Standard treatment-refractory cytomegalovirus encephalitis unmasked by immune reconstitution inflammatory syndrome and successfully treated with virus-specific hyperimmune globulin.
Cytomegalovirus (CMV)-related encephalitis is a rare but potentially life-threatening complication of CMV infection in immunocompromised patients. The high mortality rate is associated with deficient immune system reconstitution after hematopoietic stem cell transplant (HSCT) and poor bioavailability of antiviral drugs in cerebrospinal fluid (CSF). CMV-related central nervous system (CNS) infection may occur with aspecific symptoms, without evidence of either blood viral load or magnetic resonance imaging (MRI) signs of encephalitis. Here, we describe a 10-year-old girl who underwent an allogeneic HSCT and subsequently developed CMV encephalitis. Because of the absence of CMV antigen in the blood, the diagnosis of encephalitis was proposed only after a delay, following the onset of immune reconstitution inflammatory syndrome (IRIS). Two months of combined dual antiviral therapy with ganciclovir and foscarnet proved ineffective against CMV and caused significant bone marrow and renal toxicity. To avoid further toxicity, the girl was given daily treatment with CMV-hyperimmune globulins alone. After three weeks, the CSF viral load dropped significantly and was undetectable within three more weeks. In the meantime, the renal impairment resolved, and there was a complete bone marrow recovery. We suggest that this patient succeeded in achieving CMV CSF clearance with high dose of CMV-hyperimmune globulin, given alone, because of the ability of immunoglobulins to penetrate the blood-brain barrier (BBB).


Delta Opioid Receptor and Peptide: A Dynamic Therapy for Stroke and Other Neurological Disorders.
Research of the opioid system and its composite receptors and ligands has revealed its promise as a potential therapy for neurodegenerative diseases such as stroke and Parkinson's Disease. In particular, delta opioid receptors (DORs) have been elucidated as a therapeutically distinguished subset of opioid receptors and a compelling target for novel intervention techniques. Research is progressively shedding light on the underlying mechanism of DORs and has revealed two mechanisms of DOR neuroprotection; DORs function to maintain ionic homeostasis and also to trigger endogenous neuroprotective pathways. Delta opioid agonists such as (D-Ala2, D-Leu5) enkephalin (DADLE) have been shown to promote neuronal survival and decrease apoptosis, resulting in a substantial amount of research for its application as a neurological therapeutic. Most notably, DADLE has demonstrated significant potential to reduce cell death following ischemic events. Current research is working to reveal the complex mechanisms of DADLE's neuroprotective properties. Ultimately, our knowledge of the DOR receptors and agonists has made the opioid system a promising target for therapeutic intervention in many neurological disorders.


Purification and characterization of a zearalenone degrading enzyme produced byGliocladium roseum.
Enzymatic inactivation of fungal toxins is an attractive strategy for the decontamination of food and feeding stuff. A constitutively expressed enzyme opening the lactone linkage within the macrocyclic ring system of zearalenone (ZON) was isolated fromGliocladium roseum. The enzyme has been shown to catalyze the transformation of the mycotoxin ZON and therefore has been named ZON degrading enzyme. The resulting products of the enzymatic reaction are less toxic because they have lost their estrogenic capacity. In this study, we used scanning electron microscopy to evaluate the possible mycoparasitism betweenFusarium graminearum andG. roseum. The ZON-degrading enzyme could be isolated fromG. roseum cultures and biochemically characterized. It has been found to be similar to superoxide-dismutases at its N-teminus.


Assessment of the validity of self-reported smoking status among schoolchildren in Sousse, Tunisia.
Tobacco use, which begins in adolescence and childhood and continues in later life, is the major avoidable risk for non-communicable diseases and death in the world. Self-reports have frequently been used to estimate smoking prevalence and health consequences. This study explores the validity of self-reports of smoking behavior among schoolchildren in Tunisia. This study was conducted in March 2014 among a sample of 147 schoolchildren randomly selected. Data concerning the smoking habit were collected by a questionnaire designed for the purposes of this work. Then, exhaled CO, a biochemical marker of smoke exposure, was measured using piCO+ Smokerlyzer® breath CO monitor among participants. Sensitivity and specificity of self-reports were calculated. The prevalence of reported smoking was 9.5% with 16.7% and 1.7% respectively among boys and girls. Their mean age was 14.5±1.28 years old. When considering 4 ppm as the cut-off level of breath CO, sensitivity and specificity of self-reports were 100% and 93.7%, respectively. But at a breath CO cut-off of 3 ppm, self-reporting was 62.5% sensitive and 93.5% specific. According to our findings, we suggest that self-reports can be considered as a good tool to be used with a reasonable confidence to assess the smoking status.


Efficacy of peroral endoscopic myotomy for esophageal motility disorders after gastric surgery: Japan Achalasia Multicenter Study.
Patients with esophageal motility disorders (EMDs) including achalasia after gastric surgery have not been thoroughly characterized. Furthermore, the efficacy of peroral endoscopic myotomy (POEM) in this population should be clarified. In this retrospective multicenter study of 3707 patients with EMDs, 31 patients (0.8%) had a history of gastric surgery. Patient characteristics and POEM efficacy were compared between patients with and without previous gastric surgery. In patients with EMD after gastric surgery, age at EMD diagnosis was higher (72.0 years), male sex was predominant (90.3%), and the American Society of Anesthesiologists physical status score was higher (≥II, 48.4%). High-resolution manometry (HRM) findings did not reveal significant differences. In patients who underwent gastric surgery, atrophic gastritis was common (80.6%), and gastric cancer was the primary surgical indication (32.3%). Distal gastrectomy was performed in 28 patients (90.3%). POEM was effective (3.3% adverse events; 100% treatment success). The incidence rates of reflux esophagitis (RE) and symptomatic gastroesophageal reflux disease (GERD) were 60.0% and 16.7%, respectively, without significant intergroup differences, and severe RE was not observed in the long-term follow-up. Extended gastric myotomy was a risk factor for RE. Patients with gastric surgery often present severe disease manifestations; the surgical indication is mainly gastric cancer. HRM findings can be similarly used for diagnosis in patients with and without gastric surgery. POEM maintains safety and efficacy with acceptable RE and symptomatic GERD rates. To prevent RE, extended myotomy should be avoided.


Ciprofloxacin for infection prevention in patients with acute leukemia.
Ciprofloxacin, a new quinolone derivative, was given prophylactically (500 mg twice daily) to 15 patients with acute leukemia during remission induction treatment. The effect on the microbial flora of the alimentary tract was evaluated. A rapid elimination of Enterobacteriaceae was observed. Bacteriodes and Clostridium species were not affected. Few ciprofloxacin resistant strains were isolated but did not lead to colonization. In a randomized study 56 patients with acute leukemia received either ciprofloxacin or trimethoprim-sulfamethoxazole plus colistin for prevention of infections. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin. No infections caused by Gram-negative bacilli were seen in the ciprofloxacin group compared to 17 in the other group (p less than 0.02). Ciprofloxacin prevented colonization with resistant Gram-negative bacilli while 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole (p less than 0.01). Ciprofloxacin was better tolerated than trimethoprim-sulfamethoxazole + colistin; fewer side effects occurred.


Orientation illusions vary in size and direction as a function of task-dependent attention.
Adding an upright inner square frame to an outer tilted square frame causes a central rod's perceived orientation to be directionally opposite the usual rod-and-frame illusion (RFI). Zoccolotti, Antonucci, Daini, Martelli, and Spinelli (1997) attributed this double RFI (DRFI) to Rock's (1990) hierarchical organization principle. In Experiment 1, this explanation predicted results for small (11 degrees ) but not larger (22 degrees and 33 degrees ) outer frame orientations. In two experiments with the DRFI, bottom-up, goal-driven attention was varied and direct and indirect measures of the framework's influence were compared. In Experiment 2, the RFI angular function was compared with two other DRFI conditions: a direct measure of perceived rod orientation and an indirect measure of the inner frame. These conditions induced directionally opposite effects. In Experiment 3, direct and indirect measures of the inner frame's perceived tilt were compared. Angular functions differing in size and direction were obtained. Experiment 4 replicated the previous results, using a different psychophysical procedure. All the results were consistent with the hierarchical organization mechanism but suggested different processing strategies due to different attentional weights. They were also consistent with other recent findings based on the Bayesian approach to accounts of illusory phenomena (e.g., Jazayeri & Movshon, 2006, 2007; Weiss, Simoncelli, & Adelson, 2002).


Submersed macrophyte growth at low pH : II. CO2 × sediment interactions.
The submersed macrophyte Vallisneria americana was grown for seven weeks in a greenhouse to test for differences in the ability of three different sediments to support growth stimulation in response to CO2 enrichment at low pH. Plants accumulated 21- to 24-fold greater biomass at 10 × ambient CO2 concentrations than at ambient CO2 on all sediments. At both CO2 levels, plants grown on sediment from an acidified lake accumulated ca. 81%, and those grown on oligotrophic lake sediment ca. 47% as much biomass as plants grown on alkaline lake sediment. Despite striking CO2 and sediment effects on biomass accumulation, there was no significant interaction (using log-transformed data) between CO2 and sediment effects, indicating that all sediments allowed similar proportionate growth responses to CO2 enrichment. Plants grown on the less fertile sediments showed greater relative allocation to horizontal versus vertical growth by producing more rosette-bearing stolons in relation to plant height (leaf length) than plants grown on relatively fertile, alkaline lake sediment. Tissue analysis suggested that sediment effects on Vallisneria growth could be attributed neither to mineral putrient (nitrogen and phosphorus) limitation nor to aluminum toxicity in these low pH treatments. In any case, CO2 availability can be an important regulator of submersed macrophyte growth at low pH on a variety of sediment types, including those from oligotrophic and acidic lakes.


