The molecular mechanism of acute lung injury caused by Pseudomonas aeruginosa: from bacterial pathogenesis to host response.
Pseudomonas aeruginosa is the most common gram-negative pathogen causing pneumonia in immunocompromised patients. Acute lung injury induced by bacterial exoproducts is associated with a poor outcome in P. aeruginosa pneumonia. The major pathogenic toxins among the exoproducts of P. aeruginosa and the mechanism by which they cause acute lung injury have been investigated: exoenzyme S and co-regulated toxins were found to contribute to acute lung injury. P. aeruginosa secretes these toxins through the recently defined type III secretion system (TTSS), by which gram-negative bacteria directly translocate toxins into the cytosol of target eukaryotic cells. TTSS comprises the secretion apparatus (termed the injectisome), translocators, secreted toxins, and regulatory components. In the P. aeruginosa genome, a pathogenic gene cluster, the exoenzyme S regulon, encodes genes underlying the regulation, secretion, and translocation of TTSS. Four type III secretory toxins, namely ExoS, ExoT, ExoU, and ExoY, have been identified in P. aeruginosa. ExoS is a 49-kDa form of exoenzyme S, a bifunctional toxin that exerts ADP-ribosyltransferase and GTPase-activating protein (GAP) activity to disrupt endocytosis, the actin cytoskeleton, and cell proliferation. ExoT, a 53-kDa form of exoenzyme S with 75% sequence homology to ExoS, also exerts GAP activity to interfere with cell morphology and motility. ExoY is a nucleotidal cyclase that increases the intracellular levels of cyclic adenosine and guanosine monophosphates, resulting in edema formation. ExoU, which exhibits phospholipase A2 activity activated by host cell ubiquitination after translocation, is a major pathogenic cytotoxin that causes alveolar epithelial injury and macrophage necrosis. Approximately 20% of clinical isolates also secrete ExoU, a gene encoded within an insertional pathogenic gene cluster named P. aeruginosa pathogenicity island-2. The ExoU secretory phenotype is associated with a poor clinical outcome in P. aeruginosa pneumonia. Blockade of translocation by TTSS or inhibition of the enzymatic activity of translocated toxins has the potential to decrease acute lung injury and improve clinical outcome.


Spinal versus general anesthesia for day-case laparoscopic cholecystectomy: a prospective randomized study.
The aim of this study was to compare the surgical outcome of day-case laparoscopic cholecystectomy (DCLC) performed with the patient under spinal anesthesia with that performed with the patients under general anesthesia in the management of symptomatic uncomplicated gallstone disease. One hundred eighty patients were prospectively randomized to either the spinal anesthesia DCLC group (SA-DCLC group) or the general anesthesia DCLC group (GA-DCLC group). Intraoperative events related to spinal anesthesia, postoperative complications, and pain scores were recorded. The incidences of both overnight stay and readmissions were also recorded. Patient satisfaction values as to the anesthetic technique and same-day discharge were assessed by direct questionnaire at the end of the first postoperative week. In both groups, all procedures were completed laparoscopically. In the SA-DCLC group, there were 4 (4.4%) anesthetic conversions due to intolerable right shoulder pain, and those 4 patients were excluded from further analysis. In the SA-DCLC group, all patients were discharged on the same day. Overnight stay was required in 8 patients (8.9%) in the GA-DCLC group (P<.001). The cause of overnight stay was nausea and vomiting in 4 patients (4.4%), inadequate pain control in 3 patients (3.3%), and unexplained hypotension in 1 patient (1.1%). Readmission was required in 1 patient (1.1%) in the GA-DCLC group. The difference in patient satisfaction scores with regard to both anesthetic technique and same-day discharge was not statistically significant between the two groups studied. DCLC performed with the patient under spinal anesthesia is feasible and safe and is associated with less postoperative pain and lower incidence of postoperative nausea and vomiting and therefore a lower incidence of overnight stay compared with that performed with the patient under general anesthesia.


Analysis of workers' compensation disabling claims in Oregon's seafood preparation and packaging industry, 2007-2013.
Few occupational health and safety studies have focused on the US seafood preparation and packaging industry, and none on Oregon's seafood industry. Oregon workers' compensation (WC) disabling claims data were analyzed. Oregon Employment Department and US Census Bureau data were used as denominators for rates. During 2007-2013, there were 188 accepted disabling claims, with an average annual rate of 24 claims per 1000 workers. Men experienced a significantly higher rate (27.6 per 1000) than women. The most frequent incident characteristics and circumstances were: by nature-traumatic injuries to muscles, tendons, ligaments, joints (42%); by body part-upper extremities (44%); and by event-overexertion and bodily reaction (48%), and contact with objects and equipment (31%). Analyzing WC disabling claims data provides important preliminary information for understanding workplace hazards to develop control strategies. Reducing traumatic and cumulative injury risk among seafood workers is paramount.


Parity modifies endocrine hormones in urine and problem-solving strategies of captive owl monkeys (Aotus spp.).
Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species.


Portraits of Suzanne, an Osage Woman's Story of Loving the Sun and Living With Skin Cancer.
Suzanne, an elder of The Osage Nation, has been diagnosed with basal cell carcinoma, squamous cell carcinoma, and melanoma skin cancer. Her daughter, Bobbie, a cancer researcher working for the Youth Enjoy Science Research Education Program, conducted a case study to share Suzanne's story through written narrative and a series of images that present Suzanne's reflections on cancer prevention and treatment from a holistic perspective. Seven interview transcripts, as well as photographs, drawings, and paintings of Suzanne, were created and analyzed to explore Suzanne's lived experience of cancer. In her story of living with cancer, Suzanne shares an elder's love and wisdom that can inform cancer education and prevention efforts to help address Native American cancer disparities.


Interfacial and topological effects on the glass transition in free-standing polystyrene films.
United-atom molecular-dynamics computer simulations of atactic polystyrene (PS) were performed for the bulk and free-standing films of 2 nm-20 nm thickness, for both linear and cyclic polymers comprised of 80 monomers. Simulated volumetric glass-transition temperatures (Tg) show a strong dependence on the film thickness below 10 nm. The glass-transition temperature of linear PS is 13% lower than that of the bulk for 2.5 nm-thick films, as compared to less than 1% lower for 20 nm films. Our studies reveal that the fraction of the chain-end groups is larger in the interfacial layer with its outermost region approximately 1 nm below the surface than it is in the bulk. The enhanced population of the end groups is expected to result in a more mobile interfacial layer and the consequent dependence of Tg on the film thickness. In addition, the simulations show an enrichment of backbone aliphatic carbons and concomitant deficit of phenyl aromatic carbons in the interfacial film layer. This deficit would weaken the strong phenyl-phenyl aromatic (π-π) interactions and, hence, lead to a lower film-averaged Tg in thin films, as compared to the bulk sample. To investigate the relative importance of the two possible mechanisms (increased chain ends at the surface or weakened π-π interactions in the interfacial region), the data for linear PS are compared with those for cyclic PS. For the cyclic PS, the reduction of the glass-transition temperature is also significant in thin films, albeit not as much as for linear PS. Moreover, the deficit of phenyl carbons in the film interface is comparable to that observed for linear PS. Therefore, chain-end effects alone cannot explain the observed pronounced Tg dependence on the thickness of thin PS films; the weakened phenyl-phenyl interactions in the interfacial region seems to be an important cause as well.


Communication: time- and space-sliced velocity map electron imaging.
We develop a new method to achieve slice electron imaging using a conventional velocity map imaging apparatus with two additional components: a fast frame complementary metal-oxide semiconductor camera and a high-speed digitizer. The setup was previously shown to be capable of 3D detection and coincidence measurements of ions. Here, we show that when this method is applied to electron imaging, a time slice of 32 ps and a spatial slice of less than 1 mm thick can be achieved. Each slice directly extracts 3D velocity distributions of electrons and provides electron velocity distributions that are impossible or difficult to obtain with a standard 2D imaging electron detector.


Pemphigus Vegetans of Hallopeau: A Case Report.
Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly in flexural areas (1,2). This helps us to differentiate it from PV of Neumann, which is a more extensive and refractory disease, more alike to a pemphigus vulgaris outbreak with blisters which turn into vegetating plaques (3). We report the clinical presentation, course, and therapeutic response in a patient diagnosed with PV of Hallopeau from its early stage during a 3-year follow up. A 62-year-old man, non-smoker, presented at our clinic in July 2018 with hemorrhagic-serous crusts and fissures on the vermilion of the lower lip (Figure 1, a) and two merged circinate, sharply demarcated plaques on the right side of the groin (Figure 1, b). Plaque margins were elevated, with hypertrophic granulation tissue studded with pustules. Mucosal and cutaneous lesions persisted 6 and 4 weeks, respectively. The rest of the mucosa and skin were unaffected; the general state was good. The patient's family history for skin diseases was negative. The medical history included hypertension, atherosclerosis and hypercholesterolemia, hiatus hernia, and recent surgery (3 months prior) of an aortic abdominal aneurysm with reconstruction and synthetic graft placement. He was taking antihypertensives (fixed combination of 3 drugs, among them the ACE-inhibitor perindopril) with well-regulated blood pressure, statins, a pump-proton inhibitor, and acetylsalicylic acid. Differential blood count revealed eosinophilia. Histopathology finding showed acanthosis, suprabasal clefting with a suprabasilar bulla and acantholysis, prominent eosinophilic intraepidermal spongiosis, and heavy dermal infiltration of eosinophils and lymphocytes (Figure 2, a and b). The diagnosis of pemphigus was confirmed by direct immunofluorescence (DIF), which detected C3 deposits on the surface of keratinocytes throughout the epidermis of perilesional skin. Circulating pemphigus antibodies were detected by indirect IF. Only Dsg 3 antibodies were detected using an ELISA assay (233.23 RU/mL). After establishing the diagnosis of PV of Hallopeau, treatment with prednisolone 0.75 mg/kg/day orally in combination with adjuvant immunosuppression (azathioprine 100 mg daily) was started. Appropriate topical therapy with local steroids and antiseptic was applied. The steroid dose was titrated and gradually tapered down to the minimum required to control the disease - 10 mg. One-year remission was achieved. Azathioprine was withdrawn in October 2019 and since then the patient experienced a flare-up twice. The control of pemphigus flare-ups was achieved by a low dose of steroids (30 mg prednisolone orally). It remains debatable whether surgical trauma and radiology procedures such as angiographies (4) well as ACE-inhibitor drugs (5) triggered or aggravated the pemphigus. Early recognition and correct diagnosis of this rare type of pemphigus allows us to treat and control the disease successfully with lower doses of steroids, reducing complications to the minimum.


