Vocal fold mucosa "blue lines" observed on contact telescopy at Reinke's edema.
Reinke's space is a highly specific structure critical for the function of the vocal fold, involved in a majority of pathological changes of the larynx. The aim of the study was to contribute to the understanding of edematous areas of vocal fold mucosa in patients with Reinke's edema using contact telescopy (ConTel). The edematous tissue which could be identified grossly by microlaryngoscopy under general anesthesia was stained topically with methylene blue and then examined using ConTel. The observed changes on contact images were further correlated with corresponding histological sections of biopsied edematous tissue. In patients with Reinke's edema examined using ConTel, we observed longitudinal arranged mucosal "blue lines" (BL). In the histological sections of edematous tissue showing the BL on ConTel, we almost regularly observed well-developed hollow spaces in subepithelia. Also, they were regularly oriented from the middle of the membranous portion of the vocal fold toward the arcuate line distributed almost parallel to the free edge of the vocal fold. BL were a specific feature of Reinke's edema as they were not found in control groups with normal vocal fold mucosa and with vocal fold polyps. For the first time we are describing a new superficial morphological feature of Reinke's edema. The BL could present epithelial ConTel markers of the area between two enlarged neighboring subepithelial crevices of Reinke's space, as indicated on histological sections. Further characterization of BL is required for the understanding of their role in Reinke's edema.


On the arrival of fasciolosis in the Americas.
Fasciola hepatica is a worldwide emerging and re-emerging parasite heavily affecting several regions in South America. Some lymnaeid snail species of American origin are among the major hosts of F. hepatica worldwide. Recent paleoparasitological findings detected its DNA in a 2300-year-old sample in Patagonia, countering the common hypothesis of the recent arrival of F. hepatica in the Americas during European colonization. Thus, the theory of an initial introduction in the 1500s can no longer be sustained. This article discusses how it was possible for F. hepatica to reach and spread in the Americas in relation to the availability and compatibility of hosts through natural and incidental introductions. Our study will serve to better understand the ongoing Neotropical scenario of fasciolosis.


Job strain and burnout in Spanish nurses during the COVID-19: resilience as a protective factor in a cross-sectional study.
Nurses are frequently exposed to chronic stress in the workplace generating harmful effects such as job strain and burnout. On the contrary, resilience has been shown to be a beneficial variable. The objective of this study was to analyze the relationship between dimensions of the Job Demand Control-Support model, resilience and burnout in nurses, and examine the mediating role of resilience between job strain and burnout. A descriptive, cross-sectional study reported in line with the STROBE guidelines. Active nurses were invited to complete an online questionnaire in September, 2020. With snowball sampling, 1013 nurses, with a mean age of 34.71, filled out the Job Content Questionnaire, the Maslach Burnout Inventory and the Resilience Scale. The results showed the existence of four groups of professionals based on job strain. The nurses in the "High Strain" group (high demands and low control) showed higher scores in emotional exhaustion and cynicism, while those in the "Active Job" group scored higher in personal realization and resilience. The findings showed that job strain affects burnout in nurses, and this effect is mediated by resilience. The findings of this study showed that a high level of resilience could exert a fundamental role in ensuring well-being and proper job performance by nurses. Nursing managers should see to the personable variables or competencies that provide and favor an opportunity for nurses to widen and improve their practice, in pursuance of satisfying and responding better to people's needs and the systems they work for.


A 1-year-old infant with McArdle disease associated with hyper-creatine kinase-emia during febrile episodes.
A 14-month-old girl was hospitalized due to repeated hyper-creatine kinase (CK)-emia during pyrexia. Mild hypotonia was observed, but other physical and neurological findings were unremarkable. The serum CK level was normal at rest or normothermia. Open muscle biopsy was performed on the rectus femoris, and showed glycogen storage and complete lack of phosphorylase activity histochemically and biochemically, establishing the diagnosis of McArdle disease. The diagnosis of McArdle disease in early infancy is uncommon. Until this study there have been no reports of clinical symptoms or muscle biopsy findings for McArdle disease in early childhood. This disease must be considered when transient hyper-CKemia is observed in infants, even if glycogen storage is unremarkable as compared with adult cases.


Retinal microvascular changes in diabetic patients with diabetic nephropathy.
To explore the characteristics of retina microvascular changes in patients with diabetic nephropathy (DN) and its risk factors. Retrospective, observational study. 145 patients with type 2 diabetic mellitus (DM) and DN were included in the study. Demographic and clinical parameters were obtained from medical records. Presence of diabetic retinopathy (DR), hard exudates (HEs) and diabetic macular edema (DME) were evaluated according to the color fundus images, optical coherence tomography (OCT) and fluorescence angiography (FFA). DR accounted for 61.4% in type 2 DM patients with DN, of which proliferative diabetic retinopathy (PDR) accounted for 23.6% and sight threatening DR accounted for 35.7%. DR group had significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004), HbA1c (P = 0.037), Urine albumin creatine ratio (ACR) (p < 0.001) and lower level of estimated glomerular filtration rate (eGFR) (P = 0.013). Logistic regression analysis showed DR was significantly associated with ACR stage (p = 0.011). Subjects with ACR stage3 had higher incidence of DR compared with subjects with ACR stage1 (OR = 24.15, 95%CI: 2.06-282.95). 138 eyes of 138 patients were analyzed for HEs and DME, of which 23.2% had HEs in posterior pole and 9.4% had DME. Visual acuity was worse in HEs group than in non-HEs group. There was significant difference in the LDL-C cholesterol level, total cholesterol (CHOL) level and ACR between HEs group and non-HEs group. A relatively higher prevalence of DR was found in type 2 DM patients with DN. ACR stage could be recognized as a risk factor for DR in DN patients. Patients with DN needs ophthalmic examination more timely and more frequently.


Phosphoenolpyruvate carboxykinase and glucose-6-phosphate dehydrogenase expression in fetal hepatocyte primary cultures under proliferative conditions.
Fetal hepatocytes cultured for 64 h in the presence of glucagon and dexamethasone maintain a quiescent state, showing a low expression of glucose-6-phosphate dehydrogenase (G6PD) and a high induction of phosphoenolpyruvate carboxykinase (PEPCK). Under these culture conditions, the presence of EGF produced hepatocyte proliferation, with a concomitant increase of DNA synthesis, DNA content, and G6PD expression, meanwhile the expression of PEPCK was drastically reduced. The presence of forskolin plus IBMX nearly suppressed the increase in DNA synthesis and G6PD expression induced by EGF, showing a very high expression of PEPCK. Accordingly, it is possible to establish an inverse relation between G6PD, highly expressed in proliferating fetal hepatocytes, and PEPCK expression, highly expressed in quiescent fetal hepatocytes under specific hormonal stimulation.


Degradation of tetracycline by atmospheric-pressure non-thermal plasma: Enhanced performance, degradation mechanism, and toxicity evaluation.
Tetracycline is a common antibiotic and is often carelessly released into the natural environment, thus constantly posing potential threats to the environment. Currently, due to lack of effective methods to remove it from the environmental water system, researchers are still exploring new ways to deal with tetracycline. In this work, we employed atmospheric-pressure non-thermal plasma (NTP) to treat tetracycline in water and investigated the involved degradation mechanism. The enhanced degradation efficiency was acquired and investigated, and the degradation mechanism by the plasma-generated active species were explored. The tetracycline degradation pathways via especially the interactions with plasma-generated hydroxyl radical and ozone were examined by virtue of UV spectroscopy, three-dimensional fluorescence spectroscopy, high performance liquid chromatography-mass spectrometry (HPLC-MS), together with the assistance of theoretical simulations. Moreover, the toxicological evaluation of NTP treatment of tetracycline was also provided, which confirmed that the biological toxicity of tetracycline degradation products was negligible. Therefore, this work provides not only the effective way of treating antibiotics by engineered plasma technology, but also the insights into the mechanisms of degradation of antibiotics by NTP.


Experiences of maintaining awake prone positioning in non-intubated patients with COVID-19: A qualitative study.
Patient compliance is crucial to maintaining the awake prone position, which has been found to be intolerable by several patients. Addressing patients' compliance while being treated with awake prone positioning and prolonging its duration may be prerequisites for further research. This study was conducted to explore the personal experiences of non-intubated patients during the implementation of awake prone positioning. We conducted a qualitative study recruiting a purposive sample of twelve adult patients diagnosed with COVID-19 who were previously treated with awake prone positioning. They were recruited from an intermediate care unit (that provides pre- and post-intensive care) in a COVID-19-designated hospital in Nanjing, China from July 15, 2021, to September 20, 2021. Data were collected through individual in-depth interviews and then analysed using Colaizzi's phenomenological method. Content analysis of the interviews revealed two main themes, each containing three and four sub-themes, respectively, as follows: (1) barriers to the implementation of awake prone positioning, including (i) generalised discomfort, (ii) a lack of both understanding and trust, and (iii) low satisfaction with the implementation plan; (2) factors promoting the implementation of awake prone positioning, including (i) health education and supervision, (ii) self-motivation and support from healthcare staff and family members, (iii) finding a comfortable position and having access to entertainment, and (iv) symptom improvement. Healthcare staff should clarify the mechanism underlying the effectiveness of the awake prone position to patients to eliminate any doubts that they may have. Psychological support and appropriate supervision should be emphasised. Pain relief programmes should also be established, including the use of a comfortable prone posture in conjunction with access to entertainment. Finally, individualised awake prone positioning protocols should be formulated according to patients' living habits and attempted in combination with out-of-bed activities. These measures may help to enhance the experience and compliance of patients undergoing the treatment. For future instances involving the implementation of awake prone positioning, several measures should be established and implemented alongside it, including a health education programme, supervision programme, support system, and pain relief programme. Personalisation should also be considered during its implementation. These measures may help to enhance the compliance of patients and prolong the duration of the awake prone position.


