Infection phase is a predictor of pruritus in patients with hepatitis B virus infection.
Pruritus is a common pathogenesis in liver diseases, including chronic hepatitis B (CHB). The phases of hepatitis B virus (HBV) infection are defined in the American Association for the Study of Liver Diseases guidelines. However, it still remains unclear whether the phase independently affects pruritus. The aim of this study was to clarify the effect of HBV infection phase on pruritus in patients with HBV. Of the 1,631 patients that attended the joint research facilities and were interviewed regarding their pruritus between January and June 2016, 196 patients with HBV infection were selected for the present analysis. One-to-one propensity score-matching using 13 variables was performed between participants in the hepatitis B e antigen (HBe-Ag)-positive/negative immune-active phase group and the inactive CHB phase group. Data from 47 patients per group were included in the final analysis. The prevalence of pruritus in the inactive CHB phase was significantly lower than in the HBe-Ag-positive/negative immune-active phase (23 vs. 47%; P=0.031). Being in the inactive CHB phase was determined to be an independent risk factor for pruritus (odds ratio, 0.35; 95% confidence interval, 0.143-0.842; P=0.019). The progression to inactive CHB phase may contribute to the amelioration of pruritus in patients with HBV infection.


Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy.
The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.


Zn- and Cd-based Coordination Polymers Offering H-Bonding Cavities: Highly Selective Sensing of S2 O7 2- and Fe3+ Ions.
We present two ZnII - and CdII -based coordination polymers (CPs), L-Zn and L-Cd, offering H-bonding-based cavities of varying dimensions. Both CPs were used for the highly selective detection of S2 O7 2- and Fe3+ ions where H-bonding based cavities played an important role. Fluorescence quenching, competitive binding studies and binding parameters substantiated significant recognition of S2 O7 2- and Fe3+ ions by both CPs.


[A precursor of phospholipids in the treatment of severe traumatic comas].
CDP Choline, a metabolic precursor of phospholipids, has been tested against placebo in a controlled randomized double blind study concerning 60 cases of severe head injuries (wide-spread cerebral contusions and/or severe concussion). In the treated group, a shortening of the comatose period and an acceleration of neurological deficits recovery have been observed. These results are tentatively attributed to an effect of the drug against brain edema, already documented on experimental models.


Successful use of combination antifungal therapy in the treatment of coccidioides meningitis.
Coccidioidal meningitis is a highly lethal condition with a high morbidity and relapse rate caused by Coccidioides immitis. This case report highlights the difficulty in diagnosing and treating coccidioidal meningitis, and discusses a novel combination antifungal therapy (voriconazole and liposomal amphotericin B), which was used to treat this patient.


Estrogen and combined estrogen-progestogen therapy in the menopause and breast cancer.
Most of the data on menopausal hormone therapy (HT) and breast cancer risk available up to the mid-1990s were included in a collaborative reanalysis based on over 52,000 women with and 108,000 without breast cancer. HT increased the risk of breast cancer by about 2.3% per year of use. Subsequent studies have confirmed that breast cancer risk is elevated in current and recent (but not past) HT users and that the relative risk (RR) is higher for users of combined estrogen-progestin treatment than for users of estrogen only, and this higher RR is seen with various types of preparations and different routes of administration. With reference to intervention studies, information on combined HT derives from the Women's Health Initiative (WHI). After 7 years of follow-up, 166 breast cancer cases were recorded in the HT group, as against 124 in the placebo group, corresponding to a RR of 1.24. Data from two other, smaller, randomized studies are available. In a combined analysis of the three randomized trials, 205 cases of breast cancer were observed in the treated groups as against 154 in the placebo groups, corresponding to a pooled RR of 1.27. However, in the estrogen-only component of the WHI population, at 8 years of follow-up 94 cases were observed in the estrogen group, opposed to 124 in the placebo group (RR=0.77). The results recorded in the WHI and the Million Women Study do not confirm the suggestion that breast cancers in women using HT have a more favorable prognosis. HT has also been related to an increased risk of recurrent breast cancer.


Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study.
To identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls. Ninety percent of the IIH patients were women; the mean age was 33. Obesity and recent weight gain were much more common among patients than controls. Symptoms most commonly reported by IIH patients were headache (94%), transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%). Daily occurrence of these symptoms was much more common among patients than controls. Controls also reported these and other IIH symptoms, but at lower frequencies. Several conditions previously associated with IIH were no more common in patients than controls including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives. We conclude that previous studies of IIH, mostly uncontrolled and retrospective, have underestimated the frequency of symptoms in IIH patients and reported chance and spurious associations with common medical conditions and medications. The profile of a young obese woman with headaches and either TVO or ICN should alert the clinician to the diagnosis of IIH, especially when the symptoms occur daily.


Manubriosternal joint dislocation in contact sport.
A 17 year old man developed chest pain and shortness of breath immediately after a scrummage while playing rugby football. A lateral chest radiograph showed a dislocated manubriosternal joint, with no associated injuries. This has not been previously reported in a sporting setting. This injury should be considered in flexion-compression injury of the thorax.


Effectiveness of a Water Intake Program at the Workplace in Physical and Mental Health Outcomes.
Adequate water intake is a low-cost and effectively non-invasive strategy for individual health outcomes. We aimed to demonstrate the efficacy of water intake intervention in intensive-labor and static-type workplaces. Smart drinking cups were provided to the participants, and a built-in application (App) associated with the cup was downloaded on their phones. The App collected and recorded the amount of drinking water consumed by the participants set reminders for drinking water and drinking water health education information. We assessed the data, including the amount of and time interval between water intake, sedentary time, the degree of physical and psychological importance of oneself, self-satisfaction, and physical fitness. After the intervention, water intake in the two companies significantly increased during the reminder period compared with the non-reminder period. A significant increase was noted in week 3 in the amount of water intake by the participants after using the App, and the total sedentary time considerably decreased. Furthermore, the interval between water consumption decreased compared with the preintervention interval. The systolic and diastolic blood pressure decreased in the participants working at the static-type and intensive-labor workplaces after the intervention, respectively. The participants ' lower limb muscle performance also improved significantly, and the emphasis on self-care was significantly improved. The health-promoting effects of the water intake wellness intervention were akin to the butterfly effect. Besides significantly increasing water intake, the intervention improved other health behaviors, thereby benefiting physical and mental health. Hence, promoting water consumption in workplaces till it becomes a habit may benefit the employees.


The Impact of Recipient Site External Expansion in Fat Grafting Surgical Outcomes.
The fat grafting process includes the 4 phases of tissue harvesting, processing, recipient-site preparation, and reinjection. Among them, the preparation of the recipient site has never been exhaustively reviewed. We aim to provide a comprehensive overview of the methods to prepare the recipient site through external expansion with the resulting outcomes. PubMed/Medline database was searched for studies on fat grafting recipient site preparation by applying the following algorithm: ((fat grafting) OR (lipofilling) OR (lipograft) AND (recipient site)). A priori criteria were used to review the resulting articles and identify those dealing with external expansion. Fourteen studies published from 2008 through 2016 met inclusion criteria (4 case reports, 6 retrospective, and 4 prospective studies), representing 1,274 treated patients. Two devices for preexpansion were used with different protocols: BRAVA system and Kiwi VAC-6000M with a PalmPump. The 13 studies that applied the BRAVA system reported large fat volume transplantation to the breast (average > 200 cc). The most common complications were localized edema (14.2%), temporary bruising, and superficial skin blisters (11.3%), while the most serious was pneumothorax (0.5%). The majority of the studies reported enhancement of fat graft survival, which ranged between 53% and 82% at 6 months to 1 year follow-up, and high satisfaction of patients and surgeon. External expansion and fat grafting is a promising technique for breast reconstruction and augmentation. However, due to the overall low level of evidence of the available studies, further research is needed to validate the procedure.


The Rheumatoid Arthritis Risk Gene LBH Regulates Growth in Fibroblast-like Synoviocytes.
Fibroblast-like synoviocytes (FLS) are key players in the synovial pathology of rheumatoid arthritis (RA). Currently, there is no treatment that specifically targets these aggressive cells. By combining 3 different "omics" data sets, i.e., 1) risk genes in RA, 2) differentially expressed genes, and 3) differential DNA methylation in RA versus osteoarthritis (OA) FLS, we identified LBH (limb bud and heart development) as a candidate gene in RA. The present study was undertaken to define the role of this gene in FLS. Synovial tissue specimens from RA and OA patients were collected at the time of joint replacement surgery. LBH expression was silenced using small interfering RNA or overexpressed using an LBH expression vector in primary FLS. Gene expression profiles were determined by microarray and assessed using Ingenuity Pathway Analysis. Effects of modified LBH expression were investigated in functional assays. LBH was expressed in the synovial lining layer in patients with RA. Transforming growth factor β1 significantly increased LBH expression in primary FLS, and platelet-derived growth factor BB decreased it. Pathway analysis of the transcriptome of LBH-deficient FLS compared to control FLS identified "cellular growth and proliferation" as the most significantly enriched pathway. In growth assays, LBH deficiency increased FLS proliferation. Conversely, LBH overexpression significantly inhibited cell growth. Cell cycle analysis demonstrated a marked increase in cells entering the cell cycle in LBH-deficient FLS compared to controls. LBH did not alter apoptosis. LBH is a candidate gene for synovial pathology in RA. It is regulated by growth factors and modulates cell growth in primary FLS. Our data suggest a novel mechanism for synovial intimal hyperplasia and joint damage in RA.


