Chronic nitrate exposure alters reproductive physiology in fathead minnows.
Nitrate is a ubiquitous aquatic pollutant that is commonly associated with eutrophication and dead zones in estuaries around the world. At high concentrations nitrate is toxic to aquatic life but at environmental concentrations it has also been purported as an endocrine disruptor in fish. To investigate the potential for nitrate to cause endocrine disruption in fish, we conducted a lifecycle study with fathead minnows (Pimephales promelas) exposed to nitrate (0, 11.3, and 56.5 mg/L (total nitrate-nitrogen (NO3-N)) from <24 h post hatch to sexual maturity (209 days). Body mass, condition factor, gonadal somatic index (GSI), incidence of intersex, and vitellogenin induction were determined in mature male and female fish and plasma 11-keto testosterone (11-KT) was measured in males only. In nitrate-exposed males both 11-KT and vitellogenin were significantly induced when compared with controls. No significant differences occurred for body mass, condition factor, or GSI among males and intersex was not observed in any of the nitrate treatments. Nitrate-exposed females also had significant increases in vitellogenin compared to controls but no significant differences for mass, condition factor, or GSI were observed in nitrate exposed groups. Estradiol was used as a positive control for vitellogenin induction. Our findings suggest that environmentally relevant nitrate levels may disrupt steroid hormone synthesis and/or metabolism in male and female fish and may have implications for fish reproduction, watershed management, and regulation of nutrient pollution.


Alkalinisation of bupivacaine for sciatic nerve blockade.
This double-blind study investigates the effect of pH adjustment of bupivacaine 0.5% with adrenaline 1:200,000 on block latency, duration of analgesia and systemic absorption of local anaesthetic after sciatic nerve blockade. Twenty-four adult patients were randomly allocated into one of two groups: Group A (n = 12) received bupivacaine with adrenaline 1:200,000 (pH 3.9) 2 mg/kg, while Group B (n = 12) received alkalinised bupivacaine with adrenaline 1:200,000 (pH 6.4) 2 mg/kg. Increasing the pH of the local anaesthetic solution significantly reduced block latency from 25 minutes in Group A to 12.5 minutes in Group B (p less than 0.001) and prolonged the duration of useful analgesia from 14.1 hours to 18.3 hours (p less than 0.001). There was no significant difference in plasma bupivacaine levels between the two groups. The results indicate that alkalinisation of bupivacaine reduces time to onset and prolongs the duration of useful analgesia when used for sciatic nerve blockade, without significantly increasing systemic absorption.


Impact of Continuous Positive Airway Pressure on Cardiovascular Risk Factors in High-Risk Patients.
Cardiovascular disease remains the leading cause of morbidity and mortality in developed countries. Obstructive sleep apnea is a highly prevalent condition characterized by repetitive upper airway collapse during sleep. A large body of evidence suggests that obstructive sleep apnea is associated with the development of cardiovascular disease and increased cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) is the current gold standard for the treatment of obstructive sleep apnea. CPAP devices maintain upper airway patency using a pneumatic splint, thereby ameliorating the repetitive deoxygenation and reoxygenation characteristic of sleep in obstructive sleep apnea patients. Accumulating evidence suggests that CPAP treatment may lead to a reduction in blood pressure. Limited evidence also suggests that CPAP therapy may modulate glucose metabolism, serum cholesterol levels, and inflammatory biomarkers. Thus, CPAP treatment may be associated with cardiovascular risk factor modification in patients with obstructive sleep apnea, who are often obese and at an increased risk of developing cardiovascular disease. This review updates the knowledge on the effects of CPAP on cardiovascular risk factors from recently published randomized trials.


Periods of synchronized myelin changes shape brain function and plasticity.
Myelin, a lipid membrane that wraps axons, enabling fast neurotransmission and metabolic support to axons, is conventionally thought of as a static structure that is set early in development. However, recent evidence indicates that in the central nervous system (CNS), myelination is a protracted and plastic process, ongoing throughout adulthood. Importantly, myelin is emerging as a potential modulator of neuronal networks, and evidence from human studies has highlighted myelin as a major player in shaping human behavior and learning. Here we review how myelin changes throughout life and with learning. We discuss potential mechanisms of myelination at different life stages, explore whether myelin plasticity provides the regenerative potential of the CNS white matter, and question whether changes in myelin may underlie neurological disorders.


Correlation of mean apparent diffusion coefficient (ADC) and maximal standard uptake value (SUVmax) evaluated by diffusion-weighted MRI and 18F-FDG-PET/CT in children with Hodgkin lymphoma: a feasibility study.
The objective was to analyse if magnetic resonance imaging (MRI) can act as a non-radiation exposure surrogate for (18)F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in children with histologically confirmed Hodgkin lymphoma (HL) before treatment. This was done by analysing a potential correlation between apparent diffusion coefficient (ADC) in MRI and the maximum standardized uptake value (SUVmax) in FDG-PET/CT. Seventeen patients (six female, eleven male, median age: 16 years, range: 12-20 years) with histologically confirmed HL were retrospectively analysed. The patients underwent both MRI and (18)F-FDG PET/CT before the start of treatment. (18)F-FDG PET/CT data and correlating ADC maps in MRI were collected. For each HL-lesion two readers independently evaluated the SUVmax and correlating meanADC. The seventeen patients had a total of 72 evaluable lesions of HL and there was no significant difference in the number of lesions between male and female patients (median male: 15, range: 12-19 years, median female: 17 range: 12-18 years, p = 0.021). The mean duration between MRI and PET/CT was 5.9 ± 5.3 days. The inter-reader agreement as assessed by the intraclass correlation coefficient (ICC) was excellent (ICC = 0.98, 95% CI: 0.97-0.99). The correlated SUVmax and meanADC of all 17 patients (ROIs n = 72) showed a strong negative correlation of -0.75 (95% CI: -0.84, - -0.63, p = 0.001). Analysis revealed a difference in the correlations of the examination fields. The correlated SUVmax and meanADC showed a strong correlation at neck and thoracal examinations (neck: -0.83, 95% CI: -0.93, - -0.63, p < 0.0001, thoracal: -0.82, 95% CI: -0.91, - -0.64, p < 0.0001) and a fair correlation at abdominal examinations of -0.62 (95% CI: -0.83, - -0.28, p = 0.001). SUVmax and meanADC showed a strong negative correlation in paediatric HL lesions. The assessment seemed robust according to inter-reader agreements. Our results suggest that ADC maps and meanADC have the potential to replace PET/CT in the analysis of disease activity in paediatric Hodgkin lymphoma patients. This may help reduce the number of PET/CT examinations and decrease radiation exposure to children.


The effects of a caffeine containing pre-workout supplement on β2-adrenergic and MAPK signaling during resistance exercise.
The acute myocellular responses of caffeine supplementation during resistance exercise (RE) have not been investigated. β2-Adrenergic receptors (β2AR) may be a target of the stimulatory effects of caffeine and stimulate bioenergetic pathways including protein kinase A (PKA), and mitogen-activated protein kinases (MAPK). Elucidate the effects of pre-workout supplementation on signaling responses to an acute RE bout. In a randomized, counter-balanced, double-blind, placebo-controlled, within-subject crossover study, ten resistance-trained males (mean ± SD; age = 22 ± 2.4 years, height = 175 ± 7 cm, body mass = 84.1 ± 11.8 kg) consumed a caffeine containing multi-ingredient pre-workout supplement (SUPP) or color and flavor matched placebo (PL) 60 min prior to an acute RE bout of barbell back squats. Pre- and post-exercise muscle biopsies were analyzed for the phosphorylation (p-) of β2AR, PKA, and MAPK (ERK, JNK, p38). Epinephrine was determined prior to supplementation (baseline; BL), after supplementation but prior to RE (PRE), and immediately after RE (POST). Epinephrine increased at PRE in SUPP (mean ± SE: 323 ± 34 vs 457 ± 68 pmol/l; p = 0.028), and was greatest at POST in the SUPP condition compared to PL (5140 ± 852 vs 2862 ± 498 pmol/l; p = 0.006). p-β2AR and p-MAPK increased post-exercise (p < 0.05) with no differences between conditions (p > 0.05). Pearson correlations indicated there was a relationship between epinephrine and p-β2AR in PL (r = - 0.810; p = 0.008), and p-β2AR and ERK in SUPP (r = 0.941; p < 0.001). Consumption of a caffeine containing pre-workout supplement improves performance, possibly through increases in pre-exercise catecholamines. However, the acute myocellular signaling responses were largely similar post-exercise.


Treatment of suspected cardiac ischemia with aspirin by paramedics in an urban emergency medical services system.
Aspirin (ASA) has unquestioned benefit to patients with cardiac ischemia. Previous studies indicate health care providers may not adequately treat patients experiencing cardiac ischemia with ASA. To determine the rate of ASA use for patients being treated for chest pain suggestive of cardiac ischemia in the prehospital setting. This was a retrospective study of paramedic encounters identified through billing records for all patients receiving the combination of an intravenous catheter, supplemental oxygen, and cardiac monitoring from November 2001 to January 2002. Prehospital medical records were reviewed in order to determine the proportion of patients with suspected cardiac ischemia who received ASA. The setting was a single prehospital emergency medical services system serving an urban population. A total of 2,457 paramedic encounters were reviewed over a three-month period. Two hundred thirty-two patients were assessed as having cardiac ischemia, of whom 169 (73%) had no absolute or relative contraindication to ASA. Of the 169 patients, only 92 (54%) received ASA. Of the 99 patients, who received nitroglycerin for presumed cardiac ischemia and had no contraindication to receiving ASA, only 78 (79%) received ASA. Of the 453 patients complaining of nontraumatic chest pain and without a contraindication, 157 (35%) received ASA. Paramedics do not use ASA optimally and may choose therapies with less proven benefit.


Synthesis, Characterization and Reactions of (Azidoethynyl)trimethylsilane.
Synthesis of azido(trimethylsilyl)acetylene (6) was performed by treating the iodonium salt 5 with highly soluble hexadecyltributylphosphonium azide (QN₃) at -40 °C. Although this product is very unstable, it can nevertheless be trapped by the click reaction with cyclooctyne to give the corresponding 1,2,3-triazole, and also directly characterized by ¹H- and (13)C-NMR data as well as IR-spectra, which were measured in solution at low temperature and in the gas phase. The thermal or photochemical decay of azide 6 leads to cyano(trimethylsilyl)carbene. This is demonstrated not only by quantum chemical calculations, but also by the trapping reactions with the help of isobutene.