An objective evaluation of lens transparency after vitrectomy surgery with different intravitreal tamponades.
To evaluate and compare the effects of different intraocular tamponade agents on lens density after vitrectomy. The participating patients were divided into four groups according to the tamponade agent used: a sulfur hexafluoride (SF6) group, a perfluoropropane (C3F8) group, a silicone oil group, and a no tamponade group. Lens density measurements were performed preoperatively and two weeks, one month, and three months postoperatively using a Pentacam HR device with a Scheimpflug camera. The postoperative values were compared with the preoperative baseline values, also the values were compared between the four groups. The study included 82 eyes (82 patients). In the SF6 group, lens density significantly increased in all zones two weeks and one and three months postoperatively (all P < .05). In the C3F8 group, lens density significantly increased in all zones three months postoperatively (all P < .01). In the silicone oil group, the zone 1, zone 2, and average lens density (ALD) value significantly increased one and three months postoperatively (all P < .05). In the no tamponade group, the zone 1, zone 2, and ALD values significantly increased three months postoperatively (all P < .05). There were no significant differences between the four groups in any zone either preoperatively or postoperatively (all P > .05). Although increases in lens density were observed earlier in the tamponade groups than in the no tamponade group, between the groups over the follow-up period were no differences. We need the development of new surgical methods and materials to prevent post-vitrectomy lens damage in the future.


Drugs of abuse in tap water from eight European countries: Determination by use of supramolecular solvents and tentative evaluation of risks to human health.
Recent research findings have confirmed the presence of illicit drugs in tap water from some European Union (UE) member states. Contaminants in tap water come directly from drinking water sources such as rivers or lakes owing to inefficient removal at wastewater treatment and water purification plants. This work was aimed at setting a starting point for assessing the health risks of exposure to twelve drugs of abuse through consumption of tap water in the European population. For this purpose, a method using supramolecular solvents (SUPRAS) was developed to extract drugs in the opioid, amphetamine, cocaine and cannabinoid groups from tap water for their determination by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 119 tap water samples were collected from eight EU countries for analysis. Seven drugs were found at concentrations from 0.3 to 340 ng/L in 72 of the samples (60.5%). The mean exposure to the drugs through consumption of tap water was calculated to be 0.0064-3.531 ng/kg·day for adults and 0.0247-6.7580 ng/kg·day for children, whereas that resulting from dermal contact was estimated to be 4-7 orders of magnitude lower. Exposure values were compared with the minimum required performance levels (MRPL) for the drugs in urine set by the World Anti-Doping Agency (WADA). Based on the results, a need clearly exists for further research into the adverse effects on health of inadvertent, sustained exposure to low doses of drugs of abuse.


[Sensitization to aeroallergens in subjects with allergic rhinitis who live in the metropolitan zone of Guadalajara, Jalisco].
allergic rhinitis is the most common allergic disease worldwide. Aeroallergens are compromise in its presentation and its prevalence varies in different parts of the world. Aeroallergen sensitization in the Guadalajara metropolitan area is not yet documented. to determine by means of skin prick test the sensitization prevalence to aeroallergens in patients with allergic rhinitis. We retrospective evaluated the results of skin prick test to different aeroallergens and their prevalence by age group in patients with allergic rhinitis referred to our allergy department. the complete data of 965 subjects were available, 78% of these had positive skin prick tests, the age range of the patients was 16 to 78 years, 74.9% of which were women; 9% were sensitized to one allergen and 11.5% had more than 15 positive skin prick test. The most frequent interior allergens were house dust mites and outdoor allergens Quercus sp and Fraxinus sp. Males showed the highest reaction frequency to aeroallergens. The age range from 21 to 40 years presented the highest frequency of positive skin prick test. our data demonstrate that house dust mites followed by tree pollens are the most frequent aeroallergens in patient with allergic rhinitis. Positive skin prick test frequency was age associated.


Assessment of Liver Fibrosis Using Non-invasive Screening Tools in Individuals With Diabetes Mellitus and Metabolic Syndrome.
Despite the rising prevalence of liver fibrosis and its potentially life-threatening complications, there are currently no recommendations or guidelines to screen individuals with diabetes mellitus (DM) or high body mass index (BMI) for non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). This is mainly due to the uncertain performance and feasibility of presently available screening tools. This research was carried out to assess the diagnostic accuracy of non-invasive screening tools in predicting liver fibrosis in individuals with DM and metabolic syndrome. For this study, 140 patients with DM and metabolic syndrome were identified between March 2020 and October 2021. Liver stiffness measurement by point shear wave elastography was considered the gold standard in our study. Five non-invasive scores such as aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, aspartate aminotransferase to platelet ratio index (APRI) score, fibrosis-4 (FIB-4) index, BARD score, and NAFLD fibrosis score were determined in all of the participants. Using receiver operator characteristic (ROC) curve analysis, sensitivity, specificity, both negative predictive value (NPV) and positive predictive value (PPV) were calculated for each of these scores. The area under the ROC curve (AUROC) was used to calculate the diagnostic accuracy of these scores. Of the 507 individuals screened, 140 were enrolled for the study. Among the 140 participants, 83 were male (59.29%), 30 (21.43%) had liver fibrosis as per liver stiffness measurement by point shear wave elastography, and 110 (78.57%) did not have fibrosis. The mean age and mean BMI were 54.53±12.42 and 27.37±2.73 respectively in the 'Fibrosis' group and 56.20 ±11.76 and 27.10±4.22 in the 'No fibrosis' group. The major finding of our study was that all these scores had relatively high NPV (>85 %) for predicting liver fibrosis in our cohort. The AST/ALT ratio had the highest NPV (90.28%) followed by APRI Score (88.94%). The AUROC for FIB-4 Score, NAFLD-fibrosis score, APRI score, AST/ALT ratio, and BARDd score were 0.6669, 0.657, 0.655, 0.637 and 0.599, respectively. The FIB-4 index (p=0.005) had the highest AUROC, followed by the NAFLD-fibrosis score (p =0.009). But all the scores had relatively low specificity (<60 %), PPV (<35 %), and accuracy (<63 %). The FIB-4 index and NAFLD-fibrosis score can be used reliably to exclude liver fibrosis in individuals with DM and metabolic syndrome in the Indian population, but may not be useful in accurately diagnosing liver fibrosis. Utilization of these non-invasive and cost-effective screening tools in routine practice may have promising results in predicting liver fibrosis in 'at risk' populations.


Comparison of the Oxford Sleep Resistance Test and the Multiple Sleep Latency Test.
The Oxford Sleep Resistance Test (OSLER) consists of four tests over 40 min conducted in a dark and quiet room. If a dim light flashes the patient has to briefly depress a button and then press it again immediately, which indicates that the patient resists sleep. The Maintenance of Wakefulness test (MWT) is another test to assess the ability to maintain wakefulness. Previous studies found a good correlation between the sleep latencies measured with the Osler and the MWT. The most widely used Multiple Sleep Latency Test (MSLT) measures the propensity to fall asleep and not the inability to stay awake. Up to this date there have been no studies comparing the Osler and the MSLT, which is the aim of the study presented here. After a night of polysomnography we investigated the sleep latencies the following day with the Osler and the MSLT in 43 patients suffering from moderate or severe obstructive sleep apnea (OSA) (33 men and 10 women; median age 59 years; median apnea hypopnea index 30.5 per hour sleep). We analysed the correlation between these two tests and between values in the Epworth Sleepiness Scale (ESS) and the Karolinska Sleepiness Scale (KSS) and these two tests. We did not find a correlation between the Osler and the MSLT nor between these two tests and the questionnaires (ESS, KSS). The only significant correlation was found between the mean MSLT latency and the sleep onset latency in the polysomnography the night before. Seven patients stayed awake during the Osler and showed a decreased mean sleep latency in the MSLT. The Osler, the MSLT and the questionnaires measure different objective and subjective aspects of sleepiness. In untreated OSA patients an increased propensity to fall asleep was not automatically associated with the inability to stay awake.


Vectors for the expression of tagged proteins in Schizosaccharomyces pombe.
A series of vectors is described which enables the episomal expression of proteins fused to different tag sequences in Schizosaccharomyces pombe. Proteins can be expressed with their amino termini fused to GFP/EGFP, three copies of the HA or Pk epitopes or a combined tag which contains two copies of the myc epitope and six histidine residues (MH). Fusion of the carboxyl terminus of a protein to a tag is possible with GFP/EGFP or Pk. Expression of the fusion proteins is controlled by the medium strength mutant version of the regulatable nmt1 promoter.


Evaluation of whether the ultrasonographic onion skin sign is specific for the diagnosis of an appendiceal mucocele.
To evaluate whether the onion skin sign on ultrasonography (US) of the lower abdomen is specific for the diagnosis of an appendiceal mucocele. Our study included 231 lesions from 229 patients in whom transabdominal US detected lesions in the lower abdomen and who had definitive pathological diagnoses in the small bowel, ileocecal valve, cecum, appendix, mesentery, adnexa uteri or pelvic cavity outside the major organs. Patients with metastatic tumors were excluded. We reviewed the reports and images from transabdominal US and checked for the presence of the onion skin sign. The sensitivity, specificity, and accuracy of the sign for the diagnosis of an appendiceal mucocele were calculated. Five (2.2 %) of the 231 lesions showed the onion skin sign on US and all were diagnosed with an appendiceal mucocele. The sensitivity, specificity, and accuracy of the sign for the diagnosis of an appendiceal mucocele were 63, 100, and 99 %, respectively. The onion skin sign in the lower abdomen appears to be specific for the diagnosis of an appendiceal mucocele. In cases where the onion skin sign is obviously present in the lower abdomen on US, an appendiceal mucocele should be considered as the leading diagnosis.


Comparison of the acidifying activity of Lactococcus lactis subsp. lactis strains isolated from goat's milk and Valdeteja cheese.
This work was carried out to study the acid production by Lactococcus lactis subsp. lactis strains isolated from goat's milk and goat cheese (Valdeteja variety) in order to select a suitable starter culture for industrial goat cheese manufacturing. The titrable acidity of 45 Lactococcus lactis subsp. lactis strains isolated from a home-made batch of Valdeteja cheese with excellent sensory characteristics was measured over a period of 18 h. The strains were divided into two groups depending on the acid production rate: 20 fast acid producer (F) strains and 25 slow acid producer (S) strains. The kinetic parameters (lag phase, maximum acid production rate and value of upper asymptote curve) of the acid production curves for F and S strains were significantly (P < 0.001) different. Significant (P < 0.001) differences between titrable acidity of F and S strains were observed after the second hour of incubation. An F strain acetoin producer (Lactococcus lactis subsp. lactis 470Ch2) was selected as autochthonous starter culture for industrial Valdeteja goat cheese manufacturing.


