health volunteer services by Chinese volunteers based on the theory of the planned behavior expansion model.
China has the world's largest internal migrant population, called the floating population. Compared to local residents, the floating population utilizes different health services and relies heavily on health volunteer services for supplementary services. In this study, the theory of planned behavior model was used to study the willingness of volunteers to participate in floating population health volunteer services. We examined the effects of several factors on willingness to participate and found that attitude and subjective norm, but not perceived behavioral control, have significant predictive effects on willingness to participate in health volunteer services. Furthermore, altruistic values, social incentives, and personality traits not only have significant predictive effects on volunteer participation but also indirectly affect willingness through attitude and subjective norms. These findings help us understand what factors affect volunteers' willingness to provide health services to the floating population and have important implications for mobilizing volunteers for floating population health services.


Improvement of laboratory skills of Chemical and Civil Engineering students using an interdisciplinary service-learning project for water quality and supply assessment in low-income homes.
The University of Buenos Aires (UBA) develops the UBANEX program, focused on service-learning projects for students involving social, environmental and public health concerns. One of the proposals was a collaborative project between UBA and the National University of General Sarmiento. Based on the hypothesis that students' voluntary involvement in social concerns improves their attitudes towards themselves and learning, the aim was to focus on the development of social and professional skills by implementing an interdisciplinary work for water quality and supply assessment in low-income homes from a southern district of the Buenos Aires Metropolitan Area. Eighteen volunteers-Chemical and Civil Engineering students-were recruited during August-December 2016. Tasks were distributed according to their interests: survey making, sampling, lab analysis, infrastructure checking, etc. Volunteers were surveyed in social involvement, lab skills, data compilation and analysis, leading to a final report with recommendations for a proper water use. The survey results compiled their feedback: 72% admitted an update on water quality problems, 60% learned new lab techniques and were able to analyze results, 89% supported the University's involvement in social concerns and 56% expanded their opinion about the professional field. The students confirmed their interest in participating in the next UBANEX project.


Bringing HIV, Substance Abuse and Homelessness into the University of Pennsylvania Anthropology Museum through Photo-Ethnography.
In the fall of 1994 I befriended a community of some two dozen heroin injectors and crack smokers surviving under the overpasses of a tangle of freeways six blocks from where I lived in San Francisco. The full force of the Reagan-era cutbacks from the 1980s had trickled down to the street, shredding the already rachitic U.S. welfare safety-net. Inner-cities were gentrifying (especially those linked to the epicenters of global finance capital such as San Francisco). The former skid row habitat for the unstable urban poor-cheap single-residency hotels-was being converted into multi-million dollar condominiums. Urban police forces had not yet systematized, routinized and replicated their zero-tolerance enforcement, harassment/incarceration dragnets (Wacquant 2009) and homelessness, consequently, was at its most visible. Bourgeois residents like me could not walk down a block or drive up a freeway entrance ramp in downtown San Francisco without being solicited for spare change. I obtained a National Institutes of Health HIV prevention grant and for the next 12 years, together with a photographer/anthropologist collaborator Jeff Schonberg and several additional ethnographic team members, we followed the social network of homeless addicts surviving in my neighborhood, documenting the unhealthy effects of indigence and substance abuse.


The Impact of Hemodialysis and Arteriovenous Access Flow on Extracranial Hemodynamic Changes in End-Stage Renal Disease Patients.
In this study, we characterized cerebral blood flow changes by assessment of blood flow parameters in neck arteries using carotid duplex ultrasonography and predictive factors for these hemodynamic changes. Hemodynamic variables were measured before and during hemodialysis in 81 patients with an arteriovenous access in their arm. Hemodialysis produced significant lowering in peak systolic velocity and flow volume of neck arteries and calculated total cerebral blood flow (1,221.9 ± 344.9 [before hemodialysis] vs. 1,085.8 ± 319.2 [during hemodialysis], P < 0.001). Effects were greater in vessels on the same side as the arteriovenous access and these changes were influenced by arteriovenous access flow during hemodialysis, both in the CCA (r = -0.277, P = 0.015) and the VA (r = -0.239, P = 0.034). The change of total cerebral blood flow during hemodialysis was independently related with age, presence of diabetes, and systemic blood pressure.


Characterizing and Predicting Autism Spectrum Disorder by Performing Resting-State Functional Network Community Pattern Analysis.
Growing evidence indicates that autism spectrum disorder (ASD) is a neuropsychological disconnection syndrome that can be analyzed using various complex network metrics used as pathology biomarkers. Recently, community detection and analysis rooted in the complex network and graph theories have been introduced to investigate the changes in resting-state functional network community structure under neurological pathologies. However, the potential of hidden patterns in the modular organization of networks derived from resting-state functional magnetic resonance imaging to predict brain pathology has never been investigated. In this study, we present a novel analysis technique to identify alterations in community patterns in functional networks under ASD. In addition, we design machine learning classifiers to predict the clinical class of patients with ASD and controls by using only community pattern quality metrics as features. Analyses conducted on six publicly available datasets from 235 subjects, including patients with ASD and age-matched controls revealed that the modular structure is significantly disturbed in patients with ASD. Machine learning algorithms showed that the predictive power of our five metrics is relatively high (~85.16% peak accuracy for in-site data and ~75.00% peak accuracy for multisite data). These results lend further credence to the dysconnectivity theory of this pathology.


