Post-Covid condition and clinic characteristics associated with SARS-CoV-2 infection: a 2-year follow-up to Brazilian cases.
Until January 2023, Brazil recorded 37 million COVID-19 cases despite the decrease in mortality due to mass vaccination efforts against COVID-19. The infection continues to challenge researchers and health professionals with the persistent symptoms and onset manifestations after the acute phase of the disease, namely Post-Covid Condition (PCC). Being one of the countries with the highest infection rate, Brazil must prepare for a growing number of patients with chronic health consequences of COVID-19. Longitudinal studies that follow patients over extended periods are crucial in understanding the long-term impacts of COVID-19, including potential health consequences and the effects on quality of life. We describe the clinical profile of a cohort of COVID-19 patients infected during the first year of the pandemic in Brazil and a follow-up after two years to investigate the health impacts of SARS-CoV-2 infection. The first wave of SARS-CoV-2 infection in Brazil featured extensive drug misuse, notably the ineffective COVID kit comprised of ivermectin, antimalarials and azithromycin, and elevated in-hospital mortality. In the second phase of the study, Post-Covid Condition was reported by symptomatic COVID-19 subjects across different severity levels two years after infection. Long haulers are more likely to be women, previously hospitalized, and reported a range of symptoms from muscle pain to cognitive deficit. Our longitudinal study is essential to inform public health authorities to develop strategies and policies to control the spread of the virus and mitigate its impacts on society.


Evaluation and modification of spectrophotometric procedures for analysis of lactate dehydrogenase, beta-glucuronidase and arylsulphatase in human gingival crevicular fluid collected with filter-paper strips.
Filter-paper strips were used to collect GCF, and the sample eluted into a larger volume of diluent. This procedure allows for detection of site-to-site variation in GCF volume, and provides a 300-400 microliter sample for analysis of lactate dehydrogenase (LDH), beta-glucuronidase (BG) and arylsulphatase (AS) activities by a standard (serum) spectrophotometric assay modified for increased sensitivity. The results indicate that although the standard assay for LDH (based on oxidation of NADH) was adequate for detecting low activity in GCF samples, the modification doubled the sensitivity and allowed the use of less sample volume, thereby providing additional material for other assays. The standard assay for BG based on phenolphthalein being generated from phenophthalein glucuronic acid was not adequate for use in GCF analysis. The modification used increased assay sensitivity five-fold and allowed smaller samples to be used. The serum assay for AS (conversion of nitrocatechol sulphate to nitrocatechol) was accurate to the lower limit of AS activity in GCF and could be used without modification. The results emphasize the need to evaluate critically standard spectrophotometric assays for sensitivity when studying physiologically-collected GCF.


Importance of ICD-10 coding directive change for acute gastroenteritis (unspecified) for rotavirus vaccine impact studies: illustration from a population-based cohort study from Ontario, Canada.
In Ontario, Canada, we conducted an evaluation of rotavirus (RV) vaccine on hospitalizations and Emergency Department (ED) visitations for acute gastroenteritis (AGE). In our original analysis, any one of the International Classification of Disease, Version 10 (ICD-10) codes was used for outcome ascertainment: RV-specific- (A08.0), viral- (A08.3, A08. 4, A08.5), and unspecified infectious- gastroenteritis (A09). Annual age-specific rates per 10,000 population were calculated. The average monthly rate of AGE hospitalization for children under age two increased from 0.82 per 10,000 from January 2003 to March 2009, to 2.35 over the period of April 2009 to March 31, 2013. Similar trends were found for ED consultations and in other age groups. A rise in events corresponding to the A09 code was found when the outcome definition was disaggregated by ICD-10 code. Documentation obtained from the World Health Organization confirmed that a change in directive for the classification of unspecified gastroenteritis occurred with the release of ICD-10 in April 2009. AGE events previously classified under the code K52.9, are now classified under code A09.9. Based on change in the classification of unspecified gastroenteritis we modified our outcome definition to also include unspecified non-infectious-gastroenteritis (K52.9). We recommend other investigators consider using both A09.9 and K52.9 ICD-10 codes for outcome ascertainment in future rotavirus vaccine impact studies to ensure that all unspecified cases of AGE are captured, especially if the study period spans 2009.


Intracellular trafficking of FXYD1 (phospholemman) and FXYD7 proteins in Xenopus oocytes and mammalian cells.
FXYD proteins are a group of short single-span transmembrane proteins that interact with the Na(+)/K(+) ATPase and modulate its kinetic properties. This study characterizes intracellular trafficking of two FXYD family members, FXYD1 (phospholemman (PLM)) and FXYD7. Surface expression of PLM in Xenopus oocytes requires coexpression with the Na(+)/K(+) ATPase. On the other hand, the Na(+)/Ca(2+) exchanger, another PLM-interacting protein could not drive it to the cell surface. The Na(+)/K(+) ATPase-dependent surface expression of PLM could be facilitated by either a phosphorylation-mimicking mutation at Thr-69 or a truncation of three terminal arginine residues. Unlike PLM, FXYD7 could translocate to the cell surface of Xenopus oocytes independently of the coexpression of α1β1 Na(+)/K(+) ATPase. The Na(+)/K(+) ATPase-independent membrane translocation of FXYD7 requires O-glycosylation of at least two of three conserved threonines in its ectodomain. Subsequent experiments in mammalian cells confirmed the role of conserved extracellular threonine residues and demonstrated that FXYD7 protein, in which these have been mutated to alanine, is trapped in the endoplasmic reticulum and Golgi apparatus.


[Hemolysis and schizocytosis, malabsorption and the "folate trap": unusual semiological peculiarities associated with vitamin B12 deficiency].
Hemolysis and red cell fragmentation accompanying vitamin B12 deficiency may misdirect the diagnosis. Signs of malabsorption and abnormalities related to folic acid metabolism characterized by discrepancies between folic acid normal serum levels and erythrocytic folic acid levels may also exist. We report the occurrence of hemolysis and red cell fragmentation mimicking microangiopathic hemolytic anemia, malabsorption and folic acid deficiency in the course of vitamin B12 deficiency. Appropriate replacement therapy corrected all abnormalities. An association between hemolysis, malabsorption and folic acid deficiency should lead physicians to search for signs of vitamin B12 deficiency.


The management of complications of small joint arthrodesis and arthroplasty.
Arthrodesis and arthroplasty are surgical options used for the management of pain, stiffness, deformity, and instability related to arthritis and traumatic injury of the small joints of the hand. Arthrodesis and arthroplasty come with a risk of postoperative infection. Superficial soft tissue infections can often be managed with oral antibiotics alone. Deep infections and osteomyelitis frequently require removal of hardware in addition to antibiotics and may require surgical revision once the infection is cleared. Selection of the most appropriate revision technique depends on the underlying cause of the initial failure, patients' functional and outcome needs, and surgeon preference.


Pentamidine therapy in renal failure: case report and literature review.
The literature lacks adequate dosing guidelines for modifying pentamidine therapy in renal failure. This report describes a patient in renal failure undergoing intermittent peritoneal dialysis who is treated with pentamidine for Pneumocystis carinii pneumonia. Data on pentamidine's disposition are reviewed.


Neural representation of verb meaning: an fMRI study.
The neural basis for verb comprehension has proven elusive, in part because of the limited range of verb categories that have been assessed. In the present study, 16 healthy young adults were probed for the meaning associated with verbs of MOTION and verbs of COGNITION. We observed distinct patterns of activation for each verb subcategory: MOTION verbs are associated with recruitment of left ventral temporal-occipital cortex, bilateral prefrontal cortex and caudate, whereas COGNITION verbs are associated with left posterolateral temporal activation. These findings are consistent with the claim that the neural representations of verb subcategories are distinct. Although the "sensory-motor" hypothesis may play a role in explaining activation associated with MOTION verbs, the left posterolateral temporal distribution of cortical activation associated with COGNITION verbs cannot be easily explained by the "sensory-motor" hypothesis. We suggest that left posterolateral temporal activation supports aspects of lexical semantic processing concerned with the neural representation of propositional knowledge contributing to COGNITION verbs.


Diaphragm Preservation Reduces Respiratory Failure After Extent I Thoracoabdominal Aneurysm Repair.
We sought to evaluate the impact of surgical approach (thoracophrenolaparotomy vs thoracotomy crura splitting) on the outcomes of extent I thoracoabdominal aortic aneurysm repair. Patient data were extracted from our aortic surgery database. The primary endpoint was need for tracheostomy, and secondary endpoints were operative mortality, myocardial infarction, stroke, spinal cord injury, de novo dialysis, and major adverse events (composite of secondary endpoints and tracheostomy). Freedom from death and reoperation during follow-up were calculated. Risk adjustment was obtained with propensity score matching and multivariable regression. Three hundred twenty-five patients underwent extent I repair. Compared with thoracophrenolaparotomy patients (n = 226), thoracotomy crura-splitting patients (n = 99) had a higher rate of previous coronary revascularization (27.3% vs 14.2%, P = .005), valvular disease (64.6% vs 50.4%, P = .018), and chronic obstructive pulmonary disease (61.6% vs 28.3%, P = .000) and a lower forced expiratory volume in 1 second (46% vs 69%, P = .000). In a matched sample thoracotomy crura splitting was associated with a decreased need for tracheostomy (4.0% vs 13.1%, P = .035). The need for tracheostomy was predicted by female gender (odds ratio, 3.11; 95% confidence interval, 1.17-8.30; P = .023), forced expiratory volume in 1 second (odds ratio, 0.95; 95% confidence interval, 0.91-0.98; P = .003), and thoracophrenolaparotomy (odds ratio, 3.66; 95% confidence interval, 1.14-11.73; P = .029). Five-year freedom from mortality and reoperation were similar. In patients undergoing extent I thoracoabdominal aortic aneurysm repair, thoracotomy crura splitting was associated with decreased need for tracheostomy.


Cyclopiazonic acid disturbs the regulation of cytosolic calcium when repetitive action potentials are evoked in Dionaea traps.
Evoking of action potentials (APs) in the trap of Dionaea muscipula Ellis at intervals shorter than 20 s caused a gradual decrease in the amplitude of the APs. At longer intervals the amplitude was constant. The calcium ionophore A23187 (1 μM) caused a considerable decrease of AP amplitude. Pretreatment of a segment of the Dionaea trap with cyclopiazonic acid (CPA), which is a specific inhibitor of the Ca2+-ATPase in the sarcoplasmic seticulum of animal cells and in ER vesicles isolated from plant cells, only slightly affected the amplitude when APs were evoked every 10 min; however, it caused a considerable decrease in the amplitude when the stimulation was repeated every 2 min. Assuming that APs increase the concentration of cytosolic Ca2+ and the amplitude of AP depends on the gradient of Ca2+ across the plasma membrane, the effect of CPA on the AP amplitude indicates that CPA inhibits the sequestration of Ca2+ in Dionaea cells.


