Lusianthridin Exerts Streptozotocin-Induced Gestational Diabetes Mellitus in Female Rats via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.
Gestational diabetes mellitus (GDM) is characterized via enhanced the glucose intolerance in the pregnant women, which further lead the expansion of gestational hypertension, hepatic damage, pre eclampsia and renal damage. Lusianthridin is the active phytoconstituent of Dendrabium venustu and exhibited the antioxidant and anti-inflammatory effects. In this protocol, we examined the GDM protective effect of lusianthridin (LSD) against streptozotocin (STZ) induced GDM in the female rats. Single intraperitoneal injection of STZ (40 mg/kg) was used for the induction of diabetes in the pregnant female rats. The rats were orally treated with the LSD (10, 20 and 40 mg/kg, body weight) for 18 days and blood glucose level, body weight and plasma insulin were estimated at regular time intervals. at end of the study, fetal weight, placental weight, number of live and dead fetuses were estimated. The antioxidant, lipid and cytokines level were also estimated. GDM rats treated with LSD remarkably improved the body weight of female rats along with fetal weight and suppressed the placental weight. LSD enhanced the live fetuses and suppressed the dead fetuses with reduction of reduced the dead ratio. LSD considerably suppressed the glucose level and improved the insulin level and suppressed the HOMA-IR. LSD significantly (p < 0.001) increased the level of hemoglobin, glycogen and suppressed the level of glycalated hemoglobin. LSD significantly (p < 0.001) altered the level of lipid parameters and inflammatory cytokines. LSD altered the level of antioxidant parameters in the liver and pancreas tissue. LSD significantly (p < 0.001) decreased the mRNA expression of troll like receptor (TLR)4, myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa B (NF-κB)p65 and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), respectively. The results suggest that LSD has a protective effect on GDM in female rats induced by STZ, possibly through reducing the activity of the TLR4/MyD88/NF-κB signaling pathway.


An investigation into the origin and nature of 'amyloid' in a calcifying epithelial odontogenic tumour.
Fresh and fixed tissue from a resection specimen of a calcifying epithelial odontogenic tumour (CEOT) was prepared for histological, histochemical, immunological and biochemical investigation in order to study the nature of the amyloid-like material. The fixed tissue gave positive reactions with Congo-red, Thioflavin T and the dimethylamino benzene (DMAB)-method for tryptophan. The diazotization-coupling (DC) method for tyrosine was negative. The major protein purified from the unfixed tissue by sequential gel filtration had a molecular weight of 9,800. The amino acid analysis of this protein had similarities with tuft enamel protein, immune amyloid and the variable light chain component (VK). From the data obtained in this study, it is not possible to determine the precise nature of the amyloid-like material in this CEOT. However, the results do support the concept that 'amyloid' should be considered as a term describing a broad group of related proteins.


The Efficacy of Short, Skills-based Workshops in Teaching Advocacy to Medical Students: A Pilot Study.
This study evaluated the effectiveness of a short, skills-based workshop, called a Letter-Writing Lunch (LWL), in teaching advocacy to medical students. We assessed political activity, political efficacy, civic responsibility, and skill mastery via pre-, post-, and 6-month follow-up surveys. Via semistructured follow-up interviews, we explored how the intervention affected the participant's view of advocacy. Students mastered identifying and contacting their representatives. Participants' political activity scores demonstrated little to no political activity at baseline and were unchanged at 6 months. Political efficacy scores increased after the event (t[53]=8.5, P<.001), and they remained elevated at 6 months (t[25]=2.1, P=.047). Feelings of civic responsibility significantly increased from the pre-to postsurvey (z=482.5, P<.001), but returned to baseline by 6 months. Four themes emerged from the follow-up interviews: (a) A disconnect exists between what medical students believe their responsibilities are and what they are doing; (b) medical students believe their current advocacy curriculum lacks depth and applicability; (c) students want programming that is realistic in the context of their limited time, varying passions, and current skill level; and (d) the LWL changed students' views on advocacy. Current skills-based education is time-intensive and fails to engage students who are not already committed to developing advocacy skills. Keeping the LWL short in length successfully targeted students with little previous advocacy experience. The event increased political efficacy and civic responsibility while making advocacy appear more accessible. The LWL is an effective and efficient way to teach advocacy to medical students.


[P(0) protein promotes the expression of INF-γ and IL-10 in peripheral blood of n-hexane neuropathy patients].
Objective: To study the changes of monocyte cytokines in peripheral blood of n-hexane neuropathy patients induced by P(0) protein, and to explore the role of autoimmunity in n-hexane neuropathy patients. Methods: In May 2018, 5 patients with peripheral neuropathy diagnosed as n-hexane poisoning were selected as case group in Shenzhen Prevention and Treatment Center for Occupational Disease in 2017. 6 workers exposure to n-hexane and 6 workers without n-hexane exposure were selected as contact group and control group. Peripheral blood mononuclear cells(PBMC) were isolated from venous blood. Results: The number of spots produced by INF-γ and IL-10 increased after stimulation with P(0) protein in case group, and the positive rate was significantly higher than control group and the contact group. Conclusion: Autoimmunity induced by P(0) protein may be involved in the occurrence of myelin sheath damage in n-hexane neuropathy patients.


Protective effect of a nuclear factor-kappaB inhibitor on ischemia-reperfusion injury in a rat epigastric flap model.
We examined whether nuclear factor-kappa B (NF-kappaB) activation was involved in the ischemia-reperfusion (I/R) injury in a rat skin flap model and whether administration of pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, could improve flap viability. Eighty-four Sprague-Dawley rats were divided into control group (n = 28), I/R group (n = 28), and PDTC-treated group (n = 28). An abdominal skin flap (4 x 5 cm) was elevated and subjected to 10 hours of ischemia in both the I/R group and the PDTC-treated group. A bolus of PDTC (300 mg/kg) was infused 5 minutes before reperfusion, followed by a second dose during the first 30 minutes of reperfusion in the PDTC-treated group. Flap tissues were assessed by electrophoretic mobility shift assay at 1, 2, 3, and 6 hours of reperfusion, and myeloperoxidase activity and neutrophil infiltration were assessed at 12 hours of reperfusion. The viability of flaps was assessed 7 days postoperatively. NF-kappaB was activated after reperfusion in the I/R group and displayed peak activity at 1 and 3 hours of reperfusion. In the PDTC-treated group, NF-kappaB activity was significantly reduced at 1, 2, and 6 hours of reperfusion. Myeloperoxidase activity was significantly decreased, and little neutrophil infiltration could be observed. In the PDTC-treated group, the survival of flaps was 86.88 +/- 13.63%, which was significantly greater than the I/R group, in which only 19.20 +/- 7.52% of the flap survived. NF-kappaB is activated during reperfusion in a rat skin flap I/R model. Administration of PDTC can significantly improve flap survival by regulating the early activation of NF-kappaB and suppressing neutrophil infiltration within the flap.


Leigh syndrome global patient registry: uniting patients and researchers worldwide.
Leigh Syndrome (LS) is a rare genetic neurometabolic disorder, that leads to the degeneration of the central nervous system and subsequently, early death. LS can be caused by over 80 mutations in mitochondrial or nuclear DNA. Patient registries are important for many reasons, such as studying the natural history of the disease, improving the quality of care, and understanding the healthcare burden. For rare diseases, patient registries are significantly important as patient numbers are small, and funding is limited. Cure Mito Foundation started a global patient registry for LS in September 2021 to identify and learn about the LS patient population, facilitate clinical trial recruitment, and unite international patients and researchers. Priorities were to allow researchers and industry partners to access data at no cost through a clear and transparent process, active patient engagement, and sharing of results back to the community. Patient registry platform, survey design, data analysis process, and patient recruitment strategies are described. Reported results include demographics, diagnostic information, symptom history, loss of milestones, disease management, healthcare utilization, quality of life, and caregiver burden for 116 participants. Results show a high disease burden, but a relatively short time to diagnosis. Despite the challenges faced by families impacted by Leigh syndrome, participants, in general, are described as having a good quality of life and caregivers are overall resilient, while also reporting a significant amount of stress. This registry provides a straightforward, no-cost mechanism for data sharing and contacting patients for clinical trials or research participation, which is important given the recruitment challenges for clinical trials for rare diseases. This is the first publication to present results from a global patient registry for Leigh Syndrome, with details on a variety of patient-specific and caregiver outcomes reported for the first time. Additionally, this registry is the first for any mitochondrial disease with nearly 70% of participants residing outside of the United States. Future efforts include continued publication of results and further collaboration with patients, industry partners, and researchers.


Reduction of activity of cyanocobalamin in the presence of methylparaben sodium at autoclave temperature.
Reduction of activity of cyanocobalamin (vitamin B12) due to degradation or interaction with methylparaben sodium was measured by UV spectrophotometry and microbial assay. TLC of the heated mixture showed two different spots, which indicate some alteration in the structure of the cyanocobalamin molecule in the presence of methylparaben sodium at 115 degrees for 10 min. The losses were about 20% by UV measurements and 32% by microbial assay. The degree of loss was sufficient to suggest that methylparaben sodium might have considerable influence on the stability of pharmaceutical products containing cyanocobalamin. Methylparaben and sodium chloride had no effect on cyanocobalamin.


