Early-onset schizophrenia: Symptoms and social class of origin.
The genesis of schizophrenia is multifactorial, including biological and environmental risk factors. We tested for an interactive effect between early-onset schizophrenia (EOS) and social class of origins (socioeconomic status (SES)). Data were further analyzed for a possible connection to type of schizophrenic symptoms. Sampling/Methods: Data for the study are taken from the medical records of 642 patients from a large state hospital in the northeastern United States. Clinical assessments were divided into positive and negative symptomatology through application of the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Positive and Negative Syndrome Scale (PANSS). Detailed information about age of onset and SES of origin was obtained through Social Service Assessment interviews. We uncovered a significant impact of EOS among the poor that elevates risk for negative symptomatology. Poor SES alone does not increase the likelihood of EOS, but it magnifies the deleterious effect of EOS on negative symptoms. Future research on these variables may inform the relative contribution of each.


Prediction role of seven SNPs of DNA repair genes for survival of gastric cancer patients receiving chemotherapy.
We aimed to investigate DNA repair gene expression of response to chemotherapy among gastric patients, and roles in the prognosis of gastric cancer. A total of 209 gastric cancer patients were included in this study between January 2007 and December 2008, all treated with chemotherapy. Polymorphisms were detected by real time PCR with TaqMan probes, and genomic DNA was extracted from peripheral blood samples. The overall response rate was 61.2%. The median progression and overall survivals were 8.5 and 18.7 months, respectively. A significant increased treatment response was found among patients with XPG C/T+T/T or XRCC1 399G/ A+A/A genotypes, with the OR (95% CI) of 2.14 (1.15-4.01) and 1.75 (1.04-3.35) respectively. We found XPG C/T+T/T and XRCC1 399 G/A+A/A were associated with a longer survival among gastric cancer patients when compared with their wide type genotypes, with HRs and 95% CIs of 0.49 (0.27-0.89) and 0.56 (0.29-0.98) respectively. Selecting specific chemotherapy based on pretreatment genotyping may be an innovative strategy for further studies.


Difference in 24-hour urine sodium excretion between controlled and uncontrolled patients on antihypertensive drug treatment.
The objective of this study was to evaluate the association between sodium intake and blood pressure (BP) control in hypertensive patients taking antihypertensive medications by using 24-hour urine collection and 24-hour ambulatory BP. This is a cross-sectional community-based study and conducted in 2011 and 2012. A total of 1128 participants were recruited from five cities in Korea. Among them, 740 participants who had complete 24-hour urine collection and valid 24-hour ambulatory BP data were included in this study. Participants were divided into four groups: normotensives (NT, n = 441), untreated hypertensive patients (UTHT, n = 174), controlled hypertensive patients (CHT, n = 62), and uncontrolled hypertensive patients (UCHT, n = 63). UCHT and CHT groups showed higher mean age than NT and UTHT groups. UCHT and UTHT groups showed higher 24-hour systolic BP (SBP) and diastolic BP (DBP) than NT and CHT groups. UCHT group had the highest level of 24-hour urine sodium. Multivariate analysis adjusted with age, gender, body mass index, estimated glomerular filtration rate, and use of diuretics showed higher level of 24-hour urine sodium in UCHT group than that in CHT group. Multivariate logistic regression analysis revealed independent association of the amount of 24-hour urine sodium with uncontrolled BP in hypertensive patients on antihypertensive drug treatment. Higher level of 24-hour urine sodium excretion in uncontrolled hypertensive patients suggests that excessive sodium intake could be associated with blunted BP lowering efficacy of antihypertensive medications.


Quantitation of Cabozantinib in Human Plasma by LC-MS/MS.
To support a phase III randomized trial of the multi-targeted tyrosine kinase inhibitor cabozantinib in neuroendocrine tumors, we developed a high-performance liquid chromatography mass spectrometry method to quantitate cabozantinib in 50 μL of human plasma. After acetonitrile protein precipitation, chromatographic separation was achieved with a Phenomenex synergy polar reverse phase (4 μm, 2 × 50 mm) column and a gradient of 0.1% formic acid in acetonitrile and 0.1% formic acid in water over a 5-min run time. Detection was performed on a Quattromicro quadrupole mass spectrometer with electrospray, positive-mode ionization. The assay was linear over the concentration range 50-5000 ng/mL and proved to be accurate (103.4-105.4%) and precise (<5.0%CV). Hemolysis (10% RBC) and use of heparin as anticoagulant did not impact quantitation. Recovery from plasma varied between 103.0-107.7% and matrix effect was -47.5 to -41.3%. Plasma freeze-thaw stability (97.7-104.9%), stability for 3 months at -80°C (103.4-111.4%), and stability for 4 h at room temperature (100.1-104.9%) were all acceptable. Incurred sample reanalysis of (N = 64) passed: 100% samples within 20% difference, -0.7% median difference and 1.1% median absolute difference. External validation showed a bias of less than 1.1%. This assay will help further define the clinical pharmacokinetics of cabozantinib.


Detection of chimerism following vascularized bone allotransplantation by polymerase chain reaction using a Y-chromosome specific primer.
Chimerism following allogeneic organ transplantation is a phenomenon known to occur and be associated with development of immunologic tolerance in allotransplantation. However, little is known about graft cell migration following vascularized bone allografting. In this study, chimerism was assessed following vascularized tibia transplantation from male DA or PVG donors to female PVG rat recipients using a semi-quantitative polymerase chain reaction for the Y-chromosome. FK-506 (Tacrolimus) was administered after transplantation for immunosuppression. All immunosuppresssed PVG rat recipients of PVG bone grafts showed a high level of chimerism (1%) in the thymus, spleen, liver and cervical lymph nodes at 18 weeks post-transplant. Donor cells were also detected in the contralateral tibia and humerus. In non-immunosuppressed PVG rat recipients of DA bone grafts, donor cells were detected in the spleen in three of five rats within 2 weeks post-transplant. In these animals the bone grafts were severely rejected. In immunosuppressed PVG rat recipients of DA bone grafts, two of five, four of eight and eight of 10 rats showed low level chimerism (0.1%) in peripheral blood at 1, 12, and 18 weeks post-transplant. Six rats showed a high level of chimerism in the spleen and thymus. Histological studies revealed no rejection findings through 18 weeks post-transplant. Our results indicate that chimerism, or the presence of graft cells in host tissue, may occur in the face of acute rejection and be demonstrable following vascularized isograft and allograft living bone transplantation when chronic immunosuppression is maintained. Graft vascular patency during the short-term likely allows cellular migration, even in the face of acute rejection. Long-term survival and proliferation of graft marrow elements in host tissue may be possible with adequate immunosuppression.


Implementation and lessons learned from 2 online interprofessional faculty development programs for improving educational practice in the health professions in Chile and the United Kingdom from 2018 to 2021.
This study presents the design, implementation, and lessons learned from 2 fit-for-purpose online interprofessional faculty development programs for educational practice improvement in the health professions in Chile and the United Kingdom from 2018 to 2021. Both programs were designed to enhance teaching and learning practices in an interprofessional environment based on 4 pillars: professional diversity, egalitarianism, blended/online learning, and active learning strategies. A multidisciplinary mix of educators participated, showing similar results. The 3 main lessons learned were that the following factors facilitated an interprofessional environment: a professions-inclusive teaching style, a flexible learning climate, and interprofessional peer work. These lessons may be transferable to other programs seeking to enhance and support interprofessionality. Faculty development initiatives preparing educators for interprofessional practice should be an integral component of health professions education, as delivering these courses within professional silos is no longer justifiable. As the relevance of interprofessional education grows, an effective way of promoting interprofessonal education is to train the trainers in formal interprofessional settings.


Particulate phagocytosis by trabecular meshwork endothelium.
We studied the phagocytic response in the trabecular meshwork of rabbits to the debris released by photocoagulation of the iris. Four cell types exhibited phagocytosis: native meshwork endothelium, histiocytic macrophages, polymorphonuclear leukocytes and corneal endothelial cells. Nienty days after the photocoagulation both the lining cells and the trabecular beams of the meshwork had returned to normal.


Power-law distributions of particle concentration in free-surface flows.
Particles floating on the surface of a turbulent incompressible fluid accumulate along string-like structures, while leaving large regions of the flow domain empty. This is reflected experimentally by a very peaked probability distribution function of c(r), the coarse-grained particle concentration at scale r, around c(r)=0, with a power-law decay over two decades of c(r), Pi(c(r)) proportional, variant c(r)(-beta(r)). The positive exponent beta(r) decreases with scale in the inertial range and stays approximately constant in the dissipative range, thus, indicating a qualitative difference between the dissipative and the inertial ranges of scales, also visible in the first moment of c(r).


Search for Light Dark Matter with Ionization Signals in the PandaX-4T Experiment.
We report the search results of light dark matter through its interactions with shell electrons and nuclei, using the commissioning data from the PandaX-4T liquid xenon detector. Low energy events are selected to have an ionization-only signal between 60 to 200 photoelectrons, corresponding to a mean nuclear recoil energy from 0.77 to 2.54 keV and electronic recoil energy from 0.07 to 0.23 keV. With an effective exposure of 0.55 tonne·year, we set the most stringent limits within a mass range from 40 MeV/c^{2} to 10 GeV/c^{2} for pointlike dark matter-electron interaction, 100 MeV/c^{2} to 10 GeV/c^{2} for dark matter-electron interaction via a light mediator, and 3.2 to 4 GeV/c^{2} for dark matter-nucleon spin-independent interaction. For DM interaction with electrons, our limits are closing in on the parameter space predicted by the freeze-in and freeze-out mechanisms in the early Universe.


Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis.
Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, <60 mL/min per 1.73 m2) at baseline. The impact of RD on death or disability (modified Rankin Scale scores, 2-6) at 90 days, and symptomatic intracerebral hemorrhage, was assessed in logistic regression models. Compared with patients with normal renal function (>90 mL/min per 1.73 m2), those with severe RD (<30 mL/min per 1.73 m2) had increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89-4.82; P=0.04 for trend); every 10 mL/min per 1.73 m2 lower estimated glomerular filtration rate was associated with an adjusted 9% increased odds of death from thrombolysis-treated acute ischemic stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62-1.70; P=0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72-2.01; P=0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades. RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients with RD. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.


