Hypothermic cardiac arrest patients admitted to hospital who were not rewarmed with extracorporeal life support: A retrospective study.
Our goal was to study hypothermic cardiac arrest (CA) patients who were not rewarmed by Extracorporeal Life Support (ECLS) but were admitted to a hospital equipped for it. The focus was on whether the decisions of non-rewarming, meaning termination of resuscitation, were compliant with international guidelines based on serum potassium at hospital admission. We retrospectively included all hypothermic CA who were not rewarmed, from three Swiss centers between 1st January 2000 and 2nd May 2021. Data were extracted from medical charts and assembled into two groups for analysis according to serum potassium. We identified the criteria used to terminate resuscitation. We also retrospectively calculated the HOPE score, a multivariable tool predicting the survival probability in hypothermic CA undergoing ECLS rewarming. Thirty-eight victims were included in the study. The decision of non-rewarming was compliant with international guidelines for 12 (33%) patients. Among the 36 patients for whom the serum potassium was measured at hospital admission, 24 (67%) had a value that - alone - would have indicated ECLS. For 13 of these 24 (54%) patients, the HOPE score was <10%, meaning that ECLS was not indicated. The HOPE estimation of the survival probabilities, when used with a 10% threshold, supported 23 (68%) of the non-rewarming decisions made by the clinicians. This study showed a low adherence to international guidelines for hypothermic CA patients. In contrast, most of these non-rewarming decisions made by clinicians would have been compliant with current guidelines based on the HOPE score.


Clinical relevance of transient worsening renal function after initiation of sacubitril/valsartan.
The worsening of renal function after the start of valsartan therapy is relatively common in clinical practice. However, few data are available on the incidence of worsening renal function after the beginning of therapy with sacubitril/valsartan. We retrospectively enrolled 202 outpatients with HFrEF that started therapy with sacubitril/valsartan to evaluate the prevalence of worsening renal function and its clinical significance. At 1 month, a worsening renal function (defined as a > 20% decrease in eGFR occurring after 1 month of ARNi therapy) was found in 68 patients (33%), however after a mean follow-up of 650 ± 80 days, Kaplan-Meier analysis showed no significant in terms of HF-related deaths, HF-related hospitalizations, and the need for renal replacement therapy (25.2 vs. 23.6%; p = .812). In addition, the renal function recovered in patients with early WRF at 3 months (62 + 9.3 ml/min/1.73 m2 vs. 63 ± 13.8 ml/min/1.73 m2; p < .05), with an improvement in estimated glomerular filtration rate at 1 year compared with baseline value (62 ± 9.3 ml/min/1.73 m2 vs. 69 ± 8.6 ml/min/1.73 m2; p < .01). WRF occurs in nearly 30% of HFrEF patients without impacting clinical outcomes; HF specialists should be aware of these changes to avoid unnecessary discontinuation of sacubitril/valsartan therapy.


Cryptococcosis due to Cryptococcus neoformans var. gattii in Brazilian patients with AIDS. Report of three cases.
Three cases of Cryptococcus neoformans var. gattii infection in AIDS patients observed in Rio Grande do Sul (Brazil) are related. A brief comment on the epidemiology of cryptococcosis in Brazil is also made.


Management of arteriovenous malformations: a multidisciplinary approach.
Management of arteriovenous malformations (AVMs) remains challenging because of their unpredictable behavior and high recurrence rate. A multidisciplinary approach based on a new classification scheme and improved diagnostic techniques may improve their management. The purpose of this study was to review our experience with combined embolotherapy, sclerotherapy (embolo/sclerotherapy), and surgical procedures to manage AVMs. A total of 797 patients with congenital vascular malformations (January 1995 through December 2001) was investigated with noninvasive studies. Once an AVM was diagnosed, all underwent angiographic confirmation as a roadmap for treatment. Embolo/sclerotherapy and surgical procedures were instituted by the multidisciplinary team with periodic follow-up per protocol. Seventy-six patients with AVMs were reviewed retrospectively to assess the diagnosis and management by a multidisciplinary approach. Seventy-six (9.5% of all CVM) patients had AVMs, mostly infiltrating, extratruncular form (61/76). Embolo/sclerotherapy with various combinations of absolute ethanol, N-butyl cyanoacrylate (NBCA), contour particles, and coils were used in 48 patients. Sixteen patients with surgically accessible localized lesions completed preoperative embolism and sclerotherapy through 24 sessions, with subsequent surgical excision with minimal morbidity. Interim results were excellent, with no evidence of recurrence in all 16 patients with a mean follow-up of 24 months. Thirty-two patients with surgically inaccessible lesions (infiltrating) were treated with embolism and sclerotherapy alone. There were nine failures in a total of 171 sessions. Interim results with a mean of 19 months' follow-up of embolism and sclerotherapy alone were excellent in the majority (25/32) and good to fair among the rest (7/32). However, 31 complications, mostly minor (27/31), occurred in 30 sessions. Four major complications occurred, including facial nerve palsy, pulmonary embolism, deep vein thrombosis, and massive necrosis of an ear cartilage. Diagnosis and management of AVMs by a multidisciplinary approach that integrates surgical therapy with embolism and sclerotherapy appears to improve the results and management with limited morbidity and no recurrence during early follow-up.


Effects of Peripheral Neural Blocks in Laparoscopic Sleeve Gastrectomy: a Pilot Study on Cognitive Functions in Severe Obese Patients.
In addition to the analgesic effect, peripheral neural blocks also prevent cognitive impairment and peripheral inflammation induced by surgery. However, it is unknown if there is collateral impact on cognitive improvement after bariatric surgery. In this pilot study, 75 patients with severe obesity for selective laparoscopic sleeve gastrectomy (LSG) were recruited and randomized into three groups (1:1:1) as general anesthesia (GA) group, transverse abdominis plane block (TAPB) group, and quadratus lumborum block (QLB) group. Bilateral TAPB or QLB was performed (0.33% ropivacaine with dexmedetomidine 1 μg/kg) before the standardized general anesthesia. Cognitive test battery was completed before LSG and in 1-month and 3-month follow-up. The levels of peripheral inflammatory cytokines were determined at equivalent time points. Patients with LSG exhibited massive cognitive improvement in postoperative 3 month without or with TAPB or QLB (Ptime < 0.001). Compared to GA, QLB significantly strengthened performance in MoCA (β = 0.56, 95%CI: 0.08, 1.05). IL-6, IL-8, and high-sensitivity CRP significantly verified among three groups. Changes in IL-6 within postoperative 3 months were negatively correlated with MMSE and MoCA, and positively correlated with AVLT-DR for QLB group. Similar correlation was found in the GA group for changes in IL-6 and AVLT-IR. Laparoscopic sleeve gastrectomy ideally improved memory and attention as early as postoperative 1 month. QLB promoted cognitive improvement in MoCA, which was negatively correlated with changes in IL-6. More precise trials are needed to determine the overall effect of peripheral neural block on cognition following bariatric surgery.


Examining Health Care Costs: Opportunities to Provide Value in the Intensive Care Unit.
As health care costs threaten the economic stability of American society, increasing pressures to focus on value-based health care have led to the development of protocols for fast-track cardiac surgery and for delirium management. Critical care services can be led by anesthesiologists with the goal of improving ICU outcomes and at the same time decreasing the rising cost of ICU medicine.


The current role of cryotherapy for renal and prostate tumors.
Minimally invasive treatments continue to evolve as an alternative method for the treatment of kidney and prostatic tumors. Of the mainstream ablative procedures reported in the literature, the cryotherapy data appear to be the most durable. Currently, select kidney and prostatic lesions are treated using cryotherapy. Although limited long-term survival data using cryotherapy are available, recent series have provided compelling results, promoting interest in renal and prostatic cryoablation. This article assesses the current status of cryotherapy in urology, specifically the indications, techniques, and clinical results in treating kidney and prostate tumors.


On the nature of ceramide-mitochondria interactions - Dissection using comprehensive mitochondrial phenotyping.
Sphingolipids are a unique class of lipids owing to their non-glycerol-containing backbone, ceramide, that is constructed from a long-chain aliphatic amino alcohol, sphinganine, to which a fatty acid is attached via an amide bond. Ceramide plays a star role in the initiation of apoptosis by virtue of its interactions with mitochondria, a control point for a downstream array of signaling cascades culminating in apoptosis. Many pathways converge on mitochondria to elicit mitochondrial outer membrane permeabilization (MOMP), a step that corrupts bioenergetic service. Although much is known regarding ceramides interaction with mitochondria and the ensuing cell signal transduction cascades, how ceramide impacts the elements of mitochondrial bioenergetic function is poorly understood. The objective of this review is to introduce the reader to sphingolipid metabolism, present a snapshot of mitochondrial respiration, elaborate on ceramides convergence on mitochondria and the upstream players that collaborate to elicit MOMP, and introduce a mitochondrial phenotyping platform that can be of utility in dissecting the fine-points of ceramide impact on cellular bioenergetics.


Quantification by fluorescence of apurinic sites in DNA.
Time dependent fluorescence is observed when single or double stranded DNA with apurinic sites are mixed with 9-NH2-ellipticine. A concentration dependent plateau is obtained which is linearly related to the ratio of apurinic sites in DNA. We therefore suggest that it is possible to have a direct measurement of apurinic sites in DNA by fluorescence.


Nanosized TiO2 is internalized by dorsal root ganglion cells and causes damage via apoptosis.
Titanium dioxide (TiO2) is widely used as ingredient in several products in the nanoform. TiO2-nanoparticles (NPs) are also currently studied for different medical applications. A large debate exists on possible adverse health effects related to their exposure. While there is some evidence of TiO2-NP central nervous system toxicity, their effects on peripheral neurons have been poorly explored. In this study we investigated the effects of TiO2-NPs on dorsal root ganglion (DRG) sensory neurons and satellite glial cells that may be reached by nanoparticles from the bloodstream. We found that TiO2-NPs are internalized in DRG cells and induce apoptosis in a dose dependent manner in both types of cells, ROS production and changes in expression of proinflammatory cytokine IL-1β. Furthermore, we found that the axonal retrograde transport is altered in neurons upon exposure to TiO2-NPs. Overall, the results indicate a potential neurotoxic effect of TiO2-NPs on DRG cells. Exposure to titanium dioxide nanoparticles is increasing in medical practice. Little is known about their potential toxic effects on the peripheral nervous system. The authors studied this aspect and showed that titanium nanoparticles might potentially cause toxicity over long term.


