Pediatric bronchoscopy during a 17-year period.
From 1969 through 1985, 1032 pediatric bronchoscopies were performed on a total of 748 children under 16 years of age. Of the children 27.4% were under 6 months of age and the smallest patient weighed 600 g. Rigid bronchoscopes with a diameter ranging from 2.5 to 6 mm were used. A flexible fiberoptic bronchoscope with a diameter of 3.5 mm was used only occasionally, mostly for the diagnosis of laryngeal dynamics. All the endoscopies were performed under general anesthesia, except for some laryngoscopies performed with a flexible bronchoscope. The most common indications for bronchoscopy were suspected foreign body (16.7%), stridor (14.5%), recurrent respiratory infections (12.3%) and dyspnoe (9.6%). Laryngomalacia was observed in 13.8% of the children investigated and in patients with inspiratory stridor laryngomalacia was diagnosed in 39.8% of the cases. Subglottic stenosis was confirmed in 7.0% of the children. Tracheal compression was found in 10.8% and tracheal stenosis in 2.5% of the cases. Bronchiectasis was observed in 2.5% and tuberculosis in only 0.5% of the cases. Bronchoscopy was completely normal in only 10.6% of the patients investigated. The complications of pediatric bronchoscopy in this series were infrequent.


A Multi‑Center, Open‑Label, Single‑Arm Trial to Evaluate the Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects with Primary Immunodeficiency.
The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly at the same dose as the subject's previous IgG regimen (DAF 1:1); the minimum dose was 100 mg/kg/week. The primary endpoint was serious bacterial infections (SBIs [null vs alternative hypothesis: SBI rate per person per year ≥ 1 vs < 1]). IgG subclasses and specific pathogen antibody levels were also measured. Sixty-one subjects (19 children [≤ 12 years], 10 adolescents [> 12-16 years], and 32 adults) were enrolled. The rate of SBIs per person per year was 0.017. The 1-sided 99% upper confidence limit was 0.036 (< 1), and the null hypothesis was rejected. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008-0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83-1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively. Seven subjects had serious treatment-emergent adverse events (TEAEs); none was drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate. IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.


Transitions of Care in Cystic Fibrosis.
The development of formal transition models emerged to reduce variability in care, including cystic fibrosis (CF) responsibility, independence, self-care, and education (RISE), which provides a standardized transition program, including knowledge assessments, self-management checklists, and milestones for people with CF. Despite these interventions, the current landscape of health care transition (HCT) remains suboptimal, and additional focused attention on HCT is necessary. Standardization of assessment tools to gauge the efficacy of transfer from pediatric to adult care is a high priority. Such tools should incorporate both clinical and patient-centered outcomes to provide a comprehensive picture of progress and deficiencies of the HCT process.


An electron microscope study of the interaction between Trichomonas vaginalis and epithelial cells of the human amnion membrane.
The mechanism of cytopathogenicity of Trichomonas vaginalis is not well established. Adhesion of T. vaginalis to human epithelial cells is considered a prerequisite for parasitic infection and its pathogenic effect. To investigate cytopathological changes in the host caused by T. vaginalis infection, human amnion membrane was used as an in vitro model. T. vaginalis strain WAA38 from axenic culture was allowed to interact with the epithelial layer of the human amnion membrane for 6 and 9 h. Structural changes resulting from the interaction between parasite and host cells were studied with transmission (TEM) and scanning (SEM) electron microscopy. Analysis of the electron microscope data showed that T. vaginalis established contact with the host cells as early as after 6 h of incubation; however, a close attachment of parasites to the epithelial cells occurred only after 9 h. Amoeboid T. vaginalis formed numerous cytoplasmic extensions and adhered to the epithelial cells mostly through the portions of their body opposite the undulating membrane. A dense network of microfilaments was seen at the site of contact between T. vaginalis and epithelial cells. Damaged and desquamated epithelial cells were seen with TEM and SEM only in the areas where parasites were in direct contact with target cells.


Nonconforming gender expression and insufficient sleep among adolescents during COVID-19 school closure and after school reopening.
Gender nonconformity (GNC) (i.e., gender expression that differs from gender role expectations for feminine or masculine appearance and behavior) is an under-researched area of adolescent sleep health. The COVID-19 lockdown offers an opportunity to understand how the effect of GNC on adolescent health outcomes changes between school closure and reopening. We conducted a cross-sectional study in Shanghai, China, in 2020. The sample size for analysis was 3,265. The age-specific insufficient sleep was estimated according to National Sleep Foundation's sleep duration recommendations. The self-perceived and self-rated GNC were measured by the two items "On the same scale that goes from 100% as a girl to 100% as a boy, where do you think others see you?" and "On a scale that goes from feeling 100% like a girl to feeling 100% like a boy, where do you see yourself?", and birth sex. In addition, we calculated sex-stratified adjusted odds ratios (AORs) of insufficient sleep for students with high and moderate GNC compared to students with low GNC. Finally, we measured the AORs with self-perceived and self-rated GNC during COVID-19 school closure and reopening. Among 3,265 students in grade 6-12 in the analytic sample, 1,567(48.0%) were assigned female at birth (AFAB), 3,188 (97.6%) Han, and 1,921(58.8%) in grade 6-9. Among AFAB students, high self-perceived GNC was significantly associated with insufficient sleep (AOR,1.65; 95%CI,1.30-2.09) during school closure. Insufficient sleep was associated with high self-rated GNC (AOR,1.73; 95%CI,1.23-2.44) and moderate self-rated GNC (AOR,1.69; 95%CI,1.29-2.22) during school closure. After school reopening, neither self-perceived nor self-rated GNC was associated with insufficient sleep among AFAB students. Among assigned male at birth (AMAB) students, none of the two kinds of GNC was associated with insufficient sleep in the two periods during the COVID-19 pandemic. This study suggests GNC is only associated with insufficient sleep among AFAB students during school closure. Furthermore, the association is nonsignificant among AMAB students. These findings indicate that GNC-related stigma within the family could be a risk factor for insufficient sleep among AFAB adolescents.