Rhabdomyolysis following severe hypokalemia caused by familial hypokalemic periodic paralysis.
Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic paralysis without secondary causes. Primary hypokalemic periodic paralysis is a rare genetic disease characterized by episodic attacks of muscle weakness due to decreases in serum potassium. A 30-year-old woman who had 3 episodic attacks of hypokalemic periodic paralysis was admitted in emergency room with sudden onset symmetrical muscle weakness. After several hours, she started to complain myalgia and severe ache in both calves without any changes. Laboratory test showed markedly elevated creatine phosphokinase, lactic dehydrogenase levels with hypokalemia, rhabdomyolysis resulting from hypokalemia was diagnosed. Here, we report an unusual case of rhabdomyolysis caused by severe hypokalemia, which was suggested a result of familial hypokalemic periodic paralysis.


Constitutive synthesis of heat shock protein (72 kD) in human peripheral blood mononuclear cells: implications for use as a clinical test of recent thermal stress.
There is no clinical laboratory marker to enhance the diagnosis of recent thermal stress in humans. The 72 kD heat shock protein, HSP 72, which is rapidly synthesized after heat stress could be useful in the diagnosis of illnesses associated with heat stress. In humans HSP, 72 is rapidly synthesized after thermal stress; however, conflicting data suggest it may also undergo low level constitutive synthesis. If HSP 72 is constitutively synthesized, a semi-quantitative test will be necessary to detect recent heat stress; if not, a qualitative test would be sufficient, peripheral blood mononuclear cells were chosen for this investigation because they can be isolated from a small sample (clinically acceptable) of blood. Following heat stress Western analysis and autoradiography of one- and two-dimensional electrophoresis samples demonstrated low levels of HSP 72 in unstressed cells. HSP 72 increased with heat stress, and remained elevated for up to 48 h. HSP 72 mRNA was detectable in small amounts in nonheat stressed cells. Heat stress increased HSP 72 mRNA 1 and 2 h after stress and remained elevated for 6 h. HSP 72 persists long enough to be potentially useful as a diagnostic probe of recent heat injury; however, a semi-quantitative assay will be necessary.


Electric dipole moment enhancement factor of thallium.
The goal of this work is to resolve the present controversy in the value of the electric dipole moment (EDM) enhancement factor of Tl. We carry out several calculations by different high-precision methods, study previously omitted corrections, as well as test our methodology on other, parity conserving, quantities. We find the EDM enhancement factor of Tl to be equal to -573(20). This value is 20% larger than the recently published result of Nataraj et al. [Phys. Rev. Lett. 106, 200403 (2011)], but agrees very well with several earlier results.


Drought Stress Enhances Up-Regulation of Anthocyanin Biosynthesis in Grapevine leafroll-associated virus 3-Infected in vitro Grapevine (Vitis vinifera) Leaves.
Reddish-purple coloration on the leaf blades and downward rolling of leaf margins are typical symptoms of grapevine leafroll disease (GLD) in red-fruited grapevine cultivars. These typical symptoms are attributed to the expression of genes encoding enzymes for anthocyanins synthesis, and the accumulation of flavonoids in diseased leaves. Drought has been proven to accelerate development of GLD symptoms in virus-infected leaves of grapevine. However, it is not known how drought affects GLD expression nor how anthocyanin biosynthesis in virus-infected leaves is altered. The present study used HPLC to determine the types and levels of anthocyanins, and applied reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze the expression of genes encoding enzymes for anthocyanin synthesis. Plantlets of Grapevine leafroll-associated virus 3 (GLRaV-3)-infected Vitis vinifera 'Cabernet Sauvignon' were grown in vitro under PEG-induced drought stress. HPLC found no anthocyanin-related peaks in the healthy plantlets with or without PEG-induced stress, while 11 peaks were detected in the infected plantlets with or without PEG-induced drought stress, but the peaks were significantly higher in infected drought-stressed plantlets. Increased accumulation of total anthocyanin compounds was related to the development of GLD symptoms in the infected plantlets under PEG stress. The highest level of up-regulated gene expression was found in GLRaV-3-infected leaves with PEG-induced drought stress. Analyses of variance and correlation of anthocyanin accumulation with related gene expression levels found that GLRaV-3-infection was the key factor in increased anthocyanin accumulation. This accumulation involved the up-regulation of two key genes, MYBA1 and UFGT, and their expression levels were further enhanced by drought stress.


Automatic Assessment of the 2-Minute Walk Distance for Remote Monitoring of People with Multiple Sclerosis.
The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes.


Aromatization by splanchnic tissue in men.
To measure the rate of aromatization that occurs in splanchnic tissue, four men with normal liver function were infused through an arm vein with [3H]androstenedione/[14C] estrone and four men were infused with [3H]testosterone/[14C] estradiol before indicated cardiac procedures. Catheters were placed under fluoroscopic control in the hepatic vein and descending aorta. Simultaneous blood samples were then obtained from the aorta and the hepatic vein after 90 and 120 min of infusion. The samples were analyzed for radioactivity after multiple chromatographic purification steps. The MCRs, overall aromatization (fraction of androgen infused measured as estrogen in arterial blood), splanchnic extractions, and splanchnic aromatization (fraction of androgen entering the splanchnic tissue which leaves as estrogen) were determined. The mean values for MCRs of androgens and estrogens and overall aromatization for androstenedione and testosterone were similar to those reported previously. The splanchnic extraction values of androstenedione, testosterone, estrone, and estradiol were 0.57 +/- 0.10 (+/- SE), 0.39 +/- 0.12, 0.60 +/- 0.09, and 0.64 +/- 0.18, respectively. The mean splanchnic aromatization of androstenedione to estrone was 0.00086 +/- 0.00072, and the mean splanchnic aromatization of testosterone to estradiol was 0.00059 +/- 0.00020. If one assumes that the splanchnic bed receives 20% of the cardiac output, then the splanchnic bed is responsible for less than 4% of the overall peripheral aromatization of androstenedione or testosterone.


Defective glial maturation in vanishing white matter disease.
Vanishing white matter (VWM) disease is a genetic leukoencephalopathy linked to mutations in the eukaryotic translation initiation factor 2B. It is a disease of infants, children, and adults who experience a slowly progressive neurologic deterioration with episodes of rapid clinical worsening triggered by stress and eventually leading to death. Characteristic neuropathologic findings include cystic degeneration of the white matter with scarce reactive gliosis, dysmorphic astrocytes, and paucity of myelin despite an increase in oligodendrocytic density. To assess whether a defective maturation of macroglia may be responsible for the feeble gliosis and lack of myelin, weinvestigated the maturation status of astrocytes and oligodendrocytes in the brains of 8 VWM patients, 4 patients with other white matter disorders and 6 age-matched controls with a combination of immunocytochemistry, histochemistry, scratch-wound assays, Western blot, and quantitative polymerase chain reaction. We observed increased proliferation and a defect in the maturation of VWM astrocytes. They show an anomalous composition of their intermediate filament network with predominance of the δ-isoform of the glial fibrillary acidic protein and an increase in the heat shock protein αB-crystallin, supporting the possibility that a deficiency in astrocyte function may contribute to the loss of white matter in VWM. We also demonstrated a significant increase in numbers of premyelinating oligodendrocyte progenitors in VWM, which may explain the coexistence of oligodendrocytosis and myelin paucity in the patients' white matter.


A simple and inexpensive quantitative technique for determining chemical sensitivity in Saccharomyces cerevisiae.
Chemical sensitivity, growth inhibition in response to a chemical, is a powerful phenotype that can reveal insight into diverse cellular processes. Chemical sensitivity assays are used in nearly every model system, however the yeast Saccharomyces cerevisiae provides a particularly powerful platform for discovery and mechanistic insight from chemical sensitivity assays. Here we describe a simple and inexpensive approach to determine chemical sensitivity quantitatively in yeast in the form of half maximal inhibitory concentration (IC50) using common laboratory equipment. We demonstrate the utility of this method using chemicals commonly used to monitor changes in membrane traffic. When compared to traditional agar-based plating methods, this method is more sensitive and can detect defects not apparent using other protocols. Additionally, this method reduces the experimental protocol from five days to 18 hours for the toxic amino acid canavanine. Furthermore, this method provides reliable results using lower amounts of chemicals. Finally, this method is easily adapted to additional chemicals as demonstrated with an engineered system that activates the spindle assembly checkpoint in response to rapamycin with differing efficiencies. This approach provides researchers with a cost-effective method to perform chemical genetic profiling without specialized equipment.


The real-life perception of efficacy, attitude, satisfaction and safety of vardenafil therapy (REPEAT): a prospective, non-interventional, observational study.
This study assessed the improvement in relationship quality, effectiveness and safety associated with vardenafil for the treatment of erectile dysfunction (ED). The study was conducted in 1433 centres across 21 countries and comprised a baseline patient visit and up to four follow-up visits during an observational period of 1 year. Relationship quality, happiness, satisfaction with vardenafil treatment, and safety and tolerability were assessed by physician interviews and patient and partner questionnaires. Overall, 7496 patients were enrolled in the study, of which 7430 were included in the safety analyses and 6470 in the effectiveness analyses. Relationship quality, assessed by a relationship questionnaire (partnerschaftsfragebogen [PFB]), was improved at last observation carried forward, compared with baseline, in both patients and partners and satisfaction with the effectiveness of vardenafil treatment was high. Vardenafil was well tolerated and adverse events were consistent with the known safety profile of phosphodiesterase type 5 inhibitors. These results confirm the well-established effectiveness and safety profiles of vardenafil. This study is the first to demonstrate improvements in relationship quality following vardenafil therapy, in both patients and partners, using the PFB questionnaire.