Asthma in the elderly: risk factors and impact on physical function.
The incidence rate of asthma has increased in all age groups in the past 40 years. Asthma in older adults is underdiagnosed and undertreated, resulting in suboptimal asthma control. The objectives of the study are to evaluate differences in host characteristics between older patients with asthma and persons who do not have asthma and how these differences impact overall quality of life. Patients older than age 60 years were recruited from the general population for this case/control and nested cohort study. A complete medical history, physical examination, skin prick testing (SPT), spirometry, and exhaled nitric oxide (ENO) measurements were performed. Quality of life was assessed through the standardized SF-36v2 questionnaire. Quality of life scores, spirometry, ENO, and aeroallergen sensitization differences were compared between older patients with asthma and control patients. The mean age of the 77 patients evaluated was 68.7 ± 7.2 years, with 59 (77%) being female. A higher rate of SPT positivity was found in patients with asthma (88.9%) compared with controls (51.2%) (P = .007). The mean percent predicted forced expiratory volume in 1 second (FEV1) at baseline was lower in the asthma group (73.7 ± 21.9%) compared with controls (89.6 ± 19.1%) (P = .007). For quality of life assessed by the SF-36v2 questionnaire, the asthma group had worse general health, increased bodily pain, and worse overall physical health compared with controls (P = .02; .021; .01). Older adults with asthma have a higher rate of allergic sensitization, decreased lung function, and significantly worse quality of life compared with controls.


Temporal stability of the virus load of cattle infected with bovine leukemia virus.
The relative virus load of bovine leukemia virus (BLV) infected cattle was measured by an immunoperoxidase infectivity assay (IPIA), and by immunoperoxidase staining of cultured leukocytes using a monoclonal antibody to the capsid protein (p24) of BLV. The results of paired sample data taken at different time points spanning 2-3 years show that BLV-infected cattle are stable regarding the amount of BLV produced by their peripheral blood mononuclear cells (PBMCs). Spearman's Rank Correlation demonstrated significant relationships between data from individual cattle taken at four different time points. In addition, this study documents the large range of variation in the virus load of individual cattle.


Analysis of the Viability and Morphology of Gingival Cells on Materials Used in Novel Prosthetic Components: In Vitro Study.
The objective of this in vitro study was to evaluate the viability and morphology of human fibroblasts and keratinocytes cells, both grown on stainless steel (steel) (18Cr14Ni2.5Mo), and polyether-ether-ketone (PEEK) surfaces, hypothesizing the use of these surfaces as novel materials for prosthetic components. Gingival human keratinocytes and gingival human fibroblasts lines were grown on discs made by steel (n = 36), PEEK (n = 36), and titanium (Ti) (Ti6A14V) (n = 36)-control. For viability assay, cultures were grown at 24 hours (TV1), 48 hours (TV2), and 72 hours (TV3) times and evaluated by the colorimetric tetrazolium assay (MTT). For morphology and cell adhesion assays, after 24 hours (TM1), 48 hours (TM2), and 96 hours (TM3) of cell culture, cells were examined by scanning electron microscopy (SEM) and analyzed at magnifications with 500×, 1,000×, and 2,500×. Regarding the viability, the keratinocytes did not present statistical difference on the different materials, in TV1 and TV3 times of culture. Their growth rate increased on all materials, being more expressive in steel; the fibroblasts did not present statistical difference on the different materials, in TV2 and TV3 times of culture. The growth rate of these decreased on all materials, being more expressive in PEEK. The morphology analyses show increase in cell numbers, adequate spreading, and adhesion at all cultivation times (TM1, TM2, and TM3) in both cell lines, on all materials. All materials tested are suitable for use in the manufacture of prosthetic components for implant-supported rehabilitations, considering the limitations of this study. This work analyzes the cellular response of cells present in the human gingiva, as a way to simulate the peri-implant tissue response around novel angular prosthetic components made of stainless steel and PEEK.


Chemotherapy induces death receptor 5 in epithelial ovarian carcinoma.
Defects in the apoptotic pathway are a general cause for drug resistance. Chemotherapy in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has proven to be an effective strategy to induce apoptosis in vitro in ovarian tumor cells. Systemic TRAIL administration might be a therapeutic option, since no toxicity was observed in nonhuman primates. In the present study, expression of TRAIL and its apoptosis-inducing death receptors (DR4 and DR5) and inhibitory decoy receptor (DcR1) was studied in normal ovaries and in malignant ovarian tumors before and after chemotherapy to investigate the therapeutic potential of TRAIL. DR4, DR5, DcR1, and TRAIL were studied immunohistochemically in 5 normal ovaries, 15 stages I/II, and 26 stages III/IV primary ovarian cancers, including 19 paired tumor samples (pre- and post-chemotherapy). Surface epithelium of normal ovaries expressed TRAIL and its receptors; ovarian stromal cells expressed only DcR1. Of the ovarian cancers, 73% expressed DR4, 51% DR5, 46% DcR1, and 34% TRAIL. Most primary ovarian cancers (88%) expressed at least one death receptor. TRAIL expression was lower in stage III/IV than in stage I/II tumors (P<0.05). In paired samples, DR5 immunostaining was more frequently (P=0.05) and stronger (P<0.01) expressed in residual tumors. Early stage tumors expressed TRAIL more frequently than advanced stage tumors. Most primary and residual ovarian tumors expressed at least one TRAIL death receptor, while in residual tumors following chemotherapy, DR5 was more frequently expressed. Therefore, human recombinant TRAIL administration might be an interesting treatment option.


Moyamoya syndrome as a complication of radiation therapy. Case report.
A case is reported with occlusion and stenosis of the internal carotid arteries in association with basal telangiectasia. Fifteen years after postoperative irradiation for an optic glioma, radiological signs typical of the moyamoya syndrome were observed. Radiation therapy is discussed as the cause of the vascular damage in this case.


Staurosporine maintains the activation of store-operated Ca²⁺ entry even after the refilling of Ca²⁺ stores.
Store-operated Ca²⁺ entry (SOCE) from the extracellular space plays a critical role in agonist-mediated Ca²⁺ signaling in non-excitable cells. Here we show that SOCE is enhanced in COS-7 cells treated with staurosporine (ST), a protein kinase inhibitor. In COS-7 cells, stimulation with ATP induced Ca²⁺ release from intracellular Ca²⁺ stores and Ca²⁺ entry from the extracellular space. Ca²⁺ release was not affected by treatment with ST, but Ca²⁺ entry continued in the ST-treated cells even after the removal of ATP. ST did not inhibit Ca²⁺ sequestration into Ca²⁺ stores. The Ca²⁺ entry induced by cyclopiazonic acid (CPA), a reversible ER Ca²⁺ pump inhibitor, was maintained in ST-treated cells even after the removal of CPA, but was not maintained in the control cells. The sustained Ca²⁺ entry in ST-treated cells was completely attenuated by the SOCE inhibitors, La³⁺ and 2-APB. The large increase in Ca²⁺ entry produced in the cells co-expressing Venus-Orai1 and STIM1-mKO1 was stabilized with ST treatment, and confocal imaging of these cells suggested that the complex between Orai1 and STIM1 did not completely dissociate following the refilling of Ca²⁺ stores. These results show that SOCE remains activated even after the refilling of Ca²⁺ stores in ST-treated cells and that the effect of ST on SOCE may result from a stabilization of the Orai1-STIM1 interaction.


The association between the experience of lay responders and response interval to medical emergencies in a rural area: an observational study.
The aim of this retrospective observational study was to determine how response intervals correlated to the experience of the community first responders (CFRs) using data collected from the Danish Island of Langeland via a global positioning system (GPS)-based system. All medical emergency calls involving CFRs in the time period from 21st of April 2012 to 31st of December 2017 were included. Each emergency call activated 3 CFRs. Response intervals were calculated using the time from when the system alerted the CFRs to CFR time of arrival at the emergency site measured by GPS. CFRs response intervals were grouped depending on their level of experience according to ≤ 10, 11-24, 25-49, 50-99, ≥ 100 calls accepted and arrived on-site. A total of 7273 CFR activations were included. Median response interval for the CFR arriving first on-site (n = 3004) was 4:05 min (IQR 2:42-6:01) and median response interval for the arrival of the CFR with an automated external defibrillator (n = 2594) was 5:46 min (IQR 3:59-8:05). Median response intervals were 5:53 min (3:43-8:29) for ≤ 10 calls (n = 1657), 5:39 min (3:49-8:01) for 11-24 calls (n = 1396), 5:45 min (3:49-8:00) for 25-49 calls (n = 1586), 5:07 min (3:38-7:26) for 50-99 calls (n = 1548) and 4:46 min (3:14-7:32) for ≥ 100 calls (n = 1086) (p < 0.001). There was a significant negative correlation between experience and response intervals (p < 0.001, Spearman's rho = -0.0914). This study found an inverse correlation between CFR experience and response intervals, which could lead to increased survival after a time-critical incident.


Evidence for dynamics in proteins as a mechanism for ligand dissociation.
Signal transduction, regulatory processes and pharmaceutical responses are highly dependent upon ligand residence times. Gaining insight into how physical factors influence residence times (1/k(off)) should enhance our ability to manipulate biological interactions. We report experiments that yield structural insight into k(off) involving a series of eight 2,4-diaminopyrimidine inhibitors of dihydrofolate reductase whose binding affinities vary by six orders of magnitude. NMR relaxation-dispersion experiments revealed a common set of residues near the binding site that undergo a concerted millisecond-timescale switching event to a previously unidentified conformation. The rate of switching from ground to excited conformations correlates exponentially with the binding affinity K(i) and k(off), suggesting that protein dynamics serves as a mechanical initiator of ligand dissociation within this series and potentially for other macromolecule-ligand systems. Although the forward rate of conformational exchange, k(conf,forward), is faster than k(off), the use of the ligand series allowed for connections to be drawn between kinetic events on different timescales.


Type III collagen aminopropeptide and laminin P1 levels in serum of patients with silicosis-associated and idiopathic systemic scleroderma.
A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin PI (Lam PI) fragment and the acid lysosomal beta-galactosidase (beta-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of beta-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam PI were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam PI and beta-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.