Flavin-containing monooxygenase and ascorbic acid deficiency. Qualitative and quantitative differences.
Ascorbic acid deficiency causes qualitative and quantitative differences in the guinea pig hepatic flavin-containing monooxygenase (FMO). Kinetic studies with purified FMO indicated no significant change in the apparent Km of dimethylaniline or NADPH in ascorbate-supplemented or -deficient animals. Following purification of ascorbate-deficient guinea pig FMO by DEAE-cellulose and blue agarose chromatography, exogenous FAD was required for 15% of the FMO microsomal activity recovered. In contrast, only 5% of the total microsomal enzyme recovered from ascorbate-supplemented animals required exogenous FAD. Furthermore, there was an enhanced sensitivity to time-dependent nonlinearity with the purified ascorbate-deficient guinea pig FMO. The degree of time-dependent nonlinearity was related to the concentration of substrate. Also, purified ascorbate-supplemented guinea pig FMO was stable for 4 weeks at -20 degrees, whereas the ascorbate-deficient enzyme was inactivated. A decrease in the quantity of ascorbate-deficient guinea pig FMO compared to ascorbate-supplemented was indicated by a marked reduction in total FMO activity recovered from blue agarose chromatography and reduced protein staining intensity with SDS-PAGE at 56,000 daltons.


Kilimanjaro Abruzzo expedition: effects of high-altitude trekking on anthropometric, cardiovascular and blood biochemical parameters.
The effect of the combination of trekking and balanced appropriated diet were studied in mountaineers who spent 6 days at an altitude ranging from 900 to 5895 m above sea level (a.s.l.), during the Kilimanjaro Abruzzo Expedition. This study explored whether anthropometric, cardiovascular and blood biochemical parameters were significantly changed by a regular trekking performed at high altitude, with reduced oxygen levels, together with a macronutrient-containing balanced diet (total daily caloric intake: 3000-3500 Kcals). In consideration of the short period of high-altitude exposure, high-altitude exercise appeared to provide beneficial and rapid effects on the lipid profile and to modulate cardiovascular functions. These effects rely on both high-altitude hypoxia and physical activity. The most interesting observation is that even just a few days of high-altitude exercise, along with a balanced diet, was able to improve plasma lipid profiles.


Systemic Disease and the Liver Part 2: Pregnancy-Related Liver Injury, Sepsis/Critical Illness, Hypoxia, Psoriasis, Scleroderma/Sjogren's Syndrome, Sarcoidosis, Common Variable Immune Deficiency, Cystic Fibrosis, Inflammatory Bowel Disease, and Hematologic Disorders.
The liver is involved in many multisystem diseases and commonly may manifest with abnormal liver chemistry tests. The liver test perturbations may be multifactorial in nature, however, as patients are receiving many different medications and can also have intrinsic liver disease that may be exacerbated by the systemic disorder. Some disorders have typical histologic findings that can be diagnosed on liver biopsy, whereas others will show a more nonspecific histology. Clinicians should be aware of these conditions so as to consider the performance of a liver biopsy at the most opportune time and setting to help establish the diagnosis of acute or chronic liver disease.


Modified aortic cannulation for cardiopulmonary bypass in neonatal piglet model.
Animal models are still essential for studying effects of cardiopulmonary bypass. We describe modifications in cannulation technique for a neonatal piglet model, which may also serve as an "everyday" technique in congenital cardiac surgery (age of animals <7 days; mean body weight 2.9 +/- 0.5 kg). Surgical approach through median sternotomy and cardiopulmonary bypass was established by cannulating right atrium and ascending aorta with a modified aortic root cannula. Left ventricular venting was performed placing a cannula into the apex and connecting this to the venous drainage line. The described technique has been applied in 19 cases, all but one were without technical problems.


Epitopic analysis of detergent-solubilized HLA molecules by solid-phase radioimmunoassay.
A solid-phase radioimmunoanalysis of plasma membrane molecules solubilized in the presence of detergent was developed. From a crude cell lysate, membrane molecules were specifically immobilized by solid-phase adsorbed monoclonal antibodies. Analysis of these molecules was easily performed with radiolabeled monoclonal antibodies of different specificities. This technique was used to analyze the HLA-DR and HLA-A,B,C molecules expressed by RAJI cells. It was possible (a) to determine which epitopes are expressed on the same molecules; (b) to define subsets of HLA molecules according to the epitopes which they express, and (c) to perform quantitative analysis of HLA molecules on a crude cell lysate.


Alteration in community-dwelling older adults' level walking following perturbation training.
While perturbation training is promising in reducing fall-risk among older adults, its impact on altering their spontaneous gait pattern has not been investigated. The purpose of this study was to determine to what extent older adults' gait pattern would be affected by exposure to repeated slips. Seventy-three community-dwelling older adults (age: 72.6±5.4 years) underwent 24 repeated-slip exposure induced by unannounced unlocking and relocking of low-friction sections of a 7-m pathway upon which they walked. Full body kinematics and kinetics were recorded during the training. The gait parameters and the center of mass (COM) stability against backward balance loss were compared before and after the training. The results revealed that the training reduced fall incidence from 43.8% upon the novel slip to 0 at the end of training. After the training, subjects significantly improved gait stability by forward positioning of their COM relative to the base of support without altering gait speed. This forward COM shift resulted from a shortened step at the end of single stance and forward trunk leaning during double stance. They also adopted flat foot landing with knee flexed at touchdown (with an average change of 6.9 and 4.1 degrees, respectively). The perturbation training did alter community-dwelling older adults' spontaneous gait pattern. These changes enabled them to improve their volitional control of stability and their resistance to unpredictable and unpreventable slip-related postural disturbance.


Are the orientation and bond strength of the RCO2(-)···M link key factors for ultrafast electron transfers?
The photo-induced electron transfers in the "straight up" ionic assemblies [Pd3(2+)]···MCP and [Pd3(2+)]···DCP···[Pd3(2+)] ([Pd3(2+)]* → MCP or DCP) are ultrafast (<85 fs) indicating that it is not necessary to have a strong coordination bond or a bent geometry to obtain fast electron injection in porphyrin-containing DSSCs.


Inability of 50 Hz magnetic fields to regulate PKC- and Ca(2+)-dependent gene expression in Jurkat cells.
We have previously reported that the T cell line Jurkat registers the exposure of a sinusoidal extremely low frequency magnetic field at the level of the plasma membrane, resulting in activation of the tyrosine kinase p56(lck), increase in inositol-3-phosphate levels and increase in intracellular calcium concentration within minutes. To elucidate if these events associated with changes in intracellular calcium ion levels were biologically significant, transient transfections of Jurkat cells were performed with calcium-ion dependent reporter constructs. Three different enhancer/promoter constructs were studied coupled to the luciferase reporter gene. The luciferase activity of each construct was measured after treatment of transfected cells to EMF exposure alone, or in combination with ionomycin, phorbol ester or cross-linking anti-CD3 antibodies. There was no indication that the used EMFs could influence any of these reporter constructs.