Induction of resistance with heat-killed unencapsulated strains of Staphylococcus epidermidis against challenge with encapsulated strains of Staphylococcus epidermidis.
Active immunization of mice with high doses of heat-killed unencapsulated strains of Staphylococcus epidermidis, which were grown in brain heart infusion media, protected mice against challenge with encapsulated strains of S. epidermidis. The unencapsulated strains were capable of absorbing the protective antibody in rabbit hyperimmune sera prepared with the encapsulated strains. Also, mice treated with rabbit hyperimmune sera prepared with the unencapsulated strains were protected against challenge with the encapsulated strains. The protective activities of these rabbit hyperimmune sera were assumed to be essentially identical to those of the protective antibody induced by the encapsulated strains.


Effects of Corynebacterium parvum on murine myeloid leukaemia.
The effects of C. parvum on RFM/UN myeloid leukaemia were studied. Mice inoculated with 7.0 mg but not 0.7 mg C. parvum i.p. survived significantly longer than untreated leukaemic mice (P less than 0.001). Administration of silica abrogated the effects of C. parvum, whilst polyvinyl pyridine-N-oxide prevented the inhibitory effects of silica. These studies demonstrate that a single large dose of C. parvum, either before or after leukaemic-cell passage, can significantly prolong the survival of RFM mice bearing myeloid leukaemia. The effects of silica and PVNO on C. parvum suggest a critical role for macrophages in C. parvum effects on myeloid leukaemia.


Dynamic Hierarchical Self-Assemble Small Molecule Structure Hexabenzocoronene for the High-Performance Anodes Lithium Ion Storage.
This study examined the characteristics of small molecular structure nano-graphene in a dynamic hierarchical self-assembly and found that graphene is rearranged under its own pressure during dynamic aggregation and water ripples are formed by the d-spacing. The composition and structure were studied using a range of material characterization techniques. No covalent bonds were observed between molecules, and the self-assembled driving force was the only intermolecular interaction: Van der Waals' force in the intra-layer and π-π interactions between layers. The arranged-rearranged structures provided a range of lithium ion shuttle channels, including the space between layers and diffusing through the nanosheets, which decrease the diffusion distance of lithium ions remarkably and reduce the irreversible capacity of the battery.


[Superposition of noise magnetic fields inhibits clustering of fibroblast membrane surface receptors induced by 50 Hz magnetic fields in Chinese hamster lungs].
To study the possible induction effect of exposure to 50 Hz magnetic field (MF) on clustering of cell membrane surface receptors for epidermal growth factor (EGF) and tumor necrosis factor (TNF), the starting site of signals of biological effects, and its possible intervention effect. Lung fibroblasts of Chinese hamster (CHL) were exposed to EGF, TNF, 0.4 mT 50 Hz MF, 0.4 mT noise MF, and 0.4 mT 50 Hz MF combined with 0.4 mT noise MF. Respectively, for different durations, following the treatment, EGF and TNF receptors on the cell membrane were marked by corresponding antibodies with immunohistochemical method, then observed under a confocal microscope. Clustering of cell membrane receptors could be induced 5 min after treatment with EGF and TNF, as well as with 50 Hz MF at 0.4 mT, which reached the peak in 15 min. While noise MF with the same intensity did not induce clustering of cell membrane receptors. Superposition of noise MF with the same intensity could inhibit clustering of cell membrane receptors induced by 50 Hz MF. Clustering of EGF and TNF receptors on the cell membrane could be induced by 50 Hz MF, suggesting that membrane receptors would be one of the sites where MF signals coupled, and noise MF with the same intensity could inhibit these effects.


Left atrial stiffness index as a marker of early target organ damage in hypertension.
This study aimed to evaluate left atrial (LA) mechanics using two-dimensional speckle-tracking echocardiography (2DSTE) and investigate their correlations with measures of target organ damage (TOD) in hypertension. We enrolled 42 healthy controls (Group I) and 286 hypertension patients: Group II (n = 79) had an LA volume index (LAVI) <28 ml/m2; Group III (n = 92) had an LAVI ≥28 ml/m2; and Group IV (n = 115) had hypertension with left ventricular hypertrophy (LVH). We measured the following parameters: LA reservoir strain and strain rate (LAS-S, LASR-S), LA conduit strain and strain rate (LAS-E and LASR-E), and LA booster strain and strain rate (LAS-A and LASR-A). The LA stiffness index (LASI) was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LAS-S. We performed correlation and regression analyses of individual TOD with LA phasic functions, the LASI, and cardiovascular risk factors. Our findings showed that there was a trend toward a gradual increase in the LASI from controls to normal LA and enlarged LA patients and finally to hypertrophic LV patients. The LASI was significantly higher in Group III [0.28 (0.20, 0.38)] than in Group I [0.20 (0.16, 0.23)] and Group II [0.22 (0.18, 0.27)] and was the highest in Group IV [0.33 (0.26, 0.43)]. The LA reservoir and conduit function gradually decreased from Group I to Group IV. Multivariate regression analysis revealed that the LASI was independently correlated with individual TOD. In conclusion, abnormal LA mechanics precede LA enlargement and LVH, and an increased LASI can be used as a marker of early TOD in hypertension.


Bleeding assessment in haemophilia carriers-High rates of bleeding after surgical abortion and intrauterine device placement: A multicentre study in China.
An increased bleeding tendency has been shown in female haemophilia carriers compared to healthy females. Bleeding assessment tools (BATs) have mainly been performed in western cultures. It is unclear how they perform in populations with different healthcare, health/wellness concepts and awareness, as well as family planning practices. To (a) describe and compare the bleeding symptoms in carriers with healthy females, particularly for bleeding after surgical abortion and intrauterine device (IUD) placement which are performed frequently for family planning in China; (b) quantify scores of International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) and Chinese-BAT (C-BAT) developed to include surgical abortion and IUD placement as separate categories in Chinese haemophilia carriers; (c) correlate bleeding scores (BS) with factor levels. We conducted a multicentre, cross-sectional study on obligate haemophilia carriers and healthy controls using ISTH-BAT and C-BAT. We enrolled 125 haemophilia carriers and 106 controls. Carriers, compared to controls, had significantly higher median BS (3 vs 1 by both ISTH-BAT and C-BAT) and lower factor level (63.5 vs 101.8 IU/dL). Bleeding after surgical abortion and IUD placement was significantly associated with carrier status. Bleeding scores from neither ISTH-BAT nor C-BAT showed significant correlation with factor levels. Haemophilia carriers in China experienced abnormal bleeding. Unique to the Chinese carriers is significant bleeding after surgical abortion (3rd highest incidence of bleeding symptom) and IUD placement (4th highest). However, both ISTH-BAT and C-BAT exhibited no correlation between BS and factor levels in this population and neither could identify carriers with low factor level (of <50 IU/dL).


[The contribution of modern medical imaging in post-traumatic carotid-cavernous fistula. Apropos of a case].
Carotid-cavernous fistulas are unusual complications of facial traumas but this life-threatening complication requires a rapid diagnosis. Noninvasive procedures as ultrasounds will confirm the diagnosis and are helpful to demonstrate hemodynamic conditions of the fistula. Angiography remains the main radiologic examination and embolization is now the preferred method of treatment. Surgical treatment will only be required after failure of the interventional radiology.


Primary uterine osteosarcoma arising in a leiomyoma with rapid local recurrence: A case report.
Extraskeletal osteosarcoma is an extremely rare malignant neoplasm. Literature regarding primary osteosarcoma of the uterus is confined to only a small number of case reports. Case: A 57-year-old female with a history of uterine fibroids presented to the emergency department with abdominal pain. Imaging was notable for an enlarged uterus with a 15 cm calcified fibroid extending along the posterior uterus. The patient underwent a laparotomy for total hysterectomy and bilateral salpingo-oophorectomy. Pathological evaluation of the specimen yielded mesenchymal proliferation with osteoid formation and tumor cells with densely eosinophilic cytoplasm resembling osteoblasts with a final diagnosis of primary uterine osteosarcoma. Multidisciplinary tumor board recommended against adjuvant treatment, given the lack of evidence for improved outcomes for early-stage uterine sarcomas. The patient was followed up with surveillance visits every-three months, entailing physical examination and computed tomography(CT) scans. Unfortunately, she had locoregional oligometastatic recurrence of her disease at 1-year follow up. Primary uterine osteosarcoma is an extremely rare and aggressive neoplasm with limited understanding regarding optimal treatment options.


Assessing the potential cost-effectiveness of centralised versus point-of-care testing for hepatitis C virus in Pakistan: a model-based comparison.
Pakistan has a hepatitis C virus (HCV) infection prevalence of 6%-9% and aims to achieve World Health Organisation (WHO) targets for elimination of HCV by the year 2030. We aim to evaluate the potential cost-effectiveness of a reference laboratory-based (centralised laboratory testing; CEN) confirmatory testing approach versus a molecular near-patient point-of-care (POC) confirmatory approach to screen the general population for HCV in Pakistan. We used a decision tree-analytic model from a governmental (formal healthcare sector) perspective. Individuals were assumed to be initially screened with an anti-HCV test at home, followed by POC nucleic acid test (NAT) at nearby district hospitals or followed by NAT at centralised laboratories. We included the general testing population for chronic HCV in Pakistan. Screening with an anti-HCV antibody test (Anti-HCV) followed by either POC NAT (Anti-HCV-POC), or reference laboratory NAT (Anti-HCV-CEN), was compared, using data from published literature and the Pakistan Ministry of Health. Outcome measures included: number of HCV infections identified per year, percentage of individuals correctly classified, total costs, average costs per individual tested, and cost-effectiveness (assessed as cost per additional HCV infection identified). Sensitivity analysis was also performed. At a national level (25 million annual screening tests), the Anti-HCV-CEN strategy would identify 142 406 more HCV infections in 1 year and increase correct classification of individuals by 0.57% compared with the Anti-HCV-POC strategy. The total annual cost of HCV testing was reduced using the Anti-HCV-CEN strategy by US$7.68 million (US$0.31/person). Thus, incrementally, the Anti-HCV-CEN strategy costs less and identifies more HCV infections than Anti-HCV-POC. The incremental difference in HCV infections identified was most sensitive to the probability of loss to follow-up (for POC confirmatory NAT). Anti-HCV-CEN would provide the best value for money when scaling up HCV testing in Pakistan.