Identification and QTL mapping of resistance to Turnip yellows virus (TuYV) in oilseed rape, Brassica napus.
Partially dominant resistance to Turnip yellows virus associated with one major QTL was identified in the natural allotetraploid oilseed rape cultivar Yudal. Turnip yellows virus (TuYV) is transmitted by the peach-potato aphid (Myzus persicae) and causes severe yield losses in commercial oilseed rape crops (Brassica napus). There is currently only one genetic resource for resistance to TuYV available in brassica, which was identified in the re-synthesised B. napus line 'R54'. In our study, 27 mostly homozygous B. napus accessions, either doubled-haploid (DH) or inbred lines, representing a diverse subset of the B. napus genepool, were screened for TuYV resistance/susceptibility. Partial resistance to TuYV was identified in the Korean spring oilseed rape, B. napus variety Yudal, whilst the dwarf French winter oilseed rape line Darmor-bzh was susceptible. QTL mapping using the established Darmor-bzh × Yudal DH mapping population (DYDH) revealed one major QTL explaining 36% and 18% of the phenotypic variation in two independent experiments. A DYDH line was crossed to Yudal, and reciprocal backcross (BC1) populations from the F1 with either the susceptible or resistant parent revealed the dominant inheritance of the TuYV resistance. The QTL on ChrA04 was verified in the segregating BC1 population. A second minor QTL on ChrC05 was identified in one of the two DYDH experiments, and it was not observed in the BC1 population. The TuYV resistance QTL in 'R54' is within the QTL interval on Chr A04 of Yudal; however, the markers co-segregating with the 'R54' resistance are not conserved in Yudal, suggesting an independent origin of the TuYV resistances. This is the first report of the QTL mapping of TuYV resistance in natural B. napus.


Fluorides in dental public health programs.
The use of fluorides in dental public health programs has a long history. With the availability of fluoridation and other forms of fluorides, dental caries have declined dramatically in the United States. This article reviews some of the ways fluorides are used in public health programs and discusses issues related to their effectiveness, cost, and policy.


Breast, Ovarian, Uterine, Vaginal, and Vulvar Cancer Care in Low- and Middle-Income Countries: Prevalence, Screening, Treatment, Palliative Care, and Human Resources Training.
Breast, ovarian, uterine, vaginal, and vulvar cancers pose a significant risk to women's lives in low- and middle-income countries due to increasing incidence and presentation with advanced stage disease. There are challenges to screening and early detection and limitations in access to treatment and palliative care, and the current global health care workforce is insufficient. However, there is promise in development of telehealth strategies, task shifting, and increasing number of physician training programs to help address currently unmet needs.


Comparative study of CEA staining in gastric and colorectal cancer tissues.
Expression of CEA was studied in tissue sections from 140 cases of gastric and 54 cases of colorectal carcinoma by the immunoperoxidase technique. In some cases of gastric cancer, the intensity of CEA staining was compared with the CEA concentration by radioimmunoassay, and the intensity of the CEA staining was related to CEA concentration. CEA was more strongly positive in colorectal carcinomas than in gastric carcinomas. The intensity of the CEA staining was stronger in differentiated gastric and colorectal carcinomas than in anaplastic ones. No relationship was seen between the expression of CEA and the extent of disease in gastric or colorectal carcinoma. The CEA expression was related to the location of tumors in colorectal carcinomas, but not in gastric carcinomas.


Physico-chemical approach to study organotin sorption-desorption during solid-phase microextraction.
Solid-phase microextraction (SPME) has become a real alternative to liquid-liquid extraction in the field of speciation of organometallic compounds. Despite the high performance of this preconcentration technique, matrix effects in natural samples can affect the analytical precision. In order to understand the origin of these disturbances and control the extraction step as best as possible, the sorption-desorption behaviour of organotins was studied. In the first part, this paper discusses the analytical problems encountered in the daily use of SPME due to the particular problems observed for phenyltins. The sorption profile of these compounds was modelled using experimental design methodology to confirm the first-order kinetics. Desorption of the compounds was also observed after a given time and could not be attributed to competition between organotin compounds. In the same way, butyl- and phenyltins were studied in the presence of humic substances, which acted as representatives of organic matter found in natural samples. These substances drastically decrease the extraction yields, but do not affect the sorption profile of butyl- and phenyltins.


Behavioral and Cognitive Phenotypes of Patients With Amyotrophic Lateral Sclerosis Carrying SOD1 Variants.
SOD1 variants in patients with amyotrophic lateral sclerosis (ALS) have been associated to peculiar clinical features and disease progression but rarely to cognitive and behavioural impairment. This study aims at describing the features of frontotemporal syndromes in ALS patients carrying SOD1 variants. Italian patients with ALS were consecutively enrolled between 2012 and 2020 at our Motor Neuron Disease center. All underwent clinical assessment, extensive neurophysiological test battery for the evaluation of cognitive functions and behavior, and targeted next generation sequencing of SOD1, FUS, TARDBP, VCP, PFN1, TUBA4A, OPTN, SQSTM1, UBQLN2 and C9orf72 genes. Neuropsychological profiles of SOD1+ patients (SOD1+) were compared to those with no gene variants (SOD1-). To this aim, the occurrence of cognitive and behavioral impairment defined according to current guidelines, the number of pathological test performances based on Italian normative values, and scores of the Frontal Behavioural Inventory were collected. Among 288 patients consecutively examined, we identified 8 known pathogenic SOD1 variants and one variant of uncertain significance (p.Ser26Asn) not previously described in 14 ALS patients belonging to 11 families. The clinical phenotypes were mainly characterized by predominant lower motor neuron involvement with onset at the lower limbs, and one patient had bulbar onset. SOD1+ patients (n=14) were compared to SOD1- patients (N = 274). SOD1+ patients were younger than SOD1-, and both groups had similar functional motor disabilities and disease duration. Based on the overall neuropsychological findings, the percentage of SOD1+ and SOD1- patients with altered profiles were about 60%. However, behavioral impairment defined by the Strong criteria, and most commonly featuring with irritability and mental rigidity, was more frequent in SOD1+ than SOD1- patients, and mainly associated with variants in exon 5. Conversely, cognitive impairment was mainly found in SOD1- patients. Our findings from a large cohort of deeply phenotyped ALS patients demonstrated that behavioral involvement is more common than previously thought among patients harboring SOD1 variants, and that it is independent from patients' age and disease stage. These findings could be relevant for the assessment of clinical trial outcomes and disease management.


Inhibition on de novo synthesis of PCDD/Fs by an N-P-containing compound: Carbon gasification and kinetics.
In this study, an N-P-containing compound (ammonium dihydrogen phosphate (ADP)) and an auxiliary material (CaO) were used to inhibit the formation of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs). ADP significantly inhibited the formation of PCDD/Fs by the inhibition efficiencies of 98.45% for total concentration and 96.55% for toxic concentration. ADP was the best single inhibitor on toxic PCDFs (96.55%), and the inhibition on toxic PCDDs improved after ADP (90.91%) coupled with CaO (95.69%). In the temperature range of 300-350 °C, ADP inhibited the carbon gasification by reducing CO2 and CO (400%-500% (20 K/min)), which could attributed to the formation of Cu2P2O7 and copper nitrides from the Cu deactivation by P and N, respectively. However, the synergy of ADP and CaO decreased CO and CO2 by 200%-300% (20 K/min), because CaO could promote carbon gasification. In addition, the apparent activation energy (Ea) increased from 78.50 kJ/mol to 102.04 kJ/mol with the addition of ADP but decreased to 73.92 kJ/mol after adding ADP and CaO. These results revealed that one inhibition route of de novo synthesis was the inhibition of carbon gasification by ADP, while CaO mainly inhibited de novo synthesis via the consumption of HCl and Cl2. Furthermore, a reaction mechanism function in model fly ash was built as f(α)=2α-1/2/3, which included carbon gasification and de novo synthesis. The results pave the way for further research on the inhibition kinetics of PCDD/F and development of other inhibitors.


A Biomechanical Study of Hyoid Bone and Laryngeal Movements During Swallowing Comparing the Blom Low Profile Voice Inner Cannula and Passy-Muir One Way Tracheotomy Tube Speaking Valves.
The aim of this prospective, consecutive, cohort study was to investigate the biomechanical effects, if any, of the Blom low profile voice inner cannula and Passy-Muir one-way tracheotomy tube speaking valves on movement of the hyoid bone and larynx during swallowing. Ten adult patients (8 male, 2 female) with an age range of 61-89 years (mean 71 years) participated. Criteria for inclusion were ≥18 years of age, English speaking, and ability to tolerate both changing to a Blom tracheotomy tube and placement of a one-way tracheotomy tube speaking valve with a fully deflated tracheotomy tube cuff. Digitized videofluoroscopic swallow studies were performed at 30 frames/s and with each patient seated upright in the lateral plane. A total of 18 swallows (three each with 5 cc bolus volumes of single contrast barium and puree + barium × 3 conditions) were analyzed for each participant. Variables evaluated included larynx-to-hyoid bone excursion (mm), maximum hyoid bone displacement (mm), and aspiration status under three randomized conditions: 1. Tracheotomy tube open with no inner cannula; 2. Tracheotomy tube with Blom valve; and 3. Tracheotomy tube with Passy-Muir valve. Blinded reliability testing with a Pearson product moment correlation was performed on 20 % of the data. Intra- and inter-rater reliability for combined measurements of larynx-to-hyoid bone excursion and maximum hyoid bone displacement was r = 0.98. Intra- and inter-rater reliability for aspiration status was 100 %. No significant differences (p > 0.05) were found for larynx-to-hyoid bone excursion and maximum hyoid bone displacement during swallowing based upon an open tracheotomy tube, Blom valve, or Passy-Muir valve. Aspiration status was identical for all three randomized conditions. The presence of a one-way tracheotomy tube speaking valve did not significantly alter two important components of normal pharyngeal swallow biomechanics, i.e., hyoid bone and laryngeal movements. Aspiration status was similarly unaffected by valve use. Clinicians should be aware that the data do not support placement of a one-way tracheotomy tube speaking valve to reduce prandial aspiration.


An investigation of transportation logistics strategy on manufacturing supply chain responsiveness in developing countries: the mediating role of delivery reliability and delivery speed.
This study aims to investigate and examine the impact of delivery reliability (DR) and delivery speed (DS) on the relationship between a manufacturing firm's transportation logistics strategy (TLS) and supply chain responsiveness (SCR). Furthermore, it examine the impacts of SCR on manufacturing firm performance (MFP). A quantitative methodology was used for the purposes of gathering and analysing primary data for this empirical study, which included 212 participants in large-sized manufacturing firms in the Middle East Territory. A web-based survey was used for the data gathering process and applied after conducting a small pilot study. The conceptual model was tested by using a hypothesis-testing deductive approach. The findings are based on covariance-based analysis and structural equation modeling (SEM) using AMOS software. The findings show that DR is mediating partially the relationship between TLS and MSCR, and that DS is mediating fully the relationship; further, it is pointed out that SCR is supported with improved MFP. The empirical findings can have insightful implications for managers and practitioners in terms of boosting competitive advantage and financial performance.