Transcription factor Ets-1 regulates gelatinase a gene expression in mesangial cells.
Ets transcription factors are involved in cell growth and angiogenesis. Ets-1 targets include members of the matrix metalloproteinase superfamily. In inflammatory glomerular diseases, the patterns and regulation of Ets expression have not been fully characterized. In the present study, nuclear binding activities to the consensus Ets-1/PEA3 motif were detected in mesangial cells (MC), and the Ets-1 protein was positively identified by Western blotting, reverse transcription PCR (RT-PCR), and DNA-binding studies. The 5' flanking regions of the human and rat gelatinase A genes contain clusters of potential Ets-1 binding motifs, one of which is evolutionarily conserved. Using a series of 5' deletion reporter constructs of the rat gelatinase A gene and an Ets-1 expression plasmid, a concentration-dependent threefold trans-activation of gene expression mapped to the conserved Ets-1 binding motif at -1004/-1053 bps, designated responsive element-2 (RE-2). The RE-2 was operative within the context of the homologous gelatinase A promoter but not with a heterologous simian virus 40 promoter. Specific Ets-1 binding to this sequence was demonstrated by DNA-binding studies. Transient expression of an Ets-1 expression plasmid increased gelatinase A protein expression. Our findings identify an additional matrix metalloproteinase family member, gelatinase A, as an Ets-1 responsive gene in MC that may play a role in the high level expression of this enzyme in inflammatory glomerular diseases.


Collagen type I regulates beta-catenin tyrosine phosphorylation and nuclear translocation to promote migration and proliferation of gastric carcinoma cells.
The interaction between tumor cells and the stroma environment has crucial effects on tumor cell invasive behavior. As a major component of the stroma, collagen plays a key role on cellular adhesion and epithelial-mesenchymal transition (EMT). Recently, we found that collagen type I is significantly up-regulated in gastric cancer tissues compared with their adjacent non-neoplastic tissues. However, whether collagen type I contributes to gastric cancer invasion and metastasis is not clear. Herein we show that, collagen type I induces cell scattering and cytoskeleton rearrangement, prompts cell migration and proliferation, which indicates that collagen type I is involved in promoting gastric cancer invasion and metastasis. Collagen type I is able to reduce cell-cell adhesion and enhance migration by inducing disassembly of the E-cadherin/catenin complex in gastric carcinoma cells, which is related to tyrosine phosphorylation of beta-catenin. Tyrosine phosphorylation of beta-catenin dissociates it from E-cadherin and actin cytoskeleton and facilitates its entry into the nucleus, where beta-catenin acts as a transcriptional activator inducing genes involved in cell proliferation. In conclusion, collagen type I contributes to invasion and metastasis by regulating beta-catenin tyrosine phosphorylation and nuclear translocation to promote migration and proliferation of gastric carcinoma cells.


Comparison of two long-acting forms of quinidine.
The bioequivalence of two forms of long acting quinidine compounds was assessed (Kinidin durules and Longacor) using drug plasma level and QT ECG changes. Six healthy volunteers received each preparation on two occasions in random order. The wash out period between successive experiments was at least 7 days. There was no difference in tmax, Cmax and AUC for plasma level and adjusted QT. However, between patient variability was large. A 20% difference in plasma levels could not be excluded but the difference in QT max and QT AUC between the two preparations did not exceed 20% (P less than 0.05, Westlake's method). This study illustrates the fact that pharmacodynamic equivalence, let alone therapeutic equivalence, does not necessarily imply plasma level equivalence, as assessed by the current method.


7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats.
Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.


PubChem BioAssay: A Decade's Development toward Open High-Throughput Screening Data Sharing.
High-throughput screening (HTS) is now routinely conducted for drug discovery by both pharmaceutical companies and screening centers at academic institutions and universities. Rapid advance in assay development, robot automation, and computer technology has led to the generation of terabytes of data in screening laboratories. Despite the technology development toward HTS productivity, fewer efforts were devoted to HTS data integration and sharing. As a result, the huge amount of HTS data was rarely made available to the public. To fill this gap, the PubChem BioAssay database ( https://www.ncbi.nlm.nih.gov/pcassay/ ) was set up in 2004 to provide open access to the screening results tested on chemicals and RNAi reagents. With more than 10 years' development and contributions from the community, PubChem has now become the largest public repository for chemical structures and biological data, which provides an information platform to worldwide researchers supporting drug development, medicinal chemistry study, and chemical biology research. This work presents a review of the HTS data content in the PubChem BioAssay database and the progress of data deposition to stimulate knowledge discovery and data sharing. It also provides a description of the database's data standard and basic utilities facilitating information access and use for new users.


Prenatal and perinatal factors associated with isolated oral clefting.
To describe medical service utilization and maternal morbid conditions of women who carry offspring with oral clefts (OCs), to describe maternal and offspring complications during birth, and to evaluate postnatal characteristics of their newborns with isolated OCs. Two thousand four hundred thirty-seven patients with isolated OCs and 4871 unaffected matched controls meeting inclusion criteria were selected from the U.S. Natality database for 1997. Matching variables were mother's and father's race and child's race, sex, county of birth, and month of birth. Patients and controls were compared in terms of maternal demographic characteristics, gestational complications, physical characteristics of the newborns, maternal exposure to potential risk factors, and adequacy of prenatal care. Although the quality of care was very good in both groups, low gestational age, low birth weight, and low 5-minute Apgar score are more frequent among newborns with OCs than in unaffected controls. Mothers of offspring with OCs are at increased risk, compared with mothers of controls, of having hydramnios or oligohydramnios, eclampsia, and abruptio placenta. Obstetric procedures, such as amniocentesis, electronic fetal monitoring, induction of labor, tocolysis, and ultrasound, and repeat cesarean deliveries are more frequent among mothers of patients than those of controls. At birth, newborns with isolated OCs are at risk of having hyaline membrane disease and of requiring assisted ventilation, independently of gestational age. The results of this large population-based, case-control study suggest that the presence of an OC in the offspring is associated with increased risk for prenatal and perinatal complications in the mother.