A poly(L-lysine)-based hydrophilic star block co-polymer as a protein nanocarrier with facile encapsulation and pH-responsive release.
A hydrophilic star block co-polymer was synthesized, characterized, and evaluated as a protein nanocarrier. The star block co-polymer was composed of a hyperbranched polyethylenimine (PEI) core, a poly(L-lysine) (PLL) inner shell, and a poly(ethylene glycol) (PEG) outer shell. The model protein insulin can be rapidly and efficiently encapsulated by the synthesized polymer in aqueous phosphate buffer at physiological pH. Complexation between PEI-PLL-b-PEG and insulin was investigated using native polyacrylamide gel electrophoresis. The uptake of enhanced green fluorescent protein into Ad293 cells mediated by PEI-PLL-b-PEG was also investigated. The encapsulated insulin demonstrated sustained release at physiological pH and showed accelerated release when the pH was decreased. The insulin released from the star block co-polymer retained its chemical integrity and immunogenicity.


A model analysis of internal loads, energetics, and effects of wobbling mass during the whole-body vibration.
The internal loads, energetics, and the effects of wobbling mass during the whole-body vibration are studied in terms of analysis and comparison of two models: one is a system of four degrees-of-freedom with rigid and wobbling masses in both lower body and upper body (Model A), while the other one (Model B) is a system of three degrees-of-freedom with a rigid upper body and is otherwise identical to Model A. The main findings are the following: (1) The wobbling mass in the upper body is able to reduce the total internal load on the rigid mass of the upper body considerably. (2) "Partial" internal loads on a certain part of the body may be even larger than the total load on the same part of the body because of the phase differences among the partial loads. Therefore, a full consideration of safety during the whole-body vibration has to take not only the total, but also all the partial internal loads into account. (3) The fluctuation of power input and the fluctuation of mechanical energy could be much larger than the fluctuation of dissipation rate. (4) For frequencies higher than the resonance frequency range, the amplitude of the oscillation of the centre of mass of the body is so reduced that only the change of elastic potential energy dominates in the change of mechanical energy. Thus, a simple picture of energy flow is obtained as follows: for approximately one half of the oscillation period, the energy flows from the vibrator into the human body and is mainly stored in the muscle-tendon system, while for the remaining approximate half of the period, the energy flows from the muscle-tendon system back to the vibrator with a slightly smaller amount because a small part of the flown-in energy has been dissipated.


[Preserving remnant liver function after major hepatic vein occlusion].
To observe the pathological changes of the remained hepatic lobe after major hepatic vein (MHV) occlusion. Seventy-eight rats were randomly divided into the control group, the ligation group of segmental hepatic vein, the stricture group of left MHV, and the ligation group of left MHV. The pathology, hepatic microcirculation and hemodynamic changes of the involved hepatic lobe of MHV occlusion were dynamically determined. Necrosis occurred in the hepatocytes at the first postoperative day in the ligation group of MHV. Extensive collaterals between the hepatic veins and the portal veins appeared in the periphery of involved liver lobe in the stricture group of MHV. The levels of endotoxin and TXB(2)/6-Keto-PGF1alpha in the blood of portal vein obviously increased in the ligation group of MHV and also increased in the stricture group of MHV. The levels of endotoxin and TXB(2)/6-Keto-PGF1alpha in the blood of portal vein in the ligation and stricture group of MHV were apparently higher than those in the ligation group of segmental hepatic vein and in the control group. The involved liver tissue can not tolerate complete MHV occlusion. The hepatic tissue lacking of MHV drain not only loss its function, but also cause endotoxemia and disorder of hepatic microcirculation. The involved hepatic lobe after the MHV ligation should have been resected at the same time.


[Conjunctivitis lignosa and hydrocephalus (an unusual association of 2 diseases)].
Two siblings, a brother and a sister, with ligneous conjunctivitis and hydrocephalus coursing in parallel were described. Both conditions developed during the first year of life. Surgery for hydrocephalus was carried out in both children and conjunctivitis gradually subsided.


Brief Report: Switch to Ritonavir-Boosted Atazanavir Plus Raltegravir in Virologically Suppressed Patients With HIV-1 Infection: A Randomized Pilot Study.
This open-label, multinational, pilot study randomized (1:2 ratio) adults with HIV-1 RNA <40 copies per milliliter and nucleos(t)ide-related safety/tolerability issues to switch to ritonavir-boosted atazanavir (ATV/r) plus tenofovir disoproxil fumarate/emtricitabine (n = 37) or the nucleos(t)ide reverse transcriptase inhibitor-sparing regimen of ATV/r plus raltegravir (RAL) (n = 72). At 24 weeks, 35/37 (94.6%) and 58/72 (80.6%) of patients, respectively, maintained virological suppression, the primary endpoint, and 1 (2.7%) and 7 (9.7%), respectively, experienced virological rebound. Corresponding 48-week proportions were 86.5%, 69.4%, 2.7%, and 12.5%, respectively. Adherence was lower and treatment discontinuation was higher with ATV/r+RAL. In conclusion, switching to ATV/r+RAL resulted in a higher virological rebound rate than switching to ATV/r plus tenofovir disoproxil fumarate/emtricitabine.


Pulmonary embolism after lung resection: diagnosis and treatment.
Pulmonary embolism after lung resection (PEALR) has a high mortality rate, and it is one of the most severe complications after lung resection. Early diagnosis and treatment are essential for PEALR. Here we present 3 cases of severe PEALR. In these cases, transthoracic Doppler echocardiography was useful for confirming the diagnosis of PEALR. Thrombolysis with recombinant tissue plasminogen activator (r-tPA) was used to treat the embolism, and these patients were subsequently discharged. Thus echocardiography may become a primary procedure to confirm the diagnosis of severe PEALR, and thrombolysis with second-generation r-tPA may be the preferred choice for treatment.


[Specific growth rate and the rate of energy metabolism in the ontogenesis of axolotl, Ambystoma mexicanum (Amphibia: Ambystomatidae)].
Concordant changes in the rate of energy metabolism and specific growth rate of axolotls have been revealed. Several periods of ontogeny are distinguished, which differ in the ratio of energy metabolism to body weight and, therefore, are described by different allometric equations. It is suggested that the specific growth rate of an animal determines the type of dependence of energy metabolism on body weight.


Müller cells in the healthy and diseased retina.
Müller glial cells span the entire thickness of the tissue, and ensheath all retinal neurons, in vertebrate retinae of all species. This morphological relationship is reflected by a multitude of functional interactions between neurons and Müller cells, including a 'metabolic symbiosis' and the processing of visual information. Müller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neurotransmitter molecules, and pH). In vascularized retinae, Müller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Müller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration: Müller cells protect neurons via a release of neurotrophic factors, the uptake and degradation of the excitotoxin, glutamate, and the secretion of the antioxidant, glutathione. However, gliotic Müller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Müller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Müller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina. On the contrary, Müller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (somatic gene therapy), or to differentiate retinal neurons from Müller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Müller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/protective-and prevent the destructive-mechanisms of gliosis.


Masseter muscle pressure injury: First report of a prone position complication in patients with COVID-19.
We report the case of a 59-year-old, obese woman who underwent prolonged prone position during the medical management of an acute respiratory distress syndrome induced by SARS-CoV-2 infection, complicated by a masseter muscle pressure injury. Such side effect may be underestimate in intensive care units and should be prevent by prophylactic dressings on facial weight-bearing sites. The understanding of facial deep tissue injury is essential to guide clinical detection and management of such a complication in COVID-19 patients.


Factors influencing the effectiveness of multisource feedback in improving the professional practice of medical doctors: a systematic review.
Multisource feedback (MSF) is currently being introduced in the UK as part of a cycle of performance review for doctors. However, although it is suggested that the provision of feedback can lead to a positive change in performance and learning for medical professionals, the evidence supporting these assumptions is unclear. The aim of this review, therefore, was to identify the key factors that influence the effectiveness of multisource feedback in improving the professional practice of medical doctors. Relevant electronic bibliographic databases were searched for studies that aimed to assess the impact of MSF on professional practice. Two reviewers independently selected and quality assessed the studies and abstracted data regarding study design, setting, MSF instrument, behaviour changes identified and influencing factors using a standard data extraction form. A total of 16 studies met the inclusion criteria and quality assessment criteria. While seven studies reported only a general change in professional practice, a further seven studies identified specific changes in behaviour. The main professional behaviours that were found to be influenced by the feedback were communication, both with colleagues and patients and an improvement in clinical competence/skills. The main factors found to influence the acceptance and use of MSF were the format of the feedback, specifically in terms of whether it was facilitated, or if narrative comments were included in the review, and if the feedback was from sources that the physician believed to be knowledgeable and credible. While there is limited evidence suggesting that MSF can influence professional performance, the quality of this evidence is variable. Further research is necessary to establish how this type of feedback actually influences behaviours and what factors have greatest influence.


High serum cortisol levels in exercise-associated amenorrhea.
To determine whether basal cortisol levels are elevated in exercise-associated amenorrhea. Survey, with hormone levels measured weekly for 1 month and patients followed clinically for 6 months. Volunteers were recruited through media advertisements and fliers. Ninety-two women were enrolled; 71 (77%) completed the study. Subjects were grouped by menstrual and activity histories reported by a self-administered questionnaire. After 6 months, final groups were assigned: amenorrheic athletes, 19; eumenorrheic athletes, 35; a transition group of amenorrheic athletes who had resumed menses after entering the study, 7; and normal cyclic nonathletes, 10. Four weekly resting blood samples (0800 to 1000 hours) were obtained and measured for cortisol, estradiol, progesterone, and prolactin levels. Lumbar bone mineral density was measured by dual-photon densitometry. Mean (+/- SE) cortisol levels were higher in amenorrheic athletes (585 +/- 33 nmol/L) than in eumenorrheic athletes (411 +/- 14 nmol/L), transition athletes (378 +/- 33 nmol/L), or nonathletic women (397 +/- 30 nmol/L) (P less than 0.01). Of nine women with abnormally high cortisol levels (greater than 579 nmol/L), eight were amenorrheic athletes, and one was a eumenorrheic athlete. Bone mineral density was lower in amenorrheic athletes than in the other three groups (P less than 0.01). Increased glucocorticoid levels may be an etiologic factor in exercise-associated amenorrhea. High cortisol levels could also contribute to decreased bone density. The failure of amenorrheic athletes with hypercortisolemia to regain menses within 6 months suggests that they are at risk for a prolonged acyclic state.