Outcome of arthroscopically assisted lower trapezius transfer to reconstruct massive irreparable posterior-superior rotator cuff tears.
The purpose of this study is to report the outcome of arthroscopically assisted lower trapezius transfer to reconstruct irreparable posterior-superior rotator cuff tear. Forty-one consecutive patients with irreparable posterior-superior rotator cuff tears who underwent an arthroscopically assisted transfer of the lower trapezius transfer were included in this study. The patients' average age was 52 years (range 37-71), and average follow-up was 14 months (range 6-19 months). Nineteen patients had true pseudoparalysis preoperatively, whereas 66% had a prior failed rotator cuff repair. Outcome measures included visual analog scale (VAS) pain score, range of motion, Subjective Shoulder Value (SSV), and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Thirty-seven (90%) patients had significant improvement of all outcome scores: VAS, SSV, and DASH. The presence of a subscapularis tear did not affect the outcome. However, 3 patients who had preoperative rotator cuff arthropathy changes of the shoulder had persistent pain and limited range of motion of the shoulder after surgery, and 2 of them underwent reverse shoulder arthroplasty. Two additional patients had a traumatic rupture of the transfer as a result of fall (at 5 and 8 months postop). One underwent revision arthroscopic repair and did well after surgery, and the other had good pain relief but recurrent weakness and limited range of motion, and elected not to have a revision surgery. Arthroscopic-assisted lower trapezius transfer may lead to a good outcome in patients with massive irreparable posterior-superior rotator cuff tears, including patients with pseudoparalysis. The presence of an associated reparable subscapularis tear did not affect the outcome.


Fabrication of graphene with CuO islands by chemical vapor deposition.
Graphene prepared on Cu foil by chemical vapor deposition was studied as a function of post growth cooling conditions. CuO islands embedded in the graphene film were discovered and studied by scanning electron microscopy, atomic force microscopy, and X-ray photoemission spectroscopy. It is shown that nanostructured holes can be formed within a graphene film by reduction using hydrogen cooling immediately after film growth. We also observe the formation of symmetrical oxide islands in these holes. This study provides an easy way to fabricate a graphene + CuO composite, and the method may be extended to other graphene based structures.


Strong evidence that daily use of fluoride toothpaste prevents caries.
Medline, Cochrane Library, reference lists of identified articles and selected textbooks were used to source studies. Selected studies were randomized or controlled clinical trials of at least 2 years' duration with caries increment in the permanent (DMFS/T) or primary (dmfs/t) dentition as the endpoint. Reports published in Danish, English, French, German, Italian, Norwegian, Spanish or Swedish were included. For multiply reported trials the one with the longest follow-up period was included. Inclusion decisions and grading of the studies was performed independently by two of the authors. The main outcome was prevented fraction (PF). A pooled estimate was calculated for included studies. Fifty-four studies were included. There was strong evidence for a caries-preventive effect of daily use of fluoride toothpaste compared with placebo in the young permanent dentition (PF, 24.9%; standard deviation, +/-11.5%). Toothpastes containing 1500 ppm of fluoride had a superior preventive effect (additional PF, 9.7%; range 0-22%) compared with standard dentifrices of 1000 ppm fluoride. There was also strong evidence for higher caries reductions with supervised toothbrushing compared with unsupervised brushing. There was incomplete evidence regarding the effect of fluoride toothpaste in the primary dentition. This review reinforces the importance of daily toothbrushing with fluoridated toothpastes for preventing dental caries, although long-term studies in age groups other than children and adolescents are still lacking.


Obstetrical health care inequities in a universally insured health care system.
Racial and ethnic disparities in health care exist and are rooted in long-standing systemic inequities. These disparities result in significant excess health care expenditures and are due to complex interactions between patients, health care providers and systems, and social and environmental factors. In perinatal care, these inequities also exist, with Black patients being 3 to 4 times more likely to die of childbirth compared with White patients. Similar health care inequities may also exist in the Military Health System despite universal health care coverage, stable employment, and social programs that benefit military families. This study aimed to evaluate racial disparities in obstetrical outcomes in the Military Health System. This is a retrospective cohort study of deliveries from 2019 to 2021 in the Military Health System, which provides obstetrical care for approximately 35,000 annual deliveries. The study was conducted using National Perinatal Information Center data on cesarean delivery, postpartum hemorrhage, and severe maternal morbidity by race and ethnicity from direct-care military hospitals representing tertiary care medical centers and community hospitals in the United States and abroad. Chi-square analyses and binary logistic regression were used to compare groups. The cohort included 68,918 deliveries. Of these, 32,358 (47%) were White, 9594 (13.9%) Black, 3120 (4.5%) Asian Pacific Islander, 456 (0.7%) American Indian/Alaska Native, 19,543 (28.4%) other, 3976 (5.8%) unknown, 7096 (10.3%) Hispanic, 58,009 (84.2%) non-Hispanic, and 4399 (6.4%) other ethnicity. Rates of cesarean delivery were significantly higher for Black (30%; odds ratio, 1.44; 95% confidence interval, 1.37-1.52), Asian Pacific Islander (27%; odds ratio, 1.24; 95% confidence interval, 1.14-1.35), and other (26%; odds ratio, 1.20; 95% confidence interval, 1.15-1.25) compared with White race (23%) (P<.001). Postpartum hemorrhage rates were higher for Black (5.9%; odds ratio, 1.11; 95% confidence interval, 1.00-1.24) and Asian Pacific Islander (7.7%; odds ratio, 1.49; 95% confidence interval, 1.29-1.72) compared with White race (5.3%) (P<.001). Severe maternal morbidity was higher for Black (2.9%; odds ratio, 1.44; 95% confidence interval, 1.24-1.67), Asian Pacific Islander (2.9%; odds ratio, 1.45; 95% confidence interval, 1.15-1.82), and other (2.8%; odds ratio, 1.36; 95% confidence interval, 1.21-1.54) compared with White race (2.1%) (P<.001). For severe maternal morbidity excluding blood transfusions, rates were also significantly higher for Black (1%; odds ratio, 1.68; 95% confidence interval, 1.30-2.17) than for White race (0.6%) (P<.002). Hispanic ethnicity was associated with a lower rate of severe maternal morbidity excluding transfusions (0.5%; odds ratio, 0.68; 95% confidence interval, 0.48-0.98) compared with non-Hispanic ethnicity (0.7%) (P=.04). Racial disparities in obstetrical outcomes exist in the Military Health System despite universal health care coverage, with significantly higher rates of cesarean delivery and severe maternal morbidity in Black, Asian Pacific Islander, and other races compared with White race. These findings suggest that these disparities are likely related to other factors or social determinants of health rather than availability of health care and insurance coverage. Further work should include investigation into such social determinants of health to address their causes, including systemic and structural barriers.


Bronchoalveolar lavage during third-trimester pregnancy in patients with status asthmaticus: a case report.
Bronchial asthma is not uncommon among pregnant women. Especially, uncontrollable status asthmaticus may endanger both the lives of mother and fetus. We present a case of a late-phase pregnant woman in whom life-threatening status asthmaticus was relieved by repeated bronchoalveolar lavage (BAL) under controlled ventilation, followed by successful spontaneous vaginal delivery. This case may indicate that BAL should be considered as an option in status asthmaticus complicating pregnancy before terminating the pregnancy to save the lives of mother and fetus.


Comparative fractal analysis of cultured glia derived from optic nerve and brain demonstrate different rates of morphological differentiation.
O-2A progenitor cells derived from neonatal rat cerebral hemispheres or optic nerves, were induced to differentiate in culture into either oligodendrocytes or type 2 astrocytes. The fractal dimensions, a measure of morphological complexity, of the differentiating glial cells were measured over time. Analysis of the changes in fractal dimension (D) with respect to time revealed specific rates of growth for each glial phenotype and a specific final D. The time course of these changes is well fit by a simple mathematical model. While brain-derived oligodendrocytes matured faster than the astrocytes, they ultimately attained comparable levels of complexity, with similar maximum fractal dimensions. Oligodendrocytes from nerve also matured faster than nerve derived astrocytes, in contrast, however, they attained a greater morphological complexity than nerve astrocytes. While the brain-derived oligodendrocytes showed a faster rate of maturation than their optic nerve counterparts, astrocytes from both regions had similar rates of morphological differentiation. Self-similarity, a defining property of fractal objects was investigated, by determining the fractal dimension of cells over a range of magnifications. The calculated fractal dimension remained constant over a 10-fold range in optical magnification, illustrating that cultured glial cells exhibit this important characteristic of fractal objects. In addition, we analyzed the branching patterns of glial processes by the Sholl method and found that the results were not as interpretable or meaningful as those of fractal analysis.


Non-invasive coronary angiography with 16-slice spiral computed tomography: image quality in patients with high heart rates.
The purpose of this study was to assess segment image quality at high heart rates using 16-slice computed tomography and differential reconstruction for major coronary vessels. According to the following protocol, 16-slice CT coronary angiography in 46 patients with a mean heart rate of 86.3+/-11.8 was reconstructed. At three transverse planes, preview series were obtained and motion artifacts evaluated in 5% increments from 0-95% within the cardiac cycle. Relying on image quality in the previews, reconstructions were performed at three z-positions for each patient. Segment image quality was assessed in terms of artifacts and visibility. The effects of heart rate and trigger delay on image quality were analyzed. Optimal image quality was achieved at 25 to 35% of the cardiac cycle for the left circumflex (CX) and right coronary artery (RCA) or 30 to 40% for the left main (LM) and left anterior descending artery (LAD). Sixteen-slice CT and differential reconstruction produced good image quality with a low percentage of motion-degraded proximal and middle segments (8.8%). Grades were 1.5 for the LM, 1.9 for the LAD, 2.0 for the CX and 2.3 for the RCA. At high heart rates, good image quality of the coronary arteries is achieved by 16-slice CT and a sophisticated reconstruction strategy at peak to late systole.


In vitro tests in severe aplastic anaemia (SAA): a prospective study in 46 patients treated with immunosuppression.
Forty-six patients with severe aplastic anaemia (SAA) were studied for CFU-c growth on admission and 1 month post-treatment with immunosuppression (IS). Twenty-three patients became transfusion independent after IS, and were considered responders, and 23 did not. CFU-c growth from unfractionated bone marrow cells was comparable in both groups on admission and 1 month post-treatment. CFU-c growth from E rosette depleted BM cells (E-BM) was also comparable on admission. However, 1 month post-treatment, responders showed a significantly higher CFU-c growth (P = 0.02) from E-BM cells compared to non-responders. At the same time 7/8 responders studied showed T cell mediated suppression of autologous CFU-c growth. T cell depletion experiments do not give predictive information on the outcome of IS therapy on admission. They may, however, be helpful to identify responders early post-treatment.