Do late adolescent fathers have more depressive symptoms than older fathers?
Although fathers are increasingly a focus of attention in research, there is a dearth of research on depressive symptoms among fathers, especially young fathers with toddlers. This study used longitudinal data to examine what risk factors, including the age status of fathers (e.g., late adolescence, emerging adulthood, and adulthood), may be associated with depressive symptoms of fathers when their children were 3 and 5 years of age. A subsample of families for which complete data were available on all variables was used in the analyses (n = 1,403). About 46% of study sample was African American, 27% White, 23% Hispanic, and 4% other race/ethnicity. Paternal depressive symptoms were measured using Composite International Diagnostic Interview-Short Form (CIDI-SF). Late adolescent fatherhood was significantly associated with third-year paternal depressive symptoms but not with fifth-year depressive symptoms. Those who reported low social support were more likely to be depressed at both times. Fathers who did not work for regular pay were more likely to be depressed at the third-year follow-up, but not at the fifth-year follow-up. Parenting stress and being booked/charged with a crime were not associated with third-year paternal depressive symptoms, but were with fifth-year paternal depressive symptoms. This study emphasizes the importance of screening for depressive symptoms of fathers even before the birth of their child and monitoring and treating postpartum depressive symptoms, as first-year depressive symptoms was a significant predictor for third- and fifth-year depressive symptoms. Service providers should focus on the mental health of fathers as well as mothers to promote healthy environments for their children.


PEGylation of interferon α2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases.
The efficacy of protein-based therapeutics with indications in the treatment of lymphatic diseases is expected to be improved by enhancing lymphatic disposition. This study was therefore aimed at examining whether PEGylation can usefully be applied to improve the lymphatic uptake of interferon α2 and whether this ultimately translates into improved therapeutic efficacy against lymph-resident cancer. The lymphatic pharmacokinetics of interferon α2b (IFN, 19kDa) and PEGylated interferon α2b (IFN-PEG12, 31kDa) or α2a (IFN-PEG40, 60kDa) was examined in thoracic lymph duct cannulated rats. IFN was poorly absorbed from the SC injection site (Fabs 36%) and showed little uptake into lymph after SC or IV administration (≤1%). In contrast, IFN-PEG12 was efficiently absorbed from the SC injection site (Fabs 82%) and approximately 20% and 8% of the injected dose was recovered in thoracic lymph over 30h after SC or IV administration respectively. IFN-PEG40, however, was incompletely absorbed from the SC injection site (Fabs 23%) and showed similar lymphatic access after SC administration to IFN-PEG12 (21%). The recovery of IFN-PEG40 in thoracic lymph after IV administration, however, was significantly greater (29%) when compared to IV IFN-PEG12. The anti-tumour efficacy of interferon against axillary metastases of a highly lymph-metastatic variant of human breast MDA-MB-231 carcinoma was significantly increased by SC administration of lymph-targeted IFN-PEG12 when compared to the administration of IFN on the ipsilateral side to the axillary metastasis. Optimal PEGylation may therefore represent a viable approach to improving the lymphatic disposition and efficacy of therapeutic proteins against lymphatic diseases.


MiR-192-5p suppresses M1 macrophage polarization via epiregulin (EREG) downregulation in gouty arthritis.
Gouty arthritis (GA) is a chronic inflammatory disease characterized by the deposition of monosodium urate (MSU) crystals within joints. MiR-192-5p is shown to be low-expressed in GA patients. However, the potential mechanism involving miR-192-5p in GA remains unclear. In the current study, a significant reduction in miR-192-5p and an increase in epiregulin (EREG) were observed in serum of GA patients, suggesting that miR-192-5p and EREG were involved in the pathogenic process of GA. A mouse GA model was established via 0.5 mg/20 μL MSU crystal administration. To investigate the effect of miR-192-5p on GA, mice were injected with miR-192-5p agomir or NC agomir before modeling. We found that miR-192-5p overexpression induced by miR-192-5p agomir reduced EREG expression, attenuated ankle joint swelling and synovial inflammatory cell infiltration and improved bone erosion in MSU-induced GA mice. MiR-192-5p decreased CD16/32+ (M1 marker) macrophages, but increased CD206 (M2 marker) expression in synovium of GA models. In vitro, RAW264.7 macrophages were stimulated with miR-192-5p mimic or NC mimic under IFNγ plus LPS-stimulated M1 polarization condition. MiR-192-5p reduced the release of inflammatory cytokines TNF-α and IL-1β, decreased iNOS expression, and inhibited CD16/32 expression, indicating the blockade of M1 macrophage activation. Luciferase reporter system revealed the target interaction between miR-192-5p and EREG. Further rescue experiments demonstrated that EREG overexpression partly reversed the inhibitory role of miR-192-5p on M1 macrophage polarization manifested by elevated iNOS and CD16/32 levels. Collectively, miR-192-5p ameliorates inflammatory response in GA by inhibiting M1 macrophage activation via inhibiting EREG protein.


The Relationship between Coaching Behavior and Athlete Burnout: Mediating Effects of Communication and the Coach-Athlete Relationship.
The purpose of this study was to investigate the relationships between perceived coaching behavior (autonomy-supportive and controlling), communication, coach-athlete relationship, and athlete burnout. The study participants comprised 347 Korean active collegiate athletes from 10 sports. The results of the final model indicated that autonomy-supportive coaching was positively related to communication, whereas controlling coaching was negatively related to communication. Communication was positively related to coach-athlete relationship and was negatively related to athlete burnout. Autonomy-supportive coaching was significantly related to both the coach-athlete relationship (positively) and athlete burnout (negatively), whereas controlling coaching was only related to athlete burnout (positively). Coach-athlete relationship was negatively related to athlete burnout. Significant indirect effects were observed. The bootstrapping results indicated that the relationship between autonomy-supportive and athlete burnout was mediated by team communication and the coach-athlete relationship. The study findings enhance our current understanding of the relationships between perceived coaching behavior and athlete burnout and shed light on the important roles of team communication and the coach-athlete relationship in the relationship.


Self-management and quality of life in chronic obstructive pulmonary disease (COPD): The mediating effects of positive affect.
This study aimed to increase our understanding of general self-management (SM) abilities in COPD by determining if SM can predict disease specific quality of life (QoL), by investigating whether specific SM domains are significant in COPD and by exploring the mediating effect of the positive/negative affect in the association between SM and QoL. Cross-sectional study based on 292 patients with COPD. Measures included demographics, lung function, gait speed, health care utilization, positive/negative affect, SM abilities, breathlessness and disease specific QoL. We performed, correlation, multiple regression models and mediation analysis (positive/negative affect being mediator between SM and QoL association). After controlling for breathlessness, living alone, marital status, hospitalization history, age and lung function, SM related to QoL (p<0.0001). Investment in behaviors (hobbies and social relationships) and self-efficacy are SM domains independently related to QoL in COPD. Positivity measured by the positive/negative affect ratio completely mediates the relationship of SM with QoL. SM is independently associated with disease specific QoL in COPD after adjustment significant covariates but positive/negative affect ratio completely mediates the relationship of SM with QoL. Measuring positive/negative affect and addressing investment behavior and self-efficacy are important in implementing COPD-SM programs.


Dopamine levels modulate the updating of tastant values.
To survive, animals must constantly update the internal value of stimuli they encounter; a process referred to as incentive learning. Although there have been many studies investigating whether dopamine is necessary for reward, or for the association between stimuli and actions with rewards, less is known about the role of dopamine in the updating of the internal value of stimuli per se. We used a single-bottle forced-choice task to investigate the role of dopamine in learning the value of tastants. We show that dopamine transporter knock-out mice (DAT-KO), which have constitutively elevated dopamine levels, develop a more positive bias towards a hedonically positive tastant (sucrose 400 mM) than their wild-type littermates. Furthermore, when compared to wild-type littermates, DAT-KO mice develop a less negative bias towards a hedonically negative tastant (quinine HCl 10 mM). Importantly, these effects develop with training, because at the onset of training DAT-KO and wild-type mice display similar biases towards sucrose and quinine. These data suggest that dopamine levels can modulate the updating of tastant values, a finding with implications for understanding sensory-specific motivation and reward seeking.


Multiple variants of the human presequence translocase motor subunit Magmas govern the mitochondrial import.
Mitochondrial protein translocation is an intricately regulated process that requires dedicated translocases at the outer and inner membranes. The presequence translocase complex, translocase of the inner membrane 23, facilitates most of the import of preproteins containing presequences into the mitochondria, and its primary structural organization is highly conserved. As part of the translocase motor, two J-proteins, DnaJC15 and DnaJC19, are recruited to form two independent translocation machineries (translocase A and translocase B, respectively). On the other hand, the J-like protein subunit of translocase of the inner membrane 23, Mitochondria-associated granulocyte-macrophage colony-stimulating factor signaling molecule (Magmas) (orthologous to the yeast subunit Pam16), can regulate human import-motor activity by forming a heterodimer with DnaJC19 and DnaJC15. However, the precise coordinated regulation of two human import motors by a single Magmas protein is poorly understood. Here, we report two additional Magmas variants (Magmas-1 and Magmas-2) constitutively expressed in the mammalian system. Both the Magmas variants are functional orthologs of Pam16 with an evolutionarily conserved J-like domain critical for cell survival. Moreover, the Magmas variants are peripherally associated with the inner membrane as part of the human import motor for translocation. Our results demonstrate that Magmas-1 is predominantly recruited to translocase B, whereas Magmas-2 is majorly associated with translocase A. Strikingly, both the variants exhibit differential J-protein inhibitory activity in modulating import motor, thereby regulating overall translocase function. Based on our findings, we hypothesize that additional Magmas variants are of evolutionary significance in humans to maximize protein import in familial-linked pathological conditions.