Improved detection of genus-specific Alphavirus using a generic TaqMan® assay.
Alphaviruses are arthropod borne RNA viruses of medical importance. Geographical expansion of mosquitoes of the Aedes genus in the past decades has been associated with major Alphavirus-associated outbreaks. Climate changes and intensification of air travels have favored vector expansion and virus dissemination in new territories leading to virus emergence not only in tropical areas but also in temperate regions. The detection of emergence is based upon surveillance networks with epidemiological and laboratory investigation. A specific, sensitive and rapid screening test for genus-specific Alphavirus is critically required. To address this issue, we developed a new molecular assay targeting nsP4 gene and using a TaqMan® real time RT-PCR method for the specific detection of all major Alphavirus genus members. This assay was tested for specificity using several Alphavirus species. We also tested successfully clinical sensitivity using patient's samples collected during the Chikungunya outbreak of 2005-2006 in the Indian Ocean. This new pan-Alphavirus molecular diagnostic tool offers great potential for exclusion diagnosis and emergence detection given its broad specificity restricted to Alphavirus genus.


Prognostic and therapeutic significance of myeloma genetics and gene expression profiling.
Molecular diagnostic tools and novel therapeutics now offer the potential for accurate prognostic and personalized treatment road maps for patients with multiple myeloma (MM). We will review the evidence and provide specific recommendations for routine clinical molecular genetic testing and use of such information to guide therapeutic decision making. In particular, the negative prognostic impact of specific IgH translocations such as the t(4;14), t(14;16), chromosome 13 deletion by conventional cytogenetics and loss of 17p13 by interphase fluorescence in situ hybridization are now established. Preliminary gene expression profiling studies have also demonstrated that individual genes (CSK1-B) or groups of genes can define prognosis with greater accuracy than conventional genetic markers and can provide pharmacogenomic and biologic insight into the pathophysiology, therapeutics, and future targets of myeloma. Importantly, we recommend that all clinical trials now adopt routine genetic testing and risk stratification.


The age-dependent decrease in the myogenic response of retinal arterioles as studied with the Retinal Vessel Analyzer.
To study the age-dependent change in myogenic response of retinal arterioles. Fifty-one healthy volunteers with at least ten persons in each of the five age decades (I-V) between 20 and 69 years were subjected to diameter measurement of retinal arterioles using the Retinal Vessel Analyzer (RVA) during rest and during an increase in the systemic blood pressure when lifting hand weights. The transmural pressure in the retinal arterioles during the procedures was estimated from the blood pressure and the intraocular pressure and was compared to the accompanying diameter response. The retinal arteriolar diameter showed a significant decrease as a function of increasing weight for the two younger age groups below the age of 40 years (P=0.007, group I, and P=0.049, group II), compatible with perfect autoregulation, whereas no such change was observed in persons above this age (P=0.41, 0.053, 0.29 for groups III-V, respectively). Studies on autoregulation in retinal disease should consider the normal age-related decrease in diameter response of retinal arterioles when the blood pressure is changed.


Conduction Disorders in the Setting of Acute STEMI.
ST-elevation myocardial (STEMI) is frequently associated with conduction disorders. Regional myocardial ischemia or injury may affect the cardiac conduction system at various locations, and neural reflexes or changes in the balance of the autonomous nervous system may be involved. Sinoatrial and atrioventricular blocks are more frequent in inferior than anterior STEMI, while new left anterior fascicular block and right bundle branch block indicate proximal occlusion of the left anterior descending coronary artery. New left bundle branch block is associated with multi-vessel disease. Most conduction disorders associated with STEMI are reversible with reperfusion therapy, but they may still impair prognosis because they indicate a large area at risk, extensive myocardial infarction or severe coronary artery disease. Acute STEMI recognition is possible in patients with a fascicular or right bundle branch block, but future studies need to define the cut-off values for ST depression in the leads V1-V3 in inferolateral MI and for ST elevation in the same leads in anterior STEMI. In the left bundle branch block, concordant ST elevation is a specific sign of acute coronary artery occlusion, but the ECG feature has low sensitivity.


Evidence-based HIV behavioral prevention from the perspective of the CDC's HIV/AIDS Prevention Research Synthesis Team.
The evidence-based approach to health promotion and disease prevention is growing in many public health sectors, including HIV behavioral prevention. This approach is based on utilizing relevant and rigorous scientific evidence, most appropriately identified through a systematic research synthesis process. With regard to HIV behavioral prevention, this research synthesis process provides decision makers and prevention planners with the evidence base and recommendations they need to translate proven scientific research into practice. The Center for Disease Control and Prevention's HIV/AIDS Prevention Research Synthesis Team conducts such research synthesis activities to help improve HIV behavioral prevention efforts. The team's recent systematic review of the literature during 2000 to 2004 identified HIV behavioral interventions with the best scientific evidence of efficacy, called best-evidence behavioral interventions. Challenges still exist, however, for determining which of these interventions should be disseminated and implemented. Once translated into practice, if these best-evidence behavioral interventions are further evaluated for effectiveness, these findings and, perhaps, the synthesis of such findings can be used to further improve HIV behavioral prevention in the field.


Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine.
A review highlighting the application of sedatives and analgesics in the intensive care unit (ICU) setting, with a focus on the use of dexmedetomidine, is presented. Relevant and applicable clinical trials that resulted from a search of the literature from 1966 to July 2006 using key search terms such as dexmedetomidine, intensive care unit, sedation, delirium, and analgesia were evaluated. Many agents have been evaluated in the search of the optimal regimen for sedation and analgesia in the ICU, including opioids, benzodiazepines, propofol, and antipsychotic agents. Dexmedetomidine has demonstrated efficacy as a sedative analgesic on the basis of its ability to lower opioid, benzodiazepine, and propofol requirements in clinical trials. The role of dexmedetomidine in ICU clinical practice is limited because of a lack of mortality and other morbidity endpoints, such as ICU length of stay, hospital length of stay, time to extubation, long-term complications after discharge from the ICU, and delirium. The most commonly reported adverse effects of dexmedetomidine are secondary to its effects as an alpha(2)-receptor agonist and are cardiac in nature. A detailed cost analysis may be warranted to justify the relatively high acquisition cost of dexmedetomidine. Dexmedetomidine may be an effective agent for ICU sedation and analgesia. However, the lack of clinically relevant endpoints in trials, the concern about adverse cardiovascular effects, and the relatively high acquisition cost of this drug limit its use to a select number of patients who may benefit from its distinguished mechanism of action.


Metal artefacts severely hamper magnetic resonance imaging of the rotator cuff tendons after rotator cuff repair with titanium suture anchors.
The rate of retear after rotator cuff surgery is 17%. Magnetic resonance imaging (MRI) scans are used for confirmative diagnosis of retear. However, because of the presence of titanium suture anchors, metal artefacts on the MRI are common. The present study evaluated the diagnostic value of MRI after rotator cuff tendon surgery with respect to assessing the integrity as well as the degeneration and atrophy of the rotator cuff tendons when titanium anchors are in place. Twenty patients who underwent revision surgery of the rotator cuff as a result of a clinically suspected retear between 2013 and 2015 were included. The MRI scans of these patients were retrospectively analyzed by four specialized shoulder surgeons and compared with intra-operative findings (gold standard). Sensitivity and interobserver agreement among the surgeons in assessing retears as well as the Goutallier and Warner classification were examined. In 36% (range 15% to 50%) of the pre-operative MRI scans, the observers could not review the rotator cuff tendons. When the rotator cuff tendons were assessable, a diagnostic accuracy with a mean sensitivity of 0.84 (0.70 to 1.0) across the surgeons was found, with poor interobserver agreement (kappa = 0.12). Metal artefacts prevented accurate diagnosis from MRI scans of rotator cuff retear in 36% of the patients studied.


Macroprolactinemia in a young man and review of the literature.
A 21-year old man, complaining of headaches and fatigue, with a negative past medical history and a normal clinical examination, underwent a hormonal investigation which revealed hyper-prolactinemia and intact pituitary-gonadal axis. Drug-induced hyperprolactinemia was excluded. Pituitary magnetic resonance imaging indicated a microadenoma in the right part of the gland, with a diameter of 1.5mm. No medical treatment was given as the patient had no symptoms relevant to prolactin excess. The PEG precipitation test was carried out and showed 7% recovery, which was diagnostic of the macroprolactinemia. Relatively few cases of macroprolactinemia have been published in the literature, although the condition is regarded as a fairly common cause of hyperprolactinemia. Macroprolactinemic men represent 10% of published cases.


Natural Product Alantolactone Targeting AKR1C1 Suppresses Cell Proliferation and Metastasis in Non-Small-Cell Lung Cancer.
Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, characterized by high invasion and metastasis. Aldo-keto reductase family 1 member C1 (AKR1C1) plays an important role in cancer cell proliferation and metastasis, and has gained attention as an anticancer drug target. Here, we report that the natural sesquiterpene lactone alantolactone (ALA) was shown to bind directly to AKR1C1 through the Proteome Integral Solubility Alteration (PISA) analysis, a label-free target identification approach based on thermal proteome profiling. Acting as a specific inhibitor of AKR1C1, ALA selectively inhibits the activity of AKR1C1 and ALA treatment in human non-small-cell lung cancer (NSCLC) cell results in a reduction in cell proliferation and metastasis, inhibition of AKR1C1 expression, and deactivation of STAT3. Moreover, ALA inhibited tumor growth in vivo, and the inhibition of AKR1C1 and STAT3 activation were also found in the murine xenograft model. Collectively, our work not only gives mechanistic insights to explain the bioactivity of ALA in anticancer but also provides opportunities of developing novel sesquiterpene lactone-based AKR1C1 inhibitors for the treatment of NSCLC.


