Neodymium:YAG laser iridotomy.
During the past several years the Neodymium:YAG laser has become increasingly popular for performing peripheral iridotomy. Using energy levels of 2-8 millijoules per shot and 1-3 shots per treatment, most irides can be penetrated in one sitting. Nd:YAG laser iridotomies show very little tendency to close, except in patients with active intraocular inflammation. A small amount of hemorrhage is common following YAG laser iridotomy, but clinically significant hyphema is rare. Significant lenticular or corneal damage is extremely rare. Although longterm follow-up of large numbers of patients is lacking, Nd:YAG laser iridotomy appears to be a safe and effective alternative to Argon laser iridotomy in selected patients.


Walkable home neighbourhood food environment and children's overweight and obesity: Proximity, density or price?
To identify characteristics of the food environment associated with child overweight/obesity that could, if subjected to intervention, mitigate the risk of childhood overweight/obesity. We examined whether the proximity to or density of grocery and convenience stores or fast food restaurants, or the prices of healthy food options were more strongly associated with overweight/obesity risk in children. We collected geocoded data by residential addresses for 1,469 children aged 10-14 years and conducted a census of all food outlets in Saskatoon. The Nutrition Environment Measures Survey (NEMS)-Stores and the NEMS-Restaurants were used to measure availability, quality and relative price of healthy food items in stores and restaurants. Children's weight status was calculated on the basis of measured height and weight. Logistic regression was used to test the associations between overweight/obesity and food environment variables. Within an 800 m walking distance from home, 76% of children did not have access to a grocery store; 58% and 32% had access to at least one convenience store or one fast-food restaurant respectively. A significantly lower odds of overweight/obesity was associated with lower price of healthy food items/options in grocery stores (odds ratio [OR] = 0.87, 95% confidence interval [CI] 0.77-0.99) and fast-food restaurants (OR = 0.97, 95% CI 0.95-0.99) within walking distance of home. Neither the distance to the closest food outlet nor the density of food outlets around children's homes was associated with odds of overweight/obesity. Improving economic access to healthy food in food outlets or fast-food restaurants is one strategy to counter childhood overweight/ obesity.


Activation of neutrophils and monocytes after allergen- and histamine-induced bronchoconstriction.
To determine whether neutrophils and monocytes are activated after allergen-induced asthma, changes in the expression of complement (C3b) receptors were measured by use of the rosette technique. There was a time-dependent increase in the percentages of neutrophil and monocyte rosettes in 13 asthmatic patients for up to 60 min after allergen-inhalation challenge. This was preceded by elevations in the concentrations of serum neutrophil chemotactic activity and reductions in the FEV1. These changes were not observed in seven asthmatic patients who had histamine-induced bronchoconstriction. The present findings support the view that inflammatory cells are activated after allergen-induced asthma and that this may be the result of the release of mast cell-associated mediators rather than the consequence of bronchoconstriction per se.


Human brain microvascular DR-antigen.
Antigen presentation within the human central nervous system by the class II histocompatibility DR-antigen may take place at either the brain capillary-endothelial interface or at perivascular cells, such as smooth muscle or pericytes. The present studies employ a new sensitive immunoperoxidase technique, a mouse monoclonal antibody to the human DR-antigen, and microvessels isolated from autopsied human brain. The experiments show that the DR-antigen is readily detectable in human microvasculature of normal brain and is found in the smooth muscle pre-capillary arterioles and capillary pericytes with minimal, if any, staining of capillary endothelium. These results are consistent with the hypothesis that antigen presentation in the CNS occurs primarily at a site immediately distal to the blood--endothelial interface.


A Degraded Fragment of HIV-1 Gp120 in Rat Hepatocytes Forms Fibrils and Enhances HIV-1 Infection.
Identification of the host or viral factors that enhance HIV infection is critical for preventing sexual transmission of HIV. Amyloid fibrils derived from human semen, including semen-derived enhancer of virus infection and semenogelins, enhance HIV-1 infection dramatically in vitro. In this study, we reported that a short-degraded peptide fragment 1 (DPF1) derived from native HIV-1 envelope protein gp120-loaded rat hepatocytes, formed fibrils by self-assembly and thus enhanced HIV-1 infection by promoting the binding of HIV-1 to target cells. Furthermore, DPF1-formed fibrils might be used as a crossing seed to accelerate the formation of semen-derived enhancer of virus infection and semenogelin fibrils. It will be helpful to clarify the viral factors that affect HIV-1 infection. DPF1 as an analog of gp120 containing the critical residues for CD4 binding might be useful for designing of HIV vaccines and developing HIV entry inhibitors.


Aortic wall alterations after use of gelatin-resorcinol-formalin glue.
We report the case of a patient who underwent reoperation 8 years after aortic valve replacement because of aneurysmal dilatation of the aortic root. During the initial intervention, gelatin-resorcinol-formalin glue had been applied on the outside of the aortic root. Perioperative examination revealed a necrotic appearance of the right coronary sinus, with contained ruptures at two different sites. Histologic analysis showed major destruction of the aortic root media, leading to vascular wall thinning and rupture. The use of gelatin-resorcinolformalin glue may expose patients to major alterations of the aortic wall.


Efficacy of protein A-HRP in an immunological study of black rockfish (Sebastes schlegeli Higendorf) humoral immune responses.
The efficacy of protein A-horse radish peroxidase (HRP), as compared to that of mouse polyclonal antibody raised against purified Ig, in detection of black rockfish (Sebastes schlegeli Higendorf) immunoglobulin (Ig) was examined. Protein A affinity chromatography successfully purified Ig from black rockfish serum; the purified-Ig could be visualised as two protein bands (MW 70 and 25kDa) following resolution with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. In SDS-PAGE immunoblot profiles of the purified-Ig, the mouse polyclonal antibody recognised both the light chain and heavy chains of rockfish Ig, whereas protein A-HRP immunostained only the heavy chain of rockfish Ig. These results suggest that protein A-HRP may be used to detect rockfish antibody-antigen complexes in immunoassays. In a 2-DE immunoblot assay for exploring antigenic profiles of Lactococcus garvieae KG9408, protein A-HRP successfully detected specific antibodies to antigenic proteins of L. garvieae in the rockfish Ig. In addition, enzyme linked immunosorbent assay (ELISA) showed a high correlation between the results obtained for positivity of L. garvieae when protein A-HRP and the mouse polyclonal antibody-was used to analyse samples from 25 diseased rockfish. These results collectively indicate that protein A-HRP has a high affinity for Ig, and may be useful for new investigations into the humoral immune responses of rockfish.


Effects of single-mode microwave heating and dextran conjugation on the structure and functionality of ovalbumin-dextran conjugates.
The proteins modified with carbohydrates through the glycation reaction are capable of changing and improving the functional properties of proteins. In this study, dextran was conjugated to ovalbumin (OVA) by traditional wet heating (WH) or single-mode microwave heating (MH) to improve the functional properties of OVA. Compared with traditional WH, MH for 15-60 min significantly increased the grafting degree (GD). The emulsifying activity and emulsion stability of the OVA-dextran conjugates improved under both traditional WH or MH (p < 0.05), especially under MH at 90 ℃ for 20 min. Correlation analysis showed that the emulsifying activity was positively correlated with surface hydrophobicity (p < 0.05), and emulsion stability was significantly positively correlated with surface hydrophobicity (p < 0.01) and positively correlated with the β-sheet contents (p < 0.05). Moreover, traditional WH and single-mode MH treatment could decrease tan δ, especially MH at 90 °C for 20 min. High GD and long MH treatment (≥25 min) resulted in a significant decrease in ⍺-helix and an increase in β-turn and γ-random coil. The secondary structure of OVA became loose, which was disadvantageous to the thermal stability of the OVA-dextran conjugates. In conclusion, compared with traditional WH, dextran conjugation with OVA via single-mode MH was an effective and safe way to improve the utilization value of OVA.


A global regulatory science agenda for vaccines.
The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable regulators, academics, and other stakeholders to converge around transformative actions for innovation in the regulatory process to support global immunization goals.


The effectiveness of Internet-delivered treatment for generalized anxiety disorder: An updated systematic review and meta-analysis.
Generalized anxiety disorder (GAD) is a highly prevalent, chronic disorder associated with impaired quality of life, societal burden, and poor treatment rates. Internet-delivered interventions may improve the accessibility of treatments and are increasingly being used. This study aimed to update a previous meta-analysis to determine the effectiveness of available Internet-delivered interventions in treating symptoms of GAD. Systematic literature searches were conducted (through April 2020) using Embase, PubMed, PsychINFO, and Cochrane to find randomized controlled trials of Internet-delivered interventions for GAD. Risk of bias was evaluated, and Hedge's g was calculated at posttreatment and follow-up. Twenty studies met eligibility criteria and were included in the meta-analysis. Random-effect models detected large effect sizes for primary outcomes of anxiety (g = 0.79) and worry (g = 0.75), favoring treatment. Effect sizes for depression, functional impairment, and quality of life were moderate to large. Maintenance of effects at follow-up seems likely. Results support the effectiveness of Internet-delivered treatments for GAD. Considerable heterogeneity between studies appeared moderated by variability in the interventions themselves, highlighting the importance of further investigation into the characteristics that may optimize treatment outcomes. Overall, Internet-delivery appears to be a viable mode of treatment for GAD with potential to relieve existing gaps in the provision of treatment.


Dysfunction in attentional processing in patients with Parkinson's disease and visual hallucinations.
Mechanistic insights into visual hallucinations (VH) in Parkinson's disease (PD) have suggested a role for impaired attentional processes. The current study tested 25 PD patients with and 28 PD patients without VH on the attentional network test. Hallucinators had significantly lower accuracy rates compared to non-hallucinators, but no differences were found in reaction times. This suggests that hallucinators show deficits in attentional processes and conflict monitoring. Our findings provide novel behavioural insights that dovetail with current neurobiological frameworks of VH.


Effect of advanced maternal age on early mortality among quadruplets and quintuplets.
This study was undertaken to determine whether advanced maternal age has an impact on survival among quadruplets and quintuplets. A retrospective cohort study was performed on 1 448 quadruplets and 180 quintuplets delivered in the United States between 1995 and 1997. Infants of older mothers (> or =35 years old) were compared with those of younger ones (<35 years old) in terms of early mortality indices. Adjusted mortality probabilities were computed by yearly intervals of maternal age. The likelihood for neonatal (odds ratio [OR]=2.00, 95% CI=1.20-3.45), perinatal (OR=2.10, 95% CI=1.32-3.23), and infant mortality (OR=2.13, 95% CI=1.28-3.60) was significantly higher among younger mothers. For each unit decrease in maternal age, the odds of stillbirth, neonatal, perinatal, and infant death went up by 9%, 12%, 13%, and 12%, respectively, in a dose-dependent fashion (P for trend <.0001). We found increasing maternal age to be associated with favorable survival outcomes among quadruplets and quintuplets.


Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ-1 expression at mRNA and protein levels in ductal carcinoma of the breast.
DJ-1 is a molecule secreted into serum by some breast cancer cells. However, little is known about the clinical significance of the DJ-1 expression. Expression of DJ-1 protein was examined by immunohistochemistry, and expression of DJ-1 mRNA was detected using in-situ hybridization in 273 invasive ductal carcinomas (IDCs) and 41 ductal carcinomas in situ (DCISs) of the breast, and also in breast cancer cell lines. Breast cancer cells were examined for their secretion of DJ-1 using immunoblot analysis. By immunohistochemistry DJ-1 protein expression was lower than adjacent non-cancerous epithelium in 6 (14.6%) of the 41 DCISs and 146 (53%) of the 273 IDCs, even although all 314 carcinomas retained expression of DJ-1 mRNA, which was higher than that in adjacent non-cancerous epithelium in 220 cases (70%). Patients with IDC whose cancer cells showed low expression of DJ-1 protein had significantly shorter disease-free survival (P = 0.0152) and overall survival (P = 0.0196) than those whose cancer cells retained DJ-1 expression. MDA-MB-231 cells, which secreted DJ-1, showed low expression of DJ-1 protein. Low expression of DJ-1 protein with high expression of its mRNA, which may reflect a secretory expression pattern, is predictive of poor outcome in patients with IDC.


Recombinant factor VIIa used to control massive haemorrhage during renal transplantation surgery; vascular graft remained patent.
There is a growing body of evidence to support the use of rFVIIa in cases of excessive bleeding outside its approved use in haemophilia with inhibitors. We now report its use for a paediatric renal transplant case in which its use was both life saving and did not threaten the vascular grafts. To our knowledge this represents the first reported case of rFVIIa used in the setting of renal transplantation. It is reassuring that despite use of a high dose of rFVIIa (>135 mcg/kg; recommended standard dose is 90 mcg/kg) there was no evidence of anastomotic thrombosis.


Identification and estimation of the prevalence of ectoparasites of backyard chicken in Boloso Sore District, Wolaita zone, southern Ethiopia.
Poultry ectoparasites are the basic cause of retarded growth, low liveliness and poor condition of birds directly by inducing irritation, discomfort, tissue damage, blood loss, toxicosis, allergies and dermatitis which in turn reduce the quality and quantities of meat and egg production and indirectly by being mechanical or biological vectors of pathogens. A cross-sectional study was conducted from November 2020 to April 2021 to identify and estimate the prevalence of ectoparasites of chicken managed under a backyard system in the selected area of Boloso Sore district of Wolaita zone, southern Ethiopia. A total of 322 chickens of different age groups, breeds and both sexes were selected by simple random technique and examined for ectoparasite. From the total, 56.52%(182/322) of chickens were infested with one or more species of ectoparasites that mainly grouped into fleas 30.34%(98/322), lice 21.7%(70/322) and fowl tick 4.34%(14/322), there by six species of ectoparasites were identified. Among them, Echidnophaga gallinacean (stick tight flea) 30.34%(98/322) was the most prevalent ectoparasite species followed by lice species (Menopon gallinae 11.80% (38/322), Menacanthus stramineous 6.21%(20/322), Goniocotes gigas 2.48% (8/70) and Goniocotes gallinae 1.24%(4/322) while the least identified was fowl tick (Argas persicus) 4.34%(14/322). Age of the chicken was shown statistically significant (p < 0.05) association with the infestation of ectoparasites in which young chicken was found more (72.5%) infested than adults (27.5%). Also, there was a statistically significant (P < 0.05) difference in the prevalence rate of ectoparasites between both sexes of the chicken, in which females (71.4%) was higher than that of male chicken (28.6%). The local breed was found more highly infested (57.1%) than exotic breeds (42.9%) but the difference was not statistically significant (P > 0.05). There was statistically nonsignificant (P > 0.05) flea infestation in adults 34.14% (43/126) than in young 28.06% (55/196), females 31.34% (63/201) than males 20.66% (25/121), and local breed 31.76% (54/170) than exotic breed 28.95% (44/152). Lice prevalence was statistically nonsignificant (p-value >0.05) higher in adults 38.89% (49/126) than young 10.71% (21/196), female 25.87% (52/201) than males 14.88% (18/121) and local breed 24.12% (41/170) than exotic breed 19.08% (29/152). Generally, the study indicated that the external parasites were highly prevalent in backyard chickens in the study area, which was associated with a lack of attention to the hygienic management system, treatment and control practices which necessitate the application of integrated prevention and control measures like awareness creation to the community on the overall effect of ectoparasites on the productivity of poultry and prevention methods.


Orocecal transit delay in obese patients.
Orocecal transit time was assessed with lactulose hydrogen breath test in 12 obese patients during intravenous infusion of placebo or naloxone 40 micrograms/kg/hr given in randomized order and in double-blind conditions. Transit time was also evaluated in 22 healthy controls. Orocecal transit was significantly (P less than 0.01) longer in the obese patients, during placebo treatment (median 130, range 100-200 min) than in the healthy controls (median 75, range 40-170 min). Compared with placebo, transit time in the obese subjects was delayed (P less than 0.05) during naloxone treatment (median 150, range 100-230 min).


Smoking behavior among US adults with diabetes or impaired fasting glucose.
Cigarette smoking is a well-known cardiovascular risk factor and its impact on cardiovascular disease is even greater among people with diabetes. The aim of this study is to compare the prevalence and determinants of smoking among US adults with diabetes or impaired fasting glucose, and those without diabetes or impaired fasting glucose. We analyzed data from the National Health and Nutrition Examination Surveys (1999-2008). Age-adjusted prevalence of smoking was calculated, and we used logistic regression models to identify the correlates of smoking among people with diabetes, impaired fasting glucose, and normal glucose metabolism. Among 24,649 participants ≥20 years old, age-adjusted smoking prevalence was 25.7% in 3111 individuals with diabetes, 24.2% in 3557 individuals with impaired fasting glucose, and 24.1% in 17,981 individuals without diabetes. Smoking prevalence did not differ across groups or change over time (1999-2008) in any group. Younger age, less education, more alcohol consumption, less physical activity, and major depression symptoms were associated with smoking in people with diabetes, impaired fasting glucose, and normal glucose metabolism. In the US, smoking prevalence among people with diabetes and impaired fasting glucose has not changed and is comparable with the nondiabetic population. Tobacco control efforts should be intensified among this population at high risk for complications and mortality.


Reduced Inhibitory Inputs On Basolateral Amygdala Principal Neurons Following Long-Term Alcohol Consumption.
Recent studies have shown that manipulating basolateral amygdala (BLA) activity can affect alcohol consumption, particularly following chronic and/or long-term intake. Although the mechanisms underlying these effects remain unclear, the BLA is highly sensitive to emotional stimuli including stress and anxiety. Negative emotional states facilitate alcohol craving and relapse in patients with alcohol use disorders. Consequently, the aim of this study was to determine the effect of long-term (10 weeks) alcohol drinking on synaptic activity in BLA principal neurons. We utilized an intermittent drinking paradigm in rats, which facilitated escalating, binge-like alcohol intake over the 10 week drinking period. We then recorded spontaneous excitatory and inhibitory postsynaptic currents of BLA principal neurons from long-term alcohol drinking rats and aged-matched water drinking controls. Excitatory postsynaptic current properties from long-term alcohol drinking rats were unchanged compared to those from age-matched water drinking controls. Conversely, we observed significant reductions of inhibitory postsynaptic current amplitude and frequency in long-term ethanol drinking rats compared to age-matched water drinking controls. These results highlight substantive decreases in basal inhibitory synaptic activity of BLA principal neurons following long-term alcohol consumption. A loss of inhibitory control in the BLA could explain the high incidence of compulsive drinking and stress- or anxiety-induced relapse in patients with alcohol use disorders.


Case based simulation in MRI for suspected appendicitis in children.
To establish the effect on diagnostic confidence of a simulation setting, in which radiologists re-interpret anonymized pediatric MRI cases. In this IRB-approved study, participants completed surveys rating confidence before and after interpreting 10 MRI cases for suspected appendicitis in children. 18 radiologists (4 faculty, 5 fellows, and 9 residents) correctly identified an average of 7.44 cases (range 5-9). Self-described confidence regarding technique and interpretation increased from 2.0 (SD 0.77) and 2.33 (SD 0.69) to 2.83 (SD 0.71) and 2.94 (SD 0.73), respectively. Simulated interpretation of pediatric MRI in suspected appendicitis results in increased self-describe confidence without requiring additional capital/equipment expenses.


Movements and behaviors during spontaneous arousals in healthy young adults: an intermediary stage between wakefulness and sleep?
Arousals are common, sudden and transient elevations of the vigilance level during normal sleep, but arousal-associated behaviors have not yet been studied. We aimed to describe the duration as well as motor and autonomic patterns associated with arousals across sleep stages in normal subjects. The spontaneous arousals of 25 healthy young adults were randomly analyzed on polysomnography with body- and face-oriented video cameras. The duration of the heart rate response as well as the frequency, amplitude, speed, body segment and semiology of associated movements were measured. Among 624 arousals (258 in N2, 140 in N3 and 226 in REM sleep), REM sleep arousals had the shortest duration, and N3 arousals were associated with greater heart rate acceleration. Movements and behaviors (mostly involving the head and neck, then the upper limbs, with rare eyes opening and no turning in bed) were frequent during arousals (69.4% during N2 sleep, 89.3% during N3 and 93.8% during REM sleep). Arousals more frequently included ample, prolonged and whole-body movements during N3 sleep and fast movements and facial expressions during REM sleep. During N2 arousals, chewing was the most prevalent behavior. Some movements resembled orientation and comfort behaviors (flexing/rotating the neck and trunk, scratching, pulling the sheets, rubbing the nose, yawning, smiling, frowning and speaking), whereas others resembled sleep-associated automatisms (swallowing, chewing). In contrast with previous assumptions, most arousals are associated with movements. The type of movements suggests that arousal is an intermediary state between wakefulness and sleep.