A quantitative study of nuclear DNA of trophoblastic cells: proliferation kinetics.
The nuclear DNA contents of labeled and unlabeled nuclei of trophoblastic cells of 8 normal pregnancies, 2 missed abortions, and 14 cases of trophoblastic diseases were measured by Feulgen-DNA cytofluorometry combined with autoradiography. Syncytiotroblasts were rarely labeled and were considered to be inactive with regard to cell proliferation. Most of the labeled cells were cytotrophoblasts. The predominantly labeled cells ranged between 2 and 4C in cases of normal pregnancy and missed abortion, and a shift to a higher ploidy was seen in the more grave trophoblastic disease. From the point of cellular proliferation kinetics of trophoblastic cells, it is presumed that the cells in cases of normal pregnancy and type I hydatidiform mole are in the 2C cell cycle and in type II hydatidiform mole and in invasive mole there are heterogeneous cell populations, most of which are in the 2C cell cycle while the remaining are undergoing polyploidization or aneuploidization. In choriocarcinoma, the cells are not in the 2C cell cycle and also are probably undergoing polyploidization or aneuploidization in the hyper-4C area.


Responses of human fetal splenocytes and thymocytes to interleukin-2 and comparison with adult peripheral blood lymphocytes.
By means of cytotoxicity and thymidine uptake assays, the effect of human recombinant interleukin-2 (rIL-2) on the induction of lymphokine-activated killer (LAK) cell activity and cellular proliferation in splenocytes and thymocytes from human fetuses (18-22 weeks) was studied and compared with that in mononuclear cells from adult peripheral blood. It was shown that the fetal splenocytes and thymocytes incubated with low doses of rIL-2 (10-100 U/ml) developed a broad spectrum of antitumor activity (LAK cytotoxicity), although the kinetics and magnitudes of the responses were different. It was also suggested that LAK precursors were present in fetal spleen and thymus. Furthermore, rIL-2 induced a stronger proliferative and cytotoxic response in splenocytes than in thymocytes. The human fetal LAK cells isolated from the spleen were found to be 10-20 times more potent than those from adult peripheral blood with regard to cell proliferation and cytotoxicity in vitro.


Reconstructing haemodynamics quantities of interest from Doppler ultrasound imaging.
The present contribution deals with the estimation of haemodynamics Quantities of Interest by exploiting Ultrasound Doppler measurements. A fast method is proposed, based on the Parameterized Background Data-Weak (PBDW) method. Several methodological contributions are described: a sub-manifold partitioning is introduced to improve the reduced-order approximation, two different ways to estimate the pressure drop are compared, and an error estimation is derived. A fully synthetic test-case on a realistic common carotid geometry is presented, showing that the proposed approach is promising in view of realistic applications.


Diazene JK-279 induces apoptosis-like cell death in human cervical carcinoma cells.
Diazene N-phenyl-2-(2-pyridinyl)diazenecarboxamide (JK-279) is a newly synthesized compound, cytotoxic for several tumor cell lines and their drug-resistant sublines. In human cervical carcinoma cells (HeLa), this compound reduced intracellular glutathione content and increased sensitivity to cisplatin. The aim of the present study was to elucidate the molecular mechanisms involved in the cytotoxic effect of diazene JK-279 on HeLa cells. Cytotoxicity was determined by the MTT method. Flow cytometry analysis showed that diazene JK-279 induces G(2)/M phase arrest, mediated by the increase in p21 expression, and accompanied by an alteration in the expression of survivin. The highest concentration of JK-279 altered nuclear morphology in intact cells, showing "apoptosis-like" features. No cleavage of procaspase-3, procaspase-9 and PARP, or altered expression of apoptotic proteins Bcl-2 and Bax were detected. At the same time, PS externalization and internucleosomal DNA cleavage were observed. Partial necrosis was detected as well. Our results demonstrate that cytotoxicity of diazene JK-279 is mostly the consequence of caspase-independent cell death, which is in some aspects "apoptosis-like". Taking into account the multiplicity of mechanisms used by cancer cells to prevent apoptosis, the drugs (like diazene JK-279) that would activate alternative cell death pathways could provide a useful tool for new types of cancer therapy.


Oophoropexy: a relevant role in preservation of ovarian function after pelvic irradiation.
To report on our experience with girls and young women who received treatment for Hodgkin lymphoma, underwent prior oophoropexy to preserve their ovarian function, and subsequently gave birth. Retrospective monoinstitutional evaluation. National Cancer Institute. Eleven girls given treatment for Hodgkin lymphoma and undergoing bilateral ovarian transposition at a median age of 13 years. The ovaries were positioned behind the uterus by the general surgeon. Fourteen pregnancies were recorded among these 11 women, with 12 live births (1 twin) and 3 miscarriages. None of these women needed the ovaries to be relocated, and none of them resorted to artificial insemination. Their median age at the time of first pregnancy was 31 years, and the median time elapsing since ovarian transposition was 14 years. This series confirms that oophoropexy can preserve ovarian function and enable future pregnancy. We encourage pediatric oncologists, surgeons, and radiotherapists to bear this option in mind when considering female patients for pelvic irradiation.


Random convergence of olfactory inputs in the Drosophila mushroom body.
The mushroom body in the fruitfly Drosophila melanogaster is an associative brain centre that translates odour representations into learned behavioural responses. Kenyon cells, the intrinsic neurons of the mushroom body, integrate input from olfactory glomeruli to encode odours as sparse distributed patterns of neural activity. We have developed anatomic tracing techniques to identify the glomerular origin of the inputs that converge onto 200 individual Kenyon cells. Here we show that each Kenyon cell integrates input from a different and apparently random combination of glomeruli. The glomerular inputs to individual Kenyon cells show no discernible organization with respect to their odour tuning, anatomic features or developmental origins. Moreover, different classes of Kenyon cells do not seem to preferentially integrate inputs from specific combinations of glomeruli. This organization of glomerular connections to the mushroom body could allow the fly to contextualize novel sensory experiences, a feature consistent with the role of this brain centre in mediating learned olfactory associations and behaviours.


Li-Ion Battery Cathodes: Enhancing Interfacial Bonding between Anisotropically Oriented Grains Using a Glue-Nanofiller for Advanced Li-Ion Battery Cathode (Adv. Mater. 23/2016).
The formation of a spinel Lix CoO2 layer in a Ni-rich secondary particle for lithium-ion batteries is reported by S. K. Kwak, J. Cho, and co-workers on page 4705, who find that the spinel-like Lix CoO2 layer, between layered primary particles, can enhance the mechanical strength of secondary particles by enhancing the interfacial binding energy among the grains. Moreover, the layer can effectively protect the unstable surface of the primary particles and offers a fast electron-ion pathway, resulting in overall enhancements of stability and kinetics in battery performance.


Clinical, histopathological features and efficacy of elimination diet and proton-pump inhibitor therapy in achieving histological remission in Asian children with eosinophilic gastritis.
Paediatric eosinophilic gastritis (EG) is a rare disorder and existing literature on diagnostic criteria and management remains lacking. We aim to describe the clinical spectrum and assess the efficacy of dietary elimination and proton-pump inhibitor (PPI) therapy, with particular emphasis on histologic remission in children with primary EG. We performed a retrospective study of patients aged 0-18 years diagnosed with EG at a single centre in Singapore from 2013 to 2021. EG was diagnosed based on histological criteria of infiltration of >30 eosinophils per high-power film (HPF) in >5 separate HPFs from gastric biopsies, in the absence of other causes. First-line treatment consisted of PPI therapy and empiric 1-6 food elimination diet (FED). Outcomes measured were clinical, endoscopic and histological remission (defined as eosinophil count <20/HPF in gastric biopsies). Twenty-one (66.7% females) patients were included with median age at diagnosis of 15 months (range:3-192). Majority presented with vomiting (76.2%) and gastrointestinal bleeding (71.4%). Twenty patients were initiated on FED+PPI and 16 had post-treatment biopsies. Clinical, endoscopic and histologic remissions were achieved in 94.7%, 81.3% and 68.8% respectively following FED+PPI. Histologic remission was significantly associated with younger age (9 vs. 132 months; P = 0.026). Four patients who did not respond to FED+PPI were started on oral viscous budesonide, of whom one achieved histological remission and two had clinical improvement. FED+PPI is effective as first-line treatment in achieving histological remission in paediatric EG particularly in younger patients. Topical corticosteroids can be considered for those who have failed FED+PPI therapy.


S-mephenytoin hydroxylation phenotypes in a Swedish population determined after coadministration with debrisoquin.
Mephenytoin (100 mg) and debrisoquin (10 mg) were administered orally, both separately and together, to 41 healthy subjects. The ratios between the S and R enantiomers of mephenytoin and between debrisoquin and 4-OH-debrisoquin in urine were determined by use of GC. These ratios were used as measures of drug hydroxylation. There was no change in the phenotypic trait values of the two drugs when they were coadministered. Mephenytoin and debrisoquin then were coadministered to 253 healthy Swedish subjects, before bedtime, and urine samples were collected at periods of 0 to 8, 8 to 24, and 24 to 32 hours after drug administration. In the first sample, seven of the 253 subjects (2.8%, 95% confidence interval 0.8% to 4.8%) had an S/R ratio of greater than 0.8; this indicated that they were poor hydroxylators of S-mephenytoin. In the two consecutive samples, the S/R ratios of mephenytoin did not change in these seven persons, whereas it decreased to less than 0.2 in the third sample in the extensive hydroxylators. As was reported before, there was no relationship between the mephenytoin S/R ratio and the debrisoquin metabolic ratio (rs = 0.01). Coadministration of debrisoquin and mephenytoin before bedtime and urine collection during two consecutive nights allow for an accurate determination of both phenotypes in the population.


Inflammatory arthritis in HIV positive patients: A practical guide.
Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients.


Pseudallescheria boydii with Aspergillus fumigatus and Aspergillus terreus in a Critically Ill Hematopoietic Stem Cell Recipient with ARDS.
Pseudallescheria boydii is a fungal organism known to affect immunocompromised patients. This organism is known to cause, in severe cases, invasive infection of various organs such as the central nervous, cardiovascular, and respiratory systems. We report an unusual case of pulmonary P. boydii pneumonia in an immunocompromised critically ill patient with a co-infection of Aspergillus fumigatus and Aspergillus terreus with ARDS. This case highlights the importance of a high index of suspicion for superimposed fungal infections in patients who are critically ill and immunocompromised. Uncommon fungal pathogens should be considered in the differential diagnosis of respiratory failure, especially if diagnostic markers such as galactomannan (from BAL and serum) or 1,3-beta-D-glucan are elevated. Further diagnostic interventions are warranted when insufficient clinical improvement is observed to prevent treatment failure and adverse outcomes.


