Herpesviruses reactivation following COVID-19 vaccination: a systematic review and meta-analysis.
The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these viruses (HSV, VZV, EBV, and CMV) among those who got COVID-19 vaccines. In this study, we aimed to review the current evidence to assess whether HHVs reactivation has any association with the prior administration of COVID-19 vaccines. A systematic search was conducted on 25 September 2022 in PubMed/MEDLINE, Web of Science, and EMBASE. We included all observational studies, case reports, and case series which reported the reactivation of human herpesviruses following administration of COVID-19 vaccines. Our systematic search showed 80 articles that meet the eligibility criteria. Among the evaluated COVID-19 vaccines, most of the vaccines were mRNA based. Evidence from observational studies showed the possible relation between COVID-19 vaccine administration and VZV and HSV reactivation. The results of our proportion meta-analysis showed that the rate of VZV reactivation among those who received the COVID-19 vaccine was 14 persons per 1000 vaccinations (95% CI 2.97-32.80). Moreover, our meta-analysis for HSV reactivation showed the rate of 16 persons per 1000 vaccinations (95% CI 1.06-46.4). Furthermore, the evidence from case reports/series showed 149 cases of HHV reactivation. There were several vaccines that caused reactivation including BNT162b2 mRNA or Pfizer-BioNTech (n = 76), Oxford-AstraZeneca (n = 22), mRNA-1273 or Moderna (n = 17), Sinovac (n = 4), BBIBP-CorV or Sinopharm (n = 3), Covaxin (n = 3), Covishield (n = 3), and Johnson and Johnson (n = 1). Reactivated HHVs included varicella-zoster virus (VZV) (n = 114), cytomegalovirus (CMV) (n = 15), herpes simplex virus (HSV) (n = 14), Epstein-Barr virus (EBV) (n = 6), and HHV-6 (n = 2). Most cases reported their disease after the first dose of the vaccine. Many patients reported having comorbidities, of which hypertension, diabetes mellitus, dyslipidemia, chicken pox, and atrial fibrillation were common. In conclusion, our study showed the possible association between COVID-19 vaccination and herpesvirus reactivation. The evidence for VZV and HSV was supported by observational studies. However, regarding other herpesviruses (EBV and CMV), further research especially from observational studies and clinical trials is required to elucidate the interaction between COVID-19 vaccination and their reactivation.


Surveillance mechanisms monitoring chromosome breaks during mitosis and meiosis.
DNA double-strand breaks (DSBs) are highly hazardous for genome integrity, because failure to repair them can lead to genome rearrangements or chromosome loss. They can arise at unpredictable locations as a consequence of DNA damage during both the mitotic and the meiotic cell cycle or in a programmed manner during meiosis. Cellular response to accidental or programmed DSBs involves highly conserved surveillance mechanisms, called DNA damage checkpoint and recombination checkpoint, which coordinate DSB repair with mitotic or meiotic cell cycle progression, respectively. Although these protective signal-transduction pathways share several upstream components, activation of the recombination checkpoint requires meiosis-specific proteins. These proteins are structural components of the meiotic chromosomes, indicating that the system monitoring programmed meiotic DSBs is an integral part of the chromosome structure formed during meiosis.


GPCR interactions involving metabotropic glutamate receptors and their relevance to the pathophysiology and treatment of CNS disorders.
Cellular responses to metabotropic glutamate (mGlu) receptor activation are shaped by mechanisms of receptor-receptor interaction. mGlu receptor subtypes form homodimers, intra- or inter-group heterodimers, and heteromeric complexes with other G protein-coupled receptors (GPCRs). In addition, mGlu receptors may functionally interact with other receptors through the βγ subunits released from G proteins in response to receptor activation or other mechanisms. Here, we discuss the interactions between (i) mGlu1 and GABAB receptors in cerebellar Purkinje cells; (ii) mGlu2 and 5-HT2Aserotonergic receptors in the prefrontal cortex; (iii) mGlu5 and A2A receptors or mGlu5 and D1 dopamine receptors in medium spiny projection neurons of the indirect and direct pathways of the basal ganglia motor circuit; (iv) mGlu5 and A2A receptors in relation to the pathophysiology of Alzheimer's disease; and (v) mGlu7 and A1 adenosine or α- or β1 adrenergic receptors. In addition, we describe in detail a novel form of non-heterodimeric interaction between mGlu3 and mGlu5 receptors, which appears to be critically involved in mechanisms of activity-dependent synaptic plasticity in the prefrontal cortex and hippocampus. Finally, we highlight the potential implication of these interactions in the pathophysiology and treatment of cerebellar disorders, schizophrenia, Alzheimer's disease, Parkinson's disease, l-DOPA-induced dyskinesias, stress-related disorders, and cognitive dysfunctions. This article is part of the Special Issue on "The receptor-receptor interaction as a new target for therapy".


Highly chemoselective Baylis-Hillman and aldol reactions of 2H-thiopyran-4(3H)-one using tertiary amine catalysts in aqueous media.
For the first time, the Baylis-Hillman (BH) reaction of 2H-thiopyran-4(3H)-one is investigated, and surprisingly, the reaction of 2H-thiopyran-4(3H)-one with aldehydes in the presence of different tertiary amines shows excellent chemo- and regioselectivity in water. At room temperature, DBU affords BH adducts, but with DABCO, aldol products were obtained. In the case of DABCO, Et(3)N, or DMAP, domino aldol-rearrangement reactions occurred at 45-50 °C.


Reversibility of delirium in Ill-hospitalized cancer patients: Does underlying etiology matter?
The objective of this study was to explore the underlying etiologies associated with the resolution and improvement of delirium in ill-hospitalized cancer patients. We conducted a secondary analysis of a multicenter, prospective, observational study to estimate the effectiveness of pharmacotherapy for delirium. Participants were cancer patients with delirium. We assessed the Delirium Rating Scale, Revised-98 (DRS-R98) severity scale score at baseline and three days after pharmacotherapy initiation. Delirium resolution was defined as a DRS-R98 severity scale score ≤9, and improvement was defined as ≥50% reduction at Day 3. We enrolled 566 patients (491 patients had performance status of 3 or 4). The resolution and improvement rates in all patients were 22.6% and 19.3%, respectively. Univariate analysis determined that nonrespiratory infection (OR 2.18, 95% CI 1.38-3.45) was significantly associated with greater resolution, while dehydration (0.40, 0.19-0.87), organic damage to the central nervous system (CNS) (0.32, 0.43-0.72), hypoxia (0.25, 0.12-0.52), and hyponatremia (0.34, 0.12-0.97) were significantly associated with no resolution. Potential causes associated with delirium improvement were nonrespiratory infection (1.93, 1.19-3.13), organic damage to the CNS (0.40, 0.18-1.90), and hypoxia (0.32, 0.16-0.65). After multivariate analysis, dehydration (0.34, 0.15-0.76), organic damage to the CNS (0.25, 0.10-0.60), and hypoxia (0.29, 0.14-0.61) were significantly associated with no resolution. Delirium caused by nonrespiratory infection may be reversible, while delirium associated with dehydration, organic damage to the CNS, hypoxia, or hyponatremia seems to be irreversible in ill-hospitalized cancer patients.


Reoperation for pelvic organ prolapse within 10 years of primary surgery for prolapse.
A presumed high failure rate of conventional procedures for prolapse has been part of the rationale for new surgical approaches. The aim of the present retrospective cohort study was to estimate the reoperation rate for prolapse within 10 years of primary surgery for prolapse. We identified all patients who underwent primary surgery for prolapse at four large regional centers in Austria in 1997 and 1998. Hospital databases were searched to determine whether patients had been reoperated for prolapse through 2008. A total of 456 patients underwent a primary operation for prolapse in 1997 and 1998. The most common primary operation was vaginal hysterectomy with colporrhaphy (89 %). We identified 13 reoperations for prolapse, for a 10-year reoperation rate of (at least) 2.9 %. The median interval between primary and secondary surgery was 5.5 years (range 1.5-10 years). The reoperation rate for prolapse after primary vaginal hysterectomy and colporrhaphy appears to be modest in this series of patients.


A nonlinear updated gain observer for MIMO systems: Design, analysis and application to marine surface vessels.
In this paper, the state estimation problem of a class of multi-input-multi-output nonlinear systems with measurement noise is studied. We develop an extended updated-gain high gain observer to make a tradeoff between reconstruction speed and measurement noise attenuation. The designed observer, whose gains are driven by nonlinear functions of the available output estimation errors, has the ability to reconstruct system states quickly and reduce the effect of measurement noise. We establish that, if there exists a state feedback law exponentially stabilizing the system with respect to an invariant set, the estimations and estimation errors are bounded. Besides, the trajectories of state- and output-feedback (based on the proposed observer) are sufficiently close, namely performance recovery. The observer performance is illustrated by various examples in marine control, including a case of transformation into the predefined structure.


Work disability rates in RA. Results from an inception cohort with 24 years follow-up.
To explore rates of and reasons for work disability in an early RA cohort with median 10 years follow-up. One thousand four hundred and sixty patients with early RA (<2 years symptom duration) and no prior DMARD therapy were recruited from nine rheumatology outpatient departments across the UK between 1986 and 1998. Standard clinical, laboratory and radiological assessments were recorded at 6-monthly and yearly intervals. Assessment of employment included details of type and hours of paid work. The main outcomes investigated were rates of and main reasons for work cessation, analysed by age of onset of RA (<45, 45-60 years) and year of recruitment to the study (before or after 1992). Maximum follow-up was 24 years, median 10 years. Of 647 patients in paid work at baseline, the majority were <60 years old (91%). The estimated probability of stopping work due to RA was highest in patients with older age of onset (45-60 years) who were recruited before 1992, but improved in those recruited from 1992 to 1998 (P < 0.01). There was no difference seen over the study recruitment years in younger age of onset patients. Work loss related to RA occurred much earlier than for other reasons, especially in the first 5 years of RA, but improved in the later recruitment period. Work disability is multifactorial, and the gradual changes in therapies used over time in this cohort may be one explanation for the secular differences seen.


Methodical investigation of the production of antibodies towards 3,4-dimethoxyphenylethylamine.
In this study the synthesis of various antigens from 3,4-dimethoxyphenylethylamine (3,4-DMPEA) is described. Antigen A was formed by coupling the acylated side chain of 3,4-DMPEA to the protein, while antigen B was synthesized by introducing an acylated amino group to the benzene ring and linking this reactive group to the protein. With antigen A an antiserum with a titer of 1 : 16000 could be raised, while with antigen B coupled to human albumin and bovine gamma-globulin the antiserum had a titer of 1 :1000 and 1 : 4000. Antibodies formed by immunization with antigen A exhibited a high specificity for substituents of the benzene ring, but were less specific for substituents of the side chain. Antibodies formed by treatment with the antigen B were specific for both kinds of substituents. So far, it has not been possible to harvest any specific antibodies towards the corresponding antigens of dopamine.