Functional insights into the mode of DNA and ligand binding of the TetR family regulator TylP from Streptomyces fradiae.
Tetracycline repressors (TetRs) modulate multidrug efflux pathways in several pathogenic bacteria. In Streptomyces, they additionally regulate secondary metabolic pathways like antibiotic production. For instance, in the antibiotic producer Streptomyces fradiae, a layered network of TetRs regulates the levels of the commercially important antibiotic tylosin, with TylP occupying the top of this cascading network. TetRs exist in two functional states, the DNA-bound and the ligand-bound form, which are allosterically regulated. Here, to develop deeper insights into the factors that govern allostery, the crystal structure of TylP was solved to a resolution of 2.3 Å. The structure revealed that TylP possesses several unique features; notably, it harbors a unique C-terminal helix-loop extension that spans the entire length of the structure. This anchor connects the DNA-binding domain (DBD) with the ligand-binding domain (LBD) via a mix of positively charged and hydrogen-bonding interactions. Supporting EMSA studies with a series of ΔC truncated versions show that a systematic deletion of this region results in complete loss of DNA binding. The structure additionally revealed that TylP is markedly different in the orientation of its DBD and LBD architecture and the dimeric geometry from its hypothesized Streptomyces homologue CprB, which is a γ-butyrolactone regulator. Rather, TylP is closer in structural design to macrolide-binding TetRs found in pathogens. Supporting molecular dynamic studies suggested that TylP binds a macrolide intermediate in the tylosin pathway. Collectively, the structure along with corroborating biochemical studies provided insights into the novel mode of regulation of TetRs in antibiotic-producing organisms.


Proteomic changes in the xylem sap of Brassica napus under cadmium stress and functional validation.
The xylem sap of vascular plants primarily transports water and mineral nutrients from the roots to the shoots and also transports heavy metals such as cadmium (Cd). Proteomic changes in xylem sap is an important mechanism for detoxifying Cd by plants. However, it is unclear how proteins in xylem sap respond to Cd. Here, we investigated the effects of Cd stress on the xylem sap proteome of Brassica napus using a label-free shotgun proteomic approach to elucidate plant response mechanisms to Cd toxicity. We identified and quantified 672 proteins; 67% were predicted to be secretory, and 11% (73 proteins) were unique to Cd-treated samples. Cd stress caused statistically significant and biologically relevant abundance changes in 28 xylem sap proteins. Among these proteins, the metabolic pathways that were most affected were related to cell wall modifications, stress/oxidoreductases, and lipid and protein metabolism. We functionally validated a plant defensin-like protein, BnPDFL, which belongs to the stress/oxidoreductase category, that was unique to the Cd-treated samples and played a positive role in Cd tolerance. Subcellular localization analysis revealed that BnPDFL is cell wall-localized. In vitro Cd-binding assays revealed that BnPDFL has Cd-chelating activity. BnPDFL heterologous overexpression significantly enhanced Cd tolerance in E. coli and Arabidopsis. Functional disruption of Arabidopsis plant defensin genes AtPDF2.3 and AtPDF2.2, which are mainly expressed in root vascular bundles, significantly decreased Cd tolerance. Several xylem sap proteins in Brassica napus are differentially induced in response to Cd treatment, and plant defensin plays a positive role in Cd tolerance.


Providing social support in a persuasive context: forms of social support reported by organ procurement coordinators.
Eighty-five organ procurement coordinators (OPCs) completed face-to-face interviews designed to elicit the emotional and instrumental social support strategies communicated to potential donor families throughout the request for deceased organ donation. OPCs identified six forms of emotional support and eight forms of instrumental support, with greater reported use of instrumental support strategies. In terms of instrumental support, OPCs most frequently ensured in-hospital comfort (61.2%) or met the nutritional needs of family members (51.8%). With respect to emotional support, OPCs most often expressed sympathy (31.8%) to families and provided support in the form of physical contact (27.1%) with family members. Identifying the forms of social support used by OPCs is a first step toward understanding the strategies that are more (or less) effective in achieving persuasive and support goals.


Chromosome aberrations in de novo acute myeloid leukemia patients in Kuwait.
Cytogenetic analysis was successfully performed at the time of diagnosis in 45 patients with de novo acute myeloid leukemia, including 10 children and 35 adults. In approximately 73% of AML patients (35 patients) clonal chromosome abnormalities were detected at the time of diagnosis. Twelve patients (22.8%) had apparently normal karyotypes. Recurring aberrations found in 22 of patients with abnormal karyotypes included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), trisomy 8, monosomy 7 and del(5q). The highest frequency of chromosome changes was observed in AML-M3. The occurrence of the classical cytogenetic abnormalities was not a ubiquitous phenomenon. In 11 patients previously not described miscellaneous clonal chromosomal abnormalities were detected. Clonal chromosomal abnormalities detected in AML have shown correlations between specific recurrent chromosomal abnormalities and clinico-biological characteristics of the patients, therefore have been repeatedly shown to constitute markers of diagnostic and prognostic significance. Moreover, ongoing cytogenetic analysis can identify new nonrandom chromosome aberrations in AML and contribute to the identification of novel genes involved in the development of cancer, which can lead to better understanding of the disease pathogenesis.


Shock signals and the development of stress-induced analgesia.
We report five experiments in which we investigated the effects of "feedback signals" on the pattern of hypoalgesia produced by inescapable shocks. A 5-s lights-out stimulus coincident with shock termination had no effect on the naltrexone-insensitive (nonopioid) hypoalgesia, which occurred after 10 inescapable shocks, but completely blocked the naltrexone-sensitive (opioid) hypoalgesia, which followed 100 inescapable shocks. The stimulus prevented the development of the opioid hypoalgesia rather than merely masking its measurement. This effect did not depend on the use of lights-out as the stimulus but did depend on the temporal relation between the stimulus and shock. Stimuli immediately preceding or simultaneous with shock had no effect. Surprisingly, stimuli randomly related to shock also blocked the opioid hypoalgesia. Simultaneous measurement of both hypoalgesia and fear conditioned to contextual cues revealed that the level of fear did not predict the blockade of hypoalgesia. Different backward groups received different temporal gaps between shock termination and the signal. An interval between 2.5 s and 7.5 s eliminated the effect of the signal on fear, but 12.5-17.5 s were required to eliminate the effect of the signal on hypoalgesia. The opioid hypoalgesia blocking power of the random stimulus was entirely attributable to those stimuli occurring within 15 s of the termination of the preceding shock. The implications of these results for the explanation of stimulus feedback effects and for stress-induced analgesia are discussed.


A pitfall on postoperative radiographs in dogs after tibial plateau leveling osteotomy.
To identify the cause of an occasional radiolucent line in the tibia on postoperative radiographs after tibial plateau leveling osteotomy (TPLO) in dogs. Retrospective case series and ex vivo experiment. Dogs (n = 80; 87 stifles) with cranial cruciate ligament (CCL) rupture that had TPLO; and 4 canine tibia specimens. Medical records (2007-2010) and radiographs of dogs that had TPLO were reviewed and examined for presence of a radiolucent line on postoperative radiographs. The TPLO procedure was reproduced ex vivo to determine the origin of this line by use of metallic wires to identify bone contours. A curvilinear radiolucent line was visible in 14 (16%) tibias and was 5.4 times more likely to be visible with lateral misalignment of the tibial diaphysis relative to the plateau and 2.6 times more likely visible on caudocranial radiographs with the stifle in outward rotation. Fracture complication rate was higher in dogs with this radiolucent line (P = .02) and with lateral misalignment of the tibial diaphysis relative to the plateau (risk ratio, 3.8). The line could be reproduced ex vivo and caused by superimposition of the craniomedial border of osteotomy with the tibial plateau. The radiolucent line was a spurious fracture line created by the medial margin of the tibial osteotomy and confounding factors such as tibial misalignment may explain the apparently associated higher complication rate.


The case of the missing secretary: DHEW's failed efforts to create a Cabinet secretary of health.
In response to professional and political pressures in 1967, an incident occurred at the Department of Health, Education, and Welfare that illustrates the delicacy and complexity of the legislative process. In an effort to bypass interest group influences, the undersecretary of the Department undertook a maneuver that backfired and frustrated an opportunity that might have resulted in the establishment of a Cabinet office of Health. In addition to demonstrating the sensitivity of the legislative process, and the dangers of overconfidence in dealing with the process, the events also offer moral guidance: too stubborn, idealistic convictions of good people, however well intentioned the actions, may serve to defeat the desired ends.


Natural history of patients with tuberous sclerosis complex related renal angiomyolipoma.
To examine temporal relationships between tuberous sclerosis complex (TSC) and renal angiomyolipoma diagnosis and outcomes, treatment, and healthcare utilization. Administrative data from the MarketScan Commercial Database was used to select TSC-related renal angiomyolipoma patients during 1 January 2000-31 March 2013. Patients were followed until the earliest of inpatient death or end of enrollment or study. Occurrence of kidney-related outcomes, kidney-related procedures, and all-cause healthcare utilization and time to occurrence were reported. Kaplan-Meier curves were used to display the unadjusted distribution of time to outcome. A total of 605 patients were selected (<18 years N = 225; ≥18 years N = 380). Mean time from TSC to renal angiomyolipoma diagnosis was 25.7 months in younger and 16.9 months in older patients. Patients ≥18 years had higher rates of chronic kidney disease (CKD), hematuria, kidney failure, embolization (EMB), and partial and complete nephrectomy compared to patients <18 years (all p < .05). Mean time from TSC-related renal angiomyolipoma diagnosis to CKD, hematuria, kidney failure, EMB, first emergency room and inpatient visits was shorter in older compared to younger patients (all p < .05). Probability of developing CKD was approximately 0.8 and 0.95 within 3 years in younger and older patients, respectively. Patients with TSC-related renal angiomyolipoma had high rates of kidney-related outcomes and procedures. These events sometimes preceded the angiomyolipoma diagnosis. A key study limitation was that due to the small sample size, results may have been biased by outliers. Research is needed to determine whether earlier angiomyolipoma diagnosis can impact occurrence of events and reduce healthcare utilization.