Gender correlation of stress levels and sources of stress among first year students in a medical college.
Medical courses in India are very demanding for the students thus making career in medical education very stressful. The study was designed to determine the prevalence of stress levels in 100 first year medical students and to explore the sources of stress & it's relationship across the male and female students. Demographic information and Qualitative data from investigator tailored Medical Student Stress Questionnaire (MSSQ) by self rating under supervision of investigators were subjected to a thematic analysis. Stress perceived was more in males students (82.2%) as compared to females (61.8%) and their MSSQ index score was significantly different (U=985; P=0.02). Moderate to high academic stress was present among 79% of students more so in males with the academic domain score significantly different from that of females (U=883; P=0.007). Females perceived more stress in inter personal domain (12.7%) with the score significantly different from males (U=953.5; P=0.02). Group and Teaching stress was equally present in males and females.


Low-intensity pulsed ultrasound promotes cell motility through vinculin-controlled Rac1 GTPase activity.
Low-intensity pulsed ultrasound (LIPUS) is a therapy used clinically to promote healing. Using live-cell imaging we show that LIPUS stimulation, acting through integrin-mediated cell-matrix adhesions, rapidly induces Rac1 activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin, and both focal adhesion kinase (FAK, also known as PTK2) and Rab5 (both the Rab5a and Rab5b isoforms) have key roles in regulating these effects. Inhibiting the link of vinculin to the actin-cytoskeleton abolished LIPUS sensing. We show that this vinculin-mediated link was not only critical for Rac1 induction and actin rearrangements, but was also important for the induction of a Rab5-dependent increase in the number of early endosomes. Expression of dominant-negative Rab5, or inhibition of endocytosis with dynasore, also blocked LIPUS-induced Rac1 signalling events. Taken together, our data show that LIPUS is sensed by cell matrix adhesions through vinculin, which in turn modulates a Rab5-Rac1 pathway to control ultrasound-mediated endocytosis and cell motility. Finally, we demonstrate that a similar FAK-Rab5-Rac1 pathway acts to control cell spreading upon fibronectin.


Relationship of participation in specific sports to academic performance in adolescents: A 2-year longitudinal study.
Physical activity is considered a promising behavior to improve cognitive function and academic performance in adolescents. As evidence on the relationship of specific sports activity is not conclusive, this study aimed to determine the longitudinal relationships of different sports to academic performance in adolescents and evaluate the cardiorespiratory fitness mediation effect of these sports. We focused on the demands of complex motor skills and the differences between individual sports vs team sports. Four hundred and sixty-three 7th-grade students (227 girls and 236 boys) were followed up over 2 years. Data regarding participation in sports activities, types of sports activities, academic performance, and cardiorespiratory fitness were obtained at baseline and after a 2-year follow-up. Structural equation modeling revealed that participation in all sports activity was positively associated with improvement of academic performance from baseline to follow-up, and that these associations were mediated by cardiorespiratory fitness gains. Participation in sports activities that require more complex motor skills and individual sports activity was directly associated with an improvement of academic performance from baseline to follow-up. Furthermore, quitting sports activities was negatively associated with academic performance via a reversal in cardiorespiratory fitness gains. These findings indicate that participation in specific sports may have significant benefits for academic performance in adolescents. Although these relationships are presumably mediated by cardiorespiratory fitness, sports activities that require more complex motor skills and individual sports participation may be directly related to academic performance. Considering that quitting sports activities reversed these benefits, sustained participation in sports is important for academic success.


Cardiometabolic risk profile among children with migrant parents and role of parental education: the IDEFICS/I.Family cohort.
Evidence shows that migrant children have a higher risk of developing obesity than those with native parents. We aimed to investigate the association between parental migration background and cardiometabolic health in children and adolescents in Europe. We included 8745 children aged 2-17 from the second follow-up of the European IDEFICS/I.Family cohort. Linear regression models were used to investigate the association between parental migration background (one or two migrant parent(s) vs native parents) and body mass index (BMI), metabolic syndrome (MetS) score and its individual components. Outcome variables were parametrized as age and sex-specific z-scores. We adjusted for age, sex, country, and parental education, and additionally for parental income, lifestyle including dietary factors, and maternal BMI. On average, children with two migrant parents had higher z-scores of BMI (+0.24 standard deviation (SD)) and MetS score (+0.30 SD) compared to those with native parents, whereas no significant differences were seen for children with one migrant parent. Associations were attenuated when controlling for maternal BMI and sports club activity. Parental education modified the associations with BMI and MetS z-scores such that they were more pronounced in children with low parental education. Children with two migrant parents were at higher risk for adverse cardiometabolic health compared to children with native parents, especially in families with low parental education. These associations were explained by lower physical activity and maternal body weight and encourages early intervention strategies by schools and communities.


What is the best hydration regimen to prevent contrast media-induced nephrotoxicity?
Hydration is a commonly used method to prevent the decline in GFR after contrast media (CM) application. So far, there have been no controlled, randomized trials investigating the most effective route of fluid administration. Thirty-nine patients with normal renal function (65 +/- 9 years, serum creatinine 0.9 +/- 0.2 mg/dl, GFR = 110 +/- 31 ml/min/1.73 m2) receiving at least 80 ml of low-osmolality CM during an angiographic procedure were randomized to one of the following hydration regimens: Group 1: volume expansion with 300 ml saline during CM administration (n = 20, serum creatinine 0.8 +/- 0.1 mg/dl, GFR 119 +/- 27 ml/min/1.73 m2); Group 2: intravenous administration of at least 2,000 ml saline within 12 h before and after CM application (n = 19, serum creatinine 0.9 +/- 0.2 mg/dl, GFR 101 +/- 32 ml/min/1.73 m2). GFR was measured by CM clearance (Renalyzer) at baseline and 48 hours after CM administration. The primary end point was the mean change in the GFR after 48 hours, the secondary one was the incidence of CM-induced nephropathy (CMIN), defined as a decrease in GFR of more than 50% from the baseline GFR within 48 hours. Patients of group 1 showed a significantly (p < 0.05) higher decline in GFR (delta GFR 34.6 +/- 25.7 ml/min/1.73 m2) compared to patients receiving the intravenous prehydration regimen (delta GFR 18.3 +/- 25.0 ml/min/1.73 m2). The incidence of CMIN was lower in prehydrated patients (5.3%) compared to the other group (15%). In patients with normal renal function, intravenous prehydration seems to be a very effective and feasible method to prevent the decline in GFR after contrast media exposure. Volume expansion given only during the CM exposure appears not to be sufficient enough to prevent renal damage.


Public health implications of recent research in periodontal diseases.
Knowledge of the epidemiology, natural history, and bacterial etiology of the periodontal diseases has advanced considerably as a result of research conducted through the 1980s. Prevention and control of these conditions, however, remains mechanical, cumbersome, and often impractical, based as it is on bacterially nonspecific plaque removal for an indeterminate period. This research has not yet changed the content of public health programs, but it does affect the way the programs are applied. Because sever, generalized disease seems to be less prevalent than previously thought, the need of regular, routine professional care for everybody is questioned. Professional care in a public health context is likely to be more efficient when targeted toward those with severe disease. Dental health education for personal oral hygiene is still supported by scientific studies, though a targeted approach and careful assessment of educational content is needed. Until predictive screening methods for identifying susceptible individuals are developed, selection of priority groups for education and treatment should be guided by epidemiologic data.


Interplay between Hepatitis C Virus and Redox Cell Signaling.
Hepatitis C virus (HCV) infects approximately 3% of the world's population. Currently licensed treatment of HCV chronic infection with pegylated-interferon-α and ribavirin, is not fully effective against all HCV genotypes and is associated to severe side effects. Thus, development of novel therapeutics and identification of new targets for treatment of HCV infection is necessary. Current opinion is orienting to target antiviral drug discovery to the host cell pathways on which the virus relies, instead of against viral structures. Many intracellular signaling pathways manipulated by HCV for its own replication are finely regulated by the oxido-reductive (redox) state of the host cell. At the same time, HCV induces oxidative stress that has been found to affect both virus replication as well as progression and severity of HCV infection. A dual role, positive or negative, for the host cell oxidized conditions on HCV replication has been reported so far. This review examines current information about the effect of oxidative stress on HCV life cycle and the main redox-regulated intracellular pathways activated during HCV infection and involved in its replication.


Fluorocarbon Oil Reinforced Triple Emulsion Drops.
Fluorocarbon oil reinforced triple emulsion drops are prepared to encapsulate a broad range of polar and non-polar cargoes in a single platform. In addition, it is demonstrated that the fluorocarbon oil within the emulsion drop acts as an effective diffusion barrier, as well as a non-adhesive layer, enabling highly efficient encapsulation and retention of small molecules and active biomolecules in microcapsules.


Interleukin-18 polymorphism as an inflammatory index in metabolic syndrome: A preliminary study.
To assess circulatory levels of interleukin-18 (IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes. This study recruited one hundred and eighty individuals divided into three groups with sixty subjects each as: Normal weight (18.0-22.9 kg/m2), overweight (23.0-25.9 kg/m2) and obese (> 26.0 kg/m2) according to South Asian criteria of BMI. Fasting blood glucose (FBG), Lipid profile, insulin, IL-18 and tumor necrosis factor (TNF)α were measured using ELISA kits, whereas low density lipoprotein (LDL)-cholesterol, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were calculated. The body fat percentage (BF) was measured through bioelectrical impedance analysis; waist and hip circumference were measured. Genotyping of IL-18 -607 C/A polymorphism was performed by using tetra-primer amplification refractory mutation system. Student t test, One-way analysis of variance, Hardy-Weinberg equilibrium, Pearson's χ2 test and Pearson's correlation were used, where a P value < 0.05 was considered significant. In an aged matched study, obese subjects showed higher levels of FBG, cholesterol, triglycerides and LDL levels as compared to normal weight (P < 0.001). Highest levels of IL-18 and TNF levels were also seen in obese subjects (IL-18: 58.87 ± 8.59 ng/L) (TNF: 4581.93 ± 2132.05 pg/mL). The percentage of IL-18 -607 A/A polymorphism was higher in overweight and obese subjects vs normal weight subjects (P < 0.001). Moreover, subjects with AA genotype had a higher BF, insulin resistance, TNFα and IL-18 levels when compared with subjects with AC (heterozygous) or CC (wild type) genotypes. However, we did not find any difference in the lipid profile between three subgroups. This preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might cause low grade inflammation, further exacerbated by increased TNFα. All these increase the susceptibility to develop MetS. Further studies are required to validate our findings.