Modeling justice as a natural phenomenon.
Among other things, Baumard et al.'s "A Mutualistic Approach to Morality" considers the enforcement and establishment of moral norms, the interpersonal comparison of welfare, and the structure of fairness norms. This commentary draws attention to the relevance of the game theory literature to the first and second topic, and the social psychology literature to the third topic.


Effect of Interdental Enamel Reduction on Clinical Attachment Loss, Bleeding on Probing, and Incidence of Caries in Treating Class I Malocclusion Cases: A Retrospective Cohort Study.
Introduction Interdental Enamel Reduction (IER) is a clinical procedure that reduces the mesiodistal size of permanent teeth by enamel removal and anatomical re-contouring. The aim of this study was to investigate the effect of IER on patients' gingival health status, including clinical attachment loss (CAL) and bleeding on probing (BOP). Furthermore, in this study, the incidence of caries after IER with or without fluoride therapy was evaluated. Methods In this retrospective cohort study, 90 patients who had started and completed their orthodontic treatment within the past two years were divided into three groups as follows: In group 1, patients had received interproximal stripping on their anterior mandibular teeth. Patients in group 2 had also received interproximal stripping on their mandibular anterior teeth and topical fluoride had been applied after IER. Patients in group 3 had only received orthodontic treatment without any interproximal stripping. Then, patients were examined for CAL, BOP, and incidence of caries. Results CAL for patients in the IER and control groups were 2.06±0.18 and 2.08±0.16, respectively. Also, BOP for patients in the IER and control groups were 3.01±0.14 and 3.05±0.19, respectively. Incidences of caries, BOP, and CAL were not significantly different between the group of patients who received IER and the control group (P>0.05). Moreover, the incidence of caries was not significantly different between the patients who received topical fluoride after IER and those who did not receive fluoride (P=0.999). Conclusion Interproximal stripping of mandibular anterior teeth before orthodontic treatment does not significantly increase the incidence of caries, BOP, and CAL. Moreover, the application of topical fluoride after IER has no significant effect on the incidence of caries.


Effect of recycling activities on the heating value of solid waste: case study of the Greater Vancouver Regional District (Metro Vancouver).
Two main goals of the integrated solid waste management system (ISWMS) of Metro Vancouver (MV) include further recycling of waste and energy recovery via incineration of waste. These two very common goals, however, are not always compatible enough to fit in an ISWMS depending on waste characteristics and details of recycling programs. This study showed that recent recycling activities in MV have negatively affected the net heating value (NHV) of municipal solid waste (MSW) in this regional district. Results show that meeting MV's goal for additional recycling of MSW by 2015 will further reduce the NHV of waste, if additional recycling activities are solely focused on more extensive recycling of packaging materials (e.g. paper and plastic). It is concluded that 50% additional recycling of paper and plastic in MV will increase the overall recycling rate to 70% (as targeted by the MV for 2015) and result in more than 8% reduction in NHV of MSW. This reduction translates to up to 2.3 million Canadian dollar (CAD$) less revenue at a potential waste-to-energy (WTE) plant with 500 000 tonnes year(-1) capacity. Properly designed recycling programmes, however, can make this functional element of ISWMS compatible with green goals of energy recovery from waste. Herein an explanation of how communities can increase their recycling activities without affecting the feasibility of potential WTE projects is presented.


An Uncommon Complication of Esophageal Cancer.
Esophageal cancer is one of the rarer solid tumors that metastasize to the central nervous system. We describe a case of a 57-year-old male, previously confirmed to have obstructive esophageal adenocarcinoma with local mediastinal and esophagogastric lymph node involvement undergoing chemotherapy, who presented with altered mental status, headache, nausea, 15-pound weight loss, and neck stiffness. Prior staging with an MRI of the brain and spine was unrevealing, but a lumbar puncture demonstrated adenocarcinomatous spread to the cerebrospinal fluid, consistent with leptomeningeal carcinomatosis.


[Clinical research XII. From the clinical judgment to the transversal design].
A longitudinal study, such as a cohort or clinical trial, has the virtue of following the logical sequence in which occurs the components of causality phenomenon. However, in a cross-sectional survey, this logical sequence does not exist, because the three components are measured at one time: the basal state, maneuver, and result. However, the design of "clinical judgment" helps us to rebuild these components artificially in the time sequence in which they occurred. The way the population is assembled and how information is obtained, transversally and retrospectively, carries the risk of bias. While trying to associate a probable maneuver to an outcome in a pathological situation is difficult and often causes bias, a cross-sectional survey is the best to show the development of healthy people simulating a longitudinal study, like the height and weight estimation according to age. This type of design has been called "a longitudinal cross sectional study."


Affective and physiological response to a novel parent-adolescent conflict stressor.
Few laboratory paradigms exist that expose adolescents to conflict that might commonly be experienced in parent-adolescent relationships. Given the continued importance of parent-adolescent relationships on adolescent development, as well as the changing expectations in these relationships, we examined the effect of a novel parent-adolescent conflict paradigm on physiological and affective response in a sample of 52 adolescents. The parent-adolescent conflict stressor (PACS) involved adolescent participants (50% girls; M = 14.75, SD = 0.88) watching a 12-minute scripted video that asked youth to imagine that they were the teenager in the video, which consisted of parent and adolescent actors having discussions about conflict in their relationship and solving this conflict in either a positive, typical, or hostile manner. Cortisol, alpha amylase, and self-report of negative and positive affect were collected at baseline, following the video, and during a recovery period. Heart rate also was taken continuously while adolescents watched the videos. Hierarchical linear modeling (HLM) analyses indicated significant linear change in alpha amylase and linear and quadratic change in negative affect to the PACS. There also was a significant linear and quadratic change in heart rate during the portion of the video where teens and parents discussed issues of personal responsibility. The PACS marks a preliminary but important first step in developing a parent-adolescent conflict paradigm that can be used across studies to understand the impact of parent-adolescent conflict on affective and physiological markers associated with stress response.


[Clinical experience of vecuronium bromide 10 mg preparation].
The neuromuscular blocking effects of vecuronium 10 mg preparation under enflurane anesthesia have been investigated in 22 patients having elective surgeries. The effect on cardiovascular system in man and laboratory examinations were also investigated. The results are as follows; 1. Onset time (time from end of injection until maximal blockade) after the dose of 0.08 or 0.1 mg.kg-1 of vecuronium bromide was about 2.6 minutes and 1.9 minutes, respectively. 2. Clinical duration of action (time from end of injection until 25% recovery of twitch) in the 0.1 mg.kg-1 group (about 50.1 minutes) was significantly longer than that in the 0.08 mg.kg-1 group (about 35.6 minutes). 3. Recovery time (time elapsing between 25 and 75% recovery of twitch) with neostigmine was 5.3 minutes (0.08 mg.kg-1) and 4.2 minutes (0.1 mg.kg-1). 4. Blood pressure was stable before and after the injection of vecuronium and no abnormal change related to the test drug was observed in the laboratory examinations. These data show that the efficacy and safety of the vecuronium 10 mg preparation are the same as those of the 4 mg preparation reported previously. In conclusion, it is considered that vecuronium 10 mg preparation is clinically useful because it is unnecessary to dissolve the drug frequently with injectable water.


Ultrasound-Based Detection of Low Muscle Mass for Diagnosis of Sarcopenia in Older Adults.
To establish muscle-specific cut-off values for ultrasound-based detection of low muscle mass, and to assess its prevalence in a population of frail older subjects when applying the cut-points of different muscles and those of different sarcopenic indices. Cross-sectional study. Geriatric outpatient clinic and clinical research laboratory. A total of 44 older adults (30 women and 14 men, mean age 82 years, range 67-93 years) and 60 younger individuals (30 women and 30 men, mean age 26 years, range 20-36 years) participated. Body composition and thickness of 4 lower limb muscles (rectus femoris, vastus lateralis, tibialis anterior, medial gastrocnemius) were respectively assessed by bioelectrical impedance analysis (BIA) and ultrasonography. Site-specific cut-points for ultrasound-based assessment of low muscle mass (muscle thickness values 2 standard deviations below the gender-specific means of our sample of younger subjects) and comparative prevalence rates of low muscle mass. The following site-specific cut-points for muscle thickness were identified: rectus femoris: 20 mm in men and 16 mm in women; vastus lateralis: 17 mm in men and 15 mm in women; tibialis anterior: 23 mm in men and 22 mm in women; and medial gastrocnemius: 13 mm in both men and women. The prevalence of low muscle mass in older adults was highly dependent on the muscle being investigated; it varied from 86% for thigh muscles to 30% for leg muscles. Moreover, the prevalence of low muscle mass was highly dependent on the applied diagnostic criterion and on the adopted cut-off value; it ranged from 2% to 75% for different BIA-derived criteria. We suggest that muscle ultrasonography provides physiatrists with a practical and accurate tool for identifying individuals with low muscle mass. However, the usability of cut-off values established in our group of healthy younger subjects of white ethnicity to identify low muscle mass in older individuals of different ethnic groups remains to be demonstrated in future studies.


