Summary and Assessment of Studies on Cardiac Aging in Nonhuman Primates.
Nonhuman primates (NHP) are important translational models for cardiac aging. To assess progress in this research area and to provide a reference for other investigators, we identified papers indexed in PubMed to determine what species, ages, outcomes, treatments, and approaches have been studied. Since 1983, 33 studies of cardiac aging in NHP have been published. Of these, 27 used species of macaque, 6 baboon, 1 vervet, 1 orangutan, and 1 marmoset (some studies were multispecies). Common research approaches were echocardiography, ECG, and histology of the left ventricle. Only 10 studies performed sex-based analyses. The average age of the oldest macaque studied was 26 y. The reported mean lifespan of macaques in captivity is around 30 y. The age of the oldest baboon studied was 24 y. Baboons in captivity are reported to live on average to 21 y. Twelve studies took a "life course" approach, studying animals of a wide range of ages from less than or equal to 10 y through the late teens to thirties, and employing analyses designed to show change over time. Keeping NHP into old age is a major challenge for biomedical research. The ideal design is to start monitoring in early life and to track how cardiac structure and function change with age. Important issues for future research are an increased focus on life-course approaches, investment in existing life-course NHP cohorts, better reporting of study sample characteristics, more molecular studies to identify genetic risk factors and mechanisms, attention to sex as a biological variable, a move away from descriptive reports to mechanistic studies, development of biomarkers to predict disease risk, and exploration of interventions that are implemented early in life to prevent or delay age-related disease later in life. Reducing exposure to early life adversity, identifying early-life biomarkers of aging and age-related disease, and early treatment can contribute to longer health span.


Endoscopic submucosal dissection for rectal epithelial neoplasia.
The technique of endoscopic submucosal dissection (ESD) has recently been developed for en-bloc resection of gastric tumors. For oncological reasons and in order to improve the patients' quality of life, it may be desirable to use the same technique for rectal neoplasia. Thirty-five consecutive patients with rectal neoplasia who had a preoperative diagnosis of large intraepithelial neoplasias with submucosal fibrosis or located on the rectal folds were enrolled. ESD was carried out with the same technique previously described for the stomach, with some modifications. The efficacy, complications, and follow-up results of the treatment were assessed. The rates of en-bloc resection and en-bloc plus R0 resection were 88.6 % (31 of 35) and 62.9 % (22 of 35), respectively. Hemoglobin levels did not drop by more than 2 g/dl in any of the patients after ESD. None of the patients had to receive blood transfusions or undergo emergency colonoscopy due to bleeding during ESD or hematochezia after ESD. Perforation during ESD occurred in two patients (5.7 %), who were managed with conservative medical treatment after endoscopic closure of the perforation. Excluding three patients in whom additional surgery was carried out, all but one of 32 patients were free of recurrence during a mean follow-up period of 36 months (range 12 - 60 months). The exception was a patient in whom a multiple-piece resection was required; the recurrent (residual) tumor, found 2 months after ESD, was a small adenoma that was again treated endoscopically. ESD is applicable in the rectum with promising results, but the technique is still at a developmental stage and patients should be informed of the potential risks.


Course of behaviour problems of children with cerebral palsy: the role of parental stress and support.
Cerebral palsy (CP) is a well-recognized neurodevelopmental condition persisting through the lifespan. In many individuals with CP, motor disorders are accompanied by other disturbances, including emotional and behavioural problems. Little is known on the course of such problems, also in relation to possible exacerbating or mitigating factors. Aims of this study were to test whether parental stress and support, apart from the severity of CP of the child, played a significant role in the course of behaviour problems. The participants aged 9, 11 and 13 were assessed (baseline) and followed up after 1, 2 and 3 years. Situational and relational sources of support and stress for the primary caregiver were rated with a questionnaire: (CBCL), behaviour problems with the Child Behaviour Checklist. Physicians rated motor ability using the Gross Motor Function Classification System. Behaviour problems of children with CP started significantly higher than in the general population, but diminished over the 3-year period. Older children showed less problems overall, and girls showed less externalizing problems than boys. Children with the most severe CP had more externalizing problems; effects on internalizing problems were not significant. Across time, an excess of stress vs. support related to parents' socio-economic and living situation and to parents' social relationships was positively related to total behaviour problems, internalizing and externalizing behaviours of children. Levels of behaviour problems are elevated but diminish during adolescence for children with CP. Severity of CP plays a role as well as the family context in terms of the stress and support that caregivers experience.


The Application of Hough Transform and Canny Edge Detector Methods for the Visual Detection of Cumuliform Clouds.
The increase in flying time of unmanned aerial vehicles (UAV) is a relevant and difficult task for UAV designers. It is especially important in such tasks as monitoring, mapping, or signal retranslation. While the majority of research is concentrated on increasing the battery capacity, it is also important to utilize natural renewable energy sources, such as solar energy, thermals, etc. This article proposed a method for the automatic recognition of cumuliform clouds. Practical application of this method allows diverting of an unmanned aerial vehicle towards the identified cumuliform cloud and improving its probability of flying into a thermal flow, thus increasing the flight time of the UAV, as is performed by glider and paraglider pilots. The proposed method is based on the application of Hough transform and Canny edge detector methods, which have not been used for such a task before. For testing the proposed method a dataset of different clouds was generated and marked by experts. The achieved average accuracy of 87% on the unbalanced dataset demonstrates the practical applicability of the proposed method for detecting thermals related to cumuliform clouds. The article also provides the concept of VilniusTech developed UAV, implementing the proposed method.


Assembly of functional U1 and U2 human-amphibian hybrid snRNPs in Xenopus laevis oocytes.
Oligonucleotides complementary to regions of U1 and U2 small nuclear RNAs (snRNAs), when injected into Xenopus laevis oocytes, rapidly induced the specific degradation of U1 and U2 snRNAs, respectively, and then themselves were degraded. After such treatment, splicing of simian virus 40 (SV40) late pre-mRNA transcribed from microinjected viral DNA was blocked in oocytes. If before introduction of SV40 DNA into oocytes HeLa cell U1 or U2 snRNAs were injected and allowed to assemble into small nuclear ribonucleoprotein particle (snRNP)-like complexes, SV40 late RNA was as efficiently spliced as in oocytes that did not receive U1 or U2 oligonucleotides. This demonstrates that oocytes can form fully functional hybrid U1 and U2 snRNPs consisting of human snRNA and amphibian proteins.


Zaltidine: an effective but hepatotoxic H2-receptor antagonist.
Zaltidine is a new H2-receptor antagonist. This study compares the safety and efficacy of zaltidine with those of placebo in the short-term treatment of duodenal ulcer. One hundred and thirty-five patients were randomly allocated to 4 weeks' treatment with either 150 mg zaltidine once daily or placebo. Fifty-nine were treated for a full 4 weeks with zaltidine before the trial was stopped. Healing rates after 4 weeks of zaltidine and placebo were 86% and 19%, respectively (p less than 0.001). Five patients in the zaltidine group had increased serum aminotransferase levels at the final (4-week) visit. The values normalized when treatment was stopped. Liver biopsy specimens provide strong evidence of drug-induced injury. Hepatic damage was associated with plasma levels of zaltidine in the upper half of the observed range. Zaltidine appears to be an effective treatment of duodenal ulcer. However, the incidence of hepatic damage (8%) seems higher than with commonly used H2-receptor antagonists.


Genetic changes in beef cow traits following selection for calving ease.
One approach to reducing calving difficulty is to select heifers with higher breeding value for calving ease. Calving ease is often associated with lower birth weight and that may result in other possible effects on lifetime productivity. Females from experimental select and control calving ease lines within each of the seven populations were compared. Random samples of 720 heifers from lines selected for better calving ease breeding values and 190 heifers from control lines selected for average birth weights were followed through four parities. Select and control lines within the same population were selected to achieve similar yearling weight breeding values. Weights of sampled heifers in select lines were 2.6 kg (P < 0.01) lighter at birth but not different from control lines at weaning. Select lines had significantly shorter hip height, lighter mature weight, and greater calving success at second parity. Their calves were born significantly earlier with lighter weights and less assistance. Significant interactions with parity showed fewer calves assisted and greater calf survival to weaning as heifers but negligible differences with control lines in later parities. Steer progeny sampled from these dams in select lines (n = 204) were not different from steers in control lines (n = 91) for hot carcass weight but had significantly greater fat depth. Two production systems were compared considering the seven populations as replicates. The systems differed in selection history of females (select and control lines) and the use of bulls within their lines as young cows, but used the same bulls in both lines as older cows. Cows were culled after single unsuccessful breeding and kept for up to four parities. Select line cows tended (P ≤ 0.10) to wean more calves and stay in the herd longer. They were assisted significantly fewer times at calving and had greater calf weight gain to weaning when evaluated over their herd life. Mature weights were lighter in select lines, but marketable cow weight from the systems was nearly identical. Control lines did have more marketable young cow weight and select lines older cow weight. Weaned calf weight per heifer starting the system was significantly greater for the select heifer system due to greater survival of calves from heifers and greater calving success at second parity. No important unfavorable effects of genetic differences in calving ease were identified in this experiment.


Clinical reasoning and advanced practice privileges enable physical therapist point-of-care decisions in the military health care system: 3 clinical cases.
Physical therapists frequently make important point-of-care decisions for musculoskeletal injuries and conditions. In the Military Health System (MHS), these decisions may occur while therapists are deployed in support of combat troops, as well as in a more traditional hospital setting. Proficiency with the musculoskeletal examination, including a fundamental understanding of the diagnostic role of musculoskeletal imaging, is an important competency for physical therapists. The purpose of this article is to present 3 cases managed by physical therapists in unique MHS settings, highlighting relevant challenges and clinical decision making. Three cases are presented involving conditions where the physical therapist was significantly involved in the diagnosis and clinical management plan. The physical therapist's clinical privileges, including the ability to order appropriate musculoskeletal imaging procedures, were helpful in making clinical decisions that facilitate timely management. The cases involve patients with an ankle sprain and Maisonneuve fracture, a radial head fracture, and a pelvic neoplasm referred through medical channels as knee pain. Clinical pathways from point of care are discussed, as well as the reasoning that led to decisions affecting definitive care for each of these patients. In each case, emergent treatment and important combat evacuation decisions were based on a combination of examination and management decisions. Physical therapists can provide important contributions to the primary management of patients with musculoskeletal conditions in a variety of settings within the MHS. In the cases described, advanced clinical privileges contributed to the success in this role.