Comparing Outpatient Opioids, High-Risk Prescribing, and Opioid Poisoning Between Transgender and Cisgender Veterans: A Cross-sectional Analysis.
Transgender veterans have a high prevalence of substance use disorder and physical and mental-health comorbidities, which are associated with prescription opioid use and overdose risk. This study compares receipt of outpatient opioids, high-risk opioid prescribing, and opioid poisoning between transgender and cisgender (i.e., nontransgender) veterans. A secondary analysis of Veterans Health Administration health record data from January 1, 2018 to December 31, 2018 was conducted in 2021. Transgender veterans (n=9,686) were randomly matched to 3 cisgender veterans (n=29,058) on the basis of age and county. Using the same matching criteria, a second cohort was created of all transgender veterans and a matched sample of cisgender veterans who were prescribed an outpatient opioid (n=7,576). Stratified Cox proportional hazard regression measured the RR of each prescription outcome and opioid poisoning. Transgender veterans had a 20% higher risk of being prescribed any outpatient opioid than cisgender veterans (adjusted RR=1.20, 95% CI=1.13, 1.27). Transgender and cisgender veterans who were prescribed an opioid did not have different risks of high-risk prescribing: overlapping opioid prescriptions (adjusted RR=0.93, 95% CI=0.85, 1.02), daily dose >120 morphine milligram equivalents (adjusted RR=0.86, 95% CI=0.66, 1.10), or overlapping opioid and benzodiazepine prescriptions (adjusted RR=1.05, 95% CI=0.96, 1.14). Overall, transgender veterans had more than twice the risk of opioid poisoning than cisgender veterans (RR=2.76, 95% CI=1.57, 4.86). The risk of opioid poisoning did not differ between transgender and cisgender veterans who were prescribed an opioid (RR=1.09, 95% CI=0.56, 2.11). Transgender veterans had a greater risk of being prescribed an outpatient opioid than cisgender veterans but did not have different risks of high-risk opioid prescribing.


Internal mammary node irradiation improves 8-year survival in breast cancer patients: results from a retrospective cohort study in real-world setting.
Regional nodal irradiation (RNI) improves disease outcome in breast cancer patients, but the contribution of internal mammary node irradiation (IMNI) in the context of modern systemic treatment is still controversial. The aim of our study is to evaluate the effect of IMNI in patients with modern systemic treatment in real-world setting. We retrospectively analyzed patients with primary breast cancer treated with surgery followed by adjuvant chemotherapy and adjuvant chestwall/breast irradiation and RNI from 5/2007-12/2010. RNI was delivered to the ipsilateral supraclavicular region and infraclavicular region + / - IMNs. We separated two groups based on the presence and the absence of IMNI. The primary end point was disease-free survival (DFS). DFS and overall survival (OS) were evaluated with Kaplan-Meier method. Differences between two groups were compared with the log-rank test (p < 0.05 considered significant). We used two methods to account for potential confounders: propensity score matching (PSM) and Cox regression analysis. We analyzed 872 patients who received RNI with IMNI (n = 390) or without IMNI (n = 482). Median radiation dose was 50 Gy. Median follow-up was 98 months. IMNI improved 8-year DFS rates versus no IMNI: 75.9% and 64.9% (p < 0.001). After PSM, baseline characteristics were well balanced between the two groups. IMNI significantly improved DFS (p < 0.001) in patients after PSM. IMNI was an independent prognostic factor for DFS. In this study, we found that IMNI improved DFS and OS in breast cancer patients in the context of modern systemic treatment. These data continue to support that IMNI is a key component of RNI.


Terbutryn causes developmental toxicity in zebrafish (Danio rerio) via apoptosis and major organ malformation in the early stages of embryogenesis.
Terbutryn (2-(ethylamino)-4-(tert-butylamino)-6-(methylthio)-1,3,5-triazine) is a substituted symmetrical triazine herbicide used in agricultural fields to prevent undesired vegetation growth by inhibiting photosynthesis in target weeds. Although terbutryn has various benefits, long-term exposure, misuse, or abuse of terbutryn may cause non-target toxicity and severe ecosystem pollution. To provide a detailed description of the embryonic developmental toxicity of terbutryn, zebrafish (Danio rerio) were exposed to 2, 4, and 6 mg/L of terbutryn and the morphological changes, pathological abnormalities, and developmental endpoints were assessed relative to that of a solvent control. The results showed that terbutryn induces a loss of survivability, reduction in body and eye size, and edema in the yolk sac. Through fluorescence microscopy, blood vessels, motor neurons, and liver development were investigated using transgenic zebrafish models based on fluorescently tagged genes (fllk1:eGFP, olig2:dsRed, and L-fabp:dsRed). Furthermore, cell death by apoptosis in zebrafish caused by terbutryn exposure was evaluated via acridine orange staining, which is a selective fluorescent staining agent. To support the preceding results, gene expression alterations caused by terbutryn exposure in zebrafish larvae were assessed. The overall results indicate that exposure to terbutryn induces apoptosis and disrupts organ development. These embryonic developmental toxicity results suggest that terbutryn should be applied in the right areas at the appropriate rates, concentrations, and quantities.


Structurally similar small molecule photoaffinity CCK-A agonists and antagonists as novel tools for directly probing 7TM receptors-ligand interactions.
Incorporation of photolabile benzoyl (2a-d) or trifluoromethyl-3H-diazirine (3a-d) substituents into 1,5-benzodiazepine ligands did not significantly impair the rat CCK-A binding affinity of either agonists or antagonists. The modified agonist ligands also retained functional potency and efficacy in the rat amylase assay. Despite their strong structural similarity, the SAR of this limited set of compounds suggests that these small molecule antagonists and agonists might differ in their mode of binding to the CCK-A receptor. Preliminary affinity results show that representative agonists and antagonists from these series can be used to efficiently covalently label the CCK-A receptor.


The relationship between career adaptability, hope, resilience, and life satisfaction for hospitality students in times of Covid-19.
This study investigates the antecedents and effects of hospitality students' coping mechanisms during the COVID-19 pandemic. The relationship between career adaptability, hope, resilience, and life satisfaction are explored to unveil students' adaptability during times of crisis. The findings confirmed that hope is an important driver of resilience and life satisfaction. Despite all the negativity and uncertainty about jobs and careers during the COVID-19 pandemic, resilience has a double acting effect on the students' life satisfaction via individual and community resilience. Critical implications for academic institutions and the hospitality industry are presented. As the industry recovers from the pandemic and moves toward normality, the potential impact of career adaptability, hope, resilience, and life satisfaction on future job pursuit and career magnetism towards particular industry or organizations should be considered.