Non-conventional fotemustine schedule as second-line treatment in recurrent malignant gliomas: Survival across disease and treatment subgroup analysis and review of the literature.
Fotemustine (FTM) is a treatment option in recurrent malignant gliomas (MGs) after first-line Stupp treatment. The efficacy and the safety of fractionated FTM schedule proposed by Addeo et al was analysed in the present study in recurrent MGs patients. A retrospective analysis on 40 recurrent MGs patients and second-line fractionated FTM chemotherapy was performed. Response evaluation was assessed using RANO criteria and safety was assessed using CTCAE v.4.03. Subgroup analyses based on MGMT methylation, resurgery and reirradiation were performed. A review of the literature was also performed. The results revealed 5 partial responses (13%) and 19 stable diseases (47%) with a disease-control rate of 60%. Median progression-free survival (PFS) was 4 months, with a PFS of 33% at 6 months and 13% at 1 year. The median overall survival (OS) was 9 months and OS at 6 months was of 55% and at 1 year of 30%. Methylated patients experienced longer mPFS (6 vs. 3 months; p=0.004) and mOS (10 vs. 4 months; p<0.0001) compared with unmethylated patients. Patients treated with reirradiation experienced longer mPFS (5 vs. 3.5 months; p=0.48) and mOS (10 vs. 5 months; p=0.11). No survival benefit with resurgery was observed. Furthermore, the fractioned schedule was well tolerated, only 15% of patients developed severe myelotoxicities. Considering the present findings, fractionated FTM schedule is an efficient second-line option for MGs associated with an acceptable myelotoxicity profile. Additionally, MGMT methylation is associated with improved survival outcomes. However, this study highlights the requirement for further prospective randomized studies on resurgery and reirradiation.


The transcriptome of human oocytes is related to age and ovarian reserve.
How does the human oocyte transcriptome change with age and ovarian reserve? Specific sets of human oocyte messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) are affected independently by age and ovarian reserve. Although it is well established that the ovarian reserve diminishes with increasing age, and that a woman's age is correlated with lower oocyte quality, the interplay of a diminished reserve and age on oocyte developmental competence is not clear. After maturation, oocytes are mostly transcriptionally quiescent, and developmental competence prior to embryonic genome activationrelies on maternal RNA and proteins. A total of 36 vitrified/warmed MII oocytes from 30 women undergoing oocyte donation were included in this study, processed and analyzed individually. Total RNA from each oocyte was independently isolated, amplified, labeled, and hybridized on HTA 2.0 arrays (Affymetrix). Data were analyzed using TAC software, in four groups, each including nine oocytes, according to the woman's age and antral follicular count (AFC) (mean ± SD): Young with High AFC (YH; age 21 ± 1 years and 24 ± 3 follicles); Old with High AFC (OH; age 32 ± 2 years and 29 ± 7 follicles); Young with Low AFC (YL; age 24 ± 2 years and 8 ± 2 follicles); Old with Low AFC (OL; age 34 ± 1 years and 7 ± 1 follicles). qPCR was performed to validate arrays. We identified a set of 30 differentially expressed mRNAs when comparing oocytes from women with different ages and AFC. In addition, 168 non-coding RNAs (ncRNAs) were differentially expressed in relation to age and/or AFC. Few mRNAs have been identified as differentially expressed transcripts, and among ncRNAs, a set of Piwi-interacting RNAs clusters (piRNAs-c) and precursor microRNAs (pre-miRNAs) were identified as increased in high AFC and old groups, respectively. Our results indicate that age and ovarian reserve are associated with specific ncRNA profiles, suggesting that oocyte quality might be mediated by ncRNA pathways. Data can be found via GEO accession number GSE87201. The oldest woman included in the study was 35 years old, thus our results cannot readily be extrapolated to women older than 35 or infertile women. We show, for the first time, that several non-coding RNAs, usually regulating DNA transcription, are differentially expressed in relation to age and/or ovarian reserve. Interestingly, the mRNA transcriptome of in vivo matured oocytes remains remarkably stable across ages and ovarian reserve, suggesting the possibility that changes in the non-coding transcriptome might regulate some post-transcriptional/translational mechanisms which might, in turn, affect oocyte developmental competence. This work was supported by intramural funding of Clinica EUGIN and by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia. J.H. and A.S. are employees of Affymetrix, otherwise there are no competing interests.


Many-Body Theory Calculations of Positron Scattering and Annihilation in H_{2}, N_{2}, and CH_{4}.
The recently developed ab initio many-body theory of positron molecule binding [22J. Hofierka et al., Many-body theory of positron binding to polyatomic molecules, Nature (London) 606, 688 (2022)NATUAS0028-083610.1038/s41586-022-04703-3] is combined with the shifted pseudostates method [A. R. Swann and G. F. Gribakin, Model-potential calculations of positron binding, scattering, and annihilation for atoms and small molecules using a Gaussian basis, Phys. Rev. A 101, 022702 (2020)PLRAAN2469-992610.1103/PhysRevA.101.022702] to calculate positron scattering and annihilation rates on small molecules, namely H_{2}, N_{2}, and CH_{4}. The important effects of positron-molecule correlations are delineated. The method provides uniformly good results for annihilation rates on all the targets, from the simplest (H_{2}, for which only a sole previous calculation agrees with experiment), to larger targets, where high-quality calculations have not been available.


Ceftolozane/tazobactam heteroresistance in cystic fibrosis-related Pseudomonas aeruginosa infections.
Cystic fibrosis (CF) patients are often colonized with Pseudomonas aeruginosa. During treatment, P. aeruginosa can develop subpopulations exhibiting variable in vitro antimicrobial (ABX) susceptibility patterns. Heteroresistance (HR) may underlie reported discrepancies between in vitro susceptibility results and clinical responses to various ABXs. Here, we sought to examine the presence and nature of P. aeruginosa polyclonal HR (PHR) and monoclonal HR (MHR) to ceftolozane/tazobactam in isolates originating from CF pulmonary exacerbations. This was a single-centre, non-controlled study. Two hundred and forty-six P. aeruginosa isolates from 26 adult CF patients were included. PHR was defined as the presence of different ceftolozane/tazobactam minimum inhibitory concentration (MIC) values among P. aeruginosa isolates originating from a single patient specimen. Population analysis profiles (PAPs) were performed to assess the presence of MHR, defined as ≥4-fold change in the ceftolozane/tazobactam MIC from a single P. aeruginosa colony. Sixteen of 26 patient specimens (62%) contained PHR P. aeruginosa populations. Of these 16 patients, 6 (23%) had specimens in which PHR P. aeruginosa isolates exhibited ceftolozane/tazobactam MICs with categorical differences (i.e. susceptible versus resistant) compared to results reported as part of routine care. One isolate, PSA 1311, demonstrated MHR. Canonical ceftolozane/tazobactam resistance genes were not found in the MHR isolates (MHR PSA 1311 or PHR PSA 6130). Ceftolozane/tazobactam PHR exists among P. aeruginosa isolates in this work, and approximately a quarter of these populations contained isolates with ceftolozane/tazobactam susceptibiilty interpretations different from what was reported clinically, supporting concerns surrounding the utility of traditional susceptibility testing methodology in the setting of CF specimens. Genome sequencing of isolates with acquired MHR to ceftolozane/tazobactam revealed variants of unknown significance. Future work will be centred on determining the significance of these mutations to better understand these data in clinical context.


Guidelines for reporting meta-epidemiological methodology research.
Published research should be reported to evidence users with clarity and transparency that facilitate optimal appraisal and use of evidence and allow replication by other researchers. Guidelines for such reporting are available for several types of studies but not for meta-epidemiological methodology studies. Meta-epidemiological studies adopt a systematic review or meta-analysis approach to examine the impact of certain characteristics of clinical studies on the observed effect and provide empirical evidence for hypothesised associations. The unit of analysis in meta-epidemiological studies is a study, not a patient. The outcomes of meta-epidemiological studies are usually not clinical outcomes. In this guideline, we adapt items from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) to fit the context of meta-epidemiological studies.


Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine-Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled, Multicenter Study.
Arterial ex situ back-table perfusion (BP) reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation. Our prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP. The primary endpoint was the incidence of ischemic-type biliary lesions over a follow-up of 2 years after liver transplantation, whereas secondary endpoints included 2-year graft survival, initial graft damage as reflected by transaminase levels, and functional biliary parameters at 6 months after transplantation. A total of 75 livers preserved via standard aortic perfusion and 75 preserved via standard aortic perfusion plus arterial BP were treated using a standardized protocol. The incidence of clinically apparent biliary lesions after liver transplantation (n = 9 for both groups; P = 0.947), the 2-year graft survival rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP, 68%; P = 0.34), and incidence of initial graft injury did not differ between the 2 perfusion modes. Although 33 of the 77 patients with cholangiography workups exhibited injured bile ducts, only 10 had clinical symptoms. Contrary to previous findings, the present study indicated that additional ex situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion injury after liver transplantation. Moreover, there was considerable discrepancy between cholangiography findings regarding bile duct changes and clinically apparent cholangiopathy after transplantation, which should be considered when assessing ischemic-type biliary lesions.


A numerical method for resolving finite mixtures of three-dimensional inter-site distance distributions measured by single-molecule localization microscopy.
The three-dimensional (3D) inter-site distance can be measured by single-molecule localization microscopy. Existing theories and analysis tools for 3D inter-site distance measurement only consider the simplest case where all measured distances are from an identical 3D Rician distribution. There are many problems where the 3D inter-site distance measurement result is made up of multiple components, for example, the measurement of intramolecular distances of deoxyribonucleic acid with multiple possible conformations. In these cases, the overall distance distributions become finite mixtures of 3D Rician distributions (or 3D Rician mixtures). Here, we provide a numerical method using the 3D Rician mixture model to resolve the finite 3D inter-site distance mixtures, which is based on the expectation-maximization algorithm. The proposed method has been tested on simulation data of finite 3D inter-site distance mixtures. The result using the Gaussian mixture model in the developed method is also discussed for comparison.