Physical Exercise Improves Aging-Related Changes in Angiotensin, IGF-1, SIRT1, SIRT3, and VEGF in the Substantia Nigra.
Dysregulation of tissue renin-angiotensin system (RAS) is involved in oxidative and inflammatory processes observed in major aging-related diseases, including neurodegenerative diseases such as Parkinson's disease (PD). Physical exercise has beneficial effects against aging-related changes, dopaminergic neuron vulnerability, and PD progression. The present study indicates that sedentary aged rats have an increase in activity of the nigral angiotensin (Ang) II/Ang type 1 receptor (AT1) axis (ie, the pro-oxidative pro-inflammatory arm), and a decrease in the activity of the RAS protective arm (ie, Ang II/AT2 and Ang 1-7/Mas receptor axis) in comparison with young rats. In addition, sedentary aged rats showed a decrease in levels of nigral IGF-1, SIRT1, SIRT3, and VEGF. Treadmill running induced a significant increase in levels of IGF-1, SIRT1, SIRT3, and VEGF, as well as an increase in expression of the protective Ang 1-7/Mas axis and inhibition of the Ang II/AT1 axis. The exercise-induced increase in IGF-1 and sirtuins may mediate the effects of exercise on the nigral RAS. However, exercise may induce the increase in VEGF and modulation of RAS activity by different pathways. Exercise, via RAS, contributes to inhibition of the pro-oxidative and proinflammatory state that increase dopaminergic neuron vulnerability and risk of PD with aging.


Influence of Heating during Cooking on Trans Fatty Acid Content of Edible Oils: A Systematic Review and Meta-Analysis.
Consumption of trans fatty acids (TFA) is associated with adverse health outcomes and is a considerable burden on morbidity and mortality globally. TFA may be generated by common cooking practices and hence contribute to daily dietary intake. We performed a systematic review and meta-analysis to investigate the relationship between heating edible oils and change in their TFA content. A systematic search of experimental studies investigating the effect of various methods of heating on TFA content of edible oils was conducted in Medline and Embase since their inception up to 1 October 2020 without language restrictions. Comparable data were analysed using mixed multilevel linear models taking into account individual study variation. Thirty-three studies encompassing twenty-one different oils were included in this review. Overall, heating to temperatures <200 °C had no appreciable impact on different TFA levels. Between 200 and 240 °C, levels of C18:2 t (0.05% increase per 10 °C rise in temperature, 95% CI: 0.02 to 0.05%), C18:3t (0.18%, 95% CI: 0.14 to 0.21%), and total TFA (0.38%, 95% CI: 0.20 to 0.55%) increased with temperature. A further increase in total TFA was observed with prolonged heating between 200 and 240 °C. Our findings suggest that heating edible oils to common cooking temperatures (≤200 °C) has minimal effect on TFA generation whereas heating to higher temperatures can increase TFA level. This provides further evidence in favour of public health advice that heating oils to very high temperatures and prolonged heating of oils should be avoided.


Decay of dipolar order in diamagnetic and paramagnetic proteins and protein gels.
Magnetic relaxation in solids may be complicated by the creation and loss of dipolar order at finite rates. In tissues the molecular and spin dynamics may be significantly different because of the relatively high concentration of water. We have applied a modified Jeneer-Broekaert pulse sequence to measure dipolar relaxation rates in both dry and hydrated protein systems that may serve as magnetic models for tissue. In lyophilized and dry serum albumin, the dipolar relaxation time, T(1D) is on the order of 1 ms and is consistent with earlier reports. When hydrated by deuterium oxide, the dipolar relaxation times measured were on the order of tens of microseconds. When paramagnetic centers are included in the protein, the Jeneer-Broekaert echo decay times became the order of the decay time for transverse magnetization, i.e., the order of 10 micros or less. In the hydrated or paramagnetic systems, the dipolar relaxation times are too short to require inclusion in the quantitative analysis of magnetization transfer experiments.


Effect of continued stretching of the affected arm in patients with cerebrovascular diseases by examining H-reflex characteristics.
To investigate excitability of spinal neural function during stretching excises in patients with cerebrovascular disease (CVD), H-reflex was analyzed before, during and after 1 min. continued stretching of the affected arm. 10 hemiparesis patients with hypertonus and hyperreflex, mean age of 53.2 years were tested. H-reflex was recorded from the abductor pollicis brevis on the affected side after stimulation of median nerve in supine position. The persistence, amplitude and amplitude ratio of H/M during stretching were lower than those before and after in the patients with moderately increased muscle tonus. In patients with slightly and markedly increased, H-reflex was same before, during and after continued stretching. It is suggested that excitability of spinal neural function during 1 min. continued stretching was inhibited in the patients with moderately increased muscle tonus caused by CVD.


Intravenous Vancomycin Therapeutic Drug Monitoring in Children: Evaluation of a Pharmacy-Driven Protocol and Collaborative Practice Agreement.
Vancomycin optimization is challenging, requiring careful therapeutic drug monitoring (TDM) to avoid toxicity and ensure an efficacious concentration. Most prescriptions are empiric and often discontinued within 72 hours, which makes early TDM unnecessary. Although TDM using trough levels is common, the area under the concentration-time curve (AUC) is the preferred pharmacodynamic target. We studied the effect of a pharmacy-driven vancomycin collaborative practice agreement (CPA) at a children's hospital that delayed TDM up to 72 hours and targeted a 2-point 24-hour AUC of ≥400 mg × h/L. We retrospectively reviewed vancomycin courses in patients aged ≥30 days who received vancomycin between April 1, 2011, and August 30, 2017. We implemented the CPA on June 1, 2014. Outcomes included CPA use, use of TDM, dosage adjustments, and development of acute kidney injury; we compared courses given while monitoring only trough levels (TO-TDM) with those given while using the CPA (AUC-TDM). We performed interrupted time series analyses to account for preintervention trends. We included 2379 courses in the TO-TDM period and 2155 in the AUC-TDM period. During AUC-TDM, 87% of the courses were managed by the CPA. In adjusted interrupted time series analyses, CPA implementation was associated with an initial change in level of -0.265 (95% confidence interval [CI], -0.336 to -0.189) TDM and an initial change in level of -0.332 (95% CI, -0.506 to -0.163) dosage adjustments. The 1-year risk of acute kidney injury decreased after CPA implementation (odds ratio, 0.695 [95% CI, 0.539-0.91]). The pharmacy-driven vancomycin CPA resulted in less monitoring and fewer dose adjustments without increasing AKI.


Biological monitoring of roadside plants exposed to vehicular pollution in Jalgaon city.
Experiments on air and biomonitoring were conducted to evaluate pollution impact on the vegetation along the road in Jalgaon City, Maharashtra. The plantation along the roads and mainly includes neem (Aadirachta indica), peepal (Ficus religiosa), banyan (Ficus benghalensis), almond (Terminalia catapa). For biomonitoring, leaf area, total chlorophyll, plant protein were analyzed to study the impact of air pollutants. It was observed that vegetation at roadside with heavy traffic and markets was much affected by vehicular emission. Significant decrease in total chlorophyll and protein content was observed with reduced leaf area. It is concluded that plants can be used as indicators for urban air pollution, and there is need to protect the roadside plants from air pollution.


Subpopulations of cancer-associated fibroblasts link the prognosis and metabolic features of pancreatic ductal adenocarcinoma.
Cancer-associated fibroblasts (CAFs) are a vital constituent of the tumor microenvironment (TME) and have several activities, but the effect of CAF heterogeneity on the molecular features and clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) remains unknown. An algorithm "scFrac" based on single-cell sequencing data from the Gene Expression Omnibus was introduced to emulate the enrichment of CAF subtypes in a TCGA-PDAC cohort and their prognostic influence, and confirmed by an external validation group (66 patients with PDAC) with multiplex immunohistochemistry staining. A comprehensive analysis including metabolic profile and transcription factor regulon activity was carried out among CAF subtypes. Three distinct CAF populations were confirmed: myofibroblast (myCAF), inflammatory CAF (iCAF), and antigen-presenting CAF (apCAF). These subtypes expressed distinct metabolic profiles and transcriptional regulon activity. KEGG pathway annotation demonstrated that complement and coagulation cascades, as well as cytokine-cytokine receptor interaction were dominant in iCAFs, and pathways related to focal adhesion, and ECM-receptor interaction showed dominance in myCAFs, while antigen processing and presentation were the top enriched pathways in apCAFs. iCAFs trended to glycolysis with CREB3L1, EGR2 and SOX4 activation, whereas myCAFs depend on the tricarboxylic acid cycle and its derivatives with NRF2, CEBPD and YBX1 activation. iCAF is a protective factor associated with an inflammatory phenotype, but myCAF is an important factor in the poor prognosis of PDAC. We identified distinct molecular characteristics of 3 CAF subtypes in PDAC and plotted their metabolism profile. We introduced a novel algorism, scFrac, for exploring how CAF subgroups dysregulate cancer biology, and also shed a new therapeutic light on targeting the CAF subtype in TME.


Streptomycin induced protein expression analysis in Mycobacterium tuberculosis by two-dimensional gel electrophoresis & mass spectrometry.
The resistance of Mycobacterium tuberculosis to streptomycin, a core drug for treatment of category II tuberculosis (TB) has posed a major challenge to the health providers as well as research workers worldwide and has severely compromised the therapeutic options. A significant proportion of streptomycin resistant M. tuberculosis isolates failed to show mutations in conventional targets like rpsL and rrs. Although efflux, permeability, etc. are also known to contribute, yet a substantial proportion of isolates remains resistant suggesting involvement of other unknown mechanism. A resistant isolate may show altered gene as well as protein expression under drug induced conditions and a whole cell proteome analysis under induced conditions might help in further understanding the mechanisms of drug resistance. The present study was therefore designed with the objective to identify proteins related to streptomycin resistance in M. tuberculosis isolate grown in presence and absence of streptomycin (SM). A clinical isolate of M. tuberculosis from Mycobacterial Repository Centre at the Institute (NJIL & OMD), Agra was grown in Sauton's medium for 36 h with/without subinhibitory concentration of the drug (2 μg/ml) and the cell lysate of isolates was prepared by sonication and centrifugation. Two-dimensional (2D) gel electrophoresis was employed to study the protein profile. The selected proteins were finally identified by MALDI-TOF mass spectrometry. Our study revealed eight inducible proteins (DnaK, fabG4, DNA-binding, hypothetical, two 14 kDa antigen and two 10 kDa chaperonin) that were upregulated in the presence of drug. This preliminary study has thrown light on whether or not and how the resistant isolate responds to streptomycin at its non-toxic but sub-inhibitory concentration. An in-depth study of the upregulated proteins will give an insight into probable sites of drug action other than established primary sites.