Emphysematous pyelonephritis: Changing trend of clinical spectrum, pathogenesis, management and outcome.
To highlight changing trend of clinical spectrum, comparing management options and predictors of outcome of emphysematous pyelonephritis. This study included patients who were diagnosed as emphysematous pyelonephritis between August, 2001 to July, 2015. We excluded other possible causes of gas in renal system. Baseline patient characteristics, clinical spectrum, serum and urinary biochemical parameters, radiological findings, management and outcomes were recorded. Patients were classified as "responders" and "non-responders". We studied a total of 74 patients and categorised them as responders (62 patients) and non-responders (12 patients). Women outnumbered men constituting 62.16% of the study population (M: F; 1: 1.6). Fever was the most common presenting symptom followed by flank pain. Diabetes mellitus (85.14%) was the most common comorbidity followed by urolithiasis (32.43%). Escherichia coli was the commonest organism grown in urine culture (79.73%). Non-responders had distinct laboratory findings relative to responders as low hemoglobin (7.8±2.1/11.2±3.2 g/dL; p=0.0007), thrombocytopenia (91.67% vs. 11.29%; p=0.0001), proteinuria >3 g/L (50% vs. 6.45%; p=0.0008) and positive blood culture (100% vs. 67.74%; p=0.0288). Advanced age, higher body mass index, renal impairment, thrombocytopenia, altered sensorium, shock at presentation can be used as scores for poor prognosis. Emphysematous pyelonephritis management requires multidisciplinary collaboration including hydration and electrolyte management, broad spectrum antibiotics, strict glycaemic control, effective urinary drainage and lastly it may require emergency nephrectomy as a salvage procedure.


Infiltrative xanthogranulomatous cholecystitis mimicking aggressive gallbladder carcinoma: A diagnostic and therapeutic dilemma.
Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis. The perioperative findings in aggressive cases may be indistinguishable from those of gallbladder or biliary tract carcinomas. Three patients presented mass lesions that infiltrated the hepatic hilum, provoked biliary dilatation and jaundice, and were indicative of malignancy. Surgical excision was performed following oncological principles and included extirpation of the gallbladder, extrahepatic bile duct, and hilar lymph nodes, as well as partial hepatectomy. Postoperative morbidity was minimal. Surgical pathology demonstrated XGC and absence of malignancy in all three cases. All three patients are alive and well after years of follow-up. XGC may have such an aggressive presentation that carcinoma may only be ruled out on surgical pathology. In such cases, the best option may be radical resection following oncological principles performed by expert surgeons, in order that postoperative complications may be minimized if not avoided altogether.


Maternal separation on the ethanol-preferring adult rat liver structure.
Background and rationale for the study. We designed to test whether there is interaction of maternal separation (MS) on the ethanol-preferring rats liver structure. The UCh rat pups were separated daily from their mothers during the stress hyporesponsive period (SHRP), between four and 14 days-old, always at the same time for four hours in a cage containing eight subdivisions, one for each pup. Subsequently, rats that presented the highest (UChB) and the lowest (UChA) ethanol (EtOH) consumption were selected to the study. Both UChB and UChA rats received 10% (v/v) EtOH and distilled water ad libitum until the end of the experiment (120 days-old). The liver was collected to histological routine for morphometric and stereological analyses, and immunohistochemistry. There was an interaction of MS and EtOH on the liver: increased liver mass, peritubular vessels, stellate cell numbers, steatosis and cell death, decreased necrosis, sinusoidal capillary diameters and cell proliferation. While there was a decrease in FSH, testosterone and 5α-di-hidrotestosterone, and increasing corticosterone and cholesterol. There is interaction of MS and EtOH on the liver structure, dependent on the amount of EtOH intake. Furthermore, the interaction of stress and drugs can increase or decrease their effects on the liver or indirectly via hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes.


Focus on cat allergen (Fel d 1): immunological and aerodynamic characteristics, modality of airway sensitization and avoidance strategies.
The increasing frequency of pet ownership (especially cats) in many industrialized countries has raised the level of exposure to the allergens produced by these animals. Moreover, it is likely that modern energy-saving systems and the wide use of upholstered furniture has resulted in closer contact between cats (and their allergens) and humans. Many different methods have been developed to quantify the main cat allergen (Fel d 1) in settled dust and in ambient air. The threshold levels of cat allergen inducing sensitization or triggering respiratory symptoms in sensitized patients have been calculated in settled dust, but airborne amounts of Fel d 1 probably represent a more reliable index of allergen exposure. Noticeably, the amount of Fel d 1 may be relatively high also in confined environments where cats have never been kept. It has been demonstrated that clothes of cat owners are the main source for dispersal of allergens in cat-free environments. This fact may be of relevance, because recent studies have shown that allergic sensitization to cats is more likely to develop in children exposed to moderate levels of this allergen than in children exposed to high amounts of Fel d 1. The ubiquity of cat allergen may justify the common observation that allergen avoidance is often insufficient to reduce the risk of developing allergic sensitization and/or symptom exacerbation in highly susceptible patients. Further efforts are needed to improve the efficacy of Fel d 1 avoidance strategies to try to reduce the risk of allergic sensitization to this allergen.