The effect of stimulating versus nonstimulating catheters for continuous interscalene plexus blocks in short-term pain management.
To investigate whether placement, and use of stimulating catheters for interscalene brachial plexus blocks improves short-term postoperative analgesia. Controlled, prospective, randomized, pilot study. University hospital. 60 patients undergoing shoulder surgery. INTERVENTIONS AND MAIN MEASUREMENTS: The brachial plexus was identified using a stimulating needle. In conventional catheter group 1 (CC 1), local anesthetic (LA) was injected through the needle and catheters were advanced blindly thereafter. In catheter group 2 (CC 2), catheters were blindly inserted and LA was injected through the catheter. In the stimulating catheter group (SC), LA was injected only after catheter tip location was confirmed by nerve stimulation. Time required to perform the block, pain intensity at rest, and dynamic pain (defined movement: lifting of arm; numeric rating scale, 0-10), patient satisfaction (verbal rating scale, Likert scale), and plasma concentrations of ropivacaine were measured. Patients in the SC group had significantly decreased pain scores. The median block performance time was 6 minutes in CC 1 (CI 25%-75%: 4-8 min), 11 minutes in CC 2 (CI 25%-75%: 7-13 min), and 12 minutes in SC (CI 25%-75%: 10-24 min). Patient satisfaction and plasma concentrations of ropivacaine did not differ among the groups. Stimulating catheters for interscalene plexus blocks improve postoperative analgesia at rest in patients undergoing shoulder surgery.


Temperature regulation and microhabitat choice by free-ranging Galapagos fur seal pups (Arctocephalus galapagoensis).
Behavioural activity, and core and surface temperatures of 4 unrestrained Galapagos fur seals were recorded in the natural habitat during their first weeks of life. Climatic variables were registered simultaneously. Pup behaviours were divided into bouts of resting (55% of total time), sucking (23%) and other activities (22%). Pups maintained a constant body temperature from their first day. Core temperature (T e ) was 37.7° C±0.3° C (x ± SD) over 39 pup-days and 8 pup-nights. Skin temperature was correlated with T c , but flipper temperature was not. No daily T c rhythm was detected. Microclimate data were used to calculate operative temperature T e . Environmental temperatures can be very high, with T e above T c 6-9 h a day for animals exposed to the sun, but below it in the shade. T c is about 22° C at night. Pups avoid overheating mainly by withdrawing into the shade and reducing activity to a minimum during the hot hours of the day. Sun-exposed pups could be active at any time during the day if they had access to water, which was usually around high tide.


Stress in immigrant families with handicapped children: a child advocacy approach.
Poor immigrant families must cope with stress stemming from loss of home and adaptation to the host country. Those with handicapped children are also burdened with a parallel set of stressors in adapting to the handicap in an alien environment that may include a complex service system. Implications for practice are discussed with particular emphasis on advocacy to enhance delivery of services.


Prevalence of contact allergy in the general population in different European regions.
Population-based studies about contact allergy are scarce. To obtain reliable estimates of the prevalence of contact allergy in the general population in Europe. A cross-sectional study of a random sample from the general population, aged 18-74 years, in five different European countries (Sweden, the Netherlands, Germany, Italy and Portugal). In total, 12 377 subjects were interviewed and a random sample (n = 3119) patch tested to TRUE Test panels 1-3 and Fragrance Mix (FM) II, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and sesquiterpene lactone mix. A positive patch test reaction is considered as contact allergy. In total, 27·0% [95% confidence interval (CI) 25·5-28·5] had at least one positive reaction to an allergen of the European baseline series, with a significantly higher prevalence in women than in men. The highest age-standardized prevalences (≥ 1%) were found for nickel (14·5%, 95% CI 13·2-15·8), thiomersal (5·0%, 95% CI 4·2-5·8), cobalt (2·2%, 95% CI 1·7-2·7), FM II (1·9%, 95% CI 1·5-2·5), FM I (1·8%, 95% CI 1·4-2·3), HICC (1·4%, 95% CI 1·0-1·9), p-tert-butylphenol formaldehyde resin (1·3%, 95% CI 0·9-1·7) and para-phenylenediamine (1·0%, 95% CI 0·6-1·3). Only nickel and thiomersal showed a statistically significantly different prevalence for contact allergy among the different European populations. Subjects reporting contact dermatitis in their lifetime (age-standardized prevalence 15·1%, 95% CI 13·8-16·3) had an increased risk for contact allergy (odds ratio 1·9, 95% CI 1·5-2·5). The risk of having a contact allergy was not increased in those with atopic dermatitis (prevalence 7·6%, 95% CI 6·7-8·6; odds ratio 1·0, 95% CI 0·7-1·4). Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced.


Pediatric Hepatic Venous Outflow Tract Obstruction: Experience from a Transplant Center.
We performed a review of case records of children diagnosed with hepatic venous outflow tract obstruction at our center in last 10 years. Out of 11 cases identified, 6 had variable blocks in the hepatic venous system and 4 had combined hepatic venous and inferior vena cava (IVC) block. One child with paroxysmal nocturnal hemoglobinuria (PNH) had isolated IVC involvement. Angioplasty was attempted in 3 patients; among them 2 had successful outcome. Seven children with advanced liver disease underwent transplantation, which was successful in six. With availability of modalities like interventional radiology and transplantation, the overall prognosis of hepatic venous outflow tract obstruction seems to be good when managed in a well-equipped center.


Cortisol/DHEA ratio in morbidly obese patients before and after bariatric surgery: Relation to metabolic parameters and cardiovascular performance.
Bariatric surgery (BS) is the most effective therapy for morbid obesity. Cortisol and DHEA are steroid hormones with opposing effects, thus using Cortisol/DHEA ratio (C/D) rather than the use of either hormone alone has been found to predict health outcomes more reliably. It was interesting to study C/D as an indicator of favorable metabolic and cardiovascular outcomes after BS. To assess C/D in morbidly obese patients before and after BS in relation to metabolic parameters and cardiovascular performance. Forty morbidly obese patients were followed prospectively for 1 year after BS. Fasting blood glucose (FBG), fasting insulin (FI), C/D, lipid profile, high-sensitive CRP (hs-CRP), and echocardiography were done before BS and at 3 months and 1 year post BS. A total of 40 morbidly obese patients undergone sleeve gastrectomy. Blood pressure, FBG, FI, hs-CRP, C/D were significantly decreased after BS (p < 0.001). At 1 year post BS; significant reduction in left ventricular posterior wall thickness (LVPW) (p < 0.001), left ventricular mass (LVM) (p = 0.003), relative wall thickness (RWT) (p < 0.001) with a significant improvement in early diastolic velocity (E) (p < 0.001), early diastolic velocity/late diastolic velocity (E/A) (p = 0.01). After BS; C/D significantly positively correlated with FBG (p = 0.019), hs-CRP (p = 0.008), interventricular septum thickness (IVS) (p = 0.028), LVPW (p = 0.028), relative wall thickness (RWT) (p = 0.022), early diastolic velocity /early diastolic velocity (E') measured by pulsed tissue Doppler imaging (E/E') (p = 0.001), and significantly negatively correlated with E' (p = 0.032). C/D was the single significant independent variable affecting E' and E/E' post BS. C/D can be used as a surrogate marker of the improved FBG and the resolution of inflammation post BS. C/D is an independent predictor of diastolic function improvement post BS.


Short-term results of community-based interventions for improving physical activity: Isfahan Healthy Heart Programme.
To assess the effect of a comprehensive community-based programme for increasing physical activity (PA) after 2 years of interventions. A 6-year, action-oriented, comprehensive, and integrated community-based study, entitled the Isfahan Healthy Heart Programme, was conducted in Iran from the year 2000. The interventions targeted the whole population of nearly 2,180,000 living in two cities, and were compared with another city considered as a reference. Educational, environmental and legislative interventions were conducted at the community level. Annual evaluations were performed among 6,000 representative individuals. This paper presents the changes in PA habits after 2 years of interventions for increasing PA. The PA habits were assessed by using the Baecke questionnaire, and an energy expenditure of 150 kcal for daily leisure time physical activity was adopted as a cut-off for defining active and inactive lifestyle. In the intervention and reference areas, respectively 85 and 83% of the population were physically inactive. From 2000 to 2002, the daily PA among both genders decreased in both intervention and reference communities. Meanwhile, the leisure-time PA increased significantly in the intervention area, but decreased in the reference area. The transportation PA did not significantly change in the intervention area, but showed a remarkable decline in the reference area. We suggest that the synergism resulting from community collaborations has been effective in improving some aspects of PA in our community. The ongoing changes in environmental factors and policies can help in increasing the worksite and transportation PA in later stages of this community-based programme.


Characterization of human red blood cell tyrosine kinase.
A new tyrosine kinase in human red blood cells has been characterized and partially purified. The major substrate was a protein of molecular weight 93 K which could be phosphorylated both in whole red blood cells incubated with inorganic [32P] orthophosphate and in ghost preparations incubated with [gamma 32P] ATP. This tyrosine kinase displayed an alkaline isoelectric pH (around 8.5), a molecular weight of 32-33 K and does not seem to be autophosphorylable. Some kinetics of the enzyme are reported. This red blood cell tyrosine kinase is unrelated to EGF and insulin or insulin-like receptor subunits. This enzyme may represent a novel class of tyrosine kinases.


The cancer outpatient satisfaction with care questionnaire for chemotherapy, OUT-PATSAT35 CT: a validation study for Spanish patients.
The OUT-PATSAT35 CT questionnaire evaluates satisfaction with care expressed by cancer outpatients receiving chemotherapy. This study assesses the psychometric properties of the OUT-PATSAT35 CT when applied to a sample of Spanish patients. One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30, the OUT-PATSAT35 CT, the Oberst patients' perception of care quality and satisfaction scales (OS) and the item on intention to recommend the hospital (IR). Psychometric evaluation of the structure, reliability and validity of the questionnaire was conducted. Multitrait scaling analysis showed that 32 of 34 item-scale correlation coefficients met the standards for convergent validity and that many of them met the standards for discriminant validity. Cronbach's coefficients were good (0.78-0.97) for all scales except doctor availability and environment. Correlations between the QLQ-C30 and the OUT-PATSAT35 CT were low (≤0.40). Correlations between IR and the OUT-PATSAT35 CT were moderate, and correlations between this questionnaire and the OS were fairly low. Areas whose contents were more related had higher correlation coefficients (>0.50) and vice versa (<0.1). Male patients, elderly patients, those with higher education levels, those with higher scores in four OS and patients who had not received surgery showed higher satisfaction with care in several OUT-PATSAT35 CT areas. The OUT-PATSAT35 CT is a reliable and valid instrument when applied to a sample of Spanish cancer patients. These results are in line with those of the validation study conducted by the authors of the questionnaire and with the validation study for Spain of the OUT-PATSAT35 RT.