Hemodialysis for Lactic Acidosis.
Lactic acidosis (Type A) is common in critically ill patients and usually treated by correcting the underlying etiology. We present the case of a young female who presented with life-threatening lactic acidosis secondary to hematological malignancy. Timely initiation of hemodialysis was lifesaving. The case highlights the importance of considering Type B lactic acidosis (in this case secondary to a hematological malignancy) and also initiating renal replacement therapy when routine measures are ineffective.


The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs.
Pimobendan is a benzimidazole-pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three-period, nested randomized two-treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography-mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC(0-∞) and Cmax . Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half-life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described.


Relation between morphological antisymmetry and behavioral laterality in a poeciliid fish.
Many animals show lateral bias in various behaviors. In fish, behavioral laterality has been studied from the perspective of its relation with brain lateralization. On the other hands, in some fishes, head dimorphism (righty or lefty) corresponds to behavioral laterality, such as foraging behavior. To examine the correlation between morphological asymmetry and behavioral laterality associated with brain lateralization, we conducted two behavioral tests (the detour test and fast-start test) using a poeciliid fish, Girardinus metallicus. In both behavioral tests, some individuals tended to move rightward, while others tended to move leftward, in a manner associated with head incline. In the detour-test, righty individuals primarily detoured leftward, whereas lefty individuals primarily detoured rightward. In the fast-start tests, the reverse tendency was seen; righty individuals tended to escape rightward, whereas lefty individuals tended to escape leftward. Such results indicate that brain lateralization may be also associated with morphological asymmetry.


Occupational stress and failures of social support: when helping hurts.
Research, theory, and practice generally assume that contact with others, often characterized as social support, is beneficial to the recipient. The current study, however, explores the possibility that workplace social interactions, even if intended to be helpful, can sometimes be harmful. University employees (N = 403) completed an online survey examining three types of potentially supportive interactions with other people in the workplace that might be harmful: Interactions that make the person focus on how stressful the workplace is, help that makes the recipient feel inadequate or incompetent, and help that is unwanted. Results suggest that these types of social interactions at work were indeed likely to be related to worse rather than to improved psychological and physical health. The most potentially harmful forms of these three social interactions were those that drew the person's attention to stress in the workplace. These results indicate that in some instances social interactions, even if ostensibly helpful, may be harmful.


PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.
Targeted therapies such as venetoclax (VEN) (Bcl-2 inhibitor) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). We previously reported that persister CLL cells in treated patients overexpress multiple antiapoptotic proteins and display resistance to proapoptotic agents. Here, we demonstrated that multidrug-resistant CLL cells in vivo exhibited apoptosis restriction at a pre-mitochondrial level due to insufficient activation of the Bax and Bak (Bax/Bak) proteins. Co-immunoprecipitation analyses with selective BH domain antagonists revealed that the pleiotropic proapoptotic protein (Bim) was prevented from activating Bax/Bak by "switching" interactions to other upregulated antiapoptotic proteins (Mcl-1, Bcl-xL, Bcl-2). Hence, treatments that bypass Bax/Bak restriction are required to deplete these resistant cells in patients. Protein phosphatase 2A (PP2A) contributes to oncogenesis and treatment resistance. We observed that small-molecule activator of PP2A (SMAP) induced cytotoxicity in multiple cancer cell lines and CLL samples, including multidrug-resistant leukemia and lymphoma cells. The SMAP (DT-061) activated apoptosis in multidrug-resistant CLL cells through induction of mitochondrial permeability transition pores, independent of Bax/Bak. DT-061 inhibited the growth of wild-type and Bax/Bak double-knockout, multidrug-resistant CLL cells in a xenograft mouse model. Collectively, we discovered multidrug-resistant CLL cells in patients and validated a pharmacologically tractable pathway to deplete this reservoir.


Naltrexone attenuates endoplasmic reticulum stress induced hepatic injury in mice.
Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory responses, lipoprotein B100 degradation and hepatic lipogenesis. Excess accumulation of triglyceride in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Opioid peptides are involved in triglyceride and cholesterol dysregulation, inflammation and cell death. In this study, we evaluated Naltrexone effects on ER stress induced liver injury. To do so, C57/BL6 mice received saline, DMSO and Naltrexone, as control groups. ER stress was induced by tunicamycin (TM) injection. Naltrexone was given before TM administration. Liver blood flow and biochemical serum analysis were measured. Histopathological evaluations, TNF-α measurement and Real-time RT-PCR were also performed. TM challenge provokes steatosis, cellular ballooning and lobular inflammation which significantly reduced in Naltrexone treated animals. ALT, AST and TNF-α increased in the TM group and improved in the Naltrexone plus TM group. Triglyceride and cholesterol levels decreased in TM treated mice with no increase in Naltrexone treated animals. In the Naltrexone plus TM group, gene expression of Bax/Bcl-2 ratio and caspase3 significantly lowered compared with the TM group. In this study, we found that Naltrexone had a notable alleviating role in ER stress induced steatosis and liver injury.


[The basic structure of heavy-ion tumor therapy facility].
Heavy-ions have the similar characteristic of depth-dose distribution with protons, but exhibit enhanced physical and radiobiological benefits. With increasing development in technical and clinical research, more facilities are being installed in the world. At the same time, many critical techniques of heavy-ion therapy facility were optimized and completed. This paper classified and reviewed the basic structure of heavy-ion system equipments, especially the accelerator, gantry, nozzle , TPS.


Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A.
Myofibroblasts are essential during wound healing and are often found in the stroma of oral squamous cell carcinomas (OSCC). Although the molecular mechanisms by which myofibroblasts influence OSCC remain largely unknown, previous studies demonstrated that presence of myofibroblast in OSCC stroma is an important risk factor of patient's shortened survival. Here we showed that some growth factors are produced in higher levels by tumor-associated myofibroblasts compared to tumor-associated fibroblasts, including activin A. Myofibroblast-conditioned media containing activin A significantly increased OSCC cell proliferation and tumor volume, whereas down-regulation of activin A in the conditioned media decreased proliferation. In addition, myofibroblasts induced in vitro invasion of OSCC cells, which was accompanied by an increased production of matrix metalloproteinases (MMP). In vivo, a significant correlation between presence of myofibroblasts and activities of MMP-2 and MMP-9 was observed in OSCC samples. However, blockage of activin A synthesis by myofibroblasts did not affect invasion and MMP production by OSCC cells. Together, our data demonstrate that activin A is required for the proliferative effects of myofibroblasts on OSCC cells. We conclude that myofibroblasts in the stroma of OSCC may influence proliferation and invasion, resulting in more aggressive tumor.


Studies on the in vitro spermicidal activity of synthetic magainins.
Two synthetic magainins A and G are shown to have spermicidal activity. Transmission electron microscopic micrographs show that both magainins alter the plasma membranes of sperm and that these actions are rapid. Further studies will better delineate the contraceptive potential of synthetic magainins.


Rapid preparative separation of monoclonal antibody charge variants using laterally-fed membrane chromatography.
Monoclonal antibodies undergo various forms of chemical transformation which have been shown to cause loss in efficacy and alteration in pharmacokinetic properties of these molecules. Such modified antibody molecules are known as variants. They also display physical properties such as charge that are different from intact antibody molecules. However, the difference in charge is very subtle and separation based on it is quite challenging. Charge variants are usually separated using ion-exchange column chromatography or isoelectric focusing. In this paper, we report a rapid and scalable method for fractionating monoclonal antibody charge variants, based on the use of cation exchange laterally-fed membrane chromatography (LFMC). Starting with a sample of monoclonal antibody hIgG1-CD4, three well-resolved fractions were obtained using either pH or salt gradient. These fractions were identified as acidic, neutral and basic variants. Each of these fractions contained intact heavy and light chains and so antibody fragmentation had no role in variant generation. The separation was comparable to that using column chromatography but was an order of magnitude faster.


The role of intrinsic pathway in apoptosis activation and progression in Peyronie's disease.
Peyronie's disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway.


Calcium-dependent inactivation of the Ca2+-ATPase from sarcoplasmic reticulum by chemically reactive adenosine triphosphate.
1. ATP gamma P-imidazolidate, synthesized from ATP and carbonyldiimidazole, inhibits the Ca2+-ATPase of sarcoplasmic reticulum in a biphasic manner. A fast first phase is concentration-dependent while a slower second phase is independent of the inhibitor concentration. 2. The inhibition is calcium- and magnesium-dependent. No inhibition occurs in the absence of either cation. 3. Inhibition of the Ca2+-ATPase can be prevented by the protection with ATP. 4. The loss of ATPase activity is pH-dependent. Maximal inhibition coincides with maximal ATPase activity. It indicates a participation of the reacting amino acid side chain in the catalytic cycle. 5. The incorporation of radioactive inhibitor is reversed in a time-dependent fashion while the Ca2+-ATPase remains inhibited. 6. We conclude that ATP gamma P-imidazolidate initially reacts covalently with an amino acid side chain, probably Asp-351, but is subsequently expelled by a reaction with a second amino acid. 7. This two-step reaction induces an intramolecular cross-link which can be shown by the creation of a new protein band on SDS-PAGE which originates in the Ca2+-ATPase.