Emergency department vaccination of preschool-age children during a measles outbreak.
To determine the effectiveness of an emergency department vaccination program for preschool-age children during a measles outbreak. Cross-section study. Urban pediatric ED with an annual census of 24,000. Children, 12 to 59 months old, who presented to our ED between April 1 and April 30, 1994. Staff trained in rationale for and protocol of ED vaccination offered measles-mumps-rubella (MMR) vaccine, free of charge, to all eligible children. Of the 541 children seen, 7% lacked measles vaccination; MMR vaccination status could not be determined in 10%. From history it was determined that all the others had been vaccinated. Of the vaccination-eligible children, 25% were vaccinated in the ED. Of the eligible children who were not vaccinated, parents declined in half of the cases and physicians did not offer vaccination in the other half. Eligible children with physical injury were more likely to be vaccinated, and those with upper respiratory tract infections were less likely to be vaccinated than were eligible children with other diagnoses (P < .05). During a measles outbreak, few children receiving care at a busy pediatric ED were definitively identified as vaccination eligible. Only a few children identified as eligible for vaccination were vaccinated. Significant logistic barriers to effective ED vaccination exist.


Serum Cripto-1 is a novel biomarker for non-small cell lung cancer diagnosis and prognosis.
Cripto-1 (CR-1) is highly expressed in several different types of human tumors. However, the clinical significance of CR-1 expression in serum specimens from non-small cell lung cancer (NSCLC) patients has not yet been determined. The aim of this study was to explore the diagnostic and prognostic value of serum CR-1 levels in patients with NSCLC. Serum specimens from 592 NSCLC patients, 180 benign lung disease patients and 240 healthy controls were collected. The concentrations of CR-1 were measured by sandwich enzyme-linked immunosorbent assay. Patients with NSCLC had higher serum CR-1 levels than the controls (P < 0.01) and patients with benign lung diseases (P < 0.01). When a cutoff point of 1.8 ng/mL was selected (diagnostic specificity 95%), the diagnostic sensitivity for NSCLC is 56.8%. About 37.5% of carcinoembryonic antigen (CEA)-negative lung cancer patients were CR-1 positive at 95% specificity. In patients with stage I/II lung cancer, use of these two markers in combination results in almost 21% increase in sensitivity, at 95% specificity, compared with CEA alone. Uni-variate analysis revealed that NSCLC patients with positive CR-1 had a shorter overall survival (OS) and progression-free survival (PFS) than those with negative CR-1 [hazard ratio (HR) of 2.93, P = 0.005; HR of 2.12, P = 0.005]. Cox multi-variate analysis indicated that CR-1 was an independent prognostic indicator of PFS and OS (HR of 1.91, P = 0.006; HR of 1.82, P = 0.007). Kaplan-Meier survival curves further confirmed that patients with negative CR-1 had longer PFS and OS (P = 0.026 and P = 0.011, respectively). In conclusion, measurement of serum CR-1 is a useful diagnostic and prognostic marker for NSCLC patients.


Different genes may be involved in distal and local sensitization: A genome-wide gene-based association study and meta-analysis.
Neuropathic pain symptoms and signs of increased pain sensitization in osteoarthritis (OA) patients may explain persistent pain after total joint replacement (TJR). Therefore, identifying genetic markers associated with pain sensitization and neuropathic-like pain phenotypes could be clinically important in identifying targets for early intervention. We performed a genome-wide gene-based association study (GWGAS) using pressure pain detection thresholds (PPTs) from distal pain-free sites (anterior tibia), a measure of distal sensitization, and from proximal pain-affected sites (lateral joint line), a measure of local sensitization, in 320 knee OA participants from the Knee Pain and related health in the Community (KPIC) cohort. We next performed gene-based fixed-effects meta-analysis of PPTs and a neuropathic-like pain phenotype using genome-wide association study (GWAS) data from KPIC and from an independent cohort of 613 post-TJR participants, respectively. The most significant genes associated with distal and local sensitization were OR5B3 and BRDT, respectively. We also found previously identified neuropathic pain-associated genes-KCNA1, MTOR, ADORA1 and SCN3B-associated with PPT at the anterior tibia and an inflammatory pain gene-PTAFR-associated with PPT at the lateral joint line. Meta-analysis results of anterior tibia and neuropathic-like pain phenotypes revealed genes associated with bone morphogenesis, neuro-inflammation, obesity, type 2 diabetes, cardiovascular disease and cognitive function. Overall, our results suggest that different biological processes might be involved in distal and local sensitization, and common genetic mechanisms might be implicated in distal sensitization and neuropathic-like pain. Future studies are needed to replicate these findings. To the best of our knowledge, this is the first GWAS for pain sensitization and the first gene-based meta-analysis of pain sensitization and neuropathic-like pain. Higher pain sensitization and neuropathic pain symptoms are associated with persistent pain after surgery hence, identifying genetic biomarkers and molecular pathways associated with these traits is clinically relevant.


Characterization and intracellular localization of putative Chlamydia pneumoniae effector proteins.
We here describe four proteins of Chlamydia pneumoniae, which might play a role in host-pathogen interaction. The hypothetical bacterial proteins CPn0708 and CPn0712 were detected in Chlamydia pneumoniae-infected host cells by indirect immunofluorescence tests with polyclonal antisera raised against the respective proteins. While CPn0708 was localized within the inclusion body, CPn0712 was identified in the inclusion membrane and in the surrounding host cell cytosol. CPn0712 colocalizes with actin, indicating its possible interaction with components of the cytoskeleton. Investigations on CPn0809 and CPn1020, two Chlamydia pneumoniae proteins previously described to be secreted into the host cell cytosol, revealed colocalization with calnexin, a marker for the ER. Neither CPn0712, CPn0809 nor CPn1020 were able to inhibit host cell apoptosis. Furthermore, transient expression of CPn0712, CPn0809 and CPn1020 by the host cell itself had no effect on subsequent infection with Chlamydia pneumoniae. However, microarray analysis of CPn0712-expressing host cells revealed six host cell genes which were regulated as in host cells infected with Chlamydia pneumoniae, indicating the principal usefulness of heterologous expression to study the effect of Chlamydia pneumoniae proteins on host cell modulation.


The relationship between appraisals of auditory verbal hallucinations and real-time affect and social functioning.
In addition to being a hallmark symptom of schizophrenia-spectrum disorders, auditory verbal hallucinations (AVH) are present in a range of psychiatric disorders as well as among individuals who are otherwise healthy. People who experience AVH are heterogeneous, and research has aimed to better understand what characteristics distinguish, among those who experience AVH, those who experience significant disruption and distress from those who do not. The cognitive model of AVH suggests that appraisals of voices determine the extent to which voices cause distress and social dysfunction. Previous work has relied largely on comparisons of "clinical" and "non-clinical" voice hearers, and few studies have been able to provide insight into the moment-to-moment relationships between appraisals and outcomes. The current study examines longitudinal data provided through ecological momentary assessment and passive sensors of 465 individuals who experience cross-diagnostic AVH. Results demonstrated associations of AVH appraisals to negative affect and social functioning. Above and beyond within-individual averages, when a participant reported increased appraisals of their voices as powerful and difficult to control, they were more likely to feel increased negative affect and reduced feelings of safety. AVH power appraisals were also associated with next-day number and duration of phone calls placed, and AVH controllability appraisals were associated with increased time near speech and reduced next-day time away from primary location. These results suggest that appraisals are state-like characteristics linked with day-to-day and moment-to-moment changes in impactful affective and behavioral outcomes; intervention approaches should aim to address these domains in real-time.


[Bone morphogenetic protein expression in distraction osteogenesis correction for cleft palate in Rhesus monkeys].
To study the expression and distribution of bone morphogenetic protein (BMP) in newly formed bone by distraction osteogenesis (DO), and to explore the mechanism of the DO bone formation and remodeling. The cleft palate (CP) experimental animal models (23 Rhesus monkeys) were established surgically. In experimental group (21 Rhesus monkeys), the palatal defects were corrected by means of DO at the rhythm of 0.4 mm twice per day. The specimens were retrieved under euthanasia at 1, 2, 4, 6, 8, 12, 24 weeks intervals respectively in retention period. BMP immunohistochemical study was then performed. The blank control and experimental group (each of 2 animals) were set for comparison study. The immunohistochemical study showed that BMP existed mainly in cytoplasma of osteoblasts, during the process of new bone formation. In early stage of 1 or 2 weeks, abundant osteoblasts aggregating on surfaces of the new bone trabeculae with positive DAB dye were observed. Through 4 to 6 weeks, the proliferative osteoblasts with very strong positive DAB dye indicating BMP expression were recorded. From 8 to 12 weeks, the expression of BMP and quantity of osteoblasts decreased gradually while more matured new bone structures were observed. During the whole retention period, the expression of BMP showed a tendency from weak to strong and then to final cessation, this indicated a process of formation, remodeling and maturation of osteogenesis.