Synthesis of viral proteins in polymorphonuclear leukocytes infected with influenza A virus.
Various reports have indicated that infection of polymorphonuclear leukocytes (PMNL) with influenza virus causes depression of their metabolic and chemotactic responses, but the effect the PMNL has on the life cycle of influenza virus has not been well defined. The studies reported here were undertaken to determine whether influenza virus could replicate within PMNL. Virus-infected and uninfected PMNL were labeled with [35S]methionine and analyzed by gel electrophoresis and fluorography for detection of newly synthesized proteins. Both host- and virus-specific proteins were produced within PMNL. By using indirect immunofluorescence techniques combined with flow cytometry, the expression of newly synthesized viral antigens was detected in virus-infected PMNL. Plaque assays on supernatant fluid from infected PMNL showed that infectious progeny were not produced, indicating that influenza virus infection of PMNL is abortive.


Primary malignant mixed müillerian tumour of the fallopian tube. Report of a case.
Malignant mixed müllerian tumour of the fallopian tube is an extremely rare lesion and to date only approximately 50 cases have been reported. The tumour is seldom distinguished preoperatively from other more common lesions or ovarian cancer. We report a case of a 60-year-old woman who presented to our hospital with pelvic pain. There was no clinical evidence of ascites or adenopathy. Ultrasound and abdominal and pelvic computed tomography showed a left adnexal mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were carried out. Grossly the left side of the fallopian tube was dilated and the cut surface revealed a solid mass filling the entire lumen. Histological examinations showed a malignant mixed müllerian tumour. The tumor was an admixture of both carcinomatous and sarcomatous elements. The carcinomatous element was composed of well to moderately differentiated squamous cell carcinoma and the sarcomatous component was made up of anaplastic spindle shaped cells with hyperchromatic nuclei. An immunohistochemical study was performed. The patient was admitted to the anticancer hospital for further treatment. The prognosis of a primary malignancy of the fallopian tube is poor and depends more on staging than on histologic type and grade.


Corneal edema following diode laser cyclophotocoagulation in an eye with secondary glaucoma.
A 70-year-old man had undergone a complicated cataract extraction followed by repair of iris prolapse ending up with secondary glaucoma. Refusing routine filtering surgery, patient underwent contact transconjunctival diode laser cyclophotocoagulation. This report highlights the occurrence of corneal edema restricted to the inferior half of cornea following a diode laser cyclophotocoagulation performed in the inferior 180 degrees. The necessity to perform a routine specular microscopy in all such cases is highlighted, especially in eyes with good visual acuity.


Evaluation of the NHS England 'Op COURAGE' High Intensity Service for military veterans with significant mental health problems.
In November 2020, The NHS for England launched a pilot High Intensity Service (HIS) programme for treating military veterans complex mental health problems. Seven regional grants were awarded to manage the HIS, including NHS Solent, in South East England. This paper details an evaluation of the HIS, which was conducted from February 2021 to August 2022. This mixed-methods study gained quantitative data from a specifically designed questionnaire that included a number of validated psychometric questionnaires. These were completed by either HIS staff or beneficiaries at entry and exit from the HIS, and qualitative data were gained from semi-structured interviews with the HIS staff. Data were sourced from 45 pre-questionnaires, 25 post programme questionnaires and 11 interviews. This evaluation identified reductions in situational stressors, symptoms and reported illnesses for veterans in crisis. There were reductions in depression, anxiety and post-traumatic stress disorder following programme exit. Staff reported that there was no notable changes in stress levels which appeared to remain high at programme exit. Staff interviews highlighted the importance of simultaneously understanding the social and psychological needs of veterans in mental health crisis. The benefits of integrating veteran staff members into military veteran health services were identified, demonstrating improvements in education around military culture in civilian services. The importance of collaboration between clinical and veteran staff members in veteran health services was noted, demonstrating the positive impact social care provision has on veteran's overall health and well-being. Veteran engagement with the service was advocated as a result of veterans accessing the service feeling understood. This first independent evaluation of the HIS provides a positive reflection, and adds to the limited empirical evidence exploring veteran engagement in health services.


Assessment of physical function in children with cancer: A systematic review.
Appropriate selection of robust assessment tools is essential to monitor physical function in children with cancer during and after treatment. This systematic review aims to identify and critically appraise the measurement properties of physical function measures currently used for children with cancer. Two systematic searches of seven electronic databases [Cumulative Index to Nursing and Allied Health Literature (CINHAL), Medline, PubMed, PsychINFO, Sportsdiscus, EMBASE, and Allied and Complementary Medicine Database (AMED)] were completed to identify physical function measures used in children with cancer and to evaluate their measurement properties. Methodological quality and the adequacy of measurement properties specific to populations of children with cancer were critically appraised using the COSMIN framework to ascertain which measures have evidence to support their use in children with cancer. One hundred and one physical function measures were identified across 154 studies. Measurement property data were available for 12 measures. The measurement properties of only two outcome measures were assessed in more than one study. Despite some positive measurement property data, there was no assessment tool that had consistent and adequate evidence overall to recommend its use in childhood cancer populations. Poor methodological quality of the included studies was the main limiting factor. There is very limited population specific evidence to guide the selection of physical function measures in children with cancer. Further research into the reliability, validity and responsiveness of physical function measures in children with cancer is needed to provide a basis for more effective clinical assessment and management.


Genes Induced by Reovirus Infection Have a Distinct Modular Cis-Regulatory Architecture.
The availability of complete genomes and global gene expression profiling has greatly facilitated analysis of complex genetic regulatory systems. We describe the use of a bioinformatics strategy for analyzing the cis-regulatory design of genes diferentially regulated during viral infection of a target cell. The large-scale transcriptional activity of human embryonic kidney (HEK293) cells to reovirus (serotype 3 Abney) infection was measured using the Affymetrix HU-95Av2 gene array. Comparing the 2000 base pairs of 5' upstream sequence for the most differentially expressed genes revealed highly preserved sequence regions, which we call "modules". Higher-order patterns of modules, called "super-modules", were significantly over-represented in the 5' upstream regions of transcriptionally responsive genes. These supermodules contain binding sites for multiple transcription factors and tend to define the role of genes in processes associated with reovirus infection. The supermodular design encodes a cis-regulatory logic for transducing upstream signaling for the control of expression of genes involved in similar biological processes. In the case of reovirus infection, these processes recapitulate the integrated response of cells including signal transduction, transcriptional regulation, cell cycle control, and apoptosis. The computational strategies described for analyzing gene expression data to discover cis-regulatory features and associating them with pathological processes represents a novel approach to studying the interaction of a pathogen with its target cells.


Aortic stenosis of a bicuspid aortic valve in a patient with Klippel-Feil syndrome: a case report.
Klippel-Feil syndrome (KFS) is a rare congenital anomaly of the cervical spine, which is associated with a number of cardiovascular malformations, including coarctation of the aorta, bicuspid aortic valve (BAoV), and aortic aneurysm. Operative management of aortic stenosis of a BAoV in a patient with KFS has not been previously reported. A 54-year-old Caucasian woman with known KFS presented to her local hospital for elective cholecystectomy. An ejection systolic murmur was found incidentally on preoperative workup, which was confirmed to be due to a severely stenosed BAoV. The cholecystectomy was cancelled, and the patient was referred to our centre and accepted for surgical aortic valve replacement (AVR) based on symptomatic and prognostic grounds. Anaesthetic review of cervical spine imaging showed fusion of the C2-C6 vertebral bodies and a desiccated bulging disc at C4-C5 but no significant foraminal narrowing in the lower cervical spine. Valve replacement with a mechanical aortic prosthesis resulted in an uneventful recovery and the patient was discharged home to follow-up. We report the first case of severe aortic valve stenosis requiring AVR in a Klippel-Feil patient, in whom the aortic valve was confirmed to be bicuspid. This report provides further evidence of an association of KFS with BAoV and strengthens the case for screening and follow-up of KFS patients for BAoV and other cardiovascular pathologies, the consequences of which may be serious.


Distinct effects of humic acid on transport and retention of TiO2 rutile nanoparticles in saturated sand columns.
The distinct effects of humic acid (HA, 0-10 mg L(-1)) on the transport of titanium dioxide (rutile) nanoparticles (nTiO(2)) through saturated sand columns were observed under conditions of environmental relevance (ionic strength 3-200 mM NaCl, pH 5.7 and 9.0). Specifically, the transport of nTiO(2) was dramatically enhanced in the presence of HA at pH 5.7, even at a low HA concentration of 1 mg L(-1). The mobility of nTiO(2) was further increased with greater concentrations of HA. In contrast, this enhancement of the nTiO(2) transportability due to the presence of HA was limited at pH 9.0 because of the negligible adsorption of HA onto nTiO(2), regardless of the concentrations of HA examined in this study. The distinct effects can be explained by the adsorption behaviors of HA to nTiO(2) and sand surfaces and the resulting interactions between nTiO(2) and sand surfaces under different conditions, which resulted in a large variation of the nTiO(2) transport and deposition behaviors at various conditions. In addition, theoretical interaction energy calculations and additional elution experiments indicate that the secondary energy minimum played an important role in controlling the nTiO(2) transport and deposition in porous media observed in this study. Moreover, the interaction energy calculations suggest that at pH 5.7, HA affected nTiO(2) transport by increasing the negative surface charge of nTiO(2) at low HA adsorption densities; whereas, combinations of increased electrostatic and steric interactions due to the presence of HA were the main mechanisms of enhanced transportability of nTiO(2) at high HA adsorption densities. Overall, results from this study suggest that natural organic matter and solution pH are likely key factors that govern the stability and mobility of nTiO(2) in the natural aquatic environment.