Remediation of Radiation-Induced Cognitive Dysfunction through Oral Administration of the Neuroprotective Compound NSI-189.
Clinical management of primary and secondary central nervous system (CNS) malignancies frequently includes radiotherapy to forestall tumor growth and recurrence after surgical resection. While cranial radiotherapy remains beneficial, adult and pediatric brain tumor survivors suffer from a wide range of debilitating and progressive cognitive deficits. Although this has been recognized as a significant problem for decades, there remains no clinical recourse for the unintended neurocognitive sequelae associated with these types of cancer treatments. In previous work, multiple mechanisms have been identified that contribute to radiation-induced cognitive dysfunction, including the inhibition of neurogenesis caused by the depletion of radiosensitive populations of stem and progenitor cells in the hippocampus. To explore the potential neuroprotective properties of a pro-neurogenic compound NSI-189, Long-Evans rats were subjected to a clinically relevant fractionated irradiation protocol followed by four weeks of NSI-189 administered daily by oral gavage. Animals were then subjected to five different behavioral tasks followed by an analysis of neurogenesis, hippocampal volume and neuroinflammation. Irradiated cohorts manifested significant behavioral decrements on all four spontaneous exploration tasks. Importantly, NSI-189 treatment resulted in significantly improved performance in four of these tasks: novel place recognition, novel object recognition, object in place and temporal order. In addition, there was a trend of improved performance in the contextual phase of the fear conditioning task. Importantly, enhanced cognition in the NSI-189-treated cohort was found to persist one month after the cessation of drug treatment. These neurocognitive benefits of NSI-189 coincided with a significant increase in neurogenesis and a significant decrease in the numbers of activated microglia compared to the irradiated cohort that was given vehicle alone. The foregoing changes were not accompanied by major changes in hippocampal volume. These data demonstrate that oral administration of a pro-neurogenic compound exhibiting anti-inflammatory indications could impart long-term neurocognitive benefits in the irradiated brain.


Analgesic drugs in the management of pain.
The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally eliminated.


[Cyclic groups of nonlinear transformations in morphology and the conception of cyclogenesis].
When describing multiunit organic forms, it is expedient to generalize the classic science on biological symmetries of similarity at the expense of transition to symmetry operations from wider groups of transformations, first of all mebiusian and projective. A vast class of biological structures is successfully modelled on the base of cyclic groups not only the linear, but also non-linear transformations. This is evidently connected with existence of morphogenetically significant biochemical cycles. The suggested means of mathematical modelling for biological symmetries open new possibilities of morphometrical analysis and investigation of a known problem of morphogenetic parallelisms. The results obtained prove V. V. Vernadsky's hypothesis on biological significance of the non-Euclidian geometry.


A family with complement factor D deficiency.
A complement factor D deficiency was found in a young woman who had experienced a serious Neisseria meningitidis infection, in a deceased family member with a history of meningitis, and in three relatives without a history of serious infections. The patient and these three relatives showed a normal activity of the classical complement pathway, but a very low activity of the alternative complement pathway and a very low capacity to opsonize Escherichia coli and N. meningitidis (isolated from the patient) for phagocytosis by normal human neutrophils. The alternative pathway-dependent hemolytic activity and the opsonizing capacity of these sera were restored by addition of purified factor D. The family had a high degree of consanguinity, and several other family members exhibited decreased levels of factor D. The gene encoding factor D was found to contain a point mutation that changed the TCG codon for serine 42 into a TAG stop codon. This mutation was found in both alleles of the five completely factor D-deficient family members and in one allele of 21 other members of the same family who had decreased or low-normal factor D levels in their serum. The gene sequence of the signal peptide of human factor D was also identified. Our report is the first, to our knowledge, to document a Factor D gene mutation. The mode of inheritance of factor D deficiency is autosomal recessive, in accordance with the localization of the Factor D gene on chromosome 19. Increased susceptibility for infections in individuals with a partial factor D deficiency is unlikely.


Congenital infantile fibrosarcoma mimicking a cutaneous vascular lesion: a case report and review of the literature.
Congenital infantile fibrosarcoma (CIFS) is a rare neoplasm of infancy that occurs most frequently in the extremities, and when presenting in the skin, may sometimes resemble infantile hemangiomas or other vascular lesions. Clinically, these tumors differ from hemangiomas in the time of onset, morphology, and growth pattern and must be evaluated histologically for definitive diagnosis. We describe an infant with a neoplasm involving the distal left forearm initially presumed to be a vascular lesion after evaluation by two separate ultrasound studies. He presented at seven weeks of life with a multinodular lesion that had enlarged significantly since birth, and the skin biopsy revealed a fibrosarcoma. This case highlights an unusual cutaneous presentation of CIFS, which varies in appearance from the previous 12 cases reported in the literature. We review the clinical manifestations of these congenital masses and emphasize early diagnosis for conservative therapy and improved prognosis.


[Intestinal uptake and transfer of zinc after supplement of 2,4-dinitrophenol and ouabain].
The effect of the inhibitors 2,4-dinitrophenol (DNP) and g-strophantin (ouabain) on the intestinal uptake and cellular transfer of zinc (Zn) and the effect of the organic ligands histidine and EDTA were studied in vitro with everted intestinal sacs of normally maintained rats. Zn was added to the incubation solution as ZnCl2 or as ZnCl2 mixed with histidine in a molar ratio of 200 : 1 and mixed with EDTA in a molar ratio of 1 : 1 or 10 : 1. The DNP in a concentrationof 0.05 mM proved sufficient to greatly inhibit the uptake and transfer of Zn from the solution containing ZnCl2 mixed with an excess of histidine. DNP also reduced Zn absorption when ZnCl2 alone as added. On the other hand, the presence of DNP in the solution containing ZnCl2 with EDTA was found to increase the transfer of Zn and its ligand. In the presence of EDTA, Zn absorption may, therefore, be controlled by the uptake and transfer of the ligand. Ouabain at the contration of 5 mM and 10 mM greatly reduced Zn uptake by the intestinal wall and the celluar Zn transfer from the solution containing ZnCl2 and histidine. There was only a small effect of ouabain on Zn absorption whether ZnCl2 is added alone or with EDTA. The addition of an excess of histidine as ligand to ZnCl2 in the control groups markedly improved Zn absorption. In contrast to this, the addition of EDTA to ZnCl2 reduces the intestinal Zn uptake and increases the transfer of Zn compared to ZnCl2 alone.


Heart Transplantation in Adults with Congenital Heart Disease.
Steady advances in the diagnosis and management of congenital heart disease over the last few decades has resulted in a growing population of adults with congenital heart disease (ACHD). Consequently, there has been a parallel increase in the number of ACHD patients plagued with end-stage heart failure. Even so, the transplantation rate for these patients has remained low, at about 3% of all adult heart transplants. This review discusses the scope of transplantation for ACHD, including indications and contraindications, specific challenges and nuances, and post-transplant outcomes.


Spinal cord stimulation as adjuvant during chemotherapy and reirradiation treatment of recurrent high-grade gliomas.
Relapsed high-grade gliomas (HGGs) have poor prognoses and there is no standard treatment. HGGs have ischemia/hypoxia associated and, as such, drugs and oxygen have low access, with increased resistance to chemotherapy and radiotherapy. Tumor hypoxia modification can improve outcomes and overall survival in some patients with these tumors. In previous works, we have described that cervical spinal cord stimulation can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism. The aim of this current, preliminary, nonrandomized, study was to assess the clinical effect of spinal cord stimulation during brain reirradiation and chemotherapy deployed for the treatment of recurrent HGG; the hypothesis being that an improvement in oxygenated blood supply would facilitate enhanced delivery of the scheduled therapy. Seven patients had spinal cord stimulation applied during the scheduled reirradiation and chemotherapy for the treatment of recurrent HGG (6 anaplastic gliomas and 1 glioblastoma). Median dose of previous irradiation was 60 Gy (range = 56-72 Gy) and median dose of reirradiation was 46 Gy (range = 40-46 Gy). Primary end point of the study was overall survival (OS) following confirmation of HGG relapse. From the time of diagnosis of last tumor relapse before reirradiation, median OS was 39 months (95% CI = 0-93) for the overall study group: 39 months (95% CI = 9-69) for those with anaplastic gliomas and 16 months for the patient with glioblastoma. Posttreatment, doses of corticosteroids was significantly decreased (P = .026) and performance status significantly improved (P = .046). Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits further research.


The quality of ionising radiations emitted by radionuclides incorporated into mammalian cells.
Radionuclides which decay by electron capture accompanied by Auger electron cascades, or by beta emission are thought to be excessively damaging when incorporated into the molecular structure of mammalian cell nuclei and thereby pose a radiation hazard which is not assessable by conventional dosimetry. Survival data, from the literature, for 125I, 77Br, 3H and 131I have been re-analysed to extract cross sections for inactivation, by the slowing down charged particle fluence, as these are absolute specifications of the radiation quality. When comparison is made with results similarly expressed for external irradiation with heavy particle and photon beams, the qualities of the low-energy emitters 125I, 77Br and 3H are found to approach those for heavy particles. An explanation for the damage mechanism is sought in a recently developed model for radiation action. The results are consistent with the interpretation that electron damage is caused predominantly at the end of the tracks, and the actual incorporation simply ensures that the slowing down fluence of low-energy tracks interacts preferentially in the vicinity of the radiosensitive sites. The absolute biological effectiveness of these radiations can be expressed quantitatively in terms of the model parameters.