A QCM immunosensor employing signal amplification strategies by enlarging the size of nanoparticles using gold or silver staining.
We present quartz crystal microbalance (QCM) immunosensors for the detection of alpha-fetoprotein (AFP) in a human serum immunoassay with high sensitivity. In this study, we employed three types of signal amplification strategies using size enlargement and/or increase in mass of gold and titanium dioxide nanoparticles. Since the basic principle of the QCM sensor is to measure the change in resonance frequency according to the mass change caused by the molecular interactions on the sensor surface, we were able to quantitatively analyze AFP by sandwich immunoassay using gold or titanium dioxide nanoparticles conjugated with anti-AFP detection antibodies and the subsequent three signal amplification techniques in a similar manner. The signal amplification technologies provide the size expansion of gold nanoparticles by gold or silver staining reaction and mass enhancement by photocatalytic silver staining of titanium dioxide nanoparticles. The limit of detections (LODs) of the AFP immunoassay in human serum by the gold and silver staining-mediated signal amplifications for gold nanoparticles were 56 and 87 pg mL-1, respectively, but by the photocatalytic silver staining signal amplification for titanium dioxide nanoparticles was 118 pg mL-1. This means that the signal amplification method through size enhancement by gold staining of gold nanoparticles further improved the detection ability of the QCM immunosensor.


Anticardiolipin antibodies in patients with multiple sclerosis do not represent a subgroup of patients according to clinical, familial, and biological characteristics.
In multiple sclerosis (MS), case control studies have shown that anticardiolipin antibodies (aCL Ab) are more frequent than in the general population and that aCL Ab positivity may be associated with specific clinical characteristics. To determine whether patients with MS who are positive for aCL Ab have specific characteristics. 285 consecutive patients with MS were tested for aCL Ab positivity. Patients also underwent complete autoimmune screening and were systematically evaluated for clinical characteristics and individual or family history of autoimmune disease. aCL Ab positivity was found in 42 patients (15%). The main isotype was aCL IgM (32 patients, 11%). Demographics and clinical characteristics including sex, age at onset, course of the disease, expanded disability status scale score, and progression index were not different between aCL Ab positive and aCL Ab negative patients. Clinical systems involved at onset or during the course of the disease were not different from what is usually observed in MS. aCL Ab positivity was not associated with an increased frequency of autoimmune disease and was not predictive of a family history of autoimmune disease. Patients positive for aCL IgM were more frequently positive for the presence of non-organ specific antibodies (53% v 39%, respectively, p = 0.02). These results do not support the hypothesis that patients with MS with aCL Ab constitute a subgroup of MS according to demographic clinical and familial characteristics. The greater frequency of other antibodies in aCL Ab positive patients suggests that they only reflect a more general autoimmune activation in MS.


Evaluation of word embedding models to extract and predict surgical data in breast cancer.
Decisions in healthcare usually rely on the goodness and completeness of data that could be coupled with heuristics to improve the decision process itself. However, this is often an incomplete process. Structured interviews denominated Delphi surveys investigate experts' opinions and solve by consensus complex matters like those underlying surgical decision-making. Natural Language Processing (NLP) is a field of study that combines computer science, artificial intelligence, and linguistics. NLP can then be used as a valuable help in building a correct context in surgical data, contributing to the amelioration of surgical decision-making. We applied NLP coupled with machine learning approaches to predict the context (words) owning high accuracy from the words nearest to Delphi surveys, used as input. The proposed methodology has increased the usefulness of Delphi surveys favoring the extraction of keywords that can represent a specific clinical context. It permits the characterization of the clinical context suggesting words for the evaluation process of the data.


Multiparameter evaluation of acrylamide HEMA alternative monomers in 2-step adhesives.
As frequently added to adhesives, the mono-functional monomer 2-hydroxyethyl methacrylate (HEMA) acts as co-solvent and improves surface wetting. Nevertheless, HEMA promotes watersorption and hydrolysis at adhesive interfaces, affecting bond durability to dentin. This study investigated if two acrylamide co-monomer alternatives could replace HEMA in experimental adhesive-resin formulations as part of 3/2-step universal adhesives applied, respectively, in etch-and-rinse (E&R) and self-etch (SE) bonding modes. Upon priming dentin with the 10-MDP-based Clearfil SE Bond 2' primer ('C-SE2p'; Kuraray Noritake), three experimental adhesive resins, consisting of 50 wt.% Bis-GMA, 15 wt.% TEGDMA, and either 35 wt.% diethyl acrylamide ('DEAA'), hydroxyethyl acrylamide ('HEAA') or HEMA ('HEMA+'), were applied. The control HEMA-free adhesive resin contained 60 wt.% Bis-GMA and 40 wt.% TEGDMA ('HEMA-'). All adhesives were evaluated for 'immediate' and 'aged' micro-tensile bond strength (μTBS) to dentin upon, respectively, 1-week (1w) and 6-month (6m) water storage, TEM adhesive-dentin interfacial interaction, 24-h and 6m three-point bending, contact-angle wetting, viscosity and watersorption. Linear mixed-effects model statistics revealed significantly better bonding performance of the adhesives applied in E&R than SE mode, except for DEAA_1w, with the highest μTBSs recorded for DEAA and HEMA- applied in SE mode. In E&R mode, aging did not significantly reduce DEAA's μTBS. Best wetting on primed dentin was recorded for HEMA+, significantly better than DEAA, further HEAA and HEMA-, these directly related to their viscosity. HEAA absorbed significantly more water than all other adhesive-resin formulations. HEMA->DEAA>HEAA>HEMA+ was the significant order for 6m bending strength. The acrylamide co-monomer DEAA could replace HEMA, while HEAA not.


Homologous recombination within subtelomeric repeat sequences generates chromosome size polymorphisms in P. falciparum.
We present restriction maps for chromosomes 1 and 2 of six cloned lines of P. falciparum. These delineate the locations of eight genetic markers, including genes for five antigens. In parasites from diverse areas, chromosome structure is conserved in central regions but is polymorphic both in length and sequence near the telomeres. The telomeres and adjacent sequences comprise a conserved structure at the ends of most P. falciparum chromosomes. However, the subtelomeric zones are polymorphic and coincide with the locations of a repetitive element (rep20). Deletions of rep20 generate clones of P. falciparum that lack rep20 on one or both ends of chromosomes 1 or 2, and larger deletions remove telomere-proximal genes as well. The chromosome length polymorphisms can therefore be largely explained by recombination within these blocks of repeats, a mechanism that is also important in the generation of diversity in genes for repetitive antigens of P. falciparum.


GABA concentrations in forebrain areas of suicide victims.
Concentrations of GABA and seven other amino acids, including the neurotransmitters or neuromodulators taurine, glycine, aspartate, and glutamate, were determined in postmortem brain samples from suicide victims and normal controls. The five brain areas (caudate nucleus, nucleus accumbens, frontal cortex, amygdala, and hypothalamus) contained very similar concentrations of the amino acids in both groups. The only significant difference between the groups was a low glutamine concentration in the hypothalamus of suicide victims. Even when the data were adjusted for differences in tryptophan concentration, a putative biochemical index for agonal and postmortem changes of brain tissue, no new differences emerged in the concentrations of neuroactive amino acids between suicide victims and control subjects.


The conscientiousness-health link in depression: Results from a path analysis.
This was the first study aiming to develop a theory-based model to analyze the relation between conscientiousness and impaired physical health as well as between conscientiousness and subjective health-related well-being within a large clinical sample with depressive symptomatology. In addition, a mediating effect of health risk behaviors regarding the association between conscientiousness and objectively impaired physical health as well as subjective health-related well-being were exploratory examined. Individuals with depressive symptoms (n = 943) with a mean age of 52 years (ranging between 20 and 78 years) undergoing intensive psychiatric rehabilitation treatment were investigated with the Big Five Inventory-10 as well as several self-report health questionnaires (Three-Factor Eating Questionnaire, Food-Craving Inventory and lifestyle questions assessing physical inactivity and alcohol consumption). Health-related well-being was measured using the World Health Organisation Quality of Life Assessment and the construct of impaired physical health comprised anthropometric measurements (Body Mass Index, Waist-to-Height-Ratio), blood lipids, and impaired physical performance capacity on the bicycle-ergometric test. Structural path analyses revealed that unhealthy eating habits and physical inactivity partially mediated the negative relation between conscientiousness and impaired physical health as well as the positive relation between conscientiousness and health-related well-being. Possible limitations include cross-sectional study design, missing data, assessment of conscientiousness on a global level and self-report assessment of health risk behaviors. The findings highlight the importance concerning the extended inclusion of personality aspects in the treatment of depression in order to improve health.


MUC16 facilitates cervical cancer progression via JAK2/STAT3 phosphorylation-mediated cyclooxygenase-2 expression.
MUC16 (mucin 16, also known as CA-125, cancer antigen 125, carcinoma antigen 125, or carbohydrate antigen 125) has been predicted as tumor biomarker for therapy. We determined to investigate effects and regulatory mechanism of MUC16 on cervical tumorigenesis. Expression levels of MUC16 in cervical cancer cell lines was analyzed via qRT-PCR (quantitative real-time polymerase chain reaction). Knockdown of MUC16 was conducted via shRNA (Short hairpin RNA) transfection. MTT and colony formation assays were used to investigate effect of MUC16 on cell proliferation. Wound healing assay was utilized to detect migration and transwell assay to detect invasion. The underlying mechanism was demonstrated via western blot analysis. MUC16 was elevated in cervical cancer cell lines. MUC16 knockdown inhibited cell proliferation, invasion and migration. Gain- and loss-of functional assays revealed that over-expression of MUC16 activated Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) via phosphorylation, thus facilitating cyclooxygenase-2 (COX-2) expression, while knockdown of MUC16 demonstrated the reverse effect on JAK2/STAT3 activation and COX-2 expression. Moreover, inhibition of JAK2/STAT3 attenuated the regulation of MUC16 on COX-2. MUC16 enhanced proliferation and invasion of cervical cancer cells via JAK2/STAT3 phosphorylation-mediated cyclooxygenase-2 expression, suggesting the potential therapeutic target ability of MUC16 to treat cervical cancer.