Chronic rejection in human heart transplantation.
The more prevalent complication in patients with a long survival rate after heart transplantation is chronic rejection, which was studied in a series of 80 necropsies and five cardiac grafts surgically removed for retransplantation after chronic rejection. In the material obtained at necropsy, 11 of 14 patients with a survival rate of more than 6 months died from chronic rejection. Clinically, the usual manifestation was heart failure. Anatomic angiograms were performed in several cases. They demonstrated narrowing and nonopacification of small coronary arteries, often accompanied by thrombosis and ischemic complications. The histologic study detected three types of rejection. (1) The more typical rejection is observed after 6 months. It is characterized by a stenosing fibrous endarteritis. (2) Another type of rejection occurs earlier and is associated with acute rejection; its anatomic substratum is an inflammatory panarteritis. (3) This type of rejection is accompanied by large atheromatous deposits. The significance and pathogenesis of these lesions are discussed in correlation with their clinical context and with the electron microscopic observations.


[Ischemic Heart Disease: Focus on Acute Infarction of the Right Ventricular Myocardium].
Ischemic heart disease and acute myocardial infarction (AMI) in particular remain widely spread and contribute seriously in total mortality of population. This literature review is devoted to the right ventricular (RV) AMI as the least studied problem of contemporary cardiology. We present here description of specific characteristics of blood supply to ventricles of the heart, clinical picture, diagnostic criteria and prognosis of RV infarction. We also present current strategy of management of patients with RV AMI including early revascularization with the help of percutaneous coronary intervention.


The Use of Psychotropic Drug Therapy in Borderline Personality Disorder: a Case Report.
It is estimated that around 75% of patients with Borderline Personality Disorder (BPD) are prescribed psychotropic medication during their treatment course, although this is not recommended as first line therapy. In the UK, there are no guidelines to advise which drug treatments to use in BPD, however, numerous, but mostly small scale studies, show evidence that different medications target specific core symptoms. We report a case of a 25 year old woman with BPD, who has received treatment with five different psychotropic medications. We go on to assess not only the efficacy of these treatments in this individual case, but also whether the use of these treatments is in line with best evidence according to currently available research.


Surprisingly high specificity of the PPD skin test for M. tuberculosis infection from recent exposure in The Gambia.
Options for intervention against Mycobacterium tuberculosis infection are limited by the diagnostic tools available. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. We compared the PPD skin test with an ELISPOT test in The Gambia. Household contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed according to sleeping proximity to an index case using logistic regression. 615 household contacts and 105 community controls were recruited. All three tests assessed increased significantly in positivity with increasing M. tuberculosis exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6-35.3). While the PPD skin test positivity continued to trend downwards in the community with increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10 ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT-6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, p<0.0001). With increasing M. tuberculosis exposure, the proportion of ESAT-6/CFP-10 positive contacts who were PPD skin test positive increased (p<0.0001), and the proportion of ESAT-6/CFP-10 negative contacts that were PPD skin test negative decreased (p<0.0001); the converse did not occur. The PPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited.


Identification of compounds inhibiting prion replication and toxicity by removing PrPC from the cell surface.
The vast majority of therapeutic approaches tested so far for prion diseases, transmissible neurodegenerative disorders of human and animals, tackled PrPSc , the aggregated and infectious isoform of the cellular prion protein (PrPC ), with largely unsuccessful results. Conversely, targeting PrPC expression, stability or cell surface localization are poorly explored strategies. We recently characterized the mode of action of chlorpromazine, an anti-psychotic drug known to inhibit prion replication and toxicity by inducing the re-localization of PrPC from the plasma membrane. Unfortunately, chlorpromazine possesses pharmacokinetic properties unsuitable for chronic use in vivo, namely low specificity and high toxicity. Here, we employed HEK293 cells stably expressing EGFP-PrP to carry out a semi-automated high content screening (HCS) of a chemical library directed at identifying non-cytotoxic molecules capable of specifically relocalizing PrPC from the plasma membrane as well as inhibiting prion replication in N2a cell cultures. We identified four candidate hits inducing a significant reduction in cell surface PrPC , one of which also inhibited prion propagation and toxicity in cell cultures in a strain-independent fashion. This study defines a new screening method and novel anti-prion compounds supporting the notion that removing PrPC from the cell surface could represent a viable therapeutic strategy for prion diseases.


Therapeutic Hypothermia for Asphyxial Out-of-Hospital Cardiac Arrest Due to Drowning: A Systematic Review of Case Series and Case Reports.
The objective of this review was to summarize published evidence of the effectiveness of therapeutic hypothermia in patients with drowning-associated asphyxial out-of-hospital cardiac arrest (OHCA) and to explore any preliminary favorable factors in the management of therapeutic hypothermia to improve survival and neurological outcome. Drowning may result in asphyxial OHCA or hypothermic OHCA, but the former does not provide any potential neuroprotective effect as the latter may do. Electronic literature searches of Ovid Medline, Embase, Cochrane Library, and Scopus were performed for all years from inception to July 2016. Primary studies in the form of case reports, letters to the editor, and others with higher quality are included, but guidelines, reviews, editorials, textbook chapters, conference abstracts, and nonhuman studies are excluded. Non-English articles are excluded. Relevant studies are then deemed eligible if the drowning OHCA patient's initial temperature was above 28°C, which implies asphyxial cardiac arrest, and intentional therapeutic hypothermia was instituted. Because of the narrow scope of interest and strict definition of the condition, limited studies addressed it, and no randomized controlled trials (RCT) could be selected. Thirteen studies covering 35 patients are included. No quantitative synthesis, assessment of study quality, or assessment of bias was performed. It is conjectured that extended therapeutic hypothermia of 48-72 hours might help prevent reperfusion injury during the intermediate phase of postcardiac arrest care to benefit patients of drowning-associated asphyxial OHCA, but this finding only serves as preliminary observation for future research. No conclusive recommendation could be made regarding the duration of and the time of onset of therapeutic hypothermia. Future research should put effort on RCT, particularly the effect of extended duration of 48-72 hours. Important parameters should be reported in detail. Asphyxial and hypothermic OHCA should be differentiated.


High Resolution FTIR Study of the nu5 Bands of HSiD3 and H120SnD3
High resolution Fourier Transform spectra of HSiD3 and monoisotopic H120SnD3 have been recorded in the region of the nu5 fundamental at 850.68 and 646.90 cm-1 with a resolution of 3.3 and 2.8 x 10(-3) cm-1, respectively. About 2000 rovibrational transitions of each species have been assigned and fitted to two different reductions of the effective Hamiltonian, with sigma(Fit) = 1.2 x 10(-4) (HSiD3) and 1.4 x 10(-4) cm-1 (H120SnD3). The two sets of parameters were shown to be equivalent, and relations between parameters belonging to different reductions are perfectly fulfilled. Furthermore the ground state constants C0 and DK0 have been determined for the first time. For consistency the previously measured data belonging to the nu5 band of H70GeD3 have been refitted, sigma(Fit) = 1.6 x 10(-4) cm-1, on the basis of improved ground state parameters including the h'3 term accounting for the splitting of the K = 3 level. Copyright 1998 Academic Press.


A new detection method of ultrasonic flowmeter beam incident angle.
We have developed a new method of continuously measuring the angle between a pulsed Doppler blood flowmeter ultrasonic beam and the flow axis for precise blood flow velocity measurements. The transducer employed in the flowmeter system design is formed by two LZT 10 MHz crystals held in a lightweight polystyrene shell. Recessed internal cavities in the shell hold one 10 MHz crystal at a 45 degree angle for blood flow velocity measurement and the other crystal at a 90 degree angle for beam angle detection. The angle and Doppler frequency are supplied to a digital signal processor to precisely calculate instantaneous flow velocity. This automatic angle correction system is designed for applications where the transducer-flow angle is subject to change. Typical use examples are half-cylinder flow transducers that do not encircle the artery and external, hand-held, transcutaneous transducers.


Histone Deacetylase 5 Is Overexpressed in Scleroderma Endothelial Cells and Impairs Angiogenesis via Repression of Proangiogenic Factors.
Vascular dysfunction represents a disease-initiating event in systemic sclerosis (SSc; scleroderma). Results of recent studies suggest that epigenetic dysregulation impairs normal angiogenesis and can result in abnormal patterns of blood vessel growth. Histone deacetylases (HDACs) control endothelial cell (EC) proliferation and regulate EC migration. Specifically, HDAC-5 appears to be antiangiogenic. This study was undertaken to test whether HDAC-5 contributes to impaired angiogenesis in SSc by repressing proangiogenic factors in ECs. Dermal ECs were isolated from patients with diffuse cutaneous SSc and healthy controls. Angiogenesis was assessed using an in vitro Matrigel tube formation assay. An assay for transposase-accessible chromatin using sequencing (ATAC-seq) was performed to assess and localize the genome-wide effects of HDAC5 knockdown on chromatin accessibility. The expression of HDAC5 was significantly increased in ECs from patients with SSc compared to healthy control ECs. Silencing of HDAC5 in SSc ECs restored normal angiogenesis. HDAC5 knockdown followed by ATAC-seq assay in SSc ECs identified key HDAC5-regulated genes involved in angiogenesis and fibrosis, such as CYR61, PVRL2, and FSTL1. Simultaneous knockdown of HDAC5 in conjunction with either CYR61, PVRL2, or FSTL1 inhibited angiogenesis in SSc ECs. Conversely, overexpression of these genes individually led to an increase in tube formation as assessed by Matrigel assay, suggesting that these genes play functional roles in the impairment of angiogenesis in SSc. Several novel HDAC5-regulated target genes associated with impaired angiogenesis were identified in SSc ECs by ATAC-seq. The results of this study provide a potential link between epigenetic regulation and impaired angiogenesis in SSc, and identify a novel mechanism for the dysregulated angiogenesis that characterizes this disease.