Six-month outcomes in postapproval HeartMate3 patients: A single-center US experience.
The European CE Mark approval study and the MOMENTUM 3 trial demonstrated safety and a reduction in hemocompatibility-related adverse events with the use of HeartMate 3 (HM3) device. This single-center study investigated the real-world experience in HM3 patients since FDA approval. This retrospective, observational study included patients implanted with the HM3 LVAD as a primary implant between October 2017 and March 2020. Patients were divided into trial group and postapproval group. The primary endpoint was survival at 6 months. Secondary endpoints were adverse events including pump thrombosis (requiring pump exchange), stroke, renal failure, acute limb ischemia, re-exploratory for bleeding, gastrointestinal bleeding, right ventricular failure, and driveline infection. A total of 189 patients were implanted with HM3 device during the study period. 174 patients met the inclusion criteria: 82 patients in the trial group and 92 patients in the postapproval group. The postapproval group had younger patients, higher preoperative mean international normalized ratio, and greater numbers of patients with bridge to transplant (BTT) indications, IINTERMACS profile 1, and use of mechanical assist devices (other than IABP) than the trial group. Other characteristics between the two groups were comparable. Overall survival at 6 months in the postapproval group was 93.3% versus 93.8% (p = .88). The postapproval group demonstrated a statistically significant lower incidence of re-explorative surgery for bleeding (10.9% vs. 46.3, p = .01) than the trial group. In this single-center study, the real-world 6-month survival in the postapproval group was comparable to the trial results. Further studies are needed to monitor long-term outcomes.


Provasopressin-neurophysin II processing is cell-specific in heterologous cell lines expressing a metallothionein-vasopressin fusion gene.
Preprovasopressin-neurophysin II (prepro-AVP-Np), the precursor of the cyclic, amidated nonapeptide, arginine vasopressin (AVP), is present in the central and peripheral nervous systems, adrenal glands, and gonads of rats. To study cell-specific processing of prepro-AVP-Np, a fusion gene consisting of the heavy metal-inducible promoter of the mouse metallothionein I gene and the rat prepro-AVP-Np gene was introduced by cellular transfection into several defined cell phenotypes: a fibroblast line (BHK), a pituitary growth hormone and prolactin-producing cell line (GH4), a pituitary cell line that produces several amidated peptides (AtT-20), and an insulin-producing pancreatic islet line (RIN- 1046-38). Clonal cell lines were isolated and prepro-AVP-Np-specific transcripts were detected by Northern blot hybridization analyses. Fibroblast BHK and pituitary GH4 cells transfected with the fusion gene synthesized a polypeptide (Mr = 18,000) characteristic of the glycosylated precursor, pro-AVP-Np; in metal -treated cells, this protein was the major secreted cysteine-labeled polypeptide. Extracts of RIN-1046-38 and AtT-20 cells transfected with the fusion gene contained predominantly processed neurophysin and amidated arginine vasopressin, whereas extracts of BHK and GH4 cells contained mainly precursors of AVP and neurophysin. These observations indicate that the pathways involving specific post-translational processing of pro-AVP-Np are more efficiently utilized in the prohormone-producing AtT-20 and RIN-1046-38 cells than in GH4 and BHK cells that do not synthesize any recognized prohormones.


Influence of obesity, parental history of diabetes, and genes in type 2 diabetes: A case-control study.
Obesity, parental history (PH) of type 2 diabetes (T2D), and genes play an important role in T2D development. However, the influence of each factor on T2D variability is unclear. This study aimed to investigate the influence of obesity (body mass index [BMI], waist/hip ratio), PH, and 16 single-nucleotide polymorphisms (SNPs) associated with T2D on T2D variability in Mexico, comparing 1234 non-diabetic controls and 1219 diabetic patients. To replicate the data, a case-control (n = 2904) and a cross-sectional (n = 1901) study were also included. In a multivariate logistic regression model, all factors accounted for only 27.3% of T2D variability: SNPs (8.4%); PH (11.8%) and obesity (7.1%). These factors contributed more in men (33.2%) than in women (25%), specifically when the disease was diagnosed before the age of 46 (46.7% vs. 30%). Genes played a substantially more important role in men than in women (14.9% vs. 5.5%), while obesity and PH played a similar role in both genders. Genes and PH appeared to play a greater role than obesity in T2D. However, obesity contribution was calculated at the time of recruitment and may be underestimated in patients because the BMI decreased linearly with the number of years with the disease. The data suggest that sexual hormones may play important roles in genes that are associated with T2D.


Simpson-Edinburgh low-pressure air bed: an early clinical evaluation.
A simple, inexpensive low-pressure air bed has been developed for use in situations where decubitus ulcers may arise. This bed is currently being evaluated in patients with spinal injuries, both in the hospital situation and in the home. Early experience is highly encouraging as regular turning of the patient can be safely omitted. We feel that widespread use of this bed could greatly decrease the incidence of pressure sores.


Early intervention in patients with heart failure and left ventricular dysfunction.
The focus of this article is to review the process of left ventricular remodeling and discuss the results of several published large clinical trials that have demonstrated the benefit of early intervention in heart failure to prevent left ventricular remodeling and progression of cardiac dysfunction. The knowledge gained from this review should help define a strategy for the internist to initiate therapy early in the course of development of heart failure.


Overexpression and characterization of a novel endo-β-1,3(4)-glucanase from thermophilic fungus Humicola insolens Y1.
A novel endo-β-1,3(4)-glucanase gene, cel16A, was cloned from the fungus Humicola insolens Y1. The 988-bp full-length gene encoded a 286-residue polypeptide consisting of a putative signal peptide of 20 residues and a catalytic domain belonging to glycosyl hydrolase family 16. It was successfully overexpressed in Pichia pastoris GS115. The purified recombinant Cel16A exhibited highest specific activity toward barley β-glucan, followed by lichenan and laminarin, but not toward CMC-Na, birchwood xylan, Avicel and filter paper, indicating that Cel16A is an endo-β-1,3(4)-glucanases. Recombinant Cel16A had a pH optimum at 5.5 and a temperature optimum at 55 °C with a specific activity of 693 U/mg toward barley β-glucan. It exhibited good stability over pH 5.0-9.0 and at temperatures up to 50 °C, retaining over 80% maximum activity. The Km and Vmax values of Cel16A for barley β-glucan were 0.91 mg ml-1 and 1530 μmol min-1·mg-1, respectively. All these favorable enzymatic properties of Cel16A make it a good candidate for applications in various industries.


Adenovirus-mediated human topoisomerase IIalpha gene transfer increases the sensitivity of etoposide-resistant human and mouse breast cancer cells.
Cellular resistance to chemotherapeutic agents is attributable to several mechanisms, including alteration of topoisomerase IIa gene expression. Our previous studies have shown that transient transfection with a vector containing either Drosophila or human topoisomerase IIalpha gene into drug-resistant tumor cells enhanced their drug sensitivity. Furthermore, we constructed a recombinant adenovirus, Ad-hTopoIIalpha, containing the human topoisomerase IIa gene that was able to selectively increase etoposide sensitivity in drug-resistant tumor cells. We also examined Ad-hTopoIIalpha for therapeutic efficacy in vitro using additional etoposide-resistant cell lines, including a mouse breast cancer cell line and a human leukemia cell line. The etoposide-resistant mouse breast cancer cell line FvP, which is derived from FM3A, and etoposide-resistant human breast cancer cell line, MDA-VP, which derived from MDA-P cells showed increased sensitivity to etoposide as well as increased expression of human Topoisomerase IIa mRNA, but this was not seen in FM3A and MDA-P cells. On the other hand, the etoposide-resistant human leukemia cell line K562/MX2 and the parental cell line K562/P did not show enhanced sensitivity against etoposide or an increase in human Topoisomerase IIa mRNA. Using a recombinant adenovirus containing beta-galactosidase gene (Ad-beta-gal), K562 cells were not transducted by the recombinant adenovirus, while both etoposide-sensitive FM3A cells and etoposide resistant FvP cells were transducted by recombinant adenovirus. Ad-hTOP2alpha and etopside treatment showed reduced inoculated tumor weight in the mice. We concluded that a recombinant adenovirus containing the human Topoisomerase IIalpha gene might be a powerful tool for overcoming drug resistance in breast cancer cells, but not in leukemia cells.


Endoscopic ultrasonography evaluation for pancreatic cysts: Necessity or overkill?
Incidental pancreatic cysts have become gradually more recognized in clinical practice as a result of increased use of transabdominal ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). These lesions consist of inflammatory cysts (pseudocysts) and pancreatic cystic neoplasms (PCN) which have been classified as benign, premalignant and malignant. The diagnosis and management strategy of incidentally discovered pancreatic cysts can be challenging as the majority of them are PCN and CT or MRI alone may not be sufficient to provide an accurate diagnosis. Endoscopic ultrasound (EUS)-guided fine-needle aspiration provides a method to obtain cyst fluid for analysis and the recently developed EUS-based technology including contrast-enhanced ultrasound, cystoscopy and needle-based confocal laser endomicroscopy allows endosonographers to gain additional useful information. The current data suggest that EUS evaluation of pancreatic cysts offers some benefits especially in cases of inconclusive CT or MRI.


Leucine aminopeptidase from bovine lens and hog kidney. Comparison using immunological techniques, electron microscopy, and X-ray diffraction.
The crystallization of leucine aminopeptidase from hog kidney is reported for the first time. The crystals which diffract to 4-A resolution have the space group P2(1)2(1)2(1) (a = 186.3 A, b = 223.2 A, and c = 80.5 A) and contain four hexamers per unit cell, or one per asymmetric unit. Electron micrographic images of hog kidney leucine aminopeptidase are indistinguishable from micrographs of beef leucine aminopeptidase taken under the same conditions (10). These reveal an equilateral triangle of about 85 A per side, seemingly made of three 40-A diameter spheres. This triangle is circumscribed by another concentric, less-dense triangle of 120 A per side which is rotated 60 degrees with respect to the inner triangle. Immunodiffusion and microcomplement fixation assays indicate that the two enzymes share greater than 90% amino acid sequence homology. This similarity is corroborated by peptide maps of tryptic fragments of the radioiodinated enzymes. The model of the quaternary structure proposed to explain the appearance of electron micrographs of single molecule and crystalline bovine lens enzyme also describes the hog kidney enzyme equally well. That the model of leucine aminopeptidase originally proposed for the beef enzyme also can be used to describe hog kidney leucine aminopeptidase crystal packing in the highly anisometric unit cell provides further corroboration that leucine aminopeptidase in these two species is a hexamer based on two trimers each made of three bilobal promoters.