Reduction of aromatic L-amino acid decarboxylase activity in clonal pheochromocytoma PC12h cells by culture in the presence of N-methyl-4-phenylpyridinium ion (MPP+).
Rat clonal pheochromocytoma PC12h cells were cultured in the presence of N-methyl-4-phenylpyridinium ion (MPP+) and the activity of aromatic L-amino acid decarboxylase (AADC) was reduced after 3 and 6 days of culture. AADC activity in control cells was increased markedly by addition of pyridoxal 5-phosphate (PLP) to the reaction mixture, but that in the cells cultured in the presence of MPP+ was not increased by addition of PLP. After 6 days culture, AADC activity was almost negligible in the cells cultured in the presence of 1 mM MPP+, but PLP concentration in the cells was not reduced. AADC in the cells cultured in the presence of MPP+ reduced the affinity to PLP, but the affinity to a substrate, L-DOPA, did not change. Intracellular concentration of AADC protein was not reduced, as shown by an immunobinding assay with anti-AADC antibody. These data indicate that MPP+ may induce conformational changes in AADC protein and reduces its affinity to the cofactor, PLP.


Probiotic Lactobacillus rhamnosus EM1107 prevents hyperglycemia, alveolar bone loss, and inflammation in a rat model of diabetes and periodontitis.
This study evaluated the antihyperglycemic, anti-bone-resorptive, and anti-inflammatory efficacy of the probiotic Lactobacillus rhamnosus EM1107 in an experimental model of ligature-induced periodontitis in diabetic rats treated with metformin (Met). A total of 114 male Wistar rats was randomly divided into six groups: (1) control, (2) experimental periodontitis (EP), (3) EP + diabetes mellitus (DM), (4) EP + probiotic (Prob), (5) EP + DM + Prob, and (6) EP + DM + Prob + Met. The animals received probiotic gavage during the 30 days of the experiment. DM was induced on the 14th day of the experiment with a single injection of streptozotocin into the penile vein, followed by ligature for EP induction and Met gavage on the 19th day and euthanasia on the 30th day. Heart blood, gingival and periodontal tissue, and hemimaxillae were collected. Biomolecular analysis, immunoenzymatic assays, histomorphology, and microtomographic analysis were performed. Data were statistically analyzed (p < 0.05). There was a significant reduction in interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the Prob groups (p < 0.05) as well as in blood glucose levels in the Prob and Met groups (p < 0.001). In addition, histomorphological analysis revealed that the Prob groups had a reduction in inflammatory infiltrate. Tartrate-resistant acid phosphatase (TRAP) and microtomographic analyses showed that the EP/DM/Prob/Met group had significantly lower linear and volumetric bone loss than those who had no treatment (p < 0.01). SOD and GPx immunostaining decreased in all groups receiving probiotics. The findings suggest the immunoinflammatory efficacy of the probiotic L. rhamnosus EM1107 administered either alone or in association with Met in type 1 DM associated with periodontitis.


Neuroprotective effects of two selenium-containing peptides, TSeMMM and SeMDPGQQ, derived from selenium-enriched rice protein hydrolysates on Pb2+-induced oxidative stress in HT22 cells.
Immunomodulatory peptides with the sequences TSeMMM and SeMDPGQQ from selenium (Se)-enriched rice protein hydrolysates (SPHs) were identified in our previous study. We synthesized these two peptides to study whether they have neuroprotective effects on Pb2+-induced oxidative stress in mouse hippocampal HT22 cells, SPHs and a purified SPH fraction (SPHs-2) were used to compare the effects. Peptides pretreatments significantly suppressed Pb2+-induced cytotoxicity by increasing cell viability and decreasing cell apoptosis. TSeMMM and SeMDPGQQ reduced nitric oxide (NO) levels by 37.47% and 14.72% of Pb2+ group, as well as lactate dehydrogenase (LDH) release by 12.98% and 6.32% of Pb2+ group. TSeMMM and SeMDPGQQ could increase the activities of antioxidant enzymes; for example, the activity of superoxide dismutase (SOD) increased by 47.79% and 13.93%, respectively, and that of glutathione peroxidase (GSH-Px) increased by 94.7% and 78.73% of Pb2+ group. Additionally, nuclear factor erythroid 2-related factor (Nrf2) nuclear translocation and heme oxygenase 1 (HO-1) expression were triggered. These results suggest that TSeMMM and SeMDPGQQ can suppress oxidative damage caused by Pb2+; moreover, TSeMMM showed better neuroprotective potential than SeMDPGQQ.


Models of care for gender dysphoria in young persons: How Psychiatry lost and is finding its voice.
Globally, models of care for young persons with gender dysphoria differ across jurisdictions. Historically, developed countries have utilised the medical approach. More recently, broader models that place a greater emphasis on psychological interventions are emerging. This piece utilizes the Australian experience to compare models of care for gender dysphoria. Reflecting on the relative passivity of Psychiatry to date, historical reasons for this silence are explored. As relative experts in relationship dynamics and key bearers of the history of sexual health diagnoses, it is proposed that Psychiatrists have both the requisite skills and responsibility to share reflective lessons with other medical specialties in this space. Only by doing so may they provide appropriate care and treatment for young persons suffering mental distress due to gender incongruence.


Enteric fistulization of a common iliac vein aneurysm.
Iliac vein aneurysm is rare. Its complications include rupture, thromboembolism, and enteric fistulization. If a patient with surgical history presents with gastrointestinal bleeding, the veno-enteric fistula should be part of the differential diagnoses. In presence of a veno-enteric fistula, surgical treatment consists of aneurysmectomy, venorraphy, and intestinal resection.


[Establishment of a porcine model of acute hepatic failure by intraportal injection of D-galactosamine and lipopolysaccharide].
To develop a clinically relevant porcine model of acute hepatic failure (AHF). Twenty-two healthy pigs were randomly divided into 5 groups: group I (n = 3, intraportally administered with normal saline), group II [n = 5, intraportally administered with 1 microg/kg of lipopolysaccharide (LPS)], group III [n = 5, intraportally administered with 0.5 g/kg of D-galactosamine (D-Gal)], group IV (n = 6, intraportally administered with 0.5 g/kg of D-Gal plus 1 microg/kg LPS), and group V [n = 3, intraportally administered with 0.5 g/kg of D-Gal plus 1 microg/kg LPS and then receiving auxiliary partial orthotopic liver transplantation (APOLT)], Blood samples were collected to examine the arpartate transaminase (AST), total bilirubin, lactic acid, blood ammonia, prothrombin time (PT), blood sugar, and creatine at different time points. Autopsy was performed on the dead animals. Eight days after the APOLT laparotomy was performed again on the surviving pigs to take specimens of the original and transplanted liver to undergo pathological examination. All the pigs in the groups I and II survived with minimal changes in liver function tests. Two of the 5 pigs in the group III died (40%), 5 pigs in the group IV (5/6, 83%) died within 120 h, with a significant increase in aspartate transaminase 48 h after (4912 U/L +/- 759 U/L). In comparison with those of the group 1 and 2, the TBIL, blood ammonia, lactic acid, and PT 48 h after of the group 4 were all significantly higher and the blood sugar was significantly lower (all P < 0.05). Reversal of AHF in the pigs in the group V following APOLT was observed and the liver function returned near to normal level on the 7th postoperative day and regeneration of the native liver was confirmed histologically. The porcine model of AHF induced by a combination of D-gal (0.5 g/kg) and LPS (1 microg/kg) will be of much use in the development of APOLT for AHF.


Variation of Nonlinear Refraction and Three-Photon Absorption of Indium-Tin Oxide Quantum Dot Thin Films and Solutions in Near Infrared Range.
We characterize the nonlinear optical properties of indium-tin oxide (ITO) quantum dots (QDs) in the IR range using the Z-scan method. We present results of three-photon absorption (3PA), third harmonic generation (3HG), and Kerr-effect-induced nonlinear refraction in ITO QDs. Z-scan measurements were carried out for the QDs solution, while 3HG was demonstrated using QD thin films. The Kerr-induced nonlinear refractive index was analyzed along the 800-950 nm range showing an increase in this parameter from -6.7 × 10-18 to -1.5 × 10-17 m2 W-1. At longer wavelengths (1000-1100 nm), the higher-order effects started to contribute to a nonlinear refractive index. The 3PA coefficient at 950 nm was measured to be 1.42 × 10-25 m3/W2. We discuss the peculiarities in the wavelength-dependent variation of the coefficient of nonlinear absorption responsible for 3PA in the range of 800-1150 nm. Third harmonic generation was analyzed in the 1200-1550 nm spectral range. The absolute value of 3HG conversion efficiency in the 150 nm thick film at the wavelength of laser radiation (1350 nm) was estimated to be ~10-5.


Stillbirth: Perceptions among hospital staff in the Middle East and the UK.
Objectives Stillbirth is an important and yet relatively unacknowledged public health concern in many parts of the world. Public awareness of stillbirth and its potentially modifiable risk factors is a prerequisite to planning prevention measures. Cultural and regional differences may play an important role in awareness and attitudes to stillbirth prevention. The objective of this study was to evaluate and compare the awareness of stillbirth among hospital staff in Qatar and the UK, representing two culturally different regions. Study design An online population survey for anonymous completion was sent to the hospital email accounts of all grades of staff (clinical and non-clinical) at two hospitals in Qatar and one tertiary hospital Trust in the UK. The survey was used to gather information on the participants' demographic background, the experience of stillbirth, knowledge of stillbirth, awareness of information and support sources, as well as attitude towards investigation and litigation. Data were analysed using descriptive and comparative statistics (Chi-Square test and Fisher's exact test). Results 1002 respondents completed the survey, including 349 in the Qatar group and 653 in the UK group. There were significant differences in group demographics in terms of language, religion, gender, nationality and experience of stillbirth. The groups also differed significantly in the knowledge of stillbirth, its incidence and risk factors. The two groups took different views on apportioning blame on healthcare services in cases of stillbirth. The Qatar group showed significantly less awareness of available support organisations and relied significantly more on online sources of information for stillbirths (p < 0.001). Conclusions This comparative study demonstrated significant differences between the two culturally distinct regions in the awareness, knowledge and attitudes towards stillbirths. The complex cultural and other factors that may be contributory should be further studied. The results highlight the need for increasing public awareness around stillbirth as part of effective prevention strategies.