Reward value of prosodic features of language for autistic, mentally retarded, and normal children.
The present study pursued hypotheses relevant to prosodic abnormalities in the expressive language of autistic children. An operant paradigm was employed to measure the intrinsic reinforcing value of a verbally presented story for autistic, mentally retarded, and normal groups controlling for chronological age and performance mental age. Results suggested that both autistic and mentally retarded children could perceive prosodic cues, although only mentally retarded children are able to use them in their expressive language. It was also suggested that linguistic stimuli may have less intrinsic reinforcement value for autistic and mentally retarded children than for normal children. Implications for future research and treatment were discussed.


High protein diet improves the overall survival in older adults with advanced gastrointestinal cancer.
High protein diet (HDP) promotes improvement of lean body mass in elderly without cancer; but the impact of high protein intake on muscle strength and mortality in cancer patients remains to be elucidated. This study evaluates the association between HPD on handgrip strength (HGS) and survival in older adults outpatients with advanced gastrointestinal cancer. Ninety-one patients with advanced gastrointestinal cancer (>65% tumor stage III-IV) undergoing radiotherapy, chemotherapy or surgery were enrolled. Upon first oncological visit, tumor stage was assessed by a physician. Then, a nutritionist or a dietitian measured the body mass index (BMI), HGS by means of a dynamometer, and dietary food intake by using 24h food recall. Patients were stratified in HPD (i.e, ≥1.5 g/kg/d) or low protein diet (LPD: <1.5 g/kg/d). Kaplan-Meier curve was used to assess the survival since the cancer diagnosis. HPD was reported by approximately 30% of patients. Protein intake was significantly higher in HPD vs LPD patients (2.2 ± 0.8 vs. 0.8 ± 0.4 g/kg/d, respectively; p < 0.0001). No significant association was found between HPD and HGS, even after adjustment for physical activity, alcohol intake, smoking, sex, age, tumor stage, oncologic treatment and BMI (OR: 0.97 [95%CI: 0.88-1.08], p = 0.64), or for energy intake kcal/kg/day, leucine g/d and lipids g/d (OR: 0.93 [95%CI: 0.85-1.03, p = 0.19]. In addition, HPD group showed higher overall survival than LPD group (HPD: 14.7 vs. LPD: 7.3 months, p = 0.04). HPD is not associated with better muscle function as measured by HGS, but with overall survival in older adults outpatients with advanced gastrointestinal cancer. HPD may represent a strategy to mitigate the cancer-induced mortality and should be further explored.


Cirrhosis: A Questioned Risk Factor for Hepatocellular Carcinoma.
The liver is one of the major metabolic organs in the body, susceptible to injury caused by various factors. In response to injury, sophisticated mechanisms are engaged to repair and regenerate the damaged liver, preventing its failure. When the damage is chronic, regeneration goes awry, impairing liver function and causing cirrhosis. Hence, cirrhosis may rather be a protective response to injury, where wound-healing processes are set to primarily repair the damaged liver. Although cirrhosis is clinically considered a risk factor for hepatocellular carcinoma (HCC), comprehensive population-based studies demonstrate a very modest incidence, refuting the idea that cirrhosis progresses to HCC. Here, we discuss and shed light on the provocative question of whether cirrhosis predisposes to HCC.


Sensitivity of core-level spectroscopy to electrostatic environments of nitrile groups: An ab initio study.
Ab initio quantum chemistry calculations have been performed to probe the influence of hydrogen bonding on the electronic structure of hydrogen cyanide (HCN). Our calculations determine the origin of nitrogen-specific Raman spectral features from resonant inelastic X-ray scattering occurring in the presence of a water molecule and an electric dipole field. The similarity of the two interactions in altering the electronic structure of the nitrogen atom differs only in the covalent contributions from the water molecule. The CN stretching mode as a structural probe was also investigated to study the electronic origin of the anomalous frequency shift of the nitrile group when subjected to hydrogen bonding and an electrostatic dipole field. The major changes in the electronic structure of HCN are electrostatic in nature and originate from dipole-dipole interactions. The relative shifts of the CN stretching frequency are in good agreement with those experimentally observed.


Levels, profiles and source identification of PCDD/Fs in farmland soils of Guiyu, China.
The present study finished the first comprehensive survey of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) in farmland soils of Guiyu, China. Guiyu was a major electronic wastes (EWs) dismantling area, but primitive and crude EWs disposal manner had led to severe PCDD/Fs pollution there. Twenty-three farmland soil samples covering the entire Guiyu region were analyzed. Toxic equivalent quantities (I-TEQs) of soils in EWs disposal areas were 5.7-57pg TEQ g(-1), and the total concentrations of tetra- to octa-homologues were 2816-17738pgg(-1). The SL district was a heavily contaminated area, and the neighboring SMP town was influenced by Guiyu. EWs disposal might be the source of PCDD/Fs. The homologue profiles were of three types, representing different disposal manner of EWs. Tetrachlorodibenzo-p-dioxins (TCDDs) and octachlorodibenzo-p-dioxin (OCDD) could be used as indicators for source identification, open thermal disposal of EWs was inclined to lead to formation of TCDDs, OCDD was a product of non-thermal processes.


The mechanism of glucose 6-phosphate transport by Escherichia coli.
To evaluate anion exchange as the mechanistic basis of sugar phosphate transport, natural and artificial membranes were used in studies of glucose 6-phosphate (Glc-6-P) and inorganic phosphate (Pi) accumulation by the uhpT-encoded protein (UhpT) of Escherichia coli. Experiments with intact cells demonstrated that UhpT catalyzed the neutral exchange of internal and external Pi, and work with everted as well as right-side-out membrane vesicles showed further that UhpT mediated the heterologous exchange of Pi and Glc-6-P. When loaded with Pi, but not when loaded with morpholinopropanesulfonate (MOPS), everted vesicles took up Glc-6-P to levels 100-fold above medium concentration in a reaction unaffected by the ionophores valinomycin, valinomycin plus nigericin, and carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Similarly, right-side-out vesicles were capable of Glc-6-P transport, but only if a suitable internal countersubstrate was available. Thus, in MOPS-loaded vesicles, oxidative metabolism established a proton-motive force that supported proline or Pi accumulation, but transport of Glc-6-P was found only if vesicles could accumulate Pi during a preincubation. After reconstitution of UhpT into proteoliposomes it was possible to show as well that the level of accumulation of Glc-6-P (17 to 560 nmol/mg of protein) was related directly to the internal concentration of Pi. These results are most easily understood if the transport of glucose 6-phosphate in E. coli occurs by anion exchange rather than by nH+/anion support.