Fibrin-Associated Diffuse Large B Cell Lymphoma Found on Revision Arthroplasty of the Knee.
Fibrin-associated diffuse large B cell lymphoma (FA-DLBCL) is a rare Epstein-Barr viruspositive B cell lymphoma that is nonmass-forming, does not directly produce symptoms, and is incidentally discovered on histological examination of tissues excised for other reasons. Despite overlap in morphologic and immunophenotypic features with aggressive B cell neoplasms, FA-DLBCL shows an excellent clinical outcome, even with surgical excision alone. We report an extremely rare occurrence of FA-DLBCL found in association with a metallic implant on revision arthroplasty of the knee. This report also illustrates the need for an integrated multidisciplinary approach for accurate diagnosis and avoidance of overtreatment.


IL-17-induced HIF1α drives resistance to anti-PD-L1 via fibroblast-mediated immune exclusion.
Increasing evidence suggests that intratumoral inflammation has an outsized influence on antitumor immunity. Here, we report that IL-17, a proinflammatory cytokine widely associated with poor prognosis in solid tumors, drives the therapeutic failure of anti-PD-L1. By timing the deletion of IL-17 signaling specifically in cancer-associated fibroblasts (CAFs) in late-stage tumors, we show that IL-17 signaling drives immune exclusion by activating a collagen deposition program in murine models of cutaneous squamous cell carcinoma (cSCC). Ablation of IL-17 signaling in CAFs increased the infiltration of cytotoxic T cells into the tumor mass and sensitized otherwise resistant cSCC to anti-PD-L1 treatment. Mechanistically, the collagen deposition program in CAFs was driven by IL-17-induced translation of HIF1α, which was mediated by direct binding of Act1, the adaptor protein of IL-17 receptor, to a stem-loop structure in the 3' untranslated region (UTR) in Hif1α mRNA. Disruption of Act1's binding to Hif1α mRNA abolished IL-17-induced collagen deposition and enhanced anti-PD-L1-mediated tumor regression.


Ionic liquid-assisted synthesis of composition-tunable cross-linked AgPt aerogels with enhanced electrocatalysis.
A facile one-pot coreduction strategy was developed to synthesize composition-tunable cross-linked AgPt aerogels, where ionic liquid (1-aminopropyl-3-methylimidazolium bromide, [APMIm]Br) played a significant role in controlling the morphology and structure. During the synthesis progress, Br- easily reacted with Ag+ to form AgBr precipitate and consequently slowed down the reducing rate of Ag+, as well as acting as a capping agent to promote the anisotropic growth of AgPt aerogels, as mainly demonstrated by the electronic microscopy, Brunauer-Emmett-Teller, X-ray diffraction and X-ray photoelectron spectroscopy analysis. The architectures showed superior catalytic activity and enhanced durability toward ethanol oxidation reaction (EOR) and ethylene glycol oxidation reaction (EGOR) in contrast with commercial Pt black, owing to the tailored composition, morphology and electronic structure of the prepared AgPt aerogels.


Scandcleft Project Trial 2-Comparison of Speech Outcome in 1- and 2-Stage Palatal Closure in 5-Year-Olds With UCLP.
To investigate in-depth speech results in the Scandcleft Trial 2 with comparisons between surgical protocols and centers and with benchmarks from peers without cleft palate. A prospective randomized clinical trial. Two Swedish and one Finnish Cleft Palate center. One hundred twelve participants were 5-years-old born with unilateral cleft lip and palate randomized to either lip repair and soft palate closure at 4 months and hard palate closure at 12 months or lip repair at 3 to 4 months (Arm A), or a closure of both the soft and hard palate at 12 months (Arm C). A composite measure dichotomized into velopharyngeal competency (VPC) or velopharyngeal incompetency (VPI), overall assessment of velopharyngeal function (VPC-Rate), percentage of consonants correct (PCC score), and consonant errors. In addition, number of speech therapy visits, average hearing thresholds, and secondary surgeries were documented to assess burden of treatment. Across the trial, 53.5% demonstrated VPC and 46.5% VPI with no significant differences between arms or centers. In total, 27% reached age-appropriate PCC scores with no statistically significant difference between the arms. The Finnish center had significantly higher PCC scores, the Swedish centers had higher percentages of oral consonant errors. Number of speech therapy visits was significantly higher in the Finnish center. At age 5, poor speech outcomes with some differences between participating centers were seen but could not be attributed to surgical protocol. As one center had very few participants, the results from that center should be interpreted with caution.


Radiation dose escalation for locally advanced nasopharyngeal carcinoma patients with local and/or regional residual lesions after standard chemoradiotherapy: a non-randomized, observational study.
To assess the effectiveness and toxicity of radiation dose escalation for locally advanced nasopharyngeal carcinoma (LA-NPC) in patients with local and/or regional residual lesion(s) after standard treatment. From November 2011 to November 2020, 259 LA-NPC patients who had local and/or regional residual lesion(s) after induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1-74.25 Gy (median, 70.4 Gy). The boost doses were 4.0-18.0 Gy (median, 9 Gy), 1.8-2.0 Gy/fraction. For all patients, the 5-year local relapse-free survival was 90.2%, regional relapse-free survival was 89.1%, locoregional relapse-free survival (LRRFS) was 79.5%, distant metastasis-free survival (DMFS) was 87.9%, failure-free survival (FFS) was 69.0%, and overall survival (OS) was 86.3%. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma Epstein-Barr virus-deoxyribonucleic acid ≤ 500 versus > 500, T1-2 versus T3-4, N0-1 versus N2-3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002). Boost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study. Retrospectively registered.


A new tool to sense pH changes at the neuromuscular junction synaptic cleft.
Synaptic transmission triggers transient acidification of the synaptic cleft. Recently, it has been shown that pH affects the opening of postsynaptic channels and therefore the production of tools that allow to study these behaviors should result of paramount value. We fused α-bungarotoxin, a neurotoxin derived from the snake Bungarus multicinctus that binds irreversibly to the acetylcholine receptor extracellular domain, to the pH sensitive GFP Super Ecliptic pHluorin, and efficiently expressed it in Pichia pastoris. This sensor allows synaptic changes in pH to be measured without the need of incorporating transgenes into animal cells. Here, we show that incubation of the mouse levator auris muscle with a solution containing this recombinant protein is enough to fluorescently label the endplate post synaptic membrane. Furthermore, we could physiologically alter and measure post synaptic pH by evaluating changes in the fluorescent signal of pHluorin molecules bound to acetylcholine receptors. In fact, using this tool we were able to detect a drop in 0.01 to 0.05 pH units in the vicinity of the acetylcholine receptors following vesicle exocytosis triggered by nerve electrical stimulation. Further experiments will allow to learn the precise changes in pH during and after synaptic activation.


Validation of the process criteria for assessment of a hospital nursing service.
to validate an instrument containing process criteria for assessment of a hospital nursing service based on the National Accreditation Organization program. a descriptive, quantitative methodological study performed in stages. An instrument constructed with 69 process criteria was assessed by 49 nurses from accredited hospitals in 2009, according to a Likert scale, and validated by 16 judges through Delphi rounds in 2010. the original instrument assessed by nurses with 69 process criteria was judged by the degree of importance, and changed to 39 criteria. In the first Delphi round, the 39 criteria reached consensus among the 19 judges, with a medium reliability by Cronbach's alpha. In the second round, 40 converging criteria were validated by 16 judges, with high reliability. The criteria addressed management, costs, teaching, education, indicators, protocols, human resources, communication, among others. the 40 process criteria formed a validated instrument to assess the hospital nursing service which, when measured, can better direct interventions by nurses in reaching and strengthening outcomes.


Mild traumatic brain injuries in children between 0-16 years of age: a survey of activities and places when an accident occurs.
The aim of this study was to identify what activities cause most mild traumatic brain injury (MTBI) among boys and girls between 0-16 years of age. Based on a randomized controlled study, a retrospective analysis was conducted among 765 children. The most common causes of injury were falls from a height and falls from the same level. The most common place where the accident occurred was at 'home' followed by 'pre-school/school'. The highest incidence was 'play' followed by 'hit by another person', thereafter 'baby nursing'. Boys are more often injured than girls, but with no difference between boys and girls in terms of which activities that cause MTBI. Supervision during play at home as well as better designed schoolyards and playgrounds are required to prevent accidents. Furthermore, well-documented medical records are necessary to identify activities causing MTBI among children.


Refinements in abdominoplasty.
When performing traditional abdominoplasty, three fundamental defects of the abdominal wall must always be addressed by the plastic surgeon. They include redundant skin, excess fat, and musculofascial laxity. Plastic surgeons have found that this procedure consists of dermolipectomy and rectus plication, extremely effective in restoring the abdomen to its youthful shape in the vast majority of patients. This article will review the recent advancements in body contouring surgery while focusing on the recent technical refinements in abdominoplasty.


The synergistic effect of calcite and Cu2+ on the degradation of sulfadiazine via PDS activation: A role of Cu(Ⅲ).
A system of Cu2+/calcite/PDS was constructed to degrade sulfadiazine (SDZ). Different from the traditional Cu-mediated activation, a low concentration of Cu2+ that met drinking water standards (≤ 1 mg/L) transformed into Cu(Ⅱ) solid in the presence of calcite, and then enhanced the degradation of SDZ via PDS activation over a pH range from 3 to 9. According to scavenger and chemical probe experiments, Cu(Ⅲ), rather than radicals (hydroxyl radicals and sulfate radicals) and singlet oxygen, was the predominant reactive species, which was responsible for the degradation of SDZ. Based on the results of XRD, ATR-FTIR, and CV curves et al., CuCO3 was the main complex with high reactivity for PDS activation to form Cu(Ⅲ). Moreover, detailed degradation pathways of sulfadiazine were proposed according to the UPLC-ESI-MS/MS and their toxicity was predicted by ECOSAR. Besides, the real water matrix would not seriously affect the degradation of SDZ in the Cu2+/calcite/PDS system. In summary, this study reveals a new insight into the synergistic effect of Cu2+ and calcite on the SDZ degradation, and promotes an understanding of the environmental benefits of natural calcite.