Treatment of osteochondral defects of the talus.
This review article provides a current concepts overview of osteochondral defects of the talus, with special emphasis on treatment options, their indications and future developments. Osteochondral defects of the talar dome are mostly caused by a traumatic event. They may lead to deep ankle pain on weight-bearing, prolonged swelling, diminished range of motion and synovitis. Plain radiographs may disclose the lesion. For further diagnostic evaluation, computed tomography (CT) and magnetic resonance imaging (MRI) have demonstrated similar accuracy. Computed tomography is preferred for preoperative planning. Treatment options are diverse and up to the present there is no consensus. Based on the current literature, we present a treatment algorithm that is mainly guided by the size of the lesion. Asymptomatic or low-symptomatic lesions are treated nonoperatively. The primary surgical treatment of defects up to 15 mm in diameter consists of arthroscopic debridement and bone marrow stimulation. For large cystic talar lesions, retrograde drilling combined with a bone graft is an important alternative. In adolescents or in (sub)acute situations, in which the fragment is 15 mm or larger, fixation of the fragment is preferred. Osteochondral autograft transfer and autologous chondrocyte implantation (ACI), with or without a cancellous bone graft, are recommended for secondary cases as well as large lesions.


In vitro interaction of the IHF-like proteins Acinetobacter junii and Proteus vulgaris with ihf sites.
The ability of the IHF-like proteins of Acinetobacter junii and Proteus vulgaris to interact with the H' attP and pR' ihf sites of lambda DNA was investigated. IHF from A. junii and P. vulgaris was found to bind the examined ihf sites in a way similar to IHF from Escherichia coli as shown by gel mobility shift DNA binding assays and footprinting analysis. The three IHF proteins bound to the pR' ihf site that overlaps the-35 region of that promoter and in vitro repression of transcription by each IHF was observed. These results confirm that IHF-like proteins from Gram-negative bacteria can recognize the same specific DNA sequences and appear to be important in regulation of transcription.


Etiology of pediatric lower respiratory tract infections in South Korea.
Lower respiratory tract infections (LRTIs) are an important cause of death and bacterial pneumonia is one of the most common causes of mortality in South Korea, but there is little data evaluating the epidemiology of pediatric LRTI in primary care clinics. We evaluated 1,497 pediatric LRTI cases in a primary care clinic over a two-year period from 2015 to 16 for clinical and radiological signs combined with PCR for pathogen detection. In addition, a 1,837 vaccine cohort in the clinic from 2014 to 16 was analyzed separately. Fifty-two percent of cases presented with fever and 15% of 1,423 X-rayed cases had positive pneumonia findings with the grade of fever correlating positively with the proportion of cases with positive chest findings. Bacterial identification was possible for 1,376 cases with Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae most common. A higher proportion of 13-valent pneumococcal conjugate vaccinated cases had positive pneumonia findings than 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) vaccinated cases, although similar proportions for each PCV had confirmed bacterial infections. PHiD-CV vaccinated cases with positive pneumonia findings had proportionally more single S. pneumoniae infections but less co-infections and less cases with H. influenzae infection. The proportions of confirmed bacterial infections in LRTI cases observed in this pediatric primary care setting in South Korea is very high, with co-infections most common. S. pneumoniae and H. influenzae are the most common as expected but this data also highlights M. pneumoniae as an additional important cause of LRTI in primary pediatric care in Korea.


Chondrocytes in the endochondral growth cartilage are not hypoxic.
From an anatomic viewpoint, the blood supply to chondrocytes in the growth cartilage is limited. As a result, it has been suggested that these cells are hypoxic and that this condition regulates chondrocyte maturation and cartilage mineralization. We examined the state of chondrocyte oxygenation in the chick growth plate using a hypoxia-sensing drug, EF5. EF5 is a pentafluorinated derivative of the 2-nitroimidazole, etanidazole, that is metabolically reduced by oxygen-inhibitable nitroreductase(s). Reduced EF5 covalently forms adducts with cellular macromolecules that can be visualized with a highly specific fluorochrome-conjugated monoclonal antibody. When EF5 was injected into chicks and tissues were subsequently examined by immunohistochemical techniques, chondrocytes in articular, proliferating, and hypertrophic cartilage exhibited a low level of fluorescence-detectable binding, suggesting the absence of significant hypoxia. We confirmed that the results were not confounded by tissue-specific factors related to low-chondrocyte nitroreductase activity or problems from drug diffusion into cartilage. Using in vitro systems, we showed that, under conditions of imposed hypoxia, EF5 diffused into the tissue and was bound to chondrocytes. With the use of an in vivo model in which hypoxia was artificially induced by death, chick chondrocytes were found to bind the drug. Although the EF5-binding method is not optimally suited for determining the precise oxygen partial pressure in heterogeneous tissues, such as the growth plate, we concluded that chick chondrocytes are not oxygen deficient in vivo.


Automated image processing method to quantify rotating detonation wave behavior.
An image processing technique is developed to automatically determine both average and instantaneous detonation wave properties within a rotating detonation rocket engine (RDRE) using high-speed imaging. This method entails segmenting the imaged RDRE annulus into 200 azimuthal bins and tracking integrated pixel intensity in each bin. By combining individual pixel intensity temporal histories across the azimuthal bins, this provides what is termed a detonation surface that visualizes the propagation of the individual detonation fronts azimuthally around the annulus. Average detonation modal properties including wave speed Ūwv, operational frequency fdet, and the number of waves m are determined automatically through a two-dimensional Fourier analysis of the detonation surface data. Also, instantaneous wave speeds Uwv for each individual detonation are determined by taking the numerical derivative of each waves' angular position temporal history from the detonation surface. This provides useful insight into wave-to-wave variability for an operating condition, as well as denoting modal transitions and mode stability. For the flow conditions investigated, the number of waves ranges from 2 to 14, with Ūwv varying between 900 and 1700 m/s, corresponding to 33%-71% of the ideal Chapman-Jouguet detonation speed; these modes exhibit an operational frequency of 20-45 kHz, with an average of 40 kHz. Overall, these measurements advance the understanding of RDRE's and may lead to performance gains above those achievable from constant pressure engines.


Control effects of p(epsilon) and pH on the generation and stability of chlorine dioxide.
A new method, without assistance of activity ratio diagram, was applied to construct the p(epsilon)-pH diagrams for chlorine system. The optimal pH range for generation of C1O2 by contacting Cl2 (g) directly with ClO2- solution is within pH 1.35-1.94, particularly within pH 1.35-4.00 only if minimizing the formation of Cl2. It is unachievable to synthesize pure ClO2 from the reaction of Cl2 and ClO2- . Conversely, ClO2 may be present a variation of stability in different waters owing to the changed p(epsilon) and pH. ClO2 could be relatively stable if not disproportionate into ClO3-, coexisting with ClO2- (p(epsilon) 17.63 and pH > 9.68), Cl2(pH < or = 0.92) or Cl- (pH 0.92-9.68). When chlorine system has already reached the ultimate equilibria, ClO2 is a stable species in strongly acid media. As the acidity decreases, ClO2 disproportionates into ClO3- and Cl2. Aqueous ClO2 is unstable within the normal pH range. This work initially, theoretically elucidates the generation and stability of ClO2 by way of the p(epsilon)-pH diagrams.


Pseudotargeted Metabolomic Fingerprinting and Deep Learning for Identification and Visualization of Common Pathogens.
Matrix-assisted laser desorption/ionization time-of-flight mass (MALDI-TOF) spectrometry fingerprinting has reduced turnaround times, costs, and labor as conventional procedures in various laboratories. However, some species strains with high genetic correlation have not been directly distinguished using conventional standard procedures. Metabolomes can identify these strains by amplifying the minor differences because they are directly related to the phenotype. The pseudotargeted metabolomics method has the advantages of both non-targeted and targeted metabolomics. It can provide a new semi-quantitative fingerprinting with high coverage. We combined this pseudotargeted metabolomic fingerprinting with deep learning technology for the identification and visualization of the pathogen. A variational autoencoder framework was performed to identify and classify pathogenic bacteria and achieve their visualization, with prediction accuracy exceeding 99%. Therefore, this technology will be a powerful tool for rapidly and accurately identifying pathogens.


Early dutasteride monotherapy in men with detectable serum prostate-specific antigen levels following radical prostatectomy: A prospective trial.
To investigate the effects of early administration of dutasteride in patients with detectable serum prostate-specific antigen (PSA) levels after radical prostatectomy (RP). A prospective open-label study, with a cumulative analysis of asymptomatic increase in PSA following RP, was conducted from January 2005 to December 2013. An early increase in PSA level was defined as detectable serum PSA level> 0.04 ng/mL. Patients with PSA level>0.04 ng/mL were treated with dutasteride 0.5 mg daily. Serum PSA level and biochemical recurrence (BCR) were monitored. We divided the patients into 2 groups based on the serum PSA response after dutasteride treatment. Eighty patients were included in the study. At the median follow-up of 51.8 months, 56 patients (70.0%) showed a decrease of greater than 10% in serum PSA level, and 24 showed increased PSA levels. Twelve of the 56 patients with PSA response showed subsequently increased PSA. Intergroup differences in preoperative PSA levels, PSA nadir levels, and Gleason score of 6 or less were significant (p=0.028, p=0.030, and p=0.035, respectively). A multivariate analysis revealed that Gleason score of 6 or less (p=0.018) and PSA nadir levels (p=0.011) were predictive factors for PSA response after early dutasteride treatment in men with increased PSA levels following RP. Early monotherapy of dutasteride showed a decline in serum PSA levels in men with lower nadir PSA levels, and a Gleason score 6, when the serum PSA was detected after RP.


Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1.
Trigeminal nuclei and the dorsal spinal cord are first-order relay stations for processing somatic sensory information such as touch, pain, and temperature. The origins and development of these neurons are poorly understood. Here we show that relay somatic sensory neurons and D2/D4 dorsal interneurons likely derive from Mash1-positive neural precursors, and depend on two related homeobox genes, Rnx and Tlx-1, for proper formation. Rnx and Tlx-1 maintain expression of Drg11, a homeobox gene critical for the development of pain circuitry, and are essential for the ingrowth of trkA+ nociceptive/thermoceptive sensory afferents to their central targets. We showed previously that Rnx is necessary for proper formation of the nucleus of solitary tract, the target for visceral sensory afferents. Together, our studies demonstrate a central role for Rnx and Tlx-1 in the development of two major classes of relay sensory neurons, somatic and visceral.


Risk factors and visual fatigue of baggage X-ray security screeners: a structural equation modelling analysis.
This study identified the risk factors influencing visual fatigue in baggage X-ray security screeners and estimated the strength of correlations between those factors and visual fatigue using structural equation modelling approach. Two hundred and five X-ray security screeners participated in a questionnaire survey. The result showed that satisfaction with the VDT's physical features and the work environment conditions were negatively correlated with the intensity of visual fatigue, whereas job stress and job burnout had direct positive influences. The path coefficient between the image quality of VDT and visual fatigue was not significant. The total effects of job burnout, job stress, the VDT's physical features and the work environment conditions on visual fatigue were 0.471, 0.469, -0.268 and -0.251 respectively. These findings indicated that both extrinsic factors relating to VDT and workplace environment and psychological factors including job burnout and job stress should be considered in the workplace design and work organisation of security screening tasks to reduce screeners' visual fatigue. Practitioner Summary: This study identified the risk factors influencing visual fatigue in baggage X-ray security screeners and estimated the strength of correlations between those factors and visual fatigue. The findings were of great importance to the workplace design and the work organisation of security screening tasks to reduce screeners' visual fatigue.


Vascular foramina of navicular bone: a morphometric study.
The navicular bone is supplied by more than one artery. The knowledge about the vascular foramina is important to understand the pathogenesis and management of navicular fractures. The objective of the present study is to analyze the morphology and morphometry of vascular foramina of dried human navicular bone in Indian population. The study was carried out by using 100 navicular bones (50 right and 50 left) collected from our institute and other medical institutes in and around Puducherry. The bones were macroscopically studied for vascular foramina with respect to its location, number, size, and shape. The data collected were statistically analyzed. The vascular foramina were present on dorsal, plantar, medial, and lateral surfaces of navicular bone. Kruskal-Wallis test followed by series of Mann-Whitney test for post hoc analysis showed the number of nutrient foramina observed on dorsal surface were significantly greater than those observed on the plantar (U=2,755, P=0.001), medial (U=43, P=0.001), and lateral (U=626.5, P=0.001) surfaces of the navicle. About 97.6% of foramina were circular and 2.5% were oval in appearance. About 96.7% of vascular foramina were <1 mm in size and 3.3% were ≥1 mm in size. Spearman's rank correlation coefficient done showed a strong, positive correlation between vascular foramina of <1 mm size and circular shape, which was statistically significant (rs =0.981, P=0.001). We believe the present study has provided additional information on the vascular foramina of navicular bone and useful to surgeons in foot surgeries.


[Schwannoma of the endothoracic phrenic nerve. General review apropos of a case].
A new case of schwannoma of the intrathoracic phrenic nerve in a 72-year old woman is reported. A review of the literature shows that this tumour is quite exceptional and that its clinical signs are few and non-specific. The most informative examinations, including MRI, merely provide arguments in favour of the diagnosis prior to surgery. The problems of preservation and repair of the phrenic nerve are discussed in the light of new microsurgical techniques. Our knowledge concerning malignant schwannoma and its recurrent forms is updated.


Ammonium assimilation by Candida albicans and other yeasts: a 13N isotope study.
Nuclear magnetic resonance spectra of cultures of Candida albicans incubated in the presence of 15N-labelled ammonium demonstrated that glutamine and glutamate were the only initial products of ammonium assimilation. The nature of the route of assimilation in the yeasts Candida albicans, Saccharomyces cerevisiae, and Candida tropicalis was further examined by the use of the short-lived isotope 13N. [13N]ammonium was generated in the reaction 16O(p,alpha)13N, induced by proton bombardment of water in tandem accelerator. High-pressure liquid chromatography was used to separate and identify the products of assimilation, and radioactivity was detected and corrected for decay, using a computer-linked NaI scintillation detector. In the three yeasts studied, the labelled ammonium was assimilated into the acid-extractable fraction of cell suspensions within 1 min, and over 75% was converted to glutamine and glutamate. Subsequent to exhaustion of the labelled ammonium, the stoichiometry of the distribution of radiolabel was consistent with a net transfer of radiolabel from glutamine to glutamate, confirming the operation of glutamate synthase (EC 18.104.22.168) in these yeasts. Initial assimilation of label was mostly into glutamine (at a maximal rate within 10 s in C. albicans), whereas accumulation in glutamate did not occur at maximal rate until more than 70% of the labelled ammonium had been assimilated (between 30 and 60 s in C. albicans). We conclude that the glutamine synthetase-glutamate synthase pathway is the major route of ammonium assimilation in C. albicans and also in nitrogen-starved cultures of S. cerevisiae and C. tropicalis.


Chemosis as complication in transconjunctival approach for orbital trauma.
The aim of this report was to discuss a complication resulting from a transconjunctival approach to treating an orbital fracture. A 30-year-old male patient presented with a fracture to the zygomatic orbital complex. He was treated with transconjunctival conventional surgical treatment. Two days after surgical treatment, the patient presented with secondary chemosis which was initially slight and then subsequently worsened. The clinical situation was managed with topical and systemic corticosteroids and resolved within one postoperative month. Two-year follow-up showed ptosis of the upper eyelid and limited infraversion in the affected eye. This unusual complication associated with an orbital trauma was resolved with minor functional alterations, although the consequences observed after 2 years were not completely satisfactory.


Acute Calcific Tendonitis of the Longus Colli.
Acute calcific tendonitis of the longus colli (ACTLC) is an aseptic inflammatory response to deposition of calcium in the longus colli muscle tendons. Although reports in the literature are scarce, ACTLC likely represents an underreported disease process that routinely goes misdiagnosed. We report a case of ACTLC and provide a brief review of the literature. A 45-year-old otherwise healthy female presented with a 3-day history of progressive neck pain, decreased neck mobility, and odynophagia. She exhibited tenderness over the right posterolateral neck with limited neck flexion and rotation. Flexible fiber-optic laryngoscopy revealed moderate posterior pharyngeal wall edema extending from the palatal-pharyngeal sphincter down to the level of the epiglottis. A computed tomography (CT) scan of the neck with contrast revealed an amorphous calcification in the longus colli muscle and a prevertebral fluid collection without rim enhancement. A diagnosis of ACTLC was presumed. The patient was successfully managed with nonsteroidal antiinflammatory drugs, corticosteroids, and antibiotics and reported complete resolution of symptoms on follow-up. The clinical presentation and laboratory findings of ACTLC are nonspecific; however, a CT scan revealing a calcific deposition in the retropharyngeal space confirms the diagnosis. Spontaneous resolution during the course of several weeks warrants conservative treatment with analgesia and antiinflammatory medications. Awareness of ACTLC must be increased to avoid diagnostic errors and prevent unnecessary medical interventions.


Relation of serum total antioxidant status with metabolic risk factors in Korean adults.
The purpose of the present study was to examine the relation of total antioxidant status (TAS) to metabolic risk factors in Korean adults. Anthropometric measures, blood pressure, serum lipids and fasting glucose were determined in 406 men and women. TAS was measured by using commercially available Randox kit. Serum TAS was significantly positively correlated with body weight (p=0.004), body mass index (BMI) (p=0.033), waist circumference (p=0.017), total cholesterol (p=0.038) and triglyceride (TG) (p<0.001). The mean TAS of hypertriglyceridemic subjects (TG >/=150 mg/dl) was significantly higher than that of subjects whose TG was lower than 150 mg/dl (p=0.001). When central obesity, TG, high density lipoprotein cholesterol, fasting glucose and blood pressure were considered as metabolic risk factors, TAS was shown to be elevated with increased number of metabolic risk factors (p=0.004). The positive association between TAS and a number of metabolic risk factors suggests that increased TAS may not always indicate one's healthier condition. In order to help understand TAS as a marker of total antioxidant capacity in humans with various metabolic conditions, it is needed to clarify the factors affecting TAS in relation to changes in metabolic risk factors.


'Always listen more and talk less'.
Gwen Moulster devoted her 40-year nursing career to improving the care of adults and children with a learning disability, with roles including clinical nurse specialist, lead nurse, and associate director of nursing. Last year she was awarded an OBE for services to nursing and people with a learning disability, and was part of a team that won the learning disability nursing award at the RCNi Nurse Awards 2016. She retired from the NHS last year and now works as an independent consultant nurse and honorary teaching fellow at Kingston University.