Routine surveillance data on AIDS and HIV infections in the UK: a description of the data available and their use for short-term planning.
In the UK surveillance of AIDS and HIV infection is based on routine reporting systems. Whilst attempts are made to ensure that AIDS data are as complete as possible, numbers of reports fluctuate from month to month for reasons which are described. In 1986 there was an increase in death certificates naming AIDS as a cause of death in patients who were not identifiable in the surveillance data. More active surveillance is now undertaken in order to minimize this and other possible discrepancies. It is probable that most cases of AIDS are reported and therefore these data can be used to describe trends in the epidemic by 'risk group'. Laboratory reports of HIV antibody-positive tests could give an earlier indication of trends because of the long incubation period of AIDS. But these laboratory data are difficult to interpret because they represent an incomplete and biased sample of all positive persons. AIDS cases are still being reported at a rate which is increasing approximately exponentially. Short-term predictions are presented showing a growth in the epidemic which is consistent with previously published predictions. Most cases are in the homosexual risk group. New asymptomatic homosexual patients with HIV antibody are still being identified. The epidemic of AIDS in haemophilia patients should be of finite size although new cases of AIDS are likely to continue to be diagnosed for several years. AIDS due to blood transfusion given in the UK before donor screening appears to be a much smaller epidemic. The epidemic in drug abusers is increasing. Heterosexually acquired AIDS and HIV infections are being reported in small but increasing numbers.


Taxonomic study of the genus Prorophora Ragonot, 1887 (Lepidoptera, Pyralidae, Phycitinae) in China, with description of a new species.
The genus Prorophora Ragonot, 1887 is newly recorded for China. Of the three species treated here, Prorophora (Reisserempista) binacanthasp. n. is described as new; Prorophora (Prorophora) albidogilvella Roesler, 1970 and Prorophora (Reisserempista) mongolica Roesler, 1970 are diagnosed and newly recorded for China. Images of adults and illustrations of genital structures are provided, along with a key to the known species.


OXPHOS promotes apoptotic resistance and cellular persistence in TH17 cells in the periphery and tumor microenvironment.
T cell proliferation and cytokine production are bioenergetically and biosynthetically costly. The inability to meet these metabolic demands results in altered differentiation, accompanied by impaired effector function, and attrition of the immune response. Interleukin-17-producing CD4 T cells (TH17s) are mediators of host defense, autoimmunity, and antitumor immunity in the setting of adoptive T cell therapy. TH17s are long-lived cells that require mitochondrial oxidative phosphorylation (OXPHOS) for effector function in vivo. Considering that TH17s polarized under standardized culture conditions are predominately glycolytic, little is known about how OXPHOS regulates TH17 processes, such as their ability to persist and thus contribute to protracted immune responses. Here, we modified standardized culture medium and identified a culture system that reliably induces OXPHOS dependence in TH17s. We found that TH17s cultured under OXPHOS conditions metabolically resembled their in vivo counterparts, whereas glycolytic cultures were dissimilar. OXPHOS TH17s exhibited increased mitochondrial fitness, glutamine anaplerosis, and an antiapoptotic phenotype marked by high BCL-XL and low BIM. Limited mitophagy, mediated by mitochondrial fusion regulator OPA-1, was critical to apoptotic resistance in OXPHOS TH17s. By contrast, glycolytic TH17s exhibited more mitophagy and an imbalance in BCL-XL to BIM, thereby priming them for apoptosis. In addition, through adoptive transfer experiments, we demonstrated that OXPHOS protected TH17s from apoptosis while enhancing their persistence in the periphery and tumor microenvironment in a murine model of melanoma. Together, our work demonstrates how metabolism regulates TH17 cell fate and highlights the potential for therapies that target OXPHOS in TH17-driven diseases.


Age differences in source monitoring and referent discrimination.
In contrast to previous studies which addressed separately memory for source and referent, the present experiment analyzes the effects of aging on memory for both, source and referent. The experiment simulated a conversation between two people exchanging descriptors of themselves and the other speaker (e.g., "I am helpful," "you are capable"). Participants (N = 60) were divided into two age groups: younger (M = 23.47 years old, SD = 2.37), older (M = 70.30 years old, SD = 3.73). Recall, recognition, and accuracy in identifying source (e.g., "who said helpful?") and referent (e.g., "about whom was capable said?") were analyzed. Younger and older adults recalled and recognized equally well information read by the experimenter about herself, but only young adults showed better memory for the descriptors they read about themselves. Older adults were impaired in source monitoring, but not in reference discrimination. Normal referent discrimination in older adults is attributed to the fact that the referent forms part of the content of the episode, whereas who spoke it is part of its context, and older adults tend to show greater deficits in context than in content memory. These results are explained within the source and reality monitoring framework.


The formation of enzyme-bound and medium pyrophosphate and the molecular basis of the oxygen exchange reaction of yeast inorganic pyrophosphatase.
Yeast inorganic pyrophosphatase, with 10 mM 32Pi and 10 mM Mg2+ present at pH 7.3 TO 7.6, rapidly forms enzyme-bound pyrophosphate equivalent to about 5% of the total catalytic sties on the two enzyme subunits. The enzyme thus appears to bind PPi so as to favor thermodynamically its formation from Pi. The enzyme catalyzes a measurable equilibrium formation of free PPi at a much slower rate. Under similar conditions, the enzyme catalyzes a rapid exchange of oxygen atoms between Pi and water with the relative activation by metals being Mg2+ greater than Zn2+ greater than Co2+ greater than Mn2+. Millisecond mixing and quenching experiments demonstrate that the rate of formation and cleavage of the enzyme-bound PPi is rapid enough to explain most or all of the oxygen exchange reaction.


The Role of Stereotactic Laser Amygdalohippocampotomy in Mesial Temporal Lobe Epilepsy.
Stereotactic laser amygdalohippocampotomy (SLAH) uses laser interstitial thermal therapy guided by magnetic resonance thermography. This novel intervention can achieve seizure freedom while minimizing collateral damage compared to traditional open surgery, in patients with mesial temporal lobe epilepsy. An algorithm is presented to guide treatment decisions for initial and repeat procedures in patients with and without mesial temporal sclerosis. SLAH may improve access by medication-refractory patients to effective surgical treatments and thereby decrease medical complications, increase productivity, and minimize socioeconomic consequences in patients with chronic epilepsy.


A geospatial approach for assessing urban flood risk zones in Chennai, Tamil Nadu, India.
Chennai, the capital city of Tamil Nadu in India, has experienced several instances of severe flooding over the past two decades, primarily attributed to persistent heavy rainfall. Accurate mapping of flood-prone regions in the basin is crucial for the comprehensive flood risk management. This study used the GIS-MCDA model, a multi-criteria decision analysis (MCDA) model that incorporated geographic information system (GIS) technology to support decision making processes. Remote sensing, GIS, and analytical hierarchy technique (AHP) were used to identify flood-prone zones and to determine the weights of various factors affecting flood risk, such as rainfall, distance to river, elevation, slope, land use/land cover, drainage density, soil type, and lithology. Four groups (zones) were identified by the flood susceptibility map including high, medium, low, and very low. These zones occupied 16.41%, 67.33%, 16.18%, and 0.08% of the area, respectively. Historical flood events in the study area coincided with the flood risk classification and flood vulnerability map. Regions situated close to rivers, characterized by low elevation, slope, and high runoff density were found to be more susceptible to flooding. The flood susceptibility map generated by the GIS-MCDA accurately described the flood-prone regions in the study area.


Utilizing metformin to prevent metabolic syndrome due to androgen deprivation therapy (ADT): a randomized phase II study of metformin in non-diabetic men initiating ADT for advanced prostate cancer.
Androgen deprivation therapy (ADT) can lead to metabolic syndrome (MS) and is implicated in ADT-resistance. Metformin showed antineoplastic activity through mTOR inhibition secondary AMPK-activation. To investigate whether metformin mitigated ADT-related MS, we conducted a randomized double-blind phase II trial of metformin 500 mg TID or placebo in non-diabetic patients with biochemically-relapsed or advanced PC due for ADT. Fasting serum glucose, insulin, PSA, metformin, weight and waist circumference (WC) were measured at baseline, week 12 and 28. The primary endpoint was a group of MS metrics. Secondary endpoints include PSA response, safety, serum metformin concentrations and analysis of downstream an mTOR target, phospho-S6-kinase. 36 men were randomized to either metformin or placebo. Mean age was 68.4. Mean weight, WC and insulin levels increased in both arms. At week 12 and 28, no statistical differences in weight, WC or insulin were observed in either arm. No significant difference in percentage of patients with PSA <0.2 at week 28 between metformin (45.5%) vs. placebo (46.7%). Analysis in the metformin-arm showed variable down-regulation of phospho-S6 kinase. In our small study, metformin added to ADT did not show a reduced risk of ADT-related MS or differences in PSA response.


N-3 and n-6 fatty acids stimulate restitution by independent mechanisms in the IEC-6 model of intestinal wound healing.
We have shown that intestinal epithelial restitution is stimulated by n-3 and n-6 fatty acids. The current studies were undertaken to elucidate the mechanistic pathway(s) involved in this fatty acid modulation of restitution. Inhibition of phospholipase A(2) and eicosanoid synthesis and its effect on fatty acid stimulation of cellular migration in confluent, wounded IEC-6 monolayers was examined. The production of prostaglandin E(2) and transforming growth factor beta(1) were also measured in fatty acid supplemented cultures. Inhibition of phospholipase A(2) attenuated the effect of fatty acid stimulation of restitution in both n-3 and n-6 supplemented cultures. The lipoxygenase inhibitor, nordihydorguaretic acid (2 &mgr;mol/L), had no effect on stimulation of migration by fatty acids. The cyclooxygenase inhibitor piroxicam (5 &mgr;mol/L) and cyclooxygenase-2 specific inhibitors dexamethasone (2 &mgr;mol/L) and NS-398 (10 &mgr;mol/L) all attenuated the fatty acid stimulation of migration by n-6 fatty acids but had no effect on n-3 stimulated restitution. Prostaglandin E(2) production in n-6 supplemented cultures was significantly greater than in control and n-3 supplemented cultures and was partially inhibited by dexamethasone and NS-398. Latent transforming growth factor beta(1) production in n-3 supplemented cultures was significantly higher than baseline and n-6 supplemented cultures. Docosapentaenoic acid supplementation significantly enhanced the restitution process and NS-398 treatment had no effect on this stimulation of cellular migration. The liberation of fatty acid from the sn-2 position of phospholipid appears to be necessary for both n-3 and n-6 fatty acid stimulation of restitution. N-6 fatty acid modulation of restitution appears to be mediated through the production of eicosanoid products, however, prostaglandin E(2) does not appear to be the sole prostanoid involved. N-3 supplementation elevates the production of latent transforming growth factor beta(1) and may be responsible for n-3 mediated stimulation of restitution. These results further emphasize that n-3 and n-6 fatty acids convey their effects through unique pathways.