Anterograde memory loss induced by hypothermia in rats.
In contrast with the extensive animal research on retrograde amnesia, relatively little attention has been given to anterograde amnesia. Moreover, previous studies of anterograde amnesia have not always clearly separated the effects of the anterograde treatment on acquisition from those on retention. Thus, hypothermia-induced anterograde amnesia for a one-trial conditioned fear memory was examined in three experiments. Experiment 1A demonstrated an anterograde disruption of performance in subjects receiving training in the hypothermic state (29 degrees C) and tested 24 hr later. Acquisition of the target memory in animals exposed to hypothermia prior to conditioning was demonstrated in Experiment 1B. Subjects conditioned while in a hypothermic state (29 degrees C) performed similarly to noncooled subjects if tested shortly after conditioning (while still in a hypothermic state), but not 24 hr after conditioning (while in a normothermic state). Experiment 2 shows that the anterograde amnesia effect is temperature dependent. That is, of animals trained at 29 or 33 degrees C, only the more hypothermic group demonstrated deficits in retention when tested 24 hr later. This experiment also attempted, unsuccessfully, to demonstrate recovery of the amnestic memory by administration of a noncontingent footshock prior to testing. Implications of the failure to demonstrate recovery of memory are discussed along with possible mechanisms involved in producing anterograde amnesia.


Long working hours are associated with unmet dental needs in south Korean male adults who have experienced dental pain.
We explored the association between working hours and unmet dental needs among adults who have experienced dental pain, and how this relationship varied by demographic and lifestyle factors. We used the data of 9594 adults who reported dental pain from the Korea National Health and Nutrition Examination Survey (KNHANES) V and VI. We conducted a logistic regression analysis to determine the association between working hours and unmet dental needs, followed by a subgroup analysis and Cochran-Armitage trend tests. Among the 4203 male subjects, 1661 (39.5%) experienced unmet dental needs. They also showed a significant dose-response relationship between working hours and unmet dental needs (OR 1.21 [95% CI 0.97-1.51], OR 1.30 [95% CI 0.99-1.69], OR 1.33 [95% CI 1.04-1.71], OR 1.58 [95% CI 1.21-2.07] compared to no working hours), whereas female participants did not. The significance of the association was preserved among participants with increased consumption of alcohol, urban residence, and who brushed their teeth at least twice a day. It was also stronger among those who lacked access to dental services or did not perceive the need for dental care. Among adults who have experienced dental pain, unmet dental needs had higher odds of occurring in males who worked longer, and this relationship appears to be influenced by consumption of alcohol, region of residence, tooth-brushing frequency, and access to and perception of dental care. Accordingly, policies should be drafted to reduce unmet needs by considering these factors.


Neuroanatomical and functional substrates of the hypomanic personality trait and its prediction on aggression.
Hypomanic personality manifests a close link with several psychiatric disorders and its abnormality is a risk indicator for developing bipolar disorders. We systematically investigated the potential neuroanatomical and functional substrates underlying hypomanic personality trait (HPT) and its sub-dimensions (i.e., Social Vitality, Mood Volatility, and Excitement) combined with structural and functional imaging data as well as their corresponding brain networks in a large non-clinical sample across two studies (n = 464). Behaviorally, HPT, specifically Mood Volatility and Excitement, was positively associated with aggressive behaviors in both studies. Structurally, sex-specific morphological characteristics were further observed in the motor and top-down control networks especially for Mood Volatility, although HPT was generally positively associated with grey matter volumes (GMVs) in the prefrontal, temporal, visual, and limbic systems. Functionally, brain activations related to immediate or delayed losses were found to predict individual variability in HPT, specifically Social Vitality and Excitement, on the motor and prefrontal-parietal cortices. Topologically, connectome-based prediction model analysis further revealed the predictive role of individual-level morphological and resting-state functional connectivity on HPT and its sub-dimensions, although it did not reveal any links with general brain topological properties. GMVs in the temporal, limbic (e.g., amygdala), and visual cortices mediated the effects of HPT on behavioral aggression. These findings suggest that the imbalance between motor and control circuits may be critical for HPT and provide novel insights into the neuroanatomical, functional, and topological mechanisms underlying the specific temperament and its impacts on aggression.


Gap junctions in the epidermis of fetal rats studied by transmission electron microscopy.
In the ventral epidermis of fetal rats the size and distribution of intercellular gap junctions changed during differentiation. In the young fetus, between 13 and 17 days, large gap junctions sometimes exceeding 3 micron in profile length were found predominantly in basal cells. As the epidermis increased in thickness the mean profile length diminished until only small gap junctions were present mainly in more superficial layers even persisting into the stratum corneum. Endocytosis of the intercellular gap junctions gave rise to intracytoplasmic annular gap junctions (AGJs) which occurred after 17 days predominantly in the superficial three layers of the epidermis. The AGJs diminished in mean diameter with the age of the fetuses possibly as a consequence of the decreasing size of the intercellular gap junctions from which they had formed. Rarely sequestration of AGJs by cytoplasmic membranes occurred but many recognizable AGJs persisted into the stratum corneum. As in other developing systems, the function of gap junctions in epidermis is unknown but the extensive junctions of younger epidermis might be related to the maintenance of a greater level of uniformity both of mitotic activity and of differentiation.


Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting.
Prehospital providers are at increased risk for blood-borne exposure and disease due to the nature of their environment. The use if intranasal (i.n.) medications in high-risk populations may limit this risk of exposure. To determine the efficacy of i.n. naloxone in the treatment of suspected opiate overdose patients in the prehospital setting, a prospective, nonrandomized trial of administering i.n. naloxone by paramedics to patients with suspected opiate overdoses over a 6-month period was performed. All adult patients encountered in the prehospital setting as suspected opiate overdose (OD), found down (FD), or with altered mental status (AMS) who met the criteria for naloxone administration were included in the study. i.n. naloxone (2 mg) was administered immediately upon patient contact and before i.v. insertion and administration of i.v. naloxone (2 mg). Patients were then treated by EMS protocol. The main outcome measures were: time of i.n. naloxone administration, time of i.v. naloxone administration, time of appropriate patient response as reported by paramedics. Ninety-five patients received i.n. naloxone and were included in the study. A total of 52 patients responded to naloxone by either i.n. or i.v., with 43 (83%) responding to i.n. naloxone alone. Seven patients (16%) in this group required further doses of i.v. naloxone. In conclusion, i.n. naloxone is a novel alternative method for drug administration in high-risk patients in the prehospital setting with good overall effectiveness. The use of this route is further discussed in relation to efficacy of treatment and minimizing the risk of blood-borne exposures to EMS personnel.


Oral administration of Ulmus davidiana extract suppresses interleukin-1β expression in LPS-induced immune responses and lung injury.
Ulmus davidiana (UD) is a traditional Korean herb medicine that is used to treat inflammatory disorders. UD has been shown to modulate a number of inflammatory processes in vitro or in vivo studies. However, the molecular mechanisms of UD on lipopolysaccharide (LPS)-induced acute lung injury remain to be understood. The primary objective of this study is to determine the effect of UD bark water extract on LPS-induced immune responses and lung injury using both in vitro and in vivo models. RAW 264.7 cells and a rat model of acute lung injury (ALI) were used to study the effects of UD on several parameters. Nitrite level, lactate dehydrogenase (LDH) level, and superoxide dismutase (SOD) activities were measured. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and plasma transaminase activities in blood were also determined. Pathological investigations were also performed. LPS infusion resulted in elevated IL-1β mRNA expression, nitrite levels, TNF-α expression, and IL-1β expression in RAW 264.7 cells. LPS infusion also increased levels of nitrite/nitrate, total protein, LDH, and TNF-α in bronchoalveolar lavage fluid, but reduced SOD levels in ex vivo and in vivo models. UD administration ameliorated all these inflammatory markers. In particular, treatment with UD reduced LPS-induced nitrite production in RAW 264.7 cells in a dose-dependent manner. UD treatment also counteracted the LPS-induced increase in alanine aminotransferase (ALT) and aspartate transaminase (AST) activity in rat plasma, leading to a significant reduction in ALT and AST activity. The results revealed that UD treatment reduces LPS-induced nitrite production, IL-1β mRNA expression, and TNF-α expression. In addition, LPS-induced decrease in SOD level is significantly elevated by UD administration. These results indicate that UD extract merits consideration as a potential drug for treating and/or preventing ALI.


STNM1 in human cancers: role, function and potential therapy sensitizer.
STMN1 belongs to the stathmin gene family, it encodes a cytoplasmic phosphorylated protein, stathmin1, which is commonly observed in vertebrate cells. STMN1 is a structural microtubule-associated protein (MAP) that binds to microtubule protein dimers rather than microtubules, with each STMN1 binding two microtubule protein dimers and preventing their aggregation, leading to microtubule instability. STMN1 expression is elevated in a number of malignancies, and inhibition of its expression can interfere with tumor cell division. Its expression can change the division of tumor cells, thereby arresting cell growth in the G2/M phase. Moreover, STMN1 expression affects tumor cell sensitivity to anti-microtubule drug analogs, including vincristine and paclitaxel. The research on MAPs is limited, and new insights on the mechanism of STMN1 in different cancers are emerging. The effective application of STMN1 in cancer prognosis and treatment requires further understanding of this protein. Here, we summarize the general characteristics of STMN1 and outline how STMN1 plays a role in cancer development, targeting multiple signaling networks and acting as a downstream target for multiple microRNAs, circRNAs, and lincRNAs. We also summarize recent findings on the function role of STMN1 in tumor resistance and as a therapeutic target for cancer.


GABAA receptors as targets for treating affective and cognitive symptoms of depression.
In the past 20 years, our understanding of the pathophysiology of depression has evolved from a focus on an imbalance of monoaminergic neurotransmitters to a multifactorial picture including an improved understanding of the role of glutamatergic excitatory and GABAergic inhibitory neurotransmission. FDA-approved treatments targeting the glutamatergic [esketamine for major depressive disorder (MDD)] and GABAergic (brexanolone for peripartum depression) systems have become available. This review focuses on the GABAA receptor (GABAAR) system as a target for novel antidepressants and discusses the mechanisms by which modulation of δ-containing GABAARs with neuroactive steroids (NASs) or of α5-containing GABAARs results in antidepressant or antidepressant-like actions and discusses clinical data on NASs. Moreover, a potential mechanism by which α5-GABAAR-positive allosteric modulators (PAMs) may improve cognitive deficits in depression is presented.