Simultaneous confidence intervals of risk differences in stratified paired designs.
In stratified matched-pair studies, risk difference between two proportions is one of the most frequently used indices in comparing efficiency between two treatments or diagnostic tests. This article presents five simultaneous confidence intervals and two bootstrap simultaneous confidence intervals for risk differences in stratified matched-pair designs. The proposed confidence intervals are evaluated with respect to their coverage probabilities, expected widths, and ratios of the mesial noncoverage to noncoverage probability. Empirical results show that (1) hybrid simultaneous confidence intervals outperform nonhybrid simultaneous confidence intervals; (2) hybrid simultaneous confidence intervals based on median estimator outperform those based on maximum likelihood estimator; and (3) hybrid simultaneous confidence intervals incorporated with Wilson score and Agresti coull intervals and the bootstrap t-percentile simultaneous interval based on median unbiased estimators behave satisfactorily for small to large sample sizes in the sense that their empirical coverage probabilities are close to the prespecified nominal confidence level, and their ratios of the mesial noncoverage to noncoverage probabilities lie in [0.4,0.6] and are hence recommended. Real examples from clinical studies are used to illustrate the proposed methodologies.


Endocrine responses to head and neck surgery in men.
It has been well established that surgical stress leads to profound changes in endocrine function and metabolism. However, the endocrine response varies depending upon the type and the extent of surgery. As no data were available about the endocrine changes during and following major head and neck surgery, this study was performed. Plasma levels of adrenocorticotropin (ACTH), cortisol, thyroid-stimulating hormone (TSH), thyroxin (T4), triiodothyronine (T3), growth hormone (GH), prolactin (PRL), gonadotropins (LH and FSH), oestradiol and testosterone were determined in 17 patients one day before, immediately after, as well as 2 and 4 days after head and neck surgery. An increase in ACTH, cortisol, PRL and GH, and a decrease in plasma oestradiol and testosterone values occurred immediately after surgery. There was a slow fall in cortisol levels after surgery, but they remained elevated even on the fourth postoperative day, whereas GH values returned on the fourth day to the initial level. There were no changes in gonadotropins, TSH and T3, but T4 values were found to be increased on the second and fourth postoperative day. The prolonged cortisol stimulation which was not described by other researchers after other kinds of surgery might be caused by vagal stimulation during and/or after head and neck surgery. Increased needs after a major head and neck surgery could explain the increment of T4 values.


A methodology to prioritize ecosystem restoration of in-situ well pads in the Permian Basin of western Texas and southeastern New Mexico, USA.
Since the mid-2000s, drilling and production of oil and gas activities have grown exponentially in the southwestern United States. The clearing of pre-existing vegetation and topsoil to build well pads is known to have a broad range of ecological, biological, hydrological, and health impacts, therefore ecosystem restoration of the well pads is generally required. This process, however, is often complicated by limited funding, various governing bodies and ownership, and frequent extreme weather events. To ensure that well pad construction does not result in damaging, irreversible environmental change in the region, a prioritization strategy is needed to maximize the effectiveness of restoration efforts. The objective of this study is to develop a methodology to prioritize well pads where ecosystem restoration is urgently needed. In this methodology, a set of locational soil (e.g., soil fragility, wind and water erodibility) and land cover (e.g., land cover, proximity to streams) attributes were derived from publicly available datasets and a restoration priority score system along with a weighting factor were assigned to individual attributes. Accordingly, a total restoration priority score (TRPS) was calculated for individual well pads. This methodology was applied to a dataset of >10,000 well pads located in the Permian Basin and the surrounding area. This method effectively filtered out a large number of sites with low TRPS, and identified a small portion of high-score, clustered well pads. The identification of such well pads makes the logistical challenge of targeted restoration much easier for stakeholders tasked with maximizing the effectiveness of restoration efforts with limited funding. Despite some known limitations and inaccuracies, this method is low-cost and can be easily adaptable to humid and sub-humid systems, and even to restoration relevant to non-oil and gas exploration activities, such as solar and wind development, in the southwestern United States and many other areas worldwide.


ORF7 of varicella-zoster virus is a neurotropic factor.
Varicella-zoster virus (VZV) is the causative agent of chickenpox and herpes zoster (shingles). After the primary infection, the virus remains latent in sensory ganglia and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine is highly attenuated in the skin and yet retains its neurovirulence and may reactivate and damage sensory neurons. The factors involved in neuronal invasion and establishment of latency are still elusive. Previously, we constructed a library of whole-gene deletion mutants carrying a bacterial artificial chromosome sequence and a luciferase marker in order to perform a comprehensive VZV genome functional analysis. Here, screening of dispensable gene deletion mutants in differentiated neuronal cells led to the identification of ORF7 as the first known, likely a main, VZV neurotropic factor. ORF7 is a virion component localized to the Golgi compartment in infected cells, whose deletion causes loss of polykaryon formation in epithelial cell culture. Interestingly, ORF7 deletion completely abolishes viral spread in human nervous tissue ex vivo and in an in vivo mouse model. This finding adds to our previous report that ORF7 is also a skin-tropic factor. The results of our investigation will not only lead to a better understanding of VZV neurotropism but could also contribute to the development of a neuroattenuated vaccine candidate against shingles or a vector for delivery of other antigens.


In silico selection of therapeutic antibodies for development: viscosity, clearance, and chemical stability.
For mAbs to be viable therapeutics, they must be formulated to have low viscosity, be chemically stable, and have normal in vivo clearance rates. We explored these properties by observing correlations of up to 60 different antibodies of the IgG1 isotype. Unexpectedly, we observe significant correlations with simple physical properties obtainable from antibody sequences and by molecular dynamics simulations of individual antibody molecules. mAbs viscosities increase strongly with hydrophobicity and charge dipole distribution and decrease with net charge. Fast clearance correlates with high hydrophobicities of certain complementarity determining regions and with high positive or high negative net charge. Chemical degradation from tryptophan oxidation correlates with the average solvent exposure time of tryptophan residues. Aspartic acid isomerization rates can be predicted from solvent exposure and flexibility as determined by molecular dynamics simulations. These studies should aid in more rapid screening and selection of mAb candidates during early discovery.


Microfractures in metal-ceramic and all-ceramic implant-supported fixed dental prostheses caused by superstructure fixation.
The effect of ceramic veneering on the passivity of fit of cast metal and CAD/CAM-fabricated zirconia ceramic implant-supported three-unit cement-retained restorations was investigated, as well as the effect of misfit stress on the marginal integrity of ceramic veneers. Superstructures were fabricated using cast metal or by CAD/CAM milling of presintered or HIP zirconia ceramic (n=10). Before and after veneering, strain gages were used to measure in vitro the strain developed in all the restorations as a result of superstructure fixation. Fluorescent penetrant method was used to detect microcracks developed in ceramic veneers. Cast frameworks showed significantly higher strain values than CAD/CAM frameworks (p=0.000). Veneering significantly increased strain development in all CAD/CAM frameworks (p=0.000). Compared to zirconia ceramic restorations, significantly more microcracks were observed in cast restorations (p=0.000) both before and after superstructure fixation.


Inhibition of tyrosine hydroxylase, a Fe(II)-stimulated monooxygenase, by bleomycin.
Tyrosine hydroxylase was shown to be inhibited in vitro by bleomycin. At a concentration of 1 X 10(-4) M, copper-free BLM-A2 inhibited tyrosine hydroxylase activity by 50%, and all other bleomycins investigated including copper-bound BLM-A2 showed similar degrees of inhibition of tyrosine hydroxylase. The kinetic data have shown that the inhibition by BLM-A2 is competitive with a tetrahydropterin cofactor (6-methyl-tetrahydropterin) and uncompetitive with tyrosine. The inhibition of tyrosine hydroxylase by bleomycin was not reversed by Fe(II) or superoxide dismutase. These results suggest that the inhibition may be neither due to the chelating action of bleomycin with ferrous ion nor due to the production of superoxide and hydroxyl radicals by the formation of an oxygen-labile Fe(II)-bleomycin complex.


Prognostic factors of patients after liver cancer surgery: Based on Surveillance, Epidemiology, and End Results database.
This study aimed to investigate the prognostic factors of patients after liver cancer surgery and evaluate the predictive power of nomogram. Liver cancer patients with the history of surgery in the Surveillance, Epidemiology, and End Results database between 2000 and 2016 were preliminary retrieved. Patients were divided into the survival group (n = 2120, survival ≥5 years) and the death group (n = 2615, survival < 5 years). Single-factor and multi-factor Cox regression were used for analyzing the risk factors of death in patients with liver cancer after surgery. Compared with single patients, married status was the protective factor for death in patients undergoing liver cancer surgery (HR = 0.757, 95%CI: 0.685-0.837, P < .001); the risk of death in Afro-Americans (HR = 1.300, 95%CI: 1.166-1.449, P < .001) was higher than that in Caucasians, while the occurrence of death in Asians (HR = 0.821, 95%CI: 0.1754-0.895, P < .0012) was lower; female patients had a lower incidence of death (HR = 0.875, 95%CI: 0.809-0.947, P < .001); grade II (HR = 1.167, 95%CI: 1.080-1.262, P < .001), III (HR = 1.580, 95%CI: 1.433-1.744, P < .001), and IV (HR = 1.419, 95%CI: 1.145-1.758, P = 0.001) were the risk factors for death in patients with liver cancer. The prognostic factors of liver cancer patients after surgery include the marital status, race, gender, age, grade of cancer and tumor size. The nomogram with good predictive ability can provide the prediction of 5-year survival for clinical development.