11th Asia Oceania Human Proteome Organization Congress Report.
As the first in-person Asia Oceania Human Proteomics Organization (AOHUPO) congress since 2018, the 11th AOHUPO congress was an opportune time for the research community to reconnect and to renew friendships after the long period of restricted travel due to the global pandemic. Moreover, this congress was a great opportunity for the many AO regional proteomics and mass spectrometry scientists to meet in Singapore to exchange ideas and to present their latest findings. Cohosted by the Singapore Society for Mass Spectrometry and the Malaysian Proteomics Society and held in conjunction with the seventh Asia Oceania Agricultural Proteomics Organization Congress and Singapore Society for Mass Spectrometry 2023, the meeting featured both human and agricultural proteomics. Over five hundred scientists from the AO region converged on the MAX Atria @ Singapore EXPO, Changi, Singapore from May 8 to 10 for the main congress. The diverse program was made up of 64 invited speakers and panellists for seven plenary lectures, 27 concurrent symposia, precongress and postcongress workshops, and 174 poster presentations. The AOHUPO society were able to celebrate not only their 20th anniversary but also the outstanding academic research from biological and agricultural proteomics and related 'omics fields being conducted across the Asia-Oceania region.


Consumer expectations, drug effects, price and purity of heroin and cocaine purchased at drug consumption rooms.
Drug consumption rooms offer heroin and cocaine consumers a secure and hygienic environment including medical and social guidance. Despite the support and mentoring, only sparse information is available about how drug quality, drug prices and user expectations match at these locations. The present study reports analysis of these three parameters in two drug consumption rooms in Luxembourg. Drug users were invited to participate in the project by handing in a few milligrams of the product they planned to consume for chemical analysis and filling out a short questionnaire about the price and their expectations. After consumption, they were asked to report the experienced effects. Drug quality was accessed using LC-Q-ToF and HPLC-UV, and a statistical analysis was carried out of the questionnaires that were correctly filled out. A total of 513 drug samples have been analyzed. Most consumers were looking for the relaxing/calming effects of heroin and the stimulating effects of cocaine, but they generally overestimated heroin potency and underestimated cocaine potency. No strong correlation based on Spearman's ρ between drug user estimations, drug prices and drug quality was found. To the best of our knowledge, this study is the first to combine drug analysis with heroin and cocaine user feedback about expectation, drug prices and drug effects. The analytical results were of great interest for users and the staff working at the drug consumption rooms. They may be a strong supplementary communication tool for health care workers when discussing effects and risks of highly toxic substance consumption.


Impact of Disease Duration on Vascular Surrogates of Early Atherosclerosis in Childhood-Onset Systemic Lupus Erythematosus.
To determine whether longer disease duration negatively impacts carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and pulse wave velocity (PWV) in a cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare CIMT, FMD, and PWV in patients with childhood-onset SLE with those in healthy children and explore determinants of vascular test results in childhood-onset SLE. Cross-sectional analysis was performed in a prospective longitudinal cohort of patients with childhood-onset SLE at the latest followup visit. Clinical and laboratory data were collected for patients with childhood-onset SLE. CIMT, FMD, and PWV were measured using standardized protocols in patients with childhood-onset SLE and healthy children. Correlations between disease duration and results of the 3 vascular tests were performed. Vascular data in patients with childhood-onset SLE were compared with those in healthy children. Multivariable linear regression was used to identify determinants of CIMT, FMD, and PWV in childhood-onset SLE. Patients with childhood-onset SLE (n = 149) and healthy controls (n = 178) were enrolled. The median age of the patients was 17.2 years (interquartile range [IQR] 15.7-17.9 years), and their median disease duration was 3.2 years (IQR 1.8-4.9 years). The median age of the healthy children was 14.7 years (IQR 13.1-15.9 years). Longer disease duration correlated with worse FMD (r = -0.2, P = 0.031) in patients with childhood-onset SLE. Patients with childhood-onset SLE had smaller (better) CIMT, higher (better) FMD, and similar PWV compared with healthy controls. Linear regression analysis explained <24% of the variation in vascular test results in patients with childhood-onset SLE, suggesting that other variables should be explored as important determinants of CIMT, FMD, and PWV. In this cohort of 149 patients with childhood-onset SLE, patients did not have worse CIMT, FMD, or PWV than did healthy controls. Longer disease duration was associated with worse FMD, suggesting progressive endothelial dysfunction over time.


Effect of extracorporeal shock wave therapy for rotator cuff tendonitis: A protocol for systematic review and meta-analysis.
Rotator cuff tendinitis is a highly prevalent cause of shoulder pain and leads to decreased patient quality of life. Extracorporeal shock wave therapy (ESWT) and ultrasound-guided needling are considered beneficial for rotator cuff tendinitis. A systematic review and meta-analysis comparing ESWT with sham-ESWT or ultrasound-guided needling in the management of pain and calcification is lacking. We will search the following up database from its inception to August 2020 without language restriction: PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, China Biomedical Literature Database, Chinese Science Journal Database, and WangFang database. All randomized controlled trials compared the effect of ESWT and sham-ESWT or ultrasound-guided needling of rotator cuff tendinitis will be included in pain and calcification. Two researchers will operate literature retrieval, screening, information extraction, quality assessment, and data analysis independently. The analysis will be conducted using Review Manager 5.3 Software. The findings will be submitted to a peer-reviewed publication. This systematic review and meta-analysis will provide high-quality evidence for the treatment of patients with rotator cuff tendinitis. INPLASY202080028.


Visual predators select for crypticity and polymorphism in virtual prey.
Cryptically coloured animals commonly occur in several distinct pattern variants. Such phenotypic diversity may be promoted by frequency-dependent predation, in which more abundant variants are attacked disproportionately often, but the hypothesis has never been explicitly tested. Here we report the first controlled experiment on the effects of visual predators on prey crypticity and phenotypic variance, in which blue jays (Cyanocitta cristata) searched for digital moths on computer monitors. Moth phenotypes evolved via a genetic algorithm in which individuals detected by the jays were much less likely to reproduce. Jays often failed to detect atypical cryptic moths, confirming frequency-dependent selection and suggesting the use of searching images, which enhance the detection of common prey. Over successive generations, the moths evolved to become significantly harder to detect, and they showed significantly greater phenotypic variance than non-selected or frequency-independent selected controls.


Kopsanone and N-oxide isolated from Aspidosperma macrocarpon Mart. (Apocynaceae) leaves and their MAO-A inhibitory activity.
Aspidosperma macrocarpon Mart., popularly known as 'guatambu' or 'peroba', is found from North American (Mexico) to South American (Argentina) continents and in Brazil. Two indole alkaloids were isolated from leaves of A. macrocarpon, kopsanone (1) and unreported N(4)-oxide-kopsanone (2).


The influence of dopamine on active sodium transport across frog skin measured as short circuit current.
The influence of dopamine (DA) on short circuit current (SCC) across isolated Rana esculenta skin was studied to determine whethera a DA receptor system exists in that cell membrane model and what is the influence of DA on SCC. Experiments were carried out with both alpha- and beta-adrenergic blockers and cocaine present in the Ringer solution. DA in cumulative doses added to the inner Ringer solution stimulated SCC in a dose-dependent manner. Apomorphine (10(-5) M) shifted the DA dose--response curve to the left and increased the maximum DA response. Haloperidol (10(-9) M) antagonized the effects of the DA depressing maximum response as well. Imidazole (10(-8) M and 10(-9) M) antagonized the influence of DA in a manner similar to haloperidol. It appeared that there were DA receptors in frog skin and that haloperidol as well as imidazole were DA antagonists which acted non-competitively.


Corticotropin-releasing factor (CRF) is involved in the acute anorexic effect of alpha-melanocyte-stimulating hormone: a study using CRF-deficient mice.
Alpha-melanocyte-stimulating hormone (alpha-MSH) and its receptors are critical and indispensable for maintaining appropriate feeding behavior and energy homeostasis in both mice and humans. Corticotropin-releasing factor (CRF) is a candidate for mediating the anorexic effect of alpha-MSH. In the present study, we examined whether CRF and its receptors are involved in the anorexic effect of alpha-MSH, using CRF-deficient (CRFKO) mice and a CRF receptor antagonist. Intracerebroventricular administration of NDP-MSH, a synthetic alpha-MSH analogue, suppressed food intake in wild-type (WT) mice. This effect was abolished by pretreatment with a non-selective CRF receptor antagonist, astressin, suggesting that the effect of alpha-MSH-induced anorexia was mediated by a CRF receptor. In CRFKO mice, administration with NDP-MSH did not affect food intake at an early phase (0-4h). In addition, CRF mRNA levels in the hypothalamus were significantly increased in NDP-MSH-treated mice. Therefore, our findings, using CRFKO, strongly support evidence that CRF is involved in the acute anorexic effect of alpha-MSH. On the other hand, NDP-MSH administered to CRFKO mice led to suppressed food intake at the late phase (4-12h), similar to the effect in WT mice. Further, NDP-MSH similarly reduced food intake during the late phase in all types of mice, including WT, CRFKO, and CRFKO with corticosterone replacement. The results would suggest that alpha-MSH-induced suppression of food intake at late phase was independent of glucocorticoids and CRF.


Diagnosis of bovine brucellosis using a homogeneous fluorescence polarization assay.
To evaluate the fluorescence polarization assay (FPA) for the serological diagnosis of bovine brucellosis, 118 sera from cattle which were culture positive for Brucella abortus, 1751 sera from cattle from premises containing cattle infected with B. abortus, 1222 sera from cattle vaccinated with B. abortus strain 19 and 1199 sera from cattle with no evidence of brucellosis were tested in Argentina, Chile, Mexico and in the American states of Iowa, Missouri and Texas. Initial determination of serological positivity and negativity was based upon reactivity in currently used serological tests, consisting of a rapid screening test, the rose-bengal or the buffered plate antigen tests, followed by a second serological test, the complement fixation test. Sensitivity of the FPA (sera from culture positive animals) ranged from 87.5% to 100%. Serological positivity of cattle from infected premises ranged from 65.5% to 99.0% while the % negative cattle in herds without evidence of brucellosis was between 94.9 and 100%. Of B. abortus strain 19 vaccinated cattle which were positive in at least one in-use serological tests, 88.2% were negative in the FPA. In contrast, previous Canadian studies, sensitivity values were 99.0% and 100% and the specificity in both cases was 100%. This discrepancy was probably due to the use of less well characterized sera in the current study.


Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin.
Aging is an independent risk factor for hypertension, and hypertension and insulin resistance commonly coexist in the elderly. This study was designed to examine the effects of aging-related insulin resistance on blood pressure (BP) and its underlying mechanisms, with specific focus on the role of exercise in reversing hypertensive response. Adult (6-month-old) and aging (24-month-old) male Sprague-Dawley rats were subjected to a 10 weeks free-of-loading swim training (60 min/day, 5 days/week). Arterial vasorelaxation, cardiac contraction, eNOS activation, and iNOS and gp91(phox) expression were determined. Under aging-related insulin resistance conditions, insulin infusion significantly elevated BP (P < 0.05). Aging caused significant endothelial dysfunction (P < 0.05 - 0.01), which was responsible for decreased arterial vasorelaxation to insulin. Aging attenuated myocardial contractile response to insulin, decreased eNOS expression and its phosphorylation by insulin, and increased iNOS and gp91(phox) expression in aging arteries (P < 0.01). Exercise improved insulin sensitivity, potentiated insulin's positive inotropic effects, facilitated arterial vasorelaxation to insulin, increased arterial eNOS activation in adult and aging rats, and thus attenuated insulin resistance-related hypertensive response to insulin. Moreover, exercise markedly reversed increased iNOS and gp91(phox) expression in aging arteries. Inhibition of eNOS with Cavtratin or L-NAME significantly blocked exercise-facilitated arterial vasorelaxation to insulin and exercise-lowered BP response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin, but not insulin's positive inotropic effects, plays an important role in the development of aging-related hypertension. The reversal of hypertensive response to insulin by exercise is most likely associated with improved insulin sensitivity in an eNOS-dependent manner and reduced oxidative and nitrative stresses.


Why therapies for Alzheimer's disease do not work: Do we have consensus over the path to follow?
Alzheimer's disease (AD) represents a personal tragedy of enormous magnitude, which imposes a daunting worldwide challenge for health-care providers and society as well. In last five decades, global research in clinics and laboratories has illuminated many features of this sinister and eventually fatal disease. Notwithstanding this development, the Alzheimer's research apparently has come across a phase of disappointment and a little reservation about the direction to follow. Persistently distressing controversies and a significant number of missing facts shed further uncertainty about the path forward. A detailed description of some of the main controversies in AD research may assist the field towards finding a resolution. Here I reviewed some alarming concerns or controversies related to these primary issues and emphasized on a possible mechanism to settle them.


Lateral Fully Organic P-N Diodes Created in a Single Donor-Acceptor Copolymer.
P-N junctions exist in many solid-state organic devices, such as light-emitting diodes, solar cells, and thermoelectric devices. Creating P-N junctions by bulk chemical doping in a single organic material (like silicon doped by boron and phosphorus) may capitalize the vast scientific and technological groundwork established in the inorganic semiconducting field. However, high-performance single-organic-material P-N junctions are seldom reported, because the diffusion of the dopant counterions often leads to transient rectification properties. Herein, a new type of lateral fully organic diodes created in single donor-acceptor (D-A) copolymer films with only one P-type dopant is reported. The achieved lateral devices exhibit high current densities of ≈3.83 A cm-2 and a high rectification ratio of ≈2100, which are beyond the requirements for high-frequency identification tags. The P- to N-type polarity switching mechanism is proposed after spectroscopic and structural tests. Decent stability of the organic diode is obtained, which is due to the long channel length and low diffusion speed of the large size of dopants. This work opens the opportunities to create P-N junctions in ways of silicon-based inorganic semiconductors and promises new opportunities for integrating organic materials for flexible and printable organic devices.


Chemical structure of three neutral trisaccharides isolated in free form from bovine colostrum.
Three neutral trisaccharides, which comprise 25.1% of the neutral oligosaccharide other than lactose, were isolated from bovine colostrum, obtained 6 h after parturition, by l.c. on amino silica gel. The chemical structures were identified, by methylation analysis with direct m.s. and g.l.c.-m.s., and by structural analysis with 13C-n.m.r., as beta-D-Galp-(1----4)-[alpha-L-Fucp-(1----3)-]-D-GlcNAc (3-fucosyl-N-acetyllactosamine), beta-D-Galp-(1----3)-beta-D-Galp-(1----4)-D-Glc (3'-galactosyllactose), and beta-D-Galp-(1----6)-beta-D-Galp-(1----4)-D-Glc (6'-galactosyllactose). The The first-named compound was a novel oligosaccharide from mammalian milk.


Hypoxic preconditioning up-regulates glucose transport activity and glucose transporter (GLUT1 and GLUT3) gene expression after acute anoxic exposure in the cultured rat hippocampal neurons and astrocytes.
Hypoxic preconditioning has been shown to increase the hypoxic tolerance of brain neurons. However, the mechanism underlying the increased hypoxic tolerance has not been well elucidated. Since anaerobic glycolysis is the only pathway for a vertebrate cell to produce energy under anoxic conditions, which needs a large amount of glucose, we hypothesize that glucose transport, the rate-limiting step for glucose metabolism, plays a critical role in the hypoxic tolerance induced by hypoxic preconditioning. In this study, the effects of hypoxic preconditioning on glucose transport activity and the gene expression of two major forms of glucose transporters (GLUT1 and GLUT3) in the brain were investigated in cultured rat hippocampal neurons and astrocytes. The neuronal and astroglial cultures were preconditioned for 6 days by intermittently exposing the cells to sublethal hypoxic gas mixture (1% O2/10% CO2/89% N2) for 20 min each day. 24 h after the last hypoxic exposure, the cells were exposed to a lethal anoxic gas mixture (10% CO2/90% N2) for 6 h and the uptake rate of [3H] 2-deoxyglucose (2-DG) and the levels of GLUT1 and GLUT3 glucose transporter mRNAs in the cells were examined immediately after anoxic exposure. The neurons and astrocytes preconditioned with hypoxia showed higher 2-DG uptake rates than the non-preconditioned cells. Compatible with the change in 2-DG uptake, hypoxic preconditioning also increased GLUT1 mRNA levels in the astrocytes and GLUT1 and GLUT3 mRNA levels in the neurons. The neurons preconditioned by hypoxia displayed increased anoxic tolerance. However, when glucose uptake in the neurons was blocked by cytochalasin B, the anoxic tolerance was almost abolished. These results suggest that glucose transport is critical to neuronal survival during anoxic exposure and the increased glucose transport activity is probably one of the important mechanisms for the enhanced hypoxic tolerance induced by hypoxic preconditioning.


Management of seizures following a stroke: what are the options?
Post-stroke seizures are a frequent cause of remote symptomatic epilepsy in adults, especially in older age. About 10% of stroke patients will suffer a seizure, depending on risk factors, such as the type, location and severity of the stroke. Previous stroke accounts for 30-40% of all cases of epilepsy in the elderly. Compared with that in younger patients, the appearance of seizures in old age is less specific and may take time before a diagnosis can be proven. The optimal timing and type of antiepileptic drug (AED) treatment for patients with post-stroke seizures is still a controversial issue. Many population- and hospital-based studies have been performed, ending with generalized recommendations, but still the decision to initiate AED treatment after a first or second seizure should be individualized. Prospective studies in the literature showed that immediate treatment after a first unprovoked seizure does not improve the long-term remission rate. However, because of the physical and psychological influences of recurrent seizures, prophylactic treatment should be considered after a first unprovoked event in an elderly person at high risk of recurrence, taking into consideration the individuality of the patient and a discussion with the patient and his/her family about the risks and benefits of both options. The latest studies regarding post-stroke seizure treatment showed that 'new-generation' drugs, such as lamotrigine, gabapentin and levetiracetam, in low doses would be reasonable because of their high rate of long-term seizure-free periods, improved safety profile, and fewer interactions with other drugs, especially anticoagulant ones, compared with first-generation AEDs. On the other hand, first-generation drugs, such as phenytoin, carbamazepine and phenobarbital, have the potential to have a harmful impact on recovery, bone health, cognition and blood sodium levels and may interact with other treatments used by the elderly population. The drug chosen for use in the elderly population should possess a wide spectrum of activity and have few side effects. An assessment should be done to identify possible drug-drug interactions, the drug should be started at a low dose and titrated slowly to the lowest maintenance dose possible, and enhanced quality of life should be a focus of treatment. So, in the end, further research is needed to determine, more appropriately, the type of AED therapy, timing and duration of treatment.


The action of 4-hydroxyaminobiphenyl in Escherichia coli: cytotoxic and mutagenic effects in DNA repair deficient strains.
The cytotoxic and mutagenic effects of 4-hydroxyaminobiphenyl (N-OH-ABP) were studied using Escherichia coli strains with different repair capacities. N-OH-ABP was equally cytotoxic for uvrA and recA mutants as well as in wild-type cells while polA mutant strains proved particularly sensitive to its toxicity. In contrast, the mutation frequency in the uvrA strains tested was elevated to 30-400-fold the wild-type values. We suggest that aminobiphenyl-DNA adducts responsible for mutation are repaired by UVR endonuclease but different pathways exist for removal of DNA lesions responsible for bacterial killing. From the 32P-postlabeling analysis, it was concluded that ABP-DNA adducts can be relatively rapidly repaired in wild-type strains, while persisting in the uvrA strains.


Oxytocin mediates stress-induced analgesia in adult mice.
As a neurohormone and as a neurotransmitter, oxytocin has been implicated in the stress response. Descending oxytocin-containing fibres project to the dorsal horn of the spinal cord, an area important for processing nociceptive inputs. Here we tested the hypothesis that oxytocin plays a role in stress-induced analgesia and modulates spinal sensory transmission. Mice lacking oxytocin exhibited significantly reduced stress-induced antinociception following both cold-swim (10 degrees C, 3 min) and restraint stress (30 min). In contrast, the mice exhibited normal behavioural responses to thermal and mechanical noxious stimuli and morphine-induced antinociception. In wild-type mice, intrathecal injection of the oxytocin antagonist dOVT (200 microM in 5 microl) significantly attenuated antinociception induced by cold-swim. Immunocytochemical staining revealed that, in the mouse, oxytocin-containing neurones in the paraventricular nucleus of the hypothalamus are activated by stress. Furthermore, oxytocin-containing fibres were present in the dorsal horn of the spinal cord. To test whether descending oxytocin-containing fibres could alter nociceptive transmission, we performed intracellular recordings of dorsal horn neurones in spinal slices from adult mice. Bath application of oxytocin (1 and 10 microM) inhibited excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. This effect was reversed by the oxytocin antagonist dOVT (1 microM). Whole-cell recordings of dorsal horn neurones in postnatal rat slices revealed that the effect of oxytocin could be blocked by the addition of GTP-gamma-S to the recording pipette, suggesting activation of postsynaptic oxytocin receptors. We conclude that oxytocin is important for both cold-swim and restraint stress-induced antinociception, acting by inhibiting glutamatergic spinal sensory transmission.