Physical risk factors identification based on body sensor network combined to videotaping.
The aim of this study was to perform an ergonomic analysis of a material handling task by combining a subtask video analysis and a RULA computation, implemented continuously through a motion capture system combining inertial sensors and electrogoniometers. Five workers participated to the experiment. Seven inertial measurement units, placed on the worker's upper body (pelvis, thorax, head, arms, forearms), were implemented through a biomechanical model of the upper body to continuously provide trunk, neck, shoulder and elbow joint angles. Wrist joint angles were derived from electrogoniometers synchronized with the inertial measurement system. Worker's activity was simultaneously recorded using video. During post-processing, joint angles were used as inputs to a computationally implemented ergonomic evaluation based on the RULA method. Consequently a RULA score was calculated at each time step to characterize the risk of exposure of the upper body (right and left sides). Local risk scores were also computed to identify the anatomical origin of the exposure. Moreover, the video-recorded work activity was time-studied in order to classify and quantify all subtasks involved into the task. Results showed that mean RULA scores were at high risk for all participants (6 and 6.2 for right and left sides respectively). A temporal analysis demonstrated that workers spent most part of the work time at a RULA score of 7 (right: 49.19 ± 35.27%; left: 55.5 ± 29.69%). Mean local scores revealed that most exposed joints during the task were elbows, lower arms, wrists and hands. Elbows and lower arms were indeed at a high level of risk during the total time of a work cycle (100% for right and left sides). Wrist and hands were also exposed to a risky level for much of the period of work (right: 82.13 ± 7.46%; left: 77.85 ± 12.46%). Concerning the subtask analysis, subtasks called 'snow thrower', 'opening the vacuum sealer', 'cleaning' and 'storing' have been identified as the most awkward for right and left sides given mean RULA scores and percentages of time spent at risky levels. Results analysis permitted to suggest ergonomic recommendations for the redesign of the workstation. Contributions of the proposed innovative system dedicated to physical ergonomic assessment are further discussed.


Community blood supply model: development of a new model to assess the safety, sufficiency, and cost of the blood supply.
Through a combination of predonation donor screening and donated unit testing, the blood supply is safer than ever. However, as a result of increasingly stringent screening measures, one of the greatest threats may be an insufficient supply. The balance between safety and adequacy of the blood supply has not received enough attention. The authors developed a model to allow for empirical investigation of the determinants of a safe and sufficient supply. The model is a cohort simulation of allogeneic whole-blood donation, with the population of presenting donors stratified into 8 age and gender groups because the probability of donor and donation deferral varies by these characteristics. Parameters are estimated from year 2000 Blood Centers of Pacific (BCP) data. The model includes cost parameters, which were estimated using BCP expenditure data. The main outcomes are the number of transfusable units of blood and the unit cost of procurement. The model tracks the production of a supply of blood, highlighting the influence of demographic characteristics, predonation deferral, underweight collection of blood units, and associated costs. The authors sought to establish model validity by showing that modeled results closely mimic the outcomes and costs observed by blood bank administrators. The model was developed to evaluate blood safety and policy decisions; it can be used to assess the impact of predonation deferrals, such as expanded European travel deferral for variant Creutzfeldt-Jakob disease, or the impact of new testing strategies, such as nucleic acid testing for West Nile virus.


Timing interventions in relation to temporomandibular joint closed lock duration: a systematic review of 'locking duration'.
Temporomandibular joint (TMJ) 'closed lock' (CL) is a clinical condition causing TMJ pain and limited mouth opening (painful locking) that is mostly attributed to disc displacement without reduction (DDwoR), or less commonly to anchored disc phenomenon (ADP). Both conditions are described clinically as CL that can be 'acute' or 'chronic' depending on the duration of locking. There is, however, no consensus about the duration of locking that defines the acute state and its effect on the success of interventions. This review paper, therefore, aims to provide: (i) a narrative review of the pathophysiological need for early intervention in DDwoR and the clinical implications of acute/chronic CL stages on the management pathway; (ii) a systematic review investigating the effects of locking duration on the success of interventions for CL management. Electronic and manual searches until mid-August 2013 were conducted for English-language studies of any design investigating the effects of non-surgical and surgical interventions for acute or chronic CL (DDwoR or ADP). A total of 626 records were identified, and 113 studies were included. Data extraction and quality assessment were completed for all included studies. Included studies were, however, heterogeneous and mostly of poor-quality leading to contradictory and inconsistent evidence on the effect of the duration of locking on treatment outcomes. Future high-quality trials investigating the effect of CL duration on treatment outcome are needed. At present, early intervention by 'unlock' mandibular manipulation seems to be the most practical and realistic approach that can be attempted first in every CL patient as an initial diagnostic/therapeutic approach.


Enkephalinase inhibition and precursor amino acid loading improves inpatient treatment of alcohol and polydrug abusers: double-blind placebo-controlled study of the nutritional adjunct SAAVE.
We investigated the effects of the amino acid and vitamin mixture SAAVE in inpatient, chemically-dependent subjects to evaluate the role of neurotransmitters in facilitating recovery and adjustment to a detoxified, sober state. SAAVE is formulated from amino acids that are precursors for neurotransmitters and neuromodulators thought to be involved in alcohol and drug seeking behavior. In a double-blind, placebo-controlled, randomized study of 62 alcoholics and polydrug abusers, SAAVE patients had a significantly reduced stress response as measured by the skin conductance level (SCL), and significantly improved Physical Scores and BESS Scores (behavioral, emotional, social and spiritual). After detoxification there was a six-fold decrease in AMA rates when comparing SAAVE vs. placebo groups. In this inpatient treatment experience SAAVE facilitated the rate of recovery and allowed patients to respond more fully and more quickly to the behavioral goals of the program, for example as measured by the BESS Score. The use of SAAVE to achieve enkephalinase inhibition and precursor amino acid loading in the acute inpatient treatment environment provides the practitioner with the potential ability to restore the neurochemical changes inherent to alcoholism and drug abuse. These findings increase our understanding of the clinically relevant neurobiological mechanisms which underlie compulsive disease.


Correlation of humoral immunity to Lewis blood group antigens with renal transplant rejection.
Recent studies suggest that the Lewis blood group antigens are important for human renal transplantation. A possible mechanism by which Lewis blood group incompatibility could influence allograft rejection was investigated by measuring Lewis antibodies in sera from renal transplant recipients and appropriate controls using conventional hemagglutination and a sensitive and specific kinetic enzyme-linked immunosorbent assay (k-ELISA). The two methods yielded identical results with 14 positive control sera known to contain Lewis antibodies and with 43 sera from negative controls. Antibody was not detected in 16 Lewis-positive transplant patients. However, antibody was detected by k-ELISA in 4/11 Lewis-negative transplant candidates and in 8/8 Lewis-negative recipients of Lewis-incompatible grafts. All 8 grafts were rejected. The one Lewis-negative recipient of a Lewis-negative graft did not develop Lewis antibody nor reject his graft. Of the 12 renal patients in whom antibody was detected by k-ELISA, in only 4 was antibody also demonstrable by hemagglutination. These results indicate that hemagglutination may not be sensitive enough for antibody detection and that Lewis antibodies may play a role in renal allograft rejection.


Intracellular transport and compartmentation of phosphate in plants.
Phosphate (Pi) is an essential macronutrient with structural and metabolic roles within every compartment of the plant cell. Intracellular Pi transporters direct Pi to each organelle and also control its exchange between subcellular compartments thereby providing the means to coordinate compartmented metabolic processes, including glycolysis, photosynthesis, and respiration. In this review we summarize recent advances in the identification and functional analysis of Pi transporters that localize to vacuoles, chloroplasts, non-photosynthetic plastids, mitochondria, and the Golgi apparatus. Electrical potentials across intracellular membranes and the pH of subcellular environments will also be highlighted as key factors influencing the energetics of Pi transport, and therefore pose limits for Pi compartmentation.


Hypothalamic apelin/reactive oxygen species signaling controls hepatic glucose metabolism in the onset of diabetes.
We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia. We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vector-mediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. INNOVATION/CONCLUSION: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes.


Care and three-year outcomes of children with Benign Epilepsy with Centro-Temporal Spikes in England.
Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients' risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. We retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. Across ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6-8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2-16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2-12%). In this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring.


Effects of infectious bronchitis virus (Arkansas strain) on laying chickens.
Seventy-seven-week-old white leghorn layers were inoculated intraocularly with the Arkansas strain of infectious bronchitis virus (AIBV) to study the effects of the virus on egg production and on antibody response of the birds. Infected hens laid fewer eggs than the controls, and those eggs weighed less than eggs laid by controls. Further, the shell quality and internal quality of eggs laid by infected birds were inferior. The serum hemagglutination-inhibition (HI) titers of infected birds increased continuously through 4 weeks postinfection; serum HI titers of the controls were negligible.


From pandemic to endemic: Spatial-temporal patterns of influenza-like illness incidence in a Swiss canton, 1918-1924.
In pandemics, past and present, there is no textbook definition of when a pandemic is over, and how and when exactly a respiratory virus transitions from pandemic to endemic spread. In this paper we have compared the 1918/19 influenza pandemic and the subsequent spread of seasonal flu until 1924. We analysed 14,125 reports of newly stated 32,198 influenza-like illnesses from the Swiss canton of Bern. We analysed the temporal and spatial spread at the level of 497 municipalities, 9 regions, and the entire canton. We calculated incidence rates per 1000 inhabitants of newly registered cases per calendar week. Further, we illustrated the incidences of each municipality for each wave (first wave in summer 1918, second wave in fall/winter 1918/19, the strong later wave in early 1920, as well as the two seasonal waves in 1922 and 1924) on a choropleth map. We performed a spatial hotspot analysis to identify spatial clusters in each wave, using the Gi* statistic. Furthermore, we applied a robust negative binomial regression to estimate the association between selected explanatory variables and incidence on the ecological level. We show that the pandemic transitioned to endemic spread in several waves (including another strong wave in February 1920) with lower incidence and rather local spread until 1924 at least. At the municipality and regional levels, there were different patterns of spread both between pandemic and seasonal waves. In the first pandemic wave in summer 1918 the probability of higher incidence was increased in municipalities with a higher proportion of factories (OR 2.60, 95%CI 1.42-4.96), as well as in municipalities that had access to a railway station (OR 1.50, 95%CI 1.16-1.96). In contrast, the strong fall/winter wave 1918 was very widespread throughout the canton. In general, municipalities at higher altitude showed lower incidence. Our study adds to the sparse literature on incidence in the 1918/19 pandemic and subsequent years. Before Covid-19, the last pandemic that occurred in several waves and then became endemic was the 1918-19 pandemic. Such scenarios from the past can inform pandemic planning and preparedness in future outbreaks.