Abl kinase interacts with and phosphorylates vinexin.
Non-receptor tyrosine kinase Abl is a well known regulator of the actin-cytoskeleton, including the formation of stress fibers and membrane ruffles. Vinexin is an adapter protein consisting of three SH3 domains, and involved in signal transduction and the reorganization of actin cytoskeleton. In this study, we found that vinexin alpha as well as beta interacts with c-Abl mainly through the third SH3 domain, and that vinexin and c-Abl were colocalized at membrane ruffles in rat astrocytes. This interaction was reduced by latrunculin B, suggesting an F-actin-mediated regulatory mechanism. We also found that vinexin alpha but not beta was phosphorylated at tyrosine residue when c-Abl or v-Abl was co-expressed. A mutational analysis identified tyrosine 127 on vinexin alpha as a major site of phosphorylation by c- or v-Abl. These results suggest that vinexin alpha is a novel substrate for Abl.


An extended phylogenetic analysis reveals ancient origin of "non-green" phosphoribulokinase genes from two lineages of "green" secondary photosynthetic eukaryotes: Euglenophyta and Chlorarachniophyta.
Euglenophyta and Chlorarachniophyta are groups of photosynthetic eukaryotes harboring secondary plastids of distinct green algal origins. Although previous phylogenetic analyses of genes encoding Calvin cycle enzymes demonstrated the presence of genes apparently not derived from green algal endosymbionts in the nuclear genomes of Euglena gracilis (Euglenophyta) and Bigelowiella natans (Chlorarachniophyta), the origins of these "non-green" genes in "green" secondary phototrophs were unclear due to the limited taxon sampling. Here, we sequenced five new phosphoribulokinase (PRK) genes (from one euglenophyte, two chlorarachniophytes, and two glaucophytes) and performed an extended phylogenetic analysis of the genes based on a phylum-wide taxon sampling from various photosynthetic eukaryotes. Our phylogenetic analyses demonstrated that the PRK sequences form two genera of Euglenophyta formed a robust monophyletic group within a large clade including stramenopiles, haptophytes and a cryptophyte, and three genera of Chlorarachniophyta were placed within the red algal clade. These "non-green" affiliations were supported by the taxon-specific insertion/deletion sequences in the PRK alignment, especially between euglenophytes and stramenopiles. In addition, phylogenetic analysis of another Calvin cycle enzyme, plastid-targeted sedoheptulose-bisphosphatase (SBP), showed that the SBP sequences from two genera of Chlorarachniophyta were positioned within a red algal clade. Our results suggest that PRK genes may have been transferred from a "stramenopile" ancestor to Euglenophyta and from a "red algal" ancestor to Chlorarachniophyta before radiation of extant taxa of these two "green" secondary phototrophs. The presence of two of key Calvin cycle enzymes, PRK and SBP, of red algal origins in Chlorarachniophyta indicate that the contribution of "non-green" algae to the plastid proteome in the "green" secondary phototrophs is more significant than ever thought. These "non-green" putative plastid-targeted enzymes from Chlorarachniophyta are likely to have originated from an ancestral red alga via horizontal gene transfer, or from a cryptic red algal endosymbiosis in the common ancestor of the extant chlorarachniophytes.


Deep learning models for image and data processes of intracellular calcium ions.
Intracellular calcium ion (Ca2+) in cytoplasm as an intracellular second messenger is involved in almost all important cellular activities of organisms. Generally its concentration ([Ca2+]i) is tested by live imaging followed image and data processes, in which much tedious and subjective manual work is involved. Here we show a computational approach of Deep Calcium following the principles of deep learning to predict the cytoplasmic Ca2+ ranges and calcium peaks in calcium curve of objective cells. To validate Deep Calcium, chondrocytes, bone marrow stromal cells (BMSCs) and osteoblastic like cells (MC3T3-E1) from both the tissue and cell samples as well as from spontaneous and mechanical stimulated calcium response patterns are used. The good performance comparing with other relative machine learning models, as well as consistency biological results with human experts are demonstrated. Deep Calcium provides references for other image and data processes of intracellular range determination and curve peak identification.


Predictors of postoperative ventricular dysfunction in infants who have undergone primary repair of a ventricular septal defect.
By means of postoperative radionuclide angiography we identified a subset of infants undergoing primary repair of their ventricular septal defects (VSD) who had postoperative morbidity and ventricular dysfunction. Twenty-three consecutive infants undergoing repair of an uncomplicated VSD were studied. Radionuclide-determined postoperative ventricular dysfunction (VD), as defined by a left ventricular ejection fraction less than 0.30 2 to 4 hours after surgery, was correlated with clinical signs of postoperative morbidity. Six patients developed postoperative VD. Clinical correlates of VD included the use of postoperative inotropic support, increased number of postoperative intensive care days, and a low growth rate 3 months postoperatively. Potential predictors of VD were evaluated. A preoperative pulmonary-to-systemic blood flow ratio (Qp/Qs) greater than 3.0 and a pulmonary-to-systemic vascular resistance ratio (Rp/Rs) less than 0.20, taken in combination, gave a positive predictive value for VD of 100%. It is concluded that the preoperative Qp/Qs and Rp/Rs can be used to predict those infants at risk for postoperative morbidity following repair of their VSD.


Eyelid Reconstruction and Infraorbital Repair Using a Mustardé Flap Technique in a Dog.
This case report describes a 5-year-old dog with a defect in the right eyelid, absence of orbicularis musculature, and absence of cutaneous tissue in the infraorbital region, submitted to the Mustardé flap technique. A large rotational flap was performed, including a cartilage graft from the outer ear, to correct the defect in the lower eyelid and infraorbital region. Also, euryblepharon correction of the upper eyelid was performed with wedge excision. The techniques were performed in a single surgical step and with appropriated functional and aesthetic results. The described approach may be employed as a surgical option in large eyelid defects.


Liver Function Assessment Using Parenchyma-Specific Contrast-Enhanced Ultrasonography.
The aim of this study was to assess hepatic functional reserve by analyzing the hepatic parenchyma enhancement curve of parenchyma-specific contrast-enhanced ultrasonography (CEUS). Fifty-two patients with cirrhosis who underwent CEUS and indocyanine green tests (ICG) because of a focal liver lesion were enrolled. We evaluated the hemodynamic-related parameters of the time-intensity curve and compared these findings with the ICG retention rate at 15 min (ICG R15). The correlation between the time from peak to one half (s) and ICG R15 was statistically significant and was relatively proportional to the ICG R15. A cut-off value of 149 s was determined for the time from peak to one half for abnormal ICG R15 (>14). The sensitivity and specificity were 85.7% and 92.3%, respectively, for the detection of abnormal ICG R15. In conclusion, the time from peak to one half of the time-intensity curve of parenchyma-specific CEUS of the liver can be a useful parameter to predict the hepatic reserve in liver cirrhosis.


Electrophysiology of extrafetal membranes.
This paper reviews some of the equations that apply to the electrophysiology of the extrafetal membranes, and stresses the limitations that may apply to the use of these equations. A literature review of experimental data on potential differences between the fetus, the extrafetal fluid compartments and the mother leads to the conclusion that the transplacental potential difference is no more than a few millivolts and that, in some species, there is an electrical generator outside the placenta.


Intermittent infusion of progesterone potentiates whereas continuous infusion reduces amphetamine-stimulated dopamine release from ovariectomized estrogen-primed rat striatal fragments superfused in vitro.
In the present experiment we examined the effect of a direct in vitro infusion of progesterone upon spontaneous and amphetamine-stimulated in vitro dopamine (DA) release and post-superfusion DA tissue concentration of corpus striatum tissue fragments from ovariectomized and estrogen-treated female rats. An intermittent infusion of progesterone at a dose of 2 ng/ml produced a significant increase in amphetamine-stimulated DA release and post-superfusion DA tissue concentration compared to similar superfusions infused with medium alone or cholesterol (2 ng/ml). Higher (50 ng/ml) or lower (0.2 ng/ml) doses of progesterone were ineffective and a continuous infusion of progesterone at an identical total concentration to that of the intermittent 2 ng/ml dose inhibited both amphetamine-stimulated DA release and post-superfusion DA tissue concentration. With the exception of 5 alpha DHP (dihydroxyprogesterone) intermittent infusions of various metabolites, a synthetic progestin (R5020) at 2 ng/ml and estradiol at both 0.2 ng/ml and 2 ng/ml failed to modify significantly the amphetamine-stimulated DA response. However, pregnanolone, 5 alpha DHP, R5020 at 2 ng/ml and estradiol at 0.2 ng/ml increased post-superfusion DA tissue concentration to levels comparable to that of progesterone. These results demonstrate that in vitro progesterone can directly alter the amphetamine-stimulated DA release from dopaminergic terminals of corpus striatal tissue fragments. This effect appears quite specific for progesterone as well as for a specific dose and mode of infusion of this gonadal steroid. Moreover, progesterone can exert opposite effects upon the amphetamine-evoked DA release from the corpus striatum as a function of its mode of infusion suggesting a means by which one hormone can differentially alter central nervous system function.


Neurological complications after gamma-knife radiosurgery for hypothalamic hamartoma.
The Gamma-knife technique is a safe and effective option for the treatment of hypothalamic hamartomas that produce epileptic seizures refractory to medical treatment and/or serious behavioral disorders. After this type of radiosurgery, an adequate symptomatic control is normally achieved, with notable decrease or even disappearance of the seizures. Radiological changes, such as a decrease in the size of the tumor or adjacent edema secondary to non-necrotizing radioinduced inflammatory reaction are unusual consequences. Side effects and neurological complications are also rare events. This report describes an unusual case of complete radiological resolution of a hypothalamic hamartoma as well as neurological complications after Gamma-knife surgery (receiving 13 Gy to the 85% isodose line, 1 cm(3) of tumor volume) in a 8-year-old boy who suffered from severe refractory seizures. After radiosurgery, the patient experienced a notable improvement in his symptoms, achieving seizure cessation within 3 months. However, 4 months after the procedure he presented drowsiness, fever and decreased level of consciousness due to a direct effect on the hypothalamus with local and regional edema secondary to the radiosurgery that was performed. He was successfully treated with corticosteroids (with a total duration of 11 months), and twelve months after the surgery, complete disappearance of both the nodular lesion and the secondary edema was observed. The patient remains seizure-free in the last 16 months, with remarkable changes in his behavior. The present case shows that complete radiological resolution of a hypothalamic hamartoma after Gamma-knife technique is unusual but possible, without long-term neurological consequences. Nevertheless, despite its low incidence, if a patient presents neurological symptoms, primarily during the first year after intervention, possible complications of this type of surgery must be taken into account.