Nucleotide excision repair in Human cell lines lacking both XPC and CSB proteins.
Nucleotide excision repair removes UV-induced DNA damage through two distinct sub-pathways, global repair and transcription-coupled repair (TCR). Numerous studies have shown that in human and other mammalian cell lines that the XPC protein is required for repair of DNA damage from nontranscribed DNA via global repair and the CSB protein is required for repair of lesions from transcribed DNA via TCR. Therefore, it is generally assumed that abrogating both sub-pathways with an XPC-/-/CSB-/- double mutant would eliminate all nucleotide excision repair. Here we describe the construction of three different XPC-/-/CSB-/- human cell lines that, contrary to expectations, perform TCR. The XPC and CSB genes were mutated in cell lines derived from Xeroderma Pigmentosum patients as well as from normal human fibroblasts and repair was analyzed at the whole genome level using the very sensitive XR-seq method. As predicted, XPC-/- cells exhibited only TCR and CSB-/- cells exhibited only global repair. However, the XPC-/-/CSB-/- double mutant cell lines, although having greatly reduced repair, exhibited TCR. Mutating the CSA gene to generate a triple mutant XPC-/-/CSB-/-/CSA-/- cell line eliminated all residual TCR activity. Together, these findings provide new insights into the mechanistic features of mammalian nucleotide excision repair.


The association between monocytic myeloid-derived suppressor cells levels and the anti-tumor efficacy of anti-PD-1 therapy in NSCLC patients.
Monocytic myeloid-derived suppressor cells (M-MDSCs), granulocytic MDSC (G-MDSCs) and regulatory T cells (Tregs) inhibit adaptive anti-tumor immunity and undermine the efficacy of anti-PD-1 therapy. However, the impact of anti-PD-1 treatment on these immunosuppressive cells has not been clearly defined in non-small cell lung cancer (NSCLC). In this retrospective study, 27 advanced NSCLC patients were divided into partial response (PR), stable disease (SD), and progressive disease (PD) groups. The impact of anti-PD-1 therapy on circulating Tregs, G-MDSCs, and M-MDSCs was assessed by flow cytometer. Here, we found that anti-PD-1 treatment boosted circulating Tregs levels, which presented the most remarkable augment during the first two therapeutic cycles, in NSCLC patients. In contrast, anti-PD-1 therapy did not overall change G-MDSCs and M-MDSCs levels. However, the PR group had a higher baseline level of M-MDSCs, which exhibited a significant decrease after the first cycle of anti-PD-1 treatment. Besides, M-MDSCs levels in the PR group were maintained at a low level in the following therapeutic cycles. Consistently, Tregs levels robustly increased in the syngeneic tumor model after anti-mouse PD-1 Ab treatment. Accordingly, M-MDSCs neutralization by anti-mouse ly6c Ab enhanced the anti-tumor efficacy of anti-PD-1 therapy in mice. Finally, the decreased M-MDSCs levels were associated with the enhanced effector CD8+ T cells expansion in the PR group and mice. In conclusion, anti-PD-1 therapy upregulates Tregs levels in NSCLC patients, and the M-MDSC levels are associated with the anti-tumor efficacy of anti-PD-1 treatment. Neutralization of M-MDSCs may be a promising option to augment anti-PD-1 therapy efficacy in NSCLC.


Expression of Concern to: Identifying and targeting cancer stem cells in leiomyosarcoma: prognostic impact and role to overcome secondary resistance to PI3K/mTOR inhibition.
The Editor-in-Chief would like to alert readers that the ownership of some of the data presented in this article [1].


Comparison of initial and final diagnoses in children with acute febrile illness: A retrospective, descriptive study: Initial and final diagnoses in children with acute fever.
This study aimed to elucidate the etiologies and diagnostic errors of early-phase pediatric fever without an obvious cause. This single-center, retrospective, descriptive study included 1334 febrile children hospitalized at Beppu Medical Center in Japan between 2014 and 2018. Eligibility criteria were age ≤12 years, axillary temperature ≥38.0°C, and fever duration ≤7 days at admission. Initial diagnoses on the day of admission and final diagnoses at defervescence were divided into initial fever with identified source (FIS) and initial fever without source (FWS) and final FIS and final FWS, respectively. The etiology of initial FWS and diagnostic discordance between initial FIS and final FIS were investigated. Of the 1334 participants, 94 (7.0%) were diagnosed with initial FWS. Among patients with initial FWS, final diagnoses were confirmed in 40 (43%), including Kawasaki disease in 17, urinary tract infection in 5, bacteremia in 4, exanthem subitum in 3, and the others in 11. Among the 1275 patients diagnosed with final FIS, diagnostic discordances between initial and final diagnoses were observed in 131 patients (10%). The multiple logistic regression analysis identified increased serum C-reactive protein value at admission (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.06-1.13), exanthem subitum (OR: 409; 95% CI: 119-1399), and Kawasaki disease (OR: 14.3; 95% CI: 8.7-23.3) as independent risk factors for diagnostic discordance. Exanthem subitum and Kawasaki disease may be undiagnosed or misdiagnosed in febrile children with fever duration ≤7 days.


Gamma-glutamyltransferase from azo dye induced hepatoma and fetal rat liver. Similarities in their kinetic and immunological properties.
Some properties of gamma-glutamyltransferase ((gamma-glutamyl)-peptide: amino-acid gamma-glutamyltransferase EC 184.108.40.206) from azo dye induced hepatoma and fetal rat liver were studied using kinetic and immunological criteria. There was no significant difference between the hepatoma enzyme and fetal rat liver enzyme in some of their catalytic properties. Antisera against the purified hepatoma enzyme also reacted to the fetal rat liver enzyme in the inhibition test and the precipitin reaction. A structural similarity between the hepatoma enzyme and fetal rat liver enzyme was observed and the acquirement of fetal characteristics in hepatoma was discussed.


DCcov: Repositioning of drugs and drug combinations for SARS-CoV-2 infected lung through constraint-based modeling.
The 2019 coronavirus disease (COVID-19) became a worldwide pandemic with currently no approved effective antiviral drug. Flux balance analysis (FBA) is an efficient method to analyze metabolic networks. Here, FBA was applied on human lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to reposition metabolic drugs and drug combinations against the virus replication within the host tissue. Making use of expression datasets of infected lung tissue, genome-scale COVID-19-specific metabolic models were reconstructed. Then, host-specific essential genes and gene pairs were determined through in silico knockouts that permit reducing the viral biomass production without affecting the host biomass. Key pathways that are associated with COVID-19 severity in lung tissue are related to oxidative stress, ferroptosis, and pyrimidine metabolism. By in silico screening of Food and Drug Administration (FDA)-approved drugs on the putative disease-specific essential genes and gene pairs, 85 drugs and 52 drug combinations were predicted as promising candidates for COVID-19 (https://github.com/sysbiolux/DCcov).


Syringomyelia: myelography, computed tomography, and magnetic resonance imaging.
Seventeen patients with cervical spinal cord cavities were studied with myelography, postmyelographic computed tomography scanning, and magnetic resonance imaging. The three diagnostic techniques were compared for accuracy, patient comfort, and ease of procedure. Magnetic resonance imaging was the best diagnostic and most comfortable procedure. There is no need for myelography or postmyelographic computed tomography scanning for the evaluation of cervical syringomyelia.


Age-related changes in biochemical bone profile in thalassemic children.
Osteopathy is an important cause of morbidity in β-thalassemia major (TM). Although many of the etiopathological factors implicated in thalassemic osteoporosis commence in early disease phases during childhood, limited information exists on bone turnover in children with TM. This study was conducted with the objective to compare bone turnover markers (BTMs) in thalassemic children at different ages. In a cross sectional case control study, 47 children (age range, 1.5-18 years) with TM were recruited. BTMs were compared to eighteen age- and sex-matched healthy controls and to 16 adults (age range, 19.67-31.08 years) with TM. Thalassemic children displayed unbalanced bone turnover with an increased bone resorption (shown by high levels of tartrate-resistant acid phosphatase 5b (TRACP5), receptor activator of nuclear factor-kappa B ligand (sRANKL) and sRANKL/osteoprotegerin (OPG) ratio) and a decreased bone neoformation (shown by low levels of osteocalcin (OC)) when compared to healthy children. TRACP5b was the only BTMs studied that showed a significant correlation with age in thalassemic children. For the whole thalassemic children group, regression analyses showed an influence of sex hormones replacement therapy on TRACP5b; pretransfusion hemoglobin and splenectomy on sRANKL; pretransfusion hemoglobin on sRANKL/OPG; and pretransfusion hemoglobin and serum ferritin on OC. The present study confirms that TM has profound effects on bone metabolism starting from early childhood. The early onset of bone turnover disturbances in TM indicates the need to investigate possible option to intervene early.


Preconditioning of endoplasmic reticulum stress protects against acrylonitrile-induced cytotoxicity in primary rat astrocytes: The role of autophagy.
This study explored the protective effects of endoplasmic reticulum (ER) stress preconditioning induced by 2-deoxy-d-glucose (2-DG) or oxidized dithiothreitol (DTTox) on acrylonitrile (AN)-induced cytotocity in primary rat astrocytes. Cells were pretreated with 2-DG or DTTox for different times at various concentration. Next, astrocytes were treated with 2.5mM AN for an additional 12h. Cell viability and cytotoxicity were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) leakage, respectively. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were determined. Expression of glucose-regulated protein 78 (GRP78), phosphorylated-eukaryotic translation initiation factor 2α (p-eIF2α), microtubule-associated protein light chain 3 (LC3), P62, and Beclin1 were used to assess autophagy. In addition, 3-methyadenine (3-MA), an autophagy-specific inhibitor, was used to assess the role of autophagy in ER stress preconditioning-induced protection against AN cytotoxicity. The results showed that AN alone significantly decreased astrocytic viability and enhanced cytotoxicity. Compared to the AN-alone group, preconditioning with 2-DG or DTTox significantly increased cell viability and reduced cytotoxicity to indistinguishable levels. Decreased ROS generation and increased ΔΨm were also inherent to ER stress preconditioning with these compounds. Furthermore, autophagy was activated by both 2-DG and DTTox. Blockage of autophagy attenuated the protection afforded by 2-DG or DTTox preconditioning in AN-treated astrocytes. These results establish that ER stress preconditioning affords cellular protection against AN, and that activation of autophagy mediates the cytoprotection. Modulation of ER stress and resultant activation of autophagy may be a novel target for to ameliorate AN toxicity.