Physician specialty and mortality among elderly patients hospitalized with heart failure.
Whether specialty care improves survival among patients with heart failure remains controversial. We evaluated specialty care and outcomes in 25869 Medicare beneficiaries hospitalized with heart failure in the United States from 1998 through 1999. Patients were classified based on the specialty of their attending physician: cardiologist, internist, general physician, or family physician. The primary outcome of interest was all-cause mortality within 30 days of admission. Cardiologists were attending physicians for 26%, internists for 50%, and general and family physicians cared for the remainder. Mortality at 30 days was lowest for patients cared for by cardiologists (8.8%), higher for patients cared for by internists (10.0%, relative risk [RR] = 1.07; 95% confidence interval [CI]: 0.97 to 1.19; P = 0.059) and general physicians (11.1%, RR = 1.26; 95% CI: 0.99 to 1.58; P = 0.086), and highest for patients cared for by family physicians (12.0%, RR = 1.31; 95% CI: 1.15 to 1.49; P <0.001). Patients cared for by family physicians remained at higher 30-day mortality rates whether with (RR = 1.30; 95% CI: 1.11 to 1.52) or without consultation with cardiologists (RR = 1.31; 95% CI: 1.13 to 1.52). Hospitalized patients with heart failure had lower 30-day mortality when treated by cardiologists than when they were treated by other physicians. Although these differences were modest (RR = 1.07) for internists, they were substantial for general physicians (RR = 1.26) and family physicians (RR = 1.31); of note was that inpatient cardiology consultation did not appear to change this relation.


Predicting vaginal birth after cesarean delivery: a review of prognostic factors and screening tools.
Our purpose was to identify the factors associated with vaginal delivery after trial of labor in patients with a prior cesarean and to evaluate the effectiveness of existing screening tools. Studies were identified through MEDLINE and HealthSTAR (1980-2002), reference list reviews, and suggestions of national experts. Thirteen of the 100 eligible studies provided fair to good quality evidence for the predictive nature of 12 factors. Two of the six screening tools were considered promising and demonstrated reproducibility through validation studies. There is little high-quality data to guide clinical decisions regarding which women are likely to have a successful trial of labor. Although we identified two validated screening tools that may be reasonable for practitioners to use, further development is needed to deliver them in a user-friendly manner and further research is needed to determine the clinical setting in which they are most useful. Conducting high-quality research on the factors that delineate women who are at higher likelihood of vaginal delivery without complications and developing accurate user-friendly screening tools to integrate these data should be a national research priority.


CT for the follow-up of cranial trauma.
The author's experience in diagnosing lesions of cerebral trauma with the CT scanner are outlined. The study is divided into acute and chronic lesions. Special attention is drawn to the morphology of subdural and intracerebral haematomas, which is dependent upon their duration.


Stromal fibrosis of the breast: outcome analysis.
Stromal fibrosis in the breast is a non-specific benign pathologic entity with wide spectrum of imaging finding. The false-negative rates (number of cancers missed) previously reported have limited value because short follow-up period and small number of populations. To describe the mammographic and sonographic findings of stromal fibrosis of the breast diagnosed by imaging-guided biopsy and to determine the false-negative rate at percutaneous biopsy. Between January 2007 and December 2008, 3097 consecutive imaging-guided breast core biopsies were performed. Patients were included in our study if stromal fibrosis was the predominant pathologic finding. Patients who had received <2 years of follow-up were excluded. Mammographic and sonographic findings were reviewed. Follow-up imaging for >2 years and histologic data were reviewed to evaluate lesion stability. Stromal fibrosis was diagnosed in 187 (6.0%) of 3097 imaging-guided biopsies among patients with >2 years of follow-up (mean, 41.9 months). Among them, 91 (49%) of 187 lesions were not visible on mammography and calcifications were the most common findings, being identified in 33 lesions (17.6%). The most common sonographic finding was an oval hypoechoic mass with a circumscribed margin. Forty-two lesions (22.5%) were excised. Four false-negative lesions (2.1%, 4/187) were identified; all false-negative lesions were diagnosed within 6 months because of imaging-pathology discordance (75%, 3/4) or disease progression (25%, 1/4). Stromal fibrosis diagnosed by imaging-guided biopsy has a wide spectrum of imaging finding and can be managed safely with radiologic-pathologic correlation and subsequent short-term imaging follow-up.


Third-party Assessments/Independent Medical Evaluations.
A position paper developed by the Canadian Psychiatric Association's (CPA) Professional Standards and Practice Committee and approved by the CPA Board of Directors on May 25, 2020.


Association between the degree of vertebrobasilar stenosis, location, infarction pattern, and QMRA flow state.
We aimed to investigate the relationship between the degree and location of vertebrobasilar stenosis and quantitative magnetic resonance angiography (QMRA) distal flow. We retrospectively reviewed patients who presented with acute ischemic stroke with ≥50% stenosis of the extracranial or intracranial vertebral or basilar arteries, and QMRA performed within 1 year of stroke. Standardized techniques were used to measure stenosis and to dichotomize vertebrobasilar distal flow status. Patients were grouped based on the involved artery and the severity of disease. All p-values were calculated using chi-squared analysis and Fisher exact test with statistical significance defined as p < .05. Sixty-nine patients met study inclusion, consisting of 31 with low distal flow and 38 with normal distal flow. The presence of severe stenosis or occlusion was 100% sensitive, but only 47% predictive and 26% specific of a low distal flow state. Bilateral vertebral disease was only 55% sensitive but was 71% predictive and 82% specific of a low-flow state and was five times and nearly three times more likely to result in a low-flow state compared to unilateral vertebral disease (14%) and isolated basilar disease (28%), respectively. Severe stenosis of ≥70% may mark the minimal threshold required to cause hemodynamic insufficiency in the posterior circulation, but nearly half of these patients may remain hemodynamically sufficient. Bilateral vertebral stenosis resulted in a fivefold increase in QMRA low distal flow status compared to unilateral vertebral disease. These results may have implications in the design of future treatment trials of intracranial atherosclerotic disease.


Molecular biology of Pasteurella multocida toxin.
Pasteurella multocida toxin (PMT) is the causative agent of progressive atrophic rhinitis in swine. The 146 kDa single-chain toxin harbours discrete domains important for receptor binding, internalisation and biological activity. The molecular basis of the toxin's activity is the deamidation of a specific glutamine residue in the α-subunit of heterotrimeric G proteins. This results in an inhibition of the inherent GTPase activity leading to a constitutively active phenotype of the G protein. Due to the ability of the toxin to act on various families of heterotrimeric G proteins, a large subset of signal transduction pathways is stimulated.


Trends in breast cancer screening during the COVID-19 pandemic within a universally insured health system in the United States, 2017-2022.
In the United States, breast cancer is the most commonly diagnosed cancer and second leading cause of cancer death in women. Early detection through mammogram screening is instrumental in reducing mortality and incidence of disease. The COVID-19 pandemic posed unprecedented challenges to the provision of care, including delays in preventive screenings. We examined trends in breast cancer screening during the COVID-19 pandemic in a universally insured national population and evaluated rates across racial groups and socioeconomic strata. In this retrospective open cohort study, we used the Military Health System Data Repository to identify female TRICARE beneficiaries ages 40-64 at average risk for breast cancer between FY2018 and FY2022, broken down into prepandemic (September 1, 2018-February 28, 2020), early pandemic (March 1, 2020-September 30, 2020), and late pandemic periods (October 1, 2020-September 30, 2022). The primary outcome was receipt of breast cancer screening. Screening dropped 74% in the early pandemic period and 22% in the late pandemic period, compared with the prepandemic period. Compared with White women, Asian/Pacific Islander women were less likely to receive mammograms during the late pandemic period (0.92RR; 0.90-0.93 95%CI). American Indian/Alaska Native women remained less likely to receive screenings compared with White women during the early (0.87RR; 0.80-0.94 95% CI) and late pandemic (0.94RR, 0.91-0.98 95% CI). Black women had a higher likelihood of screenings during both the early pandemic (1.10RR; 1.08-1.12 95% CI) and late pandemic (1.12RR, 1.11-1.13 95% CI) periods compared with White women. During the early and late pandemic periods, disparities by rank persisted from prepandemic levels, with a decrease in likelihood of screenings across all sponsor ranks. Our results indicate the influence of race and socioeconomics on mammography screening during COVID-19. Targeted outreach and further evaluation of factors underpinning lower utilization in these populations are necessary to improve access to preventative services across the population.


Is microwave ablation therapy as effective as colorectal liver metastases in noncolorectal liver metastases?
The aim of the study was to evaluate the relationship between primary tumor type and the effectiveness of microwave ablation (MWA) therapy by comparing the technical and clinical outcomes of MWA in the treatment of colorectal liver metastases (CLM) and noncolorectal liver metastases (NCLM). Between January 2019 and March 2021, 47 consecutive patients (25 male, 22 female) with a total of 63 unresectable hepatic metastases underwent MWA under ultrasound guidance. The patients were divided into CLM (n = 29) and NCLM (n = 18) groups. Patient demographics, procedural details, and complications were noted. The overall survival (OS) and disease-free survival (DFS) rates were also analyzed. Technical success was 100% in both groups. No major complication was observed. Three minor complications [fatigue (n = 2) and subcutaneous hematoma (n = 1)] were encountered. DFS rates were 88.9%, 71.9%, 64.9%, and 44.0% at 3, 6, 12, and 24-months, respectively, with a mean DFS of 17.4 months (95% CI: 15.1, 19.7). Also, OS rates were 93.7%, 90.0%, 76.8%, and 64.3%, at 3, 6, 12, and 24-months, respectively, with a mean OS of 18.5 months (95% CI: 16.2, 20.7). There was no significant difference in recurrence between the CLM and NCLM groups (p = 0.452). The recurrence rate in liver metastases > 3 cm in size was significantly higher than in metastases ≤ 3 cm in size (p < 0.001). MWA therapy is as effective in the NCLM group as in the CLM group, regardless of histologic type. Metastasis size (>3 cm) was correlated with the recurrence rate in the CLM and NCLM groups.