A qualitative examination of the needs of families faced with the option of organ donation.
Fewer than half of families approached about organ donation provide consent. Identifying specific support needs of family members in these situations is critical to help them cope and for improving consent rates. This focus group study retrospectively investigated donor and non-donor family members' perceived social support needs while facing the death of their loved one. Implications for nursing care and other interventions are discussed for interested healthcare providers.


Synthesis of a high-mannose-type glycopeptide analog containing a glucose-asparagine linkage.
The title compound was prepared by enzymatic transfer of oligosaccharide to a synthetic pentapeptide containing the Glc-Asn linkage. The compound was not hydrolyzed by glycoamidases from plant and bacterial sources, but it inhibited both enzymes in the micromolar range. Its activity is compared to other potential inhibitors.


A role for Fas II in the stabilization of motor neuron branches during pruning in Drosophila.
During insect metamorphosis, the nervous system is extensively remodeled resulting in the development of new circuits that will execute adult-specific behaviors. The peripheral remodeling seen during development of innervation to the Dorsal Longitudinal (flight) Muscle (DLM) in Drosophila involves an initial retraction of larval neuromuscular junctions followed by adult-specific branch outgrowth. Subsequently, a phase of pruning occurs during which motor neuron branches are pruned back to reveal the stereotypic pattern of multiple contact points (or arbors) along the length of each DLM fiber. In this study, we show that the cell adhesion molecule, Fasciclin II (Fas II), is important for generating the stereotypic pattern. In Fas II hypomorphs, the number of contact points is increased, and the phenotype is rescued by targeted expression of Fas II in either synaptic partner. Arbor development has three distinct phases: outgrowth and elaboration, pruning and stabilization, and expansion of stabilized arbors. Fas II is expressed during the first two phases. A subset of branches is labeled during the elaboration phase, which is likely to initiate a stabilization pathway allowing branches to survive the pruning phase. However, since not all Fas II positive branches are retained, we propose that it primes branches for stabilization. Our data suggest that Fas II functions to restrict branch length and arbor expanse.


[Relationship among sleep quality, sleep habits and school adjustment in adolescents from an urban district of Galicia.]
The duration and the sleep quality are related to the emotional status and the academic performance in adolescents. The objective of this study was to evaluate the quality of sleep in a group of adolescents, and to explore its relationship with school adjustment and performance. A cross-sectional descriptive study was made with 56 adolescents aged 13-17 years from a high school institute in an urban district of La Coruña city was performed during the scholar´s year 2016-2017. The participants completed the Pittsburgh Sleep Quality Index (ICSP) and the Brief School Adjustment Scale, and a brief questionnaire about their sleep habits and school scores. Descriptive analysis and different comparative parametric or not parametric statistical tests were applied according to type of variable; statistical significant value was considerate for p<0.10. The 35.7% of sample was poor sleepers and sleepiness was the most altered variable in ICSP. The female participants tended to sleep less than the male participants, and all of them went to sleep 100 minutes later on the weekend. Being a good or bad sleeper did not affect academic performance. Globally the school adjustment was satisfactory. Diurnal dysfunction was related to a worse adolescent-teacher and adolescent-classmate relationship. Diurnal dysfunction was also related to a poor motivation to perform academic tasks. Sleepiness is the most relevant problem in poor sleepers. Sleepiness has a negative influence on school adjustment and motivation for school activities of all adolescents; it is frequent and underestimated in most of the cases.


Practical approach to detection and surveillance of emerging highly resistant Mycobacterium tuberculosis Beijing 1071-32-cluster.
Ancient sublineage of the Mycobacterium tuberculosis Beijing genotype is endemic and prevalent in East Asia and rare in other world regions. While these strains are mainly drug susceptible, we recently identified a novel clonal group Beijing 1071-32 within this sublineage emerging in Siberia, Russia and present in other Russian regions. This cluster included only multi/extensive drug resistant (MDR/XDR) isolates. Based on the phylogenetic analysis of the available WGS data, we identified three synonymous SNPs in the genes Rv0144, Rv0373c, and Rv0334 that were specific for the Beijing 1071-32-cluster and developed a real-time PCR assay for their detection. Analysis of the 2375 genetically diverse M. tuberculosis isolates collected between 1996 and 2020 in different locations (European and Asian parts of Russia, former Soviet Union countries, Albania, Greece, China, Vietnam, Japan and Brazil), confirmed 100% specificity and sensitivity of this real-time PCR assay. Moreover, the epidemiological importance of this strain and the newly developed screening assay is further stressed by the fact that all identified Beijing 1071-32 isolates were found to exhibit MDR genotypic profiles with concomitant resistance to additional first-line drugs due to a characteristic signature of six mutations in rpoB450, rpoC485, katG315, katG335, rpsL43 and embB497. In conclusion, this study provides a set of three concordant SNPs for the detection and screening of Beijing 1071-32 isolates along with a validated real-time PCR assay easily deployable across multiple settings for the epidemiological tracking of this significant MDR cluster.


CANFOR Portuguese version: validation study.
The increase in prisoner population is a troublesome reality in several regions of the world. Along with this growth there is increasing evidence that prisoners have a higher proportion of mental illnesses and suicide than the general population. In order to implement strategies that address criminal recidivism and the health and social status of prisoners, particularly in mental disordered offenders, it is necessary to assess their care needs in a comprehensive, but individual perspective. This assessment must include potential harmful areas like comorbid personality disorder, substance misuse and offending behaviours. The Camberwell Assessment of Need - Forensic Version (CANFOR) has proved to be a reliable tool designed to accomplish such aims. The present study aimed to validate the CANFOR Portuguese version. The translation, adaptation to the Portuguese context, back-translation and revision followed the usual procedures. The sample comprised all detainees receiving psychiatric care in four forensic facilities, over a one year period. A total of 143 subjects, and respective case manager, were selected. The forensic facilities were chosen by convenience: one prison hospital psychiatric ward (n=68; 47.6%), one male (n=24; 16.8%) and one female (n=22; 15.4%) psychiatric clinic and one civil security ward (n=29; 20.3%), all located nearby Lisbon. Basic descriptive statistics and Kappa weighted coefficients were calculated for the inter-rater and the test-retest reliability studies. The convergent validity was evaluated using the Global Assessment of Functioning and the Brief Psychiatric Rating Scale scores. The majority of the participants were male and single, with short school attendance, and accused of a crime involving violence against persons. The most frequent diagnosis was major depression (56.1%) and almost half presented positive suicide risk. The reliability study showed average Kappa weighted coefficients of 0.884 and 0.445 for inter-rater and test-retest agreement, respectively. The convergent validity study presented highly significant correlations between unmet needs scores, GAF and BPRS scores. The CANFOR Portuguese version revealed similar psychometric properties to the original English version. Moreover, the results of the reliability and validity studies indicate that the tool is appropriate for individual care needs assessment and as a guide for the mental health and social interventions in forensic psychiatric services.


Initial studies of the molecular organization of the cell-substrate adhesion site.
Using selective extraction reagents and non-penetrating probes, studies have been initiated on the molecular organization of substrate-attached material, adhesion sites which pinch off from the cell surface of normal Balb/c 3T3 or SV40-transformed Balb/c 3T3 (SVT2) cells and which remain bound to the serum-coated substrate during EGTA-mediated detachment of cells. Extraction of SVT2 adhesion sites with non-ionic detergents resulted in (a) only small amounts of leucine-radiolabeled protein and glucosamine-radiolabeled polysaccharide being solubilized; (b) selective solubilization of 80% of the adhesion site actin, and (c) solubilization of 95% of the phospholipid from these membranous pools. ATP in combination with potassium chloride extracted 60% of the actin. The 3T3 and SVT2 adhesion site proteins which are accessible to lactoperoxidase-catalyzed iodination were also determined. Many of the serum-derived proteins, bound to the substrate, were iodinated during iodination treatment of serum-coated or substrate-attached material-coated substrates, whereas the cellular proteins in the adhesion sites were not iodinated even though they were present in larger quantity as revealed by Coomassie blue staining. Iodination of cells, followed by their EGTA-mediated detachment and reattachment to fresh serum-coated substrates, indicated that the principal iodinated cell surface component deposited in new adhesion sites is the large external transformation-sensitive glycoprotein (even though large external transformation-sensitive glycoprotein is not the only principal iodinated cell surface component of these cells). These studies further establish the selective enrichment in this adhesive material of specific cell surface components and indicate that they are tenaciously bound at the interface between the serum coating and the undersurface of the adhesion site membranous pools.


Correlates of stages in the progression from everyday drinking to problem drinking.
Data is presented on the following related problems: (1) social characteristic associated with differences in drinking style; (2) variables correlated with intensified consumption; (3) variables, other than consumption level, correlated with harmful effects of alcohol. The concepts of status role, positional role and situation role were used to develop hypotheses. Drinking alcoholic beverages is considered as an element of situation roles in which drinking alcohol is considered meaningful and appropriate. The hypotheses are that status groups tend to differ in drinking style (problem 1) and because of these differences, differ also in the degree to which drinking is associated with harmful effects (problem 3). The three positional roles: living with a partner, care for children at home, and employment were combined to indicate the structure of everyday life. The hypotheses were that people with a less structured everyday life are inclined to intensify their consumption (problem 2); and are more vulnerable to harmful effects (problem 3). Most of these hypotheses were confirmed. Gender and the integration of alcohol use appear to be intervening variables concerning the effect of the structure of everyday life on intensified consumption and on harmful effects.