Improved patient access and outcomes with the integration of an eConsult program (teledermatology) within a large academic medical center.
Insurance, racial, and socioeconomic health disparities continue to pose significant challenges for access to dermatologic care. Studies applying teledermatology to increase access to underinsured individuals and ethnic minorities are limited. To determine how the implementation of a teledermatology program affects access to health care and patient outcomes. A cross-sectional evaluation was performed of all ambulatory dermatology referrals and electronic dermatology consultations (eConsults) at Ohio State University within a 25-month period. Compared with ambulatory referrals, eConsults served more nonwhite patients (612 of 1698 [36.0%] vs 4040 of 16,073 [25.1%]; P < .001) and more Medicaid enrollees (459 of 1698 patients [27.0%] vs 3266 of 16,073 [20.3%]; P < .001). In addition, ambulatory referral patients were significantly less likely to attend their scheduled appointment compared with eConsult patients, as either "no-shows" (246 of 2526 [9.7%] vs 3 of 62 [4.8%]) or cancellations (742 of 2526 [29.4%] vs 8 of 62 [12.9%]; P = .003). There were fewer median days to extirpation for eConsult patients compared with ambulatory referral patients (interquartile range; 80.7 ± 79.8 vs 116.9 ± 86.6 days; P = .004). Integrating dermatologic care through a telemedicine system can result in improved access for underserved patients through improved efficiency outcomes.


Regional procarbazine delivery reduces testicular toxicity.
Procarbazine has been implicated as a cause of infertility. Regionalization of drug delivery is a potential method to avoid this problem. We investigated the protective effect of testicular circulatory isolation (TCI) on gonadal toxicity during procarbazine administration in the Sprague-Dawley rat. Four groups (n = 10/group) were used. Animals in group 1 received no treatment. Rats in groups 2 and 3 were anaesthetized and received TCI of the left testis by clamping of the spermatic cord and gubernaculum immediately before a bolus of intravenous procarbazine (400 mg kg-1). The clamping was maintained for 15 min after procarbazine administration in group 2 and for 45 min in group 3. Rats in group 4 received sham surgery immediately before procarbazine administration. On day 70, all rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by measurements of testicular weight, sperm head count, repopulation index, and epididymal index. The results indicated that 15 min of TCI did not mitigate testicular toxicity; 45 min of TCI provided moderate protection against procarbazine-induced testicular toxicity.


Store-operated Ca2+-channels are sensitive to changes in extracellular pH.
The sensitivity of store-operated Ca(2+)-entry to changes in the extra- and intracellular pH (pH(o) and pH(i), respectively) was investigated in SH-SY5Y human neuroblastoma cells. The intracellular Ca(2+)-stores were depleted either with 1 mM carbachol (CCH) or with 2 microM thapsigargin (TG). Extracellular acidification suppressed both the CCH- and TG-mediated Ca(2+)-entry while external alkalinization augmented both the CCH- and the TG-induced Ca(2+)-influx. Mn(2+)-quenching experiments revealed that the rates of Ca(2+)-entry at the thapsigargin- or carbachol-induced plateau were both accelerated at pH(o) 8.2 and slowed down at pH(o) 6.8 with respect to the control at pH(o) 7.4. Alteration of pH(o) between 6.8 and 8.2 did not have any significant prompt effect on pH(i) and changes in pH(i) left the CCH-induced Ca(2+)-entry unaffected. These findings demonstrate that physiologically relevant changes in pH(o) affect the store-operated Ca(2+)-entry in SH-SY5Y cells and suggest that endogenous pH(o) shifts may regulate cell activity in situ via modulating the store-operated Ca(2+)-entry.


Identification of Genetic Risk Factors for Monogenic and Complex Canine Diseases.
Advances in DNA sequencing and other technologies have greatly facilitated the identification of genetic risk factors for inherited diseases in dogs. We review recent technological developments based on selected examples from canine disease genetics. The identification of disease-causing variants in dogs with monogenic diseases may become a widely employed diagnostic approach in clinical veterinary medicine in the not-too-distant future. Diseases with complex modes of inheritance continue to pose challenges to researchers but have also become much more tangible than in the past. In addition to strategies for identifying genetic risk factors, we provide some thoughts on the interpretation of sequence variants that are largely inspired by developments in human clinical genetics.


Incidence of active tuberculosis among people living with HIV receiving long-term antiretroviral therapy in high TB/HIV burden settings in Thailand: implication for tuberculosis preventive therapy.
Among high tuberculosis (TB) and HIV burden countries in Asia, tuberculosis preventive therapy (TPT) in people living with HIV (PLWH) has been underutilized despite its proven benefits independent of antiretroviral therapy (ART). Therefore, we determined the incidence of active TB and mortality among 9179 adult PLWH who attended and received ART from 15 tertiary care hospitals across Thailand. A retrospective study was conducted in 2018 using follow-up data from 1999 to 2018. The primary endpoint was incident TB disease after ART initiation. Factors associated with TB incidence were analysed using competing risk regression. The Kaplan-Meier method was used to estimate mortality after ART initiation. During a median of 5.1 years of ART (IQR 2.2-9.5 years), 442 (4.8%) PLWH developed TB (TB/HIV), giving an overall incidence of 750 (95% CI 683-823) per 100,000 persons-year of follow up (PYFU). In multivariate analysis, lower CD4 at ART initiation (≤100 cells/mm3 , adjusted sub-distribution hazard ratio [aSHR]: 2.08, 95% CI, 1.47-2.92; 101-200 cells/mm3 , aSHR: 2.21, 95% CI, 1.54-3.16; 201-350 cells/mm3 , aSHR: 1.59, 95% CI, 1.11-2.28 vs. >350 cells/mm3 ), male sex (aSHR: 1.40, 95% CI, 1.11-1.78), lower body weight (<50 kg, aSHR: 1.52, 95% CI, 1.17-1.95) and prior TB event (aSHR: 3.50, 95% CI, 2.72-4.52) were associated with TB incidence. PLWH with HIV RNA ≥50 copies/ml had 5-9 times higher risk of active TB disease higher than those with HIV RNA <50 copies/ml at the same CD4 level. The risk for developing TB was remarkably high during the initial period of ART (175,511 per 100,000 PYFU at<3 months) and was comparable to the general population after 10 years of ART (151 per 100,000 PYFU). TB/HIV had higher mortality (10% vs. 5%) and poorer HIV treatment outcomes: HIV RNA <50 copies/ml (63.8% vs. 82.8%), CD4 cells count (317 vs. 508 cells/mm3 ) at the most recent visit. In this high TB burden country, TB incidence was remarkably high during the first few years after ART initiation and thereafter decreased significantly. Rapid ART initiation and appropriate TPT can be potential key interventions to tackle the TB epidemic and reduce mortality among PLWH in TB/HIV high burden settings.


Diverse Synthetic Transformations Using 4-Bromo-3,3,4,4-tetrafluorobut-1-ene and Its Applications in the Preparation of CF2 CF2 -Containing Sugars, Liquid Crystals, and Light-Emitting Materials.
Organic molecules with fluoroalkylene scaffolds, especially a tetrafluoroethylene (CF2 CF2 ) moiety, in their molecular structures exhibit unique biological activities, or can be applied to functional materials such as liquid crystals and light-emitting materials. Although several methods for the syntheses of CF2 CF2 -containing organic molecules have been reported to date, they have been limited to methods using explosives and fluorinating agents. Therefore, there is an urgent need to develop simple and efficient approaches to synthesize CF2 CF2 -containing organic molecules from readily available fluorinated substrates using carbon-carbon bond formation reactions. This personal account summarizes the simple and efficient transformation of functional groups at both ends of 4-bromo-3,3,4,4-tetrafluorobut-1-ene and discusses its synthetic applications to biologically active fluorinated sugars and functional materials, such as liquid crystals and light-emitting molecules.


Determination of muscle-tendon unit properties during tendon transfer.
Data on passive lengthening and active shortening from electrical stimulation to give a total functional excursion are presented. Length-tension characteristics of certain muscles used for transfer are given. Electrical stimulation of the newly transferred tendon gives useful information that is reproducible. This new knowledge obtained at operation is an important adjunct to the traditional techniques and provides helpful information in performing better procedures.


The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex.
The human herpesvirus 8 (HHV8, also called Kaposi's sarcoma-associated herpesvirus) has been linked to Kaposi's sarcoma and primary effusion lymphoma (PEL) in immunocompromised individuals. We demonstrate that PEL cell lines have a constitutively active NF-kappaB pathway, which is associated with persistent phosphorylation of IkappaBalpha. To elucidate the mechanism of NF-kappaB activation in PEL cell lines, we have investigated the role of viral FLICE inhibitory protein (vFLIP) in this process. We report that stable expression of HHV8 vFLIP in a variety of cell lines is associated with persistent NF-kappaB activation caused by constitutive phosphorylation of IkappaBalpha. HHV8 vFLIP gets recruited to a approximately 700-kDa IkappaB kinase (IKK) complex and physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP. HHV8 vFLIP is incapable of activating NF-kappaB in cells deficient in NEMO/IKKgamma, thereby suggesting an essential role of an intact IKK complex in this process. Our results suggest that HHV8 vFLIP might contribute to the persistent NF-kappaB activation observed in PEL cells by associating with and stimulating the activity of the cellular IKK complex.


[Color Doppler ultrasonographic assessment of the risk of injury to major branch of the middle hepatic vein during laparoscopic cholecystectomy].
To investigate the cause of hemorrhage from the gallbladder bed during laparoscopic cholecystectomy. Color Doppler ultrasound was used to examine the cause of venous hemorrhage from the gallbladder bed during laparoscopic cholecystectomy in 1 patient postoperatively and to examine the anatomic relationship between the gallbladder bed and branches of the middle hepatic vein in 91 patients preoperatively. There is a major branch of middle hepatic vein extended close to the gallbladder bed. The branch of the middle hepatic vein was completely adherent to the gallbladder bed in 14 of 91 patients (15.4%). The mean distance between the closest point of the middle hepatic vein and the gallbladder bed is 5.0 +/- 4.6 mm, the mean diameter of this point is 3.2 +/- 1.1 mm. Patients with large branches of the middle hepatic vein close to the gallbladder bed are at risk of hemorrhage during laparoscopic cholecystectomy and should be identified preoperatively with ultrasound.