Erythropoiesis equivalence, pharmacokinetics and immune response following repeat hematide administration in cynomolgus monkeys.
Hematide is a synthetic PEGylated peptidic erythropoiesis stimulating agent (ESA) that is presently being developed for the correction of anemia in patients with chronic renal failure. Unlike currently marketed ESAs, Hematide does not possess any sequence homology to erythropoietin (EPO) and has not elicited moribund immune responses in animal safety studies thereby allowing the generation of a robust safety package. Animals administered marketed ESAs develop anti-EPO antibodies that null the effect of the administered ESA and neutralize endogenous EPO, resulting in severe anemia that precludes the interpretation of chronic safety studies. The primary objective of this study is to determine whether Hematide-specific antibodies are generated when male monkeys are exposed to high Hematide doses (10 mg/kg, intravenous [IV] and subcutaneous [SC]) administered at frequent dosing intervals (every two weeks) for a total of 9 doses; secondary objectives are to evaluate whether developed antibodies impact pharmacokinetics (PK) and pharmacology. In this study, no Hematide-specific antibodies were detected. Hematide exhibits a prolonged plasma half-life and slow clearance by either IV or SC administration. Hematide induced significant erythropoiesis with reticulocytosis and subsequent increases in red blood cells, hematocrit and hemoglobin (Hgb) levels. No erythropoietic differences were noted between the IV and the SC dosed groups with mean +/- SD Hgb levels of 20.9 +/- 2.5 and 20.3 +/- 2.1 g/dL, respectively, occurring on Day 48, corresponding to Hgb increases of 6.5 and 6.7 g/dL, respectively, over pre-dose levels. In conclusion, Hematide is a potent erythropoiesis stimulating agent that exhibits plasma persistence in monkeys. Similar erythropoietic responses were produced following IV and SC administration. The absence of antibody development suggests that Hematide, at the doses and regimen described, has a low immunogenic potential in cynomolgus monkeys.


Exploratory analysis of multi-trait coadaptations in light of population history.
During the process of range expansion, populations encounter a variety of environments. They respond to the local environments by modifying their mutually interacting traits. Common approaches of landscape analysis include first focusing on the genes that undergo diversifying selection or directional selection in response to environmental variation. To understand the whole history of populations, it is ideal to capture the history of their range expansion with reference to the series of surrounding environments and to infer the multitrait coadaptation. To this end, we propose a complementary approach; it is an exploratory analysis using up-to-date methods that integrate population genetic features and features of selection on multiple traits. First, we conduct correspondence analysis of site frequency spectra, traits, and environments with auxiliary information of population-specific fixation index (F ST). This visualizes the structure and the ages of populations and helps infer the history of range expansion, encountered environmental changes, and selection on multiple traits. Next, we further investigate the inferred history using an admixture graph that describes the population split and admixture. Finally, principal component analysis of the selection on edge-by-trait (SET) matrix identifies multitrait coadaptation and the associated edges of the admixture graph. We introduce a newly defined factor loadings of environmental variables in order to identify the environmental factors that caused the coadaptation. A numerical simulation of one-dimensional stepping-stone population expansion showed that the exploratory analysis reconstructed the pattern of the environmental selection that was missed by analysis of individual traits. Analysis of a public dataset of natural populations of black cottonwood in northwestern America identified the first principal component (PC) coadaptation of photosynthesis- vs growth-related traits responding to the geographical clines of temperature and day length. The second PC coadaptation of volume-related traits suggested that soil condition was a limiting factor for aboveground environmental selection.


Pharmacokinetics and acute effect on the renin-angiotensin system of delapril in patients with chronic renal failure.
The acute effect on the renin-angiotensin system and the pharmacokinetic properties of delapril, a new angiotensin converting enzyme inhibitor and its active diacid metabolites (delapril diacid and 5-hydroxy delapril diacid) arising from delapril in vivo were investigated in 4 hypertensive patients with chronic renal failure (CRF: 4 males, average age 49.5 (37-64) years, mean Ccr 22.2 ml/min/1.73 m2) and 9 patients with essential hypertension (EH: 6 males, 3 females, average age 42.8 (28-61) years, mean Ccr 79.3 ml/min/1.73 m2). In CRF, following a single dose of delapril hydrochloride (30 mg), the biological half lives (t1/2) of delapril diacid and 5-OH-delapril diacid were 4.69, 12.88 hours, the maximum serum concentration (Cmax) and the area under the plasma concentration-time curve ([AUC]24(0)) of delapril and its diacid metabolites were 414, 797 and 435 ng/ml, and 658, 6400 and 5068 ng X h/ml, respectively. In EH, the t1/2 of delapril diacid and 5-OH-delapril diacid were 1.21, 1.40 hours and the Cmax and [AUC]24(0) of delapril and its diacid metabolites were 489, 635 and 229 ng/ml, and 572, 1859 and 948 ng X h/ml, respectively. The [AUC]24(0) in CRF were significantly increased as compared with those in EH. The cumulative urinary excretions were significantly lower in CRF than in EH. The serum angiotensin converting enzyme (ACE) was markedly inhibited in both groups up to 24 hours. The plasma concentration of angiotensin II decreased in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


The relation of microbiologic data to aspartate aminotransferase enzyme activity in gingival crevicular fluid.
Gingival crevicular fluid (GCF), reflects the immune and inflammatory reactions and is itself a location for specific host-microbe interactions that lead to periodontal diseases. Aspartate aminotransferase (AST) is one of the components of GCF that is released as a result of cell death. In this study, 40 periodontal sites in 10 early onset periodontitis patients before and after nonsurgical periodontal therapy, with and without local metronidazole administration, were first examined for the AST enzyme levels in GCF and then evaluated for microbiological and clinical variables. In each patient, 4 sites (one site/quadrant) with a probing depth of > or = 5 mm were selected and treated with separate treatment protocols. Certain microbial species including Prevotella intermedia, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans(A. a.) were found more often and/or in higher levels in AST active sites (36/40 first measurement--9/36 second measurement), while other species (Streptococcus and Actinomyces) were found more often and/or in higher levels in AST inactive sites (4/40 first measurement--8/36 second measurement). Eight post-treatment AST active sites revealed 1.5 mm of attachment loss, whereas 8 post-treatment AST inactive sites showed 1.37 mm of attachment gain. AST activity and microbiological-clinical data presenting such an agreement suggests that, AST level assessment would be beneficial as an adjunctive method alongside other clinical criteria, in guiding the clinician in periodontal treatment.


Serotonin inhibits gastric acid secretion through a 5-hydroxytryptamine1-like receptor in the rat.
5-Hydroxytryptamine (serotonin, 5-HT) is released from the gastrointestinal tract by vagal stimulation. This biogenic amine produces many alterations in gastric functional parameters, including inhibition of gastric acid secretion. This study was designed to characterize the 5-HT receptor subtype modulating gastric acid secretion. In urethane-anesthetized acute gastric fistula rats, systemic 5-HT (3.5 mumol/kg i.v.) inhibited acid output stimulated by pentagastrin infusion by 58%. Close gastric intra-arterial (i.a.) injection of methysergide, methiothepin, metergoline or spiperone but not tropisetron, renzapride or ritanserin was effective in reversing 5-HT-induced inhibition of acid secretion. Close i.a. administration of the potent 5-HT1A/1B antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine displayed partial agonist properties in this model, but did not antagonize 5-HT-induced inhibition of acid output. In a study of 5-HT agonists given close i.a. to the gastric circulation, 5-HT (0.88 mumol/kg) inhibited acid secretion by 48%. A 3-fold higher dose (2.6 mumol/kg) of the general 5-HT1 agonist, 5-carboxamidotryptamine (5-CT), was needed to inhibit acid secretion significantly. In contrast, neither the selective 5-HT1A agonist (+-)-8-hydroxy-2-(n-dipropylamino)-tetralin nor 5-HT2 agonist (+-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (0.88 or 2.6 mumol/kg) attenuated gastric acid secretion. Thus, the data suggest that the site mediating inhibition of acid secretion by exogenous 5-HT belongs to the 5-HT1 family, but may not be of the 5-HT1A subtype.


Mutational analysis of peptidyl carrier protein and acyl carrier protein synthase unveils residues involved in protein-protein recognition.
4'-Phosphopantetheinyl transferases (PPTases) are essential for the production of fatty acids by fatty acid synthases (primary metabolism) and natural products by nonribosomal peptide synthetases and polyketide synthases (secondary metabolism). These systems contain carrier proteins (CPs) for the covalent binding of reaction intermediates during synthesis. PPTases transfer the 4'-phosphopantetheine moiety from coenzyme A (CoA) onto conserved serine residues of the apo-CPs to convert them to their functionally active holo form. In bacteria, two types of PPTases exist that are evolutionary related but differ in their substrate spectrum. Acyl carrier protein synthases (AcpSs) recognize CPs from primary metabolism, whereas Sfp- (surfactin production-) type PPTases have a preference for CPs of secondary metabolism. Previous investigations showed that a peptidyl carrier protein (PCP) of secondary metabolism can be altered to serve as substrate for AcpS. We demonstrate here that a single mutation in PCP suffices for the modification of this CP by AcpS, and we have identified by mutational analysis several other PCP residues and two AcpS residues involved in substrate discrimination by this PPTase. These altered PCPs were still capable of serving their designated function in NRPS modules, and selective use of AcpS or Sfp leads to production of two different products by a trimodular NRPS.


Simultaneous determination of antiretroviral drugs in human hair with liquid chromatography-electrospray ionization-tandem mass spectrometry.
The determination of the concentrations of antiretroviral drugs in hair is believed to be an important means for the assessment of the long-term adherence to highly active antiretroviral therapy. At present, the combination of tenofovir, lamivudine and nevirapine is widely used in China. However, there was no research reporting simultaneous determination of the three drugs in hair. The present study aimed to develop a sensitive method for simultaneous determination of the three drugs in 2-mg and 10-mg natural hair (Method 1 and Method 2). Hair samples were incubated in methanol at 37 °C for 16 h after being rinsed with methanol twice. The analysis was performed on high performance liquid chromatography tandem mass spectrometry with electronic spray ionization in positive mode and multiple reactions monitoring. Method 1 and Method 2 showed the limits of detection at 160 and 30 pg/mg for tenofovir, at 5 and 6 pg/mg for lamivudine and at 15 and 3 pg/mg for nevirapine. The two methods showed good linearity with the square of correlation coefficient >0.99 at the ranges of 416-5000 and 77-5000 pg/mg for tenofovir, 12-5000 and 15-5000 pg/mg for lamivudine and 39-50,000 and 6-50,000 pg/mg for nevirapine. They gave intra-day and inter-day coefficient of variation <15% and the recoveries ranging from 80.6 to 122.3% and from 83.1 to 114.4%. Method 2 showed LOD and LOQ better than Method 1 for tenofovir and nevirapine and matched Method 1 for lamivudine, but there was high consistency between them in the determination of the three drugs in hair. The population analysis with Method 2 revealed that the concentrations in hair were decreased with the distance of hair segment away from the scalp for the three antiretroviral drugs.