Integrated electromyography and performance outcomes to inertial resistance exercise.
Integrated electromyography (IEMG) and performance outcomes from resistance exercise may be influenced by gender, repetition order, and contractile mode. A novel strength training apparatus employing inertial resistance operates unlike standard exercise equipment and may therefore evoke different IEMG and performance outcomes. Subjects performed 3-set, 10-repetition calf press workouts on an inertial device while IEMG and flywheel velocity were recorded. Dependent variables were examined with 2 (men, women) x 2 (first vs. 10th repetition) x 2 (concentric, eccentric) analyses of variance. Performance outcomes showed gender-by-repetition and gender-by-contractile-mode interactions, with men's 10th-repetition and men's concentric data, respectively, causing these effects. Medial gastrocnemius (MG) IEMG showed a gender-by-repetition interaction resulting from men's first-repetition data. Greater 10th-repetition performance despite higher first-repetition MG IEMG may result from heightened triceps surae elastic energy utilization and/or maintained cross-bridges during transitions from lengthening-to-shortening actions. Inertial strength training may improve performance outcomes without additional motor unit recruitment.


Self-regulation and the management of stuttering.
Self-regulation refers to a process by which individuals learn to direct and control their own behavior, thoughts, and feelings to manage or eliminate their stuttering. As a concept, it has been a vital and enduring component of most approaches to managing persistent and chronic stuttering. The theoretical basis for self-regulation is briefly reviewed and the main principles of self-regulation--goal setting, cue management, self-monitoring, and self-evaluation--are described and illustrated with clinical examples. Factors related to self-regulatory failure are also discussed.


Laparoscopy in Acute Care Surgery: Repair of Perforated Duodenal Ulcer.
The use of laparoscopic management as a first choice for the treatment of duodenal perforation is gaining ground but is not routine in many centers. In this report, we aim to report our experience with laparoscopy as the first approach for the repair of duodenal perforation. This is a retrospective review of patients during our initial experience with the use of laparoscopy for the treatment of duodenal perforation between 2009 and 2013. A total of 100 patients underwent management of duodenal perforation. Laparoscopy was attempted initially in 76 patients (76%) and completed in 64 patients (64%). The length of hospital stay was shorter in the laparoscopic group (mean 2.6) than in the open group (mean 3.1) (p = 0.008). Complications developed in 14 patients (20%). There was a tendency towards fewer admissions to intensive care, less acute kidney injuries, and less acute respiratory distress syndrome in the laparoscopic group. In patients who underwent laparoscopic surgery, the chances of uneventful recovery were 4.3 times higher than in those patients who underwent open surgery (95% CI 1.3-13.5, p = 0.014). Laparoscopy in the treatment of perforated duodenal ulcer is safe and can be utilized as a routine approach for the treatment of this pathology.


Sensory recovery following total and subtotal amputations distal to the wrist and digital replantations.
Apart from the basic aim of revascularization, other criteria for the success of digital replantation are functional and sensory recovery. Tactile gnosis can only be restored in cases of replantation distal to the wrist by paying great attention to the technical details for nerve repair. Of 253 patients who underwent 312 digital replantations, after total or subtotal amputations, over 16 years, 162 with 215 successful replantations and 377 nerve reconstructions returned for follow-up evaluations. Of 320 patients who underwent 395 nerve repairs after isolated severed digital nerves, 198 with 249 nerve reconstructions returned for follow-up. Our aim was to determine in both groups, the level of sensory recovery for primary nerve repair as well as for primary and secondary nerve grafting by evaluating the results according to the score of Highet. The majority of the patients in both groups reached stage S3 to S4 on the sensory recovery score of Highet. Patients with isolated severed nerve reached stage S3+ more often than the patients with nerve reconstruction after replantation. The evaluation of results takes into consideration factors influencing digital sensibility such as the level and type of injury, the length nerve grafts, cold intolerance and the patient's age.


A particular difficulty in discriminating between mirror images.
We investigated the selective impairment of mirror image discrimination in a patient with bilateral parieto-occipital lesions (FIM). We report a difficulty with the discrimination between mirror images more selective than has been previously reported (Turnbull OH, McCarthy RA. Failure to discriminate between mirror-image objects: a case of viewpoint-independent object recognition? Neurocase 1996;2:63). FIM was asked to judge, in five same/different experiments, whether pairs of simultaneously presented line drawings of objects were identical. FIM demonstrated only a minor impairment in discriminating between orientations in the picture plane but was at chance in making discrimination between mirror images. An experiment with normal observers established that our results were not due to differences in task difficulty. Two further experiments investigated the effects of rotation on the discrimination of letters and geometric shapes. FIM's impairment extended to geometric shapes but not to letters. These results would be consistent with the preservation of an abstract representation for object recognition that did not code the difference between mirror image views.


Characterization of adrenergic receptors of the cat iris and nictitating membrane.
Graded pupillary dilations and nictitating membrane (NM) contractions were elicited in anesthetized cats by electrical stimulation of the preganglionic sympathetic nerve or by i.a. administration of norepinephrine (NE) or phenylephrine into the carotid artery. Pupil and NM responses were measured simultaneously from the same side. Alpha-adrenoceptor antagonists were administered intravenously. All of the alpha 1-adrenoceptor blockers tested produced a dose-related reduction of NM responses to both neural and agonist activation; the potency rank order was prazosin greater than WB-4101 greater than phentolamine greater than phenoxybenzamine (PBZ). In contrast, responses of the iris dilator were antagonized only by WB-4101 and PBZ. The iris was almost totally refractory to doses of prazosin and phentolamine that blocked NM responses by more than 75% of control. Neither alpha 2- nor beta-adrenoceptor antagonism produced significant inhibition of neural or agonist activation of either organ (with the exception of high doses of yohimbine on the NM). These results suggest that the postjunctional adrenoceptors of the NM are exclusively of the alpha 1-adrenoceptor subtype. In contrast, those of the iris dilator muscle cannot be easily classified pharmacologically as either alpha 1 or alpha 2-adrenoceptors.


The complexities of PKCα signaling in cancer.
Protein kinase C α (PKCα) is a ubiquitously expressed member of the PKC family of serine/threonine kinases with diverse functions in normal and neoplastic cells. Early studies identified anti-proliferative and differentiation-inducing functions for PKCα in some normal tissues (e.g., regenerating epithelia) and pro-proliferative effects in others (e.g., cells of the hematopoietic system, smooth muscle cells). Additional well documented roles of PKCα signaling in normal cells include regulation of the cytoskeleton, cell adhesion, and cell migration, and PKCα can function as a survival factor in many contexts. While a majority of tumors lose expression of PKCα, others display aberrant overexpression of the enzyme. Cancer-related mutations in PKCα are uncommon, but rare examples of driver mutations have been detected in certain cancer types (e. g., choroid gliomas). Here we review the role of PKCα in various cancers, describe mechanisms by which PKCα affects cancer-related cell functions, and discuss how the diverse functions of PKCα contribute to tumor suppressive and tumor promoting activities of the enzyme. We end the discussion by addressing mutations and expression of PKCα in tumors and the clinical relevance of these findings.


Video-assisted thoracic lobectomy for lung cancer in Italy: the 'VATS Group' Project.
As part of the third Mediterranean Symposium in Thoracic Surgical Oncology, we introduce the Italian VATS Group ( http://vatsgroup.org/sito/index.php ). This national collaborative initiative was established in 2013 and started to recruit patients in January 2014; as of July 2016, 3680 patients have been enrolled in the database. Three different video-assisted thoracic surgery approaches have been predominantly used by Italian thoracic surgery centers, 71% of them preferentially adopting a multi-portal approach, with a 20% recorded morbidity. The majority of the cases were stage I adenocarcinomas of the lung. Conversion to open surgery occurred in 9% of the cases. The study suggests video-assisted thoracic surgery lobectomy as a 'gold standard' for the surgical treatment of early-stage lung cancer in Italy.


[The unstable spine--an "in vitro" and "in vivo study" on better understanding of clinical instability].
In cases of suspected painful instability of a cervical segment, temporary external fixation by means of external fixator was applied. The segmental immobilization caused immediate relief of pain. The pain reoccurred after removal of the immobilization. The effect of immobilization by external fixation was investigated in biomechanical tests using fresh cadaveric C4-7 specimens. Multidirectional flexibility was measured before and after application of the fixator at C4/C5, C5/C6 and C4-6. We measured the reduction in motion between the different segments. In every situation the neutral zone decreased more than the range of motion. The findings are helpful to understand the clinical instability of the spine and support the hypothesis that the neutral zone is more closely associated with clinical instability than range of motion. The combination of clinical application and biomechanical investigation allowed us to establish a direct correlation between instability and pain.


Loss of stability and unfolding cooperativity in hPGK1 upon gradual structural perturbation of its N-terminal domain hydrophobic core.
Phosphoglycerate kinase has been a model for the stability, folding cooperativity and catalysis of a two-domain protein. The human isoform 1 (hPGK1) is associated with cancer development and rare genetic diseases that affect several of its features. To investigate how mutations affect hPGK1 folding landscape and interaction networks, we have introduced mutations at a buried site in the N-terminal domain (F25 mutants) that either created cavities (F25L, F25V, F25A), enhanced conformational entropy (F25G) or introduced structural strain (F25W) and evaluated their effects using biophysical experimental and theoretical methods. All F25 mutants folded well, but showed reduced unfolding cooperativity, kinetic stability and altered activation energetics according to the results from thermal and chemical denaturation analyses. These alterations correlated well with the structural perturbation caused by mutations in the N-terminal domain and the destabilization caused in the interdomain interface as revealed by H/D exchange under native conditions. Importantly, experimental and theoretical analyses showed that these effects are significant even when the perturbation is mild and local. Our approach will be useful to establish the molecular basis of hPGK1 genotype-phenotype correlations due to phosphorylation events and single amino acid substitutions associated with disease.