The pathology of the involved tendons in patients with familial arthropathy and congenital camptodactyly.
In 2 sisters with congenital camptodactyly and joint effusions, abnormalities in tendons were restricted to the portion within synovial sheaths. This implied a disease of the tenosynovium, rather than one of the tendon itself. In areas of chronic involvement, some tendons were replaced by fibrous tissue. Significant portions of the tendons in fingers with camptodactyly were replaced by hard scars. Congenital camptodactyly is probably the result of an intrauterine tenosynovitis, rather than an isolated congenital anomaly.


Meta-analysis of the safety and efficacy of droxidopa for neurogenic orthostatic hypotension.
Droxidopa has been approved for the treatment of neurogenic orthostatic hypotension (NOH) under the US Food and Drug Administration accelerated approval program, which warrants confirmatory evidence on long-term efficacy of droxidopa. Hereby, we synthesize evidence from published randomized controlled trials (RCTs) about the safety and efficacy of droxidopa for patients with neurogenic orthostatic hypotension. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager version 5.3 for Windows. Subgroup analysis and sensitivity analysis were conducted to investigate long-term durability of droxidopa against placebo. Four RCTs with a total of 485 patients (droxidopa, n = 246; placebo, n = 239) were eligible for the final analysis. The mean difference (MD) of change in the main outcomes from baseline to endpoint favored droxidopa than placebo [Orthostatic Hypotension Questionnaire (OHQ) MD -0.61, P = 0.004; dizziness/lightheadedness score MD -0.83, P = 0.008; and standing systolic blood pressure (SBP) MD 4.09, P = 0.03]. The efficacy of droxidopa decreased gradually after 2 weeks, and its statistical significance was lost after 8 weeks (OHQ score MD -0.18, P = 0.61; dizziness/lightheadedness score MD -0.71, P = 0.11; and standing SBP MD 2.96, P = 0.29). None of the adverse events were significantly higher in the case of droxidopa compared to placebo. Droxidopa is a safe and effective drug for the short-term management of NOH symptoms. However, current evidence is insufficient to confirm the efficacy of droxidopa for long-term use. Therefore, further studies with increased sample size are needed.


Automated Decision Support System for Detection of Leukemia from Peripheral Blood Smear Images.
Peripheral blood smear analysis plays a vital role in diagnosing many diseases including cancer. Leukemia is a type of cancer which begins in bone marrow and results in increased number of white blood cells in peripheral blood. Unusual variations in appearance of white blood cells indicate leukemia. In this paper, an automated method for detection of leukemia using image processing approach is proposed. In the present study, 1159 images of different brightness levels and color shades were acquired from Leishman stained peripheral blood smears. SVM classifier was used for classification of white blood cells into normal and abnormal, and also for detection of leukemic WBCs from the abnormal class. Classification of the normal white blood cells into five sub-types was performed using NN classifier. Overall classification accuracy of 98.8% was obtained using the combination of NN and SVM.


Development of A recombinant nucleocapsid based indirect ELISA for the detection of antibodies to avian metapneumovirus subtypes, A, B, and C.
Nucleocapsid (N) protein is the most highly expressed of all avian metapneumovirus (aMPV) viral proteins and stimulates a substantial immune response in infected animals. Codon optimized recombinant N (rec-N) protein from aMPV subtypes A, B, and C were expressed using the baculoviral expression system in Trichoplusia ni (Tni) insect cells. A mixture of purified rec-N antigens from each subtype was used as a coating antigen and was evaluated in indirect ELISA (iELISA) to assess antibody response in serum samples collected from experimentally infected chickens and turkeys with different aMPV subtypes. Also, archived field serum samples that were collected from different poultry submissions were used. Receiver operating characteristic (ROC) analysis was performed using chicken and turkey serum samples that were confirmed by indirect fluorescent antibody (IFA) test for serostatus (positive n = 270, negative n = 610). The ROC analysis showed sensitivity and specificity of 97 % at a cut-off value of 0.25. The rec-N iELISA was compared with a commercial whole virus-based APV kit. The rec-N iELISA showed comparable results in detecting antibody response in aMPV infected chicken sera but was more sensitive in detecting early antibody response in aMPV infected turkey serum samples. Our results further confirm the presence of aMPV antibodies in Canadian domestic poultry populations. The developed aMPV-rec N iELISA offers a safe and valuable alternative to whole virus-based iELISA for serodiagnosis and seroepidemiological surveillance of the disease in domestic poultry.


A comparative analysis of label-free liquid chromatography-mass spectrometry liver proteomic profiles highlights metabolic differences between pig breeds.
The liver is a complex organ governing several physiological processes that define biological mechanisms affecting growth, feed efficiency and performance traits in all livestock species, including pig. Proteomics may contribute to a better understanding of the relationship between liver functions and complex production traits in pigs and to characterize this species as biomedical model. This study applied, for the first time, a label-free liquid chromatography-mass spectrometry (LC-MS) proteomic approach to compare the liver proteome profiles of two important heavy pig breeds, Italian Duroc and Italian Large White. Liver specimens were collected (after slaughtering) from performance tested pigs of these two breeds, raised in standard conditions. The label-free LC-MS method captured a total of 501 proteins of which 200 were subsequently considered in the between breeds comparison. A statistical pipeline based on the sparse Partial Least Squares Discriminant Analysis (sPLS-DA), coupled with stability and significance tests, was applied for the identification of up or down regulated proteins between breeds. This analysis revealed a total of 25 proteins clearly separating Italian Duroc and Italian Large White pigs. Among the top proteins differentiating the two breeds, 3-ketoacyl-CoA thiolase, mitochondrial (ACAA2) and histone H2B type 2-F (HIST2H2BF) were up-regulated in Italian Duroc pigs and carboxylesterase 3 (CES3) and ketohexokinase (KHK) were up-regulated in Italian Large White pigs. Fatty acid synthase (FASN), involved in fatty acid metabolism and encoded by a gene located in a QTL region for fatty acid composition, was up-regulated in Italian Large White pigs. The in silico protein interaction analysis showed that 16 of these proteins were connected in one big module. Bioinformatic functional analysis indicated that differentially expressed proteins were involved in several biological processes related to the metabolism of lipids, amino-acids, carbohydrates, cofactors and antibiotics/drugs, suggesting that these functions might distinguish Italian Duroc and Italian Large White pigs. This pilot comparative proteomic analysis of the porcine liver highlighted several biological factors that could determine the peculiar production potentials of these two heavy pig breeds, derived by their different genetic backgrounds.


Recommendations of mental health professionals and the general population on how to treat mental disorders.
The objectives of the study are (1) to assess the mental health literacy of mental health professionals, (2) to determine whether there is agreement between different professional groups with respect to different psychopathological conditions and (3) to compare the professionals' knowledge with that of the general population. Two representative samples of mental health professionals and laypersons were presented with a vignette depicting either a person with schizophrenia, major depression or without any psychiatric symptoms ('non-case'). Out of 18 treatment proposals, the respondents were asked to indicate the proposals regarded as helpful and those considered as being harmful, respectively, for the person depicted. Mental health professionals view their profession and less often their treatment methods as helpful. Dealing with the situation alone, electroconvulsive therapy, hypnotics and sedatives are consistently regarded as harmful. For the individual with schizophrenia, mental health professionals agree about helpful treatments. Regarding depression, a lack of consensus is found about treatment proposals such as psychiatric hospitalisation, antidepressants and complementary and alternative medicine. An important part of mental health professionals suggests medical help (psychologists and general practitioners) for the non-case vignette. Fewer nurses, social workers, vocational workers and occupational therapists ('other therapists') as compared to psychiatrists and psychologists recommend standard treatment methods. Professionals and the general population significantly differ in their attitudes towards the treatment suggestions, especially regarding medication and alternative medicine. To improve the treatment of mental disorders, various strategies must be considered. These include permanent education of all mental health professionals, especially nurses and other therapists. A special focus must be given to affective disorders and a potential (over-) treatment of normal behaviour.


Detection of fatty acid composition of trabecular bone marrow by localized iDQC MRS at 3 T: A pilot study in healthy volunteers.
Although a growing body of research shows that the bone marrow adipose tissue (BMAT) may play an essential role in bone inflammation and energy metabolism, available noninvasive methods for distinguishing different fatty acids in BMAT are still limited, in spite of their potential to provide novel biomarkers for bone related diseases. To assess the ability of a localized intermolecular double quantum coherence (iDQC) spectroscopy sequence to resolve more fatty acid peaks than conventional MR spectroscopy (MRS), like polyunsaturated fatty acids (PUFA), from the human BMAT in the presence of trabecular bone; To preliminarily investigate whether the fatty acids composition is different between different regions and groups. Compared with conventional MRS results, additional four fatty acids peaks were well resolved using the proposed method in human BMAT in the presence of trabecular bone. In addition, a different fat composition was found between distal femur and proximal tibia: fat was more unsaturated (vinyl, *p < 0.01; diallylic, *p < 0.01) in distal femur bone marrow than in proximal tibia, and this higher unsaturation level was caused by PUFA (r = 0.67, diallylic, *p < 0.01). No significant difference in fatty acid composition were found either between left and right legs, or between female and male in the healthy young subjects studied. This study demonstrated that the unsaturated fatty acids information of human BMAT in the presence of trabecular bone can be clearly identified with the localized iDQC at 3 T. The resolved peaks, especially PUFA, may serve as additional diagnostic biomarkers for BMAT related diseases in the future.