Geographical variation in life-history traits suggests an environmental-dependent trade-off between juvenile growth rate and adult lifespan in a moth.
Life-history theory predicts a trade-off between the juvenile growth rate and adult traits related to survival. However, this hypothesized negative correlation is difficult to test robustly because many trade-offs are mild, and environmental variables, such as changes in nutrient availability, can ameliorate the trade-off or make it more pronounced. Thus, it is reasonable to expect that the expression of the trade-off can be condition-dependent. In the present study, we first examined the pre-adult life-history traits of the cotton bollworm, Helicoverpa armigera, collected from northern, central, and southern China at different temperatures. We found that the northern China population has a significantly shorter pre-adult developmental time and higher growth rate than the southern China population as a result of adaptation to the decreased seasonal length. Then, we tested for a trade-off between the juvenile growth rate and adult lifespan in different temperature and nutrient conditions. We found a negative relationship between juvenile growth rate and adult lifespan under starvation or desiccation conditions; however, a continuous supply of sugar can diminish or obviate the apparent negative relationship, in which the adult lifespan did not show a significant difference in most of the comparisons. These results suggested a resource-mediated trade-off may exist between juvenile growth rate and adult lifespan. However, the adult size may have some positive effect on the lifespan under starvation and desiccation conditions, which may affect the expression of trade-off.


[A meta-analysis of the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer].
To evaluate whether there is a difference in the curative effect of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer (NSCLC). The databases PudMed, CENTRAL, and Chinese biomedical database were retrieved by using the key words "non-small cell lung cancer" or "carcinoma, non-small cell lung" so as to search the materials about the randomized controlled clinical trials that had compared the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance NSCLC. A meta-analysis was conducted. Eighteen documents about randomized controlled clinical trials, including 6478 patients, from the retrieved 3531 documents accorded to the demand of enrollment. The overall response rates of the carboplatin-based and cisplatin-based chemotherapeutic groups were both 27% (RR = 0.93, 95% CI = 0.86 approximately 1.01, P = 0.10). Neither funnel plot nor rank correlation test regarding response rate indicated the existence of publication bias (chi(2) = 18.63, P = 0.63). The 0ne-year survival rate of the carboplatin-based regimen group was 36%, not significantly different from that of the cisplatin-based regimen group (35%, RR = 1.04, 95% CI = 0.93 - 1.17, P = 0.5). Sensitive analysis confirmed the non-existence of differences in the overall response rate and one-year survival rate between these 2 groups. The curative effects of the carboplatin-based and cisplatin-based chemotherapeutic regimens are similar. The choice of carboplatin or cisplatin depends on the toxicity of the drugs and the patients' tolerance.


Factors associated with postprandial lipemia and apolipoprotein A-V levels in individuals with familial combined hyperlipidemia.
Alterations in postprandial metabolism have been described in familial combined hyperlipidemia (FCH); however, their underlying mechanisms are not well characterized. We aimed to identify factors related to the magnitude of postprandial lipemia and apolipoprotein (apo) A-V levels in subjects with FCH. FCH cases (n = 99) were studied using a standardized meal test. Abdominal obesity was assessed using the waist to hip ratio (WHR). A linear regression model was performed to investigate the variables associated with the triglycerides incremental area under the curve (iAUC). Independent associations between metabolic variables and apo A-V iAUC were also investigated in a randomly selected subgroup (n = 44). The study sample was classified according to the presence of fasting hypertriglyceridemia (≥150 mg/dL) and abdominal obesity (WHR ≥0.92 in men and ≥0.85 in women) to explore differences in parameters. The fasting apo B-48 levels (r = 0.404), and the WHR (r = 0.359) were independent factors contributing to the triglycerides iAUC (r2 = 0.29, P < 0.001). The triglycerides iAUC was independently associated with the apo A-V iAUC (r2 = 0.54, P < 0.01). Patients with both hypertriglyceridemia and abdominal obesity showed the most robust triglycerides and apo A-V postprandial responses. In patients with FCH the fasting apo B-48 level is the main factor associated with postprandial lipemia. Abdominal obesity also contributes to the magnitude of the postprandial response.The triglycerides postprandial increment is the principal factor associated with the apo A-V postprandial response.


Racial and Ethnic Disparities in Dietary Intake among California Children.
The prevalence of childhood obesity among racial and ethnic minority groups is high. Multiple factors affect the development of childhood obesity, including dietary practices. To examine the racial and ethnic differences in reported dietary practices among the largest minority groups of California children. Data from the 2007 and 2009 California Health Interview Survey were analyzed using multivariate regression with survey weights to examine how race, ethnicity, sociodemographic characteristics, and child factors were associated with specific dietary practices. The sample included 15,902 children aged 2 to 11 years. In multivariate regressions, substantial differences in fruit juice, fruit, vegetable, sugar-sweetened beverages, sweets, and fast-food consumption were found among the major racial and ethnic groups of children. Asians regardless of interview language were more likely than whites to have low vegetable intake consumption (Asians English interview odds ratio [OR] 1.20, 95% CI 1.01 to 1.43; Asians non-English-interview OR 2.09, 95% CI 1.23 to 3.57) and low fruit consumption (Asians English interview OR 1.69, 95% CI 1.41 to 2.03; Asians non-English interview OR 3.04, 95% CI 2.00 to 4.6). Latinos regardless of interview language were also more likely than whites to have high fruit juice (Latinos English interview OR 1.54, 95% CI 1.28 to 1.84 and Latinos non-English interview OR 1.29, 95% CI 1.02 to 1.62) and fast-food consumption (Latinos English interview OR 1.74, 95% CI 1.46 to 2.08 and Latinos non-English interview OR 1.48, 95% CI 1.16 to 1.91); but Latinos were less likely than whites to consume sweets (Latinos English interview OR 0.81, 95% CI 0.66 to 0.99 and Latinos non-English interview OR 0.56, 95% CI 1.16 to 1.91). Significant racial and ethnic differences exist in the dietary practices of California children. Increased fruit and vegetable consumption appears to be associated with parent education but not income. Our findings suggest that anticipatory guidance and dietary counseling might benefit from tailoring to specific ethnic groups to potentially address disparities in overweight and obesity.


The development of equine immunity: Current knowledge on immunology in the young horse.
The development of equine immunity from the fetus to adulthood is complex. The foal's immune response and the immune mechanisms that they are equipped with, along with changes over the first months of life until the immune system becomes adult-like, are only partially understood. While several innate immune responses seem to be fully functional from birth, the onset of adaptive immune response is delayed. For some adaptive immune parameters, such as immunoglobin (Ig)G1, IgG3, IgG5 and IgA antibodies, the immune response starts before or at birth and matures within 3 months of life. Other antibody responses, such as IgG4, IgG7 and IgE production, slowly develop within the first year of life until they reach adult levels. Similar differences have been observed for adaptive T cell responses. Interferon-gamma (IFN-γ) production by T helper 1 (Th1)-cells and cytotoxic T cells starts shortly after birth with low level production that gradually increases during the first year of life. In contrast, interleukin-4 (IL-4) produced by Th2-cells is almost undetectable in the first 3 months of life. These findings offer some explanation for the increased susceptibility of foals to certain pathogens such as Rhodococcus equi. The delay in Th-cell development and in particular Th2 immunity during the first months of life also provides an explanation for the reduced responsiveness of young horses to most traditional vaccines. In summary, all immune components of adult horses seem to exist in foals but the orchestrating and regulation of the immune response in immature horses is strikingly different. Young foals are fully competent and can perform certain immune responses but many mechanisms have yet to mature. Additional work is needed to improve our understanding of immunity and immune regulation in young horses, to identify the preferred immune pathways that they are using and ultimately provide new preventive strategies to protect against infectious disease.


The relationship between education and food consumption in the 1995 Australian National Nutrition Survey.
To assess the relationship between education and the intake of a variety of individual foods, as well as groups of foods, for Australian men and women in different age groups. Cross-sectional national survey of free-living men and women. A sample of 2501 men and 2739 women aged 18 years and over who completed the National Nutrition Survey (NNS) 1995. Information about the frequency of consumption of 88 food items was obtained using a food-frequency questionnaire in a nation-wide nutrition survey. Irregular and regular consumers of foods were identified according to whether they consumed individual foods less than or more than once per month. The relationship between single foods and an index of education (no post-school qualifications, vocational, university) was analysed via contingency table chi-square statistics for men and women. Food group variety scores were derived by assigning individual foods to conventional food group taxonomies, and then summing the dichotomised intake scores for individual foods within each food group. Two-way analyses of variance (education by age groups) were performed on food variety scores for men and women, separately. While university-educated men and women consumed many individual foods more regularly than less-educated people, they were less likely to be regular consumers of several meat products. The relationship between education and food consumption was less apparent when individual food scores were aggregated into food group scores. University-educated men and women exhibited higher scores on total food group variety than the other educational groups. Higher education is associated with the regular consumption of a wider variety of foods. Aggregation of individual food consumption indices into food variety scores may mask the apparent effects of educational background on food consumption.