In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Menière's Disease Ears and Normal Hearing Ears.
Analysis of neural structures in Menière's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this patient group but has yet to be confirmed. This protocol describes a method of in vivo evaluation of neural changes especially well suitable for cranial nerve analysis using magnetic resonance imaging (MRI). MD-patients and normal hearing persons were examined in a 3-T MR-scanner using a scan protocol including strongly T2-weighted 3D gradient-echo-sequence (3D-CISS). In the patient group, MD was additionally confirmed using MRI-based assessment of endolymphatic hydrops. Morphometric analysis was performed using a freeware DICOM viewer. Evaluation of cranial nerves included measurements of cross-sectional areas (CSAs) of the nerves at different levels as well as orthogonal diametric measurements.


Integrated single-cell transcriptomic and epigenetic study of cell state transition and lineage commitment in embryonic mouse cerebellum.
Recent studies using single-cell RNA-sequencing have revealed cellular heterogeneity in the developing mammalian cerebellum, yet the regulatory logic underlying this cellular diversity remains to be elucidated. Using integrated single-cell RNA and ATAC analyses, we resolved developmental trajectories of cerebellar progenitors and identified putative trans- and cis-elements that control cell state transition. We reverse engineered gene regulatory networks (GRNs) of each cerebellar cell type. Through in silico simulations and in vivo experiments, we validated the efficacy of GRN analyses and uncovered the molecular control of a posterior transitory zone (PTZ), a distinct progenitor zone residing immediately anterior to the morphologically defined rhombic lip (RL). We showed that perturbing cell fate specification in the PTZ and RL causes posterior cerebellar vermis hypoplasia, the most common cerebellar birth defect in humans. Our study provides a foundation for comprehensive studies of developmental programs of the mammalian cerebellum.


Nonlinear spectrotemporal sound analysis by neurons in the auditory midbrain.
The auditory system of humans and animals must process information from sounds that dynamically vary along multiple stimulus dimensions, including time, frequency, and intensity. Therefore, to understand neuronal mechanisms underlying acoustic processing in the central auditory pathway, it is essential to characterize how spectral and temporal acoustic dimensions are jointly processed by the brain. We use acoustic signals with a structurally rich time-varying spectrum to study linear and nonlinear spectrotemporal interactions in the central nucleus of the inferior colliculus (ICC). Our stimuli, the dynamic moving ripple (DMR) and ripple noise (RN), allow us to systematically characterize response attributes with the spectrotemporal receptive field (STRF) methods to a rich and dynamic stimulus ensemble. Theoretically, we expect that STRFs derived with DMR and RN would be identical for a linear integrating neuron, and we find that approximately 60% of ICC neurons meet this basic requirement. We find that the remaining neurons are distinctly nonlinear; these could either respond selectively to DMR or produce no STRFs despite selective activation to spectrotemporal acoustic attributes. Our findings delineate rules for spectrotemporal integration in the ICC that cannot be accounted for by conventional linear-energy integration models.


Bridging Therapy Versus Direct Mechanical Thrombectomy in Patients with Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: A Clinical- Histological Analysis of Retrieved Thrombi.
Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.


Analysis by capillary electrophoresis of the kinetics of charge ladder formation for bovine carbonic anhydrase.
A series of charge ladders of bovine carbonic anhydrase II were synthesized and the relative abundances of the rungs analyzed by capillary electrophoresis as a function of the quantity of acylating agent used. A simulation that models the kinetics of formation of the members of the charge ladders is described. The observed rate constants decreased as the extent of acylation increased. These rate constants correlated adequately with theoretical rate constants calculated using Debye-Hückel theory. The data are compatible with, but do not demand, a model for the formation of this charge ladder in which all unacetylated amino groups in each rung have indistinguishable reactivity and in which the reactivity of the amines in each rung decreases as the net charge on the protein increases; in this model, decreased reactivity is due to increased extent of protonation. This agreement between experiment and model suggests that the charge shielding that results from an ionic strength of 130 mM is not sufficient to suppress the influence of the increasingly negative charge of the protein with acetylation on the extent of protonation of Lys epsilon-NH2 groups.


Health workers' and hospital administrators' perspectives on mistreatment of women during facility-based childbirth: a multicenter qualitative study in Ghana.
Globally, mistreatment of women during facility-based childbirth continues to impact negatively on the quality of maternal healthcare provision and utilization. The views of health workers are vital in achieving comprehensive understanding of mistreatment of women, and to design evidence-based interventions to prevent it. We explored the perspectives of health workers and hospital administrators on mistreatment of women during childbirth to identify opportunity for improvement in the quality of maternal care in health facilities. A qualitative study comprising in-depth interviews (IDIs) with 24 health workers and hospital administrators was conducted in two major towns (Koforidua and Nsawam) in the Eastern region of Ghana. The study was part of a formative mixed-methods project to develop an evidence-based definition, identification criteria and two tools for measuring mistreatment of women in facilities during childbirth. Data analysis was undertaken based on thematic content via the inductive analytic framework approach, using Nvivo version 12.6.0. Health workers and hospital administrators reported mixed feelings regarding the quality of care women receive. Almost all respondents were aware of mistreatment occurring during childbirth, describing physical and verbal abuse and denial of preferred birthing positions and companionship. Rationalizations for mistreatment included limited staff capacity, high workload, perceptions of women's non-compliance and their attitudes towards staff. Health workers had mixed responses regarding the acceptability of mistreatment of women, although most argued against it. Increasing staff strength, number of health facilities, refresher training for health workers and adequate education of women about pregnancy and childbirth were suggestions to minimize such mistreatment. Health workers indicated that some women are mistreated during birth in the study sites and provided various rationalizations for why this occurred. There is urgent need to motivate, retrain or otherwise encourage health workers to prevent mistreatment of women and promote respectful maternity care. Further research on implementation of evidence-based interventions could help mitigate mistreatment of women in health facilities.


Community based screening for sickle haemoglobin among pregnant women in Benue State, Nigeria: I-Care-to-Know, a Healthy Beginning Initiative.
Haemoglobin genotype screening at prenatal care offers women an opportunity to be aware of their genotype, receive education on sickle cell disease (SCD) and may increase maternal demand for SCD newborn screening. In developed countries, most pregnant women who access prenatal care and deliver at the hospital receive haemoglobin genotype screening. In settings with low prenatal care attendance and low hospital deliveries, community-based screening may provide similar opportunity for pregnant women. We assessed the feasibility and acceptability of integrating haemoglobin genotype screening into an existing community-based HIV program. Onsite community-based integrated testing for HIV, hepatitis B virus and haemoglobin electrophoresis, were conducted for pregnant women and their male partners. Community Health Advisors implementing the NIH and PEPFAR-supported Healthy Beginning Initiative (HBI) program provided education on SCD, collected blood sample for haemoglobin electrophoresis and provided test results to participants enrolled into the HBI program. We concurrently conducted a cross-sectional study using a pretested, semi-structured, interviewer administered questionnaire to collect demographic data and assess awareness of individual haemoglobin "genotype" among HBI pregnant women participants. In this study, 99.9% (10,167/10,168) of pregnant women who received education on SCD accepted and completed the survey, had blood drawn for haemoglobin electrophoresis and received their results. A majority of participating pregnant women (97.0%) were not aware of their haemoglobin "genotype". Among the participants who were incorrect about their haemoglobin "genotype", 41.1% (23/56) of women who reported their haemoglobin "genotype" as AA were actually AS. The odds of haemoglobin "genotype" awareness was higher among participants who were in younger age group, completed tertiary education, had less number of pregnancies, and attended antenatal care. Overall prevalence of sickle cell trait (AS) was 18.7%. It is feasible to integrate haemoglobin "genotype" testing into an existing community-based maternal-child program. Most pregnant women who were unaware of their haemoglobin "genotype" accepted and had haemoglobin genotype testing, and received their test results. Increasing parental awareness of their own haemoglobin "genotype" could increase their likelihood of accepting newborn screening for SCD.


Ross operation for bicuspid aortic valve disease in adults: is it a valid surgical option?
The validity of the Ross operation as freestanding root replacement in adult patients with bicuspid aortic valve disease has lately been questioned. We have analyzed retrospectively our results in 23 adult patients (19 males) operated for bicuspid aortic valve disease ad modum "Ross" employing a freestanding root replacement technique. In 9 patients the dominant aortic valve lesion was stenotic (aortic stenosis group) and in the remaining 14 patients it was aortic insufficiency (aortic insufficiency group). The fate of the pulmonary autograft in the two groups was studied. The intraoperatively measured aortic and pulmonary annuli diameters from the two groups were compared with those from a population of normal looking aortic and pulmonary valves matched for body surface area. The aortic insufficiency group needed significant reduction of the aortic annulus diameter to conform to the size of the pulmonary autograft. The pulmonary autograft annuli in this group were significantly larger in diameter than the ones in the aortic stenosis group. The mean pulmonary annulus diameter in the aortic stenosis group was, on the other hand, significantly smaller when compared with that in the normal matched population. After a mean follow-up period of about 19 months, the aortic insufficiency group showed significant dilatation of the neo-aortic sinuses. Between the two groups, the remaining echocardiographic variables remained either stable or improved at follow-up. Pre-existing larger diameters of the aortic and pulmonary annuli in the aortic insufficiency group combined with the significantly increased left ventricular end-diastolic diameters, may predispose these patients to significant dilatation of the unsupported aortic sinuses after a Ross operation. This dilatation does not, however, lead to increase in the autograft valve insufficiency at short-term follow-up if the aortic annulus and the distal ascending aorta are tailored to the size of the pulmonary autograft. Ross operation, employing freestanding aortic root replacement technique, may therefore be recommended in adult patients with bicuspid aortic valve disease with excellent short-term results.