Squamous cell carcinoma in Kauai, Hawaii.
It is estimated that over 100,000 new cases of squamous cell carcinoma are diagnosed in the United States annually. This number is compounded by an increasing concern over the ozone layer depletion and the continued sunbathing behavior of many individuals. This could be particularly acute in Hawaii, which may have the highest rates of skin cancer in the country. We believe the updated information on skin cancer is essential to address the magnitude of the problem. A prospective 5-year population-based incidence study was conducted on Kauai, Hawaii, between 1983 and 1987 to investigate the frequency of squamous cell carcinomas in resident Caucasians. A total of 58 residents, 37 men and 21 women, were identified with an initial episode of squamous cell carcinoma during the 5-year period. The average annual incidence rate per 100,000 Kauai Caucasian residents, standardized to the 1980 U.S. white population, was 153 for men and 92 for women with a combined rate of 118. The average patient age was 66.4 years. The head and neck was the most common anatomic site, with the extremities second. Subsequent new squamous cell carcinoma occurred in 13.8% of patients. Only one patient (2%) developed a recurrence after treatment. Twenty-five patients (43%) had basal cell carcinoma simultaneously or at other earlier times. In Kauai the incidence rate of squamous cell carcinoma is the highest yet documented in the United States. No consistent trend in incidence rates was appreciated during this 5-year period.


Is the SII portion of the cross-bridge in glycerinated rabbit psoas fibers compliant in the rigor state?
To see whether the SII portion of the cross-bridge in rigor fibers is longitudinally compliant, we chemically cross-linked with dimethyl suberimidate the entire rod portion (including the SII portion) of myosin onto the surface of thick filaments in glycerinated rabbit psoas fibers, and studied the effect of the SII fixation on the stiffness of the rigor fibers. The cross-linking of fiber segments with full filament overlap increased the rigor stiffness by approximately 25%. Almost the same absolute amount of the stiffness increase was also observed in rigor fibers with half- or no filament overlap after the cross-linking, and a similar but somewhat larger increment of stiffness was observed in fiber segments cross-linked in relaxing solution. These results indicate that the stiffness increase is not produced by the fixation of the SII portion onto the thick filament surface, but is caused instead by the cross-linking of some parallel elastic elements in muscle, and therefore indicate that the SII portion of the cross-bridge is hardly longitudinally compliant in rigor fibers.


Use of patient-controlled psychiatric hospital admissions: mental health professionals' perspective.
In a patient-controlled admission (PCA) programme, the decision about hospital admission is made solely by the patient, with no gatekeeper function allocated to the mental health professionals (MHPs). Current knowledge about how MHPs experience and evaluate PCA is sparse. This Danish multi-centre study examined the MHP assessment of the PCA programme in daily clinical practice, and compared PCA evaluations made by MHPs and patients. A questionnaire was developed and a survey conducted over the course of a year at all Danish mental health units included in the PCA programme. MHPs made an overall evaluation of the PCA programme. At each unique PCA, both patient and MHP evaluated the specific admission when the patient entered the unit and at discharge. In total, 546 questionnaires were included in the survey, based on 252 unique MHPs. The MHPs rated the PCA programme positively. The MHPs believed that PCA helped patients receive early help and avoid long admissions. Overall, agreement was poor when comparing patients' and MHPs' evaluation of the same PCA. MHPs (and patients) seem to be in favour of implementing the PCA programme. However, results revealed that MHPs and patients have different views of what caused the patient to admit themselves and why patients were discharged. MHPs should be aware that patients might have other reasons for admitting and discharging themselves than what seems most obvious to the MHP.


Nucleotide composition and synonymous codon usage of open reading frames in Norovirus GII.4 variants.
Norovirus GII.4 variants, a genotype in genogroup II belonging to the genus Norovirus, is a single-strand positive sense RNA containing three open reading frames (ORF1, ORF2 and ORF3) and is the most important pathogen causing nonbacterial gastroenteritis outbreaks. By using bioinformatic softwares such as Codon W, SPSS and so on, a total of 292 strains of the viruses isolated from 1974 to 2016 were analyzed for nucleotide composition and synonymous codon usage in each ORF. The result shows that it is enriched for A over the other bases in nucleotide composition, G behind the other bases in the 3rd site of all synonymous codons in the three ORFs. The patterns of nucleotide composition and codon bias of ORF2 are similar to those of ORF3 and different from those of ORF1. There are generally UpA motif and CpG motif in the codons with the lowest proportion. Correspondence analysis indicates that the codon usage may be changing over a certain time period for ORF1 in 2006 and 2012, ORF2 in 2012, and ORF3 in 2013. ENC (effective number of codons) plot and other analyses indicate that both natural selection and mutational pressure play partly roles in the ORFs, but natural selection is more important for ORF2 and ORF3. Besides, we also found all optimal codons in the ORFs. The study provides a basic understanding of the mechanism for norovirus GII.4 codon usage bias. AbbreviationsORFOpen Reading FrameENCEffective Number of CodonsCOAcorrespondence analysisRSCURelative Synonymous Codon UsageCAICodon Adaptation IndexCBICodon Bias IndexFopfrequency of optimal codonsL_symnumber of synonymous codonsL_aalength amino acidsGRAVYgrand average of hydropathicityAromaaromaticityCommunicated by Ramaswamy H. Sarma.


Sorption of copper(II) and silver(I) by four bacterial exopolysaccharides.
Metal remediation was studied by the sorption of analytical grade copper Cu(II) and silver Ag(I) by four exopolysaccharides (EPS) produced by marine bacteria. Colorimetric analysis showed that these EPS were composed of neutral sugars, uronic acids (>20 %), acetate, and sulfate (29 %). Metal sorption experiments were conducted in batch process. Results showed that the maximum sorption capacities calculated according to Langmuir model were 400 mg g(-1) EPS (6.29 mmol g(-1)) and 333 mg g(-1) EPS (3.09 mmol g(-1)) for Cu(II) and Ag(I), respectively. Optimum pH values of Ag(I) sorption were determined as 5.7. Experiment results also demonstrated the influence of initial silver concentration and EPS concentrations. Microanalyzing coupled with scanning electron microscopy demonstrated the presence of metal and morphological changes of the EPS by the sorption of metallic cations. The Fourier transform infrared spectroscopy analysis indicated possible functional groups (e.g., carboxyl, hydroxyl, and sulfate) of EPS involved in the metal sorption processes. These results showed that EPS from marine bacteria are very promising for copper and silver remediation. Further development in dynamic and continuous process at the industrial scale will be established next.


Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core.
Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine. To extend previous findings of striatal hypersensitivity with behavioral observations and with cellular activity in the nucleus accumbens and prefrontal cortex in sensitized animals. Rats treated acutely with 0, 1, 2.5, or 5 mg/kg i.p. amphetamine and sensitized rats challenged with 1 mg/kg i.p. amphetamine were scored for stereotypy, rearing, and grooming, and locomotor activity recorded. c-fos positive nuclei were quantified in the nucleus accumbens and prefrontal cortex after expression of sensitization with 1 mg/kg i.p. amphetamine. Intense stereotypy was seen in animals treated acutely with 5 mg/kg amphetamine, but not in the sensitized group treated with 1 mg/kg amphetamine. The c-fos response to amphetamine in the accumbens core was augmented in amphetamine-pretreated animals with a shift in the distribution of optical density, while no effect of sensitization was seen in the nucleus accumbens shell or prefrontal cortex. A lack of stereotypy in the sensitized group indicates a dissociation of behavioral responses to amphetamine and striatal immediate-early gene activation patterns. The increase in c-fos positive nuclei and shift in the distribution of optical density observed in the nucleus accumbens core suggests recruitment of a new population of neurons during expression of sensitization.


Effect of enzymic assay conditions on sulfite reduction catalysed by desulfoviridin from Desulfovibrio gigas.
The type and the amount of end products resulting from sulfite reduction catalysed by a single partially purified desulfoviridin preparation from Desulfovibrio gigas were shown to depend upon the enzymic assay conditions employed. Both manometric and spectrophotometric assays were used, with reduced methyl viologen serving as the electron donor in each system. Trithionate, thiosulfate, tetrathionate and sulfide were identified as possible end products. In the manometric assays, sulfide production was favoured by high reduced methyl viologen concentrations, low sulfite concentrations and a pH value of 7.0 as opposed to 6.0. In the spectrophotometric assays, results approaching the stoichiometric conversion of sulfite to sulfide were obtained only at high initial reduced methyl viologen concentrations.


Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin.
To examine the role of ductus arteriosus (DA) constriction and loss of luminal blood flow in producing permanent closure of the DA in human infants. We studied 77 newborn infants (gestational age, 23 to 33 weeks) with asymptomatic patent ductus arteriosus (PDA), who had "complete clinical closure" (defined as the disappearance of all PDA signs) after treatment with indomethacin (three doses within 36 hours). All infants had an echocardiogram 24 to 36 hours after the last dose of indomethacin. They were then followed for the development of ductus reopening. Despite the absence of clinical signs, 18 (23%) of 77 infants still had some residual luminal blood flow according to their echocardiograms. The failure to obliterate luminal blood flow completely was directly related to the infant's postnatal age when treatment was begun and to the amount of fluid administered before treatment. Subsequently the DA reopened in 16 (21%) of 77 infants. As predicted, infants with residual luminal blood flow after indomethacin treatment had a higher rate of subsequent clinical reopening than did those with no luminal flow. In addition, immature infants had a significantly higher reopening rate than did more mature infants. The increased risk of reopening in immature infants was seen even when indomethacin caused complete obliteration of ductus luminal blood flow. The DA of immature infants is resistant to the constriction-induced ischemic damage that is necessary for subsequent permanent closure of the vessel.


SDT analysis of experimental thermal pain, with "signal" and "no-signal" being determined psychophysically.
In a signal-detection experiment, the effects of repeated pain stimulation and the induction of fear on pain thresholds and SDT parameters were studied. "Signal" and "no-signal" were not defined physically, but by means of an independent criterion as the primary sensations "pain" and "no-pain." First, the relationship between sensation levels for "phasic" (short stimulus, used in the SDT procedure) and "tonic" (longer stimulus, used in the criterion measurement) heat stimuli was determined in 14 subjects. It was quadratic (polynomial regression) and sufficient to define the distinction between "signal/pain" and "no-signal/no-pain." In the signal-detection experiment, a significant upward trend (adaptation) in threshold parameters, but no systematic change in the SDT parameters (discrimination ability and response bias) was found. Manipulation of anxiety by instructions caused unsystematic changes in discrimination ability. The procedure employed determines both the absolute strength of pain sensation and the ability to discriminate pain from no pain. These variables proved to be independent.