Risk factors for the recurrence of primary spontaneous pneumothorax after video-assisted thoracoscopic surgery in patients younger than 40 years.
Video-assisted thoracoscopic surgery (VATS) is a standard primary spontaneous pneumothorax (PSP) procedure. However, its high recurrence rate compared to open thoracotomy is a problem. Therefore, various methods to prevent recurrence have been developed. The present study investigated the risk factors for postoperative recurrence of PSP after VATS. From January 2008 to November 2022, 207 patients younger than 40 years of age without underlying pulmonary disease underwent thoracoscopic bullectomy for PSP. Among them, 96 underwent staple line reinforcement with a polyglycolic acid (PGA) sheet and autologous blood spraying. Patient characteristics and surgical outcomes were analyzed to determine the prognostic factors for postoperative recurrence. Twenty-seven patients (13.0%) experienced recurrences. A multivariate analysis using Cox regression analysis revealed that age younger than 20 years [P=0.039; hazard ratio (HR) =2.337; 95% confidence interval (CI): 3.283-17.287], history of contralateral pneumothorax (P<0.001; HR =7.533; 95% CI, 1.486-12.336), and no staple line reinforcement (P=0.007; HR =4.282; 95% CI, 1.043-5.236) were risk factors for recurrence after pneumothorax surgery. Age younger than 20 years and history of contralateral pneumothorax were risk factors for postoperative recurrence of pneumothorax. Staple line reinforcement with a PGA sheet and spraying of autologous blood reduced the postoperative recurrence rate of PSP.


Evidence for in vitro translesion DNA synthesis past a site-specific aminofluorene adduct.
The ability of Escherichia coli DNA polymerase I and T7 DNA polymerase to bypass bulky C-8 guanyl-2-aminofluorene adducts in DNA was studied by in vitro DNA synthesis reactions on a site-specific aminofluorene-modified M13mp9 template. This site-specifically modified DNA was prepared by ligating an oligonucleotide containing a single aminofluorene adduct into a gapped heteroduplex of M13mp9 DNA (Johnson, D. L., Reid, T. M., Lee, M.-S., King, C. M., and Romano, L. J. (1986) Biochemistry 25, 449-456). The resulting covalently closed duplex DNA molecule was then cleaved with a restriction endonuclease, denatured, and annealed to a primer on the 3' side of the adduct to form a template specifically designed to study bypass. In this system, any synthesis that was not blocked by the bulky aminofluorene adduct would proceed to the 5' terminus of the single-stranded template, while synthesis interrupted by the adduct would terminate at or near the adduct location. We have measured DNA synthesis on this template and find that the amount of radiolabeled nucleotide incorporated by either E. coli DNA polymerase I (large fragment) or T7 DNA polymerase was much greater than would be predicted if the aminofluorene adduct were an absolute block to DNA synthesis. Furthermore, the products of similar reactions electrophoresed on polyacrylamide gels showed conclusively that the majority of the DNA synthesized by either the T7 DNA polymerase or E. coli DNA polymerase I bypassed the aminofluorene lesion. Substitution of Mn2+ for Mg2+ as the divalent cation resulted in even higher levels of translesion synthesis.


[Development of impact acceleration measurement facility in return-cabin of spacecraft].
To provide the basis for medical evaluation of spacecraft, and to measure the impact acceleration of return-cabin of spacecraft. A facility to measure the impact acceleration of "SZ-3" and "SZ-4" during landing was developed and the acquired test data were analyzed. The data of impact acceleration of return-cabins of "SZ-3" and "SZ-4" were accurately recorded during landing. Most reliable and scientific data were gotten. This facility could validate and evaluate the specifications of relevant systems of spacecraft, and provided the scientific basis for the decision if "SZ-5", the manned spacecraft, could be launched.


Use of specific PCR primers for the study of sulfate-reducing bacteria diversity in microbial mats of Ebro Delta, Spain.
Microbial mats are prokaryotic communities that provide model systems to analyze microbial diversity and ecophysiological interactions. Sulfate-reducing bacteria (SRB) play a key role in sulfur and nutrient recycling in these ecosystems. In this work, specific primers for 16S rRNA encoding gene, previously described, were used to study the diversity of SRB in microbial mats of the Ebro Delta. We confirm that this method is reliable to identify the diversity of SRB in these ecosystems. However, some mismatches in obtained sequences had been observed in our system and must be taken under consideration. Various genera of SRB in Ebro Delta microbial mats were identified, such as Desulfonema, Desulfatitalea, Desulfosalsimonas, Desulfoccocus, and Desulfovibrio. The diversity observed in our samples is very similar to previously reported in other microbial mats communities.


Assessment of patterns of fluctuating asymmetry and sexual dimorphism in carabid body shape.
The measurement tool most used to estimate developmental stability (DS) is fluctuating asymmetry (FA), which is a measure of the small random deviations that occur between the left and right sides of bilaterally symmetrical traits. In the Biobío Region of Chile, forest plantations are a widely extended phenomenon, which affect 27% of the surface area of the region and which are dominated by the monoculture of Pinus radiata. This study evaluated the presence of FA in the body shape of two populations of Ceroglossus chilensis (Eschscholtz) in two 13-year-old forest plantations (commercial thinning) using insects collected with interception traps. Since the biotic and abiotic components of forest plantations are subject to continual anthropic modifications that affect almost all ecological processes, including population dynamics, community composition, and material and energy flows, these characteristics are reflected in the DS of individuals. The results showed that there was greater precision using geometric morphometrics to detect the presence of asymmetry in plantations due to shape analysis, as proposed by studies in antennal morphology using traditional measures. It should be noted that the populations were exposed to different environments; the population in the Coast Range is more humid, while the Andes Foothills population is in a drier area with drier soils. In spite of this, there was minimum phenotypic variation detected at the population level, which reflected the different environments and may be associated with patterns of environmental phenotypic plasticity.


Visual evoked potential changes induced by methylphenidate in hyperactive children: dose/response effects.
Visual event related potentials (ERP) were recorded from 21 hyperactive children aged 7-13 years under two attention conditions at 4 levels of methylphenidate dose (placebo, low, medium and high). ERP measures were very sensitive to age (under or over 10 years) and attention condition, but less sensitive to drug dose. There appeared to be two classes of drug dose effect on ERP amplitude, those that changed monotonically with dose and those from which dose interacted with attention non-monotonically. Drug effect on ERP amplitude may also depend on age so that opposite effects may occur in young and old children. No latency measures showed a dose effect. It appears that methylphenidate can speed reaction times without shortening ERP latency. This suggests the drug acts more on response-related processes than on stimulus evaluation.


A challenging task for assessment of checking behaviors in obsessive-compulsive disorder.
The present study concerns the objective and quantitative measurement of checking activity, which represents the most frequently observed compulsions in obsessive-compulsive disorder (OCD). To address this issue, we developed an instrumental task producing repetitive checking in OCD subjects. Fifty OCD subjects and 50 normal volunteers (NV) were administered a delayed matching-to-sample task that offered the unrestricted opportunity to verify the choice made. Response accuracy, number of verifications, and response time for choice taken to reflect the degree of uncertainty and doubt were recorded over 50 consecutive trials. Despite similar levels of performance, patients with OCD demonstrated a greater number of verifications and a longer response time for choice before checking than NV. Such behavioral patterns were more pronounced in OCD subjects currently experiencing checking compulsions. The present task might be of special relevance for the quantitative assessment of checking behaviors and for determining relationships with cognitive processes.


Parainfluenza virus as a cause of acute respiratory infection in hospitalized children.
Human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children. To assess the prevalence of Human parainfluenza viruses as a cause of acute respiratory infection and to compare clinical data for this infection against those of the human respiratory syncytial virus. A prospective study in children younger than five years with acute respiratory infection was conducted. Detection of respiratory viruses in nasopharyngeal aspirate samples was performed using the indirect immunofluorescence reaction. Length of hospital stay, age, clinical history and physical exam, clinical diagnoses, and evolution (admission to Intensive Care Unit or general ward, discharge or death) were assessed. Past personal (premature birth and cardiopathy) as well as family (smoking and atopy) medical factors were also assessed. A total of 585 patients were included with a median age of 7.9 months and median hospital stay of six days. No difference between the HRSV+ and HPIV+ groups was found in terms of age, gender or length of hospital stay. The HRSV+ group had more fever and cough. Need for admission to the Intensive Care Unit was similar for both groups but more deaths were recorded in the HPIV+ group. The occurrence of parainfluenza peaked during the autumn in the first two years of the study. Parainfluenza was responsible for significant morbidity, proving to be the second-most prevalent viral agent in this population after respiratory syncytial virus. No difference in clinical presentation was found between the two groups, but mortality was higher in the HPIV+ group.


Factors associated with breast and cervical cancer screening behavior among African immigrant women in Minnesota.
Immigrant populations in the United States (US) have lower cancer screening rates compared to none immigrant populations. The purpose of this study was to assess the rates of cancer screening and examine factors associated with cancer screening behavior among African immigrant women in Minnesota. A cross sectional survey of a community based sample was conducted among African immigrants in the Twin Cities. Cancer screening outcome measures were mammography and Papanicolau smear test. The revised theoretical model of health care access and utilization and the behavioral model for vulnerable populations were utilized to assess factors associated with cancer screening. Only 61 and 52% of the age eligible women in the sample had ever been screened for breast and cervical cancer respectively. Among these women, duration of residence in the US and ethnicity were significant determinants associated with non-screening. Programs to enhance screening rates among this population must begin to address barriers identified by the community.


Thermal inactivation of SARS COVID-2 virus: Are steam inhalations a potential treatment?
The emergence of SARS-CoV-2 pandemic has upset health systems around the world and caused immeasurable losses and costs. Until a vaccine will become available, the recommended prevention measures remain physical distancing and enhanced hygiene. The proteic structure external to the virus is the main target that may eventually lead to reduce or block its replication in the upper airways. We developed a protocol based of repeated steam inhalation cycles aimed at reducing the risk of progression to full blown infection if performed soon after contagion. The protocol has been used in a single-center open label trial on ten infected asymptomatic or pauci-symptomatic health care professionals. The promising results we obtained with this easily accessible, non-invasive and inexpensive procedure should prompt controlled trials.