ROS generation is involved in titanium dioxide nanoparticle-induced AP-1 activation through p38 MAPK and ERK pathways in JB6 cells.
Titanium dioxide (TiO2 ) is generally regarded as a nontoxic and nongenotoxic white mineral, which is mainly applied in the manufacture of paper, paint, plastic, sunscreen lotion and other products. Recently, TiO2 nanoparticles (TiO2 NPs) have been demonstrated to cause chronic inflammation and lung tumor formation in rats, which may be associated with the particle size of TiO2 . Considering the important role of activator protein-1 (AP-1) in regulating multiple genes involved in the cell proliferation and inflammation and the induction of neoplastic transformation, we aimed to evaluate the potency of TiO2 NPs (≤ 20 nm) on the activation of AP-1 signaling pathway and the generation of reactive oxygen species (ROS) in a mouse epidermal cell line, JB6 cells. MTT, electron spin resonance (ESR), AP-1 luciferase activity assay in vitro and in vivo, and Western blotting assay were used to clarify this problem. Our results indicated that TiO2 NPs dose-dependently caused the hydroxyl radical (·OH) generation and sequentially increased the AP-1 activity in JB6 cells. Using AP-1-luciferase reporter transgenic mice models, an obvious increased AP-1 activity was detected in dermal tissue after exposure to TiO2 NPs for 24 h. Interestingly, TiO2 NPs increased the AP-1 activity via stimulating the expression of mitogen-activated protein kinases (MAPKs) family members, including extracellular signal-regulated protein kinases (ERKs), p38 kinase, and C-Jun N-terminal kinases (JNKs). Of note, the AP-1 activation induced by TiO2 NPs could be blocked by specific inhibitors (SB203580, PD98059, and SP 600125, respectively) that inhibit ERKs and p38 kinase but not JNKs. These findings indicate that ROS generation is involved in TiO2 NPs-induced AP-1 activation mediated by MAPKs signal pathway.


[Effect of tuberculostatic agents and sodium succinate on the functional state of liver mitochondria in tuberculosis].
Effects of isoniazide and of new tuberculostatic drug of long-term action on functions of guinea pig liver mitochondria were studied in experimental tuberculosis. Significant changes in oxidative phosphorylation were found. The combination of sodium succinate with tuberculostatic drugs improved the bioenergetic functions of liver mitochondria under the conditions of antibacterial therapy of experimental tuberculosis.


Comparative photosynthesis of three gap phase successional tree species.
Photosynthesis was measured in situ on trees growing in an open, gap-like site and under a closed canopy. Photosynthetic responses also were monitored on trees grown in the laboratory under either a high or low light regime or on those trees transferred from a low to a high light regime. All three species studied, Liriodendron tulipifera, Acer rubrum and Cornus florida, were able to acclimate to a high light environment as evidenced by their higher photosynthetic rates. This acclimation was achieved by an increase in transfer conductance and was ultimately due to changes in leaf anatomy. Species avoided photo-bleaching primarily by changes in leaf orientation and canopy structure. Species-specific physiological responses to high light intensity may account for each species' known growth response following canopy opening.


Diffusion-weighted MRI in neurodegenerative and psychiatric animal models: Experimental strategies and main outcomes.
Preclinical MRI approaches constitute a key tool to study a wide variety of neurological and psychiatric illnesses, allowing a more direct investigation of the disorder substrate and, at the same time, the possibility of back-translating such findings to human subjects. However, the lack of consensus on the optimal experimental scheme used to acquire the data has led to relatively high heterogeneity in the choice of protocols, which can potentially impact the comparison between results obtained by different groups, even using the same animal model. This is especially true for diffusion-weighted MRI data, where certain experimental choices can impact not only on the accuracy and precision of the extracted biomarkers, but also on their biological meaning. With this in mind, we extensively examined preclinical imaging studies that used diffusion-weighted MRI to investigate neurodegenerative, neurodevelopmental and psychiatric disorders in rodent models. In this review, we discuss the main findings for each preclinical model, with a special focus on the analysis and comparison of the different acquisition strategies used across studies and their impact on the heterogeneity of the findings.


Nutrient constraints in the feeding ecology of an omnivore in a seasonal environment.
Nutrient requirements of adult, nonreproductive, omnivorous antelope ground squirrels (Ammospermophilus leucurus) were compared with the nutritional value of their food resources. It was found that nutrient constraints would be important factors in ground squirrel feeding ecology primarily in winter. Potentially important constraints were the requirement for water and nitrogen, and a digestive requirement that average dry matter digestibility of the diet exceed ca. 50%. An unlikely constraint was the requirement for any specific mineral. A linear programming model was used to determine potential diets ground squirrels could consume which satisfied these nutritional requirements and also the ground squirrel's daily energy requirements. During spring ground squirrels could be strict herbivores, but during winter before winter rains ground squirrels had to eat some arthropods to satisfy water requirements.These ground squirrels are not energy maximizers because they spend only one third of their activity period feeding and do not accumulate excess energy as fat. Thus, optimum diets were predicted for winter and spring assuming the goal of feeding time minimization. The model correctly predicted that in wintertime ground squirrels would be primarily granivorous but would consume about 20% arthropods, and that they would switch to herbivory in springtime. Ground squirrels, however, selected a wider dietary range than predicted in both winter and spring. Possible reasons for this discrepancy include an inappropriate assumption that ground squirrels forage for food classes nonsimultaneously, and the possibility that ground squirrels employ sampling as part of their foraging behavior.


The effect of direct and counter-current flow-through delignification on enzymatic hydrolysis of wheat straw, and flow limits due to compressibility.
This article compares the processes for wheat straw lignocellulose fractionation by percolation, counter-current progressing batch percolation and batch reaction at low NaOH-loadings (3-6% of DM). The flow-through processes were found to improve delignification and subsequent enzymatic saccharification, reduce NaOH-consumption and allow reduction of thermal severity, whereas hemicellulose dissolution was unaffected. However, contrary to previous expectations, a counter-current process did not provide additional benefits to regular percolation. The compressibility and flow properties of a straw bed were determined and used for simulation of the packing density profile and dynamic pressure in an industrial scale column. After dissolution of 30% of the straw DM by delignification, a pressure drop above 100 kPa m-1 led to clogging of the flow due to compaction of straw. Accordingly, the maximum applicable feed pressure and volumetric straw throughput was determined as a function of column height, indicating that a 10 m column can be operated at a maximum feed pressure of 530 kPa, corresponding to an operation time of 50 min and a throughput of 163 kg m-3 h-1 . Biotechnol. Bioeng. 2016;113: 2605-2613. © 2016 Wiley Periodicals, Inc.


Disparities in type 2 diabetes prevalence among ethnic minority groups resident in Europe: a systematic review and meta-analysis.
Many ethnic minorities in Europe have a higher type 2 diabetes (T2D) prevalence than their host European populations. The risk size differs between ethnic groups, but the extent of the differences in the various ethnic minority groups has not yet been systematically quantified. We conducted a meta-analysis of published data on T2D in various ethnic minority populations resident in Europe compared to their host European populations. We systematically searched MEDLINE (using PUBMED) and EMBASE for papers on T2D prevalence in ethnic minorities in Europe published between 1994 and 2014. The ethnic minority groups were classified into five population groups by geographical origin: South Asian (SA), Sub-Saharan African (SSA), Middle Eastern and North African (MENA), South and Central American (SCA), and Western Pacific (WP). Pooled odds ratios with corresponding 95 % confidence interval (CI) were calculated using Review Manager 5.3. Twenty articles were included in the analysis. Compared with the host populations, SA origin populations had the highest odds for T2D (3.7, 95 % CI 2.7-5.1), followed by MENA (2.7, 95 % CI 1.8-3.9), SSA (2.6, 95 % CI 2.0-3.5), WP (2.3, 95 % CI 1.2-4.1), and lastly SCA (1.3, 95 % CI 1.1-1.6). Odds ratios were in all ethnic minority populations higher for women than for men except for SCA. Among SA subgroups, compared with Europeans, Bangladeshi had the highest odds ratio of 6.2 (95 % CI 3.9-9.8), followed by Pakistani (5.4, 95 % CI 3.2-9.3) and Indians (4.1, 95 % CI 3.0-5.7). The risk of T2D among ethnic minority groups living in Europe compared to Europeans varies by geographical origin of the group: three to five times higher among SA, two to four times higher among MENA, and two to three times higher among SSA origin. Future research and policy initiatives on T2D among ethnic minority groups should take the interethnic differences into account.


Dietary habits and Helicobacter pylori infection: is there an association?
Helicobacter pylori (H. pylori) is a group 1 carcinogen and the etiological agent of gastric diseases such as gastritis, ulcers, and gastric cancer. It infects approximately half of the world's population. Risk factors associated with H. pylori infection include socioeconomic status, lifestyle, and diet. This study aimed to evaluate the association between eating habits and H. pylori infection in patients from a reference hospital in Central Brazil. This cross-sectional study included 156 patients from 2019 to 2022. Data were collected using a structured questionnaire on sociodemographic and lifestyle characteristics and a validated food frequency questionnaire. The H. pylori infection status (positive versus negative) was determined using the histopathological method. After grams/day, foods were stratified into tertiles of consumption (low, medium, and high). Simple and multiple binary logistic regression models were used in the analysis of odds ratios (ORs) and their respective 95% confidence intervals (CIs), with a 5% significance level. The prevalence of H. pylori infection was 44.2% (69/156 patients). Infected individuals had a mean age of 49.6 ± 14.6 years; 40.6% were men, 34.8% were aged 60 years or older, 42.0% were unmarried, 7.2% had higher education, 72.5% were non-white, and 30.4% were obese. In the H. pylori-positive group, 55.1% were alcohol drinkers and 42.0% were smokers. The results of multiple analyses showed that the chance of H. pylori infection was higher among male participants (OR = 2.25; CI = 1.09-4.68) and individuals with obesity (OR = 2.68; CI = 1.10-6.51). Participants with moderate consumption of refined grains (bread, cookies, cakes, breakfast cereal) (OR = 2.41; CI = 1.04-5.62) and fruits (OR = 2.53; CI = 1.08-5.94) were more likely to be infected. In this study, male sex, obesity, and the consumption of refined grains and fruits were positively associated with H. pylori infection. Further research is needed to investigate this association and elucidate the underlying mechanisms.