Revisiting the dystrophin-ATP connection: How half a century of research still implicates mitochondrial dysfunction in Duchenne Muscular Dystrophy aetiology.
Duchenne Muscular Dystrophy (DMD) is a fatal neuromuscular disease that is characterised by dystrophin-deficiency and chronic Ca(2+)-induced skeletal muscle wasting, which currently has no cure. DMD was once considered predominantly as a metabolic disease due to the myriad of metabolic insufficiencies evident in the musculature, however this aspect of the disease has been extensively ignored since the discovery of dystrophin. The collective historical and contemporary literature documenting these metabolic nuances has culminated in a series of studies that importantly demonstrate that metabolic dysfunction exists independent of dystrophin expression and a mild disease phenotype can be expressed even in the complete absence of dystrophin expression. Targeting and supporting metabolic pathways with anaplerotic and other energy-enhancing supplements has also shown therapeutic value. We explore the hypothesis that DMD is characterised by a systemic mitochondrial impairment that is central to disease aetiology rather than a secondary pathophysiological consequence of dystrophin-deficiency.


Generic sofosbuvir-based interferon-free direct acting antiviral agents for patients with chronic hepatitis C virus infection: a real-world multicenter observational study.
Real-world data regarding the effectiveness and safety of generic sofosbuvir (SOF)-based interferon-free direct acting antiviral agents (DAAs) for patients with chronic hepatitis C virus (HCV) infection remain limited. A total of 517 chronic HCV-infected patients receiving 12 or 24 weeks of SOF-based therapies were retrospectively enrolled in 4 academic centers in Taiwan. The rate of sustained virologic response at week 12 off-therapy (SVR12) and that of treatment completion were assessed. The baseline characteristics and on-treatment HCV viral kinetics to predict SVR12 were analyzed. By evaluable population (EP) analysis, the SVR12 rate was 95.4% (95% confidence interval [CI]: 93.2-96.9%). The SVR12 was achieved in 29 of 34 patients (85.3%, 95% CI: 69.6-93.6%), 130 of 139 patients (93.5%, 95% CI: 88.2-96.6%), 119 of 124 patients (96.0%, 95% CI: 90.9-98.3%) and 215 of 220 patients (97.7%, 95% CI: 94.8-99.0%) who received SOF in combination with ribavirin (RBV), ledipasvir (LDV), daclatasvir (DCV) and velpatasvir (VEL), respectively. Of 517 patients, 514 (99.4%) completed the scheduled treatment. All 15 patients with true virologic failures were relapsers. Two decompensated cirrhotic patients had on-treatment deaths which were not related to DAAs. All 7 patients who were lost to follow-up had undetectable HCV RNA level at the last visit. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment. In conclusion, generic SOF-based regimens are well tolerated and provide high SVR12 rates in patients with chronic HCV infection.


Regulation of water flow by actin-binding protein-induced actin gelatin.
Actin filaments inhibit osmotically driven water flow (Ito, T., K.S. Zaner, and T.P. Stossel. 1987. Biophys. J. 51: 745-753). Here we show that the actin gelation protein, actin-binding protein (ABP), impedes both osmotic shrinkage and swelling of an actin filament solution and reduces markedly the concentration of actin filaments required for this inhibition. These effects depend on actin filament immobilization, because the ABP concentration that causes initial impairment of water flow by actin filaments corresponds to the gel point measured viscometrically and because gelsolin, which noncovalently severs actin filaments, solates actin gels and restores water flow in a solution of actin cross-linked by ABP. Since ABP gels actin filaments in the periphery of many eukaryotic cells, such actin networks may contribute to physiological cell volume regulation.


Effect of ultrasound on structure and functional properties of antithrombin III and proteins of PPSB complex.
A combination of gel-permeation HPLC, affinity chromatography on heparin-Sepharose, gel electrophoresis, and estimation of inhibitory activity showed that effect of low-frequency ultrasound (26 W/cm(2), 37 degrees C, pH 7.4) on homogeneous antithrombin III was accompanied by formation of aggregates and a latent form of serpin. Heparin and pentosan polysulfate stabilized antithrombin III; this resulted in decrease in ultrasonic-induced formation of the aggregate and latent forms. The influence of ultrasound was not accompanied by significant changes in the contents of non-activated blood coagulation factors in the PPSB complex.


[Hybrid room technology as a prerequisite for the modern therapy of aortic dissection].
With the establishment of a hybrid room 7 years ago, it was possible for the first time to unite a full range of diagnostics and surgical therapy under the sterile conditions of an operating theatre in life-threatening aortic dissection. Thus, the early phase associated with high mortality rates (3%-5% per hour) could be significantly reduced from 8 h to 4 h. Multidisciplinary teams consisting of a cardiac surgeon, a cardiologist and an anaesthetist enable competent and rapid life-saving measures. In the case of acute and persistent visceral and/or peripheral malperfusion over many hours, primary endovascular reconstitution of perfusion precedes delayed surgical replacement of the ascending aorta with or without the aortic arch. Additional strategic and technical surgical developments have helped reduce overall hospital mortality from 15%-20% to 10%-15%. Though expensive to build, a high-technology hybrid room enables interdisciplinary specialization and concentration, as demonstrated by the exponential growth in the development of transcatheter aortic valve implants or the endovascular treatment of aortic disease.


Genefu: an R/Bioconductor package for computation of gene expression-based signatures in breast cancer.
Breast cancer is one of the most frequent cancers among women. Extensive studies into the molecular heterogeneity of breast cancer have produced a plethora of molecular subtype classification and prognosis prediction algorithms, as well as numerous gene expression signatures. However, reimplementation of these algorithms is a tedious but important task to enable comparison of existing signatures and classification models between each other and with new models. Here, we present the genefu R/Bioconductor package, a multi-tiered compendium of bioinformatics algorithms and gene signatures for molecular subtyping and prognostication in breast cancer. The genefu package is available from Bioconductor. http://www.bioconductor.org/packages/devel/bioc/html/genefu.html Source code is also available on Github https://github.com/bhklab/genefu firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Separation of the myogenic and chondrogenic progenitor cells of undifferentiated limb mesenchyme.
Undifferentiated limb bud mesenchyme consists of at least two separate, possibly predetermined, populations of progenitor cells, one derived from somitic mesoderm that gives rise exclusively to skeletal muscle and one derived from somatopleural mesoderm that gives rise to the cartilage and connective tissue of the limb. In the present study, we demonstrate that the inherent migratory capacity of myogenic precursor cells can be used to physically separate the myogenic and chondrogenic progenitor cells of the undifferentiated limb mesenchyme at the earliest stages of limb development. When the undifferentiated mesenchyme of stage 18/19 chick embryo wing buds or from the distal subridge region of stage 22 wing buds is placed intact upon the surface of fibronectin (FN)-coated petri dishes, a large population of cells emigrates out of the explants onto the FN substrates and differentiates into an extensive interlacing network of bipolar spindle-shaped myoblasts and multinucleated myotubes that stain with monoclonal antibody against muscle-specific fast myosin light chain. In contrast, the cells of the explants that remain in place and do not migrate away undergo extensive cartilage differentiation. Significantly, there is no emigration of myogenic cells out of explants of stage 25 distal subridge mesenchyme, which lacks myogenic progenitor cells. Myogenic precursor cells stream out of mesenchyme explants in one or occasionally two discrete locations, suggesting they are spatially segregated in discrete regions of tissue at the time of its explantation. There are subtle overall differences in the morphologies of the myogenic cells that form in stage 18/19 and stage 22 distal subridge mesenchyme explants. Finally, groups of nonmyogenic nonfibroblastic cells which are fusiform-shaped and oriented in distinct parallel arrays characteristically are found along the periphery of stage 18/19 wing mesenchyme explants. Our observations provide support for the concept that undifferentiated limb mesenchyme consists of independent subpopulations of committed precursor cells and provides a system for studying the early determinative and regulatory events involved in myogenesis or chondrogenesis.