Seroprevalence of Rickettsia typhi and Rickettsia conorii infection among rodents and dogs in Egypt.
A serological survey of 1813 rodent and 549 dog sera, collected from 1979 to 1986 from animals in 16 Egyptian Governorates were tested for antibody to Rickettsia typhi and Rickettsia conorii by the indirect fluorescent antibody test. Only three of 82 (4%) sera from Rattus rattus collected near Aswan had antibody to R. conorii. The prevalence of R. typhi antibody in dog sera was only 0.4% (n = 549) while 25% (n = 547) of Rattus norvegicus and 11% (n = 1138) of R. rattus had measurable antibodies. Among the other rodents, antibody was demonstrated in only 2% (n = 45) of Arvicanthis spp., and 1% (n = 83) of Acomys spp. Collectively, rodents captured in the Nile Delta had a higher prevalence (mean 24% (n = 787] than those captured in the Nile Valley (mean 4% (n = 650]. Antibody to R. typhi was detected in rodents collected in all port cities: ismailiya, 13%; Port Said, 9%; Suez, 9%; Safaga, 16%; Quseir, 32% and Alexandria, 34%. These data showed evidence of R. typhi infection among rodents in widespread geographic localities of Egypt and suggested that infected rodents may be a source of human infections.


Managing angina in the elderly: an update.
Angina pectoris in the elderly is usually due to fixed coronary arteriosclerotic disease. Management includes the use of nitrates and beta- and calcium-blocking drugs. A combination of these drugs may be necessary in patients with severe symptoms. Each of these drugs has potential side effects. These drugs should be started in small dosages and gradually increased, determined by the patient's response. Angina with associated disease states should determine what specific drugs are selected.


Characterisation of immune responses in healthy foals when a multivalent vaccine protocol was initiated at age 90 or 180 days.
Protection from infectious disease requires antigen-specific immunity. In foals, most vaccine protocols are delayed until 6 months to avoid maternal antibody interference. Susceptibility to disease may exist prior to administration of vaccination at age 4-6 months. The aim of this investigation was to characterise immune activation among healthy foals in response to a multivalent vaccine protocol and compare immune responses when foals were vaccinated at age either 90 or 180 days. Randomised block design. Twelve healthy foals with colostral transfer were blocked for age and randomly assigned to vaccination at age 90 days (treatment) or at age 180 days (control). Vaccination protocols included a 3-dose series and booster vaccine administered at age 11 months. Immune response following vaccination at age 90 or 180 days was comparable for several measures of cellular immunity. Antigen specific CD4+ and CD8+ expression of interleukin-4, interferon-γ and granzyme B to eastern equine encephalomyelitis, western equine encephalomyelitis, West Nile virus, tetanus toxoid, equine influenza and equine herpesvirus-1/4 antigens were evident for both groups 30 days after initial vaccine and at age 344 days. Both groups showed a significant increase in antigen-specific immunoglobulin G expression following booster vaccine at age 11 months, thereby indicating memory immune responses. The data presented in this report demonstrate that young foals are capable of immune activation following a 3-dose series with a multivalent vaccine, despite presence of maternal antibodies. Although immune activation does not automatically confer protection, several of the immune indicators measured showed comparable expression in foals vaccinated at 3 months relative to control foals vaccinated at age 6 months. In high-risk situations where immunity may be required earlier than following a conventional vaccine series, our data provide evidence that foals respond to immunisation initiated at 3 months in a comparable manner to foals initiated at an older age.


The tolerability of a combined hepatitis A and typhoid vaccine in children aged 2-16 years: an observational study.
Combined hepatitis A and typhoid vaccines have been widely used globally and proven to be safe, well tolerated and efficacious in adults. The combined hepatitis A and typhoid vaccine (Vivaxim) available in Australia is licenced for use from age 16 years but the monovalent components are approved for use from age 2 years. Advantages of a single injection have led to widespread 'off-label' use of Vivaxim in children. This study aimed to investigate the tolerability of Vivaxim in children aged 2-16 years. A prospective observational study was conducted at Travel Medicine Alliance clinics across Australia. Children who required vaccination for both hepatitis A and typhoid were offered the option of receiving Vivaxim. Parents were contacted 3 days post-vaccination and asked to respond to a questionnaire on adverse events following immunization (AEFIs). Reactions to Vivaxim were compared with reported reactions to the monovalent vaccines. Our study included 425 children who received Vivaxim, including 189 (44.5%) who received other vaccines on the same day. No serious AEFIs were reported, and 26.8% did not experience any side effects. In children who did not receive other vaccines in the same arm as Vivaxim (n = 325), most common local reactions were sore arm (70.5%), redness (16.0%) and swelling (11.1%). Reports of local AEFIs in our subjects was significantly more common than those reported for the individual monovalent vaccines. In children who did not receive other vaccines on the same day (n = 236), the most common systemic reactions were tiredness/lethargy/malaise (5.9%), headache (4.2%), fever (3.4%) and sore muscles and joints (3.4%). Fever was more common in children aged <6 years. Less than 5% of children reported missing school, sport or other regular activities. Vivaxim was well tolerated in children aged 2-16 years. Parents should be advised about AEFIs to Vivaxim so that they can make informed decisions about vaccination options.


Histopathology is required to identify and characterize myopathies in high-throughput phenotype screening of genetically engineered mice.
The development of mouse models that replicate the genetic and pathological features of human disease is important in preclinical research because these types of models enable the completion of meaningful pharmacokinetic, safety, and efficacy studies. Numerous relevant mouse models of human disease have been discovered in high-throughput screening programs, but there are important specific phenotypes revealed by histopathology that are not reliably detected by any other physiological or behavioral screening tests. As part of comprehensive phenotypic analyses of over 4000 knockout (KO) mice, histopathology identified 12 lines of KO mice with lesions indicative of an autosomal recessive myopathy. This report includes a brief summary of histological and other findings in these 12 lines. Notably, the inverted screen test detected muscle weakness in only 4 of these 12 lines (Scyl1, Plpp7, Chkb, and Asnsd1), all 4 of which have been previously recognized and published. In contrast, 6 of 8 KO lines showing negative or inconclusive findings on the inverted screen test (Plppr2, Pnpla7, Tenm1, Srpk3, Sidt2, Yif1b, Mrs2, and Pnpla2) had not been previously identified as having myopathies. These findings support the need to include histopathology in phenotype screening protocols in order to identify novel genetic myopathies that are not clinically evident or not detected by the inverted screen test.


Sex differences in heart failure medications targeting the renin-angiotensin-aldosterone system.
Heart failure (HF) is a major healthcare problem. Sex-related differences in clinical manifestations, outcomes, risk factors and symptoms in HF have been described in the literature. Sex-related differences have also been described in the regulation of the renin-angiotensin-aldosterone system (RAAS), which is at the core of the pathophysiology of HF. Considering that drugs targeting RAAS are cornerstones in the treatment of HF, it is important to determine whether sex-related differences exist in the use of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs) and ARB/neprilysin inhibitors (ARNIs). In regards to the relative efficacy of RAAS drugs in men vs. women in HF, there are conflicting results, which may stem from the fact that a lot of clinical trials were not specifically designed to investigate sex differences, with many of them having an underrepresentation of women. With respect to optimal dosage of RAAS drugs, even though, current HF guidelines, recommend up-titration to the same target dose in both men and women, evidence suggests that lower doses could be used in women. Furthermore, several studies have reported underutilization of guideline-directed medical therapy in women, including ACEIs, ARBs and MRAs, which may be at least partially attributed to increased prevalence of HF with a preserved ejection fraction and increased propensity for adverse effects in women. Overall, these investigations have shed some light on sex-related differences but there is scope for conducting further studies to determine the optimal use of RAAS drugs in men and women with failing hearts.


Neuropathy of metachromatic leukodystrophy: improvement with immunomodulation.
A 4-year-old child with metachromatic leukodystrophy was initially diagnosed with chronic immune demyelinating polyneuropathy and treated with immunosuppressive therapy. Physical examination revealed diffuse, distal > proximal weakness and areflexia. Electro-diagnostic studies revealed nerve conduction velocities that were slowed to variable degrees in different nerves. In the 18 months after institution of immunomodulating therapy, she had functionally significant improvement and a quantitative increase in her strength. Treatment was discontinued at age 6 years when the patient developed urinary incontinence, followed by loss of motor and cognitive skills. We conclude that immunomodulation early in the course of metachromatic leukodystrophy presenting as a neuropathy may result in temporary functional improvement. Whether the immunomodulation altered the disease progression or had direct effects on the function of the dysmyelinated axons is not known.


After the eradication of Helicobacter pylori infection, relapse is a serious problem in Turkey.
Eradication of Helicobacter pylori (Hp) infection is strongly recommended in duodenal and gastric ulcer. In developed countries the recurrence rate is low; however, in Turkey, the Hp recurrence rate is suspected to be high as the prevalence of Hp infection is--as high as 70-80% in the asymptomatic population. We planned this study to determine the relapse rate of Hp infection after successful eradication therapy in Turkey. Fifty-two cases including 24 patients with duodenal ulcer and 28 patients with nonulcer dyspepsia were examined in this study. The eradication regimen was omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg three times a day for 1 week. All patients underwent upper gastrointestinal tract endoscopy. At least four samples from antrum and corpus were taken to enable histologic diagnosis of Hp infection. After the eradication therapy, endoscopy was repeated at 1, 3, 6, and 12 months, and Hp-positive patients were dropped from study. With the use of this regimen, the Hp eradication rate was 92.3% (48/52). After the eradication of Hp infection, relapse rates were 6.97%, 27.5%, and 11.11% at 3, 6, and 12 months, respectively. The cumulative relapse rate for 1 year was 41.46%. The results of this study revealed that after the eradication of Hp infection, recurrence is encountered very often as a problem in Turkey. We concluded that hygienic and environmental factors can affect these high relapse rates.