Penalized canonical correlation analysis to quantify the association between gene expression and DNA markers.
Inter-individual variation in gene expression levels can arise as an effect of variation in DNA markers. When associating multiple gene expression variables with multiple DNA marker variables, multivariate techniques, such as canonical correlation analysis, should be used to deal with the effect of co-regulating genes. We adapted the elastic net, a penalized approach proposed for variable selection in regression context, to canonical correlation analysis. The number of variables within each canonical component could be greatly reduced without too much loss of information, so the canonical components become easier to interpret. Another advantage is that it groups co-regulating genes, so that they end up in the same canonical components. Furthermore, our adaptation works well in situations where the number of variables greatly exceeds the number of subjects.


Outbreak of Q fever among US military in western Iraq, June-July 2005.
An outbreak of Q fever occurred in 22 (58%) of 38 Marines deployed to Iraq in 2005. Fever (in 100% of patients), respiratory symptoms (76%), and gastrointestinal symptoms (53%) were common. Possible risk factors included dust and exposure to animals and ticks.


A multi-analytical evaluation of the depositional pattern on open-air rock art panels at "Abrigo del Lince" (Badajoz, Spain).
Microscopic observation correlated with chemical-mineralogical characterization was performed on pigment samples from "Abrigo del Lince" rock art site (V-IV millennium BC), in order to provide contributions to the study of prehistoric schematic art on granite in the province of Badajoz (Spain). The research objectives include the understanding of technological and cultural aspects, as well as of conservation and deterioration issues related to the pictographs. The multi-analytical approach encompasses the integration of microscopic observation, SEM-EDS analysis, micro-Raman spectroscopy, and ATR-FTIR and allowed to achieve a multispectral overview of the samples and to describe their varied composition and the alteration pattern which connects them. The main phases overlying the granitic bedrock and involved in this sequence are as follows: hematite, whewellite, and gypsum. While hematite could be stratigraphically considered the most ancient layer and assigned to the use of red ochre as a pigment, whewellite and gypsum are the main constituent of the alteration layer which forms a patina over the pictographs, due to weathering processes. Finally, the role of biofilms in rock art conservation is discussed, suggesting that, especially for what concern thin and homogenous layers of oxalates, their presence should not be necessarily considered an issue.


Elimination kinetics of L-alanyl-L-glutamine in ICU patients.
A randomised, double blind, placebo-controlled study was performed giving 0.5 g x kg(-1) x day(-1) of undiluted alanyl-glutamine (20%) or saline in a peripheral vein during 4 hours in ICU patients (n = 20). During the infusion period a steady state in plasma concentration was reached for alanyl-glutamine, but not for alanine, glutamine or glutamate. On the other hand there was no accumulation of any of the amino acids, as the pre-infusion concentrations were reached within 8 hours after the end of infusion. The half-life of the dipeptide was 0.26 hours (range, 0.15-0.63 h). The distribution volume of alanyl-glutamine was larger than the extracellular water volume, indicating a rapid hydrolysis of the dipeptide. There was no detectable alanyl-glutamine in the urine of any of the patients. All patients had excretion of small amounts of amino acids in urine, but the renal clearance of alanine, glutamine and glutamate were not different between the two groups.


Heterogeneous NADH fluorescence during post-anoxic reactive hyperemia in saline perfused rat heart.
In the present study epicardial NADH fluorescence photographs were taken of rat hearts during dynamic transitions of oxygen content of the myocardium. Hearts were perfused in a Langendorff set-up where it was possible to switch between low and high-pO2 perfusates. NADH fluorescence photographs were taken with a suitable fluorescence set-up and photo negatives digitized and analyzed by use of a computer. Restoration of perfusion with a high-pO2 solution resulted in a reactive hyperemic flow being established. Prior to the occlusion being lifted high NADH fluorescence was observed. Reactive hyperemic flow was associated with heterogenic NADH fluorescence patterns which diminished as control flow was restored. The patterns observed during reactive hyperemia were identical to those observed when tissue oxygen was restored by high-pO2 perfusion following high flow hypoxia achieved by low-pO2 perfusion. This study shows that heterogenic epicardial flow patterns are associated with reactive hyperemia.


Cultural beliefs about rape and victims' response in three ethnic groups.
Cultural definitions of rape were assessed among 101 African-American, Hispanic, and non-Hispanic white female rape victims and 89 nonvictims matched for ethnicity, age, marital status, and socioeconomic status. Hispanics scored highest and whites lowest both in perceived community victim-blaming and in victims' psychological distress. Social and treatment implications are discussed.


[Effectiveness of BNT162b2 vaccine to preventing COVID-19 in healthcare personnel].
To assess the effectiveness of the vaccine against SARS-CoV-2 (BNT162b2) in healthcare personnel of a health department. Test-negative case̶control study. Healthcare personnel with suspected COVID-19 and healthcare personnel close contacts of COVID-19 cases were included between January 27th and June 6th, 2021. They were PCR tested for SARS-CoV-2; those with positive PCR were considered cases and those with negative PCR were considered controls. The adjusted vaccine effectiveness (aVE) to prevent COVID-19 cases and their 95% confidence interval (95%CI) were calculated using the formula VE=(1-odds ratio)×100. 624 healthcare personnel were included, of which 43 (6.9%) were considered cases and 581 (93.8%) controls. The aVE of the complete regimen was 96.3% (95%CI: 82.5̶99.2). The aVE of the incomplete pattern was 68.0% (95%CI: 30.0̶85.4). The administration of the complete pattern of BNT162b2 vaccine against SARS-CoV-2 is effective for the prevention of cases of COVID-19 in healthcare personnel.


N-terminal domains in two-domain proteins are biased to be shorter and predicted to fold faster than their C-terminal counterparts.
Computational analysis of proteomes in all kingdoms of life reveals a strong tendency for N-terminal domains in two-domain proteins to have shorter sequences than their neighboring C-terminal domains. Given that folding rates are affected by chain length, we asked whether the tendency for N-terminal domains to be shorter than their neighboring C-terminal domains reflects selection for faster-folding N-terminal domains. Calculations of absolute contact order, another predictor of folding rate, provide additional evidence that N-terminal domains tend to fold faster than their neighboring C-terminal domains. A possible explanation for this bias, which is more pronounced in prokaryotes than in eukaryotes, is that faster folding of N-terminal domains reduces the risk for protein aggregation during folding by preventing formation of nonnative interdomain interactions. This explanation is supported by our finding that two-domain proteins with a shorter N-terminal domain are much more abundant than those with a shorter C-terminal domain.


Treating post-traumatic tremor with deep brain stimulation: report of five cases.
Post-traumatic tremor is one of the most common movement disorders resulting from severe head trauma. However, literature regarding successful deep brain stimulation (DBS) treatment is scarce, resulting in ambiguity regarding the optimal lead location. Most cases support the ventral intermediate nucleus, but there is evidence to defend DBS of the zona incerta, ventral oralis anterior/posterior, and/or a combination of these targets. We report five patients with disabling post-traumatic tremor treated with DBS of the ventral intermediate nucleus and of the globus pallidus internus. Patients were referred to the Vanderbilt Movement Disorders Division, and surgical intervention was determined by a DBS Multidisciplinary Committee. Standard DBS procedure was followed. Patients 1-4 sustained severe diffuse axonal injuries. Patients 1-3 underwent unilateral ventral intermediate nucleus DBS for contralateral tremor, while Patient 4 underwent bilateral ventral intermediate nucleus DBS. Patients 1-3 experienced good tremor reduction, while Patient 4 experienced moderate tremor reduction with some dystonic posturing of the hands. Patient 5 had dystonic posturing of the right upper extremity with tremor of the left upper extremity. He was treated with bilateral DBS of the globus pallidus internus and showed good tremor reduction at follow-up. Unilateral or bilateral DBS of the ventral intermediate nucleus and bilateral DBS of the globus pallidus internus may be effective and safe treatment modalities for intractable post-traumatic tremor. Further studies are needed to clarify the optimal target for surgical treatment of post-traumatic tremor.


Cytochrome b as a useful tool for the identification of blowflies of forensic interest (Diptera, Calliphoridae).
In Forensic Entomology the fast and accurate identification of insects collected at the scene of events is essential if errors are to be avoided in estimating infestation times of interest and determining the post-mortem interval (PMI). Traditional identification based on morphological characteristics can be complicated due to physical similarities between different species, especially at immature stages. Genetic analysis provides a fast and reliable identification method. In this paper, molecular analysis is focused on a fragment of 307bp of the mitochondrial DNA region that codes for cytochrome b (cyt b). Six species belonging three genera of Calliphoridae of forensic interest (Calliphora vicina, Calliphora vomitoria, Lucilia sericata, Lucilia caesar, Lucilia ampullacea, Chrysomya albiceps) were collected and identified. These are the most common species of cadaveric entomofauna on the Atlantic seaboard of the Iberian Peninsula. The results show the robustness of the cyt b locus as a diagnostic tool, since its nucleotide variability enables reliable distinctions to be drawn between species. This study also contributes new consense sequences which may be of interest for correct species identification.


Molecular mechanism of vitamin D receptor action.
The vitamin D system is unique in that distinct calcium homeostatic functions and cell growth regulatory activities are mediated through a single ligand, calcitriol, acting through a specific receptor exhibiting ubiquitous tissue expression, the vitamin D receptor (VDR). The VDR is a member of a superfamily of nuclear steroid hormone receptors which regulate gene transcription by interacting with response elements in gene promoters. Structure-function analysis of the VDR protein has defined distinct domains involved in DNA binding, ligand binding, receptor dimerisation and gene transactivation, including a C-terminal activation function domain (AF-2) that is important for cofactor interaction. A model for regulation of gene transcription by the VDR is evolving and proposes VDR interaction with various components of the basal transcriptional machinery, including newly defined coactivators and corepressors, which may act to regulate gene transcription by altering histone acetylation and chromatin structure. This review describes the vitamin D endocrine system and the role of the VDR in regulating this system, including the molecular basis for the diverse actions of synthetic calcitriol analogues in the treatment of autoimmune disease and cancer.