Activated charcoal-a potential material in glucoamylase recovery.
The potential of activated charcoal in the purification of fungal glucoamylase was investigated. Various concentrations of activated charcoal (1-4% w/v) were used to concentrate crude glucoamylase from Rhizopus oligosporus at different temperature values (30-50°C). Effects of pH (3.0-6.0) and contact time (0-60 min) on enzyme purification were also monitored. Activated charcoal (3% w/v) gave a 16-fold purification in a single-step purification at 50°C for 20 min and pH 5.5. The result of SDS-PAGE analysis of purified glucoamylase showed two major protein bands with corresponding molecular weight of 36 kDa and 50 kDa. The method is inexpensive, rapid, and simple which could facilitate downstream processing of industrial enzyme.


Impact of Juice Extraction Method (Flash Détente vs. Conventional Must Heating) and Chemical Treatments on Color Stability of Rubired Juice Concentrates under Accelerated Aging Conditions.
Low color stability of Rubired food and beverage coloring negatively impacts color yield during production and storage while also limiting the use of this type of food colorant in applications where color stability is a key requirement. This study investigated the impact on color stability of using flash détente (FD) for Rubired color extraction in comparison to a conventional must heating (CMH) extraction process, in conjunction with the use of commercial seed tannin, acetaldehyde, or acid to lower the pH. Rubired concentrate color was evaluated under accelerated aging conditions at 50, 60, and 70 °C, over zero, three, six, and nine days for the different treatments. FD concentrate had lower color stability, with a half-life of 203.3 h and activation energy of 59.2 kJ/mol at 50 °C compared to the CMH concentrate with 233.9 h and 65.2 kJ/mol. FD concentrate generated less 5-hydroxymethylfurfural (5-HMF) during accelerated aging regardless of treatment. Acetaldehyde, low pH, and the combination of these two treatments increased red color stability as well as violet and brown color, whereas seed tannin had no effect. Low pH treatments increased 5-HMF formation and browning, which was detrimental to concentrate quality. Although promising in terms of color stabilization, implementation of these treatments will require development of solutions to mitigate the production of 5-HMF.


Subjective morbidity and quality of life after sentinel node biopsy and axillary lymph node dissection for breast cancer.
Sentinel node (SN) biopsy is a minimally invasive surgical method for axillary staging in patients with breast cancer. The aim of this study was to evaluate mid-term morbidity after SN biopsy and axillary lymph node (ALN) dissection in patients with breast cancer receiving breast-sparing treatment, and to determine its impact on quality of life (QOL). One hundred fifteen patients with breast cancer underwent breast-conserving treatment with SN biopsy alone (Group 1: n = 54), ALN dissection with or without SN biopsy (Group 2: n = 51), or SN biopsy followed by later ALN dissection (Group 3: n = 10). The mean post-operative follow-up was 20.3 months (range: 10-31 months) in Group 1, 24.3 months (range: 10-33 months) in Group 2, and 19.1 months (range: 12-28 months) in Group 3. Arm-shoulder pain was reported by 21.2% of patients in Group 1, 52.9% in Group 2, and 60% in Group 3 (P = 0.002). An arm swelling sensation was reported by 0% of patients in Group 1, 21.6% in Group 2, and 10% in Group 3. Dysesthesias were reported by 5.7% of patients in Group 1, 51% in Group 2, and 50% in Group 3 (P < 0.001). The mean global QOL self-rating score was 7.6 in Group 1, 7.6 in Group 2, and 7.7 in Group 3 (no significant difference). SN biopsy is associated with significantly lower mid-term morbidity than ALN dissection.


Effect of exercise training in supervised cardiac rehabilitation programs on prognostic variables from the exercise tolerance test.
Meta-analyses showed that exercise training decreased mortality in patients after myocardial infarction, but no single adequately powered trial has shown this benefit. The purpose of this study was to evaluate the effect of cardiac rehabilitative exercise training on prognostic variables derived from the exercise tolerance test and whether these changes had an effect on predicted cardiovascular and all-cause mortality using externally validated risk scores. Two hundred ten consecutive patients who completed a 12-week cardiac rehabilitation program were analyzed. Peak MET level, heart rate recovery, chronotropic index, Duke prognostic score, and Cleveland Clinic Foundation risk score obtained at program entry and exit were compared. All prognostic variables and risk score-derived predicted 5-year mortality rates improved significantly after cardiac rehabilitation. Exercise capacity increased by 32% (6.6 +/- 2.7 to 8.7 +/- 2.9 METS; p <0.0001), heart rate recovery increased by 20% (15 +/- 9 to 18 +/- 10 beats/min; p <0.0001), and chronotropic index increased by 11% (56 +/- 22% to 62 +/- 22%; p <0.0001). Duke prognostic score 5-year predicted cardiovascular mortality rate decreased by 33% (6 +/- 4% to 4 +/- 2%; p <0.0001), and Cleveland Clinic Foundation risk score 5-year predicted total mortality rate decreased by 40% (5 +/- 7% to 3 +/- 5%; p <0.0001). These improvements remained significant in high-risk subgroups. When controlled for age, gender, diabetes, MET level achieved, ejection fraction, and beta-blocker use, changes remained significant (p <0.0001) for each outcome measure. In conclusion, exercise training in supervised cardiac rehabilitation programs significantly improved exercise capacity, measures of chronotropic dynamics, and prognostic risk scores. These differences translate into a decrease in predicted mortality.