Reframing care while enduring the traumatic nature of witnessing disrupted family-patient-nurses' relationships during COVID-19.
To describe the lived experiences of nurses caring for patients and families in the context of COVID-19 in Brazil and United States. A phenomenological philosophical approach following the van Manen analysis method. Participants were recruited in Brazil and the United States, including nurses working in health care settings caring for COVID-19 patients. Recruitment used purposive and snowball sampling. Participants completed a demographic survey and semi-structured interviews that were audio-recorded and transcribed for analysis. A cross-cultural examination occurred among researchers from each country. The result was described (n = 35) by the themes, representing the essences of each lifeworld (relationship, time, space and body). The nurses' lived experience was one of reframing care while enduring repeated trauma of witnessing disrupted patient-family-nurse relationships. Themes were as follows: (a) Living a silent and lonely experience; (b) Providing connectedness for disrupted patient and family relationships; (c) Feeling the burden of the demands; (d) Being a helping connector; (e) Reshaping spaces amidst evolving interventions and policies; (f) Creating safe spaces, surrounded by turmoil, threat, and distress within an unsafe environment; (g) Reorganizing care and reframing time; (h) Reconciling losses, regrets, victories and lessons. The nurses' lived experience of caring for patients and families during the COVID-19 pandemic prompted the need to respond to repeated traumas and distress posed by interrupted patient-family and nurse-own family relationships, vulnerable bodies, threatened space and dynamic and volatile time. Cultural nuances were discovered depending on the practice setting, political discourse and the autonomy of the nurse. Innovative models of care that create structures and processes to support nurses in caring for patients in threatening environments and the commitment to connecting family members have potential to contribute to the ongoing health of the nursing profession.


Prevalent class I-restricted T-cell response to the Theiler's virus epitope Db:VP2121-130 in the absence of endogenous CD4 help, tumor necrosis factor alpha, gamma interferon, perforin, or costimulation through CD28.
C57BL/6 mice mount a cytotoxic T-lymphocyte (CTL) response against the Daniel's strain of Theiler's murine encephalomyelitis virus (TMEV) 7 days after infection and do not develop persistent infection or the demyelinating syndrome similar to multiple sclerosis seen in susceptible mice. The TMEV capsid peptide VP2121-130 sensitizes H-2Db+ target cells for killing by central-nervous-system-infiltrating lymphocytes (CNS-ILs) isolated from C57BL/6 mice infected intracranially. Db:VP2121-130 peptide tetramers were used to stain CD8(+) CNS-ILs, revealing that 50 to 63% of these cells bear receptors specific for VP2121-130 presented in the context of Db. No T cells bearing this specificity were found in the cervical lymph nodes or spleens of TMEV-infected mice. H-2(b) mice lacking CD4, class II, gamma interferon, or CD28 expression are susceptible to persistent virus infection but surprisingly still generate high frequencies of CD8(+), Db:VP2121-130-specific T cells. However, CD4-negative mice generate a lower frequency of Db:VP2121-130-specific T cells than do class II negative or normal H-2(b) animals. Resistant tumor necrosis factor alpha receptor I knockout mice also generate a high frequency of CD8(+) CNS-ILs specific for Db:VP2121-130. Furthermore, normally susceptible FVB mice that express a Db transgene generate Db:VP2121-130-specific CD8(+) CNS-ILs at a frequency similar to that of C57BL/6 mice. These results demonstrate that VP2121-130 presented in the context of Db is an immunodominant epitope in TMEV infection and that the frequency of the VP2121-130-specific CTLs appears to be independent of several key inflammatory mediators and genetic background but is regulated in part by the expression of CD4.


Brazilian experience with the medium-term multi-organ bioassay: scientific and regulatory developments.
In 1996 the Brazilian Institute for the Environment (IBAMA) officially adopted a variation of the multi-organ initiation-promotion DMBDD bioassay as a valid source of evidence of the carcinogenic potential of pesticides. The protocol adopted by IBAMA was a modification of the one originally proposed by researchers led by Nobuyuki Ito, from the Nagoya City University Medical School. Among the modifications established in the Brazilian protocol were the use of both sexes of the outbreed Wistar strain of rats and two positive control test chemicals. The adoption of the modified DMBDD protocol was instrumental during the last decade for qualifying technical people and to spread knowledge on chemical carcinogenesis in Brazil.


The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma.
The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1alpha-TGF-beta1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.


Digit ratio (2Dratio4D) differences between 20 strains of inbred mice.
The second to fourth digit ratio (2Dratio4D) is sexually differentiated in a variety of species, including humans, rats, birds, and lizards. In humans, this ratio tends to be lower in males than in females. Lower digit ratios are believed to indicate increased prenatal testosterone exposure, and are associated with more masculinized behavior across a range of traits. The story seems more complicated in laboratory mice. We have previously shown that there is no sex difference in the digit ratios of inbred mice, but found behavioral evidence to suggest that higher 2Dratio4D is associated with more masculinized behaviors. Work examining intrauterine position effects show that neighbouring males raise pup digit ratio, suggesting again that higher digit ratios are associated with increased developmental androgens. Other work has suggested that masculinization is associated with lower digit ratios in lab mice. Here, we examine the fore- and hindlimb digit ratios of 20 inbred mouse strains. We find large inter-strain differences, but no sexual dimorphism. Digit ratios also did not correlate with mice behavioral traits. This result calls into question the use of this trait as a broadly applicable indicator for prenatal androgen exposure. We suggest that the inbred mice model presents an opportunity for researchers to investigate the genetic, and gene-environmental influence on the development of digit ratios.


The AGT Gene M235T Polymorphism and Response of Power-Related Variables to Aerobic Training.
The C allele of the M235T (rs699) polymorphism of the AGT gene correlates with higher levels of angiotensin II and has been associated with power and strength sport performance. The aim of the study was to investigate whether or not selected power-related variables and their response to a 12-week program of aerobic dance training are modulated by the AGT M235T genotype in healthy participants. Two hundred and one Polish Caucasian women aged 21 ± 1 years met the inclusion criteria and were included in the study. All women completed a 12-week program of low and high impact aerobics. Wingate peak power and total work capacity, 5 m, 10 m, and 30 m running times and jump height and jump power were determined before and after the training programme. All power-related variables improved significantly in response to aerobic dance training. We found a significant association between the M235T polymorphism and jump-based variables (squat jump (SJ) height, p = 0.005; SJ power, p = 0.015; countermovement jump height, p = 0.025; average of 10 countermovement jumps with arm swing (ACMJ) height, p = 0.001; ACMJ power, p = 0.035). Specifically, greater improvements were observed in the C allele carriers in comparison with TT homozygotes. In conclusion, aerobic dance, one of the most commonly practiced adult fitness activities in the world, provides sufficient training stimuli for augmenting the explosive strength necessary to increase vertical jump performance. The AGT gene M235T polymorphism seems to be not only a candidate gene variant for power/strength related phenotypes, but also a genetic marker for predicting response to training.


A kinetic study on the stereospecific inhibition of KCNQ1 and I(Ks) by the chromanol 293B.
1. Recently we and others have demonstrated a stereoselective inhibition of slowly activating human I(Ks) (KCNQ1/MinK) and homomeric KCNQ1 potassium channels by the enantiomers of the chromanol 293B. Here, we further characterized the mechanism of the 293B block and studied the influence of the 293B enantiomers on the gating kinetics of both channels after their heterologous expression in Xenopus oocytes. 2. Kinetic analysis of currents partially blocked with 10 microM of each 293B enantiomer revealed that only 3R,4S-293B but not 3S,4R-293B exhibited a time-dependent block of I(Ks) and KCNQ1 currents, indicating preferential open channel block activity. 3. Inhibition of both KCNQ1 and I(Ks) channels by 3R,4S-293B but not by 3S,4R-293B increased during a 2 Hz train of stimuli. 4. At high extracellular potassium concentrations the inhibition of KCNQ1 by 3R,4S-293B and 3S,4R-293B was unaffected. Drug inhibition of KCNQ1 and I(Ks) by both enantiomers also did not display a significant voltage-dependence, indicating that 293B does not strongly interact with permeant ions in the pore. 5. The inhibitory properties of 3R,4S-293B on I(Ks)-channels but not those of 3S,4R-293B fulfill the theoretical requirements for a novel class III antiarrhythmic drug, i.e. positive use-dependency. This enantiomer therefore represents a valuable pharmacological tool to evaluate the therapeutic efficiency of I(Ks)blockade.


[The role of heparin in the realization of the effect of various protein hormones].
In immature female rats the ovarian mass increased by 74.3% 48 h after the administration of 50 units of LH. The stimulating LH effect on the ovary did not show itself against a background of the binding of circulatory heparin by multiple administration of protamine-sulphate (P-S) for 3 days. The blockade could be abolished by compensatory administration of heparin (twice at a dose of 50 units/100 g. Likewise, the stimulating ACTH effect on corticosterone secretion in adult male rats did not show itself in P-S-heparin binding. If in the blockade of discharge of the animal own ACTH by dexamethasone 2.5 units of exogenous ACTH resulted in an increase in corticosterone concentration from 9 to 16.2 Mg% in 15 min, in P-S single administration 5-10 min before ACTH, corticosterone concentration remained practically at the basal level. Heparin injection within the interval between P-S and ACTH administration ensured the manifestation of the stimulating ACTH effect, and blood corticosterone concentration increased in the same degree as in the administration of ACTH only. Thus, it can be assumed that the presence of reactive heparin in the blood is necessary for the implementation of action of some protein hormones.