A Retrospective Study of Transaxillary Endoscopic Breast Augmentation Using Ultrasonic Scalpel or Conventional Electrocautery for Implant Pocket Dissection.
Ultrasonic scalpel has been reported to be superior to conventional electrocautery in many studies. However, with respect to transaxillary endoscopic breast augmentation, few studies on the effect of ultrasonic scalpel are available in the literature. The medical records of 173 female patients who underwent breast augmentation via endoscopic transaxillary approach from January 2018 to December 2020 were reviewed retrospectively. The patients were divided into two groups according to the implant pocket dissection instruments. In group A, the implant pockets were dissected with conventional electrocautery (EC group) on 81 patients, and in group B, ultrasonic scalpel (US group) was used for implant pockets on 92 patients. All operations were performed by the same senior plastic surgeon and the same surgical team. The operation time, intraoperative blood loss, postoperative total drainage volume, days of drainage, postoperative surgical site pain and hospital stay time of the two groups were compared and analyzed statistically. The average operation time of the US group (83.82 ± 11.57 min) was significantly shorter than that of the EC group (101.40 ± 14.36 min), intraoperative blood loss in the US group was significantly less than that of the EC group (18.67 ± 6.20 ml vs. 21.59 ± 6.44 ml), the mean hospital stay days (2.96 ± 0.69 vs. 4.30 ± 1.11), total drainage volume (122.24 ± 43.81 vs. 232.37 ± 99.15), and duration of drain (2.52 ± 0.54 vs. 3.77 ± 1.10), mean VAS score for surgical site pain on 3 postoperative days (5.08 ± 1.35 vs. 6.51 ± 1.36, 4.08 ± 1.16 vs. 5.40 ± 1.32, 3.04 ± 0.91 vs. 4.06 ± 1.11) were significantly lower in the US group compared to the EC group. The ultrasonic scalpel reduces operative time, intraoperative blood loss, postoperative drainage, postoperative pain, hospital stay time, and incidence of complications. The ultrasonic scalpel is safe and reliable for transaxillary endoscopic breast augmentation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Diabetes and Cardiovascular Disease Risk Perception and Risk Indicators: a 5-Year Follow-up.
Perceived disease risk may reflect actual risk indicators and/or motivation to change lifestyle. Yet, few longitudinal studies have assessed how perceived risk relates to risk indicators among different disease risk groups. We examined in a 5-year follow-up, whether perceived risks of diabetes and cardiovascular disease predicted physical activity, body mass index (BMI kg/m2), and blood glucose level, or the reverse. We examined further whether perceived risk, self-efficacy, and outcome beliefs together predicted changes in these risk indicators. Participants were high diabetes risk participants (N = 432) and low/moderate-risk participants (N = 477) from the national FINRISK 2002 study who were followed up in 2007. Both study phases included questionnaires and health examinations with individual feedback letters. Data were analyzed using gender- and age-adjusted structural equation models. In cross-lagged autoregressive models, perceived risks were not found to predict 5-year changes in physical activity, BMI, or 2-h glucose. In contrast, higher BMI and 2-h glucose predicted 5-year increases in perceived risks (β-values 0.07-0.15, P-values < 0.001-0.138). These associations were similar among high- and low/moderate-risk samples. In further structural equation models, higher self-efficacy predicted increased physical activity among both samples (β-values 0.10-0.16, P-values 0.005-0.034). Higher outcome beliefs predicted lower BMI among the low/moderate-risk sample (β-values - 0.04 to - 0.05, P-values 0.008-0.011). Perceived risk of chronic disease rather follows risk indicators than predicts long-term lifestyle changes. To promote sustained lifestyle changes, future intervention studies need to examine the best ways to combine risk feedback with efficient behavior change techniques.


Erratum: Quality Improvement Initiative to Reduce Intravenous Line-related Infiltration and Phlebitis Incidence in Pediatric Emergency Room.
[This corrects the article on p. 557 in vol. 25, PMID: 34177176.].


Aids in diagnosis of suspect ectopic ureters in female patients.
When suspected ectopic ureters cannot be visualized by conventional methods, such as excretory urogram, nephrotomograms, or by intravenous indigo carmine, then direct injection of vaginal, suburethral, or paraurethral "swellings," which are in effect dilated terminal ureters, may confirm the diagnosis.


"Exotic Sensation" or "Völkisch Art"? Press Reviews of the Indisches Ballett Menaka (Menaka Indian Ballet) on Tour Through Germany, 1936-1938.
The tour of the Indian Ballet Menaka through hundreds of German cities between 1936 and 1938 left a large footprint in the form of theatre reviews. This article focuses on the role of these performances in actualizing a specific knowledge about India that was, firstly, based on the assumption of the consanguinity of Indo-German peoples and, secondly, on a vision of history as a realization of the utopian ideal of cultural regeneration through art. This article thus hopes to articulate the ways in which the unique experience of this Indian theatre event served as an instrument for consolidating a völkisch/racialized perception of art in general, and of music in particular.


Quantitative determination of diterpenoid alkaloids in four species of Aconitum by HPLC.
A high performance liquid chromatography (HPLC) method has been developed for the determination of five principal alkaloids (benzoylmesaconine, mesaconitine, aconitine, hypaconitine and deoxyaconitine) found in four species of genus Aconitum. The five alkaloids were analyzed simultaneously with an XTerraRP18 column by gradient elution using 0.03 M ammonium hydrogen carbonate-acetonitrile as mobile phase. The recovery of the method was 94.6-101.9%, and all the alkaloids showed good linearity (gamma = 0.9999) in a relatively wide concentration range. The results indicated that contents of alkaloids in Aconitum varied significantly from species to species; hence quality control of Aconitum drugs is very necessary.


Ectoenzymes of the kidney microvillar membrane. Aminopeptidase P is anchored by a glycosyl-phosphatidylinositol moiety.
The mode of membrane anchorage of three kidney microvillar membrane ectoenzymes has been examined. The release of aminopeptidase P (EC 18.104.22.168) from kidney membranes by bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) and the pattern of detergent solubilization of this ectoenzyme implies that it is anchored to the membrane via a covalently attached glycosyl-phosphatidylinositol moiety. As deduced by phase separation in Triton X-114, octyl-glucoside solubilized the amphipathic form of aminopeptidase P, whereas the PI-PLC-released form displayed hydrophilic properties. In contrast, the pattern of detergent solubilization of two microvillar carboxypeptidases and their resistance to release from the membrane by bacterial PI-PLC suggest that these two ectoenzymes are not anchored via phosphatidylinositol.


Specific antibiotic prophylaxis based on bile cultures is required to prevent postoperative infectious complications in pancreatoduodenectomy patients who have undergone preoperative biliary drainage.
Preoperative biliary drainage (PBD) is associated with bacterial contamination of bile, but the effects of PBD on morbidity after pancreatoduodenectomy remain controversial. The aim of this study was to characterize bile contamination to develop successful specific antibiotic prophylactic strategies for pancreatoduodenectomy. Ninety-one consecutive patients who underwent pancreatoduodenectomy for periampullary tumor were prospectively evaluated. Prophylactic antibiotics were selected based on preoperative bile cultures. Bile cultures and postoperative complications were compared in 46 patients who underwent PBD (drainage group) versus 45 patients who did not (nondrainage group). The incidence of positive bile cultures was higher in the drainage group (78%) than in the nondrainage group (36%) (P < 0.001). In the drainage group, positive bile cultures were frequently polymicrobial (61%) and demonstrated resistance to several antibiotics, including cefazolin (83%), cefmetazole (72%), and cefpirome (64%). Overall morbidity (30% and 22%) and infectious morbidity (13% and 11%) did not differ significantly between the drainage and nondrainage groups, respectively. PBD had a notable influence on bile microbial contamination, including a higher rate of antibiotic resistance. Therefore, specific antibiotic prophylaxis based on bile culture is required for preventing infectious complications in pancreatoduodenectomy patients who undergo PBD.


Uranium-contaminated soils: ultramicrotomy and electron beam analysis.
Uranium-contaminated soils from the U.S. Department of Energy (DOE) Fernald Site, Ohio, have been examined by a combination of backscattered electron imaging (BSE) and analytical electron microscopy with electron diffraction (AEM). The inhomogeneous distribution of particulate uranium phases in the soil required the development of a method for using ultramicrotomy to prepare transmission electron microscopy (TEM) thin sections from the SEM mounts. A water-miscible resin was selected that allowed comparison between SEM and TEM images, permitting representative sampling of the soil. Uranium was found in iron oxides, silicates (soddyite), phosphates (autunites), and uraninite (UO2 + x). No uranium was detected in association with phyllosilicates in the soil.


Clinical evaluation of [18F]pitavastatin for quantitative analysis of hepatobiliary transporter activity.
It is widely accepted that uptake and efflux transporters on clearance organs play crucial roles in drug disposition. Although in vitro transporter assay system can identify the intrinsic properties of the target transporters, it is not so easy to precisely predict in vivo pharmacokinetic parameters from in vitro data. Positron emission tomography (PET) imaging is a useful tool to directly assess the activity of drug transporters in humans. We recently developed a practical synthetic method for fluorine-18-labeled pitavastatin ([18F]PTV) as a PET probe for quantitative evaluation of hepatobiliary transport. In the present study, we conducted clinical PET imaging with [18F]PTV and compared the pharmacokinetic properties of the probe for healthy subjects with or without rifampicin pretreatment. Rifampicin pretreatment significantly suppressed the hepatic maximum concentration and biliary excretion of the probe to 52% and 34% of the control values, respectively. Rifampicin treatment markedly decreased hepatic uptake clearance (21% of the control), and moderately canalicular efflux clearance with regard to hepatic concentration (52% of the control). These results demonstrate that [18F]PTV is a useful probe for clinical investigation of the activities of hepatobiliary uptake/efflux transporters in humans.


The effects of busulphan on the chromosomes of normal human lymphocytes.
In vitro exposure of human lymphocytes to busulphan (BUS) produced an increase in chromosome aberrations and in sister-chromatid exchange (SCE) frequency. The distribution of chromosome breaks throughout the karyotype was non-random and they occurred mainly in the G-negative bands. Certain bands had a marked susceptibility to BUS and comparisons with the human chromosome-break distributions reported for a number of drugs revealed that some of these bands were equally susceptible to other alkylating agents. Both the number of chromosome gaps and breaks and the SCE frequency increased with BUS concentration, but only the SCE dose--response was a clearly defined linear relationship. Therefore a standard SCE dose--response curve was constructed for future comparison with the results of similar investigations of patients on BUS therapy.


Decreased cAMP levels in human diploid cells exposed to cholinergic stimuli.
Carbachol at a concentration of 1 micron caused very significant decreases in PGE1 stimulated cAMP levels in three human diploid lung fibroblasts, WI-38, MRC-5, and IMR-90. Detailed studies with WI-38 cells showed that carbachol acted at low concentrations and very rapidly, cAMP levels being reduced by 50% in about 1 minute. The effect was moderately reduced but still very significant in Ca++ free medium containing 10(-5)M EGTA. Acetylcholine (in the presence of physostigmine), pilocarpine, and muscarine lowered cAMP levels at concentrations of 1 or 10 micron. The effects of carbachol were exquisitely sensitive to atropine but were unaffected by hexomethonium or d-tubocurarine. These data suggested that the cholinergic response of WI-38 cells was of the muscarinic type.