Analysis of β2-agonists in cattle hair samples using a rapid UHPLC-ESI-MS/MS method.
A simple and efficient method was developed for simultaneous analysis of five illegal residual β2-agonists in cattle hair. β2-Agonists were quantified by ultra high performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry operating in positive multiple-reaction monitoring mode. The method was validated as quantitative confirmatory method according to the EU Decision 2002/657/EC: instrumental linearity, specificity, precision, recovery, decision limit (CCα) and detection capability (CCβ) were evaluated. The recovery were greater than 90% and the method appeared suitable for the control of these β2-agonists in cattle hair samples with LOQ values between 4.9 and 5.5 μg/kg. This method could represent a simple and cheap approach to confirm β2-agonists contamination of cattle for feeding in a not invasive way and before slaughter operations.


Exercise stress alters murine lymphocyte subset distribution in spleen, lymph nodes and thymus.
Our previous work indicated that exercise stress in mice was associated with reduced splenic lymphocyte proliferation to T cell mitogens. The purpose of this study was to determine the effect of acute exercise stress and exercise training on the phenotype distribution of murine lymphocytes in the spleen, lymph nodes and thymus. In mice given an exhaustive bout of treadmill exercise, the percentage of Thy 1.2 and Lyt2 antigen bearing cells decreased in the thymus, but the percentage of L3T4-positive cells did not change significantly. Acute exercise did not alter the percentage of Thy1.2, L3T4 or Lyt2-positive cells in the secondary lymphoid compartments (nodes, spleen). By contrast, in mice given a chronic exercise training programme (8 weeks duration; 30 m/min, 8 degrees slope, 30 min/session, 5 daily sessions/week) followed by a 72 h rest period, the percentage of L3T4-positive cells increased by 53% in the spleen, 19% in the lymph nodes and 29% in the thymus compared with sedentary controls; no parallel increase in the percentage of Thy1.2 antigen bearing cells was observed. These results suggest that the effect of exercise on the frequencies of lymphocyte subpopulations in murine lymphoid compartments is dependent upon the chronicity of the stress and probably on the accompanying physiological adaptations to the stress.


Lymphocyte populations and subpopulations in some lymphoproliferative dermatoses.
We present a study of lymphocyte populations and subpopulations as seen in histological cuts of skin with malignant and benign lymphoproliferative alterations using the immunological and histochemical techniques later described. Disclosed are the results of samples obtained of lymphocyte populations which were used to help differentiate between said alterations. It is proven that in T cell lymphomas. The infiltrate is dominated by markers for EA IgM which correlates with the results of other authors in peripheral blood.


Disseminated atypical mycobacteriosis.
Two cases of disseminated infection caused by Mycobacterium intracellulare were reported and discussed. In the first case, the patient was a fifty-seven-year-old male who complained of general fatigue, weight loss, and fever. Biopsy of the right inguinal lymph nodes and the liver revealed infiltration by histiocytes engulfing many acid-fast bacilli. At autopsy and egg-sized abscess was found is the region of the right iliac lymph nodes. Histological examination showed histiocytic infiltration in the abscess wall, neighboring lymph nodes, liver, and spleen. In the second case, the patient was a four-year-old boy, who had persistent fever and splenomegaly. Splenectomy was performed and histological examination of the spleen revealed multiple nodular infiltration by swollen histiocytes with many acid-fast bacilli in their cytoplasm. The bone marrow aspirates and liver tissue obtained in the necropsy also showed many histiocytes containing many acid-fast bacilli. The authors emphasized the importance of paying special attention to atypical mycobacteriosis in feverish patients having lesions with a proliferation of histiocytes.


Crystallization and crystallographic analysis of human NUDT16.
Human NUDT16, a decapping enzyme belonging to the Nudix superfamily, plays a pivotal role in U8 snoRNA stability. Recombinant NUDT16 expressed in Escherichia coli was crystallized using the hanging-drop vapour-diffusion method. The crystals, which diffracted to 2.10 A resolution, belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 44.47, b = 79.32, c = 97.20 A. The Matthews coefficient and the solvent content were calculated to be 1.92 A(3) Da(-1) and 35.84%, respectively, for two molecules per asymmetric unit.


Procoagulant genes may affect angiogenesis, epithelial-mesenchymal transition, survival prognosis and tumor immune microenvironment in patients with urothelial carcinoma.
Factors related to coagulation regulation are closely related to angiogenesis, epithelial-mesenchymal transition, tumor proliferation and metastasis, and tumor immune microenvironment remodeling in tumors. To date, there are no quantitative indicators of coagulation associated with urothelial cancer. We classified urothelial cancer into high coagulation and low coagulation subtypes by screening for procoagulant-related molecular features and screened out relevant genes representing the coagulation state of urothelial carcinoma. Tumors with increased procoagulant gene expression were consistently associated with higher T-staging (p < 0.001), lymph node metastasis (p < 0.001), stage (p < 0.001), and grade (p = 0.046). Furthermore, high expression of procoagulant genes predicts a worse prognosis, a higher tumor proliferation rate and increased angiogenesis within the tumor. In addition, according to cibersort algorithm, the increased expression of procoagulant gene was negatively correlated with the degree of T-lymphocyte infiltration and positively correlated with the degree of M2 macrophage infiltration. Increased expression of procoagulant genes in data sets treated with immune checkpoints also predicted worse response and worse prognosis. At the same time, the expression of procoagulant genes in bladder cancer promoted the activation of coagulation, EMT, TGF-β and WNT pathways.