Prolongation of QT interval and antiarrhythmic action of bepridil.
Studies were undertaken with bepridil, a new calcium blocker that prolongs the QT interval, to determine the antiarrhythmic and possible arrhythmogenic properties of this agent. The technique of programmed electrical stimulation was employed to evaluate bepridil in 15 patients with symptomatic ventricular tachycardia (VT). Bepridil prevented VT induction in 7 of 15 patients. Bepridil prolonged the QT and refractoriness and a linear correlation could be demonstrated between the percent change in QTc and refractory period prolongation for the bepridil-protected group. Bepridil in one patient reduced by one the number of stimuli required to induce VT, but no spontaneous arrhythmias were noted. Bepridil thus possesses antiarrhythmic properties with a minimal proarrhythmic effect.


Speech processing ability in alcoholics: a transient impairment and its relation to field dependence.
Alcoholic and non-alcoholic subjects received a test of the ability to identify speech presented against competing speech (Synthetic Sentence Identification) and a test of field dependence (Embedded-Figures Test (EFT). Performance on the speech task (which involved auditory figure-ground differentiation) bore no special relationship to performance on the field-dependence test. However, cross-sectional and longitudinal data suggested that recently-drinking alcoholics are temporarily impaired in their speech-processing ability, recovering this ability after several months of alcohol-abstinence. A relationship between chronicity of alcoholism and field dependence was also observed. The latter relationship, along with findings on auditory tests, were discussed in terms of their relevance to the issue of whether field dependence is an antecedent to or a consequence of alcoholism.


Thermodynamic analysis of the aggregation propensity of oxidized Alzheimer's beta-amyloid variants.
We have determined the critical concentrations of a set of 18 variants of Alzheimer's Abeta(1-40) peptide, each carrying a different residue at position 18. We find that the critical concentrations depend on the hydrophobicity and beta-sheet propensity of residue 18, and therefore on properties that we identified previously to affect also the kinetics by which these peptides aggregate. Since the critical concentrations can be related to the Gibbs free energy of aggregation (DeltaG), these data imply a link between the thermodynamics and the kinetics of aggregation in that sequences that form very stable aggregates are also those that form such aggregates very rapidly.


Age and Gender-Related Changes in Biogenic Amine Metabolites in Cerebrospinal Fluid in Children.
Metabolites of cerebrospinal biogenic amines (dopamine and serotonin)are an important tool in clinical research and diagnosis of children with neurotransmitter disorders. In this article we focused on finding relationships between the concentration of biogenic amine metabolites, age, and gender. We analyzed 148 samples from children with drug resistant seizures of unknown etiology and children with mild stable encephalopathy aged 0-18 years. A normal profile of biogenic amineswas found in 107 children and those children were enrolled to the study group. The CSF samples were analyzed by HPLC with an electrochemical detector. The concentrations of the dopamine and serotonin metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), respectively, were high at birth, gradually decreasing afterward until the 18 years of age. Nevertheless, the HVA/5-HIAA ratio did not vary with age, except in the children below 1 year of age. In the youngest group we observed a strong relationship between the HVA/5-HIAA ratio and age (r = 0.69, p < 0.001). There were no statistical differences in the level of both dopamine and serotonin metabolites between boys and girls, although a tread toward lower HVA and 5-HIAA in the boys was noticeable. Significant inter-gender differences in the level of HVA and 5-HIAA were noted only in the age-group of 1-4 years, with 5-HIAA being higher in the girls than boys (p = 0.004). In conclusion, the study revealed that the concentration of biogenic amine metabolites is age and sex dependent.


The mosquito genome--a turning point?
Of the insects that serve as vectors for parasitic diseases, the genus Anopheles is the most important. Of the approximately 400 species, about twelve serve as vectors for human pathogens. Months have passed since the sequenced genomes of the malaria parasite, Plasmodium falciparum, and its vector, Anopheles gambiae, were published. Sequences were compared, gene and protein predictions were made, new research areas evolved and many ongoing projects gained new momentum. A general belief is that we are at a turning point: we are now in a position to tackle both the parasite and the vector from new angles and with new force, for example, by identifying new drug targets and obtaining a deeper insight into molecular mechanisms of the insect, the parasite and the interactions between them.


Bilateral dysplasia epiphysealis hemimelica of the talus associated with a lower leg intramuscular cartilaginous mass.
Dysplasia epiphysealis hemimelica (DEH), or Trevor disease, is a rare skeletal dysplasia characterised by an osteocartilaginous mass arising from an epiphysis. It affects single or multiple epiphyses in children, usually in the lower limb, predominantly the knee and ankle. Bilateral involvement is extremely rare, with only four cases reported in the literature to date. We report an additional case of bilateral DEH of the talus in a 14-year-old girl with an associated, not previously reported, intramuscular cartilaginous mass of the left lower leg. Clinical, radiological and pathological findings are presented. We emphasise the role of MRI and US in the diagnosis of DEH.


Characterization of cardiac amyloidosis using cardiac magnetic resonance fingerprinting.
Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy with poor prognosis absent appropriate treatment. Elevated native myocardial T1 and T2 have been reported for CA, and tissue characterization by cardiac MRI may expedite diagnosis and treatment. Cardiac Magnetic Resonance Fingerprinting (cMRF) has the potential to enable tissue characterization for CA through rapid, simultaneous T1 and T2 mapping. Furthermore, cMRF signal timecourses may provide additional information beyond myocardial T1 and T2. Nine CA patients and five controls were scanned at 3 T using a prospectively gated cMRF acquisition. Two cMRF-based analysis approaches were examined: (1) relaxometric-based linear discriminant analysis (LDA) using native T1 and T2, and (2) signal timecourse-based LDA. The Fisher coefficient was used to compare the separability of patient and control groups from both approaches. Leave-two-out cross-validation was employed to evaluate the classification error rates of both approaches. Elevated myocardial T1 and T2 was observed in patients vs controls (T1: 1395 ± 121 vs 1240 ± 36.4 ms, p < 0.05; T2: 36.8 ± 3.3 vs 31.8 ± 2.6 ms, p < 0.05). LDA scores were elevated in patients for relaxometric-based LDA (0.56 ± 0.28 vs 0.18 ± 0.13, p < 0.05) and timecourse-based LDA (0.97 ± 0.02 vs 0.02 ± 0.02, p < 0.05). The Fisher coefficient was greater for timecourse-based LDA (60.8) vs relaxometric-based LDA (1.6). Classification error rates were lower for timecourse-based LDA vs relaxometric-based LDA (12.6 ± 24.3 vs 22.5 ± 30.1%, p < 0.05). These findings suggest that cMRF may be a valuable technique for the detection and characterization of CA. Analysis of cMRF signal timecourse data may improve tissue characterization as compared to analysis of native T1 and T2 alone.


Blood compatibility of polyethersulfone membrane by blending a sulfated derivative of chitosan.
In this study, a novel sulfated derivative of chitosan, which could be dissolved in many common organic solvents, is conveniently synthesized for the modification of polyethersulfone (PES) membrane. Elemental analysis, FTIR, (1)H NMR and X-ray diffraction diagrams (XRD) are used to demonstrate the introduction of functional groups. Owing to the solubility in organic solvents, the sulfated derivative of chitosan could be directly blended with PES in organic solvent to prepare membrane by means of a liquid-liquid phase separation technique. The modified membrane showed lower protein (bovine serum albumin (BSA) and bovine serum fibrinogen (BFG)) adsorption and suppressed platelet adhesion. Moreover, the activated partial thromboplastin time (APTT) for the modified membrane was enhanced as high as 60% compared to pure PES membrane. The lower protein adsorption, suppressed platelet adhesion and increased APTT confirmed that the blood compatibility of the modified PES membrane by the sulfated derivative of chitosan was significantly improved.


Direct inhibition, but indirect sensitization of pacemaker activity to sympathetic tone by the interaction of endotoxin with HCN-channels.
In critically ill patients regulation of heart-rate is often severely disturbed. Interaction of bacterial endotoxin (lipopolysaccharide, LPS) with hyperpolarization-activated cyclic nucleotide-gated cation-(HCN)-channels may interfere with heart-rate regulation. This study analyzes the effect of LPS, the HCN-channel blocker ivabradine or Ca(2+) -channel blockers (nifedipine, verapamil) on pacemaking in spontaneously beating neonatal rat cardiomyocytes (CM) in vitro. In vivo, the effect of LPS on the heart-rate of adult CD1-mice with and without autonomic blockade is analyzed telemetrically. LPS (100 ng/mL) and ivabradine (5 μg/mL) reduced the beating-rate of CM by 20.1% and 24.6%, respectively. Coincubation of CM with both, LPS and ivabradine, did not further reduce the beating-rate, indicating interaction of both compounds with HCN-channels, while coincubation with Ca(2+) -channel blockers and LPS caused additive beating-rate reduction. In CD1-mice (containing an active autonomic-nervous-system), injection of LPS (0.4 mg/kg) expectedly resulted in increased heart-rate. However, if the autonomic nervous system was blocked by propranolol and atropine, in line with the in vitro data, LPS induced a significant reduction of heart-rate, which was not additive to ivabradine. The in vivo and in vitro results indicate that LPS interacts with HCN-channels of cardiomyocytes. Thus, LPS indirectly sensitizes HCN-channels for sympathetic activation (tachycardic-effect), and in parallel directly inhibits channel activity (bradycardic-effect). Both effects may contribute to the detrimental effects of septic cardiomyopathy and septic autonomic dysfunction.


Risk of thromboembolic events after recurrent spontaneous abortion in antiphospholipid syndrome: a case-control study.
To investigate whether patients having antiphospholipid syndrome (APS) as the only aetiological factor for recurrent spontaneous abortion (RSA) are at increased risk of thrombosis later in life. A case-control study at a tertiary university referral centre. The study group consisted of 57 primary APS and RSA women (APS-RSA group). Control groups included: 86 patients with RSA of unknown aetiology (uRSA group), 42 patients with RSA and thrombophilic genetic defects as the only aetiologic factor for RSA (tRSA group) and 30 antiphospholipid antibody (aPL) positive but otherwise healthy women (aPL group). The main measurement was the thrombosis rate after long-term follow-up. APS-RSA patients had a significantly higher 12-year cumulative thrombotic incidence rate compared with the three comparator groups (19.3% vs 4.8%, 0.0% and 0.0%, respectively (log rank), p<0.001). Patients in the APS-RSA group had 25.6 thrombotic events per 1000 patient-years (95% CI 12.8 to 45.9). The OR of thrombosis in relation to the presence (APS-RSA group) or absence (uRSA and tRSA groups) of aPL in patients with RSA was 15.06 (95% CI 3.2 to 70.5). Our data indicate that a history of RSA associated with aPL is a risk factor for subsequent thrombosis in the long term.