Ruling out coronary heart disease in primary care: external validation of a clinical prediction rule.
The Marburg Heart Score (MHS) aims to assist GPs in safely ruling out coronary heart disease (CHD) in patients presenting with chest pain, and to guide management decisions. To investigate the diagnostic accuracy of the MHS in an independent sample and to evaluate the generalisability to new patients. Cross-sectional diagnostic study with delayed-type reference standard in general practice in Hesse, Germany. Fifty-six German GPs recruited 844 males and females aged ≥ 35 years, presenting between July 2009 and February 2010 with chest pain. Baseline data included the items of the MHS. Data on the subsequent course of chest pain, investigations, hospitalisations, and medication were collected over 6 months and were reviewed by an independent expert panel. CHD was the reference condition. Measures of diagnostic accuracy included the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, likelihood ratios, and predictive values. The AUC was 0.84 (95% confidence interval [CI] = 0.80 to 0.88). For a cut-off value of 3, the MHS showed a sensitivity of 89.1% (95% CI = 81.1% to 94.0%), a specificity of 63.5% (95% CI = 60.0% to 66.9%), a positive predictive value of 23.3% (95% CI = 19.2% to 28.0%), and a negative predictive value of 97.9% (95% CI = 96.2% to 98.9%). Considering the diagnostic accuracy of the MHS, its generalisability, and ease of application, its use in clinical practice is recommended.


Phase II trial in China of a new, rapidly-acting and effective oral antimalarial, CGP 56697, for the treatment of Plasmodium falciparum malaria.
One hundred and two Chinese out-patients with naturally acquired, previously untreated, falciparum malaria were selected to evaluate the efficacy of a new combination anti-malaria therapy, CGP 56697 (artemether plus benflumetol). In this open non-comparative trial each patient received a combination of 80 mg artemether and 480 mg benflumetol given orally at 0, 8, 24 and 48 hours (total: 320 mg artemether, 1,920 mg benflumetol). Patients were kept for 28 days in a transmission-free hospital in an area with chloroquine resistant falciparum malaria to prevent reinfection and to aid diagnosis of recrudescence. Progress and possible adverse effects were monitored by blood film parasitology, blood biochemistry assays, urinalysis, ECG and X-ray. Ninety-eight of the 102 patients were shown to be free of infection at 28 days, a 96.1% cure rate. Parasite reduction at 24 hours was 99.4%. Time to effect complete parasite clearance ranged from 24 to 54 hours (median 30 hours). Time for fever clearance ranged from 6 to 78 hours (median 18 hours). Recrudescence was low (3.9%). No significant adverse side-effects were encountered. It is concluded that CGP 56697, a combination anti-malaria therapy of artemether with benflumetol, offered a rapid and highly effective treatment for acute uncomplicated falciparum malaria in an area of chloroquine-resistant malaria in China.


Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7.
The F-box and WD repeat domain containing 7 (FBXW7) tumour suppressor gene encodes a substrate-recognition subunit of Skp, cullin, F-box (SCF)-containing complexes. The tumour-suppressive role of FBXW7 is ascribed to its ability to drive ubiquitination and degradation of oncoproteins. Despite this molecular understanding, therapeutic approaches that target defective FBXW7 have not been identified. Using genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screens, focussed RNA-interference screens and whole and phospho-proteome mass spectrometry profiling in multiple FBXW7 wild-type and defective isogenic cell lines, we identified a number of FBXW7 synthetic lethal targets, including proteins involved in the response to replication fork stress and proteins involved in replication origin firing, such as cell division cycle 7-related protein kinase (CDC7) and its substrate, DNA replication complex GINS protein SLD5 (GINS4). The CDC7 synthetic lethal effect was confirmed using small-molecule inhibitors. Mechanistically, FBXW7/CDC7 synthetic lethality is dependent upon the replication factor telomere-associated protein RIF1 (RIF1), with RIF1 silencing reversing the FBXW7-selective effects of CDC7 inhibition. The delineation of FBXW7 synthetic lethal effects we describe here could serve as the starting point for subsequent drug discovery and/or development in this area.


Preparation and testing of vaccines prepared from the envelopes of Venezuelan, eastern, and western equine encephalomyelitis viruses.
Envelope components were separated from Venezuelan, Eastern, and Western equine encephalomyelitis viruses after treatment of the virions with detergent. Vaccines prepared from the envelope component were capable of stimulating mice to produce humoral antibodies. Protective efficacy studies were performed using mono-, di-, and trivalent vaccine combinations. These elicited varying degrees of homologous protection, and Eastern and Venezuelan equine encephalomyelitis envelope products appeared to confer protection to mice challenged with Western equine encephalomyelitis virus.


Electrode reaction of Pu3+/Pu couple in LiCl-KCl eutectic melts: comparison of the electrode reaction at the surface of liquid Bi with that at a solid Mo electrode.
The electrode reaction of Pu3+/Pu couple at the interface between LiCl-KCl eutectic melt containing PuCl3 and liquid Bi phase was investigated by cyclic voltammetry at 723, 773 and 823 K. For comparison, the system was also studied using a solid Mo electrode in place of the liquid Bi electrode. It was found that the electrode reaction of Pu3+/Pu couple at the Bi electrode was almost reversible. The redox potentials of Pu3+/Pu couple at the liquid Bi electrode in the LiCl-KCl eutectic melt containing 0.87 wt% PuCl3 (0.0014 mole fraction) at 723, 773 and 823 K were observed to be more positive by 0.575, 0.572 and 0.566 V, respectively, than those at the Mo electrode. These differences in potential were thermodynamically analyzed by assuming a lowering of the activity of Pu in Bi phase according to the alloy formation of PuBi2.


Diagnostic value and implications of vimentin expression in normal, reactive and neoplastic endocervical epithelium.
To assess vimentin immunoreactivity in normal, reactive and neoplastic endocervical epithelium, and compare the results with p16 protein, Ki-67 and bcl-2 expression. Sixty-two cervical biopsy specimens including normal endocervical epithelium, tubo-endometrioid metaplasia, adenocarcinoma in situ, stratified mucin producing intraepithelial lesions (SMILE), and invasive adenocarcinomas were stained immunohistochemically for vimentin and for p16 protein, Ki-67 and bcl-2. Twelve cases also included areas of high grade cervical intraepithelial neoplasia (CIN). Normal endocervical epithelium usually showed subtle but distinct sub-nuclear and delicate lateral cell border vimentin expression while tubo-endometrioid metaplasia exhibited more diffuse cytoplasmic immunoreactivity. Usually adenocarcinoma in situ was completely negative and therefore vimentin staining sharply distinguished the benign and neoplastic epithelial elements. The SMILE lesions and high grade CIN were also vimentin negative in most cases. Most invasive adenocarcinomas were not stained but focal vimentin immunoreactivity was observed in 7/18 cases, and was restricted to small glands and infiltrating cell clusters at the deep (advancing) tumour margin. Normal endocervical cells often exhibit vimentin staining, and this is increased in reactive and metaplastic situations, whereas adenocarcinoma in situ is usually completely negative. Therefore vimentin is a useful additional diagnostic marker in the assessment of problematic cervical glandular lesions. The localised re-expression of vimentin at the deep margin of some endocervical adenocarcinomas may be relevant to the process of tumour progression and invasion in these cases.


The RNA-activated protein kinase enhances the induction of interferon-beta and apoptosis mediated by cytoplasmic RNA sensors.
Detection of foreign RNA by the innate immune system can trigger the induction of type I interferon (IFN) and apoptosis. Important antiviral defense pathways that result in type I IFN production following the recognition of foreign double-stranded RNA (dsRNA) include the RIG-I family helicases and IPS-1 adaptor cytosolic pathway and the Toll-like receptor 3 and TIR domain-containing adaptor-inducing IFN-beta (TRIF) adaptor membrane-associated pathway, both of which activate IFN regulatory factor 3 (IRF3). In addition to triggering an innate immune response, dsRNAs are widely used to mediate gene-selective silencing in mammalian cells by the RNA interference pathway. We investigated the ability of short interfering RNAs, including T7 phage polymerase-synthesized RNA (PRNA), which like some viral RNAs contains a 5'-triphosphate, to selectively silence gene expression and to cause induction of IFN-beta and apoptosis. We found that PRNA-mediated gene silencing and associated nonspecific pro-apoptotic and IFN-inducing effects were dependent on the cell line and RNA length. Double-stranded PRNAs 50 nucleotides long as well as polyinosinic-polycytidylic acid activated the RNA-dependent protein kinase (PKR) and induced significant levels of IFN-beta and apoptosis, whereas shorter PRNAs and chemically synthesized dsRNAs did not. Effector caspase activation and apoptosis following RNA transfection was enhanced by pretreatment with IFN, and removal of the 5'-phosphate from PRNAs decreased induction of both IFN-beta and apoptosis. PKR, in addition to IPS-1 and IRF3 but not TRIF, was required for maximal type I IFN-beta induction and the induction of apoptosis by both transfected PRNAs and polyinosinic-polycytidylic acid.


Low CA II expression is associated with tumor aggressiveness and poor prognosis in gastric cancer patients.
Carbonic anhydrase II is present in normal gastric mucosa; thus, this study aimed to investigate whether its expression persisted in neoplastic gastric tissues, as well as its prognostic value for gastric cancer patients. The protein CA II expression pattern was retrospectively analyzed by immunohistochemistry in 181 gastric cancer patients who had undergone gastrectomy. The relationship between the CA II expression level and clinicopathological parameters was investigated. Survival analysis according to CA II expression was measured by Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of CA II expression. CA II expression was significantly decreased in gastric cancer tissues compared with normal stomach mucosa. Low expression was significantly associated with tumor size, depth of invasion, lymph node involvement, distant metastasis and TNM stage, and it predicted poor survival in gastric cancer patients. Moreover, CA II was an independent prognosis indicator for the overall survival of gastric cancer patients. The down-regulation of CA II expression was observed in gastric cancer and may serve as an independent prognostic factor for the overall survival of gastric cancer patients.