Metabolic and Blood Pressure Effects of Walnut Supplementation in a Mouse Model of the Metabolic Syndrome.
There is extensive evidence that walnut consumption is protective against cardiovascular disease and diabetes in the healthy population, but the beneficial effects of walnut consumption in individuals with the metabolic syndrome (MetS) remain uncertain. We compared a range of cardio-metabolic traits and related tissue gene expression associated with 21 weeks of dietary walnut supplementation in a mouse model of MetS (MetS-Tg) and wild-type (WT) mice (n = 10 per genotype per diet, equal males and females). Compared to standard diet, walnuts did not significantly alter food consumption or body weight trajectory of either MetS-Tg or WT mice. In MetS-Tg mice, walnuts were associated with reductions in oral glucose area under the curve (gAUC, standard diet 1455 ± 54, walnut 1146 ± 91, p = 0.006) and mean arterial blood pressure (MAP, standard diet 100.6 ± 1.9, walnut 73.2 ± 1.8 mmHg, p < 0.001), with neutral effects on gAUC and MAP in WT mice. However, in MetS-Tg mice, walnuts were also associated with trends for higher plasma cholesterol (standard diet 4.73 ± 0.18, walnut 7.03 ± 1.99 mmol/L, p = 0.140) and triglyceride levels (standard diet 2.4 ± 0.5, walnut 5.4 ± 1.6 mmol/L, p = 0.061), despite lowering cholesterol and having no effect on triglycerides in WT mice. Moreover, in both MetS-Tg and WT mice, walnuts were associated with significantly increased liver expression of genes associated with metabolism (Fabp1, Insr), cell stress (Atf6, Ddit3, Eif2ak3), fibrosis (Hgf, Sp1, Timp1) and inflammation (Tnf, Ptpn22, Pparg). In conclusion, dietary walnuts were associated with modest favourable effects in WT mice, but a combination of beneficial and adverse effects in MetS-Tg mice, and up-regulation of hepatic pro-fibrotic and pro-inflammatory genes in both mouse strains.


c-Myc and transforming growth factor α enhance the development of hepatic lesions due to mutant β-catenin in transgenic mice.
Alterations in the Wnt signaling pathway are associated with diverse cancers, including hepatocellular carcinoma (HCC). The development of HCC is thought to be a multistage process in which multiple genetic alterations are necessary. Few studies have assessed the effect of aberrant Wnt signaling activity in association with other molecular alterations in HCC. Here we sought to determine whether co-overexpression of c-Myc or TGFα, 2 signaling molecules known to contribute to HCC development, enhanced the development of hepatic lesions associated with a stabilized β-catenin. The coexpression of mutant β-catenin with either c-Myc or TGFα within hepatocytes increased the severity of hepatic lesions compared with that associated with any of the transgenes expressed individually. The coexpression of mutant β-catenin with c-Myc or TGFα resulted in severe hepatomegaly necessitating the euthanasia of mice by an average of 156 and 128 d, respectively, after the cessation of doxycycline. The expression of mutant β-catenin alone resulted in mild to moderate hepatomegaly that prompted the euthanasia of mice by an average of 75 d after the cessation of doxycycline. Collectively, these findings indicate that coexpression of c-Myc or TGFα delays the onset of endstage hepatic disease yet enhances the severity of hepatic lesions due to mutant β-catenin.


Social influences on sorority and fraternity member smoking.
To understand how the Greek system uniquely influences smoking attitudes, beliefs, and behaviors among college students who belong to a social sorority or fraternity. Active members of sororities (n = 16) and fraternities (n = 17) were interviewed between February 2013 and October 2015. In-depth interviews were conducted examining the social influences of the Greek system on member smoking. Transcribed interviews were coded and analyzed for themes. Sorority and fraternity members experienced different social influences on smoking. Sorority stigmatization of smoking outside bars or parties caused sorority members to hide their smoking. Fraternity members had no social penalties for smoking and allowed smoking at the fraternity house. Fraternity members influenced both fraternity members and sorority members to smoke by sharing cigarettes and smoking at parties. Sororities and fraternities have created social environments that both promote smoking and stigmatize it, presenting unique challenges in college student smoking prevention and cessation efforts.


Integrating Psychosocial Risks With Emerging Evidence for Borderline Personality Disorders in Adolescence: An Update for Clinicians.
Borderline personality disorder (BPD) has seen significant advances in the knowledge of its developmental phenomenology during late childhood and adolescence. Various genetic, neurobiological, psychological, and social factors are implicated in the etiology of BPD. With emerging evidence on BPD development in adolescence, the review focused on recent literature to understand the role of psychosocial risk factors. The effects of adverse familial environment, physical, emotional, verbal, and sexual abuse, intergenerational transmission of psychopathological traits, maternal neglect and rejection, low socioeconomic status, bullying victimization, and dating violence were reviewed to understand their role in the development of BPD. BPD is a highly complex, serious, and enduring mental illness that has now been widely accepted to have symptoms that onset in early adolescence and could be diagnosed as early as age 12. BPD symptoms are stable, phenomenologically distinct from externalizing and internalizing disorders, and often present with co-occurring disorders, which during assessment could not explain impairments associated with BPD. New measures like the Difficulties in Emotion Regulation Scale (DERS), detailed developmental histories, understanding of psychosocial risks, shared decision-making, and psychoeducation could assist in early diagnosis and improvement of long-term outcomes. The implementation of evidence-based treatments is a challenge given higher costs and access to services; therefore, modifications in the treatment based on the core principles of these strategies should be considered. It is imperative to screen for psychosocial factors early in higher-risk groups. The assessment of familial factors, parental histories of psychopathologies, and histories of childhood abuse is important in context with impairing symptoms of clinical presentation and dimensional aspects of self-functioning. The role of family therapies, parental psychoeducation, and the integration of trauma-informed care approaches are important for clinical outcomes. Also, coordinated efforts with multiple stakeholders like school awareness programs, anti-bullying policies, legislation, and enforcement of existing laws might be instrumental in addressing issues related to victimization by peers.