Synchrotron X-ray and ab initio studies of beta-Si3N4.
Almost absorption- and extinction-free single-crystal synchrotron X-ray diffraction data were measured at 150, 200 and 295 K for beta-Si3N4, silicon nitride, at a wavelength of 0.7 A. The true symmetry of this material has been the subject of minor controversy for several decades. No compelling evidence favouring the low-symmetry P6(3) model was identified in this study.


A microfluidic device for uniform-sized cell spheroids formation, culture, harvesting and flow cytometry analysis.
Culture of cells as three-dimensional (3D) aggregates, named spheroids, possesses great potential to improve in vitro cell models for basic biomedical research. However, such cell spheroid models are often complicated, cumbersome, and expensive compared to conventional Petri-dish cell cultures. In this work, we developed a simple microfluidic device for cell spheroid formation, culture, and harvesting. Using this device, cells could form uniformly sized spheroids due to strong cell-cell interactions and the spatial confinement of microfluidic culture chambers. We demonstrated cell spheroid formation and culture in the designed devices using embryonic stem cells, carcinoma cells, and fibroblasts. We further scaled up the device capable of simultaneously forming and culturing 5000 spheroids in a single chip. Finally, we demonstrated harvesting of the cultured spheroids from the device with a simple setup. The harvested spheroids possess great integrity, and the cells can be exploited for further flow cytometry assays due to the ample cell numbers.


Cerebrospinal fluid GAP-43 in early multiple sclerosis.
Novel biomarkers identifying and predicting disease activity in multiple sclerosis (MS) would be valuable for primary diagnosis and as outcome measures for monitoring therapeutic effects in clinical trials. Axonal loss is present from the earliest stages of MS and correlates with disability measures. Growth-associated protein 43 (GAP-43) is a presynaptic protein with induced expression during axonal growth. We hypothesized this protein could serve as a biomarker of axonal regeneration capacity in MS. We developed a novel GAP-43 enzyme-linked immunosorbent assay for quantification in cerebrospinal fluid (CSF) and measured GAP-43 levels in 71 patients with clinically isolated syndrome, 139 MS patients and 51 controls. GAP-43 concentrations were similar in patients and controls. Nevertheless, GAP-43 levels were higher in patients with >10 T2-magnetic resonance imaging (MRI) lesions (p = 0.005). CSF GAP-43 concentrations correlated with CSF mononuclear cell counts (p = 0.031) and were inversely correlated with patient age (p = 0.038) with a trend for higher CSF GAP-43 concentrations in patients with gadolinium-enhancing MRI lesions and positive CSF oligoclonal immunoglobulin G status. Our results suggest that axonal regeneration capacity is relatively preserved in early MS. CSF GAP-43 concentration is positively associated with markers of inflammation, suggesting possible inflammatory-driven expression of this growth-associated protein in early MS.


Sulfite oxidase deficiency--an unusual late and mild presentation.
Sulfite oxidase deficiency (SOD) is an autosomal recessive inherited disease usually presenting in the neonatal period with severe neurological symptoms including seizures, often refractory to anticonvulsant therapy, and a rapidly progressive encephalopathy resembling neonatal hypoxic ischemia, with premature death. Most patients develop dislocated ocular lenses. Later or milder presentations of SOD are being reported with increasing frequency. These presentations include neurological regression with loss of previously acquired milestones or movement disorders. We report a four years old girl presenting with intermittent ataxia and uncoordinated limb movements. A similar episode of ataxia had occurred previously, one year before, with complete neurologic recovery and normal developmental milestones. Bilateral lens dislocation had been recently diagnosed. Cranial MRI demonstrated bilateral globus pallidus enhancement. Low homocysteine was found in plasma and Sulfitest(R) was positive. Further investigations led to confirmation of isolated sulfite oxidase deficiency with no enzyme activity detected on skin fibroblasts culture. This case illustrates the clinical variability of SOD and it is not only atypical but also seems to be the mildest form described so far. The association of ectopia lentis with a movement disorder, even without psychomotor regression, should prompt us to look for this diagnosis.


Carbon nanotubes induce granulomas but not mesotheliomas.
Different types of carbon nanotubes may represent toxic hazards due to their size distribution and massive surface area. They may adsorb other toxic agents that can consequently be transported into the body. Hence the aim of this study was to confirm or reject the hypothesis of carcinogenicity of two types of carbon nanotubes. Well-defined single-walled and multi-walled carbon nanotubes were studied in a specific animal model for mesothelioma induction. Short-term pilot studies were published on the asbestos fibre-like mesothelioma-inducing effects of carbon nanotubes based on the proposed mechanistic correlation on health effects of fibres of the same size. Our results with a simple in vivo, peritoneal exposure model refute such an interpretation. The present studies with rats indicate that early granuloma formation does not lead to the development of mesotheliomas during chronic exposure of peritoneal mesothelium to either single- or multi-walled carbon nanotubes of varied size. Due to the limited toxicity data on carbon nanotubes, these results may be particularly important for risk assessment purposes.


Development, Validation, and Feasibility Testing of a Yoga Module for Opioid Use Disorder.
Opioid use disorder (OUD) involves excessive use of opioids-such as heroin, morphine, fentanyl, codeine, oxycodone, and hydrocodone-leading to major health, social, and economic consequences. Yoga lifestyle interventions have been found to be useful as adjunct therapies in management of substance use disorders and chronic pain conditions. The research team intended to develop, validate, and test for feasibility a yoga program for OUD patients that could reduce opiate withdrawal symptoms-such as pain, fatigue, low mood, anxiety and sleep disturbances-and cravings associated with drugs. The research team first performed a literature review of traditional and contemporary yoga texts, such as Hatha Yoga Pradipika and Light on Yoga, as well as modern scientific literature in the following search engines-Google Scholar, PubMed, and PsychInfo, using the keywords yoga, pranayama, hatha yoga, relaxation. meditation, substance use, addiction, impulsivity, craving, sleep quality, and fatigue. Using the information obtained, the team developed a yoga program and designed a pilot study that used the program. The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bangalore, India. Participants in the pilot study were 8 inpatients, 6 males and 2 females, who were on opioid agonist treatment (buprenorphine) for OUD. The intervention was the yoga program previously validated by the research team. In the pilot study, participants were taught a one-hour, yoga-based intervention, with sessions occurring once per day, for 10 sessions. For validation, 13 experts scored the yoga program that the research team had developed and gave suggestions for each yogic practice for use during the acute phase of withdrawal and the maintenance phase respectively. A content validity ratio (CVR) was calculated from their scoring, and the research team made changes to the program base on the scoring and suggestions. For the pilot study, assessments occurred at baseline and postintervention. The participants' yoga performance was rated by the yoga trainer on a yoga performance assessment scale (YPA). Other measurements included: (1) the Clinical Opiate Withdrawal Scale (COWS), (2) the Hamilton's anxiety rating scale (HAM-A), (3) the Hamilton's depression rating scale (HAM-D), (4) buprenorphine dosage, (5) the Clinical Global Impression Severity (CGI-S) scale, (6) a visual analog scale (VAS) for pain, (7) sleep quality (latency and duration), and (8) the module's safety. Four practices were removed from the program due to CVR scores below the cutoff, and one practice was found not to be feasible (Kapalabhati). Two categories of yoga modules emerged: (1) for the acute symptomatic phase (40 minutes) and (2) for the maintenance phase (one hour). Practices were added or excluded based on the phase. The yoga module that was developed for reducing withdrawal symptoms and cravings in OUD patients was found to be safe, feasible, and potentially useful as an adjunct therapy to conventional treatment.


[Classification of periodontal diseases].
During the past centuries the basic understanding of periodontal disease and the concepts of etiopathogenesis have evolved and substantially changed. The changes in paradigm has always been followed by the conceptual changes in the classification of periodontal disease. The earliest entirely descriptive classifications were based on the clinical signs and symptoms of periodontal disease. These were followed by a classification system based on the classical pathology paradigm established by Orban and Gottlieb. This was replaced by the next classification reflecting the infection/host response paradigm during the late '60s started with the pioneering works by Loe and coworkers. It is because many data indicated that the host response (determined by genetics, immunology and behavioral factors) was at least as important in the clinical manifestation of periodontal destruction than the bacterial biofilm this classification had been also updated. The AAP published its latest official classification system in 1999. Nevertheless this new system is far from perfect and should evolve as soon as enough data are collected by periodontal research to answer many controversy still existing to day.


Revealing the Wonder of Natural Photonics by Nonlinear Optics.
Nano-optics explores linear and nonlinear phenomena at the nanoscale to advance fundamental knowledge about materials and their interaction with light in the classical and quantum domains in order to develop new photonics-based technologies. In this perspective article, we review recent progress regarding the application of nonlinear optical methods to reveal the links between photonic structures and functions of natural photonic geometries. Furthermore, nonlinear optics offers a way to unveil and exploit the complexity of the natural world for developing new materials and technologies for the generation, detection, manipulation, and storage of light at the nanoscale, as well as sensing, metrology, and communication.


Sporotrichosis: Part II.
Sporotrichosis is a subcutaneous mycosis of implantation. It is the only subcutaneous mycosis for which direct examination or histology is of little or no value for diagnosis. The diagnosis solely rests on the isolation of Sporothrix schenckii in culture. On pathologic examination, causative organisms are rarely seen. Staining with fluorescent-labeled antibodies may aid in visualizing the cigar-shaped yeast forms; however, the organisms are still difficult to identify. Topical therapy is not effective. Potassium iodide is an effective treatment for sporotrichosis, but this agent has not been subjected to specific treatment trials comparing its efficacy against azoles or allylamine alternatives. Itraconazole is generally safe and well tolerated, and the relapse rate is low. Terbinafine could be another therapeutic alternative to treat the disease. Since 1998, researchers from Brazil suggested that feline transmission of sporotrichosis in Rio de Janeiro city was associated with a large and long-lasting outbreak of the disease. To understand the outbreak, there have been studies on the epidemiology and antifungal susceptibility of the S schenckii strains through molecular diagnosis. Data suggest that all isolated strains were genetically related.