Thyrotropin receptor-adenylate cyclase system in plasma membranes from normal and diseased human thyroid glands.
Thyrotropin binding characteristics and adenylate cyclase (AC) activity of thyroid plasma membranes were studied in 52 tissues from normal and diseased human thyroids. Data from normal glands, Graves' goiters, non toxic multinodular goiters and nodular and perinodular tissue of toxic nodular goiters show the same basal, TSH- and NaF- stimulated adenylate cyclase activities (no. = 45; 34.1 +/- 3.2 (m +/- SE), 378 +/- 43, 298 +/- 48 pmol cAMP x min-1 x mg membrane protein-1), the same stimulability of AC by TSH (11.3 +/- 1.4--fold over basal level) and by NaF (8.1 +/- 1.8-fold), the same apparent TSH binding equilibrium constants (5.6 +/- 0.7 and 406 +/- 57 nM) and the same TSH binding site concentrations (2.2 +/- 0.4, 27.8 +/- 5.9 pmol x mg membrane protein-1). Alterations of the TSH receptor and of the AC were detected in membranes from tumoral and metastatic lymph node tissues from thyroid papillary carcinoma and in the thyroid tissue from post-radioiodide therapy thyroiditis. These observations suggest that: (i) hyperthyroidism in Graves' disease or toxic nodular goiter does not result in and is not a consequence of an alteration in the TSH receptor-adenylate cyclase system; (ii) there is no evidence supporting a relationship between the studied membrane properties and clinical or histological status; (iii) membrane abnormalities detected in thyroid carcinoma vary widely; (iv) studies of these membrane alterations might be of interest in the therapeutic management of thyroid carcinoma and may lead to a better understanding of the receptor-adenylate system.


Impact of the COVID-19 Pandemic on the Psychosexual Functions of Healthcare Workers.
A novel infection, COVID-19, emerged in China and soon became a global pandemic. Pandemic conditions have resulted in stress in the workplace and led to anxiety among healthcare workers (HCWs), having negative impacts on different aspects of their lives, including their sexual function. To evaluate the changes in the anxiety status of HCWs during the COVID-19 pandemic and the impact of anxiety on their sexual functions. This is a longitudinal study based on an online survey conducted from April 2020 to February 2021 in hospitals designated as pandemic healthcare centers. An online survey link was sent to HCWs that provided consent for participation in the study. The anxiety status of the participants was assessed using the State Anxiety Inventory, and sexual function was evaluated using the International Index of Erectile Function-15 for men and Female Sexual Function Index for women. Scores obtained at the beginning of the pandemic were compared with those obtained at 6 months into the pandemic to determine the changes in the anxiety levels and sexual functions of the HCWs. A total of 399 HCWs participated in the survey, and the median age was 32 (20-60) years. Compared to the beginning of the pandemic, there was a significant increase in the State Anxiety Inventory score of the female and male HCWs at the sixth month of the pandemic. Among the women, the mean total Female Sexual Function Index score was 23.55 ± 8.69 at the beginning of the pandemic and 21.42 ± 8.91 at the sixth month, and there was a significant decrease in all parameters except pain. Among the men, the International Index of Erectile Function-15 total score was 62.75 ± 12.51 at the beginning of the pandemic and 55.1 ± 12.87 at the sixth month, indicating a significant decrease in all parameters. Considering that the pandemic will continue for a long time, more psychological support should be provided, and interventions should be made to protect the mental health of HCWs. The strength of the study is that it had a fairly high number of participants across several institutions. However, being conducted in one country and the sample not being randomly selected and being based on voluntariness can be considered as limitations. Our results show that the COVID-19 pandemic has led to an increase in the anxiety levels of both female and male HCWs, and this situation has negatively affected their sexual functions. Eroglu U, Balci M, Coser S, et al, Impact of the COVID-19 Pandemic on the Psychosexual Functions of Healthcare Workers. J Sex Med 2022;19:182-187.


Demonstration of innominate artery aneurysm by magnetic resonance/imaging.
Solitary innominate artery aneurysms are very rare in the pediatric age group. They may be seen in association with multiple aneurysms or occasionally in patients with connective tissue disease. Magnetic resonance appears to be a very useful noninvasive technique capable of demonstrating flowing blood and vascular lumen without injection of contrast media.


Prevalence of Refractive Errors and Number Needed to Screen among Rural High School Children in Southern India: A Cross-sectional Study.
Avoidable blindness is mainly due to uncorrected refractive errors (URE). School Eye Screening (SES) can be used as an initiative to address this issue. To determine prevalence of URE and Number Needed to Screen (NNS) to find one child with low vision or blindness from URE among rural school children. A cross-sectional study was performed in 22 government schools with sixth to ninth grades in Kaniyambadi block of Vellore District of Tamil Nadu, India. There were 4739 children on the rolls. Among children present, all those identified to have a visual deficit in either eye, using a single line 20/40 Snellen's optotype E chart at 6 m, were referred to the hospital for confirmatory evaluation. Blindness (uncorrected) was defined as inability to see 20/200 in the better eye. In two of these schools, visual deficits were validated through a second school based examination by a clinician. Of the 4739 children on rolls, 601 were absent; all 4138 (87.3%) who were present underwent screening; 2.3% (98) {95% Confidence Interval (CI) 1.8 to 2.8} failed the screening test in at least one eye and were referred for examination. Only 28 (28.6%) of 98 children who were referred came for examination to the hospital. In the 2 of the 22 schools where the visual deficit was validated, there were no false positives. The prevalence of refractive error in these two schools was 2.2% (95% CI 1.7 - 2.7). NNS to detect one child with low vision or blindness from URE was 147. Magnitude of refractive error, low NNS, low response to referral necessitates complete care at school and hence a relook at the current SES program.


Development and characterization of microsatellite loci for the endemic Thalictrum smithii (Ranunculaceae).
Microsatellite primers were developed for the gynodioecious Chinese endemic Thalictrum smithii (Ranunculaceae). Thirty-nine microsatellite primers were developed using the Fast Isolation by AFLP of Sequences COntaining repeats (FIASCO) method. Thirteen microsatellite loci were found to be highly polymorphic after screening 114 specimens (60 hermaphrodite and 54 female) from three T. smithii populations. The number of alleles per locus ranged from three to 13, and the levels of observed and expected heterozygosity per locus ranged from 0.000 to 1.000 and from 0.204 to 0.834, respectively. Twenty-six of these primers were polymorphic in T. petaloideum and T. finetii. These markers will be useful for examining genetic diversity, polyploidy, and mating system in populations of T. smithii and for guiding study on the evolution of speciation in Thalictrum.


APPL1 gates long-term potentiation through its plekstrin homology domain.
Hippocampal synaptic plasticity involves both membrane trafficking events and intracellular signaling, but how these are coordinated is far from clear. The endosomal transport of glutamate receptors in and out of the postsynaptic membrane responds to multiple signaling cascades triggered by synaptic activity. In this work, we have identified adaptor protein containing a plekstrin homology domain, phosphotyrosine-binding domain and leucine zipper motif 1 (APPL1) as a crucial element linking trafficking and signaling during synaptic plasticity. We show that APPL1 knockdown specifically impairs PI3K-dependent forms of synaptic plasticity, such as long-term potentiation (LTP) and metabotropic-glutamate-receptor-dependent long-term depression (mGluR-LTD). Indeed, we demonstrate that APPL1 is required for the activation of the phosphatidylinositol triphosphate (PIP3) pathway in response to LTP induction. This requirement can be bypassed by membrane localization of PI3K and is related to phosphoinositide binding. Interestingly, inhibitors of PDK1 (also known as PDPK1) and Akt have no effect on LTP expression. Therefore, we conclude that APPL1 gates PI3K activation at the plasma membrane upon LTP induction, which is then relayed by downstream PIP3 effectors that are different from PDK1 and Akt.


Cost of prostate image-guided radiation therapy: results of a randomized trial.
This cost analysis aimed to quantify the cost of IGRT in relation to IGRT frequency and modality with Cone Beam Computed Tomography (CBCT) or orthogonal electronic portal imaging with fiducial markers (EPI-FM). Patients undergoing IGRT for localized prostate cancer were randomized into two prostate control frequencies (daily or weekly). Costs were calculated based on the micro-costing results according to hospitals' perspectives (in Euros, 2009) and the time horizon was radiation therapy. A total of 208 patients were enrolled in seven French cancer centers. A total of 6865 fractions were individually analyzed. The mean total treatment fraction duration was 21.0 min for daily CBCT and 18.3 min for daily EPI-FM. Increasing the control frequency from weekly to daily increased the mean treatment fraction duration by 7.3 min (+53%) for CBCT and 1.7 min (+10%) for EPI-FM (p ≤ 0.01). The mean additional cost per patient of daily controls compared with weekly controls was €679 and €187 for CBCT and EPI-FM, respectively (p<0.0001). The incremental costs due to different prostate IGRT strategies are relatively moderate, suggesting that daily IGRT combined with intensity-modulated RT (IMRT) could be administered in cases of high-dose radiation delivery to the prostate.


Birinapant (TL32711) Improves Responses to GEM/AZD7762 Combination Therapy in Triple-negative Breast Cancer Cell Lines.
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer currently lacking targeted therapies. Our previous work demonstrated a therapeutic synergism with gemcitabine (GEM) and the CHK1 inhibitor (AZD7762) combination treatment in a TNBC cell line. We hypothesized that the response to this combination therapy would differ among heterogeneous TNBC patients and that addition of a SMAC mimetic (TL32711) could improve efficacy. Therapeutic responses to GEM, GEM/AZD7762, and GEM/AZD7762/TL32711 combinations were investigated by XTT assays and western blotting of cell cycle and apoptosis-related proteins in ten TNBC cell lines. TNBC cell lines harboring low levels of endogenous CHK1, cIAP1 and cIAP2 were responsive to GEM alone, whereas cell lines demonstrating a minimal increase in phospho-S345 CHK1 after treatment were responsive to GEM/AZD7762 or GEM/AZD7762/TL32711 combination. The response of TNBC cells to particular therapies varies and will require development of predictive biomarkers.