Dose frequency of prostaglandin F2α administration to dairy cows exposed to presynchronization and either 5- or 7-day Ovsynch program durations: Ovulatory and luteolytic risks.
We hypothesized (1) that neither duration of the Ovsynch program nor dose frequency of PGF2α would change the proportion of cows with complete luteolysis (progesterone <0.4 ng/mL 72 h after PGF2α) and (2) that the additional GnRH treatment administered as part of a presynchronization program would not alter the proportion of anovulatory cows starting the timed artificial insemination (AI) program compared with an alternative shorter presynch program including only 1 GnRH treatment. Lactating Holstein cows (n = 406) were milked 3 times daily and enrolled in a 2 × 2 × 2 factorial experiment consisting of 8 treatments before the first postpartum AI. Treatments were used to test ovulatory, luteal, and luteolytic outcomes to 3 main effects: (1) 2 GnRH-PGF2α presynchronization programs (PG-3-G vs. Double Ovsynch), (2) 2 Ovsynch program durations [5 d: GnRH (GnRH-1)-5 d-PGF2α-24 h-PGF2α-32 h-GnRH (GnRH-2)-16 h-timed AI; 7 d: GnRH-1-7 d-PGF2α-56 h-GnRH-2-16 h-timed AI], and (3) 2 PGF2α dose frequency treatments (2 × 25 mg) 24 h apart versus 1 dose (1 × 50 mg) of PGF2α administered 72 h before timed AI. The presynchronization treatments of PG-3-G and Double Ovsynch had no effect on the proportion of cows with luteal function at the onset of the Ovsynch treatments (87.9 vs. 86.2%). Although ovulatory responses were similar after GnRH-1 (>60%), Double Ovsynch cows tended to have greater ovulatory responses than PG-3-G after GnRH-2 (95.3 vs. 90.6%). The 2 × 25-mg doses of PGF2α and the 1 × 50-mg dose induced luteolysis in both Ovsynch treatment durations, but the 1 × 50-mg dose was less effective in the 5-d program. More pregnancy per AI (P/AI; 49.2%) tended to occur in the PG-3-G cows in the 7-d program compared with the other treatment combinations (range: 32.4-37.4%; Ovsynch × presynch interaction). In addition, an Ovsynch × PGF2α dose frequency interaction resulted in cows receiving the 1 × 50-mg dose in the 7-d program having the greatest P/AI (46.1%) and cows receiving the 1 × 50-mg dose in the 5-d program having the least P/AI (30.6%). We conclude that complete luteolysis was less effective in the 5-d program when the 1 × 50-mg dose was applied, but both PGF2α dose frequencies (1 × 50 mg and 2 × 25 mg 24 h apart) effectively induced complete luteolysis in the 7-d program. Treatments producing complete luteolysis tended to be related to subsequent pregnancy outcomes.


Mood, Anxiety and Olfactory Dysfunction in COVID-19: Evidence of Central Nervous System Involvement?
The objective of this study was to determine the burden of depressed mood and anxiety in COVID-19, and associated disease characteristics. This is a prospective, cross-sectional study of 114 COVID-19 positive patients diagnosed using RT-PCR-based testing over a 6-week period. The two-item Patient Health Questionnaire (PHQ-2) and the two-item Generalized Anxiety Disorder questionnaire (GAD-2) were used to measure depressed mood and anxiety level, respectively, at enrollment and for participants' baseline, pre-COVID-19 state. Severity of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough, and shortness of breath (SOB) during COVID-19 were assessed. PHQ-2 and GAD-2 significantly (P < .001) increased from baseline to enrollment. PHQ-2 was associated with smell loss (adjusted incidence rate ratio [aIRR] = 1.40, 95% CI, 1.10-1.78, P = .006), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .006), and baseline PHQ-2 score (aIRR = 1.39, 95% CI, 1.09-1.76, P = .007). GAD-2 score was associated with smell loss (aIRR = 1.29, 95% CI, 1.02-1.62, P = .035), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .025) and baseline GAD-2 score (aIRR = 1.55, 95% CI, 1.24-1.93, P < .001). Loss of taste also exhibited similar associations with PHQ-2 and GAD-2. PHQ-2 and GAD-2 scores were not associated with severities of any other symptoms during the COVID-19 course. Despite the occurrence of symptoms-such as SOB-associated with severe manifestations of COVID-19, only the severities of smell and taste loss were associated with depressed mood and anxiety. These results may raise the novel possibility of emotional disturbance as a CNS manifestation of COVID-19 given trans-olfactory tract penetration of the central nervous system (CNS) by coronaviruses. 3 Laryngoscope, 130:2520-2525, 2020.