Support, needs and expectations of family caregivers regarding general practitioners - results from an online survey.
Family caregivers are often the first line of support for people requiring care; although they may personally stand to benefit, these activities substantially increase the risk of physical and emotional stress. General practitioners (GPs) may provide important support and stabilisation, but need to adjust to the needs and expectations of this group in order to do so. The aim of the study was to compare the needs of family caregivers from GPs to the support they actually experience. Additional aims included determining the main factors affecting satisfaction amongst family caregivers with support from GPs. The results were used to develop possible approaches towards optimisation within the purview of general medical practice. Between January and July 2020, 612 people supporting or caring for a family member responded to an online survey posted in seventeen internet forums focused on family caregivers. In addition to the descriptive analysis, a t-test with independent samples was used to identify significant differences between two groups. We also used binary logistic regression analysis to identify indications of potentially influential factors regarding the experienced support from GPs. Around three out of every four respondents (72%) consulted GPs in care matters. The respondents gave positive responses on their GP's knowledge of the care situation (71%), approachability in various issues connecting with care and service towards the caregiver (82%). GPs' efforts in meeting the needs and requirements of the care recipient were also rated positively (82%). Weaknesses in support from GPs mainly involved the lack of information on advice and assistance services (55%) as well as frequently not identifying or involving caregivers as such soon enough (42%). Results from regression analysis show that the last two aspects play a major role in subjective satisfaction amongst family caregivers with support from GPs. We recommend that GPs undergo further training to reinforce awareness that the care triad of needs, requirements and stresses amongst family caregivers also plays a vital role in care outcomes. With this in mind, general practice staff should adopt a pre-emptive strategy towards approaching family members about potential issues and informing them about existing assistance and support services.


Single-copy DNA relationships between diploid and tetraploid teleostean fish species.
The degree of single-copy DNA relatedness among nine Salmonid, Osmerid, and Clupeid species (teleosts, order Isospondyli) was explored by interspecific DNA hybridization and the determination of the thermal stability of these hybrids. It is shown that the extent of base substitution and the amount of shared sequences is largely consistent with the systematic interrelationship of the species compared. A tentative estimate of the average base substitution rate is about 0.1-0.25% per million years, which is in the range typical for animal and plant nuclear genomes. The results are also discussed in view of the phylogenetically tetraploid state of the Salmonid genomes. A comparison of the amount of intra-genomic and inter-genomic divergence in the tetraploids suggests that a polyploidization event occurred recently in Salmonid evolution.


[Relation between the occurrence of acute cerebral circulatory disorders and changes in meteorologic factors].
The results obtained concern the dependence of acute brain blood circulation pathology (ABBCP) frequency on several meteorological factors: wind speed, barometrical pressure, interdaily barometrical pressure changes, relative air humidity, air temperature, interdaily air temperature changes, oxygen content in air and interdaily oxygen content variability in the air. The mean daily number of patients was taken into account. 4023 ABBCP observations were analyzed. Wind, relative air humidity and interdaily changes of oxygen content in air were determined to influence greatly the ABBCP frequency under conditions of Middle Russia Hills region. Meteorological factors enumerated are supposed to be used in further multifactorial statistical analyses for comprehensive estimation of weather elements as well as for scientifically based prognoses of the ABBCP number and carrying out the preventive measures.


Protein phosphatase 2A mediates resensitization of the neurokinin 1 receptor.
Activated G protein-coupled receptors (GPCRs) are phosphorylated and interact with β-arrestins, which mediate desensitization and endocytosis. Endothelin-converting enzyme-1 (ECE-1) degrades neuropeptides in endosomes and can promote recycling. Although endocytosis, dephosphorylation, and recycling are accepted mechanisms of receptor resensitization, a large proportion of desensitized receptors can remain at the cell surface. We investigated whether reactivation of noninternalized, desensitized (phosphorylated) receptors mediates resensitization of the substance P (SP) neurokinin 1 receptor (NK(1)R). Herein, we report a novel mechanism of resensitization by which protein phosphatase 2A (PP2A) is recruited to dephosphorylate noninternalized NK(1)R. A desensitizing concentration of SP reduced cell-surface SP binding sites by only 25%, and SP-induced Ca(2+) signals were fully resensitized before cell-surface binding sites started to recover, suggesting resensitization of cell-surface-retained NK(1)R. SP induced association of β-arrestin1 and PP2A with noninternalized NK(1)R. β-Arrestin1 small interfering RNA knockdown prevented SP-induced association of cell-surface NK(1)R with PP2A, indicating that β-arrestin1 mediates this interaction. ECE-1 inhibition, by trapping β-arrestin1 in endosomes, also impeded SP-induced association of cell-surface NK(1)R with PP2A. Resensitization of NK(1)R signaling required both PP2A and ECE-1 activity. Thus, after stimulation with SP, PP2A interacts with noninternalized NK(1)R and mediates resensitization. PP2A interaction with NK(1)R requires β-arrestin1. ECE-1 promotes this process by releasing β-arrestin1 from NK(1)R in endosomes. These findings represent a novel mechanism of PP2A- and ECE-1-dependent resensitization of GPCRs.


DNA metabarcoding quantifies the relative biomass of arthropod taxa in songbird diets: Validation with camera-recorded diets.
Ecological research is often hampered by the inability to quantify animal diets. Diet composition can be tracked through DNA metabarcoding of fecal samples, but whether (complex) diets can be quantitatively determined with metabarcoding is still debated and needs validation using free-living animals. This study validates that DNA metabarcoding of feces can retrieve actual ingested taxa, and most importantly, that read numbers retrieved from sequencing can also be used to quantify the relative biomass of dietary taxa. Validation was done with the hole-nesting insectivorous Pied Flycatcher whose diet was quantified using camera footage. Size-adjusted counts of food items delivered to nestlings were used as a proxy for provided biomass of prey orders and families, and subsequently, nestling feces were assessed through DNA metabarcoding. To explore potential effects of digestion, gizzard and lower intestine samples of freshly collected birds were subjected to DNA metabarcoding. For metabarcoding with Cytochrome Oxidase subunit I (COI), we modified published invertebrate COI primers LCO1490 and HCO1777, which reduced host reads to 0.03%, and amplified Arachnida DNA without significant changing the recovery of other arthropod taxa. DNA metabarcoding retrieved all commonly camera-recorded taxa. Overall, and in each replicate year (N = 3), the relative scaled biomass of prey taxa and COI read numbers correlated at R = .85 (95CI:0.68-0.94) at order level and at R = .75 (CI:0.67-0.82) at family level. Similarity in arthropod community composition between gizzard and intestines suggested limited digestive bias. This DNA metabarcoding validation demonstrates that quantitative analyses of arthropod diet is possible. We discuss the ecological applications for insectivorous birds.


Multi PCET in symmetrically substituted benzimidazoles.
Proton-coupled electron transfer (PCET) reactions depend on the hydrogen-bond connectivity between sites of proton donors and acceptors. The 2-(2'-hydroxyphenyl) benzimidazole (BIP) based systems, which mimic the natural TyrZ-His190 pair of Photosystem II, have been useful for understanding the associated PCET process triggered by one-electron oxidation of the phenol. Substitution of the benzimidazole by an appropriate terminal proton acceptor (TPA) group allows for two-proton translocations. However, the prototropic properties of substituted benzimidazole rings and rotation around the bond linking the phenol and the benzimidazole can lead to isomers that interrupt the intramolecular hydrogen-bonded network and thereby prevent a second proton translocation. Herein, a strategic symmetrization of a benzimidazole based system with two identical TPAs yields an uninterrupted network of intramolecular hydrogen bonds regardless of the isomeric form. NMR data confirms the presence of a single isomeric form in the disubstituted system but not in the monosubstituted system in certain solvents. Infrared spectroelectrochemistry demonstrates a two-proton transfer process associated with the oxidation of the phenol occurring at a lower redox potential in the disubstituted system relative to its monosubstituted analogue. Computational studies support these findings and show that the disubstituted system stabilizes the oxidized two-proton transfer product through the formation of a bifurcated hydrogen bond. Considering the prototropic properties of the benzimidazole heterocycle in the context of multiple PCET will improve the next generation of novel, bioinspired constructs built by concatenated units of benzimidazoles, thus allowing proton translocations at nanoscale length.


Family and peer predictors of substance use from early adolescence to early adulthood: an 11-year prospective analysis.
The focus of this study was social (i.e., family and peer) influences on substance use from early adolescence to early adulthood. A large, ethnically diverse sample of early adolescents (N=998) was followed from age 12 to age 23. We tested direct and indirect effects of parental monitoring, family relationship quality, and association with deviant peers on change in substance use across time. Outcomes for tobacco, alcohol, and marijuana use were analyzed as separate pathways within the same overall model. The results suggest that a significant shift in the nature of family influence occurred across adolescence and into early adulthood, but deviant peer influence was relatively consistent across this period. Specifically, parental monitoring and deviant peer association were predictive of substance use in early adolescence, but family relationship quality was a significant predictor across the transition to high school and generally continued to predict use into later adolescence, as did association with deviant peers. Deviant peers were the only significant predictor in early adulthood. Our results also suggested that parental monitoring and family relationship quality indirectly predicted later substance use by way of deviant peers, implying that an important aspect of the family context is its influence on choice of friends and peer group composition. Implications for family-based prevention and intervention are discussed.


The prevalence of antibody to hepatitis C virus (anti-HCV) in patients with acute and chronic liver diseases in Jakarta, Indonesia.
The seroepidemiology of HBV and HCV infections in the patients with acute and chronic liver diseases in Jakarta was investigated. The sera from 141 cases with acute hepatitis, 176 liver cirrhosis and 70 hepatocellular carcinoma (HCC) were examined. Anti-HA IgM, HBsAg, anti-HBc IgM and anti HCV (Ortho) were detected by Elisa method. In acute hepatitis, 83 cases (58.9%) out of 141 cases were hepatitis A and 9 cases (6.4%) hepatitis B. The others were diagnosed non-A, non-B (NANB) hepatitis and anti-HCV in 4 cases (11.8%) out of 34 cases with NANB hepatitis was positive. The low prevalence of anti-HCV in acute NANB hepatitis seems to be due to inadequate date of serum sampling. HBsAg and anti-HCV in liver cirrhosis were positive 36.5% and 73.9% respectively, including 22.7% of double infection. HBsAg and anti-HCV in HCC were 58.6% and 34.2%, including 17.1% of double infection. In 16.7% fo chronic liver disease (liver cirrhosis and HCC), neither HBsAg nor anti-HCV were detected.