Sternocleidomastoid Muscle Flap after Parotidectomy.
Introduction Most patients after either superficial or total parotidectomy develop facial deformity and Frey syndrome, which leads to a significant degree of patient dissatisfaction. Objective Assess the functional outcome and esthetic results of the superiorly based sternocleidomastoid muscle (SCM) flap after superficial or total parotidectomy. Methods A prospective cohort study for 11 patients subjected to parotidectomy using a partial-thickness superiorly based SCM flap. The functional outcome (Frey syndrome, facial nerve involvement, and ear lobule sensation) and the esthetic results were evaluated subjectively and objectively. Results Facial nerve palsy occurred in 5 cases (45%), and all of them recovered completely within 6 months. The Minor starch iodine test was positive in 3 patients (27%), although only 1 (9%) subjectively complained of gustatory sweating. The designed visual analog score completed by the patients themselves ranged from 0 to 3 with a mean of 1.55 ± 0.93; the scores from the blinded evaluators ranged from 1 to 3 with a mean 1.64 ± 0.67. Conclusion The partial-thickness superiorly based SCM flap offers a reasonable cosmetic option for reconstruction following either superficial or total parotidectomy by improving the facial deformity. The flap also lowers the incidence of Frey syndrome objectively and subjectively with no reported hazard of the spinal accessory nerve.


The role of the chinchilla pinna and ear canal in electrophysiological measures of hearing thresholds.
Measurements of the acoustic transfer function (ATF) of the pinnae of 8 chinchillas were compared with the auditory-evoked potential (AEP) thresholds of 16 chinchillas measured in free field and with insert earphones. The ATF was measured in anesthetized chinchillas in a far-field condition in a semi-anechoic room using a logarithmic frequency sweep from 100 Hz to 20 kHz. Probe microphone measurements were collected with the probe opening at the tympanic membrane and in the same approximate position with the chinchilla removed from the sound field. For each animal's acoustic transfer function, the average of five in-the-ear and three free-field measurements were determined. The ATF exhibited a 5-dB passive gain at about 1 kHz and a broad resonance between 2.5 and 6 kHz of about a 10-dB gain. AEP thresholds were obtained from monaural chronically implanted chinchillas at 0.5, 1, 2, 4, and 8 kHz using first free-field and then insert earphone stimuli. The free-field sound pressure was measured with a microphone in the approximate position of the chinchilla's head. The earphone sound pressures were measured with a probe microphone positioned near the tympanic membrane. The free-field AEP hearing thresholds exhibited +10-dB gain at 4 kHz compared to the insert earphone AEP thresholds. The agreement between the ATF and AEP derived transfer function suggested that the threshold differences at 4 kHz between the two testing configurations can be accounted for by the pinna and ear canal gain.


Expression of E-cadherin and alpha- and beta-catenin mRNAs in ovarian cancers.
To know the biological role of the adherens junction, mainly consisting of E-cadherin and alpha- and beta-catenins, associated with invasion and metastasis of ovarian cancers, we studied the expressions of E-cadherin and alpha- and beta-catenin mRNAs in the cancers in comparison with those in normal counterparts. The integral expression of E-cadherin and alpha- and, beta-catenin mRNAs was suppressed in the metastatic lesions of advanced ovarian cancers, while it was not in the primary tumors. Therefore, the suppressed expression of main adhesion molecules in the adherens junction might contribute to adherens junctional dysfunction, which might lead to the acquirement of invasiveness and metastatic potential by advanced ovarian cancers as one of the rate-limiting steps.


Development of flexible antimicrobial films using essential oils as active agents.
The antimicrobial activity in the vapor-phase of laboratory-made flexible films of polypropylene (PP) and polyethylene/ethylene vinyl alcohol copolymer (PE/EVOH) incorporating essential oil of cinnamon ( Cinnamomum zeylanicum), oregano ( Origanum vulgare), clove ( Syzygium aromaticum), or cinnamon fortified with cinnamaldehyde was evaluated against a wide range of microorganisms: the Gram-negative bacteria Escherichia coli, Yersinia enterocolitica, Pseudomonas aeruginosa, and Salmonella choleraesuis; the Gram-positive bacteria Listeria monocytogenes, Staphylococcus aureus, Bacillus cereus, and Enterococcus faecalis; the molds Penicillium islandicum, Penicillium roqueforti, Penicillium nalgiovense, Eurotium repens, and A spergillus flavus and the yeasts Candida albicans, Debaryomyces hansenii, and Zigosaccharomyces rouxii. Films with a nominal concentration of 4% (w/w) of fortified cinnamon or oregano essential oil completely inhibited the growth of the fungi; higher concentrations were required to inhibit the Gram-positive bacteria (8 and 10%, respectively), and higher concentrations still were necessary to inhibit the Gram-negative bacteria. PP films were more effective than PE/EVOH films. The atmospheres generated by the antimicrobial films inside Petri dishes were quantitatively analyzed using headspace-single drop microextraction (HS-SDME) in combination with gas chromatography-mass spectrometry (GC-MS). The analyses showed that the oregano-fortified PP films released higher levels of carvacrol and thymol, and the cinnamon-fortified PP films released higher levels of cinnamaldehyde, during the first 3-6 h of incubation, than the corresponding PE/EVOH films. Shelf-life tests were also performed, demonstrating that the antifungal activities of the films persisted for more than two months after their manufacture. In addition, migration tests (overall and specific) were performed, using both aqueous and fatty simulants, to ensure that the films meet EU regulations regarding food contact materials. Following contact with the tested films, the substances that had migrated into the aqueous simulants were recovered by direct immersion-single drop extraction (DI-SDME) and then analyzed by GC-MS. The fatty stimulant (isooctane) was directly injected into the chromatographic system.


Preparation and characterization of a new monoclonal antibody CAF7 specific for a leukocyte activation antigen.
A new murine hybridoma, CAF7, is raised using as an antigen the T-leukemic cell line CEM. It produces a monoclonal antibody (mAb) specific for an activation antigen on human lymphocytes. CAF7 stains monocytes, very weakly resting lymphocytes, and granulocytes, part of the thrombocytes, but not erythrocytes. After activation with phytohemagglutinin (PHA), CAF7 expression on peripheral lymphocytes rises as early as 5 hr post stimulation and 72-hr blasts express it at a considerable level. The cell lines Jurkat, CEM, MOLT4, Raji, Reh, K562, and MONOMAC6 are positive for CAF7. CAF7 immunoprecipitated an antigen, which when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions migrated as a single band with a molecular weight of 120-140 kD. Under reducing conditions, it appears as two bands at 90-100 and 40 kD. The pattern of expression and the biochemical characteristics of CAF7 do not match any of the clusters defined in the Leukocyte Typing Workshops, but do resemble that of a previously described antigen, 4F2.


Preliminary effects of a WeChat-based educational intervention on social participation among older adults in a community.
The social participation of older people should be encouraged, as it is fundamental to their well-being and the practice of aged care. Therefore, the ability of older persons to participate in society should be strengthened. To evaluate the preliminary effects of a WeChat-based educational intervention on the social participation of community-dwelling older adults in China. This study was a quasi-experimental design. Twenty-eight community-dwelling older adults participated in a WeChat-based educational intervention. The intervention contents included concepts and preparation of social participation, analysis of participation resources and capabilities, technological adaptation, emotional management, setting of to-do lists, etc. Social participation, self-worth and subjective well-being were measured via the WeChat application on smartphones at baseline, immediately after the intervention, and a 3-month follow-up. We analysed data using paired t-tests and analysis of variance (ANOVA). We found statistically significant improvements in social participation (active aging) (F = 4.408; p < .05) as well as the self-worth dimensions of moral worth (F = 4.135; p < .05) and psychological worth (F = 3.234; p < .05), and the negative-affect dimension of subjective well-being being decreased (F = 2.484; p < .05). The WeChat-based education intervention can effectively improve social participation and self-worth, and may provide effective preventive healthcare solutions for older adults in China. The enormous value of the social participation of independent older adults must be recognised. Nurses can use smartphones to deliver health and social participation information in routine programs in aged care.


The Pocket-Creation Method Facilitates Endoscopic Submucosal Dissection of Gastric Neoplasms Along the Lesser Curvature at the Gastric Angle.
Endoscopic submucosal dissection (ESD) of superficial gastric lesions located along the lesser curvature at the gastric angle is a challenging situation due to paradoxical movement and a protruding angle. The pocket-creation method (PCM) can overcome this difficulty by stabilizing the tip of the endoscope in the pocket and minimizing insufflation of the stomach, which enables horizontal and straight dissection. This study aims to clarify whether the PCM improves the technical outcomes of ESD of superficial gastric neoplasms along the lesser curvature at the angle. From October 2006 to June 2021, 158 gastric lesions along the lesser curvature at the angle were resected with needle-type knives. We retrospectively reviewed the records and divided them into the PCM group (n = 61) and the conventional method (CM) group (n = 97). The primary outcome measurement was dissection speed (in mm2/min). The two groups were not significantly different for baseline characteristics such as macroscopic type and size except for the proportion of adenomas. The proportion of expert endoscopists was not significantly different between the two groups (P = 0.141). The dissection speed was significantly faster in the PCM group than in the CM group (P = 0.001). There were no holes in the resected specimens in the PCM group, while five lesions in the CM group (5%) had a hole (P = 0.182). There were no significant differences in the incidence of adverse events. This is the first study to show that the PCM outperforms the CM for ESD of lesions located along the lesser curvature at the gastric angle. The PCM facilitated ESD of these lesions by significantly increasing dissection speed when a needle-type knife is used with no increase in adverse events.