Isolation and characterization of epidermal growth factor from human milk.
Epidermal growth factor (EGF) has been purified from human milk. The purification was monitored with a human placental membrane radioreceptor assay using murine salivary epidermal growth factor I (mEGF I) as a competitive ligand and was achieved exclusively by the use of reverse-phase liquid chromatography (RPLC). The sequential use of preparative, semipreparative and analytical RPLC on an octylsilica support with solvent systems of different solute selectivity such as pyridine formate, triethylammonnium phosphate or perfluorocarbonic acids in the presence of n-propanol or acetonitrile allowed purification to homogeneity with 5 consecutive runs. The molecular mass, amino acid composition and NH2-terminal sequence of human EGF were determined. Gas-phase microsequencing of residues 1-17 revealed the following sequence: Asn-Ser-Asp-Ser-Glu-X-Pro-Leu-Ser-His-Asp-Gly-Tyr-X-Leu-X-Asp which is identical with the NH2-terminof urogastrone from human urine. The purified polypeptide competes with mEGF for the placental membrane receptor with a ki of 1 ng. Furthermore, it stimulates the anchorage-dependent as well as -independent proliferation of human and rat indicator cells with half-maximal stimulation at 1 and 2.5 ng/ml, respectively. Although human epidermal growth factor has been unequivocally identified in human milk and -for the first time-shown to be identical with urogastrone from human urine, the high-resolution techniques employed have also revealed the presence of EGF-related molecules which await further characterization. It is possible that EGF and the EGF-related growth factors possess important regulatory functions in normal growth of the human breast during pregnancy and lactation as well as in abnormal growth during mammary tumor formation and progression.


A new efficient method to monitor precocious puberty nationwide in France.
Clinical precocious puberty (PP) is a disease, reputed to be on the increase and suspected to be linked to endocrine disrupting chemicals (EDC) exposure. Population-based epidemiological data are lacking in France and scarce elsewhere. We accessed the feasibility of monitoring PP nationwide in France in this context, using a nationwide existing database, the French National Health Insurance Information System. Here, we present the method we used with a step-by-step approach to build and select the most suitable indicator. We built three indicators reflecting the incidence of idiopathic central precocious puberty (ICPP), the most frequent form of PP, and we compared these indicators according to their strengths and weaknesses with respect to surveillance purposes. Monitoring ICPP in France proved feasible using a Drug reimbursement indicator. Our method is cost efficient and highly relevant in public health surveillance. Our step-by-step approach proved helpful to achieve this project and could be proposed for assessing the feasibility of monitoring health outcomes of interest using existing data bases. What is known: • Precocious puberty (PP) is suspected to be related to EDC exposure and it is believed to be on the increase in France and in others countries. • Very few epidemiologic data on PP are currently available in the world at the national scale. What is new: • This is the first study describing a method to monitor the most frequent form of PP, idiopathic central PP (ICPP) nationwide in a cost-efficient way, using health insurance databases. • This cost-effective method will allow to estimate and monitor the incidence of ICPP in France and to analyze spatial variations at a very precise scale, which will be very useful to examine the role of environmental exposures, especially to EDCs.


Highly active enzymes produced by directed evolution with stability-based selection.
In a directed evolution aimed at improving enzymatic activity, a situation occurs where highly active variants can no longer be obtained from a template protein because the template is already located at a peak (local maximum) in the fitness landscape of activity for the sequence space. To overcome this situation, the template needs to descend the mountain (lose activity) once and climb another higher mountain. However, there is no solid guideline of how the template should go down. Here, we propose a stability index. Previous studies have shown that protein evolution is potentially governed by stability, and that proteins with low activity but high stability are more favorable templates for producing highly active variants. In our earlier works on conventional directed evolution by random mutagenesis of an esterase from Sulfolobus tokodaii, we identified variants with 3-fold higher activity than the wild-type as the highest activity variants. In this work, as a first step, stability-keeping variants were selected by five rounds of random mutagenesis and screening based on halo formation assay using the substrate tributyrin at 70 °C after heat treatment for 30 min at 90 °C. These variants are likely to be scattered at the feet of various mountains in the fitness landscape. Next, these variants were pooled and used as parental proteins for a conventional experiment with activity-based selection, where the activity of variants was assayed using their cell-free extracts on the substrate p-nitrophenyl butyrate at 75 °C. After two rounds of random mutagenesis, we successfully obtained a variant with 9-fold higher activity than the wild-type. These results indicate that the two-step selection by stability and activity enables us more easily to produce markedly activity-improving variants.


Ultrastructure of electrophysiologically-characterized synapses formed by serotonergic raphe neurons in culture.
Recent electrophysiological investigations in this laboratory have shown that cultured mesopontine serotonergic neurons from neonatal rats evoke serotonergic and/or glutamatergic responses in themselves and in non-serotonergic neurons. Serotonergic nerve terminals in vivo are heterogeneous with respect to vesicle type, synaptic structure, and the frequency with which they form conventional synaptic contacts, but the functional correlates of this heterogeneity are unclear. We have therefore examined the ultrastructure of electrophysiologically-characterized synapses formed by cultured serotonergic neurons, and have compared the findings with the ultrastructural characteristics of serotonergic synapses reported in vivo. Dissociated rat serotonergic neurons in microcultures were identified by serotonin immunocytochemistry or by uptake of the autofluorescent serotonin analogue 5,7-dihydroxytryptamine, and were subsequently processed for electron microscopy. Unlabeled axon terminals formed numerous synapses on serotonin-immunoreactive somata and dendrites. Serotonin-immunoreactive axon terminals formed synapses on the somata, dendrites and somatodendritic spine-like appendages of serotonergic and non-serotonergic neurons. In microcultures containing a solitary serotonergic neuron that evoked glutamatergic or serotonergic/glutamatergic autaptic responses, both symmetric and asymmetric synapses were present. In addition to large dense core vesicles, individual neurons contained either microcanaliculi and microvesicles, clear round vesicles, or clear pleiomorphic vesicles. For a given cell, however, the subtypes of vesicles present in each axon terminal were similar. Thus, dissociated serotonergic and non-serotonergic raphe neurons formed functional, morphological synapses in culture. A direct examination of both the synaptic physiology and ultrastructure of single cultured serotonergic neurons indicated that these cells released serotonin and glutamate at synapses that were morphologically similar to synapses formed by serotonergic neurons in vivo. The findings also suggested that individual serotonergic neurons differ with respect to synaptic vesicle morphology, and are capable of simultaneously forming symmetric and asymmetric synapses with target cells.


"It shows we are serious": Young people in Australia discuss climate justice protests as a mechanism for climate change advocacy and action.
This article aims to understand young Australians' perspectives of climate justice protests as a mechanism for climate change advocacy and action. A qualitatively led online survey was conducted with n=511 young Australians (15-24 years). Open-text questions prompted for young people's perceptions of the appeal, accessibility, and effectiveness of climate justice protests in climate change action. A reflexive thematic analysis was conducted to construct themes from the data. Participants perceived that protests were an important mechanism for young people to draw attention to the need for climate action. However, they also stated that the clear messages that were sent to governments via protests did not necessarily lead to government action. Young people perceived that there were some structural issues that prevented them from taking part in these types of activities, including living far away from protests, not being accessible for young people with disabilities, and limited support from family members and/or friends to participate. Climate justice activities engage young people and give them hope. The public health community has a role to play in supporting access to these activities and championing young people as genuine political actors in addressing the climate crisis.


One-stage ultrasound screening in pregnancy. An evaluation.
A one-stage ultrasound screening program was evaluated, using a pregnancy/perinatal database containing information from 2766 pregnancies and deliveries. Among women who did not have a second-trimester ultrasound examination, labor was induced for presumed post-term pregnancy in 4.0% versus 1.6% of pregnancies in the screening group (p = 0.007). In the group with second-trimester ultrasound scanning other than screening, the frequency was 3.2%. Of women with spontaneous labor or who were induced for presumed post-term pregnancy, 3.8% in a screening group and 8.0% in a group with other second-trimester ultrasound examination were post-term according to BPD measurements (p = 0.0003). In the screening group, 6.2% of liveborn singletons were small for gestational age (less than the 10th percentile) compared with 8.5% in the non-screening group (p less than 0.05). A subset of 365 screened women with optimal menstrual history had spontaneous labor or were induced for presumed post-term pregnancy. According to menstrual history and ultrasound examination, 7.4% and 3.8% of these were post-term, respectively (p = 0.04). It is concluded that the main value of screening lies in a more accurate dating of pregnancy, even when menstrual history is optimal, with a lower incidence of induced labor for believed post-term pregnancies. In addition, there may be an improvement in the obstetric management of pregnancy, reflected in our study as a lower incidence of small for gestational age infants.


Life history of the endemic Hawaiian hogfish Bodianus albotaeniatus: age, growth and reproduction.
Growth rate, longevity, maturity and spawning seasonality were estimated for the endemic Hawaiian hogfish Bodianus albotaeniatus. The sex-specific von Bertalanffy growth parameters are L∞ = 339 mm fork length (LF ) and K = 0.66 year-1 for females and L∞ = 417 mm LF and K = 0.33 year-1 for males. The maximum age is 22 years. Histological gonad analysis and the absence of small and young males indicate a monandric protogynous hermaphrodite. Size and age at maturity for combined sexes are L50 = 238 mm LF and A50 = 1.6 years.


N-methylnicotinamide is an endogenous probe for evaluation of drug-drug interactions involving multidrug and toxin extrusions (MATE1 and MATE2-K).
Multidrug and toxin extrusion 1 (MATE1) and MATE2-K are H(+)/organic cation exchangers mediating the efflux of cationic drugs into the urine. N-methylnicotinamide (NMN) was found to be an endogenous substrate of MATE1 (Michaelis constant (K(m)) 301 ± 18 µmol/l) and MATE2-K (K(m) 422 ± 63 µmol/l) as well as a basolateral influx transporter, organic cation transporter 2 (K(m) 318 ± 29 µmol/l). A potent MATE inhibitor, pyrimethamine, competitively inhibited the uptake by MATE1 and MATE2-K with inhibition constant (K(i)) values of 83 ± 15 and 56 ± 11 nmol/l, respectively. The uptake of NMN by human kidney brush border membrane vesicles with a H(+) gradient was saturable (K(m) 360 ± 55 µmol/l) and completely inhibited by pyrimethamine. The renal clearance of endogenous NMN was 403 ± 61 in healthy male subjects, and it was significantly decreased to 119 ± 16 ml/min/kg by an oral dose of pyrimethamine (50 mg). These results support the utility of NMN as an endogenous in vivo probe for investigating MATE1 and MATE2-K in humans.