Mesotocin and nonapeptide receptors promote estrildid flocking behavior.
Proximate neural mechanisms that influence preferences for groups of a given size are almost wholly unknown. In the highly gregarious zebra finch (Estrildidae: Taeniopygia guttata), blockade of nonapeptide receptors by an oxytocin (OT) antagonist significantly reduced time spent with large groups and familiar social partners independent of time spent in social contact. Opposing effects were produced by central infusions of mesotocin (MT, avian homolog of OT). Most drug effects appeared to be female-specific. Across five estrildid finch species, species-typical group size correlates with nonapeptide receptor distributions in the lateral septum, and sociality in female zebra finches was reduced by OT antagonist infusions into the septum but not a control area. We propose that titration of sociality by MT represents a phylogenetically deep framework for the evolution of OT's female-specific roles in pair bonding and maternal functions.


Signs and symptoms of suspected myocardial ischemia in women: results from the What is the Optimal Method for Ischemia Evaluation in WomeN? Trial.
Much of our understanding of gender differences in chest pain was derived from noncontemporary reports. The aim of the current report was to compare the frequency of chest pain by measures of ischemia in 824 women with suspected myocardial ischemia prospectively enrolled in a clinical trial of exercise testing with electrocardiography (ETT-ECG) alone compared to myocardial perfusion single photon emission computed tomography (SPECT) (ETT-MPS). Women seeking evaluation of chest pain or anginal equivalent symptoms were randomized to ETT-ECG or ETT-MPS with Tc-99m tetrofosmin. The Women's Ischemia Syndrome Evaluation (WISE) and Seattle Angina Questionnaire (SAQ) chest pain and Duke Activity Status Index (DASI) questionnaires were employed in enrolled women. Higher SAQ scores denote improved symptoms or functioning. Eight hundred twenty-four women, average age 63 years, at intermediate-high coronary artery disease (CAD) likelihood were enrolled from 43 North American centers. Traditional cardiac risk factors were prevalent, with nearly half of women having a family history of premature coronary disease, hypertension, and hyperlipidemia. Chest pain symptoms occurring at least one to three times per week were reported in 60% of women. An examination of the SAQ domains revealed that although women reported minimal physical limitations (median, interquartile range [IQR] 88, 75-100), there was a greater frequency of stable chest pain symptoms (median, IQR=40, 30-50). The majority of women (79%) reported moderate to heavy physical activity levels at home, with the average ETT and DASI estimated metabolic equivalents (METs) of 8.6±2.6 and 11.5±3.8. Women with more frequent daily episodes of chest pain were more likely to have a lower Duke Treadmill Score (DTS), 1 or mm of ST segment depression, and an abnormal MPS. The current report details a contemporary evaluation of female-specific symptomatology and measures of myocardial ischemia. Women reporting frequent angina were more likely to exhibit ischemia and this may characterize a female-specific typical angina pattern.


High-Pressure Polymorph of Thulium: An X-ray Diffraction Study.
An x-ray diffractiotn study of thulium at room temperature and high pressure by means of a diamond-anvil press has shown that thulium transforms from a hexagonal close-packed structure to the samarium type, as other rareearth elements (gadolinium, terbium, dysprosium, and holmium) do. Unlike the other rare-earth elements, thulium (hexagonal close-packed) has an axial ratio (c/a) that is independent of pressure within experimental error and the transition is reversible. The transition occurs with increasing pressure in the range of 60 to 116 kilobars. The lattice paralieters of the samarium-type phase of thulium at about 116 kilobars are a = 3.327 +/- 0.005 angstroms and c = 23.48 +/- 0.04 angstroms, and the volume change at the transition is estimated to be - 0.5 percent of the volume of the hexagonal close-packed phase at the transition.


A method for the simultaneous determination of chlorogenic acid and sesquiterpene lactone content in industrial chicory root foodstuffs.
A method for the simultaneous determination of free chlorogenic acids (CGA) and sesquiterpene lactones (STL) in chicory root and its dried (flour) and roasted (grain) forms is described. The method uses one extraction and one analysis for all chicory root products. Various solvents with low to high polarity, such as methanol, chloroform, or n-hexane, were tested alone, in combination in different proportions or with acidified or neutral aqueous solvent. The water/chloroform/methanol (30/30/40, v/v/v) mixture generated the best extraction yield, 21% higher than alcohol mixtures. The profiling of CGA and STL content was performed through a conventional HPLC-DAD method using a PFP core shell column in a fast single run. Good retention time and area repeatability (RDD mean % 0.46 and 5.6, resp.) and linearity (R2≥0.96) were obtained. The STL and chlorogenic acids levels determined were 254.7 and 100.2 μg/g of dry matter in the root, 792.5 and 1,547 μg/g in flour, and 160.4 and 822.5 μg/g in the roasted grains, respectively. With an average recovery of 106% and precision of 90%, this method is rapid, reproducible, and straightforward way to quantify the chlorogenic acids and STL in chicory raw material and end products.


A questionnaire based survey among pharmacy practitioners to evaluate the level of knowledge and confidence towards antimicrobial stewardship.
Our study aimed to assess the knowledge, understanding and confidence of the practicing pharmacists in UAE as an antimicrobial Stewards. Antimicrobial resistance threatens the achievements of modern medicine globally, and it's highly required for the AMS principles to be implemented in our communities. A cross-sectional online- questionnaire based survey was used among UAE pharmacy practitioners from different areas of practice who are holding pharmaceutical degrees and/or licensed pharmacists. The questionnaire was sent to the participants via social media platforms. The questionnaire was validated, and reliability assessment was made prior to the conduct. A total of 117 pharmacists responded to this study, out of which (70.9%, n=83) were females. Pharmacists which are from various practice fields participated in the survey, but the majority were pharmacists in Hospital pharmacies or Clinical pharmacists (47%, n=55), also community pharmacists (35.9%, n=42), while only (16.9%, n=20) ware from other areas of pharmacy including industrial pharmacy and academia. The majority of participants 88.9% (n= 104) were interested in pursuing their career as an Infectious disease pharmacist or getting a certificate in antimicrobial stewardship. The mean scores in the knowledge towards antimicrobial resistance was 3.75 (poor: 1-1.6, moderate: 1.7-3.3. 3.4-5), indicates that the pharmacists have a good level of knowledge towards AMR. A total of 84.3% of participants succeeded in Identifying the correct intervention for antibiotic resistance. The findings also showed that the total mean score of hospital pharmacists (mean=10.6±1.12), and the average of the scores of community pharmacists (mean=9.8±1.38), were non-significant between the different area of practice. 52.3% of the participants had a training on antimicrobial stewardship during their experiential rotation which reflected on their confidence in their performance and knowledge assessment (p value < 0.05). The study concluded good knowledge and high confidence levels among practicing pharmacists in UAE. However, the findings also identify areas of improvement in the practicing pharmacist, and the significant relationship between the knowledge and confidence scores reflects the ability of the practicing pharmacists to integrate the AMS principles within the UAE, which aligns with the attainability of the improvement.


European health examination surveys - a tool for collecting objective information about the health of the population.
Representative and reliable data on health and health determinants of the population and population sub-groups are needed for evidence-informed policy making; planning and evaluation of prevention programmes; and research. Health examination surveys (HESs) including questionnaires, objective health measurements and analysis of biological samples, provide information on many health indicators that are available not at all or less reliably or completely through administrative registers or health interview surveys. Standardized cross-sectional HESs were already conducted in the 1980's and 1990's, in the framework of the WHO MONICA Project. The methodology was developed and finally, in 2010-2012, a European Health Examination Survey (EHES) Pilot Project was conducted. During this pilot phase, an EHES Coordinating Centre (EHES CC, formerly EHES Reference Centre) was established. Standardized protocols, guidelines and quality control procedures were prepared and tested in 12 countries which conducted pilot surveys, demonstrating the feasibility of standardized HES data collection in the European Union (EU).Currently, the EHES CC operates at the National Institute for Health and Welfare (THL), Finland. Its activities include maintaining and developing the standardized protocols, guidelines and training programme; maintaining the EHES network; providing professional support for countries planning and organizing their national HESs; external quality assessment for surveys organized in the EU Member States; and development of a centralized database and joint reporting system for HES data. An increasing number of EU Member States are conducting national HESs, demonstrating a strong need for such surveys as part of the national health monitoring systems. Standardization of the data collection is essential to ensure that HES data are comparable across countries and over time. The work of the EHES CC helps to ensure the quality and comparability of HES data across the EU. HES data have been used for health monitoring and identifying public health problems; to develop health and prevention programmes; to support health policies and preparation of health-related legislation and regulations; and to develop clinical treatment guidelines and population reference values. HESs have also been utilized to prepare health measurement tools and diagnostic methods; in training and research and to increase health awareness among population.


Conduct disorder subtype and comorbidity.
Conduct disorder is considered difficult to treat, but comorbid psychiatric disorders may be a basis for treating some youths with conduct disorder. We sought to identify patterns of comorbid psychiatric diagnoses and psychopathology associated with conduct disorder by reported age-of-onset. Referred children and adolescents, aged 4-17 years old, were clinically evaluated. Ages of onset of CD symptoms (N=53) were ascertained and divided according to DSM-IV criteria as childhood onset (<10 years old) or adolescent onset (>or=10 years old). Childhood-onset conduct disorder was associated with higher rates of ADHD and anxiety disorders, male gender, and perceived and total hostility scores than adolescent-onset conduct disorder. Adolescent-onset was associated with higher rates of PTSD, alcohol and substance use disorders, complex comorbidity (i.e., 6+ diagnoses lifetime), and female gender. Understanding age-of-onset-related patterns of comorbidity may facilitate psychiatric treatment planning in children and adolescents with conduct disorder.