Engineering catalyst microenvironments for metal-catalyzed hydrogenation of biologically derived platform chemicals.
It is shown that microenvironments formed around catalytically active sites mitigate catalyst deactivation by biogenic impurities that are present during the production of biorenewable chemicals from biologically derived species. Palladium and ruthenium catalysts are inhibited by the presence of sulfur-containing amino acids; however, these supported metal catalysts are stabilized by overcoating with poly(vinyl alcohol) (PVA), which creates a microenvironment unfavorable for biogenic impurities. Moreover, deactivation of Pd catalysts by carbon deposition from the decomposition of highly reactive species is suppressed by the formation of bimetallic PdAu nanoparticles. Thus, a PVA-overcoated PdAu catalyst was an order of magnitude more stable than a simple Pd catalyst in the hydrogenation of triacetic acid lactone, which is the first step in the production of biobased sorbic acid. A PVA-overcoated Ru catalyst showed a similar improvement in stability during lactic acid hydrogenation to propylene glycol in the presence of methionine.


Management of anterior triangle swellings in a tertiary vascular centre with emphasis on the roles of duplex ultrasound, computed tomography angiogram and magnetic resonance angiogram: a case series.
Anterior triangle masses pose an important clinical dilemma. It is very difficult to distinguish the potential pathologies pre operatively by clinical and radiological assessment. The first case highlights the management of a bilateral chemodectoma, the second case is a presentation of castleman's disease and the third is that of metastatic tonsillar adenocarcinoma. All three cases had a similar presentation and radiological appearance pre-operatively. Anterior triangle masses span the clinical spectrum of pathologies from chemodectoma to castleman's disease to carcinoma. Expert vascular and radiological management is required for optimum patient care and should take place in a tertiary referral centre. Duplex US, CTA and MRA are important pre operative assessment tools to ensure that adequate information regarding the relationship of the lesion to the carotid artery is available to the operating surgeon who should have vascular expertise as deliberate practice volume has been repeatedly shown to result in improved patient outcome.


Sequence-specific assignment of the 1H and 15N nuclear magnetic resonance spectra of the reduced recombinant high-potential iron-sulfur protein I from Ectothiorhodospira halophila.
A 1H and 15N NMR investigation through two-dimensional and three-dimensional spectroscopy has been performed on the reduced form ([Fe4S4]2+) of the recombinant high-potential iron-sulfur protein (HiPIP) I from Ectothiorhodospira halophila expressed in Escherichia coli. [Fe4S4]2+ clusters in proteins are paramagnetic with a relatively low mu eff of about 0.8 mu B/iron ion, but the paramagnetic effects on nuclear relaxation are so strong as to yield T1 values of a few milliseconds and linewidths of hundreds of hertz for the nuclei closet to the paramagnetic center. Despite these features, 71 out of 73 residues were identified, most of which were assigned completely as far as proton resonances are concerned; as many as 68 residues could be assigned without any reference to the existing X-ray structure. A total of 88% of all protein protons and 58 out of 69 peptide HN nitrogen signals were assigned. To the best of our knowledge, this is the most extensive 1H assignment of a paramagnetic protein to date. Protons sensitive to the proximity of the cluster were assigned through suitable NOE spectroscopy experiments. Three out of the four coordinated cysteines were assigned, and two residues have been identified whose peptide HN protons give rise to H bonds with coordinated sulfur atoms. The inter-residue NOE cross peaks are in qualitative agreement with the secondary and tertiary structure as obtained from the available X-ray crystallographic analysis of the wild-type protein at 250-pm resolution. It is therefore shown that the expressed protein is properly folded and that it is a reliable model for the wild-type protein. These data are meaningful for the detection of structural differences among mutants in future studies.


Muscle spindles in the digastric muscle of the rabbit.
The digastric muscle of the rabbit was studied for the presence of muscle spindles. One of the 19 adult digastric muscles we examined contained in excess of 12 spindles scattered throughout the belly. No spindles were found in the contralateral muscle, or in any of the digastric muscles from other animals. Although jaw depressor muscles of most mammals contain few, if any, muscle spindles, their occasional presence suggests that these muscles have a potential for spindle formation.


A Platform for Collection and Analysis of Image Data on Stroke.
Identifying imaging biomarkers (IBs) of stroke remains a priority in neurodiagnostics. There is a number of different methods for image analysis and learning rules applicable in this field, but all of them require large arrays of DICOM images and clinical data. In order to amass such dataset,we havedesigneda platform for systematic collection of clinical data and medical images in different modalities. The platform provides easy-to-use tools to create formalized radiology reports, contour and tag the regions of interest (ROIs) on the DICOM images, and extract radiomics data. Subsequent analysis of the obtained data will allow identifying the most relevant IBs that predict clinical outcome and possible complications. The results of the analysis will be used to develop predictive algorithms for stroke diagnostics.


Nursing-sensitive benchmarks for hospitals to gauge high-reliability performance.
Benchmarking expedites the quest for best practices and is crucial to hospitals' effective, reliable, and superior performance. Comparative performance data are used by accrediting and regulatory bodies to evaluate performance and by consumers in making decisions on where to seek healthcare. Nursing-sensitive quality measures affirmed by the National Quality Forum are now used in public reporting and pay-for-performance in addition to traditional medical outcome metrics. This report provides hospital nursing-sensitive benchmarks from medical/surgical, critical care, and step-down units drawn from 196 hospitals during six quarters in 2007 and 2008. Outcome measures include pressure ulcer prevalence rates and fall/falls with injury rates. Additional indicators that describe nursing care (nurse staffing care hours, skill mix, nurse/patient ratios, workload intensity, voluntary turnover, and use of sitters) and patient descriptors (age, gender, and diagnosis description) were also included. Specific benchmarks are provided using the 10th and the 90th percentiles, as well as quartiles to allow hospitals an opportunity to understand comparative performance with specificity. The purpose of this article is to provide hospitals not currently participating in comparative benchmarking databases with nursing-sensitive data from the Collaborative Alliance for Nursing Outcomes for use in performance improvement processes.


Transfusion Triggers for Platelets and Other Blood Products.
How to cite this article: Karanth S. Transfusion Triggers for Platelets and Other Blood Products. Indian J Crit Care Med 2019;23(Suppl 3):S189-S190.


Metronidazole is still the drug of choice for treatment of anaerobic infections.
Metronidazole has been used for the treatment of infections for >45 years and is still successfully used for the treatment of trichomoniasis, amoebiasis, and giardiasis. Anaerobic bacterial infections caused by Bacteroides species, fusobacteria, and clostridia respond favorably to metronidazole therapy. Good clinical results in the treatment of vaginosis due to Gardnerella vaginalis have also been reported. Rates of resistance to metronidazole are still generally low; however, several studies have reported decreased susceptibility among Bacteroides species, as well as different mechanisms of resistance. Metronidazole-resistant Helicobacter pylori strains have been described, but combination therapy (eg, metronidazole, amoxicillin, or clarithromycin plus omeprazole) is still recommended for eradication of this pathogen in patients with gastroduodenal ulcers. Metronidazole is considered to be a cost-effective drug because of its low cost, good activity against pathogenic anaerobic bacteria, favorable pharmacokinetic and pharmacodynamic properties, and minor adverse effects. Metronidazole is still the criterion standard for therapy of anaerobic infections, as was described by Tally and colleagues 35 years ago.


Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: a 3-year controlled clinical trial.
A 3-year, double-blind, randomized caries trial was conducted to evaluate the relative anticaries efficacy of four sodium fluoride dentifrices containing 250 ppm fluoride, 1,000 ppm fluoride in combination with 1% disodium 1-hydroxyethylidene-1.1-bisphosphonate (HEBP), and 1,000 ppm fluoride in combination with 1% disodium azacycloheptylidene-2.2-bisphosphonate (AHBP). As a positive control, a monofluorophosphate dentifrice (1,000 ppm fluoride) was used. At outset 1,161 Icelandic children, 11 and 12 years of age, were randomly assigned to one of the five treatment groups and 1,035 subjects completed the trial. After 3 years of unsupervised brushing, the dentifrice containing 250 ppm fluoride was significantly less effective in controlling the caries increment. The combination of sodium fluoride and AHBP was significantly more effective than the positive control.


Expression of statin, a non-proliferation-dependent nuclear protein, in the postnatal rat brain: evidence for substantial retention of neuroglial proliferative capacity with aging.
Statin is a 57 kDa protein expressed in nuclei of reversibly and irreversibly growth-arrested (Go-phase) cells. In this report, immunohistochemical localization of statin in the developing and aging rat brain was achieved using the monoclonal antibody, S-44. On postnatal day 2, post-migratory neurons in the developing cerebral cortex were statin-positive. Many statin-negative cells were observed in the lateral subependymal zone of the lateral ventricle. By postnatal day 10, most neuronal nuclei were statin-positive although small numbers of statin-negative neurons were still encountered in the lateral subependymal zone and hippocampal dentate gyrus. At 3, 18 and 33 months, all neuronal nuclei surveyed were statin-positive. These results support the contention that, save for the postnatal persistence of 'germinal zones' such as the subependymal region and dentate gyrus, neuronal proliferation in the rat is largely completed by the time of birth. In striking contrast to neuronal statin expression, a significant fraction of neuroglia in both grey and white matter remains statin-negative at all ages examined. In the corpus callosum, 33.2%, 34.0% and 34.7% of glial nuclei were statin-negative at 3, 18 and 33 months, respectively. These findings indicate that: (i) even in senescent brain, the cycling (statin-negative) glial pool is substantially larger than previously surmised from S-phase labeling experiments; and (ii) during aging, the ratio of noncycling-to-cycling neuroglia remains very tightly regulated. Examination of other non-neuronal cell types revealed that most, if not all, ependymal and choroid plexus epithelial cells were statin-positive in the neonatal and adult brains in keeping with the predominantly prenatal proliferation of these tissues. Our results indicate that statin immunolabeling using the S-44 antibody is a powerful technique for the in situ identification of non-proliferating cells in the developing and aging nervous system.