Vulvar cancer in high-income countries: Increasing burden of disease.
The aim of this study was to assess trends in the age-specific incidence of vulvar cancer in 13 high-income countries satisfying a priori conditions regarding the availability of cancer registry data over a 20-year period; these were Canada, the United States, nine European countries, Australia and Japan. Five-yearly incidence and population at risk were obtained from the International Agency for Research on Cancer's Cancer Incidence in Five Continents for the years 1988-1992 (Volume 7) to 2003-2007 (Volume 10). The 5-yearly average percent change (AvPC) over the period and standardised rate ratios (SRRs) for 2003-2007 versus 1988-1992 were used to assess changes in the age-standardised incidence rates of vulvar cancer for all ages, and for <60 years and 60+ years. During the study period, the 5-yearly AvPC across the 13 countries increased by 4.6% (p = 0.005) in women of all ages, and 11.6% (p = 0.02) in those <60 years. No change was observed in women aged 60+ years (5-yearly AvPC = 0.1%, p = 0.94). The SRR for 2003-2007 versus 1988-1992 was significantly elevated in women <60 years of age (SRR = 1.38, 95% CI: 1.30-1.46), but not in women of 60+ years (SRR = 1.01, 95% CI: 0.97-1.05). The increase in incidence in women <60 years of age drove a significant increase in the overall SRR in women of all ages (SRR = 1.14, 95% CI: 1.11-1.18). Some differences in the specific findings at the individual country level were observed. The findings are consistent with changing sexual behaviours and increasing levels of exposure to human papillomavirus (HPV) in cohorts born around/after about 1950, but younger cohorts offered HPV vaccination are likely to receive some protection against developing vulvar cancer in the future.


Comparative evaluation of thrombocytopenia in adult patients receiving linezolid or glycopeptides in a respiratory intensive care unit.
Linezolid is an oxazolidinone antibiotic agent, active against gram-positive bacteria that are resistant to traditional antibiotics, including glycopeptides. Linezolid is generally well tolerated, but has been associated with hematologic adverse effects such as thrombocytopenia. The primary objective of this study was to compare the incidence of thrombocytopenia between patients receiving linezolid or glycopeptides in different age groups. The secondary objective was to assess the association between the time-to-event and occurrence of thrombocytopenia. This retrospective study reviewed the medical records of patients who were treated with linezolid or glycopeptides (vancomycin or teicoplanin) between January 2010 and June 2013 in a respiratory intensive care unit. Data were extracted from the patients' electronic medical records, which were obtained from a central database in the hospital, and multivariate analyses were performed. In total, the study included 225 patients who received linezolid or glycopeptides. The cumulative probability of thrombocytopenia was higher in the patients receiving linezolid than in those receiving glycopeptides (P<0.05), however the cumulative probability of thrombocytopenia did not differ significantly between patients receiving linezolid or glycopeptides in the subgroup whose age was <65 years (P>0.05). With a treatment duration of ≥7 days, the incidence of thrombocytopenia and the mean platelet count reduction in the patients receiving linezolid was significantly higher than in those receiving glycopeptides (P<0.05). No significant difference was identified in the mean platelet counts between the patients receiving linezolid and those receiving glycopeptides. In conclusion, it was identified that patients in a respiratory intensive care unit, aged ≥65 years or with a treatment duration of ≥7 days who were treated with linezolid were more likely to develop thrombocytopenia than patients of the same subgroup who were treated with glycopeptides.


OsbZIP76 interacts with OsNF-YBs and regulates endosperm cellularization in rice (Oryza sativa).
Following double fertilization, plant endosperm nuclei undergo syncytial divisions, followed by synchronous cellularization. Cellularization is a key event during endosperm development, but our understanding of its regulation is limited to Arabidopsis. In this study we show that OsbZIP76 regulates cellularization in rice (Oryza sativa). Activation of OsbZIP76 coincided with the initiation of cellularization, and its knockdown or knockout mutants exhibited precocious cellularization. Genes involved in endosperm development or starch biosynthesis were prematurely activated in the osbzip76 caryopsis. As a putative transcription factor, OsbZIP76 alone lacked transcriptional activation activity; however, it interacted with the nuclear factor Y (NF-Y) family transcription factors OsNF-YB9 and OsNF-YB1 in yeast and in planta. OsbZIP76 and OsNF-YB9 were predominantly expressed in the endosperm and the proteins colocalized. Seeds of osnf-yb1 and osbzip76 mutants showed reduced size and reduced apparent amylose content. The parent-of-origin-dependent expression of OsbZIP76 is variable in different rice accessions. In summary, OsbZIP76 is an endosperm-expressed imprinted gene that regulates endosperm development in rice.


Influence of vitamins C and E on cytotoxic activity of adriamycin in chosen cell cultures.
Influence of different concentrations of ascorbic acid (vitamin C) and dl-alpha-tocopherol acetate (vitamin E) on in vitro cytotoxic adriamycin activity, in: embryonic human fibroblasts (CLV102), human melanoma cells (ME18) and adriamycin-resistant subline cells (ME18/R), was studied. IC50 value for each compound (compound concentration in the culture medium, for which 50% of cells survive) was determined. Cells' survival after the used agent was examined with trypan blue test. The relationship between different concentrations of vitamin C and toxicity of adriamycin, used at appropriate IC50 concentrations, was expressed for all the examined cells as their survival decrease, being in direct proportion to the concentration increase of this vitamin in the medium. In the case of influence of vitamin E on adriamycin cytotoxicity, the protective effect of this vitamin was observed in the concentration range: from 5 to 300 microg/ml (p < or = 0.0001), as an increase of the examined cell survival for ME18, ME18/R as well as for CLV102, comparing to the control (p=0.05) without this vitamin. Parallelly, a statistically significant survival decrease was observed, if the concentration of vitamin E in the culture medium exceeded 500 microg/ml. Received results showed different, in defined concentration range, effects of the vitamin C or vitamin E activity for adriamycin cytotoxicity. These effects were similar for all the examined cells.