Insight into the surfactin production of Bacillus velezensis B006 through metabolomics analysis.
Bacillus velezensis B006 is a biocontrol agent which functions through effective colonization and surfactin production. To reveal the surfactin-producing mechanism, gas chromatography-mass spectrometry based untargeted metabolomics was performed to compare the metabolite profiles of strain B006 grown in industrial media M3 and M4. Based on the statistical and pathway topology analyses, a total of 31 metabolites with a fold change of less than - 1.0 were screened as the significantly altered metabolites, which distributed in 15 metabolic pathways. Fourteen amino acids involving in the metabolisms of alanine/aspartate/glutamate, glycine/serine/threonine, arginine/proline, glutathione/cysteine/methionine and valine/leucine/isoleucine as well as succinic acid in TCA cycle were identified to be the hub metabolites. Aminoacyl-tRNA biosynthesis, glycerolipid metabolism, and pantothenate/CoA biosynthesis also contributed to surfactin production. To the best of our knowledge, this study is the first to investigate the metabolic pathways of B. velezensis on surfactin production, and will benefit the optimization of commercial fermentation for higher surfactin yield.


A multi-technique analytical approach for impurity profiling during synthesis: The case of difluprednate.
A methodology for the qualitative analysis of a mixture of compounds obtained during the synthesis of difluprednate is described herein for the first time. For this scope a multi-technique analytical approach was developed, combining Liquid Chromatography/Mass Spectrometry (LC/MS), Nuclear Magnetic Resonance (NMR) and computational chemistry. Separation of isomers is frequently required for the identification of impurities in active pharmaceutical ingredients (APIs) to assess the impact they may exhibit on public health. During the final step of the difluprednate synthesis apart from the desired product, various by-products may be obtained. Structural analysis of the products using LC/MS and NMR indicated that the steroid difluprednate was obtained along with its acetyl/butyryl regional isomers, whereas the results were further supported by semi-empirical calculations of the MS-derived data. Following the proposed approach, we managed to elucidate the structures of the challenging 11-acetate, 17-butyrate from the 17-acetate, 21-butyrate, 6α,9α-difluoro prednisolone isomers. The approach utilized may be of general applicability for the analysis of impurities in active pharmaceutical ingredients obtained during chemical synthesis.


Energy metabolism in patients with acute and chronic liver disease.
Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS)


Environmental impact of a 290.4 kWp grid-connected photovoltaic system in Kocaeli, Turkey.
This paper examines the environmental impact of a grid-connected PV system in Kocaeli, Turkey, supported by East Marmara Development Agency to contribute local economic and environmental sustainability goals. For this purpose, energy payback time and greenhouse payback time analysis is carried out in terms of calculated total embodied data and measured annual operation data. The results indicate that the system spends approximately 12.68% of its lifetime to payback its total embodied energy and 10.67% to save its total embodied greenhouse gas emissions.


Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).
We re-analysed prospective data collected by anaesthetists in the Anaesthesia Sprint Audit of Practice (ASAP-1) to describe associations with linked outcome data. Mortality was 165/11,085 (1.5%) 5 days and 563/11,085 (5.1%) 30 days after surgery and was not associated with anaesthetic technique (general vs. spinal, with or without peripheral nerve blockade). The risk of death increased as blood pressure fell: the odds ratio (95% CI) for mortality within five days after surgery was 0.983 (0.973-0.994) for each 5 mmHg intra-operative increment in systolic blood pressure, p = 0.0016, and 0.980 (0.967-0.993) for each mmHg increment in mean pressure, p = 0.0039. The equivalent odds ratios (95% CI) for 30-day mortality were 0.968 (0.951-0.985), p = 0.0003 and 0.976 (0.964-0.988), p = 0.0001, respectively. The lowest systolic blood pressure after intrathecal local anaesthetic relative to before induction was weakly correlated with a higher volume of subarachnoid bupivacaine: r(2) -0.10 and -0.16 for hyperbaric and isobaric bupivacaine, respectively. A mean 20% relative fall in systolic blood pressure correlated with an administered volume of 1.44 ml hyperbaric bupivacaine. Future research should focus on refining standardised anaesthesia towards administering lower doses of spinal (and general) anaesthesia and maintaining normotension.


Cognitive basis about risk level classifications for the self-assessment of older drivers.
[Purpose] This study analyzed the cognitive functions according to risk level for the Driver 65 Plus measure, and examined the cognitive basis of self-assessment for screening the driving risk of elderly drivers. [Subjects and Methods] A total of 46 older drivers with a driver's license participated in this study. All participants were evaluated with Driver 65 Plus. They were classified into three groups of "safe," "caution" and "stop," and examined for cognitive functions with Trail Making Test and Montreal Cognitive Assessment-K. The cognitive test results of the three groups were compared. [Results] Trail Making Test-A, Trail Making Test-B, and Montreal Cognitive Assessment-K showed a significant difference between the three groups. The safe group showed significantly higher ability than the caution and stop groups in the three cognitive tests. In addition, cognitive functions of naming, attention, language, and delayed recall were significantly different between the three groups. [Conclusion] Self-assessment of older drivers is a useful tool for screening the cognitive aspects of driving risk. The cognitive functions, such as attention and recall, are the critical factors for screening the driving risk of elderly drivers.


Arginine vasotocin V1a2 receptor and GnRH-I co-localize in preoptic neurons of the sex changing grouper, Epinephelus adscensionis.
The arginine vasotocin/vasopressin (AVT/AVP) and gonadotropin releasing hormone (GnRH) systems are known to control sexual behaviors and reproduction, respectively, in different vertebrate groups. However, a direct functional connection between these two neuroendocrine systems has not been demonstrated for any vertebrate species. Therefore, the objective of this research was to test the hypothesis that AVT acts on the GnRH system via an AVT V1a receptor in a sex changing grouper species, the rock hind, Epinephelus adscensionis. AVT V1a2 receptors were co-localized with GnRH-I on neurons in the preoptic anterior hypothalamus identifying a structural linkage between the AVT system and GnRH-I. Transcripts for avt, gnrh-I, and two AVT receptor subtypes (v1a1 and v1a2) were isolated and characterized for E. adscensionis and their expression was measured in males and females by q-RT-PCR. Translation of V1a-type cDNA sequences revealed two distinct forms of the AVT V1a receptor in E. adscensionis brain similar to those reported for other species. The observation of significantly higher gnrh-I mRNA in the POA+H of rock hind males as compared to females suggests differential regulation of the gnrh-I transcripts in the two sexes of this protogynous species. In male E. adscensionis, but not in females, a negative relationship was seen between plasma 11-ketotestosterone (11-KT) and the v1a1 receptor mRNA levels in the POA+H, while a positive trend was observed between 11-KT and v1a2 receptor mRNA levels, indicating that these receptor forms may be differentially regulated.


Role of cytokines in the treatment of acute leukemias: a review.
Myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, have been used to decrease the duration of chemotherapy-induced neutropenia and thereby reduce the incidence and severity of infections in various regimens used to treat acute myeloid leukemia and acute lymphoblastic leukemia. These growth factors have also been used to recruit dormant myeloid leukemia cells into the S phase of cell cycle in order to increase their susceptibility to the antileukemic effects of agents such as cytarabine. Multiple prospective randomized trials have examined the benefit and safety of the addition of growth factors before, during, and after chemotherapy. A reduction in the duration of neutropenia has been the most consistent finding; this has not been associated with stimulation of leukemia cells, the main concern of using this strategy. Unfortunately, few studies have reported a benefit in prolonging the duration of disease-free survival or overall survival. Other cytokines, including interleukins and thrombopoietin, have also been evaluated for their theoretical ability to recruit immune mechanisms to eradicate residual leukemia burden after chemotherapy, and to stimulate platelet production. In this review, we summarize the clinical experience with these growth factors in treating acute leukemias.


Alterations of the lipid profile after 7.5 years of low-dose antioxidant supplementation in the SU.VI.MAX Study.
Antioxidant micronutrients have been reported to be associated with an improvement in the blood profile, but the results are not consistent. The aim of the present study was to assess the effects of antioxidant supplementation on changes in the serum lipid profile of adult participants in the SU.VI.MAX study. French adults (n = 12,741: 7,713 females aged 35-60 yr, and 5,028 males aged 45-60 yr) received daily antioxidant supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium, and 20 mg zinc) or a matching placebo. Median follow-up time was 7.5 yr. After 7.5 yr, no effect of supplementation on total cholesterol was observed in men or women after adjusting for baseline total cholesterol levels and lipid-lowering medications. The prevalence of hypercholesterolemia (> or =6.5 mmol/L) showed a trend toward being higher in women who received supplements compared with those who received the placebo (P= 0.06). In both sexes, the group receiving supplements exhibited higher mean serum TG concentrations than did the placebo group (P= 0.06 in men; P= 0.05 in women). The prevalence of hypertriglyceridemia (> or =2.3 mmol/L) was also significantly higher in men who received supplements (P= 0.03), but not in women. Our results suggest than long-term daily supplementation with low doses of beta-carotene, vitamins C and E, selenium, and zinc does not result in an improved lipid profile and could even adversely affect some blood lipids, possibly with a higher risk of hyperlipidemia in women.


Comparison of micromotion in mobile bearing and posterior stabilized total knee prostheses: a randomized RSA study of 40 knees followed for 2 years.
On theoretical grounds mobile bearing total knees should reduce the micromotion of the tibial component relative to the bone. We used radiostereometric analysis to measure the three-dimensional micromotio in 42 tibial components during 2 years of follow-up. The patients had been randomized as to whether they would receive a mobile bearing (MB) or posterior stabilized (PS) design. We expected that the MB knee would facilitate dissipation of forces from the prosthesis-bone interface by the motion of the bearing and by load sharing with the soft tissues, leading to less micromotion. In the PS designs, limited free rotation caused by the cam-post articulation might cause additional stress at the bone prosthesis interface. We found no significant differences between the MB and PS group at the 2-year follow-up evaluation with respect to Knee Society scores and radiographi results. The PS group had a higher variability in subsidence and anterior-posterior tilting of the component than the MB group. The low variability of the data in the MB knee prosthesis group suggests that this design more predictable and forgiving with respect to micromotion of the tibial component.