Engineering therapeutic phages for enhanced antibacterial efficacy.
The alarming rise in antimicrobial resistance coupled with a lack of innovation in antibiotics has renewed interest in the development of alternative therapies to combat bacterial infections. Despite phage therapy demonstrating success in various individual cases, a comprehensive and unequivocal demonstration of the therapeutic potential of phages remains to be shown. The co-evolution of phages and their bacterial hosts resulted in several inherent limitations for the use of natural phages as therapeutics such as restricted host range, moderate antibacterial efficacy, and frequent emergence of phage-resistance. However, these constraints can be overcome by leveraging recent advances in synthetic biology and genetic engineering to provide phages with additional therapeutic capabilities, improved safety profiles, and adaptable host ranges. Here, we examine different ways phages can be engineered to deliver heterologous therapeutic payloads to enhance their antibacterial efficacy and discuss their versatile applicability to combat bacterial pathogens.


The Sp1 transcription factor is essential for the expression of gliostatin/thymidine phosphorylase in rheumatoid fibroblast-like synoviocytes.
Gliostatin/thymidine phosphorylase (GLS/TP) has angiogenic and arthritogenic activities, and aberrant GLS production has been observed in the active synovial membranes of rheumatoid arthritis (RA) patients. The human GLS gene promoter contains at least seven consensus binding sites for the DNA binding protein Sp1. Here we examined whether Sp1 is necessary for GLS production in RA. We also studied the effects of the Sp1 inhibitor mithramycin on GLS production in RA fibroblast-like synoviocytes (FLSs). FLSs from RA patients were treated with specific inhibitors. The gene and protein expression of GLS were studied using the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and an enzyme immunoassay. Intracellular signalling pathway activation was determined by western blotting analysis, a luciferase assay, a chromatin immunoprecipitation (ChIP) assay and a small interfering RNA (siRNA) transfection. The luciferase and ChIP assays showed that Sp1 binding sites in the GLS promoter were essential for GLS messenger RNA (mRNA) expression. GLS production was suppressed in FLSs by siRNA against Sp1 transfection. Mithramycin decreased GLS promoter activity, mRNA and protein expression in FLSs. Tumour necrosis factor-α (TNF-α) significantly increased GLS expression in RA FLSs; this effect was reduced by pre-treatment with cycloheximide and mithramycin. Pretreatment of mithramycin and Sp1 silencing resulted in a significant suppression of GLS production in TNF-α-stimulated FLSs compared to controls. GLS gene expression enhanced by TNF-α was partly mediated through Sp1. As physiological concentrations of mithramycin can regulate GLS production in RA, mithramycin is a promising candidate for anti-rheumatic therapy.


Investigation of mechanisms underlying transient T2 normalization in longitudinal studies of ischemic stroke.
To determine if the phenomenon of transient normalization of T2 relaxation in the subacute stage of ischemic stroke is associated with either magnetic susceptibility effects secondary to hemorrhage or changes in tissue water content. We utilized a rat model of transient, focal, cerebral ischemia. The possibility of hemorrhage was evaluated with T2*-weighted (T2*W) imaging and histology. Changes in water content were assessed by brain wet-to-dry weight. Susceptibility effects were not evident in T2*W images, and neither red blood cells nor unchelated Fe(III) was found in hematoxylin and eosin (H-E)- or Prussian Blue-stained sections, respectively. However, between the peak of T2 contrast and the point of transient T2 normalization, water content consistently decreased by an average of 3%. Transient T2 normalization is associated with normalization of water content and can occur without evidence of hemorrhage.


Attainment of normal lipid levels among high cardiovascular risk patients: pooled analysis of observational studies from the United Kingdom, Sweden, Spain and Canada.
Although low-density lipoprotein cholesterol (LDL-C) is the primary lipid target for cardiovascular disease (CVD) risk reduction, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) have also emerged as risk factors. This study evaluated attainment of goal/normal lipid levels in current clinical practice among high-risk patients following lipid-modifying therapy (LMT). Data for patients aged ≥35years and on LMT for ≥12months were identified from electronic medical records (United Kingdom and Sweden) and extracted from medical charts (Canada and Spain). High CVD risk was defined according to the Adult Treatment Panel III guidelines. An index period was defined, from January 1995-July 2008, during which patients received an initial LMT prescription. Prevalence of lipid abnormalities was assessed 12months before and after the index date. Multivariate logistic regressions evaluated predictors of attaining goal/normal lipid levels. Among 12,768 high-risk patients, 75% had elevated LDL-C, 37% low HDL-C, and 30% elevated TG before LMT. Despite therapy (97% statins only), 23% had elevated LDL-C, 36% low HDL-C, 16% elevated TG, and 17% had ≥2 abnormal lipid levels. Framingham risk score >20% (Odds Ratio, 95% confidence interval: 0.37,0.31-0.43), diabetes (0.75,0.64-0.88), hypertension (1.26,1.09-1.46), current smoker (0.82,0.70-0.95) and increased body mass index (0.95,0.94-0.96) were associated with the likelihood of attaining ≥2 normal lipid levels (vs. LDL-C goal only). Current approaches to lipid management improve LDL-C goal attainment; however, control of multiple lipid risk factors remains poor. Patients may benefit from more comprehensive approaches to lipid management, which treat multiple lipid abnormalities, as suggested in clinical guidelines.


Volatile organic compounds in ambient air of a major Asian port: spatiotemporal variation and source apportionment.
This study investigated the spatiotemporal variation and source characteristics of volatile organic compounds (VOCs) in Kaohsiung Harbor, one of the busiest ports in the world. The VOCs' potential to form ozone (O3) and secondary organic aerosols (SOAs) was also examined. The temporal variation was studied in February, May, July, and November of 2020, while the spatial distribution was investigated in the export processing zone (KEPZ) and at the two port entrances (E1 and E2). The most polluted month in the harbor was November (37.7 ± 12.6 ppbv), while the most polluted site was the industrial area (KEPZ). A significant positive correlation was found between VOCs and O3 (r = 0.985). Meanwhile, a moderate positive correlation (r = 0.449) was observed between VOCs and secondary organic aerosol formation potential (SOAFP), mainly affected by the concentration of toluene in the study area. The diagnostic ratios indicated that the air parcels in the site were "fresh," and three possible ambient sources of VOC were identified by the positive matrix factorization (PMF): industrial emissions (53.6%), freight transport emissions (29.6%), and others (17.7%). The study highlights the current state of VOCs and their potential sources in the port city of Kaohsiung, which can be used to enhance the strategies for regulating and controlling industrial activities and improving air pollution control measures to reduce VOC emissions.


Traumatic Life Events and Psychopathology in a High Risk, Ethnically Diverse Sample of Young Children: A Person-Centered Approach.
Studies of the association between traumatic experiences and psychopathology in early childhood have primarily focused on specific types of events (e.g., sexual abuse) or aggregated different types of events without differentiating among them. We extend this body of work by investigating patterns of traumatic event exposure in a high-risk, ethnically diverse sample of children ages 3-6 (N = 211; 51 % female) and relating these different patterns to parents' reports of child externalizing, internalizing, and post-traumatic stress symptomatology. Using latent class analysis, which divides a heterogeneous population into homogenous subpopulations, we identified three patterns of traumatic events based on parents' responses to an interview-based assessment of trauma exposure in young children: (1) severe exposure, characterized by a combination of family violence and victimization; (2) witnessing family violence without victimization; and (3) moderate exposure, characterized by an absence of family violence but a moderate probability of other events. The severe exposure class exhibited elevated internalizing and post-traumatic stress symptoms relative to the witness to violence and moderate exposure classes, controlling for average number of traumatic events. Results highlight the need for differentiation between profiles of traumatic life event exposure and the potential for person-centered methods to complement the cumulative risk perspective.


The standardized and mini versions of the PAQLQ are valid, reliable, and responsive measurement tools.
The Paediatric Asthma Quality of Life Questionnaire (PAQLQ) is a validated tool developed to assess the impact of symptoms on quality of life. Here we assess the validity, reliability and responsiveness of two new simpler versions of this questionnaire: the Standardised PAQLQ and the MiniPAQLQ. Participants included 42 children with asthma, who completed the PAQLQ, PAQLQ(S), MiniPAQLQ, Asthma Control Questionnaire, and Health Utilities Index at baseline, one, five and nine weeks. Concordance between questionnaires was examined using intraclass correlation coefficients (ICC), bias by paired Student's t-tests and closeness of association by Pearson correlation coefficients. Correlation coefficients for each of the corresponding domains of the PAQLQ with the PAQLQ(S) were strong (r>0.97), and moderate to strong (r=0.50-0.94) with the MiniPAQLQ. Reliability was strong for both the PAQLQ(S) (ICC>0.89) and MiniPAQLQ (ICC>0.91). The responsiveness index values for the PAQLQ(S) (0.96) and the MiniPAQLQ (1.05) were both higher than that of the original PAQLQ (0.90). Cross sectional and longitudinal correlation coefficients were similar for all three instruments. The PAQLQ(S) and the MiniPAQLQ are valid, reliable and responsive to change. They can be used with confidence for long-term monitoring in clinical trials.


Simultaneous determination of pesticides, polycyclic aromatic hydrocarbons, polychlorinated biphenyls and phthalate esters in human adipose tissue by gas chromatography-tandem mass spectrometry.
This paper describes a method for the simultaneous determination of 284 environmental contaminants, including 57 pesticides, 15 polycyclic aromatic hydrocarbons (PAHs), 209 polychlorinated biphenyls (PCBs) and 3 phthalate esters (PAEs), in adipose tissue samples. For the first time, a gas chromatography-tandem mass spectrometry (GC-MS/MS) method following a homogenised extraction using acetonitrile and purification by gel permeation chromatography (GPC) was used. Various performance characteristics, such as the limit of detection (LOD), limit of quantification (LOQ), linear range, recovery and precision, were determined for each analyte. The LOD for most analytes was below 0.01 mg/kg. The recoveries and relative standard deviations (RSDs) were determined by spiking untreated samples with the analytes at the LOQ, 2×LOQ and 4×LOQ levels. The average recovery for most pesticides was between 70% and 120% and the precision values, expressed as RSD, were all below 20.4% (n=6). This method may provide an efficient tool for evaluating the extent of exposure to organic contaminants using human adipose tissue.