Cocooning strategy: Pertussis vaccination coverage rate of parents with a new-born in 2016 and 2017 in France.
The "cocooning" strategy was introduced in 2004 to protect infants too young to be vaccinated against pertussis, by immunizing their parents and close relatives. The study objective was to assess its implementation 12 years after its introduction by estimating the pertussis vaccination coverage rates (VCR) among parents of newborns. Pertussis VCR were estimated among all women who gave birth and men who took paternity leave, in 2016 or 2017, from a 1/97th random sample of French claims data. Two distinct study periods were defined based on current recommendations for the cocooning strategy: the "common practice" and the "parental project" periods. In 2016, the pertussis VCR of women having given birth and men having taken paternity leave was 47.2 and 47.1%, respectively (46.1 and 45.6% in 2017, respectively). About one quarter of vaccinations were performed during the "parental project" period, with the vaccine most frequently reimbursed during the month of childbirth for women (57.1% in 2016 and 49.4% in 2017) and before or during the month the paternity leave began for men (about 78% in both 2016 and 2017). General practitioners were the main prescribers in private practice, even during the "parental project" period. To optimize the protection for infants, the main objective of the cocooning strategy, pertussis immunization coverage of adults and seniors needs to be improved. Moreover, cocooning vaccination linked to a parental project needs to be performed earlier, during pregnancy (for those around the mother) or in immediate post-partum (e.g., during the maternity stay).


Kallikrein proteoforms and reproductive parameters in stallion are conditioned by climate.
Horses are seasonal polyoestrous animals, and the photoperiod is the main factor modulating their reproductive activity. There is no consensus on the andrological and biochemical factors that influence breeding seasonality. To assess the involvement of climate in reproduction, Mangalarga Marchador stallions were monitored over 1 year regarding semen quality and seminal plasma proteome. Here, we show that kallikrein (KLKs) proteoforms in seminal plasma are involved in climate conditioning of reproduction. During the breeding season, greater abundance and different types of KLKs occurred simultaneously to lower sperm motility, greater semen volumes and higher concentrations of glucose and cholesterol. Considering that vasodilation due to activation of the kallikrein-kinin system and the consequent inhibition of the renin-angiotensin system may be associated with lower sperm motility, unravelling the involvement of KLK proteoforms in reproductive seasonality is a priority in horse breeding.


What makes a life event traumatic for a child? The predictive values of DSM-Criteria A1 and A2.
The Diagnostic and Statistical Manual of Mental Disorders (DSM)-Criteria A1 and A2 for posttraumatic stress disorder (PTSD) have been discussed extensively, with several studies in adults or adolescents supporting the removal of Criterion A2. However, solid research in children is missing. This study evaluated the DSM-Criteria A1 and A2 in predicting posttraumatic stress in children. A sample of 588 Dutch school children, aged 8-18 years, completed a self-report questionnaire to determine if they met Criteria A1 and/or A2. Their posttraumatic stress response was assessed using the Children's Revised Impact of Event Scale. The contribution of Criterion A2 to the prediction of posttraumatic stress in children is of greater importance than the contribution of Criterion A1. Children who met Criterion A2 reported significantly higher levels of posttraumatic stress and were nine times more likely to develop probable PTSD than children who did not meet Criterion A2. When Criterion A1 was met, a child was only two times more likely to develop probable PTSD as compared with those where Criterion A1 was not met. Furthermore, the low sensitivity of Criterion A1 suggests that children may regularly develop severe posttraumatic stress in the absence of Criterion A1. The remarkably high negative predictive value of Criterion A2 indicates that if a child does not have a subjective reaction during an event that it is unlikely that he or she will develop PTSD. In contrast to most adult studies, the findings of this study emphasize the significant contribution of Criterion A2 to the prediction of posttraumatic stress in children and raise fundamental questions about the value of the current Criterion A1.


Performance index for quality response of dynamical systems.
The use of performance indices to measure the quality response of dynamical systems is studied in this paper. A definition of a general performance index is proposed which is easy to compute, easy to interpret, and flexible enough to account for different cases commonly presented in practice. The index is tested over several dynamical responses obtained from different systems obtaining good results, in the sense that it is able to rank the behaviors from best to worse, compared with a pattern response.


Improving fermentation, protein preservation and antioxidant activity of Moringa oleifera leaves silage with gallic acid and tannin acid.
Whether tannins reducing proteolysis is related to protease or the antioxidant capacity could be preserved during Moringa oleifera leaves (MOL) ensiling are unclear. In the present study, MOL ensiled with 1% and 2% gallic acid (GA) or tannic acid (TA) were analyzed for fermentation parameters, protein fractions, protease activities and antioxidant capacity on day 3, 7, 14 and 30 of ensiling. The results showed that GA and TA decreased dry matter loss (11.13% vs 8.35% and 3.11%, in the level of 2%) and proteolysis (nonprotein-N: 56.31% vs 32.64% and 26.04% TN). Meanwhile, GA and TA increased pH, yeasts number, ammonia-N content and aminopeptidase activity. The antioxidant capacity of MOL silage gradually increased during ensiling, and was dramatically enhanced by the addition of GA and TA. In conclusion, this study suggests that GA and TA could help to improve the preservation of protein and antioxidant capacity during MOL ensiling.


Ozone reduces lifespan and alters gene expression profiles in Rhyzopertha dominica (Fabricius).
Rhyzopertha dominica is one of the most important stored grain pests that seriously damage rice and wheat. At present, the method of controlling stored grain pests mainly relies on insecticide fumigation. However, the excessive use of pesticides not only leaves pesticide residues, with harmful effects on human health and the environment, but also induces insect resistance. Ozone is a strong oxidant with the characteristics of easy decomposition and without residue. Although ozone has been widely used in the food industry in recent years, research on the control of stored grain pests is limited. In this research, we used ozone treatment to control R. dominica adults and explore the molecular mechanisms that affect them. Here, we found that ozone treatment on R. dominica adults could decrease life span and increase malondialdehyde (MDA) content, as well as reduce activity of total superoxide dismutase (SOD) and catalase (CAT). Using RNA-seq technology, we identified 641 genes that were differentially expressed between ozone-treated and control R. dominica adults [fold-change of ≥ 2 (q-value < 5%)]. When comparing ozone treatment with control R. dominica adults, 330 genes were significantly upregulated and 311 were downregulated. RT-qPCR confirmed that 11 genes were differentially expressed in ozone-treated and control R. dominica adults. These genes were involved in insect cuticle protein and antioxidant system. This research showed that ozone treatment could reduce the lifespan of R. dominica through antioxidant system. It is an environmentally benign method for the control of stored grain pests and has great development potential.


Second fertility-sparing surgery and fertility-outcomes in patients with recurrent borderline ovarian tumors.
At the time of recurrence, many borderline ovarian tumor (BOT) patients are still young with fertility needs. The purpose of this study is to evaluate the reproductive outcomes and recurrence rate of second fertility-sparing surgery (FSS) in women with recurrent BOTs. Seventy-eight women of childbearing age diagnosed with recurrent BOTs from November 2009 to 2020 whose primary treatment was FSS were included. The FIGO stage I disease accounted for 46.2% and serous BOT accounted for 87.2% in the study group. Forty-seven patients underwent second FSS, and the remaining 31 underwent radical surgery (RS). Seventeen patients relapsed again after second surgery, but no malignant transformation and tumor-associated deaths were reported. Compared to FIGO stage I, the FIGO stage III tumors were more likely to relapse, but there was no statistical difference in pregnancy rate among patients with different stages. In the second FSS group, recurrence rate was higher in patients who underwent oophorocystectomy compared to patients with unilateral salpingo-oophorectomy (USO), but the pregnancy rate was similar. There was no significant difference in postoperative recurrence risk between USO and RS. The recurrence rate was not associated with operative route (laparoscopy or laparotomy), or lymphadenectomy, or postoperative chemotherapy. Among the 32 patients who tried to conceive, the pregnancy rate was 46.9% and live birth rate was 81.3%. Unilateral salpingo-oophorectomy is a safe procedure for FIGO stage I recurrent BOT patients with fertility needs, and can achieve a high postoperative pregnancy rate and live birth rate.


Perioperative treatment and biomarker analysis of LP002, an anti-PD-L1 antibody, plus chemotherapy in resectable gastric and gastroesophageal junction cancer.
The addition of immune checkpoint inhibitors to perioperative chemotherapy in operable gastric or gastroesophageal junction (GEJ) cancer has become one of the research hotspots, while reliable biomarkers for efficacy are lacking. We conducted a phase 1 trial to assess the safety and efficacy of LP002, an anti-PD-L1 antibody, plus chemotherapy as perioperative treatment in patients with gastric or GEJ cancer. We enrolled patients with resectable and PD-L1 positive gastric or GEJ cancers. Eligible patients received three preoperative and six postoperative cycles of intravenous LP002 with cisplatin and 5-fluorouracil, repeated every 2 weeks. The primary endpoint was safety. Secondary endpoints included rate of margin-free (R0) resection and pathological complete response (pCR). We also characterized changes in the tumor immune microenvironment using multiplex immunofluorescence (MIF) staining and next-generation sequencing (NGS) with pre- and post-treatment tumor samples. Thirty patients were enrolled, of whom 28 had GEJ cancer. With a median follow-up of 7.9 months, all patients completed preoperative treatment, and 27 patients underwent surgery. Twenty-four patients underwent R0 resection. Six patients (20.0%) had Mandard tumor regression grade (TRG) 1-3, including one achieving pCR. Twenty-seven patients had treatment-related adverse events (TRAEs), while grade 3-4 TRAEs were observed in 11 patients. No treatment-related deaths occurred. MIF staining revealed that TRG 1-3 group was associated with a higher density of PD-L1+/CD68+ cells in the pre-treatment tumor parenchyma than TRG 4-5 group (p = 0.048). NGS studies with paired pre- and post-treatment tumor samples revealed the disappearance of pre-existing mutations, the emergence of new mutations, and variations in the abundance of mutations after preoperative LP002 and chemotherapy. Meanwhile, tumor mutational burden decreased in patients with TRG 1-3 (p = 0.0313). LP002 plus cisplatin and 5-fluorouracil are safe in patients with gastric or GEJ cancer, and patient selection via appropriate biomarkers is needed in the future.


A Retrospective Study of Maxillofacial Fractures at a Tertiary Care Centre in North India: A Review of 1674 Cases.
To examine the pattern of maxillofacial fractures in patients treated at the SMS Hospital in Jaipur, India, over a two-year period. A retrospective study was conducted from October 2019 to September 2021, which recorded various data of patients with maxillofacial fractures, including age, sex, site distribution, cause of injury, type of facial bone fractures, soft tissue injuries, dentoalveolar trauma, and type of treatment. The days spent in the hospital before and after surgery were also recorded. The study included 1674 patients, with a male-to-female ratio of 4.07:1 and males being the most affected at 80.3%. The most common cause of injury was road traffic accidents (53.5%), followed by falls (18.6%) and assaults (16.1%). Mandibular fractures accounted for 38% of all fractures, with the parasymphysis being the most common site for fractures. Open reduction and internal fixation (ORIF) and intermaxillary fixation (IMF) were the most common treatment options for mandibular fractures. The study highlights the need for strict enforcement of traffic rules and road safety laws, along with education and preventive measures to reduce the incidence of maxillofacial trauma. The pattern of maxillofacial injuries can provide useful information for designing programs towards the prevention and management of maxillofacial trauma.