Blood pressure parameters affecting ventricular repolarization in obese children.
Ventricular repolarization (VR) increases the risk of sudden cardiac death due to ventricular arrhythmia. We aimed to evaluate the blood pressure (BP) parameters affecting VR in obese children. Obese (BMI ≥ 95p) and healthy children ≥ 120 cm between January 2017 and June 2019 were included. Demographic and laboratory data, peripheral and central BPs evaluated by a device capable of ambulatory blood pressure monitoring (ABPM), and pulse wave analysis were assessed. Electrocardiographic ventricular repolarization indices, left ventricular mass index (LVMI), and relative wall thickness (RWT) were calculated. A total of 52 obese and 41 control patients were included. Uric acid, triglyceride, total cholesterol, LDL, and ALT values, systolic and diastolic office BPs, 24-h, daytime and nighttime systolic and mean arterial BPs, daytime diastolic BP SDS levels, daytime and nighttime systolic loads, daytime diastolic load, 24-h, daytime and nighttime central systolic and diastolic BPs, and pulse wave velocity values were significantly higher, whereas 24-h, daytime and nighttime AIx@75 were similar between the groups. fT4 levels of obese cases were significantly lower. QTcd and Tp-ed were higher in obese patients. Although RWT was higher in obese cases, LVMI values and cardiac geometry classifications were similar. The independent factors affecting VR in obese cases were younger age and higher diastolic load at night (B = - 2.83, p = 0.010; B = 0.257, p = 0.007, respectively). Obese patients have higher peripheral and central BP, arterial stiffness, and higher VR indices that develop before an increase in LVMI. It would be useful to prevent obesity from an early age and follow up nighttime diastolic load to control VR associated sudden cardiac death in obese children. A higher resolution version of the Graphical abstract is available as Supplementary information.


Project TEAMS (Talking about Eating, Activity, and Mutual Support): a randomized controlled trial of a theory-based weight loss program for couples.
Obesity risk is shared between spouses, yet existing weight loss programs focus on individuals and not the marital dyad. Given the interdependence of weight in couples, weight management outcomes might be improved by targeting joint weight loss and the creation of an interpersonal milieu that supports long-term behavior change. According to Self-Determination Theory (SDT), greater autonomous self-regulation of behaviors, and subsequently better treatment outcomes, are observed in needs supportive environments in which personally meaningful choice is supported and criticism and control are minimized. Correlational analyses confirm these pathways in weight management, with needs support from one's spouse or partner emerging as a distinct predictor of weight loss success. Research is now needed to establish causal links and to develop and test weight loss interventions designed to facilitate the needs supportive behavior of spouses. Project TEAMS (Talking about Eating, Activity, and Mutual Support) is a randomized controlled trial testing a couples-based intervention, grounded in SDT, designed to change the social context of weight loss by training spouses to provide needs support for each other's eating and physical activity behavior. Sixty-four couples will be randomized to either 6 months of behavioral weight loss treatment informed by SDT (SDT-WL) or to 6 months of standard behavioral weight loss treatment (BWL). Couples will attend weekly sessions for 6 months and will be assessed at 0, 3, 6, and 12 months. By bolstering needs support, SDT-WL is predicted to increase autonomous self-regulation and perceived competence and produce greater weight loss and maintenance than standard behavioral treatment. Exploratory analyses will examine the SDT process model prediction that the influence of needs support on treatment outcomes will be mediated by autonomous self-regulation and perceived competence. This study addresses the fundamental importance of interpersonal support in weight management by focusing on couples rather than individuals and using a rich theoretical framework to train spouses in supportive behaviors. Clinicaltrials.gov ; NCT02570009 .


Extracranial vertebral artery aneurysm with neurofibromatosis. Endovascular treatment by detachable balloon.
An extracranial vertebral artery aneurysm in a patient with neurofibromatosis is described. The aneurysm was treated by endovascular balloon occlusion of the proximal vertebral artery. The details of the therapeutic management are discussed, and the vascular manifestations of neurofibromatosis are reviewed.


Development of multiplex TaqMan qPCR for simultaneous detection and differentiation of eight common swine viral and bacterial pathogens.
It is laborious to diagnose the infections of classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), and Suid herpesvirus 1 (SuHV-1) because of the similar clinical symptoms in piglets. Staphylococcus aureus (S. aureus), Streptococcus suis (S. suis), Salmonella choleraesuis (S. choleraesuis, serotype: 6,7:c:1,5), and Escherichia coli (E. coli) are common secondary bacterial pathogens in viral infections. Furthermore, the mixed infection of these viral and bacterial pathogens is more and more common in practical swine breeding. Therefore, a TaqMan multiplex qPCR method for simultaneous detection and differentiation of their pathogen was established in this study by designing specific primers and probes for the E2 gene of CSFV, the ORF7 gene of PRRSV, the ORF1 gene of PCV2 and the gE gene of SuHV-1, the nuc gene of S. aureus, the ef-tu gene of S. suis, the ivnA gene of S. choleraesuis, and the 23S rRNA gene of E. coli, and its specificity, sensitivity, and reproducibility were subsequently tested. The results showed that TaqMan multiplex qPCR method showed a high specificity with no cross reaction between different viruses, and a good repeatability with its coefficient of variation lower than 5%. Besides, the sensitivity of this method was also at least 10 times higher compared with conventional PCR. Overall, this study provided a reliable multiplex TaqMan qPCR method for the diagnosis and differentiation of the mentioned pathogens in pigs, laying a certain technical basis for disease prevention and control.


Available instruments for measurement of psychosocial factors in the work environment.
To provide an overview of the spectrum of available for measurement and evaluation of work-related psychosocial factors. We systematically searched the literature/internet to identify and describe the main available questionnaires and observational instruments for assessment of work-related psychosocial factors (with/without other job stressors). A total of 33 instruments were identified (26 questionnaires, 7 observational), many (11 questionnaires, 5 observational) linked to national institutions/intiatives. Accessibility of relevant information (on the internet or elsewhere) regarding the instruments varied widely. This summary of the range of instruments currently available for evaluation of multiple work stressors at individual, group and/or organizational levels may provide a useful tool for operators and researchers.


From molecular biology to pharmacogenetics: a review of the literature on antidepressant treatment and suggestions of possible candidate genes.
Pharmacogenetic studies in mood disorders are raising increasing interest, after the first findings of a significant association between antidepressant response and a functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR). However, the results of published studies are not unequivocal. The reasons of these discordances could be various: the small samples, which could affect the power to detect a good effect size, the use of different and often not comparable scales and methodologies to assess the response rates. Notwithstanding all these limitations, the choice of candidate genes involved in antidepressant response is one of the crucial steps to target future research. In the present paper, we reviewed the literature concerning pharmacogenetic studies on antidepressant response. This analysis evidenced a number of studies consistently confirming the association of the SERTPR short variant with a poorer response to antidepressants, at least for the Caucasian samples. Further unreplicated positive findings included tryptophan hydroxylase (TPH), G-protein beta(3)-subunit (Gbeta(3)) and serotonin receptor 2A gene polymorphisms. Through the review, we also suggested possible candidate genes for future studies, which are involved in the main monoaminergic neurotransmitters pathways (norepinephrine, dopamine, serotonin), in substance P, neurokinines and glutamate systems, in the intracellular signal transduction pathway, in the phosphorylation process and in the control of the transcriptional activity system.


A Study to Assess The Efficacy of Local Application of Oral Probiotic in Treating Recurrent Aphthous Ulcer and Oral Candidiasis.
To study the efficacy of local application of oral probiotics in improving oral health in recurrent aphthous ulcer and oral candidiasis. Eighty patients with diagnosis of recurrent aphthous ulcer and oral candidiasis were included in the study. They were divided into group A = 40 patients (patients treated with oral application of probiotic as an adjuvant) and group B = 40 patients (patients treated without probiotic). Both the groups were divided into two subgroups, group AU and group BU for recurrent aphthous ulcer and group AC and BC for oral candidiasis. Clinical signs and symptoms were assessed at the beginning of the study and at the end of the study. Pregnant or lactating women, patients with localised or systemic diseases such as Steven Johnson syndrome, ulcerative colitis, Behcet's syndrome and patients on chemotherapy or radiotherapy were excluded from the study. Bacillus Clausii, was used as a probiotic in our study. Patients in group A showed significant improvement in erythema (p = 0.001), pain reduction (p = 0.0001), decreased oral thrush (p = 0.006) and burning sensation in the mouth (p = 0.005) on day 5, whereas there was no significant difference on day 10 follow up. The study demonstrated the efficacy and rapidity of response to oral probiotic as an adjuvant in treating aphthous ulcer and oral candidiasis. Hence, oral application of probiotics can be used as an adjuvant in treating various oral pathology.


Expression of hypoxia-inducible factor 1alpha gene affects the outcome in patients with ovarian cancer.
We conducted study to determine whether and how the expression of the hypoxia-inducible factor 1alpha (HIF-1alpha) gene relates to outcome in patients with epithelial ovarian cancer. A total of 66 patients with epithelial ovarian cancer, who underwent primary surgery followed by platinum-based chemotherapy, were entered into this study. We confirmed the expression of HIF-1alpha and the vascular endothelial growth factor (VEGF) by immunohistochemistry. To determine the quantity of HIF-1alpha and VEGF expression, messenger RNA of each gene was measured by real-time reverse transcription-polymerase chain reaction. The cutoff values were determined by the receiver-operating characteristic curve according to survival. The protein expressions of HIF-1alpha and VEGF were strongly observed in the cancer cells. The cutoff value of HIF-1alpha and VEGF gene expression was 6.0 and 3.0, respectively. The expression of HIF-1alpha did not relate to clinical stage, but tumor with low VEGF expression was observed more frequently in stage I patients. The response rate to chemotherapy did not differ between high and low expression of both genes. The overall survival for patients with high expression of HIF-1alpha was significantly lower, but disease-free survival did not differ between high and low expression of HIF-1alpha, whereas both overall and disease-free survival for patients with high expression of VEGF were significantly lower. Multivariate analysis revealed that FIGO stage and HIF-1alpha expression were independent prognostic factors but that VEGF was not. The present study suggested that the expression level of HIF-1alpha could be an independent prognostic factor in epithelial ovarian cancer.