Tumor extracellular vesicles loaded with exogenous Let-7i and miR-142 can modulate both immune response and tumor microenvironment to initiate a powerful anti-tumor response.
Despite recent advances in cancer immunotherapy, there have been limitations in cancer treatment and patient survival due to a lack of antigen recognition and immunosuppressive tumor microenvironment. To overcome this issue, we have shown that miRNA modified tumor-derived Extracellular Vesicles (mt-EVs) would be an advantageous prospect since they are tumor specific and associated antigen sources which cause increase in maturation and antigen-presenting function of dendritic cells. Also, miRNAs are promising candidates for cancer therapy because of their ability to control several host immune subsets to respond against cancer cells as well as tumor microenvironment remodeling. Here, we report that mt-EVs containing tumor specific antigens loaded with miRNAs (Let-7i, miR-142 and, miR-155) could increase the survival rate of tumor-bearing mice and induce reduction in tumor growth. Importantly, the administration of mt-EVs elicited cytotoxic T cells with increasing in IFNγ and Granzyme B production ability. Notably, intramuscular (IM) injection of let7i, miR142-EVs had a significant effect on dendritic cell (DC) maturation and T cell activation along with tumor shrinkage. Collectively, our findings suggest that administration of miRNA containing EVs may be effective immunotherapy against solid tumors.


Sonography of chronic Achilles tendinopathy: a case-control study.
To describe the sonographic appearance of Achilles tendon in normal subjects and patients with chronic Achilles tendinopathy with the aim of establishing diagnostic sonographic criteria for Achilles tendinopathy. A prospective, cross-sectional, case-control sonographic study of the Achilles tendon was undertaken. Thirty tendons in 21 patients and 100 tendons in 50 control subjects were selected. Sonographic assessment included tendon thickness, echogenicity, fibrillar pattern, and presence of calcifications. Power Doppler imaging was used to assess tendon vascularity. Paratendinous structures and plantar fascia were also examined. Tendinopathic tendons were larger than normal tendons in both cross-sectional area and antero-posterior diameter. Hypoechoic areas within the tendon were more commonly seen in patients. Disruption of fibrillar pattern, increase in tendon vascularity, increased Kager's fat pad echogenicity, and paratenon thickening were solely seen in patients. Fluid in the retrocalcaneal bursa and calcaneal bony abnormalities were seen in both groups without a significant difference. Achilles tendinopathy results in enlargement, particularly of the mid- and distal portions of the tendon, disruption of fibrillar pattern, and increase in tendon vascularity. Additional signs are increased Kager's fat pad echogenicity and paratenon thickening. Tendon calcification, changes in retrocalcaneal bursae, and calcaneal contour are not specific for Achilles tendinopathy.


Patient characteristics, management and outcomes in a Nordic subset of the "large observational study to understand the global impact of severe acute respiratory failure" (LUNG SAFE) study.
The "Large observational study to understand the global impact of severe acute respiratory failure" (LUNG SAFE) study described the worldwide epidemiology and management of patients with acute hypoxaemic respiratory failure (AHRF). Here, we present the Nordic subset of data from the LUNG SAFE cohort. We extracted LUNG SAFE data for adults fulfilling criteria for AHRF in intensive care units (ICU) in Denmark, Norway and Sweden, including demographics, co-morbidities, clinical assessment and management characteristics, 90-day survival and length-of-stay (LOS). We analysed ICU LOS with linear regression, and associations between risk factors and mortality were quantified using Cox regression. We included 192 patients, with a median age of 64 years (IQR 55, 72), and a male-to-female ratio of 2:1. The majority had one or more co-morbidities, and clinicians identified pneumonia as the primary cause of respiratory failure in 56% and acute respiratory distress syndrome (ARDS) in 21%. Median ICU LOS and duration of invasive mechanical ventilation (IMV) were 5 and 3 days. Tidal volumes (TV) were frequently larger than that supported by evidence and IMV allowing for spontaneous ventilation was common. Younger age, co-morbidity, surgical admission and ARDS were associated with ICU LOS. Sixty-one patients (32%) were dead at 90 days. Age and a non-surgical cause of admission were associated with death. In this subset of LUNG SAFE, ARDS was often not recognised in patients with AHRF and management frequently deviated from evidence-based practices. ICU LOS was generally short, and mortality was attributable to known risk factors.


Mima mounds in the Kenya highlands: significance for the Dalquest-Scheffer hypothesis.
The Dalquest-Scheffer Hypothesis that Mima mounds in western North America are the long-term product of burrowing activities of geomyid pocket gophers was tested by examination of areas of similar topography in the highlands of Kenya. Two mound areas, located near Nyahururu at an elevation of about 2,400 m, were studied in detail. The mounds ranged from less than 25 cm to 2 m in height and from a few m to about 20 m in diameter, and were not the remains of large termite nests. Populations of the rhizomyid mole rat, Tachyoryctes splendens, a fossorial rodent similar in morphology and social behavior to geomyid pocket gophers, were associated with these mounds. Mound density and dispersion pattern were similar to North American Mima mounds, and the distribution of fresh soil heaps indicated that the activities of these animals were mound-centered. A shallow laterite hardpan underlay these mound areas, fulfilling another requirement of the Dalquest-Scheffer hypothesis. It is concluded that Mima mounds are the product of the burrowing of fossorial rodents such as pocket gophers and mole rats, and that these two groups are convergent in morphology, burrowing behavior, and impact on the landscape.


Do men develop type 2 diabetes at lower body mass indices than women?
To describe the associations between age, sex and BMI at diagnosis of type 2 diabetes, and test the hypothesis that men are diagnosed with diabetes at lower average BMI than women of similar age. Linear regression was used to estimate and compare the relationship between age and BMI at diagnosis among 51,920 men and 43,137 women included in a population-based diabetes register in Scotland for whom an index BMI measurement was taken within 1 year of diabetes diagnosis. We also examined HbA(1c) values by sex within the same timescale. Mean BMI closest to date of diagnosis of type 2 diabetes mellitus was 31.83 kg/m(2) (SD 5.13) in men and 33.69 kg/m(2) (SD 6.43) in women. The inverse relationship between age and BMI at diagnosis of type 2 diabetes mellitus was significantly steeper in women than in men (slope estimate in men -0.12 kg/m(2) per year [95% CI -0.13, -0.12] women -0.18 kg/m(2) per year [95% CI -0.18, -0.17], p < 0.0001 for formal test of interaction). Mean BMI difference was most marked at younger ages and narrowed with advancing age. However, HbA(1c) levels within 1 year of diagnoses were broadly similar in men and women. Men are diagnosed with type 2 diabetes at lower BMI than women across the age range. This observation may help explain why type 2 diabetes is more common among middle-aged men in populations of European extraction. Whether the same pattern is also observed in other ethnic groups requires confirmation.


[Increased genomic instability in somatic cells of the progeny of female mice exposed to acute X-radiation in the preconceptional period].
The level of genome instability (GI) was studied in the progeny of female mice exposed in the preconceptional period to radiation doses of 0.5, 1, and 2 Gy in comparison to that in the progeny of the same parent pairs born before irradiation of the females. To assess the level of genome instability, we analyzed polymorphism of DNA fragments from postmitotic (blood and brain) and proliferating (spleen and tail tip) tissues amplified by AP-PCR (PCR amplification with an arbitrary primer). It was found that polymorphism of the spectrum of AP-PCR products, which is a multilocus genetic marker (MGM), in the genome of somatic cells in the progeny of female mice exposed to 2 Gy was higher than in the progeny of male mice exposed to the same doses. In the progenies of female mice born before and after irradiation, tissue-specific variations in the level of DNA polymorphism were detected. The maximum value of this polymorphism (with respect to the frequency of "nonparental bands") was determined for peripheral blood DNA in comparison with the other tissues. Estimations of the MGM polymorphism with the AP-PCR method demonstrate an increased level of genome instability in somatic cells of offsprings from female mice exposed to a single acute dose of X-rays (0.5, 1, and 2 Gy) in the pre-conceptional period. Radiation-induced transgenerational genome instability with an increase in the dose of preconceptional irradiation of female mice was more pronounced in DNA of the postmitotic tissues (blood and brain DNA) than in DNA of the proliferating tissues (spleen and tail tip epithelium).


Non-communicable disease (NCD) risk factors and diabetes among adults living in slum areas of Dhaka, Bangladesh.
Despite one-third of the urban population in Bangladesh living in urban slums and at increased risk of non-communicable diseases (NCDs), little is known about the NCD risk profile of this at-risk population. The aim of the study was to identify the prevalence of the NCD risk factors and the association of NCD risk factors with socio-demographic factors among the adults of urban slums in Dhaka, Bangladesh. A cross-sectional study was conducted among adult slum dwellers (aged 25 and above) residing in three purposively selected urban slums of Dhaka for at least six months preceding the survey. The risk factors assessed were- currently smoking, fruit and vegetable intake, physical activity, hypertension and body mass index (BMI). Information on self-reported diabetes was also taken. A total of 507 participants (252 females; 49.7%) were interviewed and their physical measures were taken using the WHO NCD STEPS instrument. The overall prevalence of NCD risk factors was: 36.0% (95% CI: 31.82-40.41) for smoking; 95.60% (95% CI: 93.60-97.40) for insufficient fruit and vegetable intake; 15.30% (95% CI:12.12-18.71) for low physical activity;13.70% (95% CI: 10.71-16.92) for hypertension; 22.70% (95% CI: 19.31-26.02) for overweight or obesity; and 5.00% (95%: 3.20-7.00) for self-reported diabetes. In the logistic regression model, the clustering of three or more NCD risk factors was positively associated with younger age groups (p = 0.02), no formal education (p <0.001) and primary education level (p = 0.01), but did not differ by sex of the participants, monthly income and occupation. All NCD risk factors are markedly high among the urban slum adults. These findings are important to support the formulation and implementation of NCD-related polices and plan of actions that recognize urban slum populations in Bangladesh as a priority sub-population.


Systemic effects of isolated brain injury: an experimental animal study.
Although various experimental works of neurotrauma research are performed, little attention has been paid to the concomitant systemic changes following isolated traumatic brain injury (TBI). Such investigations seem to be a prerequisite condition for evaluation of experimental drugs, which may diminish the secondary damage following TBI. We describe histopathologic findings of the lung, liver, spleen and kidney 96 hours following an experimental TBI. Ten male C57BI/6 mice were subjected to a controlled cortical impact (CCI) over the left parietotemporal cortex using rounded-tip impounder for application of a standardized brain injury. Subjects were killed 96 hours following trauma. Brain, lung, liver, kidney and spleen were preserved for morphologic examinations. Moderate histopathologic changes were evident in the lung and liver. The kidney and spleen seem not to be affected by the trauma regarding our examination. The findings of this study show that even isolated TBI can lead to a migration of immunocompetent cells to peripheral organs potentially leading to dysfunctions of peripheral organs to various extents. More attention to peripheral organs during experimental TBI research is indicated.