Electroacupuncture ameliorates pain in cervical spondylotic radiculopathy rat by inhibiting the CaMKII/CREB/BDNF signaling pathway and regulating spinal synaptic plasticity.
Central sensitization is one of the important mechanisms underlying neuropathic and radicular pain due to cervical spondylotic radiculopathy (CSR). Recent studies have shown that the calmodulin-dependent protein kinase II (CaMKII)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway mediates central sensitization through its involvement in spinal cord synaptic plasticity. Our group has previously found that electroacupuncture (EA) has a good analgesic effect on CSR. However, the central analgesic mechanism of EA for CSR is not yet clear. The rats were randomly divided into Blank group, Sham-operated group, CSR group, and EA group. We prepared the CSR rat model using the fish wire extrusion method. The behavioral and mechanical pain thresholds of the rats in each group were measured 5 days after successful modeling and 7 days after the intervention. The first intervention was started 5 days after successful modeling, and the EA group was treated by acupuncture at the bilateral LI4 and LR3 points on the same side as one group, connected to a G6805-I electroacupuncture apparatus with continuous waves at 1.5 Hz. The remaining groups were not subjected to EA intervention. The treatment was administered once a day for 7 consecutive days and then executed. We used WB, immunofluorescence, and qRT-PCR to detect the expression of CaMKII/CREB/BDNF signaling pathway-related factors in the synaptic of rat spinal cord in each group. EA improved pain threshold and motor function in CSR rats, inhibited the expression of BDNF, P-TrkB, CAMKII, and P-CREB in spinal cord synapses, reduced the expression of pain factor c-fos and postsynaptic membrane protein molecule neuroligin2, exerted a modulating effect on spinal cord synaptic plasticity in CSR rats, and suppressed the overactive synaptic efficacy. EA mediates central sensitization and exerts analgesic effects on CSR by modulating spinal synaptic plasticity, which may be related to the inhibition of CaMKII/CREB/BDNF signaling pathway.


Disparities in the experience and treatment of dental caries among children aged 9-18 years: the cross-sectional study of Korean National Health and Nutrition Examination Survey (2012-2013).
The aim of this study is to examine the association between parental socioeconomic status (SES) and the experience as well as treatment of dental caries among children aged 9 to 18 years. Data from 1253 children aged 9-18 years from the Korean National Health and Nutrition Examination Survey (2012-2013) were analyzed. Parental socioeconomic status was measured using household income level and maternal educational level. The decayed, missing, and filled teeth (DMFT) index was used to measure experience of dental caries (DMFT ≥ 1). Non-treatment of dental caries was measured according to whether the participants who experienced dental caries used a dental service at a dental clinic to treat caries during the previous year. Logistic regression was used to investigate the association between parental socioeconomic status and the experience of dental caries as well as the association between parental socioeconomic status and the non-treatment of dental caries among children that have experienced caries. A total of 808 subjects (64.5 %) experienced dental caries among 1253 participants, and 582 of these 808 subjects (72.0 %) did not receive treatment among those having experience of dental caries. Parental socioeconomic status was not associated with experience of dental caries. However, those from low- and middle-income households were less likely to receive treatment than those from high-income households (odds ratio [OR] 2.11 [95 % confidence interval (CI) 1.16-3.86], OR 2.14 [95 % CI 1.27-3.62]). In particular, those from low- and middle-income households who had regular dental checkups were more likely to have untreated caries than those from high-income households (OR 3.58 [95 % CI 1.25-10.24]). This study demonstrates the parental household income-related disparities in children's dental health treatment. Efforts should be made to lower financial barriers to dental health services, particularly among those from low-income households, in order to reduce dental health disparities in the treatment of caries in children.


Detection and sequencing of Zika virus in normocephalic newborns with congenital Zika infection.
Fourteen asymptomatic normocephalic newborns with confirmed congenital Zika infection were investigated. All newborns presented Zika virus (ZIKV) positivity on reverse transcriptase polymerase chain reaction. Following ZIKV-specific NS5 gene fragment sequencing in one child, phylogenetic analysis revealed that this isolate belonged to the Asian genotype, and clustered closely with other sequences previously isolated in north-east and northern regions of Brazil.


Natural History Studies and Clinical Trial Readiness for Genetic Developmental and Epileptic Encephalopathies.
The developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies. They usually begin in infancy or childhood with drug-resistant seizures, epileptiform EEG patterns, developmental slowing or regression, and cognitive impairment. DEEs have a high mortality and profound morbidity; comorbidities are common including autism spectrum disorders. With advances in genetic sequencing, over 400 genes have been implicated in DEEs, with a genetic cause now identified in over 50% patients. Each genetic DEE typically has a broad genotypic-phenotypic spectrum, based on the underlying pathophysiology. There is a pressing need to improve health outcomes by developing novel targeted therapies for specific genetic DEE phenotypes that not only improve seizure control, but also developmental outcomes and comorbidities. Clinical trial readiness relies firstly on a deep understanding of phenotype-genotype correlation and evolution of a condition over time, in order to select appropriate patients for clinical trials. Understanding the natural history of the disorder informs assessment of treatment efficacy in terms of both clinical outcome and biomarker utility. Natural history studies (NHS) provide a high quality, integrated, comprehensive approach to understanding a complex disease and underpin clinical trial design for novel therapies. NHS are pre-planned observational studies designed to track the course of a disease and identify demographic, genetic, environmental, and other variables, including biomarkers, that correlate with the disease's evolution and outcomes. Due to the rarity of individual genetic DEEs, appropriately funded high-quality DEE NHS will be required, with sustainable frameworks and equitable access to affected individuals globally.


Electroretinography in the evaluation of childhood myotonic dystrophy.
Electroretinography (ERG) may provide laboratory support for the diagnosis of childhood myotonic dystrophy. The sensitivity of ERG may exceed that of electromyography for early detection of the disease. The electroretinographic abnormalities are not specific for myotonic dystrophy.


Nerve conduits for treating peripheral nerve injuries: A systematic literature review.
Peripheral nerve injuries are a major public health problem. Nerve conduits have been developed in the recent years, although it is still not clear if they should replace nerve grafting and neurorrhaphy. This systematic review aims to gather evidence regarding the use of nerve conduits for peripheral nerve repair. The following electronic databases were searched: MEDLINE, Cochrane Library (CENTRAL) and Embase. Study selection and data extraction followed the PRISMA guidelines. The systematic review of the literature retrieved 6767 articles. Only 27 studies were retained accounting for 1022 patients: 10 randomized controlled trials, 15 case series and 2 cohort studies. Ten different types of tubes were described and a variety of evaluation methods were used to assess outcomes in terms of efficacy (motor and sensory recovery) and complications. The Semmes-Weinstein monofilament test and the static and moving 2-point discrimination test were the most commonly applied tests to evaluate nerve recovery. In general, outcomes showed no significant difference between groups. Synthetic conduits had more complications. Despite major methodological limitations in the studies, we can conclude that use of nerve conduits is preferable over suture repair and nerve grafting, as the functional recovery rates are above 80%. The choice of conduit is based on the surgeon's expertise, but use of synthetic conduits is discouraged due to their higher complication rates.