Whole-exome sequencing of secondary tumors arising from nevus sebaceous revealed additional genomic alterations besides RAS mutations.
Nevus sebaceous (NS) is a congenital hamartoma associated with an increased risk of secondary neoplasms in approximately 10%-20% of patients. However, additional genomic alterations underlying tumorigenesis in NS lesions have not been clarified. We performed whole-exome sequencing of archived tumor tissues (n = 8; six basal cell carcinomas and two trichoepitheliomas) and matched germline tissues (n = 7) with from seven patients with secondary tumors arising from NS. We also analyzed NS lesions without secondary tumors (n = 8). Somatic mutations and copy number alterations (CNAs) were analyzed. We identified a median of 129 somatic mutations (corresponding to 2.6/Mb in target regions, range 26-336) for eight tumors, while a median of 118 somatic mutations (2.3/Mb, range 1-196) for eight NS lesions. Known RAS hotspot mutations were found in seven of the eight tumors (six for HRAS p.G13R and one for HRAS p.Q61R) and in six of the eight NS lesions (four for HRAS p.G13R, one for KRAS p.G12C, and one KRAS p.G12D). Except RAS mutations, several putative driver mutations were detected in tumors: TP53 p.F134L/p.R213*, MYCN p.P59L, OR2Z1 p.P167S, PTPN14 p.Q768*, and SMO p.W535L. As for CNAs, two tumors harbored copy-loss in regions encompassing PTCH1 gene. However, eight NS lesions did not harbor both putative driver mutations and CNAs. In conclusion, our study revealed that secondary tumors arising from NS harbor known RAS hotspot mutations and additional genomic alterations, including putative driver mutations and PTCH1 copy-loss. These results could help to define the high-risk group for tumor development in patients with NS and provide evidence for prophylactic resection.


DNA damage and inflammatory response in workers exposed to fuels and paints.
Workers exposed to fuels and paints may present alterations in several parameters. Thus, we assessed potential biomarkers, with the aim of detecting early changes in gasoline station attendants and painters. Blood samples were collected for the analysis of inflammatory and DNA damage markers, besides biochemical, haematological and oxidative stress parameters. Biochemical and haematological parameters, which are assessed with routine exams, showed few changes. However, these findings could mask the workers' real health status. Besides, markers of oxidative damage were not modified. Levels of inflammatory parameters (cytokines and nitric oxide levels) and the DNA damage marker 8-hydroxydeoxyguanosine were significantly changed in the workers. Our results suggest that inflammatory and DNA damage parameters can be potential biomarkers for the biological monitoring of workers exposed to fuels and paints and may contribute to the development of occupational protection standards.


Phenotypic and Genotypic Characterization of DEPDC5-Related Familial Focal Epilepsy: Case Series and Literature Review.
Mutations in the disheveled, Egl-10 and domain-containing protein 5 (DEPDC5) recently have been identified as a common cause of focal epilepsy syndromes. The association between phenotype and genotype of DEPDC5 mutation has not been adequately characterized. We studied four families with familial focal epilepsy carrying DEPDC5 mutations. Four novel DEPDC5 mutations were identified by next-generation sequencing, including two missense mutations (c.1729 >A and c.3260G>A), one splicing mutation (c.280-1G>A), and one frameshift mutation (c.515_516delinsT). We found that patients carrying different DEPDC5 mutation have different clinical manifestations. Incomplete penetrance is a prominent feature of DEPDC5-related epilepsy, with the rate of penetrance ranging from 25 to 100%. About 21.4% of patients with DEPDC5-related familial focal epilepsy are refractory to treatments. We further reviewed the correlation of genotype and phenotype in all previous literature regarding DEPDC5-related epilepsy. Our study suggested that the type of DEPDC5 mutation might provide important information for the prognosis evaluation.


Engineering Ca2+-Dependent DNA Polymerase Activity.
Advancements in synthetic biology have provided new opportunities in biosensing, with applications ranging from genetic programming to diagnostics. Next generation biosensors aim to expand the number of accessible environments for measurements, increase the number of measurable phenomena, and improve the quality of the measurement. To this end, an emerging area in the field has been the integration of DNA as an information storage medium within biosensor outputs, leveraging nucleic acids to record the biosensor state over time. However, slow signal transduction steps, due to the time scales of transcription and translation, bottleneck many sensing-DNA recording approaches. DNA polymerases (DNAPs) have been proposed as a solution to the signal transduction problem by operating as both the sensor and responder, but there is presently a lack of DNAPs with functional sensitivity to many desirable target ligands. Here, we engineer components of the Pol δ replicative polymerase complex of Saccharomyces cerevisiae to sense and respond to Ca2+, a metal cofactor relevant to numerous biological phenomena. Through domain insertion and binding site grafting to Pol δ subunits, we demonstrate functional allosteric sensitivity to Ca2+. Together, this work provides an important foundation for future efforts in the development of DNAP-based biosensors.