Utility of dobutamine stress echocardiography as part of the pre-liver transplant evaluation: an evaluation of its efficacy.
Dobutamine stress echocardiography (DSE) is commonly used to risk stratify patients in the cardiac evaluation prior to orthotopic liver transplantation (OLT). Data remain limited regarding the accuracy to predict obstructive coronary artery disease (CAD) using this approach. We hypothesize that DSE may have limitations in the investigation of underlying CAD in patients with end-stage liver disease. A retrospective chart review of all patients who underwent OLT at Mayo Clinic in Florida between 1998 and 2010 was performed. Sixty-six underwent invasive coronary angiography (ICA) within 1 year of DSE and were included in our study. Based on DSE results, patients were stratified into 1 of 3 groups: nonischemic, ischemic, and indeterminate. The relationship between DSE, ICA, and death from all cause and cardiac-related cause with a minimum 3-year follow-up period were analyzed. A total of 66 patients were included in our cohort. There was no difference in age, gender, severity of liver disease, and echocardiographic findings among the groups. Forty-three percent of patients (n = 12) with an abnormal result on DSE were found to have moderate or severe obstructive CAD on cardiac catheterization, whereas 49% of patients (n = 17) with a normal finding on DSE had moderate or severe CAD. Of 5 patients who died from a documented cardiac etiology, 3 had normal stress test results, 1 had abnormal findings, and 1 had an indeterminate DSE result. When compared with ICA, our study demonstrated that DSE has a sensitivity of 41.4% (95% confidence interval [CI]: 0.24-0.61), specificity of 47.1% (95% CI: 0.30-0.65), positive predictive value of 40.0% (95% CI: 0.23-0.59), and negative predictive value of 48.0% (95% CI: 0.31-0.66) in identification of underlying CAD. Although widely used, DSE may not always accurately reflect the severity of obstructive CAD in patients undergoing OLT.


Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle.
Reduced oxidative capacity of the mitochondria in skeletal muscle has been suggested to contribute to insulin resistance and type 2 diabetes. Moreover, a set of genes influencing oxidative phosphorylation (OXPHOS) is downregulated in diabetic muscle. Here we studied whether genetic, epigenetic and non-genetic factors influence a component of the respiratory chain, COX7A1, previously shown to be downregulated in skeletal muscle from patients with type 2 diabetes. The specific aims were to: (1) evaluate the impact of genetic (single nucleotide polymorphisms [SNPs]), epigenetic (DNA methylation) and non-genetic (age) factors on the expression of COX7A1 in human skeletal muscle; and (2) investigate whether common variants in the COX7A1 gene are associated with increased risk of type 2 diabetes. COX7A1 mRNA expression was analysed in muscle biopsies from young (n = 110) and elderly (n = 86) non-diabetic twins and related to measures of in vivo metabolism. Genetic variants (three SNPs) from the COX7A1 locus were genotyped in the twins and in two independent type 2 diabetes case-control cohorts (n = 1466 and 6380, respectively). DNA methylation of the COX7A1 promoter was analysed in a subset of twins (ten young, ten elderly) using bisulphite sequencing. While DNA methylation of the COX7A1 promoter was increased in muscle from elderly compared with young twins (19.9 +/- 8.3% vs 1.8 +/- 2.7%; p = 0.035), the opposite was found for COX7A1 mRNA expression (elderly 1.00 +/- 0.05 vs young 1.68 +/- 0.06; p = 0.0005). The heritability of COX7A1 expression was estimated to be 50% in young and 72% in elderly twins. One of the polymorphisms investigated, rs753420, influenced basal COX7A1 expression in muscle of young (p = 0.0001) but not of elderly twins. The transcript level of COX7A1 was associated with increased in vivo glucose uptake and VO(2max) (p = 0.009 and p = 0.001, respectively). We did not observe any genetic association between COX7A1 polymorphisms and type 2 diabetes after correcting for multiple testing. Our results provide further evidence for age as a factor influencing DNA methylation and expression of OXPHOS genes, and thereby in vivo metabolism.


Biochemical characterization of a human spermatozoal sialoglycoprotein with respect to antigenicity masking by its sialic acid moieties.
Four O-glycosidic oligosaccharides (I, II, III, IV) were purified from a human spermatozoal sialoglycoprotein antigen following quantitative beta-elimination and reduction of the linkage sugar by KHB4+. The four oligosaccharides showed a similar carbohydrate composition consisting of sialic acids, galactose, fucose, galactosamine and N-acetylgalactosamine, except for the lack of fucose in II. The linkage sugar was identified as N-acetylgalactosamine at a molar ratio of 23.8 to 1 glycoprotein. The sialic acid moieties of the oligosaccharides were tentatively identified by gas-liquid chromatography following trimethylsilylation. A biological function for these sialic acids is suggested by a significantly increased antibody binding after desialization, as compared to the intact sialoglycoprotein molecule. This masking effect of the sialic acids could raise important questions about the etiology of the naturally occurring antispermatozoal antibodies in sera of sterile man, about which is little known.


Malonate utilization by Pseudomonas aeruginosa affects quorum-sensing and virulence and leads to formation of mineralized biofilm-like structures.
Pseudomonas aeruginosa is an opportunistic pathogen that uses malonate among its many carbon sources. We recently reported that, when grown in blood from trauma patients, P. aeruginosa expression of malonate utilization genes was upregulated. In this study, we explored the role of malonate utilization and its contribution to P. aeruginosa virulence. We grew P. aeruginosa strain PA14 in M9 minimal medium containing malonate (MM9) or glycerol (GM9) as a sole carbon source and assessed the effect of the growth on quorum sensing, virulence factors, and antibiotic resistance. Growth of PA14 in MM9, compared to GM9, reduced the production of elastases, rhamnolipids, and pyoverdine; enhanced the production of pyocyanin and catalase; and increased its sensitivity to norfloxacin. Growth in MM9 decreased extracellular levels of N-acylhomoserine lactone autoinducers, an effect likely associated with increased pH of the culture medium; but had little effect on extracellular levels of PQS. At 18 hr of growth in MM9, PA14 formed biofilm-like structures or aggregates that were associated with biomineralization, which was related to increased pH of the culture medium. These results suggest that malonate significantly impacts P. aeruginosa pathogenesis by influencing the quorum sensing systems, the production of virulence factors, biofilm formation, and antibiotic resistance.


Positive effect of dietary soy in ESRD patients with systemic inflammation--correlation between blood levels of the soy isoflavones and the acute-phase reactants.
Inflammation is commonly associated with malnutrition and cardiovascular disease in end-stage renal failure patients. Anti-inflammatory properties of the isoflavones, a micronutrient component of soy, have been reported in several experimental models and disease conditions, but never in renal failure. We hypothesized that dietary soy isoflavones correct laboratory evidence of systemic inflammation in haemodialysis (HD) patients with underlying high blood levels of C-reactive protein (CRP). End-stage renal disease patients on chronic HD, with elevated CRP (>10.0 mg/l) were enrolled in this pilot study. The subjects were double-blind randomly distributed with 2 : 1 ratio to receive isoflavone-containing soy-based nutritional supplements (soy group) or isoflavone-free milk protein (control group) for 8 weeks. Serum isoflavone, inflammatory markers and nutrition markers were assessed at baseline and at the end of the treatment. Thirty-two subjects were enrolled. Fifteen subjects in the soy group and 10 in the control group completed the study; five dropouts were due to acute illness and two due to food intolerance. After intervention, blood isoflavone levels were 5- to 10-fold higher in the soy group than in the control group [e.g. median genistein (25-75th percentile): 337.9 (175.5-1007) nM in the soy group vs 41.4 (22.9-100.4) nM in the control group; P < 0.001]. However, the isoflavone levels ranged widely in the soy group (e.g. genistein: 33-1868 nM) and, depending on the individual compound, four to seven subjects had end-of-treatment levels that were not different from baseline. Variation from baseline of the individual serum isoflavone levels (Delta-isoflavone) and CRP displayed a strong inverse correlation in the soy group (R = -0.599, P < 0.02). In addition, Delta-isoflavone correlated positively with the variation of albumin (R = 0.522, P = 0.05) and insulin-like growth factor-1 (R = 0.518, P < 0.05). Group levels of CRP were not statistically different after intervention although a trend towards lower levels was noted in the soy group [18.2 (12.7-29.1) mg/l at baseline vs 9.7 (5.2-20.7) mg/l at week 8; NS] but not in the control group [20.6 (9.2-38.5) vs 17.6 (9.1-40.7) mg/l]. These data suggest the possibility of beneficial effects of isoflavone-rich soy foods on the inflammatory and nutritional status of HD patients with underlying systemic inflammation.


Plasma corticosterone and its relation to susceptibility to animal hypnosis in rabbits.
Plasma corticosterone has been correlated with the susceptibility to animal hypnosis in male rabbits. Subjects (Ss) were considered susceptible when mean hypnosis duration was above 30 sec or when initial duration (duration of trial 1) was greater than 0. A positive significant correlation was found between mean and initial duration. A significant difference was found between corticosterone levels in susceptible and unsusceptible Ss: higher values were associated with susceptible SS and with SS with initial duration greater than 0. These results indicate a higher susceptibility to animal hypnosis in rabbits with a more active adrenocortical system.