Working from home in Australia during the COVID-19 pandemic: cross-sectional results from the Employees Working From Home (EWFH) study.
To investigate the impacts, on mental and physical health, of a mandatory shift to working from home during the COVID-19 pandemic. Cross sectional, online survey. Online survey was conducted from September 2020 to November 2020 in the general population. Australian residents working from home for at least 2 days a week at some time in 2020 during the COVID-19 pandemic. Demographics, caring responsibilities, working from home arrangements, work-related technology, work-family interface, psychosocial and physical working conditions, and reported stress and musculoskeletal pain. 924 Australians responded to the online questionnaire. Respondents were mostly women (75.5%) based in Victoria (83.7%) and employed in the education and training and healthcare sectors. Approximately 70% of respondents worked five or more days from home, with only 60% having a dedicated workstation in an uninterrupted space. Over 70% of all respondents reported experiencing musculoskeletal pain or discomfort. Gendered differences were observed; men reported higher levels of family to work conflict (3.16±1.52 to 2.94±1.59, p=0.031), and lower levels of recognition for their work (3.75±1.03 to 3.96±1.06, p=0.004), compared with women. For women, stress (2.94±0.92 to 2.66±0.88, p<0.001) and neck/shoulder pain (4.50±2.90 to 3.51±2.84, p<0.001) were higher than men and they also reported more concerns about their job security than men (3.01±1.33 to 2.78±1.40, p=0.043). Preliminary evidence from the current study suggests that working from home may impact employees' physical and mental health, and that this impact is likely to be gendered. Although further analysis is required, these data provide insights into further research opportunities needed to assist employers in optimising working from home conditions and reduce the potential negative physical and mental health impacts on their employees.


Bioavailability evaluation of a controlled-release dextromethorphan liquid.
A randomized, two-way, steady-state crossover study was performed in 24 healthy male volunteers to evaluate the bioavailability of a controlled-release (CR) dextromethorphan (DM) suspension. Only slow and intermediate DM metabolizers were allowed to participate in the study; determination of metabolizer status was performed before study enrollment. Each volunteer was administered 30 mg of an immediate-release (IR) DM solution qid or 60 mg DM as a CR suspension bid for two weeks, for a total daily dose of 120 mg. After a two-week washout period, the subjects were administered the alternate treatment. Blood samples were collected over a 12-hour dosing period on the last day of each treatment and analyzed for DM and its active metabolite, dextrorphan (DP). In addition, urine was collected over the 12-hour steady-state dosing interval and measured for DM and two metabolites. Pharmacokinetic determinations were made from plasma DM and DP data, and total urinary excretion was determined. All comparisons made between the two formulations indicated that the CR DM suspension was bioequivalent to the IR DM solution at steady state, while producing a prolonged release of the drug over time.


How did intraoperative neuromonitorization prevent tetraplegia?
Patients with mucopolysaccharidosis type IVA (MPS IVA) have many risk factors for myelopathy and paresis. These are spinal cord compression, bone stenosis, and soft tissue thickening with ligament laxity, deformity, odontoid hypoplasia, and atlantoaxial instability. Although most patients with MPS IVA appear generally healthy at birth, patients often show skeletal deformities within a few years. Surgical indications are difficult to determine. Historically, many physicians have used prophylactic decompression and fusion in young, asymptomatic MPS IVA patients to prevent cord compression. Although spinal cord decompression is usually required at the craniocervical junction in patients with MPS IVA, decompression may be required at other spinal cord levels as well. There is a risk of developing neurological damage during surgery. The most common causes are ischemia secondary to cardiac output deteriorated in the prone position or due to artery damage, and local trauma due to neck movements or traction while bringing the patient to the prone position. Neurophysiological monitoring is very important during surgery to reduce the risk of neurological damage in spinal cord surgery. In this case report, a case with loss of lower extremity neuromonitorization motor evoked potential (MEP) responses in the early period of surgery without any intervention to the craniocervical junction after prone positioning will be presented.


Clinical implementation of a new HDR brachytherapy device for partial breast irradiation.
To present the clinical implementation of a new HDR device for partial breast irradiation, the Strut-Adjusted Volume Implant (SAVI), at the University of California, San Diego. The SAVI device has multiple peripheral struts that can be differentially loaded with the HDR source. Planning criteria used for evaluation of the treatment plans included the following dose volume histogram (DVH) criteria: V90 >90%, V150 <50cc and V200 <20cc. SAVI has been used on 20 patients to date at UC San Diego. In each case, the dose was modulated according to patient-specific anatomy to cover the tumor bed, while sparing normal tissues. The dosimetric data show that we can achieve greater than 90% coverage with respect to V90 (median of 95.3%) and also keep a low V150 and V200 dose at 24.5 and 11.2cc, respectively. Complete treatment can be done within a 30-min time slot, which includes implant verification, setup, and irradiation time as well as wound dressing. SAVI has been implemented at UC San Diego for accelerated partial breast irradiation with excellent tumor bed conformance and minimal normal tissue exposure. Patient positioning is the key to identifying any inter-fraction device motion. Device asymmetry or tissue conformance has been shown to resolve itself 24h after the device implantation. The device can be implemented into an existing HDR program with minimal effort.


Antibacterial activities of the methanol extracts, fractions and compounds from Fagara tessmannii.
Fagara tessmannii is a shrub of the African rainforests used to treat bacterial infections, cancers, swellings and inflammation. In the present study, the methanol extract from the leaves (FTL), bark (FTB), and roots (FTR) of this plant as well as fractions (FTR1-5) and compounds isolated from FTR namely β-sitosterol-3-O-β-d-glucopyranoside (1), nitidine chloride (2) and buesgenine (3), were tested for their antimicrobial activities against a panel of Gram-negative bacteria including multidrug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; Column chromatography was used for the fractionation and purification of the roots extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Results of the MIC determinations indicated that the crude extracts from the roots as well as fraction FTRa4 were active on all the 26 tested bacterial strains. MIC values below 100µg/mL were obtained with roots, leaves and bark extract respectively against 30.8%, 15.4% and 11.5% tested bacteria. The lowest MIC value below of 8µg/mL was obtained with extract from the roots against Escherichia coli MC100 strain. The lowest MIC value of 4µg/mL was also obtained with compound 3 against E. coli AG102 and Klebsiella pneumoniae ATCC11296 CONCLUSIONS: The present study demonstrates that F. tessmannii is a potential source of antimicrobial drugs to fight against MDR bacteria. Benzophenanthrine alkaloids 2 and 3 are the main antibacterial consituents of the roots of the plant.


Super-stiff guidewire or loach guidewire during percutaneous nephrolithotomy?
The objectives of this work are to compare the outcomes between loach guidewire and super-stiff guidewire during percutaneous nephrolithotomy (PCNL) and find potential indications of different guidewires. We retrospectively reviewed our institutional PCNL database from 2017 to 2021. Patients who underwent PCNL guided by loach guidewire were assigned to group A (489 patients); patients who received super-stiff guidewire were assigned to group B (269 patients). Preoperative demographic data, intraoperative parameters, and postoperative complications were compared. The conditions and reasons of failed placement of guidewire needed readjustment were evaluated as well. Preoperative demographic data and most intraoperative parameters were not statistically different between the groups. Postoperative Clavien-Dindo complications were also comparable, with low rate of complications. However, failed placement of guidewire more occurred in group A (8.2% vs. 4.0%, respectively, p = 0.03). Compared with the super-stiff guidewire, the loach guidewire was easier pass/slip into any place either it be perinephric or blood vessels. In most failed group A cases and all failed group B cases, the guidewire was placed in the perirenal fat. Six patients (15%) in group A, the guidewires entered into vessels. Our results support that the faulty placement of loach guidewire is significantly more common compared with super-stiff guidewire. Double confirmation is needed to prevent a major complication out of wrong dilatation whenever there is doubt about the wrong location of the guidewire.


Virus infection as a stressor: influenza virus elevates plasma concentrations of corticosterone, and brain concentrations of MHPG and tryptophan.
Balb/c mice were infected with influenza virus PR8 (H1N1) by the intranasal route. At various subsequent times, brain samples were examined for their content of catecholamine and indoleamine metabolites, and plasma corticosterone was measured. Virus infection was associated with a progressive loss of body and thymus weights, and an increase in plasma corticosterone. Spleen weight initially increased then decreased. There were also increases in the cerebral content of free tryptophan throughout the brain, and of MHPG, a major catabolite of norepinephrine, especially prominent in the hypothalamus. Thus influenza virus can be regarded as a stressor because, like behavioral stressors, it activates the hypothalamic-pituitary-adrenal axis, and increases cerebral concentrations of tryptophan and norepinephrine catabolites. These changes resemble those observed following administration of sheep red blood cells and Newcastle disease virus, noninfectious activators of the immune system, suggesting that noradrenergic and HPA activation are common concomitants of antigenic stimulation. The mediator of these effects may be interleukin-1 released by activated macrophages. It should be noted that animals infected with viruses can be expected to exhibit stress-like endocrine and neurochemical changes.


Single and Repeated Episodes of Candida Species Isolated From Cerebrospinal Fluid for Diagnosing Probable Candida meningitis.
Background: The clinical relevance of single or repeated episodes of Candida spp. in cerebrospinal fluid (CSF) in adult patients is debatable. Methods: Forty-two patients with positive Candida episodes in CSF were enrolled in this retrospective study. Results: A total of 42.9% (18/42) were determined to have probable Candida meningitis (PCM). Neurosurgery [odds ratio (OR) (95% confidence interval), OR: 14.4 (1.6-126.1), P = 0.004], lumbar drainage [OR: 5.8 (1.5-23.3), P = 0.009], VP shunt [(OR: 5.6 (1.2-25.8), P = 0.020)], external ventricular drainage [OR: 4.7 (1.3-17.7), P = 0.018], CRP ≥ 10.0 mg/L [OR: 4.9 (1.3-18.1), P = 0.034], and postsurgical broad-spectrum antibiotics [OR: 9.5 (1.8-50.5), P = 0.004] were risk factors associated with PCM. A single CSF Candida episode for the diagnosis of PCM had 7.7% (0.4-37.9%) sensitivity and 20.7% (8.7-40.3%) specificity, whereas repeated episodes of Candida had 66.7% (41.2-85.6%) sensitivity and 95.8% (76.9-99.8%) specificity. No significant difference was found in radiological imaging or CSF profiles between PCM and non-PCM patients. A total of 37.5% (9/24) of patients without PCM received empirical antifungal treatment, and 88.9% (16/18) of patients with PCM received preemptive antifungal treatment. PCM patients had hospitalized mortality rates of 50.0% (9/18). The odds ratio of mortality was 23.0 (2.5-208.6) for PCM patients compared with non-PCM patients (P = 0.001). Conclusion: Both single and repeated positive CSF samples have low validity for the diagnosis of PCM, suggesting that novel strategies for diagnosis algorithms of PCM are urgently needed. Empirical antifungal treatment should be started immediately for suspicious patients with risk factors.