Is Social Capital a Determinant of Oral Health among Older Adults? Findings from the English Longitudinal Study of Ageing.
There are a number of studies linking social capital to oral health among older adults, although the evidence base mainly relies on cross-sectional study designs. The possibility of reverse causality is seldom discussed, even though oral health problems could potentially lead to lower social participation. Furthermore, few studies clearly distinguish between the effects of different dimensions of social capital on oral health. The objective of the study was to examine the longitudinal associations between individual social capital and oral health among older adults. We analyzed longitudinal data from the 3rd and 5th waves of the English Longitudinal Study of Ageing (ELSA). Structural social capital was operationalized using measures of social participation, and volunteering. Number of close ties and perceived emotional support comprised the functional dimension of social capital. Oral health measures were having no natural teeth (edentate vs. dentate), self-rated oral health and oral health-related quality of life. Time-lag and autoregressive models were used to explore the longitudinal associations between social capital and oral health. We imputed all missing data, using multivariate imputation by chained equations. We found evidence of bi-directional longitudinal associations between self-rated oral health, volunteering and functional social capital. Functional social capital was a strong predictor of change in oral health-related quality of life - the adjusted odds ratio of reporting poor oral health-related quality of life was 1.75 (1.33-2.30) for older adults with low vs. high social support. However in the reverse direction, poor oral health-related quality of life was not associated with changes in social capital. This suggests that oral health may not be a determinant of social capital. In conclusion, social capital may be a determinant of subjective oral health among older adults rather than edentulousness, despite many cross-sectional studies on the latter.


Conformational sampling of oligosaccharides using Hamiltonian replica exchange with two-dimensional dihedral biasing potentials and the weighted histogram analysis method (WHAM).
Oligosaccharides and polysaccharides exert numerous functional roles in biology through their structural diversity and conformational properties. To investigate their conformational properties using computational methods, Hamiltonian replica exchange (H-REX) combined with two-dimensional grid-based correction maps as biasing potentials (bpCMAP) significantly improves the sampling efficiency about glycosidic linkages. In the current study, we extend the application of H-REX with bpCMAP to complex saccharides and establish systematic procedures for bpCMAP construction, determination of replica distribution, and data analysis. Our main findings are that (1) the bpCMAP for each type of glycosidic linkage can be constructed from the corresponding disaccharide using gas-phase umbrella sampling simulations, (2) the replica distribution can be conveniently determined following the exact definition of the average acceptance ratio based on the assigned distribution of biasing potentials, and (3) the extracted free energy surface (or potential of mean force (PMF)) can be improved using the weighted histogram analysis method (WHAM) allowing for the inclusion of data from the excited state replicas in the calculated probability distribution. The method is applied to a branched N-glycan found on the HIV gp120 protein, and a linear N-glycan. Considering the general importance of N-glycans and the wide appreciation of the sampling problem, the present method represents an efficient procedure for the conformational sampling of complex oligo- and polysaccharides under explicit solvent conditions. More generally, the use of WHAM is anticipated to be of general utility for the calculation of PMFs from H-REX simulations in a wide range of macromolecular systems.


Primary care physicians' dementia care practices: evidence of geographic variation.
This article explores primary care physicians' (PCPs) self-reported approaches and barriers to management of patients with dementia, with a focus on comparisons in dementia care practices between PCPs in 2 states. In this cross-sectional study, questionnaires were mailed to 600 randomly selected licensed PCPs in Connecticut and to all 1,017 licensed PCPs in Maine. A total of 422 eligible PCPs responded. Nearly 90% of PCPs prescribed donepezil in the previous year for their dementia patients. Connecticut PCPs were more likely to prescribe several other therapeutics than their Maine counterparts. Connecticut PCPs were more likely to refer dementia patients to adult day care (85% vs. 59%) but less likely to refer to Area Agencies on Aging (21% vs. 44%; both ps < .05); referral rates to Alzheimer's Association chapters were low in both states (30%). A greater proportion of Connecticut PCPs reported barriers to optimal dementia care, including time constraints (54% vs. 31% of Maine PCPs), unfamiliarity with community resources (46% vs. 30%), and reimbursement constraints (45% vs. 23%; all ps <or= .05). Two thirds of PCPs were "very" or "somewhat" interested in using information technology to assist with dementia diagnosis and management; controlling for other variables, youngest PCPs were more than twice as likely as oldest to profess such interest (adjusted odds ratio = 2.04; 95% confidence interval [CI] = 1.02-4.08). Geographic variations are evident in PCP medication prescription patterns, community resource referral patterns, and reported barriers to optimal dementia care. Younger PCPs are more likely to adopt information technology to assist in dementia diagnosis and management.


Restructuring of the plasma membrane upon damage by LC3-associated macropinocytosis.
The plasma membrane shapes and protects the eukaryotic cell from its surroundings and is crucial for cell life. Although initial repair mechanisms to reseal injured membranes are well established, less is known about how cells restructure damaged membranes in the aftermath to restore homeostasis. Here, we show that cells respond to plasma membrane injury by activating proteins associated with macropinocytosis specifically at the damaged membrane. Subsequent to membrane resealing, cells form large macropinosomes originating from the repair site, which eventually become positive for autophagy-related LC3B protein. This process occurs independent of ULK1, ATG13, and WIPI2 but dependent on ATG7, p62, and Rubicon. Internalized macropinosomes shrink in the cytoplasm, likely by osmotic draining, and eventually fuse with lysosomes. We propose that a form of macropinocytosis coupled to noncanonical autophagy, which we term LC3-associated macropinocytosis (LAM) functions to remove damaged material from the plasma membrane and restore membrane integrity upon injury.


Relationship between ankle brachial index (ABI), high sensitivity C-reactive protein (hs-CRP) and initial disability level in acute ischemic stroke.
Relationship between high sensitivity C-reactive protein (hs-CRP), Ankle Brachial index (ABI), severity of atherosclerosis and risk of ischemic stroke has been well documented. Studies concerning the association of ABI, hs-CRP and initial disability level in acute ischemic stroke are scarce. This study aimed to investigate the relationship between hs-CRP, ABI and level of initial disability in acute stroke setting. We conducted a prospective observational study in patients with acute ischemic stroke within 48 hours of onset. Initial ABI, hs-CRP were measured. Disability level was assessed at admission and 3 months using the modified Rankin scale (mRS) and the National Institue of Health Stroke scale (NIHSS). Statistical analysis was performed using Pearson's correlation coefficient. This study included 36 patients with a mean +/-SD age of 67.8 +/- 9.3 years. Sixteen (44.4%) were male. Median NIHSS and mRS were 10 and 4 respectively. Correlation between initial ABI and hs-CRP was poor (r(s) = -0.11, p = 0.57). There was a significant negative relationship between ABI and mRS at 0 and 3 months with a correlation coefficient of -0.45 (p = 0.006) and -0.41 (p = 0.02), respectively. There was a significant inverse relationship between ABI and initial stroke disability. However, correlation coefficient indicated only fair agreement beyond chance. This findings suggest that ABI may be used as a clinical predictor of initial disability level in acute stroke.


The social reception of mainstreamed children in the regular classroom.
The purpose of the present study was to learn how a mainstreamed mentally retarded or emotionally disturbed child is received in a regular classroom by the other pupils in the class. Each of 36 fifth grade boys interacted with one of three male confederates and 36 eighth grade boys interacted with one of three other male confederates. In each case the confederate was of the same age and grade as the subjects. He was presented to the subject as an ordinary child, as a mentally retarded child, or as an emotionally disturbed child who might soon attend their school and the subject was asked to estimate how the confederate would fit into the school. The confederate was always blind to condition and, after the interaction, the subject was questioned about the confederate by an experimenter also blind to condition. Behavioural measures taken from the sound recordings of the interaction showed that the subjects in the mentally retarded and emotionally disturbed conditions behaved in a less friendly and more anxious manner than in the control condition. They also wanted more social distance from the 'retarded' and the 'disturbed' confederate and expected their peers to be more rejecting toward them relative to the control condition. Essentially the same results were obtained for fifth and eighth grade boys and little difference was found between the two types of mental handicaps. The implication of the study for deinstitutionalization are discussed.


Biochemical analysis of glycophospholipids from wild-type mouse lymphoma cells and from Thy-1 negative mutants which do not add glycolipid-anchored proteins.
Thy-1 is a major glycophospholipid (GPL)-anchored protein found on the surface of neurons, epithelial cells, fibroblasts and murine T-lymphomas. Biochemical studies were undertaken to determine if murine T-lymphomas contain glycolipids which may be on the path of GPL-anchor biosynthesis. Biosynthetic labeling experiments on Thy-1-positive (wild-type) cells followed by battery of chemical and enzymatic diagnostics on the isolated [3H]mannolipids have, for the first time, led to description of a set of glycolipids which have properties consistent with their being GPL-anchor precursors. Using these results as a guide, major differences have been observed upon analysis of the radiolabeled mannolipids of Thy-1-negative mutants from 7 complementation classes, A-C, E, F, H and I. The biosynthetic lesions in anchor synthesis have been identified in some of the mutants.


The time for cost-effectiveness in the new European Union member states: the development and role of health economics and technology assessment in the mirror of the Hungarian experience.
Sophisticated methodology and research centres of health economics and health technology assessment were established in the developed countries over the past 30 years, releasing more and more studies of better and better quality every year. A crucial factor in health policy and reimbursement decisions in these countries is cost-effectiveness results. Due to methodological diversification, results of locally performed health economics studies are constrained in international utility. This fact encourages us to set the current goal of greatest importance, i.e. to standardise country-specific methods, thereby promoting transferability and adaptability of results, being backed by each important health care organisation all over Europe. The situation in the new member states [European Union (EU)12] is profoundly different compared with EU15. In these countries, neither the necessary research institutions nor professionals are in place in sufficient numbers; even in most EU12 countries, the importance of cost-effectiveness has not yet been realised. The present study focuses mainly on the EU12. These countries are absolutely dependent on cost-effectiveness results from abroad, and this seems to persist in the long-term. Transferability and adaptability of the results of health economics studies carried out elsewhere through European collaboration is vital for these countries.