Comparative productive performance of cows born through embryo transfer, artificial insemination and natural mating in dairy and dual-purpose herds raised in tropical conditions.
A populational, observational and longitudinal-retrospective study with records of 28 dairy-specialized and dual-purpose farms was carried out to compare the productive performance of cows born by embryo transfer (ET), artificial insemination (AI) and natural mating (NM), using the database of Centro Regional de Investigación para la Producción Animal Sostenible (CRIPAS) of cattle herds in Costa Rica. Herds (system × altitude), conception method (ET, AI and NM), genetic background (DSpB: specialized dairy breeds [Bos taurus] and crosses, GYR × HOL: Gyr × Holstein Crossbred and DSpB × BI: crosses between dairy breeds and Bos indicus), year of birth (or at calving), lactation number and days in milk were evaluated for the productive parameters age at first calving (AFC), calving to conception interval (CCI) and lactation milk yield (LMY) using a GLIMMIX procedure on SAS. The AFC, CCI and LMY were affected (p < .0001) by all factors considered in each parameter. ET has lower (p < .0001) AFC in months (33.1) than AI (35.2) and NM (36.44). NM had lower (p = .004) CCI (110 days) than AI or ET (121 days) values which were similar (p > .05). The higher LMY (p < .0001) was observed in ET (4140 kg), compared to AI (3706 kg) and NM (3595 kg). There was no difference between AI and NM. In conclusion, the method of conception in calves affected their future reproduction and production during puberty, postpartum and lactation. The effects on management decisions will require a rigorous economical study to discern whether ET would be a cost-effective alternative to AI or NM.


Prevalence and burden of coconut allergy in the United States.
Epidemiologic data on coconut allergy remains sparse in the United States despite the labeling requirement by the Food Allergen Labeling and Consumer Protection Act for products containing coconut. To provide current estimates of the prevalence, severity, determinants, and distribution of coconut allergy in the United States. A comprehensive food allergy prevalence survey was administered to a nationally representative, probability-based sample of US households between October 1, 2015 and September 30, 2016. Eligible respondents included adults who were able to complete self- and parent-proxy report surveys in English or Spanish by means of web or phone. Using survey responses from 78,851 individuals, 0.39% (95% confidence interval [CI], 0.33-0.45) of the US general population were categorized as having convincing coconut allergy. Among children, 0.22% (95% CI, 0.16-0.30) were estimated to have coconut allergy compared with 0.43% (95% CI, 0.37-0.51) of adults, whereas only 0.12% (95% CI, 0.08-0.18) of these children and 0.20% (95% CI, 0.16-0.24) of adults with convincing immunoglobulin E (IgE)-mediated coconut allergy reported physician-confirmed diagnoses. A current epinephrine prescription was reported by 40.1% (95% CI, 33.3-47.4) of those with convincing coconut allergy. Reactions involving multiple organ systems were reported by 47.5% (95% CI, 40.1-54.9) of those with convincing coconut allergy. Roughly 1 in 260 Americans report symptoms consistent with an IgE-mediated allergy to coconut, although fewer than half of these individuals report receiving a physician diagnosis. Our data indicate that most individuals with reported coconut allergy meeting symptom-based criteria for convincingly IgE-mediated disease have comorbid FAs, and for many patients, clinical management seems to be suboptimal.


Treatment of vitiligo with local khellin and UVA: comparison with systemic PUVA.
Vitiligo is an idiopathic leukoderma often with a progressive course causing destruction of melanocytes. The best methods for achieving cosmetically acceptable re-pigmentation of affected skin appear to be both local and systemic PUVA. They may, however, cause serious side effects, which is an argument for conducting research into new, equally effective photo-chemotherapeutic agents. One of these agents is khellin. We conducted a pilot study in 33 patients to evaluate the effectiveness of local KUVA and systemic PUVA therapy for vitiligo and to compare them in terms of the degree of re-pigmentation, duration of treatment, number of procedures, total UVA dose and side effects. Local KUVA required longer duration of treatment and higher UVA doses. KUVA-induced re-pigmentation depended on the age of the patients (r = -0.61, P = 0.001), and better results were achieved with younger individuals [% re-pigmentation = 81.76 - (1.48 x age in years)]. No side effects were observed in cases of local KUVA treatment. Erythema, itching and gastro-intestinal disturbances occurred with some patients treated with PUVA. The results demonstrate that local KUVA may effectively induce re-pigmentation of vitiligo-affected skin areas to a degree comparable to that achieved when using systemic PUVA, provided that treatment duration is long enough.


A case of drug-facilitated sexual assault leading to death by chloroform poisoning.
The purpose of this investigation was to determine the cause of death of a 13-year-old girl, where none was immediately evident. Our analysis showed it to be a very unusual case of a drug-facilitated sexual assault (DFSA), which led to the tragic death of the young rape victim and then to the suicide of the rapist. The incapacitating agent used was chloroform. The post-mortem analysis revealed a blood concentration of 833.9 mg/l for the girl, whereas the quantitation of chloroform in various fluids and viscera of the rapist proved that he had recently been handling the solvent (with concentrations in fat tissues 20 times higher than in his blood). This case draws attention to the need for broad searches for volatile substances in such investigations.


Cardiff puerperal mood and hormone study. 1. Saliva steroid hormone profiles in late pregnancy and the puerperium: endocrine factors and parturition.
Participants were 120 primiparous women who had vaginal delivery of a non-handicapped child. Saliva was collected twice daily through parturition to day 35 post-partum. In the prepartum, a highly significant circadian rhythm was seen in cortisol, with a lower-amplitude rhythm in progesterone (AM/PM = 1.12). Evening samples showed a rise in cortisol, with a highly significant rise on day -1. The rise was small. The fall in progesterone in the 3 days before parturition was also small (approximately 6%). Neither change provides an obvious trigger for parturition.


Gas1 expression in parietal cells of Bowman's capsule in experimental diabetic nephropathy.
Gas1 (Growth Arrest-Specific 1) is a pleiotropic protein with novel functions including anti-proliferative and proapoptotic activities. In the kidney, the expression of Gas1 has been described in mesangial cells. In this study, we described that renal parietal cells of Bowman's capsule (BC) and the distal nephron cells also express Gas1. The role of Gas1 in the kidney is not yet known. There is a subpopulation of progenitor cells in Bowman's capsule with self-renewal properties which can eventually differentiate into podocytes as a possible mechanism of regeneration in the early stages of diabetic nephropathy. We analyzed the expression of Gas1 in the parietal cells of Bowman's capsule in murine experimental diabetes. We found that diabetes reduced the expression of Gas1 and increased the expression of progenitor markers like NCAM, CD24, and SIX1/2, and mesenchymal markers like PAX2 in the Bowman's capsule. We also analyzed the expression of WT1 (a podocyte-specific marker) on BC and observed an increase in the number of WT1 positive cells in diabetes. In contrast, nephrin, another podocyte-specific protein, decreases its expression in the first week of diabetes in the glomerular tuft, which is gradually restored during the second and third weeks of diabetes. These results suggest that in diabetes the decrease of Gas1 promotes the activation of parietal progenitor cells of Bowman's capsule that might differentiate into podocytes and compensate their loss observed in this pathology.


Cross-sectional area of the tendon and the muscle of the biceps brachii in shoulders with rotator cuff tears: a study of 14 cadaveric shoulders.
The intraarticular portion of the long head of the biceps tendon is often widened in shoulders with cuff tears. It is unclear whether this is a local phenomen or is caused by muscle hypertrophy. We investigated morphological changes of the biceps brachii in 14 embalmed shoulders: 7 with intact rotator cuff and 7 with rotator cuff tears. We measured the cross-sectional area (CSA) of the tendon of the long head of the biceps (LHB) at 9 levels between the glenoid origin and the musculotendinous junction. The muscle volume and the muscle fiber length of the long and short heads of the biceps were measured to calculate the physiological CSA (PCSA) by dividing the volume by the fiber length. The CSA of the LHB tendon at the entrance to the bicipital groove was greater in cuff tear shoulders than in normal shoulders. The PCSA of the biceps was similar in normal and cuff tear shoulders. Hypertrophy of the LHB tendon appears to be a localized morphological change near the entrance to the bicipital groove.


An Observation-Based Dataset of Global Sub-Daily Precipitation Indices (GSDR-I).
Precipitation indices based on daily gauge observations are well established, openly available and widely used to detect and understand climate change. However, in many areas of climate science and risk management, it has become increasingly important to understand precipitation characteristics, variability and extremes at shorter (sub-daily) durations. Yet, no unified dataset of sub-daily indices has previously been available, due in large part to the lesser availability of suitable observations. Following extensive efforts in data collection and quality control, this study presents a new global dataset of sub-daily precipitation indices calculated from a unique database of 18,591 gauge time series. Developed together with prospective users, the indices describe sub-daily precipitation variability and extremes in terms of intensity, duration and frequency properties. The indices are published for each gauge where possible, alongside a gridded data product based on all gauges. The dataset will be useful in many fields concerned with variability and extremes in the climate system, as well as in climate model evaluation and management of floods and other risks.


Should benefit-risk assessment have its own drug "label"?
Many consumers and clinicians incorrectly believe that the Food and Drug Administration (FDA) approval of a new therapeutic implies that its benefits have been proven to exceed its harms. While the FDA could require proof that benefits exceed harms prior to approval, it has been argued that this approach would be infeasible because of prohibitively large sample sizes. One possible alternative would be for the FDA to supplement its standard "label" denoting "safe and effective" with a secondary "label" denoting benefits have been demonstrated to exceed harms, which would be granted only after sufficient post-marketing data had accumulated to prove that its benefits exceeded its harms. This secondary label would not necessarily be linked to marketing restrictions or other commercial prohibitions but, rather, would be only information for consumers and clinicians. Strengths, weaknesses, and feasibility challenges of this approach are discussed.


Autoantibodies to recombinant canine proinsulin in canine diabetic patients.
To determine whether dogs with spontaneously-occurring diabetes mellitus demonstrate serological reactivity to proinsulin. Serum samples were collected from 15 newly-diagnosed diabetic, 15 insulin-treated diabetic and 15 non-diabetic control dogs. Canine proinsulin was cloned into a prokaryotic expression vector to generate recombinant poly-histidine-tagged protein in Escherichia coli. A Western blotting assay was developed for detection of proinsulin autoantibodies in canine sera. Reactivity to canine proinsulin was detected in 3 of 15 control dogs, 8 of 15 newly-diagnosed diabetic dogs and 6 of 15 insulin-treated diabetic patients. Of these reactors, only 1 control dog, 1 newly-diagnosed diabetic dog and 3 insulin-treated diabetic dogs recognised porcine insulin by ELISA, suggesting that the remaining proinsulin reactors might have been recognising proinsulin-specific epitopes. This study suggests that proinsulin autoantibodies are present in a proportion of diabetic dogs. Further work is required to refine the assay and clarify the significance of these autoantibodies.