Moringa oleifera Extract Extenuates Echis ocellatus Venom-Induced Toxicities, Histopathological Impairments and Inflammation via Enhancement of Nrf2 Expression in Rats.
Echis ocellatus snakebite causes more fatalities than all other African snake species combined. Moringa oleifera reportedly possesses an antivenom property. Therefore, we evaluated the effectiveness of M. oleifera ethanol extract (MOE) against E. ocellatus venom (EOV) toxicities. Thirty male rats were grouped as follows (n = 5): Group 1 (normal control received saline), groups 2 to 6 were administered intraperitoneally, 0.22 mg/kg (LD50) of EOV. Group 2 was left untreated while group 3 to 6 were treated post-envenoming with 0.2 mL of polyvalent antivenom, 200, 400, and 600 mg/kg of MOE respectively. MOE significantly (p < 0.05) normalized the altered haematological indices and blood electrolytes profiles. MOE attenuated venom-induced cellular dysfunctions, characterized by a significant increase in NRF2, and concomitant downregulation of increased antioxidant enzymes (SOD and CAT) activities in the serum and heart of the treated rats. MOE normalized the elevated TNF-α and IL-1β in serum and heart tissues. Furthermore, the IgG titre value was significantly (p < 0.5) higher in the envenomed untreated group compared to the MOE-treated groups. Hemorrhagic, hemolytic and coagulant activities of the venom were strongly inhibited by the MOE dose, dependently. Lesions noticed on tissues of vital organs of untreated rats were abolished by MOE. Our findings substantiate the effectiveness of MOE as a potential remedy against EOV toxicities.


[Treatment of intracerebral hemorrhage - An overview].
Intracerebral hemorrhage (ICH) carries the highest mortality and morbidity of all stroke types. Although small vessel disease accounts for the majority of ICH, there is a broad spectrum of other etiologies. Modern imaging techniques are a cornerstone of the work-up process. The goals of acute management are to prevent hematoma expansion, stabilize and prevent failure of vital functions, and establish the cause of ICH. ICH expansion can be alleviated by rapid correction of any contributing coagulopathy and antihypertensive treatment. Early prognostication within 24 hours after onset is imprecise. For this reason, international guidelines recommend postponing decision-making on withdrawal or limitation of care until at least the second full day of hospitalization. Indications for intensive care differ from those for neurosurgical treatment and should be assessed separately. Neurosurgical treatment is commonly recommended to reduce mortality in the presence of hydrocephalus or infratentorial hematomas with significant mass effect. In deteriorating patients with supratentorial ICH, surgical treatment can be considered as a life-saving treatment on an individual basis, with consideration given to anatomical location, level of consciousness and medical history.


Effects of inhibition of gastric secretion on antral gastrin and somatostatin gene expression in rats.
Antral gastrin and somatostatin mRNA concentrations were measured in rats during gastric neutralization produced either by resection of the acid-secreting portion of the stomach (fundectomy) or by omeprazole treatment. Fundectomy caused increases in gastrin mRNA concentrations to 570% of sham control after 4 days and to 650% after 28 days. Daily administration of omeprazole resulted in significant dose- and time-dependent increases in antral gastrin mRNA concentrations. Four-day treatment with omeprazole caused threefold increased gastrin mRNA. Antral somatostatin mRNA concentrations decreased significantly after fundectomy to 66% of sham control after 4 days and to 23% after 28 days. Omeprazole produced a more profound decrease in somatostatin mRNA to 22% of the vehicle control after 4 days. Antral beta-actin mRNA concentrations did not differ significantly between control and experimental animals. Transcription of gastrin mRNA in isolated antral mucosal nuclei, measured by a nuclear run on technique, was significantly increased after omeprazole treatment in vivo. Increases in plasma and antral gastrin concentrations in response to gastric neutralization were closely associated with increases in gastrin mRNA and were accompanied by reductions in somatostatin mRNA in the antrum. However, fundectomy produced relatively greater increases in gastrin mRNA and lesser reductions in somatostatin mRNA than observed after omeprazole pretreatment.


Compact inductive energy storage pulse power system.
An inductive energy storage pulse power system is being developed in BARC, India. Simple, compact, and robust opening switches, capable of generating hundreds of kV, are key elements in the development of inductive energy storage pulsed power sources. It employs an inductive energy storage and opening switch power conditioning techniques with high energy density capacitors as the primary energy store. The energy stored in the capacitor bank is transferred to an air cored storage inductor in 5.5 μs through wire fuses. By optimizing the exploding wire parameters, a compact, robust, high voltage pulse power system, capable of generating reproducibly 240 kV, is developed. This paper presents the full details of the system along with the experimental data.


Characterization of a possible amyloidogenic precursor in glutamine-repeat neurodegenerative diseases.
Several neurodegenerative diseases are linked to expanded repeats of glutamine residues, which lead to the formation of amyloid fibrils and neuronal death. The length of the repeats correlates with the onset of Huntington's disease, such that healthy individuals have <38 residues and individuals with >38 repeats exhibit symptoms. Because it is difficult to obtain atomic-resolution structural information for poly(l-glutamine) (polyQ) in aqueous solution experimentally, we performed molecular dynamics simulations to investigate the conformational behavior of this homopolymer. In simulations of 20-, 40-, and 80-mer polyQ, we observed the formation of the "alpha-extended chain" conformation, which is characterized by alternating residues in the alpha(L) and alpha(R) conformations to yield a sheet. The structural transition from disordered random-coil conformations to the alpha-extended chain conformation exhibits modest length and temperature dependence, in agreement with the experimental observation that aggregation depends on length and temperature. We propose that fibril formation in polyQ may occur through an alpha-sheet structure, which was proposed by Pauling and Corey. Also, we propose an atomic-resolution model of how the inhibitory peptide QBP1 (polyQ-binding peptide 1) may bind to polyQ in an alpha-extended chain conformation to inhibit fibril formation.


Role of particle size in assessment of physico-chemical properties and trace elements of Indian fly ash.
In this paper, the effect of particle size on the physico-chemical, mineralogical, and leaching behavior of Indian fly ash was studied. Experiments were carried out to study the leaching of different elements such as Mg, Cr, Zn, Pb, Mn, Fe, Cu, Co, Mo, and Ni from Indian fly ash. During the experiments, the liquid-to-solid (L/S) ratio of the fly ash was taken as 9/1, 8/2, 7/3, 3/2, 1/1, and 2/3. The effect of four different particle size ranges (below 53, 53-75, 75-106, and 106-150 μm) of fly ash was analyzed. The ASTMD-3987 method was used to analyze the presence of trace elements from fly ash. In the ASTM D-3987 method, distilled water was used for extraction of leachate. Fly ash slurry samples were agitated in a lubricating type temperature-controlled Remi orbital shaker for a time duration of 18 hours with speed of 100 revolutions per minute (rpm) at a temperature of 25ºC. Distilled water does not save cost as well as being easily available. The leaching test of trace elements from fly ash was investigated at different pH conditions in order to predict the environmental effect from the ash disposal on the groundwater quality. Results revealed that pH of slurry suspension increases with increase in particle size. The pH value of fly ash slurries was negligibly affected by the decrease in L/S ratio for all particle sizes. Fine particles of fly ash produce a more harmful effect as compared to the coarser range of fly ash particles.


Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids.
Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1-7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P < 0.05). By comparison, neither mixed saturated fatty acid (100, 250, or 500 microM for <or=6 h) nor palmitate exposure alone (200 microM for <or=24 h) caused inflammatory activation or insulin resistance in cultured hypothalamic neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.


No Increased Risk of Aseptic Loosening with Tourniquetless Cemented Total Knee Arthroplasty.
Our study examined whether risk of revision for aseptic loosening following cemented total knee arthroplasty (TKA) is (1) increased with tourniquetless surgery and (2) affected by patient characteristics or surgical factors. Primary cemented TKAs from 2005-2012 with 2-year follow up were analyzed (n = 5,508 with tourniquet; n=101 without). Revision for aseptic loosening was compared between TKA performed with and without a tourniquet. Patient characteristics were recorded. At mean 4.8-year follow up, risk of aseptic loosening was similar between TKA performed with or without a tourniquet (p = 0.3151). Aseptic loosening was more likely in men (p = 0.0018) and patients younger than 50 (p < 0.0001). No difference was observed between cruciate-retaining and posterior-stabilized implants (p = 0.1250). With the numbers available for study, we did not observe an increased risk of aseptic loosening with tourniquetless cemented primary TKA. Patients younger than 50, particularly men, should be counselled on the increased risk of TKA revision for aseptic loosening. (Journal of Surgical Orthopaedic Advances 32(2):111-113, 2023).


Modified liberatory maneuver: effective treatment for benign paroxysmal positional vertigo.
A modification of the liberatory maneuver was used to treat 25 patients with benign paroxysmal positional vertigo (BPPV). The modified liberatory maneuver relieved symptoms without recurrence in 11 (44%) patients. A partial response was noted in 6 (24%) patients, and there was no improvement in 8 (32%) patients. Follow-up ranged from 1 to 20 months (median 4.0 months). Patient age was not predictive of response to treatment. Duration of symptoms before treatment, however, was greater in nonresponders (median 15.5 months) than in complete (median 5.0 months) or partial (median 3.5 months) responders. The modified liberatory maneuver takes approximately 5 minutes to perform and provides effective treatment in two thirds of patients who suffer from BPPV.