Effect of cadmium on lipid peroxidation and activities of antioxidant enzymes in growing pigs.
Malondialdehyde (MDA), glutathione (GSH) content, total antioxidant capacity (T-AOC) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were studied in serum, liver, and kidney of growing pigs after graded doses of cadmium administration in diets. One hundred ninety-two barrows (Duroc x Landrace x Yorkshire), with similar initial body weight 27.67 +/- 1.33 kg, were randomly allotted into 4 different treatments with 3 replications (16 pigs per replication). The treatments received the same basal diet added with 0, 0.5, 5.0, and 10.0 mg/kg cadmium (as CdCl2), respectively. The results showed pigs treated with 10 mg/kg cadmium significantly decreased average daily gain (ADG) (p<0.05) and increased feed/gain ratio (F/G) (p<0.05) compared to the control. In this treatment, the contents of MDA increased significantly (p<0.05), GSH concentrations, T-AOC levels, and the activities of SOD, GSH-PX, and GST decreased significantly (p<0.05). The results indicate 10 mg/kg cadmium could decrease pig antioxidant capacity after extended exposure and cadmium-induced increase lipid peroxidation might not be only the result of the possibility of lower level of GSH but could also be as a result of direct action of cadmium on peroxidation reaction.


Measuring cell-cell tugging forces using bowtie-patterned mPADs (microarray post detectors).
Cells generate traction forces upon adhesion to the extracellular matrix as well as to neighboring cells. These forces are important for the growth and maintenance of adhesion structures such as focal adhesions and adherens junctions, and may play roles in tissue development. Here, we describe a method for measuring the tugging force transmitted across the cell-cell junction between two paired cells.


Association of ambient air pollution with risk of hemorrhagic stroke: A time-stratified case crossover analysis of the Singapore stroke registry.
Haemorrhagic stroke (HS) is a major cause of mortality and disability. Previous studies reported inconsistent associations between ambient air pollutants and HS risk. We evaluated the association between air pollutant exposure and the risk of HS in a cosmopolitan city in the tropics. We performed a nationwide, population-based, time-stratified case-crossover analysis on all HS cases reported to the Singapore Stroke Registry from 2009 to 2018 (n = 12,636). We estimated the risk of HS across tertiles of air pollutant concentrations in conditional Poisson models, adjusting for meteorological confounders. We stratified our analysis by age, atrial fibrillation and smoking status, and investigated the lagged effects of each pollutant on the risk of HS up to 5 days. All 12,636 episodes of HS were included. The median (1st-to 3rd-quartile) daily pollutant levels from 22 remote stations deployed across the island were as follows: (PM2.5 = 15.9 (12.7-20.5), PM10 = 27.3 (22.7-33.4), O3 = 22.5 (17.3-29.8), NO2 = 23.3 (18.8-28.4), SO2 = 10.2 (5.6-14.4), CO = 0.5 (0.5-0.6). The median (1st-to 3rd-quartile) temperature (°C) was 27.9 (27.1-28.7), that of relative humidity (%) was 79.4 (75.6-83.2), and that of total rainfall (mm) was 0.0 (0.0-4.2). Higher levels of CO were significantly associated with an increased risk of HS (3rd tertile vs 1st tertile: Incidence Rate Ratio (IRR) = 1.06, 95% CI = 1.01-1.12). The increased risk of HS due to CO persisted for at least 5 days after exposure. Individuals under 65 years old and non-smokers had a higher risk of HS when exposed to CO. O3 was associated with increased risk of HS up to 5 days (3rd tertile vs 1st tertile: IRRday 1 = 1.07, 95% CI = 1.02-1.12; IRRday 5 = 1.07, 95% CI = 1.02-1.13). Short-term exposure to ambient CO levels was associated with an increased risk of HS. A reduction in CO emissions may reduce the burden of HS in the population.


Pentachlorophenol and hexachlorobenzene in serum and urine of the population of Barcelona.
1 Urinary chlorophenols of the general population of Barcelona, Spain were determined. Pentachlorophenol (PCP: 25.0 +/- 3.9 ng/ml; mean +/- s.e.m., n = 50) and tetrachlorophenol (TCP: 6.2 +/- 1.6 ng/ml; mean +/- s.e.m., n = 25) were found in all samples. 2 Pentachlorophenol and hexachlorobenzene were also determined in serum. Both were present in all samples (PCP: 21.9 +/- 1.9 ng/ml; HCB: 11.1 +/- 1.1 ng/ml; mean +/- s.e.m., n = 100). Their concentrations do not show any correlation, suggesting no metabolic relation between them.


Evidence for respiratory and nonrespiratory subtypes in panic disorder.
Recently researchers have posited a "respiratory" subtype of panic disorder (PD), which differs from "nonrespiratory" subtypes in phenomenology and perhaps treatment response. This study was designed to further examine evidence for the existence of a respiratory subtype in PD. Individuals with PD with prominent respiratory symptoms (PD-R; n=10) and without prominent respiratory symptoms (PD-NR; n=23), as well as healthy controls (n=27), underwent a standardized 5% CO(2) rebreathing challenge. Ventilatory response and subjective sensation of suffocation were continuously recorded. The PD-R group exhibited greater subjective suffocation levels, rates of respiration, and propensity to terminate the procedure voluntarily than did the other two groups, which in turn did not differ on these measures. Findings are consistent with the existence of a respiratory subtype of PD, which differs from nonrespiratory subtypes in CO(2) sensitivity.


[Effect of time elapsed from spontaneous syncope on the diagnostic performance of the head-up tilt table test].
The propensity for spontaneous and tilt-induced neurocardiogenic syncope may exhibit temporal variations. Therefore the diagnostic performance of the head-up tilt test could be improved if it were performed soon after the occurrence of spontaneous syncope. The objective of this study was to assess whether the time interval between the last syncopal episode and tilt table testing influenced the outcome of the test. Three hundred and fifteen patients undergoing diagnostic tilt table testing potentiated with nitroglycerin for suspected neurocardiogenic syncope were included in the study. The time between the last spontaneous syncope and the tilt table test was recorded and its relationship with the results of the test was analyzed. The tilt table test was positive in 211 patients (67.0%). The time from syncope to test was similar for patients with positive and negative tilt table test results: 28 (1-500) vs 32 (2-700) days (NS). No significant relation was observed between the results of the test and the occurrence of spontaneous syncope during the week, the month or the three months previous to the procedure. However, in men and in patients older than 50 years a higher rate of positive tests was observed if the tilt test was performed within the first month after the last spontaneous syncope. The time from the last previous spontaneous syncope to the head-up tilt test does not have a significant impact on test outcome in the overall population with suspected neurocardiogenic syncope. However, the rate of positivity might decrease in men and patients older than 50 years if the test is performed later than one month after the spontaneous syncopal episode.


Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin.
N-arachidonoylethanolamine (anandamide, AEA), is a full agonist at both cannabinoid CB(1) receptors and "transient receptor potential vanilloid" type 1 (TRPV1) channels, and N-palmitoylethanolamine (PEA) potentiates these effects. In neurons of the rat dorsal root ganglia (DRG), TRPV1 is activated and/or sensitised by AEA as well as upon activation of protein kinases C (PKC) and A (PKA). We investigated here the effect on AEA levels of PKC and PKA activators in DRG neurons. AEA levels were significantly enhanced by both phorbol-miristoyl-acetate (PMA), a typical PKC activator, and forskolin (FSK), an adenylate cyclase stimulant, as well as by thrombin, which also activates PKC by stimulating protease-activated receptors (PARs). The levels of the other endocannabinoid and TRPV1-inactive compound, 2-arachidonoylglycerol (2-AG), were enhanced only by thrombin and to a lesser extent than AEA, whereas PEA was not affected by any of the treatments. Importantly, FSK- and PMA-induced elevation of AEA levels was not sensitive to intracellular Ca2+ chelation with BAPTA-acetoxymethyl (AM) ester. In human embryonic kidney (HEK-293) cells, which constitutively express PARs, thrombin, PMA and FSK elevated AEA levels, and the effects of the two former compounds were counteracted by the PKC inhibitor, RO318220, whereas the effect of FSK was reduced by the PKA inhibitor RpcAMPs. In conclusion, we report that AEA levels are stimulated by both PKC, either directly or after thrombin receptor activation, and PKA, possibly in a way independent from intracellular calcium. Since AEA activates TRPV1, these findings may suggest the existence of an amplificatory cascades on this receptor in sensory neurons.


The effect of obesity on the mortality of hospitalized adults with COVID-19 considering the human development index: A systematic review and meta-analysis.
The objective of this study is to verify the association between obesity and mortality in hospitalized patients with SARS-CoV-2 taking into account the Human Development Index (HDI). A search was performed in the PubMed, Virtual Health Library (Lilacs/Bireme/VHL Brazil), Embase, Web of Science, and Scopus databases from inception to May 2022. To be eligible, studies had to have cohort or case-control designs, be conducted with hospitalized adults (≥18 years old), and evaluate mortality rates between with obesity and without obesity individuals with SARS-CoV-2 confirmed by laboratory tests. The analyses were performed in Stata 12.0 using relative risk (RR) as a summary measure. Heterogeneity was explored by meta-regression and subgroup analyses considering the HDI, age, sex, and follow-up period. Out of 912 studies screened, 49 studies were eligible for qualitative synthesis, and 33 studies were eligible for quantitative analysis, representing 42,905 patients. The mortality risk from SARS-CoV-2 was higher in individuals with obesity compared with without obesity individuals only in the subgroups of patients <60 years old (RR = 1.31; 95% CI 1.18-1.45, I2 = 0.0%) and living in countries with a low HDI (RR = 1.28; 95% CI 1.10-1.48, I2 = 45.4%).


Pseudopeptides and beta folding: x-ray structures compared with structures in solution.
In order to restrain the flexibility of the peptide molecules and reduce their biodegradation, modifications of the main chain are now introduced in pseudopeptide analogues. Surprisingly, there is very little data on the conformational properties of these derivatives. We have examined pseudopeptide analogues of RCO-X-Y-NHR' model dipeptides in the depsi, N-methylated, reduced, retro, alpha, beta-dehydro, beta-amino acid, and hydrazino series, in the solid state by x-ray diffraction, and in solution by ir and 1H-nmr spectroscopy. This study provides us with accurate dimensions of the peptide surrogates, and gives some information on the conformational tendencies induced by these substitutions, with reference to those of the related dipeptide sequences.