Reactivity and suitability of t-Boc-protected thiophosphotyrosine intermediate analogs for the solid or solution phase peptide synthesis.
N-(tert-Butoxycarbonyl)-O-(dimethylthiophosphono)-L-tyrosine (6) and N-(tert-butoxycarbony)-O-(dicyanoethylthiophosphono)-L-tyros ine (15) were prepared as intermediates for the synthesis of thiophosphotyrosine-containing peptides. The reactivity and suitability of two compounds for the solid phase or solution phase peptide synthesis utilizing t-Boc chemistry were examined.


Intestinal ischaemia associated with ileal carcinoid tumours.
A case of intestinal infarction due to multiple ileal carcinoid tumours is presented in which abdominal pain due to intestinal ischaemia was the first manifestation of the underlying tumour. It is postulated that intestinal ischaemia may be of more importance in the production of abdominal pain by carcinoid tumours than has been generally accepted, and that it is the result of functional and structural changes in the around the mesenteric blood vessels, caused by substances secreted by the carcinoid tumour.


Effect of age, gender, menopausal status, and ovarian hormonal level on rTMS in treatment-resistant depression.
This study examines how gender and menopausal status contribute to age effect on the antidepressant efficacy of repetitive transcranial stimulation (rTMS). Thirty-one women (17 premenopausal, 14 postmenopausal), and 16 men with treatment-refractory bipolar/major depression underwent 10 consecutive sessions of rTMS. Mood symptoms and female hormones were measured. ANOVA-R revealed a significant gender (p<0.05) and time effect (p<0.001) on the Hamilton Depression Rating Scale (HAM-D) score. Percentage reduction of the rating correlated negatively with age in women (p<0.001). While no difference in the rTMS response was observed between male and premenopausal female patients (68.8% and 70.6%, respectively), postmenopausal women responded least (0%). We also found that greater improvement of depression score was associated with a higher estradiol/progesterone ratio in premenopausal women (p<0.05), suggesting an important role of female hormones in the therapeutic response. Regression analysis revealed that menopausal status and ovarian steroid levels, but not age, were the main determinants of antidepressant efficacy of rTMS in females. This is the first study to specifically investigate the effect of female hormones on rTMS therapeutic effect. Our data support changes in menopausal status and ovarian steroid levels as effectors of mood and the CNS neural substrate response to rTMS in refractory depression. However, the restricted number of patients and the shorter duration of rTMS treatment and follow-up might influence its generalization. Further study examining the interactions between mood, ovarian hormones, and rTMS treatment is warranted.


Nerve specific modulation of somatosensory inflow to cerebral cortex during submaximal sustained contraction in first dorsal interosseous muscle.
Modulation of the early component (latency approximately 20-30 ms) of somatosensory evoked potentials (SEPs) and that of the middle and long latency cutaneous reflexes was examined in 13 healthy volunteers during fatiguing submaximal voluntary contraction (20% maximum) of the first dorsal interosseous muscle (FDI). The SEP was evoked by stimulating the ulnar nerve (U-SEP), a mixed nerve innervating the FDI muscle, the purely cutaneous nerves of the 2nd digit (D2-SEP) and the 5th digit (D5-SEP). The cutaneous reflex was recorded concurrently with D2-SEP. The size of D2- and D5-SEP significantly decreased during fatiguing contraction as compared to rest, and the decrease in both SEPs persisted throughout fatiguing contraction. In contrast, the significant decrease in the gating of U-SEP disappeared during the latter phase of fatiguing contraction. The ratio (reflex response/background EMG) of excitatory E2 (latency approximately 60-90 ms) and E3 (approximately 120-180 ms) responses following D2 stimulation significantly increased during the middle or latter phase of fatiguing contraction. In contrast, no significant changes in inhibitory I1 and I2 were seen. The release of the attenuation of U-SEP and a constant gating of the D2- and D5-SEP suggests that the brain selectively permits the muscular afferent inflow into the cortex during fatiguing contraction. An increase in the E2 and E3 reflex ratio of cutaneous reflexes during the later phase of fatiguing contraction most likely results from an increase in the excitability of the motor cortex.


Short coupling interval with high burden of atrial ectopy predicts recurrence after atrial fibrillation ablation.
Atrial ectopy (AE) with a short coupling interval (S-AE) causes atrial fibrillation (AF). A higher burden of AE is associated with recurrence after AF ablation. However, a few reports have evaluated the prognostic impact of both AE burden and S-AE after the acute phase of ablation. This study aimed to assess the characteristics of AE beyond the blanking period in predicting the recurrence. We retrospectively analyzed 173 patients who underwent first catheter ablation for AF and 24-h Holter recording following a 3-month blanking period. AE was defined as a narrow QRS complex occurring < 75% earlier than the prior reference R-R interval. We investigated the relationship between the AE's characteristics in Holter recordings and atrial arrhythmia recurrence. Forty-two patients (24%) had a recurrence during a median 488-day follow-up. Patients with S-AE (minimum coupling interval ratio of AE ≤ 45%) had a higher recurrence rate than those without S-AE (44.9% vs. 16.1%, p < 0.001). Moreover, patients with AE ≥ 241/day exhibited a significantly higher recurrence rate than those with AE < 241/day (44.3% vs. 10.7%, p < 0.001). In multivariate analysis, S-AE with a higher AE burden was an independent predictor of recurrence (hazard ratio 5.82, 95% confidence interval: 2.64-12.82, p < 0.001). Kaplan-Meier analysis showed that patients with S-AE and a higher AE burden had the worst prognosis for recurrence (p < 0.001). The combination of a higher AE burden with S-AE could be an efficient predictor of recurrence. These results can help to develop follow-up strategies after AF ablation.


Strategy for Local Plant-Based Material Valorisation to Higher-Value Feed Stock for Piglets.
In this study, a 41-day experiment was conducted using 300 (21-day-old) Large White/Norwegian Landrace piglets (100 piglets in each group). Three dietary treatments were compared: (i) a basal diet (C-I), (ii) a basal diet with the addition of extruded-fermented wheat bran (Wex130/screwspeed25Lpa) (TG-II), and (iii) a basal diet with the addition of dried sugar beet pulp (TG-III). Analyses of piglets' blood parameters, faecal microbial and physico-chemical characteristics, and piglets' growth performance were performed. It was found that the extrusion and fermentation combination led to an additional functional value of Wex130/screwspeed25Lpa, which showed desirable antimicrobial and antifungal properties in vitro (inhibited 5 out of 10 tested pathogenic strains and 3 out of 11 tested fungi). Both treatments reduced total enterobacteria and increased lactic acid bacteria counts in piglets' faeces. The consistency of the piglets' faeces (in all three groups) was within a physiological range throughout the whole experiment. Strong positive correlations were found between the LAB count in piglets' faeces and butanoic acid; butanoic acid, 3-methyl-; butyric acid (2-methyl-); pentanoic acid. The treatment groups obtained a significantly higher body weight gain and average daily gain. Finally, substituting the piglets' diet with Wex130/screwspeed25Lpa and sugar beet pulp led to favourable changes in micro-organism populations in the piglets' faeces as well as better growth performance.


Characterisation of microbial communities for improved management of anaerobic digestion of food waste.
Anaerobic digestion of food waste is an attractive and increasingly popular technology within waste management and energy recovery. A better understanding of the microbiology associated with anaerobic digestion of food waste will provide new insight into the operational conditions required for optimizing this process, as well as its potential for utilisation in co-digestion systems. Eighteen full-scale reactors processing varying proportions of food waste under diverse operational configurations were subjected to microbial community analysis by amplicon sequencing of the 16S rRNA and mcrA genes to capture the bacterial and methanogenic populations. Statistical correlations between microbial populations, plant design and operating conditions revealed that the microbial communities were shaped by operational parameters such as the primary substrate type and operational temperature, while the methanogenic communities showed a more reactor specific distribution. The distribution of microbes based on the waste processed in the surveyed digesters was explored, as well as the presence of specialist populations such as syntrophs and methanogens. Food waste digester communities were not associated with a strong microbial fingerprint compared to other waste types (wastewater and manure) but contained greater abundance and unique syntrophic acetate oxidising populations, suggesting that co-digestion with food waste may improve the functional diversity of anaerobic digesters.


Customized Microenvironments Spontaneously Facilitate Coupled Engineering of Real-Life Large-Scale Clean Water Capture and Pollution Remediation.
Harnessing abundant renewable resources and pollutants on a large scale to address environmental challenges, while providing sustainable freshwater, is a significant endeavour. This study presents the design of fully functional solar vaporization devices (SVD) based on organic-inorganic hybrid nanocomposites (CCMs-x). These devices exhibit efficient photothermal properties that facilitate multitargeted interfacial reactions, enabling simultaneous catalysis of sewage and desalination. The localized interfacial heating generated by the photothermal effect of CCMs-x triggers surface-dominated catalysis and steam generation. The CCMs-x SVD achieves a solar water-vapor generation rate of 1.41 kg m-2 h-1 (90.8%), and it achieves over 95% removal of pollutants within 60 min under one-sun for practical application. The exceptional photothermal conversion rate of wastewater for environmental remediation and water capture is attributed to customized microenvironments within the system. The integrated parallel reaction system in SVD ensures it is a real-life application in multiple scenarios such as municipal/medical wastewater and brine containing high concentrations. Additionally, the SVD exhibits long-term durability, antifouling functionality toward complex ionic contaminants. This study not only demonstrates a one-stone-two-birds strategy for large-scale direct production of potable water from polluted seawater, but also opens up exciting possibilities for parallel production of energy and water resources.


Effects of Dietary Thraustochytrid Schizochytrium sp. and Other Omega-3 Sources on Growth Performance, Carcass Characteristics, and Meat Quality of Broilers.
Looking for alternative omega-3 sources in broiler nutrition, microalgae began to get attention. We suspected that schizochytrium might play a similar role as other omega-3 sources that have been used before. 20 g/kg schizochytrium powder (SP), salmon oil (SO), and flaxseed oil (FO) in each of the three treatment groups were supplemented in the basal diet (CON), and productive performance, carcass traits, and thigh meat quality of broilers were evaluated. There was a significantly higher weight gain in the SP treatment compared to the other groups, but no difference was found in feed intake and feed conversion ratio. Thiobarbituric acid reactive substance values increased during storage in all the treatments but were significantly lower for SP than for SO and FO after 7 days of storage. Among the ω-3 fatty acids (FAs), α-linolenic acid increased the most in the FO treatment, eicosapentaenoic acid increased the most in the SO treatment, and docosahexaenoic acid increased the most in the SP treatment in thigh meat, reflecting the FA composition of the lipid source diets. We suggested that all the dietary ω-3 FA sources could improve the FA composition of chicken meat and our results indicated the possibility to supplement broiler diets with 2% level of SP, SO, and FO as ω-3 FA sources to produce meat with a good nutritional quality for consumer's health benefits.