Expression of bcl-2, bcl-x, bax and bak in renal parenchyma, oncocytomas and renal cell carcinomas.
Proteins of the bcl-2 family are important regulators of programmed cell death. Alterations in the expression of these proteins may contribute to the progression of cancer. Expression of bcl-2, bcl-x, bax and bak was investigated by immunohistochemistry and Western-blotting of regular and alterated renal parenchyma as well as in 57 renal cell carcinomas. Bcl-2, bcl-x and in part bax were found to be overexpressed in inflammed renal parenchyma, whereas atrophic tubuli predominantly stained for bcl-2 and to a lesser degree for bcl-x and bax. Only little bak expression was detected in alterated tubuli. Moderate to strong expression for bcl-2, bcl-x, bax and bak was found in 24, 38, 2 and 13 of 57 carcinomas, respectively. Bcl-2, bcl-x, bax and bak expression were correlated to tumor type. Chromophilic carcinomas stained stronger for bcl-2, bcl-x and bax, whereas chromophobic carcinomas stained stronger for bcl-x, bax and bak compared to clear cell carcinomas. Expression of bak correlated with that of bcl-x and with an unfavorable histology as indicated by nuclear grading in these tumors. Our findings suggest that expression of bcl-2 and bcl-x may be important for cell survival only in a subset of renal cell carcinomas, and that the anti-apoptotic effect of these proteins appears to be frequently bypassed possibly by other factors impeding programmed cell death.


Cooperative binding of Stat1-2 heterodimers and ISGF3 to tandem DNA elements.
Interferon (IFN)-alpha-activated Stat1 homodimers and Stat1-2 heterodimers bind to GAS elements, whereas the transcription factor ISGF3, which contains Stat1, Stat2 and p48, binds to ISREs. We now find that Stat1-2 dimers can form heterotetramers on tandem GAS sites and that the heterotetramers have a much higher binding affinity for a double GAS site than do heterodimers for a single site, suggesting cooperativity mediated through protein-protein interactions. Stat1-2 heterotetramers can also be detected with a single GAS site, again indicating cooperativity mediated through protein-protein interactions. Deleting 40 amino acid residues from the N-terminus of Stat1 abolished Stat1-Stat2 heterotetramer formation, but did not affect heterodimer formation and an N-terminal peptide containing the first 120 residues of Stat2 inhibited heterotetramer formation but did not affect heterodimer formation. Thus, the N-terminal regions of both Stat1 and Stat2 are important for cooperative DNA binding, and heterodimers probably interact with each other through these regions. Cooperative binding of ISGF3 was also observed using the tandem ISREs from the IFN-alpha responsive promoter of the 6-16 gene. A more abundant and larger complex was formed with a probe containing two ISREs than with a probe containing a single ISRE. The N-terminal regions of both Stat1 and Stat2 are important for the cooperative binding of ISGF3 to tandem ISREs but not to a single site. The cooperative DNA-binding activities of ISGF3 and Stat1-2 dimers are likely to contribute to the transcriptional activation of those IFN-alpha-responsive genes that have tandem DNA elements.


[Morphologic characterization and biological aspects of evolutive forms of Babesia bigemina (Smith and Kilborne, 1893) (Protozoa: Babesiidae) in Boophilus microplus (Canestrini, 1887)].
The development of Babesia bigemina in Boophilus microplus were studied in experimental conditions, using crossed-breed bovine from free-area of these parasites. Stages of the hemoparasites were observed in the tick vector, starting from the infected red-blood cells observed in the gut of engorged females, from the first 24 hours after detachment to the emergence of sporokinets in the larvas. In the period from 24 to 48 hours after detachment of the engorged females (DEF), the presence of some infected red-blood cells was verified, beside the occurrence of ray bodies and of vermiculars forms, known as oocynets. Since 72 hours after the DEF, the of okinets presence was observed in the cytoplasm of the epithelium cells besides of great sporokinets number in development. At same period, the presence of sporokinets of B. bigemina in the hemolymph samples was observed inside the hemocytes. After the fourth day of incubation beside the presence of the sporokinets was also verified in the Malpighi's tubes and ovaries. As well as in the ticks eggs from the sporokinets were also observed ticks eggs from the fourty day after the natural detachment of the engorged females of the host.


The role of PP2A-associated proteins and signal pathways in microcystin-LR toxicity.
Microcystins are a family of monocyclic heptapeptides produced by cyanobacteria during water blooms. Microcystin-LR (MC-LR) is the most common member of this family. Microcystins induce a variety of toxic cellular effects, including oxidative damage, apoptosis, cytoskeletal destabilization, and cancer cell invasion. Recent studies have examined the molecular mechanism of their toxicity. Protein phosphatase 2A (PP2A) is emerging as a critical regulator of the microcystin-induced molecular network. Furthermore, it has been shown that several molecules or signal pathways associated with PP2A play important roles in microcystin-induced toxic effects. This review summarizes the recent research progress of the molecular mechanism and focuses on the role of PP2A in MC-LR toxicity, which will contribute to a better understanding of the mechanism of microcystin toxicity, and will provide biomarkers for toxicity assessment and control.


Impact of COVID-19 on Public Mental Health and the Buffering Effect of a Sense of Coherence.
It is claimed that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on mental health. However, to date, prospective studies are lacking. Moreover, it is important to identify which factors modulate the stress response to the pandemic. Previously, sense of coherence (SOC) has emerged as a particularly important resistance factor. This prospective study aimed to assess the impact of the COVID-19 outbreak on mental health and to investigate the ability of pre-outbreak SOC levels to predict changes in psychopathological symptoms. This study assessed psychopathological symptoms and SOC before and after the COVID-19 outbreak as well as post-outbreak COVID-19-related traumatic distress in a German-speaking sample (n =1,591). Bivariate latent change score (BLCS) modeling was used to analyze pre- to post-outbreak changes in psychopathological symptoms and the ability of SOC to predict symptom changes. Overall, there was no change in psychopathological symptoms. However, on an individual-respondent level, 10% experienced a clinically significant increase in psychopathological symptoms and 15% met cut-off criteria for COVID-19-related traumatic distress. Using BLCS modeling, we identified a high-stress group experiencing an increase in psychopathological symptoms and a decrease in SOC and a low-stress group showing the reversed pattern. Changes in SOC and psychopathological symptoms were predicted by pre-outbreak SOC and psychopathological symptom levels. Although mental health was stable in most respondents, a small group of respondents characterized by low levels of SOC experienced increased psychopathological symptoms from pre- to post-outbreak. Thus, SOC training might be a promising approach to enhance the resistance to stressors.


Development of an Online Curriculum for Surgeons on the Use of Pelvic Magnetic Resonance Imaging in Rectal Cancer and Results of a Pilot Study.
High-resolution pelvic magnetic resonance imaging (MRI) is a critical tool in the management of patients with rectal cancer. An on-line curriculum was developed for surgical trainees on the interpretation of pelvic MRI in rectal cancer for clinical staging and surgical planning. The online curriculum was developed using the six-step approach to curriculum development for medical education. The curriculum incorporated case-based learning, annotated videos, and narrated presentations on key aspects of pelvic MRI in rectal cancer. A pilot study was conducted to assess curriculum effectiveness among Complex General Surgical Oncology (CGSO) fellows using pre- and post-intervention assessments. Of 15 eligible fellows, nine completed the pilot study (60%). The fellows' median confidence score after completing the online curriculum (40, IQR: 33-46) was significantly higher than their baseline median confidence score (23, IQR: 14-30), P = 0.0039. The total practical assessment score significantly increased from a pre-median score of 9 (IQR: 8-11) to a post-median score of 14 (IQR: 13-14), P = 0.0078. A subgroup analysis revealed a significant change in the knowledge assessment with a median score of 7 compared to a baseline median score of 4, Z = 2.64, P = 0.0078. However, the skills assessment showed no significant change. The case-based online curriculum had a positive impact on CGSO fellows' knowledge and confidence in the utilization of pelvic MRI for patients with rectal cancer. This unique on-line curriculum demonstrates a mechanism to enhance shared educational collaboration across CGSO fellowships and other surgical training programs.


Influence of L-arginine and vitamin C on the autonomic nervous system in chronic heart failure secondary to ischemic cardiomyopathy.
In this study, we used spectral analysis to assess changes in respiratory recording variability during infusion of L-arginine and vitamin C, individually or together, in patients with chronic heart failure. We found that healthy subjects have a substantial ability to modulate sympathetic-mediated peripheral vascular resistance through endothelial synthesis of nitric oxide. Patients with chronic heart failure lose this ability.


Role of ketogenic metabolic therapy in malignant glioma: A systematic review.
Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including malignant glioma. Ketogenic metabolic therapy (KMT), i.e. nutritional intervention with ketogenic or low-glycemic diets, has been proposed as an anti-neoplastic strategy in glioma patients. We here review the rationale and existing data investigating KMT in management of patients with malignant glioma and discuss the promise and potential challenges of this novel strategy. Results from published clinical studies and ongoing clinical trials on the topic are systematically reviewed, including 6 published original articles and 10 ongoing clinical trials. Search criteria for this review entailed the databases MEDLINE, EMBASE, Cochrane CENTRAL, and Google Scholar, as well as ICTRP (WHO) and ClinicalTrials.gov (NIH) registries. A substantial amount of preclinical literature demonstrates KMT efficacy and safety in model systems of malignant glioma. Clinical literature indicates KMT safety and feasibility; 2 clinical studies suggest KMT-associated anti-neoplastic efficacy and clinical benefit. Ongoing clinical trials address KMT safety and metabolic impact, patient compliance, and patient clinical/survival benefit. While clinical evidence is still limited in this evolving field, increasing numbers of ongoing clinical trials suggest that KMT is emerging as a potential therapeutic option and might be combinable with existing anti-neoplastic treatments for malignant glioma. Emerging clinical data will help answer questions concerning safety and efficacy of KMT, and are aiming to identify the most promising KMT regimen, compatibility with other anti-cancer treatments, ethical aspects, and impact on quality of life of cancer patients.