Role of gap junctions in the contractile response to agonists in the mesenteric resistance artery of rats with acute hypoxia.
Hypoxic exposure results in the vascular dysfunction and reduction of vasomotor responses and thus disrupts or reduces blood flow in the resistance arteries. Connexin (Cx)-mediated gap junctional intercellular communication (GJIC) serves a critical role in the regulation of vasomotor tone and the synchronized contraction of arteries, however whether the adverse effect of hypoxia on vasomotor responses in vascular smooth muscle layer of resistance arteries is involved in changes in the GJIC and the expression of Cx43 and Cx45 remains to be elucidated. Pressure myography, whole-cell patch clamp and western blot analysis were used to investigate the differences in expression and function of gap junction (GJ) in the vascular smooth muscle cells (VSMCs) of the mesenteric resistance artery (MRA) from Sprague‑Dawley (SD) rats in normoxia and acute hypoxia groups. In the present study, whole‑cell patch clamp measurements demonstrated a significant reduction in the membrane capacitance and conductance in the VSMCs of the MRAs in the acute hypoxia (5 min) group (n=13) compared with the normoxia group (n=13), which suggested that exposure to acute hypoxia of 5 min decreased the coupling of the GJ between the VSMCs of MRAs in SD rats. Pressure myographic analysis demonstrated that 0.1‑100 µM phenylephrine (PE)‑induced MRA vasoconstriction was less sensitive under the acute hypoxic condition (n=7) compared with the normoxia condition (n=9) following treatment with 100 µM 2‑aminoethoxydiphenyl borate for 20 min. Compared with SD rats under normoxia, the PE‑initiated vasoconstrictive frequency and amplitude under acute hypoxia for 20, 40 and 60 min in the MRAs of SD rats was markedly attenuated (n=7). The results of western blot analysis indicated that the expression levels of Cx43 and Cx45 in MRA under acute hypoxia (1 h) were lower compared with normoxia. Cx43‑and Cx45‑mediated GJs serve a significant role in the regulation of the vasomotor function of MRA during hypoxia and may be essential for the adjustment of vasomotor tone in response to acute hypoxia.


Feasibility of computerized adventitious respiratory sounds to assess the effects of airway clearance techniques in patients with bronchiectasis.
Objective: To examine the feasibility of adventitious respiratory sound (ARS) as an outcome measure to assess the effects of airway clearance techniques (ACTs) in outpatients with bronchiectasis. Methods: ARS were registered pre/post four ACTs sessions. Clinical outcomes included: number of crackles (coarse and fine), number of wheezes (monophonic and polyphonic), wheezes occupation rate (%) and sputum quantity. Feasibility outcomes of ARS included: reasons for exclusion, suitability, safety, equipment and time required, magnitude of change after intervention and sample size estimation. Results: Seven patients (49.7 ± 20.5 years; FEV1 69.3 ± 15.8% predicted) were included. Recordings from four patients were excluded due to excessive environment noise. All ARS measurements were completed without any adverse events. An electronic stethoscope was acquired and the time spent to complete each assessment was 6 ± 3.5 min. The largest changes were observed for number of expiratory coarse crackles [effect size (95%CI) ES = 0.40 (0.01-0.79)], which correlated moderately with sputum quantity (r = 0.56), and inspiratory monophonic wheezes [ES = 0.61 (0.22-1.00)]. The estimated sample size for a full crossover trial was 46. Conclusions: ARS is feasible to assess the effects of ACTs in patients with bronchiectasis. Expiratory coarse crackles seem to be the most appropriate ARS parameter, but this finding needs to be confirmed in an adequately powered trial.


Surgical treatment for epilepsy.
Surgical treatment for epilepsy remains highly underutilized: in the United States, there has been no increase in the number of surgical procedures performed annually since 19901; for most patients referred, the average duration of epilepsy is 22 years2; and there has been no change in this delay to surgery3, despite two randomized controlled trials4, 5 and an American Academy of Neurology practice parameter that recommended surgery as the treatment of choice for medically refractory temporal lobe epilepsy6. This session addressed issues relevant to increasing the availability of epilepsy surgery, particularly in countries with limited resources.


Spectrum of Extramammary Malignant Neoplasms in the Breast With Radiologic-Pathologic Correlation.
Although primary breast cancer is the most common malignancy identified by breast imaging, extramammary malignancies may also rarely be encountered. These uncommon lesions may reflect primary neoplasms of nonmammary origin as well as secondary metastatic lesions, and include lymphoma, melanoma, neuroendocrine tumors, gastrointestinal tract malignancies, and angiosarcoma among other entities. Malignant extramammary breast lesions may be encountered during routine mammographic screening, identified during the diagnostic evaluation of a palpable breast abnormality, or may be detected incidentally during imaging of other organs of interest. As such, the radiologist should have familiarity with the appearance of these lesions. This article focuses on a review of several of the most common extramammary metastases to the breast, as well as a few lesions that may develop as either primary or secondary lesions.


Ontogenesis of monoamine oxidase and catechol-O-methyl transferase in various tissues of domestic swine.
Activities of monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT) in liver, kidney, heart, spleen, hindbrain, and adrenal glands were compared in adult dogs, cats, guinea-pigs, rabbits, rats, sheep, and 150-day-old swine. Swine had the highest COMT activity and dogs or cats, the lowest in most tissues. MAO was more tissue and species variable. The ontogenesis of MAO or COMT was evaluated in the same six tissues of swine from 10 days before birth through 150 days of age. COMT and MAO generally increased in swine kidney and liver with age, but the developmental patterns were more variable in other tissues. COMT increased in heart, spleen, and adrenals through 14 days of age, decreased in spleen and adrenals to 150 days, but remained elevated in heart. Brain MAO activities were near or above 150-day-old levels at birth and changed little with age. Cardiac MAO fell from birth to 70 days of age, while splenic and adrenal activities increased with age. MAO substrate specificity to tyramine, benzylamine, and serotinin along with selective inhibition by harmine, pargyline, and clorgyline were used as indices of multiple enzymic forms. Type B MAO may dominate in all swine tussues except spleen, although the biochemical characteristics of this enzyme form do not seem to fit all of the patterns described for other species. Thermal stability of MAO in swine resembles that in the guinea-pig.


[Strategies to optimize the use of antibiotics in hospitals].
The inadequate use of antibiotics is a clinical reality we are faced with day by day. The great peculiarity of this group of drugs is the influence they have not only on the patients and at the time of their use, but also of future infections and the general population, by favoring alterations in the resistance patterns of the bacterial microflora that colonize people. It is our obligation as experts in infectious diseases to work on improving the use of antimicrobials.


Accidental bladder injury during elective inguinal hernia repair: a preventable complication with high morbidity.
Bladder injury (BI) represents a rare complication of inguinal hernia surgery. Protrusions of the urinary bladder through the deep inguinal ring ("bladder ears") have been reported with an incidence of 9% in infants younger than 6 months of age and may be misinterpreted as the hernia sac. This literature review was designed to determine incidence and outcomes of bladder injuries during pediatric inguinal hernia repair. A literature review of the literature (1967-2017) was performed using the keywords "bladder ears", "inguinal hernia", "iatrogenic bladder injury" and "bladder hernia". Publications were reviewed for epidemiology, presentation and extent of injury, treatment and outcome. Thirteen articles reporting on 30 cases of BI during inguinal hernia repair from 1967 to 2017 were included (19 boys, 2 girls, 9 unknown). Median age at herniotomy was 10.5 months (1 month-6 years). Out of 30 children, 14 (47%) experienced mild complications. Sixteen patients (53%) had severe complications after initial surgery and needed revisional surgery. Complications were noticed up to 4 years after the initial surgery. In 9 (56%) of the 16 severe cases, major damage to the bladder wall and impairment of bladder capacity occurred. In seven patients (44%), secondary closure was successful. In ten patients (63%), the bladder was partially resected, and in one child (6%), the entire bladder was removed. The degree of accidental BI during inguinal hernia repair was severe in in the majority of reported cases in the literature. Surgeons should be aware of the high prevalence of "bladder ears" in infants to prevent injury to the urinary tract.


Viscoelastic properties of elastomeric impression materials: polysulphide, silicone and polyether rubbers.
Creep compliance measurements were shown to be effective in characterizing the elastic, retarded elastic, and viscous properties of polysulphide, silicone, and polyether impression materials. The test is particularly valuable in that the creep compliance was independent of load, allowing the mechanical properties to be represented by a single total creep compliance curve which can be used to determine the various creep components. The total recovered compliance was shown to be independent of time provided the polymerization had progressed sufficiently before testing was done. The retarded elastic and viscous compliances contributed proportionally to the total creep compliance and thus did not affect the rankings of materials. The viscous compliance of polysulphide A decreased enough after 1 h so that the creep compliance of A and D were not different. The creep compliance measurements showed that the polysulphide materials were the most viscoelastic followed by silicone and polyether impression materials. The polyether was the most nearly ideal elastic material but it had a flexibility comparable to heavy body polysulphide. Of particular interest was the observation that polyether with thinner in ratios up to 1 : 1 by length had no practical effect on the viscoelastic properties.


[Antidepressants in epilepsy].
Depression is a common condition in patients with epilepsy that entails a deterioration of the quality of life of this population and that, therefore, requires appropriate treatment. The potential risk of antidepressants in relation to the seizure threshold is overestimated by many professionals, and this has an influence when it comes to making the decision to treat them. It sometimes means that the patients do not receive antidepressant drugs. In this regard, the aim of this review is to present the current state of the art in terms of the safety of antidepressants in patients with epilepsy. A search of the medical literature was conducted and, following its analysis, the most significant results are presented. Current information indicates that most antidepressants are safe for epileptic patients at therapeutic doses and that the risk of seizures occurs mainly in cases of overdose. Preferred drugs for treating depression in epilepsy are serotonin reuptake inhibitors. Bupropion and tricyclic antidepressants must be avoided.