Moving the Needle Toward Equity: What NIH Is Doing to Promote Diversity, Inclusion, and Accessibility in Research on Intellectual and Developmental Disabilities.
As a major funder of research on intellectual and developmental disabilities (IDD), NIH has a broad view of the profound impact of cultural and structural barriers on the characteristics of IDD study populations and the composition of the IDD research workforce. While long overdue, multiple efforts are currently underway across NIH aimed at addressing these barriers and increasing meaningful representation in biomedical and behavioral research.


Generation of Self-Renewing Hepatoblasts From Human Embryonic Stem Cells by Chemical Approaches.
Somatic stem cells play crucial roles in organogenesis and tissue homeostasis and regeneration and may ultimately prove useful for cell therapy for a variety of degenerative diseases and injuries; however, isolation and expansion of most types of somatic stem cells from tissues are technically challenging. Human pluripotent stem cells are a renewable source for any adult cell types, including somatic stem cells. Generation of somatic stem cells from human pluripotent stem cells is a promising strategy to get these therapeutically valuable cells. Previously, we developed a chemically defined condition for mouse hepatoblast self-renewal through a reiterative screening strategy. In the present study, we efficiently generated hepatoblasts from human embryonic stem cells by a stepwise induction strategy. Importantly, these human embryonic stem cell-derived hepatoblasts can be captured and stably maintained using conditions previously established for mouse hepatoblast self-renewal, which includes basal media supplemented with insulin, transferrin, sodium selenite, epidermal growth factor, glycogen synthase kinase 3 inhibitor, transforming growth factor β receptor inhibitor, lysophosphatidic acid, and sphingosine 1-phosphate. The cells can stably retain hepatoblast phenotypes during prolonged culture and can differentiate into mature hepatocytes through in vitro provision of hepatocyte lineage developmental cues. After being embedded into three-dimensional Matrigel, these cells efficiently formed bile duct-like structures resembling native bile duct tissues. These human embryonic stem cell-derived hepatoblasts would be useful as a renewable source for cell therapy of liver diseases. Somatic stem cells have been proposed as promising candidates for cell-based therapy; however, isolation of somatic stem cells from adult tissues is usually invasive and technically challenging. In the present study, hepatoblasts from human embryonic stem cells were efficiently generated. These human hepatoblasts were then stably captured and maintained by a growth factor and small molecule cocktail, which included epidermal growth factor, glycogen synthase kinase 3 inhibitor, transforming growth factor β receptor inhibitor, lysophosphatidic acid, and sphingosine 1-phosphate. These human embryonic stem cell-derived hepatoblasts would be useful as a renewable source for cell therapy of liver diseases.


Neck Pain: Differential Diagnosis and Management.
Axial neck pain is a common and important problem in the outpatient setting. In isolation, neck pain tends to have a musculoskeletal etiology and responds best to medication and targeted physical therapy. Careful history and physical examination are required to ascertain if there is a neurologic component in addition to the patient's neck pain. For patients needing surgical intervention, there are a variety of approaches and operations that can decompress the appropriate nerve root or the spinal cord itself. These operations are generally well-tolerated and provide significant benefit for appropriately selected patients.


Comparative effects of opiate agonists on proximal and distal colonic motility in dogs.
The colonic motility index was measured in dogs, by using strain-gauge transducers, before and after administration of opiate agonists. Fentanyl, a mu-compound, ethylketazocine (EKC), a kappa-compound, and [D-Ala2,Leu5]enkephalin (DADLE), a delta-agonist, were administered by intravenous (i.v.) or intrathecal (i.t.) routes. Fentanyl (2-10 nmol X kg-1 i.v.) induced a dose-related period of hyperactivity characterized by an increase in both tone and frequency of contractions in the distal portion of the colon, whereas a period of hypomotility following a short-lived period of increased activity was elicited on the proximal colon. Fentanyl (0.1, 0.2 nmol X kg-1 i.t.) had inhibitory effects on both proximal and distal colon. Small doses of EKC (2-4 nmol X kg-1) administered i.t. or larger doses (20-40 nmol X kg-1 i.v.) inhibited colonic motility for a dose-related duration, the effects of EKC being more marked on the distal colon than on the proximal colon. The administration of DADLE, 1-2 nmol X kg-1 i.t., and 40-20 nmol X kg-1 i.v., inhibited and stimulated the colonic contractions, respectively, in both proximal and distal colon. The results demonstrated that the colonic opiate-mediated responses may vary according to the route of administration, the portion of the colon studied and the opioid agonist used. Opiate agonists when administered centrally show a tendency to modulate colonic activity in a similar way whatever the type of agonist.


Analysis of clinical characteristics and risk factors for mortality in human status epilepticus.
To analyse clinical data including aetiology, age, antecedents, classification and mortality in human status epilepticus (SE), and to assess prognostic factors for mortality. A prospective study was performed, including detailed analysis of clinical and laboratorial data of SE in individuals of any age, except neonates. One hundred and eleven SE were included, with patients' age ranging from 3 months to 98 years. SE incidence peaked in the first year of life, and 59.4% of the individuals had previous epilepsy while 40.6% had not. The main underlying causes were noncompliance to treatment in the first group, and CNS infection, stroke and metabolic disturbances in the second group. Overall mortality was 19.8%, and deaths were correlated to aetiology and patient's age. Refractory SE affected 11.7% of the cases. Clinical types included focal, secondarily generalised and generalised SE. Clinical and clinicoelectrographic classifications were convergent, but EEG was essential for the diagnosis in 4.5% of the cases. Epileptic patients are at greater risk to develop SE, however, individuals with no prior history of epilepsy and acute neurological problems can also present SE. Aetiology varies with patient's age, and mortality is high and related to age and underlying causes. Clinical and clinicoelectrographic classifications are usually convergent, but in some cases the diagnosis of SE would not be established without the EEG.


Modeling PAH mass transfer in a slurry of contaminated soil or sediment amended with organic sorbents.
A three-compartment kinetic partitioning model was employed to assess contaminant mass transfer and intraparticle diffusion in systems comprising dense slurries of polluted soil or aquifer sediment with or without sorbent amendments to sequester polycyclic aromatic hydrocarbons (PAHs). The model was applied to simulate temporal changes in aqueous and particle-bound PAH concentrations comparing different pollution sources (heavy oil or tar sludge) and various sorbent amendments (polyoxymethylene (POM), coke breeze, and activated carbon). For the model evaluation, all the parameters needed were directly measured from a series of experiments, allowing full calibration and verification of model predictions without parameter fitting. The numerical model reproduced two separate laboratory-scale experiments reasonably: PAH uptake in POM beads and PAH uptake by semipermeable membrane devices. PAH mass transfer was then simulated for various scenarios, considering different sorbent doses and mass transfer rates as well as biodegradation. Such model predictions provide a quick assessment tool for identifying mass transfer limitations during washing, stabilization, or bioslurry treatments of polluted soil or sediment in mixed systems. It appears that PAHs would be readily released from materials contaminated by small oil droplets, but not tar decanter sludge. Released PAHs would be sequestered rapidly by activated carbon amendment but to a much lesser extent by coke breeze. If sorbing black carbon is present in the slurries, POM pellets would not be effective as a sequestration amendment. High first-order biodegradation rates in the free aqueous phase, e.g., in the order of 0.001 s(-1) for phenanthrene, would be required to compete effectively with adsorption and mass transfer for strong sorbents.


Studies on the degradation of high mobility group non-histone chromosomal proteins.
During the isolation of high mobility group non-histone proteins from calf thymus chromatin by methods described previously (e.g. Goodwin, G.H., Nicolas, R.H. and Johns, E.W. (1975) Biochim. Biophys, Acta. 405, 280--291) protein degradation occurs resulting in a number of proteins appearing in the chromatin extracts which are not present in high mobility group protein preparations in which proteolysis has been completely inhibited. These extra proteins, formerly numbered high mobility group proteins 3, 5, 6 and 8, are thus probably degradation products of other nuclear proteins, produced during the isolation procedure. From the amino acid analyses, tryptic peptides and N-terminal sequences, it is concluded that high mobility group protein 3 is probably a degradation product of high mobility group protein 1. The amino acid analysis of high mobility group protein 8 is very similar to that of the N-terminal half of histone H1 suggesting that high mobility group protein 8 is a degradation product of this histone.


A comparative study of some properties of vitellogenin (Vg) and yolk proteins in a number of freshwater and marine teleost fishes.
1. Injection of oestradiol results in induction of vitellogenic proteins in the plasma of stickleback, sea bass, sea horse, pipe-fish, rainbow trout and roach. 2. Immunoblotting after SDS-PAA gradient gel electrophoresis of plasma proteins of stickleback, sea bass and rainbow trout reveals that vitellogenins from these species share common antigenic determinants. 3. Yolk proteins are recognized by antivitellogenin antisera which shows that proteolytical cleavage does not destroy all antigenic determinants. 4. Vitellogenic proteins are present only in the yolk granules and near the theca cell layer as is shown by immunocytochemical methods.


Synthesis of MAX Phase Nanofibers and Nanoflakes and the Resulting MXenes.
Layered ternary carbides and nitrides, also known as MAX phases, have attracted enormous attention for many applications, especially as precursors to produce 2D metal carbides and nitrides called MXenes. However, it is still challenging to tune and control the shape/morphology of MAX phase particles at the nanoscale, as they are typically manufactured as large grains using ceramic technology. Herein, nanostructured Ti-Al-C MAX phases with fine-tuned morphology of nanofibers and nanoflakes are prepared by using 1D and 2D carbon precursors at a synthesis temperature of 900 °C. The nanostructured MAX phases are used as precursors to produce nanosized multilayered MXenes, with a considerably shorter etching time and a low reaction temperature. These nanosized MXenes exhibit good electrochemical lithium-ion storage properties and a pseudocapacitive electrochemical signature. The obtained Ti2 CTx MXene electrode can deliver delithiation capacity of 300 mAh g-1 at low rates and 100 mAh g-1 when the lithiation/delithiation cycle happens within 30 s. Availability of nanoscale MAX phases and MXene nanoflakes with small lateral size may open new opportunities for both classes of materials.