Shear-thickening in mixed suspensions of silica colloid and oppositely charged polyethyleneimine.
The liquid-gel-liquid transition tuned by increasing concentration of linear and hyperbranched polyethyleneimine in suspension of silica colloids, and the accompanying shear-thickening phenomena, were investigated by rheological measurements. The influence from linear and hyperbranched polymer conformation and from different size-ratio between particle and polymer on the rheological properties of suspensions flocculated by absorbing polyelectrolyte were considered. Charge neutralization and bridging mechanism are the main reasons for the flocculation of silica colloid in this study. Because of charge reversal, the irreversible bridges are turned into flexible reversible bridges with increasing adsorption amount of oppositely charged polymer, which leads to an abrupt transition from gel to liquid. Over a narrow composition range, around the gel to liquid transition region, shear-thickening flow is observed. It is found that, for given particle volume fraction, the composition region exhibiting shear-thickening for mixed suspension with linear polyethyleneimine is broader than that for mixed suspension with hyperbranched polyethyleneimine, and the onset of shear-thickening depends only on size-ratio, regardless of the actual size of particle and polymer in the range of this study. The relationship between the gel to liquid transition and shear-thickening was discussed.


Signaling alkaline pH stress in the yeast Saccharomyces cerevisiae through the Wsc1 cell surface sensor and the Slt2 MAPK pathway.
Alkalinization of the external environment represents a stress situation for Saccharomyces cerevisiae. Adaptation to this circumstance involves the activation of diverse response mechanisms, the components of which are still largely unknown. We show here that mutation of members of the cell integrity Pkc1/Slt2 MAPK module, as well as upstream and downstream elements of the system, confers sensitivity to alkali. Alkalinization resulted in fast and transient activation of the Slt2 MAPK, which depended on the integrity of the kinase module and was largely abolished by sorbitol. Lack of Wsc1, removal of specific extracellular and intracellular domains, or substitution of Tyr(303) in this putative membrane stress sensor rendered cells sensitive to alkali and considerably decreased alkali-induced Slt2 activation. In contrast, constitutive activation of Slt2 by the bck1-20 allele increased pH tolerance in the wsc1 mutant. DNA microarray analysis revealed that several genes encoding cell wall proteins, such as GSC2/FKS2, DFG5, SKT5, and CRH1, were induced, at least in part, by high pH in an Slt2-dependent manner. We observed that dfg5, skt5, and particularly dfg5 skt5 cells were alkali-sensitive. Therefore, our results show that an alkaline environment imposes a stress condition on the yeast cell wall. We propose that the Slt2-mediated MAPK pathway plays an important role in the adaptive response to this insult and that Wsc1 participates as an essential cell-surface pH sensor. Moreover, these results provide a new example of the complexity of the response of budding yeast to the alkalinization of the environment.


Psychiatric staff attitudes toward coercive measures: An experimental design.
To evaluate the effectiveness of a training program on the attitudes of psychiatric nurses toward using coercive measures. A repeated measures time-series design with two-equivalent groups was used. A convenience sample of 48 psychiatric nurses were recruited. Data collection was conducted using the Staff Attitude to Coercion Scale. Results showed the effectiveness of the training program in improving nurses' attitude toward coercive measures. After 4 weeks of the training, nurses in the intervention group demonstrated significant improvements in their attitude mean scores. Equipping the psychiatric nurses with essential clinical knowledge and skills concerning the appropriate application of coercive measures policy were imperative issues that might help the nurses in dealing with these clinical complex situations effectively.


Parallel tempering Monte Carlo simulations of lysozyme orientation on charged surfaces.
In this work, the parallel tempering Monte Carlo (PTMC) algorithm is applied to accurately and efficiently identify the global-minimum-energy orientation of a protein adsorbed on a surface in a single simulation. When applying the PTMC method to simulate lysozyme orientation on charged surfaces, it is found that lysozyme could easily be adsorbed on negatively charged surfaces with "side-on" and "back-on" orientations. When driven by dominant electrostatic interactions, lysozyme tends to be adsorbed on negatively charged surfaces with the side-on orientation for which the active site of lysozyme faces sideways. The side-on orientation agrees well with the experimental results where the adsorbed orientation of lysozyme is determined by electrostatic interactions. As the contribution from van der Waals interactions gradually dominates, the back-on orientation becomes the preferred one. For this orientation, the active site of lysozyme faces outward, which conforms to the experimental results where the orientation of adsorbed lysozyme is co-determined by electrostatic interactions and van der Waals interactions. It is also found that despite of its net positive charge, lysozyme could be adsorbed on positively charged surfaces with both "end-on" and back-on orientations owing to the nonuniform charge distribution over lysozyme surface and the screening effect from ions in solution. The PTMC simulation method provides a way to determine the preferred orientation of proteins on surfaces for biosensor and biomaterial applications.


Sequencing and Genomic Analysis of Sorghum DNA Introgression Variant Line R21 and Recipient Rice Jin Hui 1 Revealed Repetitive Element Variation.
Transferring the genome of distant species to crops is an efficient way to create new germplasms. However, the molecular mechanisms involved are unclear. In this study, a new rice restorer line R21 with heat tolerance was created by introgressing the genomic DNA of sorghum into the recipient restorer line Jin Hui 1. Assembly of rice R21 and Jin Hui 1 genomes was performed using PacBio sequencing technology. Comparative genome analysis and coverage statistics showed that the repetitive sequence atr0026 was a candidate introgression fragment of sorghum DNA. Sequence similarity analysis revealed that atr0026 was distributed at different copy numbers on the telomeric position of chromosomes 9 or 10 in R21, Jin Hui 1, and several rice varieties, indicating that the repetitive sequence from sorghum was highly conserved in rice. The repeat annotation in Gramineae indicated that ribosomal DNA loci that existed in atr0026 may be cause a rearrangement of chromosomes 9 and 10 of the R21 genome, resulting in a copy number variation at the 5' end of it. Our study lays the foundation for further elucidation of the molecular mechanisms underlying the heat tolerance of sorghum DNA introgression variant line R21, which is of great significance for guiding crop genetic breeding.


Total synthesis of (-)-exiguolide.
Total synthesis of (-)-exiguolide, the natural enantiomer, has been accomplished for the first time. The bis(tetrahydropyran) subunit was efficiently synthesized via consecutive olefin cross-metathesis/intramolecular oxa-conjugate addition/reductive etherification. Construction of the 20-membered macrocycle was achieved by Yamaguchi macrolactonization. Stereoselective introduction of the (E,Z,E)-triene side chain via Suzuki-Miyaura coupling completed the total synthesis.


A new Mapinguari Papavero & Wilcox (Diptera, Mydidae, Mydinae) from Minas Gerais State, Brazil.
Mapinguari Papavero & Wilcox, 1974 (Diptera, Mydidae, Mydinae) is a very rare monotypic genus, with the type-species, M. politus (Wiedemann, 1828), occurring exclusively in Amazonia. With the description of Mapinguari uai sp. nov. from a remnant of the Atlantic Forest in southeastern Brazil, the distribution of the genus is greatly expanded. In addition, an updated diagnosis for the genus and its type-species is provided.


Identifying Predictive Bacterial Markers from Cervical Swab Microbiota on Pregnancy Outcome in Woman Undergoing Assisted Reproductive Technologies.
Failure of the embryo to implant causes about three-fourths of lost pregnancies. Female genital tract microbiota has been associated to Assisted Reproductive Technologies (ART) outcomes. The objective of this study was to analyze the microbiota of human cervical swab and to correlate these findings with the ART outcomes. In this study, 88 cervical swabs were collected from women undergoing ART cycles, with various causes of infertility, at the beginning of the ART protocols. After microbial DNA extraction, V3-V4 variable regions of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. PEnalized LOgistic Regression Analysis (PELORA) was performed to identify clusters of bacterial populations with differential abundances between patients with unfavorable and favorable pregnancy outcome groups, respectively. We identified a core of microorganisms at lower taxonomic levels that were predictive of women's pregnancy outcomes. Statistically significant differences were identified at species levels with Lactobacillus salivarius, Lactobacillus rhamnosus among others. Moreover the abundance of Lactobacillus crispatus and iners, respectively increased and decreased in favorable group as compared to unfavorable group, resulted within the core of microorganisms associated to positive ART outcome. Although the predominance of lactobacilli is generally considered to be advantageous for ART outcome, we found that also the presence of Bifidobacterium (together with the other lactobacilli) was more abundant in the favorable group. Cervix is colonized by microorganisms which can play a role in ART outcomes as seen by an overall decrease in embryo attachment rates and pregnancy rates in both fertile and infertile women. If confirmed in a larger cohort, the abundance of these bacteria can be useful not only as a marker of unfavorable pregnancy outcome but also they may open the way to new interventional strategies based on genital tract microbiota manipulation in order to increase the pregnancy rates in woman undergoing assisted reproductive technologies.


Essential veterinary education in the virology of domestic animals, wild animals and birds: diagnosis and pathogenesis of viral infections.
An education in veterinary virology should establish a basis for life-long learning and enable veterinary graduates to address professionally the control and eradication of viral diseases, both locally and globally. It is therefore more important that the curriculum focuses on a sound understanding of the nature and behaviour of viruses and their interactions with animal hosts, rather than imparting detailed information on an ever-increasing number of individual viral diseases in a widening range of animal species. Graduate veterinarians should be prepared with a comprehensive knowledge of the nature of viruses and their close dependence on the hosts thatthey infect, as well as a good understanding of pathogenesis, immunology, epidemiology, diagnostic approaches and control options. All these are necessary if the profession is successfully to meet familiar and new challenges in viral diseases in a wide range of host species, under different management conditions, in various geographic areas of the world.