Treadmill workstations in office workers who are overweight or obese: a randomised controlled trial.
Treadmill workstations that enable office workers to walk on a treadmill while working at their computers might increase physical activity in offices, but long-term effects are unknown. We therefore investigated whether treadmill workstations in offices increased daily walking time. We did a randomised controlled trial of healthy office workers who were either overweight or obese. We recruited participants from 13 different companies, which comprised 17 offices, in Umeå, Sweden. We included people who were aged 40-67 years, had sedentary work tasks, and had a body-mass index (BMI) between 25 kg/m2 and 40 kg/m2. After the baseline measurement, we stratified participants by their BMI (25-30 kg/m2 and >30 to 40 kg/m2); subsequently, an external statistician randomly assigned these participants (1:1) to either the intervention group (who received treadmill workstations for optional use) or the control group (who continued to work at their sit-stand desks as usual). Participants in the intervention group received reminders in boosting emails sent out to them at four occasions during the study period. Researchers were masked to group assignment until after analysis of the primary outcome. After the baseline measurement, participants were not masked to group belongings. The primary outcome was total daily walking time at weekdays and weekends, measured at baseline, 2 months, 6 months, 10 months, and 13 months with the accelerometer activPAL (PAL Technologies, Glasgow, UK), which was worn on the thigh of participants for 24 h a day for 7 consecutive days. We used an intention-to-treat approach for our analyses. This trial is registered with ClinicalTrials.gov, number NCT01997970, and is closed to new participants. Between Nov 1, 2013, and June 30, 2014, a total of 80 participants were recruited and enrolled (n=40 in both the intervention and control groups). Daily walking time during total time awake at weekdays increased between baseline and 13 months by 18 min (95% CI 9 to 26) in the intervention group and 1 min (-7 to 9) in the control group (difference 22 min [95% CI 7 to 37], pinteraction=0·00045); for weekend walking, the change from baseline to 13 months was 5 min (-8 to 18) in the intervention group and 8 min (-5 to 21) in the control group (difference -1 min [-19 to 17]; pinteraction=0·00045). Neither measure met our predetermined primary outcome of 30 min difference in total walking time between the intervention and control group, so the primary outcome of the trial was not met. One adverse event was reported in a participant who accidently stepped on their Achilles tendon. In a sedentary work environment, treadmill workstations result in a statistically significant but smaller-than-expected increase in daily walking time. Future studies need to investigate how increasing physical activity at work might have potentially compensatory effects on non-work activity. Umeå University, the Västerbotten County Council, and the Mayo Clinic Foundation for Research.


Improved soybean protein sources for early-weaned pigs: II. Effects on ileal amino acid digestibility.
Early-weaned gilts fitted with simple ileal T-cannulas were used to determine the effect of protein source on N and amino acid (AA) digestibility. The digestibilities of N and AA in 25- to 53-d-old pigs fed either dried skim milk (DSM), isolated soybean protein (ISP), soybean protein concentrate (SPC), or soybean meal (SBM) as the only protein source were determined. The pigs were fed semipurified diets formulated to contain 22% CP. Digestibility of N and overall essential amino acids (EAA) and nonessential amino acids (NEAA) both at the terminal ileum and over the total digestive tract of early-weaned pigs was greater (P < .01) by pigs fed the DSM, ISP, and SPC diets than by those fed the SBM diet. The ileal and total tract digestibilities for N and all AA except glutamic acid (P < .05) increased with increasing age of pigs. Digestibility both at the ileum and total digestive tract for lysine was greater (P < .01) in pigs fed the DSM diet than in those fed any of the soybean protein diets. Digestibility values over the total tract were greater than values estimated at the ileum, indicating a net disappearance of both N and AA in the hindgut. This study suggests that low digestibility of the first-limiting AA, lysine, may limit performance of pigs fed a SBM diet.


Viking: Mars atmospheric water vapor mapping experiment--preliminary report of results.
Observations made from the Viking I orbiter show very little water vapor in the Mars atmosphere in the southern hemisphere (0 to 3 precipitable micrometers) with a gradual increase across the equator to northern latitudes. Maximum amounts between 20 and 30 micrometers have been observed in the short period covered by the observations to date. The season, northern midsummer, corresponds to the beginning of the water vapor cycle in that hemisphere. A strong repetitive diurnal cycling between the solid and vapor phases is observed at a site to the east of the Tharsis Ridge at 10 degrees north latitude; the vapor lies close to the martian surface and is most probably in saturation equilibrium with a surface haze or fog throughout much of the day.


[Health Effects Caused by Soil Fumigant Chloropicrin, Reduction of Exposure to Chloropicrin, and Alternative Technology of Soil Fumigants].
Pesticides are essentially toxic to living things and are used openly, so it is necessary to monitor them to prevent their adverse effects. We have studied farmers'exposure to pesticides during soil fumigation operations with chloropicrin, and have noted a danger to the farmers in the form of dyspnea. We examined accidents/symptoms of residents from chloropicrin reported by the Ministry of Agriculture, Forestry, and Fishery from 2010 to 2019. Eighty percent of the cause of these manifestations was the failure to cover fumigated soil with plastic film. Symptoms shown by residents included eye pain (91%), sore throat (35%), and headache (14%). The most common film used for covering fumigated soil in Japan is polyethylene. The agricultural technology centers in Japan have studied the use of gas barrier films, and found it possible to decrease the amount of chloropicrin used to 1/3, and leakage into the atmosphere to less than 1/10. This technology has become popular in the production of sweet potatoes in Tokushima Prefecture. Soil disinfection by solar heat has also been studied in Japan. These studies have shown positive advancements in the fertilization of soil and in the control of microbes. Chloropicrin has caused occupational exposure to farmers and environmental exposure to local residents. It is advisable that the technologies mentioned above become common practice.


Mentors and role models for women in academic medicine.
Senior mentors and role models have a positive influence on the career advancement of junior professionals in law, business, and medicine. In medicine an increasing number of women are pursuing academic careers, but available senior mentors to provide career guidance are often lacking. We report on the results of a national survey of 558 full-time faculty women, aged 50 years and younger, in departments of medicine in the United States, regarding their experience with role models and mentors. Women with mentors report more publications and more time spent on research activity than those without mentors. Women with a role model reported higher overall career satisfaction. This report, with illustrative examples, may be helpful to other women pursuing academic careers and to physicians who serve as mentors or role models to others.


Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.
Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity; however, heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. Surprisingly, we also observed intradonor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the antibacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the antibacterial BrmIgA reactivity displays interindividual heterogeneity but intraindividual stability. These findings have important implications for how breast milk shapes the development of the preterm infant microbiota and protects against necrotizing enterocolitis.


Splenorenal reflex regulation of arterial pressure.
During the course of our studies into the control of fluid extravasation from the splenic vasculature, we found that intrasplenic inhibition of NO biosynthesis caused an increase in systemic blood pressure. The present experiments were designed to investigate the mechanisms underlying this novel observation. There was an increase in mean arterial pressure when the nonspecific NO inhibitor N(G)-monomethyl-L-arginine (L-NMMA) was infused via the splenic artery but not when the same dose was administered systemically. Conversely, blood pressure decreased after intrasplenic but not systemic administration of the NO donor S-nitroso-N-acetyl-D,L-penicillamine. There was no pressor response to intrasplenic administration of either the inducible or neuronal NO synthase inhibitors N-[3-(aminomethyl)-benzyl] aceramidine and L-N(5)-(1-imino-3-butenyl)-ornithine. The pressor response to L-NMMA was abolished by denervation of either the spleen or the kidney and by pretreatment with the ACE inhibitor enalapril. We propose that the spleen influences systemic blood pressure through a reflex pathway comprising splenic afferent nerves and renal sympathetic control of renin release.


Chlamydia pneumoniae in patients undergoing surgery for thoracic aortic disease.
To investigate if Chlamydia pneumoniae is present in the wall of the thoracic aorta in patients operated on for aneurysm or aortic dissection. Consecutive patients undergoing surgery for thoracic aortic aneurysm (TAA, 32 patients) and for aortic dissection (6 patients) were included in this prospective study. Tissue samples from the aorta were analysed for the presence of C. pneumoniae by polymerase chain reaction (PCR), histopathology, immunohistochemistry and in one aortic tissue sample C. pneumoniae was verified by electron microscopy and immunogold labelling technique. Cultured Hep 2 cells infected with C. pneumoniae were used as a positive control for electron microscopy. Sera for microimmunofluorescence were obtained in 36/38 and throat swabs for C. pneumoniae PCR in 17/38 patients. Chlamydia pneumoniae was detected by PCR in 4 of 32 TAA tissue samples (12%) and in 0 of 6 patients operated on for aortic dissection. Chlamydia pneumoniae inclusion bodies in one of the PCR positive tissue samples were verified by electron microscopy. IgG antibodies to C. pneumoniae were present in 17/31 (55%) and IgA in 15/31 (48%) of the TAA patients and in none of five tested patients with dissection. None of the tested throat swabs was positive. In this study we report the presence of C. pneumoniae by PCR and electron microscopy in the wall of TAA. A high prevalence of serum IgA antibodies to C. pneumoniae was found in TAA patients. In contrast no signs of C. pneumoniae were detected in patients with thoracic aortic dissection.


A complicated relationship: fulfilling the interactive needs of the T lymphocyte and the dendritic cell.
T cells recognize antigenic peptides displayed on the surface of MHC-bearing antigen-presenting cells (APCs), and with sufficient costimulation become activated. However, the ability of an APC (even bearing the correct peptide) to initiate and fulfill the requirements for T cell activation is not easily achieved. Naive T cells use multiple copies of a single receptor to survey the vast array of peptides presented on an APC, and require multiple receptor engagements to initiate T cell activation. Dendritic cells (DCs) are specialized cells with optimal capabilities for priming naive CD4+ T cells. Activation occurs, after initial antigen recognition by T cells, followed by a rapid dialogue between the T cells and the DCs. The resulting changes in both the cytoskeleton and the expression or regulation of cell-surface molecules on both cell types act to further strengthen engagement. In this report, we review the fundamentals of CD4+ T helper cell : DC interactions and discuss recent data concerning the molecular characteristics of this engagement.