Combination of simvastatin administration and EPC transplantation enhances angiogenesis and protects against apoptosis for hindlimb ischemia.
The aim of this present study is to investigate the impacts of combinatorial simvastatin administration and endothelial progenitor cell (EPC) transplantation on therapeutic angiogenesis in an athymic nude mouse model of hind limb ischemia. Athymic nude mice were divided into four groups (n = 10/group): vehicle administration plus PBS injection (control), simvastatin administration plus PBS injection (simvastatin), vehicle administration plus EPC transplantation (EPC), and simvastatin administration plus EPC transplantation (combination). The combination therapy had the greatest laser Doppler blood perfusion imager (LDPI) index and capillary density among the four groups. Importantly, this combination therapy significantly reduced apoptosis of ischemic skeletal muscle cells in part through downregulation of Bax and upregulation of Bcl-2 compared with the other groups. Moreover, the combination therapy exhibited the highest efficacy of increasing the ratio of phospho-Akt to Akt among the four groups. Taken together, the simvastatin and EPC combination therapy promotes powerful angiogenesis in hindlimb ischemia. The combination therapy not only inhibites apoptosis of ischemic skeletal muscle cells partially via downregulation of Bax and upregulation of Bcl-2, but also activates Akt phosphorylation significantly. These efficacies may be mediated by the angiogenic potency of simvastatin, EPCs, and by the beneficial effects of simvastatin on transplanted EPCs as well.


Single nucleotide polymorphisms in AGTR1, TFAP2B, and TRAF1 are not associated with the incidence of patent ductus arteriosus in Japanese preterm infants.
Persistent patent ductus arteriosus (PDA) is a frequent complication in preterm infants. Single nucleotide polymorphisms (SNP) in several genes, including angiotensin II receptor, type 1 (AGTR1), transcription factor AP-2 beta (TFAP2B) and tumor necrosis factor receptor-associated factor 1 (TRAF1), have been reported to be associated with PDA in preterm infants. The aim of this study was to evaluate the relationships between PDA in preterm infants and polymorphisms in AGTR1, TFAP2B and TRAF1 in the Japanese population. The subjects consisted of 107 preterm infants with gestational age <32 weeks. Extremely low-birthweight infants were treated with prophylactic indomethacin during the first 24 h after birth. Five SNP, namely, rs5186 in AGTR1, rs987237 and rs6930924 in TFAP2B, and rs1056567 and rs10985070 in TRAF1, were genotyped using TaqMan SNP genotyping assays. There were no significant differences in the distributions of the genotypes and allele frequencies of all studied SNP between the PDA group (n = 46) and the non-PDA group (n = 61). There were no significant associations between the studied SNP and the incidence of PDA in Japanese preterm infants. These SNP may not be clinically important predisposing factors for PDA in Japanese preterm infants.


Aluminium phosphate potentiates the efficacy of DNA vaccines against Leishmania mexicana.
DNA vaccines have been able to induce partial protection against infection with Leishmania in mice, but it is still necessary to increase their efficacy. In the present study we evaluated aluminium phosphate as an adjuvant of different formulations and doses of DNA vaccines against L. mexicana in BALB/c mice. Aluminium phosphate had no effect on the humoral response induced by a high dose (100 microg) DNA vaccine, but slightly increased the cellular response and the protection against infection. It also allowed a non-immunoprotective low dose (20 microg) DNA vaccine encoding L. mexicana GP63 and Leishmania donovani NH36 to become protective. Aluminium phosphate may thus be an effective, low cost and safe adjuvant for DNA vaccines, and the vaccine formulation described here may be an excellent candidate for further vaccine development against Leishmania.


Conjugation reactions in hepatocytes isolated from streptozotocin-induced diabetic rats.
The activities of three drug conjugation reactions, glutathione, glucuronic acid and sulphate conjugation and the synthesis of glutathione, have been measured in hepatocytes isolated from streptozotocin-induced male diabetic rats. The intracellular content of reduced glutathione (GSH) was decreased in diabetic rat hepatocytes compared with controls. Following depletion of the intracellular GSH stores with diethylmaleate, the resynthesis of GSH in the presence of 0.5 mM L-methionine, occurred faster in diabetic rat hepatocytes than in those from control rats indicating that the cystathione pathway may be more efficient in the diabetic animals. In contrast, there was no significant difference in the resynthesis of GSH between control and diabetic rat hepatocytes in the presence of L-cysteine. The GSH conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB) was deficient in diabetic rat hepatocytes, although only the effect on the former reaction was statistically significant (P less than 0.05). The Vmax for CDNB conjugation was significantly lower (P less than 0.05) in cytosolic fractions prepared from diabetic rat liver than in control rat liver fractions. This was accompanied by an increase in the affinity of the enzyme for CDNB. In contrast, the Vmax and Km for the conjugation of DCNB in cytosolic fractions were unaffected by the induced-diabetes. Glucuronic acid conjugation of both 1-naphthol and phenolphthalein was markedly deficient in diabetic rat hepatocytes. The intracellular concentrations of the cofactor for glucuronidation, UDP-glucuronic acid, were decreased in diabetic rat liver and this was thought to contribute to the defect in glucuronidation. The sulphation of 1-naphthol was not significantly altered by the induced diabetes. Deficiencies in glutathione and glucuronic acid conjugation in streptozotocin-induced diabetic rats may result in an increased susceptibility to xenobiotic induced cytotoxicity.


[Angiolymphoid hyperplasia with eosinophilia or Kimura's disease].
A rare affection of unknown etiology that is benign but frequently recurrent, Kimura's disease involves infiltration of the dermis and hypodermis usually of the face. Documented data exists describing clinical findings and results of histopathology that are analogous but are grouped under other names: angiolymphoid hyperplasia with eosinophilia, pyogenic pseudogranuloma, atypical pyogenic granuloma. A case followed up for 13 years is reported.


A life-threatening tracheal localization of lymphoma in a patient with AIDS.
Lymphoma is a frequent complication of HIV infection, but we report a rare localization in the subglottic tracheal area. A case of tracheal stenosis due to lymphoma in an HIV-infected patient is presented. The main complaint was severe dyspnea. Chemotherapy was ineffective but radiotherapy improved the patient's condition and increased the caliber of the tracheal lumen.


The importance of an ethics curriculum in surgical education.
The nature of surgical work provides fertile ground in which ethical problems can grow. The concept of what it means to be a "good surgeon" includes the ability to reason and deliberate about how the surgeon's unique technical capabilities integrate with larger society. Ethics education at the resident level is important for several reasons. It can ensure that care is delivered in a socially and ethically responsible manner through global and emergent effects on institutions and traditions. It will prepare residents for leadership positions. It can allow residents to confront issues, such as the scientific underdetermination of surgical practice, the application of new technologies to trusting patients that have been developed by for-profit companies, and a surgical environment that is becoming increasingly institutionalized. Resident ethics education provides the opportunity for a model of collective deliberation to be developed that can be used to make sense of ethical problems as they arise.


Novel Marker for Premature Ejaculation: Serum Leptin Level.
Leptin, which was only discovered in humans in 1994, has recently been shown to have a possible link with premature ejaculation. To evaluate whether serum leptin levels differed between patients with premature ejaculation and healthy men, and to analyze the changes in leptin levels before and after treatment. Six studies assessing the relationship between leptin and premature ejaculation published up to October 2021 were identified from multiple databases (PubMed, Web of Science, Cochrane) and the data were analyzed by Stata software. Differences in leptin levels in premature ejaculation patients and healthy people, and changes of leptin levels in premature ejaculation population before and after treatment. Analysis of studies assessing differences in leptin concentrations between patients with PE and healthy men showed that there was a statistically significant difference in leptin levels between PE patients and controls (WMD (95% CI) = 17.89 (8.64, 27.14), P < .001). On the other hand, the analysis of data from 3 studies describing serum leptin levels in PE patients before and after treatment with selective serotonin reuptake inhibitors (SSRIs) showed that there was a significant decrease with leptin levels in PE patients after treatment (WMD (95%CI) = 22.06 (17.21, 26.92), P < .001). It is possible that leptin can be used as a new marker for premature ejaculation. The strength of this study is that it is the first meta- analysis to assess the differences of serum leptin levels between patients with premature ejaculation and healthy subjects and the changes of leptin levels before and after treatment in patients with premature ejaculation. A major limitation is that a greater heterogeneity was identified through our analysis, however we did not find a definitive source of heterogeneity. There was a statistically significant relationship between serum leptin levels and patients with PE. In addition, serum leptin levels in patients with PE decreased significantly after 8 weeks of treatment with SSRIs. Liu G, Zhang Y, Zhang W, et al. Novel Marker for Premature Ejaculation: Serum Leptin Level. Sex Med 2022;10:100509.


[Victimization and problems of behavior. Two components of profile types of runaway adolescents].
This study examines the relationship between two explanatory factors connected to the phenomena of runaways and the homeless among adolescents: behavioral problems of youths and parental violence to which they are subjected. The study demonstrates that these two factors are independently related to the different categories of homeless and runaway adolescents. The data was collected from 130 adolescents (12 to 17 years of age) who were runaways for short periods on a recurring basis. Two subgroups were formed: Group A consisted of 79 adolescents who did not exhibit behavioral problems; Group B consisted of the other 51 who did exhibit them. The two groups had certain similar family characteristics (income levels, parents' occupations, structure and stability of the family). The bivariate analyses reveal significant differences between the two groups of runaways relating to: (1) gender, (2) a diagnosed conduct disorder, (3) affiliations with deviant peers, and (4) experiences of parental violence. The discriminant analysis demonstrates that these four variables clearly differentiate the two groups of runaways and predict the appropriate group membership for 84% of the cases. Therefore, the members of Group B have a higher probability of being diagnosed as having a conduct disorder, being male, and associating with delinquent peers. This group had not experienced a higher level of parental violence. The opposite is true for the members of Group A. Our study demonstrates that parental violence and behavioral problems are variables that are independently related to the defined categories of runaways. Therefore, these variables do not constitute, as some thinkers have claimed, the components of a unique dynamic able to explain the phenomenon of the runaway. Our results vitiate the doubts sometimes expressed by researchers about the importance of parental violence to the phenomenon of adolescent runaways.