Skipping breakfast is detrimental for primary school children: cross-sectional analysis of determinants for targeted prevention.
Skipping breakfast was found to be associated with abdominal obesity in primary school children. The aim of this research was to examine factors associated with skipping breakfast in primary school children in order to develop targeted preventive measures. Baseline data assessment (2010) of a cluster-randomized controlled trial for the evaluation of a school-based health promotion program in primary school children in the state of Baden-Württemberg, Germany. Anthropometric measures of 1,943 primary school children aged 7.1 ± 0.6 years (51.2% boys) were conducted according to ISAK-standards (International Standard for Anthropometric Assessment) by trained staff. Further information on the health and living conditions of the children and their parents were assessed in parental questionnaires. Generalized linear mixed regression analysis was calculated to define correlates for skipping breakfast in terms of odds ratios (OR) and 95% confidence intervals (CI). According to the final regression models, significant correlates of skipping breakfast can be divided into modifiable behavioral components (high consumption of soft drinks (OR 2.49, 95% CI 1.81; 3.43), screen media (OR 2.48, 95% CI 1.77; 3.46) and high levels of physical activity (OR 0.64, 95% CI 0.44; 0.93)) on the one hand, and more or less static socio-economic factors (migration background (OR 2.81, 95% CI 2.02; 3.91), single parenting (OR 2.13, 95% CI 1.34; 3.40), and high family education level (OR 0.42, 95% CI 0.28; 0.64)) on the other hand, and finally individual factors (female gender (OR 1.43, 95% CI 1.03; 1.99) and having a percentage of body fat at or above the 95th percentile (OR 1.47, 95% CI 1.00; 2.17)). Targeted prevention should aim at health-related behaviors accompanying the habit of skipping breakfast. Focusing on vulnerable groups, characterized by not so easily modifiable socio-economic as well as individual factors, may improve results. Interventions should synergistically promote children's health and involve their parents in order to be successful. To reach all children and to avoid skipping breakfast, schools should offer regular breakfast at the start of a school day. Policy makers should support healthy eating habits at all times.


Application of Internet of Things and Naive Bayes in Public Health Environmental Management of Government Institutions in China.
As the builder and maintainer of the city appearance and environment, the city appearance and environmental service industry provides urban residents with a beautiful, livable, and comfortable living environment and is also responsible for providing city appearance and environmental public health services for the economic and social functions carried by the global cities task. Based on this problem, this study has carried out the work of government agencies' public health environmental management and influencing factors based on the Internet of Things and edge computing. This study analyzes the influencing factors of public health environmental management of government agencies based on traditional research and conducts data analysis through the Naive Bayes algorithm. On this basis, the study combines the Internet of Things technology to construct system architecture for public health environmental management. The proposed management system is used to manage government agencies, which meets security, privacy and efficiency, and data security requirements. Experimental results prove that after algorithm optimization and architecture design, the evaluation level of the public health environment is significantly improved.


Vulvar varicosities: diagnosis, treatment, and prevention.
Vulvar varicosity is a relatively common venous disorder in women with varicose veins of the pelvis and lower extremities and in pregnant women, but there is little information in the medical literature concerning its diagnosis and management. The aim of this study was to describe our experience with 101 women with vulvar varicosities who were examined and treated at our center during 2000-2014. Patients were divided into two groups: group 1 with 61 women with varicose veins of the pelvis and enlarged vulvar veins, and group 2 with 40 pregnant women (11-38 weeks of pregnancy) with vulvar varicosities. In most cases, vulvar varicosities were able to be diagnosed at clinical examination. In both groups, duplex ultrasound of the veins of the pelvis and lower extremities was used to confirm the presence of varicose veins, identify any retrograde flow, accurately determine vein diameter, and to reveal any anatomical feature of the intrapelvic veins. Treatment approaches varied significantly between the two groups from purely conservative measures during pregnancy to surgical procedures on the ovarian and vulvar veins in group 1. The venoactive agent, micronized purified flavonoid fraction, was effective at reducing the symptoms of vulvar varicosities in both groups. A tailored approach to the diagnosis and treatment of vulvar varicosities can significantly improve the quality of care of women with this disorder.


Distribution and Retention Trends of Obstetricians and Gynecologists in Japan: A Longitudinal Study.
This longitudinal study aimed to investigate the distribution and retention of obstetricians and gynecologists in Japan. I used descriptive statistics and multivariate logistic regression to analyze data from National Census surveys administered during 1996-2016. Between 1996 and 2016, the number of obstetricians and gynecologists increased by 6% and urban physicians by 15%, whereas the number of rural physicians decreased by 25%. The annual retention rate, which was calculated using the square root of the biannual rates [the number of physicians still working as obstetricians and gynecologists at the time of the subsequent survey (e.g., in 1998) divided by the number of obstetricians and gynecologists in the original survey (e.g., in 1996)], was >90%. Obstetricians and gynecologists were less likely to continue to work as obstetricians and gynecologists after 30-44 years of experience (1996-2006 cohort: OR = 0.20, 95% CI = 0.17-0.25; 2006-2016 cohort: OR = 0.32, 95% CI = 0.25-0.41) and >45 years of experience (1996-2006 cohort: OR = 0.14, 95% CI = 0.11-0.17; 2006-2016 cohort: OR = 0.11, 95% CI = 0.08-0.15). The odds were lower for rural obstetricians and gynecologists (1996-2006 cohort: OR = 0.65, 95% CI = 0.51-0.82; 2006-2016 cohort: OR = 0.59, 95% CI = 0.43-0.80). As the number of female physicians increased, the number of practicing obstetricians and gynecologists also increased. In 2004, the mandatory postgraduate clinical training that was newly implemented caused a drop in the number of young doctors; however, this reversed in 2006. Rural to urban migration was steady, and the working hours were consistently long. To stabilize high retention rates, the working environments need to be improved. The present study clearly indicated the trend of the distribution of obstetricians and gynecologists in Japan. The result may be especially important for the health policy making in Japan.


suPAR as a biomarker for risk of readmission and mortality in the acute medical setting.
The urokinase-type plasminogen activator receptor (uPAR) and its ligand (suPAR) are involved in numerous physiological and pathological pathways. Previous studies have shown that an elevated plasma suPAR level is associated with disease severity and mortality. The aim of this prospective observational study was to determine if the suPAR level was associated with readmission and mortality in the acute medical setting. Plasma suPAR levels were measured in 1,036 patients at admission. Follow-up ranged 3-10 months. Cox proportional hazards model was used to assess the relative contribution of different risk factors to mortality and readmission. The ANOVA test and Pearson's chi-squared test were used to compare suPAR tertile level with various variables. The highest suPAR tertile level was significantly associated with mortality within 30 days after discharge, with a 6.66 hazard ratio (HR). Similar associations were found with readmission within the maximum observation period (HR = 2.26) and within 30 days (HR = 2.08), although the latter became insignificant when covariates were included. This study confirms previous findings of increased mortality and adds the finding that increased long-term readmission rates are associated with elevated suPAR levels. The present data do, however, not indicate that suPAR may serve as an independent biomarker for increased risk of short-term readmission in the acute medical setting. This study was funded by a grant from ViroGates A/S, the company that produces the suPARnostic assay. No: H-B-2009-075.


Evidence of incipient bond-stretching isomerism in Sr2.04(1)Ca0.96(1)Sn5 from variable-temperature structural studies.
The title compound was found to crystallize in the Pu3Pd5 structure type (SG Cmcm) with cell dimensions of a = 10.5179(9) A, b = 8.4789(8) A, and c = 10.7623(10) A. The structure consists of isolated Sn5(6-) square-pyramidal units surrounded by cations that seem to play a crucial role in stabilizing the Zintl polyanions. The square pyramids contract at low temperatures (100 K) leading to the shortening of the basal intracluster Sn-Sn bond (2.74 A), while the intercluster bonds become very large, indicating features of bond stretching isomerism as is known for Ba3Ge4. A study of different crystals shows a slight variation in the lattice parameters, suggesting the presence of a definite phase width which was substantiated by the successful synthesis of monophasic samples of Sr(3-x)CaxSn5 (0.5 <or= x <or= 2.5). However, all attempts to obtain the pure Ca phase, Ca3Sn5 have been unsuccessful. The compounds show a weakly metallic behavior, as shown by the electrodeless Q method. Magnetic studies show a very low susceptibility (nearly temperature independent till 5 K). Our studies suggest that the "Sn" polyanions in Ca(2.04)Sr(0.96)Sn(5) may be described as an arachno-Sn5(-6) Zintl cluster.


Cotrimoxazole, a wonder drug in the era of multiresistance: Case report and review of literature.
Antimicrobial resistance is one of the greatest threats to human health worldwide. The rate of development of newer antibiotics is much slower than the rate of development of antibiotic resistance. A survey reported that it takes 15 years and US$800 million (including preclinical and clinical costs) to bring a single drug to the market, whereas the reuse of the older drugs for antimicrobial use takes $17 million, thereby circumventing 40% of the overall cost. The first case is a patient with nosocomial pyrexia of unknown origin who was given treatment with tigecycline and cefepime/tazobactam but failed to respond to the same. However, the patient responded to the treatment with cotrimoxazole. The second case is a patient with meningitis caused by an atypical zoonotic pathogen, Staphylococcus chromogenes. This is the first report of human infection with S. chromogenes, this being a common cause of bovine mastitis. The isolate was obtained from a patient of neurotrauma who developed meningitis after decompressive craniotomy. The strain was obtained from cerebrospinal fluid, blood, and shunt chamber pus. Cotrimoxazole was given for the treatment, and the patient improved after the treatment. Although the newer antibiotics have replaced sulfonamides in the treatment of many infections, they are still of great value and are the agents of choice in many infections. Sulfonamides have wide antimicrobial activity against both Gram-positive and Gram-negative bacteria, but their usefulness has diminished with the emergence of resistant strains. This paper reports cases of two different kinds of infections from a level 1 trauma center, who failed to respond to the newer antibiotics but showed a response to administration of cotrimoxazole.


Amino-terminal blocking group and sequence of the animal fatty acid synthase.
We have cloned and sequenced the cDNA encoding the chicken fatty acid synthase. Based on the nucleotide-derived amino acid sequence of the chicken synthase, the N-terminal sequences are highly conserved among animal species, suggesting that translation of the animal synthases initiates with the same ATG codon. Like other fatty acid synthases, the NH2-terminal sequence of the chicken enzyme is blocked. We have isolated and purified the blocked NH2-terminal peptide from a tryptic digest of chicken synthase and have established that the blocking group is an acetyl group. The sequence of the native tryptic peptide confirmed the cDNA-derived amino acid sequence and suggested that all animal synthases begin with this homologous sequence. We developed simple procedures that can be used to isolate and characterize any blocked NH2-terminal peptide.