Mouse model implicates GNB3 duplication in a childhood obesity syndrome.
Obesity is a highly heritable condition and a risk factor for other diseases, including type 2 diabetes, cardiovascular disease, hypertension, and cancer. Recently, genomic copy number variation (CNV) has been implicated in cases of early onset obesity that may be comorbid with intellectual disability. Here, we describe a recurrent CNV that causes a syndrome associated with intellectual disability, seizures, macrocephaly, and obesity. This unbalanced chromosome translocation leads to duplication of over 100 genes on chromosome 12, including the obesity candidate gene G protein β3 (GNB3). We generated a transgenic mouse model that carries an extra copy of GNB3, weighs significantly more than its wild-type littermates, and has excess intraabdominal fat accumulation. GNB3 is highly expressed in the brain, consistent with G-protein signaling involved in satiety and/or metabolism. These functional data connect GNB3 duplication and overexpression to elevated body mass index and provide evidence for a genetic syndrome caused by a recurrent CNV.


Taste responses in the facial lobe of the carp, Cyprinus carpio L.
Single unitary discharges in the facial lobe of carp, Cyprinus carpio L., were studied electrophysiologically in response to chemical stimulation of the chemoreceptors of the facial skin. Of 258 neurons recorded, 95% were facilitated by taste stimuli and 5% were inhibited. According to responsiveness to the 4 basic tasting substances, the taste neurons were classified into 5 types: type I which was activated by one stimulus (43% of total neurons), type II by two (35%), type III by three (12%), type IV by 4 (5%), and type V which was inhibited by certain qualities (5%). Statical analysis revealed that responsiveness of taste neurons differed somewhat in receptive fields of the face. The taste neurons in the barbel and lip areas of the facial lobe showed variable responsiveness to chemical solutions, but those in other areas belonged generally to types I or II and did not respond to sucrose. Sodium chloride solution was the most effective among the 4 basic stimuli in this experiment. About 90% of the taste neurons also responded to mechanical stimulation of taste receptive fields. Tactile neurons in the facial lobe were localized in a topographical manner and the taste neurons were arranged in the tactile areas, but chemotopical organization was not recognized in the present study.


Increased telomerase activity in intrahepatic cholangiocellular carcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters.
Telomerase activities in intrahepatic cholangiocarcinomas induced by N-nitrosobis(2-oxopropyl)amine (BOP) in female hamsters were determined using a telomeric repeat amplification protocol (TRAP) assay followed by densitometric quantification. Each determination was repeated to confirm the results and telomerase activity was also detected by gel electrophoresis. An increase was evident in all of 10 cholangiocarcinomas examined, with levels ranging from 2.48 to 4.40 times the normal liver value by densitometric quantification. This finding of a consistent increase suggests that telomerase activation is involved in the development of intrahepatic cholangiocarcinomas and immortalization of cancer cells.


Retrospective detection of exposure to organophosphorus anti-cholinesterases: mass spectrometric analysis of phosphylated human butyrylcholinesterase.
In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this method is exemplified by the positive analysis of serum samples from Japanese victims of the terrorist attack with sarin in the Tokyo subway in 1995.


Comparison of methods with respect to efficiencies, recoveries, and quantitation of mercury species interconversions in food demonstrated using tuna fish.
Eight different analytical extraction procedures commonly used to extract mercury species from biological samples were evaluated by analyzing Tuna Fish Tissue Certified Reference Material (ERM-CE464) certified for the content of total mercury and methylmercury. Speciated isotope dilution mass spectrometry (SIDMS; US Environmental Protection Agency's method 6800) was utilized to evaluate and effectively compensate for potential errors during measurement and accurately quantify mercury species using all the extraction methods. SIDMS was used to accurately evaluate species transformations during sample pretreatment, preparation and analysis protocols. The extraction methods tested in this paper were based on alkaline extraction with KOH or tetramethylammonium hydroxide; acid leaching with HCl, HNO(3) or CH(3)COOH; extraction with L: -cysteine hydrochloride; and enzymatic digestion with protease XIV. Detection of total mercury and mercury species from all extraction methods was carried out by inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography-ICP-MS, respectively. Microwave-assisted extraction and ultrasound-assisted extraction were found to be the most efficient alkaline digestion protocols that caused the lowest levels of transformation of mercury species (6% or less). Extraction with 5 M HCl or enzymatic digestion with protease resulted in the second-highest extraction efficiency, with relatively lower transformation of methylmercury to inorganic mercury (3 and 1.4%, respectively). Despite frequent use of acid leaching for the extraction of mercury species from tuna fish samples, the lowest extraction efficiencies and the highest mercury species transformation were obtained when microwave-assisted extraction with 4 M HNO(3) or CH(3)COOH was used. Transformations as high as 30% were found using some literature protocols; however, all the extractions tested produced accurate quantitation when corrected in accordance with the SIDMS method standardized in the US Environmental Protection Agency's method 6800. [figure: see text]


Optimization of arc angles in rotational therapy.
Data is presented that will aid in optimizing the arc angles used for rotational therapy for a 6 Mv x-ray beam. Computer calculations of isodose distributions were carried out and the Ap and Lateral dimensions of the 95 and 100% isodose line were tabularized as a function of the field width (6-14 cm), distance between isocenter and patient midline (0-3 cm), and bilateral 120 or 100 degrees arc angle. The 300 degrees rotation cases we studied were generally found to be inferior to 120 degrees or 100 degrees bilateral arc rotations. 120 degrees arcs are best when the target center is within 2 cm of the patient's Ap center. As that separation increases, the bilateral arc angle should be decreased or wedges should be rotated through 300 degrees to avoid maximum doses greater than 105%. The data tables can be used as a starting point for computer calculations to select the field width and the arc angle for a particular target location and size. Of note is the degree to which the dimensions of the 100% isodose line decreases for small field widths and large isocenter to patient midline distances.


Doppler color flow mapping studies of jet formation and spatial orientation in obstructive hypertrophic cardiomyopathy.
To help clarify the mechanism of outflow tract obstruction and systolic anterior motion of the anterior leaflet of the mitral valve and their relation to the geometry of the left ventricle, we studied left ventricular outflow tract flow in 20 patients with hypertrophic cardiomyopathy (HCM) using two-dimensional Doppler flow mapping. We compared our results with outflow tract flow in 10 patients with isolated valvular aortic stenosis, (AS) and with those in 10 healthy volunteers. In HCM, a 94- to 145-degree angle (mean 111.4 +/- 11.9 degrees) developed between the direction of left ventricular outflow tract flow acceleration and aortic valve outflow, resulting in posterolaterally directed left ventricular outflow jets. The angle of the outflow jet and the peak velocity of the jet measured with continuous wave Doppler (as an indicator of the severity of obstruction) correlated well (r = -0.81, SEE = 7.8 degrees). Jet narrowing during ejection measured just proximal to the point of systolic anterior motion was 42 +/- 11% in HCM and was weakly correlated with peak jet velocity (r = 0.61, SEE = 8.9 degrees). Aliasing of left ventricular outflow occurred proximal to systolic anterior motion of the mitral valve, and color M-mode demonstrated temporal and spatial flow acceleration proximal to systolic anterior motion, providing evidence for obstruction at that site. In AS, left ventricular outflow tract jets were more parallel to the axis of aortic outflow (129 to 153 degree, 138.4 +/- 8.1 degrees). Jet narrowing was only 8 +/- 5% compared to HCM (both p less than 0.05), and flow acceleration occurred proximal to the stenotic valve.(ABSTRACT TRUNCATED AT 250 WORDS)


Multiple orofacial malformations in a boy who was conceived by intracytoplasmic sperm injection.
Intracytoplasmic sperm injection (ICSI) and other assisted reproductive technologies (ART) are effective treatments for infertility and are widely used at infertility clinics. Although ICSI is generally considered safe, some studies have suggested an excess occurrence of major birth defects resulting from the procedure. Here, we present a rare case of a boy with multiple orofacial malformations who was conceived by ICSI. We suggest therefore that the risk of genetics abnormalities should be discussed in detail with the parents and sufficient informed consent should be obtained before starting ICSI procedures.


Biomechanical and Cortical Control of Tongue Movements During Chewing and Swallowing.
Tongue function is vital for chewing and swallowing and lingual dysfunction is often associated with dysphagia. Better treatment of dysphagia depends on a better understanding of hyolingual morphology, biomechanics, and neural control in humans and animal models. Recent research has revealed significant variation among animal models in morphology of the hyoid chain and suprahyoid muscles which may be associated with variation in swallowing mechanisms. The recent deployment of XROMM (X-ray Reconstruction of Moving Morphology) to quantify 3D hyolingual kinematics has revealed new details on flexion and roll of the tongue during chewing in animal models, movements similar to those used by humans. XROMM-based studies of swallowing in macaques have falsified traditional hypotheses of mechanisms of tongue base retraction during swallowing, and literature review suggests that other animal models may employ a diversity of mechanisms of tongue base retraction. There is variation among animal models in distribution of hyolingual proprioceptors but how that might be related to lingual mechanics is unknown. In macaque monkeys, tongue kinematics-shape and movement-are strongly encoded in neural activity in orofacial primary motor cortex, giving optimism for development of brain-machine interfaces for assisting recovery of lingual function after stroke. However, more research on hyolingual biomechanics and control is needed for technologies interfacing the nervous system with the hyolingual apparatus to become a reality.


[Sergentomyia berentiensis N. sp. (Diptera, Psychodidae). Description of a female specimen collected in Madagascar].
The authors describe, from a single female caught in Madagascar, a new species of sandfly: Sergentomyia berentiensis. They give mensurations and specific features (spermatheca, cibarium, pharynx). They note some similitudes with American species.


Determination of radial bone mineral content in low birth weight infants by photon absorptiometry.
Studies at the University of Wisconsin have demonstrated that photon absorptiometry is a precise, accurate, and reproducible technique for measuring bone mineral content in premature infants and can be used to establish an "intrauterine" curve of bone mineralization in the fetus. Photon absorptiometry can also be used to measure bone width, thereby documenting appositional bone growth. The bone mineral content/bone width ratio may be helpful in identifying disorders of bone mineral metabolism in premature infants. The technique has been used to demonstrate that relatively poor bone mineralization (compared with the intrauterine curve) occurs in very low birth weight infants after birth, regardless of the type of feeding or the presence or absence of bronchopulmonary dysplasia.