Effect of retinoid pretreatment on outcomes of patients treated by photodynamic therapy for actinic keratosis of the hand and forearm.
Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been shown to be useful in both spot and field treatments of actinic keratoses (AK). This study evaluates the safety and efficacy of pretreatment of AK lesions on the dorsal hands and forearms with tazarotene gel (0.1%) twice a day for one week before broad-area ALA PDT. Ten subjects aged 75.4 ± 11.6 years (mean plus minus SD) with at least four AK lesions on their dorsal forearm or hand were randomized so that one dorsal hand or forearm was pretreated with tazarotene gel (0.1%) twice daily for one week before ALA PDT with blue light. The other hand or forearm (control) was not pretreated. After seven days, ALA was applied to both sides and incubated 60 minutes before irradiation with blue light. ALA was applied first only to the AK lesions and then to the entire treatment area (defined as the extensor surface of the hand or forearm between the elbow and the base of the fingers) before 60-minute incubation. The ALA area on the control side was occluded during the 60-minute incubation. Efficacy and adverse effects were evaluated within 48 hours and eight weeks later. For both the pretreated and control group, lesion counts of the target areas decreased significantly from baseline to eight weeks after ALA PDT. Reduction percentages of the target area, however, did not differ significantly between the two groups. When reduction percentages of the entire treatment area for both groups were compared the difference between the two groups was of borderline significance (P=0.0547). When the entire treatment area was analyzed, lesion counts of the tazarotene group differed significantly from baseline at eight weeks (P=0.0002), but this was not the case with the control group (P=0.0365). Adverse events were limited to those expected after ALA PDT. Erythema was significantly more severe (P=0.0029) in the pretreated arm five minutes after ALA PDT. Pretreatment of AK lesions on the dorsal hand and forearm with tazarotene gel (0.1%) may enhance the therapeutic effect of ALA PDT without serious side effects.


The potential of Escherichia coli in enteral feeds to cause food poisoning: a study under simulated ward conditions.
The growth of Escherichia coli over a period of 8 h under simulated ward conditions was compared in feeding systems containing either Clinifeed ISO or Nutrient Broth. In both, counts increased from 10(2) to 10(7) ml-1. Other systems containing Clinifeed ISO were inoculated with E. coli and sampled over 24 h. At 8 and 16 h the contaminated reservoir was replaced, refilled or replaced together with the gastric drip line. When the reservoir was replaced or refilled it was always recontaminated by residual organisms. Even when the reservoir and drip line were replaced, although the contents of the reservoir were sterile, E. coli was still detected in feed collected from the end of the fine-bore tube. Experiments with varying numbers of E. coli in the inoculum demonstrated that even one organism in the reservoir could, within 16 h, multiply to a level that might be harmful, especially to compromised patients.


Synthesis, characterization and biological activity of three square-planar complexes of Ni(II) with ethyl (2E)-2-[2-(diphenylphosphino)benzylidene]hydrazinecarboxylate and monodentate pseudohalides.
Three square-planar complexes of nickel(II) with the tridentate condensation derivative of 2-(diphenylphosphino)benzaldehyde and ethyl carbazate, and monodentate pseudohalides, have been synthesized. Their crystal structures have been determined. All the complexes showed a significant antifungal activity, while only the azido complex displayed antibacterial activity. All the complexes were cytotoxic to a panel of six tumor cell lines, the azido complex showing a similar activity as cisplatin to leukemia cell line K562 and lower toxicity to normal MRC-5 cells than that anticancer agent. The complexes interfered with cell cycle of tumor cells and induced plasmid DNA cleavage.


Responding to the needs of the terminally ill through laughter and play.
Care for the terminally ill has greatly expanded. Humor and play, however, remain largely unexplored, surrendered to the cultural expectation of dignity and respect for the dying. This paper suggests several uses of humor and play with the dying, and the benefits of these interventions with patients, families, and care givers.


MiRNAs regulate cell communication in osteogenesis-angiogenesis coupling during bone regeneration.
Bone regeneration is a complex process that requires not only the participation of multiple cell types, but also signal communication between cells. The two basic processes of osteogenesis and angiogenesis are closely related to bone regeneration and bone homeostasis. H-type vessels are a subtype of bone vessels characterized by high expression of CD31 and EMCN. These vessels play a key role in the regulation of bone regeneration and are important mediators of coupling between osteogenesis and angiogenesis. Molecular regulation between different cell types is important for coordination of osteogenesis and angiogenesis that promotes bone regeneration. MiRNAs are small non-coding RNAs that predominantly regulate gene expression at the post-transcriptional level and are closely related to cell communication. Specifically, miRNAs transduce external stimuli through various cell signaling pathways and cause a series of physiological and pathological effects. They are also deeply involved in the bone repair process. This review focuses on three signaling pathways related to osteogenesis-angiogenesis coupling, as well as the miRNAs involved in these pathways. Elucidation of the molecular mechanisms governing osteogenesis and angiogenesis is of great significance for bone regeneration.


Sequential versus concomitant therapy for treatment of Helicobacter pylori infection: an updated systematic review and meta-analysis.
Sequential and concomitant therapies are two innovative therapies for Helicobacter pylori (H. pylori) eradication. However, the comparative efficacy and safety of these treatments are controversial. Therefore, we aimed to conduct an updated systematic review and meta-analysis of studies that compared these two treatments. A search of PubMed, Embase, the Cochrane Library, and Web of Science was carried out. Randomized controlled trials (RCTs) that compared sequential with concomitant therapies were selected for meta-analysis. Twenty RCTs were included in the analysis. The eradication rate of 10-day sequential therapy was superior to that of 5-day concomitant therapy (82.09 versus 77.79%, relative risk (RR) 1.052 (95% confidence interval (CI) 1.004-1.103), P = 0.035)), similar to that of 7-day concomitant therapy (82.40 versus 86.99%, RR 0.959 (95% CI 0.874-1.053), P = 0.382), and inferior to that of 10-day concomitant therapy (78.39 versus 83.32%, RR 0.945 (95% CI 0.907-0.984, P = 0.006); the occurrence of diarrhea was higher in 10-day concomitant therapy than that in 10-day sequential therapy. Compared with the eradication rate of sequential therapy, that of concomitant therapy was higher in metronidazole-resistant strains (RR 0.912 (95% CI 0.844-0.986, P = 0.020)) and strains resistant to metronidazole and clarithromycin (RR 0.542 (95% CI 0.308-0.956, P = 0.035)). The efficacy of concomitant therapy was duration dependent, and 10-day concomitant therapy was superior to 10-day sequential therapy. Compared to sequential therapy, concomitant therapy was more efficacious for metronidazole-resistant strains and metronidazole plus clarithromycin-resistant strains. However, diarrhea was more frequent with concomitant therapy than with sequential therapy.


Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro.
Dysfunction of the orexin/hypocretin neurotransmitter system leads to the sleep disorder narcolepsy. Narcolepsy is characterized by excessive daytime sleepiness and the occurrence of cataplexy--a sudden loss of muscle tone triggered by emotionally arousing events. Both symptoms can be treated with drugs that act on dopaminergic systems. Here we have investigated the effect of orexins on the firing of dopaminergic and GABAergic neurons of the substantia nigra (SN) in brain slices. Surprisingly, dopaminergic neurons in pars compacta were unaffected by orexins. In contrast, bath application of orexin A (100 nM) or orexin B (5-300 nM) greatly increased the firing rate of GABAergic neurons in pars reticulata. The orexin B-mediated excitation was unaffected by blocking synaptic transmission (using low-Ca2+/high-Mg2+ solution). However, the effect of orexin B was reduced significantly by thapsigargin (1 microM) and inhibitors of protein kinase A. The presence of orexinergic fibres in the SN pars reticulata was demonstrated by immunohistochemical methods with the fibre density increasing in the rostrocaudal direction. The orexin excitation of SN reticulata cells may help to maintain their high firing rate during waking. Furthermore, the absence of orexin effects in narcolepsy may predispose affected individuals to attacks of cataplexy.


Holistic and Affordable Analyses of MicroRNA Expression Profiles Using Tagged cDNA Libraries and a Multiplex Sequencing Strategy.
Small and long noncoding RNAs (ncRNAs) are key regulators of gene expression. Variations in ncRNA expression patterns can consequently affect the control of many cellular processes. Not just since 2006, when Andrew Z Fire and Craig C Mello were jointly awarded The Nobel Prize in Physiology or Medicine for their discovery of RNA interference, great efforts were undertaken to unleash the biomedical applicability of small noncoding RNAs, in particular microRNAs. With the technological evolution of massive parallel sequencing technologies over the last years, which now are available for an increasing number of scientists, there is a demand for comprehensible and efficient workflows reliable even for unique and valuable clinical specimens. Here we describe a highly reproducible low-cost protocol for analyses of miRNA expression patterns using tagged cDNA libraries and a multiplex sequencing strategy following an Illumina-like protocol. This protocol easily allows the identification of expression differences from samples of tissues of 1-2 mm3 and fluids of 50-200 μL. We further provide entry points into useful computational biology applications, whose target groups explicitly involve non-bioinformaticians.