Infant oral mutilation: a New Zealand case series.
Infant oral mutilation is a practice performed by traditional healers in many Eastern African countries. The sequelae of this practice have been recognised and reported on in many developed countries due to the migration of populations, customs and beliefs. This article describes three cases of infant oral mutilation that have been diagnosed in the Dental Department at Hutt Hospital, Lower Hutt.


The synthetic gestagen levonorgestrel impairs metamorphosis in Xenopus laevis by disruption of the thyroid system.
Synthetic gestagens, including levonorgestrel (LNG), are active compounds in contraceptives, and several studies report their occurrence in surface waters. However, information about endocrine-disrupting effects in nontarget organisms is scarce. The present study investigated effects of LNG exposure on thyroid hormone-dependent metamorphosis of Xenopus laevis. Premetamorphic X. laevis tadpoles at Nieuwkoop and Faber (NF) stage 48 were exposed in a flow-through culture system to four LNG concentrations (10(-11), 10(-10), 10(-9), and 10(-8)M) over the period of metamorphosis. At NF 58 and 66, tadpoles were examined sex specifically. Developmental time and organismal responses were recorded and correlated with molecular and histopathological endpoints. Exposure to 10(-8)M LNG caused an inhibition of metamorphosis resulting in developmental arrest at early climax stages as giant tadpoles or tailed frogs. In brain-pituitary tissue of NF 58 tadpoles, gene expression of thyroid-stimulating hormone (β-subunit; TSHβ), TH receptor β (TRβ), and deiodinase type 3 (D3) was not changed. Instead, prolactin (PRL) messenger RNA (mRNA) was significantly increased by 10(-9)M LNG in females and by 10(-8)M LNG in both sexes. In NF 66 tadpoles, mRNA levels of TSHβ mRNA were significantly increased in the 10(-9) and 10(-8)M LNG treatment groups indicating a hypothyroid state. No changes of TRβ, D3, and PRL gene expression were detected. Histopathological evaluation of thyroid gland sections revealed no typical sign of hypothyroidism but rather an inactivated appearance of the thyroid. In conclusion, our data demonstrate for the first time a completely new aspect of thyroid system disruption caused by synthetic gestagens in developing amphibians.


Genotypic characterization of rickettsiae by DNA probes generated from Rickettsia prowazekii DNA.
Southern blot analysis of HindIII-cleaved rickettsial DNA was used for genotypic characterization of the typhus group (TG) species (R. prowazekii, R. typhi, R. canada) and a few species of the spotted fever group (SFG) rickettsiae (R. sibirica, R. conorii, R. akari). Four different DNA probes were employed. PBH11 and PBH13 probes were morphospecific HindIII fragments of R. prowazekii DNA. MW218 probe contained the gene for 51 K antigen and MW264 probe contained the citrate synthase gene of R. prowazekii. All the probes hybridized with the tested TG and SFG rickettsial DNAs, forming from 1 to 5 bands, but they did not with R. tsutsugamushi or C. burnetii DNAs. All the probes demonstrated specific hybridization patterns with TG species and R. akari. PBH11, PBH13 and MW264 probes clearly distinguished R. sibirica and R. conorii from the other tested rickettsiae, but not from each other. However, these two species differed slightly with MW218 probe. Several strains of each species were analyzed in this way and except for strains of R. conorii identical intraspecies patterns were obtained. These data lead us to consider the obtained hybridization patterns as criteria for genotypic identification.


Dietary magnesium supplementation affects bone metabolism and dynamic strength of bone in ovariectomized rats.
We evaluated the effect of magnesium supplementation on apparent calcium absorption, bone metabolism and dynamic bone strength in ovariectomized (OVX) rats as a model of postmenopausal women. Two groups of OVX rats were fed a 0.05% Mg diet or a 0.15% Mg diet, and one group of sham-operated rats was fed the 0.05% Mg diet for 42 d. We collected feces and urine of all rats for 3-d periods starting from d 3, 10, 17, 24, 31 and 38 of the feeding experiment for calcium and magnesium balance studies. Urine was collected for 24 h from d 41 of the feeding experiment for measuring deoxypyridinoline. After the 42 d, the rats were killed, serum prepared and femora excised. The apparent calcium absorption in the OVX rats fed 0.15% Mg was significantly lower than both other groups. Additionally, the urinary excretion of deoxypyridinoline (a bone resorption marker) and the serum parathyroid hormone level of the OVX rats fed the 0.15% Mg diet were significantly lower than in the OVX rats fed 0.05% Mg. Serum osteocalcin (a bone formation marker) in the OVX rats fed the 0.15% Mg diet was significantly higher than in the OVX rats fed 0.05% Mg. The breaking force and breaking energy of the femur in the OVX rats fed the 0.15% Mg diet were significantly higher than in the OVX rats fed the 0.05% Mg diet. These results indicate that magnesium supplementation reduces apparent calcium absorption, but promotes bone formation and prevents bone resorption in OVX rats. Moreover, our results indicate magnesium supplementation increases the dynamic strength of bone.


Multijoint grasping movements. Simulated and observed effects of object location, object size, and initial aperture.
Studies of human prehension have revealed characteristic patterns of grasping kinematics. We sought to gain insight into the determinants of those patterns by means of a computer simulation and accompanying behavioral experiment concerning multijoint, planar grasping behavior. The simulation was based on a recent theory of posture-based motion planning which hypothesizes that movement preparation entails time-limited, multiple task-constraint satisfaction. Prehension was modeled with a stick-figure animation involving 12 series of 81 grasping movements. Circular objects to be grasped were located at three angles (45 degrees, 90 degrees, and 135 degrees) and at three distances (20 cm, 30 cm, and 40 cm) relative to the initial location of the hand in the workplane. Additionally, three object sizes (2 cm, 4 cm, and 6 cm in diameter) and three initial aperture sizes (0.3 cm, 3.3 cm, and 7.0 cm) were used. Analyses of the simulated grasping movements focused on the time course of the hand opening, the tangential velocity of the wrist, and the rotations of the joints in the arm, hand, and fingers. The results showed that the model accurately mimicked detailed kinematics of prehension observed in earlier studies. With respect to the frequently reported relationship between object size and hand opening, the simulations further revealed an effect of initial aperture. This predicted effect was confirmed in an experiment in which four participants performed analogous planar grasping tasks. An analysis of the time course of the opening of the hand showed that maximum aperture covaried with initial aperture. A conclusion of this work is that a major determinant of grasping kinematics is avoidance of collisions with objects that are to be grasped.


CT-guided fine needle aspiration biopsy in the diagnosis of mediastinal tuberculosis.
Twenty-two patients with mediastinal tuberculosis were reviewed. The most common symptoms were chest pain, cough, fever, and weight loss. Results of the physical examination were unremarkable. The chest radiographs of all 22 patients showed abnormal mediastinum with no evidence of extramediastinal disease. Most (62%) had right-sided paratracheal lymphadenopathy. Mantoux skin test was positive (> 15 mm) in all patients, whereas sputum smears and cultures for acid-fast bacilli were negative. Computed tomographic (CT) guided fine needle aspiration biopsies (FNAB) were performed in 12 patients using 22- to 25-gauge needles. Ten patients had fiberoptic bronchoscopic (FOB) examination with brushings and biopsies. Mediastinoscopy (n = 8) or thoracotomy (n = 6) was performed in patients where either FNAB or FOB was not diagnostic or where lymphoma was suspected clinically. The rates of true-positive diagnoses were 20%, 66%, 75%, and 100% for FOB, FNAB, mediastinoscopy, and thoracotomy, respectively. The rate of false-negative for FNAB was 34%. Only one patient developed nonsignificant pneumothorax after FNAB. These findings suggest that CT-guided FNAB is a useful and safe procedure and should be considered in the initial evaluation of patients suspected of having mediastinal tuberculosis.


Metal vinylidenes and allenylidenes in catalysis: applications in anti-Markovnikov additions to terminal alkynes and alkene metathesis.
The involvement of a catalytic metal vinylidene species was proposed for the first time in 1986 to explain the regioselective formation of vinyl carbamates directly from terminal alkynes, carbon dioxide, and amines. Since this initial report, various metal vinylidenes and allenylidenes, which are key activation intermediates, have proved extremely useful for many alkyne transformations. They have contributed to the rational design of new catalytic reactions. This 20th anniversary is a suitable occasion to present the advancement of organometallic vinylidenes and allenylidenes in catalysis.


End-stage liver cirrhosis with severe autoimmune hemolytic anemia, treated by blood type-incompatible living donor liver transplantation: a case report.
We present a case of successful living donor liver transplantation (LDLT) for liver cirrhosis caused by hepatitis B virus with severe autoimmune hemolytic anemia (AIHA) using an ABO-incompatible (ABOi) graft. The patient was a 47-year-old woman who had a history of ruptured esophageal varices, accumulation of intractable ascites, frequent hepatic encephalopathy and severe anemia, with a hemoglobin value of approximately 3 g/dL due to AIHA. We treated the patient by LDLT using an ABOi liver graft. The treatment strategy included anti-CD20 antibody, plasma exchange and transfusion before LDLT. The patient's anemia improved after surgery; she required only 2 units of irradiated red blood cell concentrates-leukocytes reduced. The patient was discharged from the hospital on postoperative day 35. Two years after surgery, the patient still shows normal hepatic and hematological findings. The immunomodulation protocol for ABOi LDLT was effective not only to avoid humoral reactions associated with ABOi LDLT, but also those associated with AIHA.