Evaluation of fungal- and photo-degradation as potential treatments for the removal of sunscreens BP3 and BP1.
Photodecomposition might be regarded as one of the most important abiotic factors affecting the fate of UV absorbing compounds in the environment and photocatalysis has been suggested as an effective method to degrade organic pollutants. However, UV filters transformation appears to be a complex process, barely addressed to date. The white rot fungus Trametes versicolor is considered as a promising alternative to conventional aerobic bacterial degradation, as it is able to metabolise a wide range of xenobiotics. This study focused on both degradation processes of two widely used UV filters, benzophenone-3 (BP3) and benzophenone-1 (BP1). Fungal treatment resulted in the degradation of more than 99% for both sunscreens in less than 24 h, whereas photodegradation was very inefficient, especially for BP3, which remained unaltered upon 24 h of simulated sunlight irradiation. Analysis of metabolic compounds generated showed BP1 as a minor by-product of BP3 degradation by T. versicolor while the main intermediate metabolites were glycoconjugate derivatives. BP1 and BP3 showed a weak, but significant estrogenic activity (EC50 values of 0.058 mg/L and 12.5 mg/L, respectively) when tested by recombinant yeast assay (RYA), being BP1 200-folds more estrogenic than BP3. Estrogenic activity was eliminated during T. versicolor degradation of both compounds, showing that none of the resulting metabolites possessed significant estrogenic activity at the concentrations produced. These results demonstrate the suitability of this method to degrade both sunscreen agents and to eliminate estrogenic activity.


Defective AMPK regulation of cholesterol metabolism accelerates atherosclerosis by promoting HSPC mobilization and myelopoiesis.
Dysregulation of cholesterol metabolism in the liver and hematopoietic stem and progenitor cells (HSPCs) promotes atherosclerosis development. Previously, it has been shown that HMG-CoA-Reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway, can be phosphorylated and inactivated by the metabolic stress sensor AMP-activated protein kinase (AMPK). However, the physiological significance of AMPK regulation of HMGCR to atherogenesis has yet to be elucidated. The aim of this study was to determine the role of AMPK/HMGCR axis in the development of atherosclerosis. We have generated a novel atherosclerotic-prone mouse model with defects in the AMPK regulation of HMGCR (Apoe-/-/Hmgcr KI mice). Atherosclerotic lesion size, plaque composition, immune cell and lipid profiles were assessed in Apoe-/- and Apoe-/-/Hmgcr KI mice. In this study, we showed that both male and female atherosclerotic-prone mice with a disruption of HMGCR regulation by AMPK (Apoe-/-/Hmgcr KI mice) display increased aortic lesion size concomitant with an increase in plaque-associated macrophages and lipid accumulation. Consistent with this, Apoe-/-/Hmgcr KI mice exhibited an increase in total circulating cholesterol and atherogenic monocytes, Ly6-Chi subset. Mechanistically, increased circulating atherogenic monocytes in Apoe-/-/Hmgcr KI mice was associated with enhanced egress of bone marrow HSPCs and extramedullary myelopoiesis, driven by a combination of elevated circulating 27-hydroxycholesterol and intracellular cholesterol in HSPCs. Our results uncovered a novel signalling pathway involving AMPK-HMGCR axis in the regulation of cholesterol homeostasis in HSPCs, and that inhibition of this regulatory mechanism accelerates the development and progression of atherosclerosis. These findings provide a molecular basis to support the use of AMPK activators that currently undergoing Phase II clinical trial such as O-3O4 and PXL 770 for reducing atherosclerotic cardiovascular disease risks.


Advanced cervical squamous cell carcinoma with skin metastasis.
Although cervical cancer is a very common gynecologic malignancy, skin metastasis presenting as an initial sign of recurrent or persistent disease is extremely rare. A 72-year-old woman was diagnosed with squamous cell carcinoma of the cervix (FIGO stage, IIB), which was treated with concurrent chemoradiation. After treatment, she was followed up regularly, without evidence of disease. One year later, many erythematous lesions were noted on the extremities, trunk, and scalp. Some of skin lesions grew rapidly. Excision biopsy was performed and showed metastatic carcinoma, favoring a squamous cell type. The patient then underwent a series of imaging examinations, including magnetic resonance imaging of the pelvis and computed tomography of the chest, and a whole body bone scan showed disseminated diseases involving the lung and bone. Palliative chemotherapy was prescribed, and the skin lesions responded relatively well, but disease involving the vital organs still progressed during treatment. The patient died of the disease 6 months after the appearance of the skin lesion. This report supports the concept that skin metastasis is a late manifestation and an ominous sign for cervical cancer patients, and also indicates the uncontrolled or widespread metastasis of the disease.


Conceptual model of the Bahamian Platform for the last 135 million years.
The subsidence history of the Bahamian Platform points to a non-uniform rate of sea-floor spreading since the beginning of the Cretaceous. Lower Cretaceous rates of perhaps 5 cm/yr led to an active trench system at the boundary between the American and Caribbean lithosphere plates, and the rapid subsidence of the continental margin produced graben faults on the Bahamian Platform and normal faults in Cuba.


Effect of treatment with myo-inositol on semen parameters of patients undergoing an IVF cycle: in vivo study.
Myo-inositol (MI) is a precursor for the synthesis of phosphatidylinositol polyphosphates (PIPs). The aim of the study is to evaluate the effect of its administration on semen parameters of male patients undergoing an in vitro fertilization cycles. In vivo study. Samples were semen of 62 patients divided into three different groups: healthy fertile patients (Group A); patients with oligoasthenospermia (OA) (Group B); control group (CTR). The collected samples were analyzed by optic microscopy in order to evaluate semen's volume, spermatozoa's number and motility before and after density-gradient separation method. These parameters were evaluated before and after administration of 4000 mg/die of MI and 400 µg of folic acid for 2 months. The results were analyzed statistically with Student's t-test. After treatment there was a significant increase of basal and after density-gradient separation method spermatozoa concentration in Group B, and a significant increase of spermatozoa count after density-gradient separation method in Group A. The motility values were higher in healthy men than patients with OA before treatment, but there was no improvement in both groups after treatment. Exogenous administration of MI significantly improves semen's parameters both in patients with OA and in normal fertile men.


A learning rule for dynamic recruitment and decorrelation.
The interest in neuronal networks originates for a good part in the option not to construct, but to train them. The mechanisms governing synaptic modifications during such training are assumed to depend on signals locally available at the synapses. In contrast, the performance of a network is suitably measured on a global scale. Here we propose a learning rule that addresses this conflict. It is inspired by recent physiological experiments and exploits the interaction of inhibitory input and backpropagating action potentials in pyramidal neurons. This mechanism makes information on the global scale available as a local signal. As a result, several desirable features can be combined: the learning rule allows fast synaptic modifications approaching one-shot learning. Nevertheless, it leads to stable representations during ongoing learning. Furthermore, the response properties of the neurons are not globally correlated, but cover the whole stimulus space.


Leaf Species-Dependent Fungicide Effects on the Function and Abundance of Associated Microbial Communities.
Microbially-mediated leaf litter decomposition is a critical ecosystem function in running waters within forested areas, which can be affected by fungicides. However, fungicide effects on leaf litter decomposition have been investigated almost exclusively with black alder leaves, a leaf species with traits favourable to consumers (i.e., low recalcitrance and high nutrient content). At the same time, little is known about fungicide effects on microbial colonisation and decomposition of other leaf species with less favourable traits. In this 21 day lasting study, we explore the effects of increasing fungicide sum concentrations (0-3000 µg/L) on microbial colonisation and decomposition of three leaf species (black alder, Norway maple and European beech) differing in terms of recalcitrance and nutrient content. Leaf litter decomposition rate, leaf-associated fungal biomass and bacterial density were quantified to observe potential effects at the functional level. Beech, as the species with the least favourable leaf traits, showed a substantially lower decomposition rate (50%) in absence of fungicides than alder and maple. In the presence of high fungicide concentrations (300-3000 µg/L), beech showed a concentration-related decrease not only in microbial leaf litter decomposition but also fungal biomass. This suggests that favourable traits of leaf litter (as for alder and maple) enable leaf-associated microorganisms to acquire leaf-bound energy more easily to withstand potential effects induced by fungicide exposure. Our results indicate the need to deepen our understanding on how leaf species' traits interact with the impact of chemical stressors on the leaf decomposition activity of microbial communities.


[Relationship between lower urinary tract symptoms in men and erectile dysfunction].
The relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) is the result of their greater association in advanced age. Nevertheless, several investigations show that urinary tract symptoms have an independent relationship with sexual dysfunction and lower satisfaction. Likewise, the severity of LUTS correlates with the magnitude of sexual dysfunction, which suggests a possible causal relationship. The combined therapeutic approach of these 2 entities (ED and LUTS) brings a benefit to the patient both in urinary symptoms and sexual sphere. This review focuses on the relationship between ED, LUTS due to benign prostatic hyperplasia, and related therapies.


Rapid Access to Azabicyclo[3.3.1]nonanes by a Tandem Diverted Tsuji-Trost Process.
A three-step synthesis of the 2-azabicyclo[3.3.1]nonane ring system from simple pyrroles, employing a combined photochemical/palladium-catalysed approach is reported. Substrate scope is broad, allowing the incorporation of a wide range of functionality relevant to medicinal chemistry. Mechanistic studies demonstrate that the process occurs by acid-assisted C-N bond cleavage followed by β-hydride elimination to form a reactive diene, demonstrating that efficient control of what might be considered off-cycle reactions can result in productive tandem catalytic processes. This represents a short and versatile route to the biologically important morphan scaffold.


Short-term hyperglycemic dysregulation in patients with type 1 diabetes does not change myocardial triglyceride content or myocardial function.
To evaluate the effects of hyperglycemia due to partial insulin deprivation on myocardial triglyceride (TG) content and myocardial function in patients with type 1 diabetes. Myocardial and hepatic TG content and left ventricular (LV) function were measured by magnetic resonance (MR) spectroscopy and MR imaging during optimal glucoregulation and after 24 h of partial insulin deprivation (n = 10). Mean insulin infusion rate was 45 +/- 5 units at baseline, whereas it was 27 +/- 5 units during hyperglycemia (per 24 h, P < 0.001). Plasma glucose levels increased from 8.4 +/- 0.6 to 15.9 +/- 0.8 mmol/l (P < 0.001), and plasma levels of nonesterified fatty acids from 0.31 +/- 0.05 to 0.46 +/- 0.07 mmol/l (P = 0.015). Hyperglycemia had no effects on myocardial or hepatic TG content and LV function. Short-term hyperglycemic dysregulation does not modulate myocardial or hepatic TG content or myocardial function, despite considerable metabolic adaptations.