Inhibition of DNA methyltransferase reverses cisplatin induced drug resistance in murine neuroblastoma cells.
Acquired drug resistance is a major obstacle to the successful treatment of neuroblastoma by chemotherapy. Recent studies from our laboratory have demonstrated that drug-induced alterations in DNA methylation play an important role in this process. The reversal of resistance to cisplatin in murine neuroblastoma (MNB) was induced by inhibition of DNA methyltransferase activity. MNB cells overexpressing DNA methyltransferase activity (Dnmt3a or Dnmt3b) were established by stable co-transfection of wild type MNB cells with plasmids containing Dnmt3a or Dnmt3b cDNA. Cytotoxic response (IC50), total DNA methyltransferase activity and expression of Dnmt3a or Dnmt3b methyltransferase were determined in Dnmt3a or Dnmt3b transfected MNB cells, respectively. These data demonstrated that total DNA methyltransferase activity was increased to 3-fold above controls (P<0.001) in cisplatin resistant MNB cells, 3-fold in Dnmt3a and 4-fold in Dnmt3b transfected MNB cells. Western blot and RT-PCR data confirmed a corresponding increase in Dnmt3a and 3b expression in cisplatin resistant and transfected cells when compared with control MNB cells (P<0.001). MNB clones overexpressing Dnmt3a or Dnmt3b proteins were resistant to cisplatin treatment (10(-6) M). Incubation of cisplatin resistant, Dnmt3a or Dnmt3b overexpressing MNB cells with 5'-azacytidine (5'-azaC), a methylation inhibitor (2.5 microM) significantly decreased DNA methyltransferase activity, expression of Dnmt3a and Dnmt3b proteins and mRNA levels of cisplatin resistant, Dnmt3a and Dnmt3b transfected MNB cells. Cytotoxicity studies using the MTT assay demonstrated that the sensitivity of cisplatin resistant, Dnmt3a and Dnmt3b overexpressing MNB cells to cisplatin was increased 10-fold (P<0.001) following 5'-azaC treatment. These findings suggest that the overexpression of DNA methyltransferase is associated with a cisplatin resistant phenotype in MNB cells that may or may not be true in animal studies or in the clinical setup. Thus, DNA methylation plays a central role in onset of drug resistance in cisplatin resistant neuroblastoma cells in vitro.


Carbohydrate metabolism prospectively studied in women using a low-estrogen oral contraceptive for six months.
Twenty-four women were prospectively evaluated for their carbohydrate metabolic status before and after six months of using an oral contraceptive containing 0.035 mg ethinyl estradiol and 0.4 mg of norethindrone. At each testing, a 100-gm oral glucose load was administered and blood glucose and plasma insulin values were measured over a three-hour period. Nineteen women with "normal" control tests demonstrated a significant decrease in their fasting glucose values and two of these women (10.5%) had a slight deterioration of their glucose curves. There were no other significant glucose or insulin changes. They had no change in weight and there was a significant reduction in their blood pressure during the treatment time. Five women had "borderline abnormal" control glucose tests, and four of these (80%) improved during the six months of treatment, and two of them (40%) became "normal." Thus, there is no evidence of an adverse effect of this low-estrogen oral contraceptive on carbohydrate metabolism during six months of therapy.


Development of a PCR assay for the detection of human herpes virus type 7.
A PCR assay has been developed to identify the DNA of the human herpes virus type 7. The search and selection of conserved regions was carried out by comparing the whole genome nucleotide sequences of HHV-7. A fragment duplicated in the HHV-7 genomes was chosen as a target for amplification. The performance of the assay was tested on a synthetic matrix and clinical samples. The developed assay has high sensitivity and specificity and showed good efficiency in detecting HHV-7 DNA in clinical samples.


Rare actinomycetes Nocardia caishijiensis and Pseudonocardia carboxydivorans as endophytes, their bioactivity and metabolites evaluation.
Two strains identified as Nocardia caishijiensis (SORS 64b) and Pseudonocardia carboxydivorans (AGLS 2) were isolated as endophytes from Sonchus oleraceus and Ageratum conyzoides respectively. The analysis of their extracts revealed them to be strongly bioactive. The N. caishijiensis extract gave an LC50 of 570 μg/ml(-1) in the brine shrimp cytotoxicity assay and an EC50 of 0.552 μg/ml(-1) in the DPPH antioxidant assay. Antimicrobial activity was observed against Methicillin resistant Staphlococcus aureus (MRSA) and Escherichia coli ATCC 25922 (14 mm), Klebsiella pneumoniae ATCC 706003 (13 mm), S. aureus ATCC 25923 (11 mm) and Candida tropicalis (20 mm). For the extract of P. carboxydivorans the EC50 was 0.670 μg/ml(-1) and it was observed to be more bioactive against Bacillus subtilis DSM 10 ATCC 6051 (21 mm), C. tropicalis (20 mm), S. aureus ATCC 25923 (17 mm), MRSA (17 mm), E. coli K12 (W1130) (16 mm) and Chlorella vulgaris (10 mm). The genotoxicity testing revealed a 20 mm zone of inhibition against the polA mutant strain E. coli K-12 AB 3027 suggesting damage to the DNA and polA genes. The TLC and bioautography screening revealed a diversity of active bands of medium polar and nonpolar compounds. Metabolite analysis by HPLC-DAD via UV/vis spectral screening suggested the possibility of stenothricin and bagremycin A in the mycelium extract of N. caishijiensis respectively. In the broth and mycelium extract of P. carboxydivorans borrelidin was suggested along with α-pyrone. The HPLC-MS revealed bioactive long chained amide derivatives such as 7-Octadecenamide, 9, 12 octadecandienamide. This study reports the rare actinomycetes N. caishijiensis and P. carboxydivorans as endophytes and evaluates their bioactive metabolites.


Up to 8-year follow-up of valve replacement with carbomedics valve.
The aim of this study was to report midterm valve replacement (VR) results with the Carbo-Medics valve (Sulzer Carbomedics, Austin, TX). From 1991 to 1999, 468 patients aged 13 to 76 years (mean 56 years) underwent VR with CarboMedics valve: 239 aortic (A), 167 mitral (M), and 62 A+M or double valve replacement (DVR). Mean follow-up time was 4.4 years; follow-up was 99.1% complete for 2,016 patient-years (PY). The anticoagulation level was targeted to an international normalized ratio of 1.47 to 2.8. The hospital mortality rate was 1.2%. Actuarial analysis for the entire group at 7 years for survival was 87%+/-2.3%. Freedom from valve-related death was 94%+/-1.9%. Freedom from thromboembolic and bleeding events, respectively, were as follows: for AVR, 82%+/-4.9% (2.4%/PY) and 88%+/-2.9% (1.6%/PY); for MVR, 95%+/-2.1% (0.8%/PY) and 91%+/-3.1% (1.3%/PY); and for DVR, 96%+/-3.2% (0.7%/PY) and 85%+/-9.7% (1.0%/PY). Actuarial freedom from reoperation was 98%+/-1.4%. The CarboMedics valve can be implanted with satisfactory early mortality and a low incidence of valve-related events even under low-intensity anticoagulation, as shown in a Japanese population.


Expression of the albumin gene in rat hepatoma cells and their dedifferentiated variants.
Rat hepatoma clones whose cells do and do not produce albumin, as well as somatic hybrid between the two types of cells, have been examined for albumin mRNA. A direct proportionality between the rate of albumin production and the concentration of albumin mRNA sequences was found for all albumin-producing hepatoma and hybrid clones, indicating that rate of synthesis of the protein is determined by the concentration of its mRNA. Albumin-negative dedifferentiated variant and somatic hybrid cells contain fewer than one to five molecules of albumin mRNA per cell; the block in expression of the gene appears to be at the same (probably transcriptional) level in variants and their somatic hybrids.


MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma.
MicroRNAs (miRNAs) are known to be involved in carcinogenesis and tumor progression in hepatocellular carcinoma (HCC). Recently, microRNA-7 (miR-7) has been proven to play a substantial role in glioblastoma and breast cancer, but its functions in the context of HCC remain unknown. Here, we demonstrate that miR-7 inhibits HCC cell growth and metastasis in vitro and in vivo. We first screened and identified a novel miR-7 target, phosphoinositide 3-kinase catalytic subunit delta (PIK3CD). Overexpression of miR-7 would specifically and markedly down-regulate its expression. miR-7-overexpressing subclones showed significant cell growth inhibition by G(0) /G(1) -phase cell-cycle arrest and significant impairment of cell migration in vitro. To identify the mechanisms, we investigated the phosphoinositide 3-kinase (PI3K)/Akt pathway and found that Akt, mammalian target of rapamycin (mTOR), and p70S6K were down-regulated, whereas 4EBP1 was up-regulated in miR-7-overexpressing subclones. We also identified two novel, putative miR-7 target genes, mTOR and p70S6K, which further suggests that miR-7 may be a key regulator of the PI3K/Akt pathway. In xenograft animal experiments, we found that overexpressed miR-7 effectively repressed tumor growth (3.5-fold decrease in mean tumor volume; n = 5) and abolished extrahepatic migration from liver to lung in a nude mouse model of metastasis (n = 5). The number of visible nodules on the lung surface was reduced by 32-fold. A correlation between miR-7 and PIK3CD expression was also confirmed in clinical samples of HCC. These findings indicate that miR-7 functions as a tumor suppressor and plays a substantial role in inhibiting the tumorigenesis and reversing the metastasis of HCC through the PI3K/Akt/mTOR-signaling pathway in vitro and in vivo. By targeting PIK3CD, mTOR, and p70S6K, miR-7 efficiently regulates the PI3K/Akt pathway. Given these results, miR-7 may be a potential therapeutic or diagnostic/prognostic target for treating HCC.


Malignant tumours of the sinuses. Radiologic evaluation, including CT scanning, with clinical and pathologic correlation.
This study is based on experience with 100 patients. The clinical and pathologic features of carcinoma of the sinuses are analyzed. The various radiologic modalities are described and evaluated with respect to diagnosis and treatment.


Influence of estimators of spectral density on the analysis of electromyographic and vibromyographic signals.
Electromyographic (EMG) and vibromyographic (VMG) signals are related to electrical and mechanical muscle activity, respectively. It is known that variations in their frequency components are related to changes in muscle activity and fatigue. The aims of this study were: (1) to analyse the resolution, variance and bias of different estimations of power spectral density function (PSD); and (2) to evaluate the influence of the spectral estimation method on three indices calculated from the PSD of EMG and VMG signals: mean (f(m)) and median (f(c)) frequencies and the ratio of high and low frequency components (H/L ratio) to select the most suitable estimator. Myographic signals were recorded from the sternomastoid muscle, an accessory respiratory muscle, during breathing. For non-parametric methods, Welch periodograms and correlograms were analysed with different windows. Autoregressive (AR) moving average (MA) and ARMA models with different orders were evaluated in the parametric methods. The reproducibility of the results was also studied. Frequency indices, particularly the H/L ratio and f(c), changed considerably when varying the following parameters of the estimators: periodogram with segment durations longer than 150 ms in EMG and with any duration in VMG signals; correlogram with window length shorter than 10% of the total number of samples; and AR models with an order lower than 10, 20 and 40 in f(c), fm and H/L ratio, respectively, in both myographic signals.