Pirfenidone prevents capsular contracture after mammary implantation.
Pirfenidone (PFD), a new antifibrotic and antiinflammatory agent, prevents and resolves fibrous tissue. This study evaluated the effect of PFD on adverse events in mammary implants using an animal model. Mammary implantation, the most frequent aesthetic surgery, may present several complications after surgery such as swelling, capsule contracture, hardness, and pain. Wistar rats underwent submammary implantation with either smooth or textured silicone gel implants and were administrated 200 mg/kg of PFD daily. The control group received saline. The animals were killed at 8 weeks. The capsular tissue of both implants was removed for histologic and molecular analyses. Typical postaugmentation periimplant capsules with opacity on adjacent tissues developed 8 weeks after silicone implantation. No significant differences were observed between the textured and smooth implants in any analyzed parameter. Clearly, PFD reduced capsule thickness around submmamary tissue, fibroblast-like cell proliferation, and recruitment of inflammatory cells. The total cell numbers per field were reduced as well. In contrast, the control group presented abundant mononuclear cell infiltration and fibroblast-like cell proliferation. The total content of collagen in the PFD group was 50% less than in the control group. Fibroblast cells displayed 45% less activated phenotype in the PFD group than in the control group, as determined by immunohistochemistry techniques. In the PFD animals, transforming growth factor-beta (TGF-beta) decreased 85% and collagen 1 gene expression 60%, compared with the control group. The findings show a positive effect of PFD on mammary contracture in 10 rats. Despite the small number of animals, the differences found in 10 control rats encourage the authors to propose a larger study later and to suggest PFD as a potential preventive strategy in human mammary implantation surgery.


Analysis of a four-year experience with depth electrodes and a two-year experience with subdural electrodes in the evaluation of ablative seizure surgery candidates.
Chronically implanted depth and subdural electrodes have both been shown to be satisfactory means of localizing epileptogenic foci. Utilizing bilateral mesial temporal depth electrodes, we have localized mesial temporal foci in a large percentage of patients. Depth electrode investigation of a more limited number of patients with suspected extramesial temporal foci has not been as reliable in giving localizing information. We have more recently used subdural electrodes to investigate this latter category of patients, and preliminary findings suggest that this technique may be of localizing value in several subcategories.


Single-Layer MoS2 Mechanical Resonant Piezo-Sensors with High Mass Sensitivity.
Thin-film resonators and scanning probe microscopies (SPM) are usually used on low-frequency mechanical systems at the nanoscale or larger. Generally, off-chip approaches are applied to detect mechanical vibrations in these systems, but these methods are not much appropriate for atomic-thin-layer devices with ultrahigh characteristic frequencies and ultrathin thickness. Primarily, those mechanical devices based on atomic-layers provide highly improved properties, which are inapproachable with conventional nanoelectromechanical systems (NEMS). In this report, the assembly and manipulation of single-atomic-layer piezo-resonators as mass sensors with eigen mechanical resonances up to gigahertz are described. The resonators utilize electronic vibration transducers based on piezo-electric polarization charges, allowing direct and optimal atomic-layer sensor exports. This direct detection affords practical applications with the previously inapproachable Q-factor and sensitivity rather than photoelectric conversion. Exploration of a 2406.26 MHz membrane vibration is indicated with a thermo-noise-limited mass resolution of ∼3.0 zg (10-21 g) in room temperature. The fabricated mass sensors are contactless and fast and can afford a method for precision measurements of the ultrasmall mass with two-dimentional materials.


Conditionally essential genes for survival during starvation in Enterococcus faecium E745.
The nosocomial pathogen Enterococcus faecium can survive for prolonged periods of time on surfaces in the absence of nutrients. This trait is thought to contribute to the ability of E. faecium to spread among patients in hospitals. There is currently a lack of data on the mechanisms that are responsible for the ability of E. faecium to survive in the absence of nutrients. We performed a high-throughput transposon mutant library screening (Tn-seq) to identify genes that have a role in long-term survival during incubation in phosphate-buffered saline (PBS) at 20 °C. A total of 24 genes were identified by Tn-seq to contribute to survival in PBS, with functions associated with the general stress response, DNA repair, metabolism, and membrane homeostasis. The gene which was quantitatively most important for survival in PBS was usp (locus tag: EfmE745_02439), which is predicted to encode a 17.4 kDa universal stress protein. After generating a targeted deletion mutant in usp, we were able to confirm that usp significantly contributes to survival in PBS and this defect was restored by in trans complementation. The usp gene is present in 99% of a set of 1644 E. faecium genomes that collectively span the diversity of the species. We postulate that usp is a key determinant for the remarkable environmental robustness of E. faecium. Further mechanistic studies into usp and other genes identified in this study may shed further light on the mechanisms by which E. faecium can survive in the absence of nutrients for prolonged periods of time.


Determination of trace elements in serum by dynamic reaction cell inductively coupled plasma mass spectrometry: developing of a method with a desolvating system nebulizer.
An inductively coupled plasma mass spectrometer (ICP-MS), equipped with a dynamic reaction cell (DRC) and coupled with a desolvating nebulizing system (Apex-ACM) to reduce the oxide formation, was used in the determination of Al, Co, Cr, Mn, Ni and Se in serum samples. The effect of the operating conditions of the DRC system was studied to get the best signal-to-background (S/B) ratio. The potentially interfering molecular ions at the masses m/z27Al, 59Co, 52Cr, 55Mn, 60Ni and 78Se, were significantly reduced in intensity by using NH3 and H2, as the reaction cell gases in the DRC, while a proper Dynamic Bandpass Tuning parameter q (RPq) value was optimized. The detection limits for 27Al, 59Co, 52Cr, 55Mn, 60Ni and 78Se, estimated with 3-sigma method, resulted to be 0.14, 0.003, 0.002, 0.01, 0.01 and 1.8 microg L(-1), respectively. This analytical method was developed on both a human serum certified reference material and a lyophilized animal serum produced and proposed in an intercomparison study. The results obtained for the reference samples agreed satisfactorily with the certified values. Precision (expressed as CV%) between sample replicates was better than 10% for elements determination, with the only exception of aluminium (14%).


Chlamydia psittaci-negative ocular adnexal marginal zone B-cell lymphomas have biased VH4-34 immunoglobulin gene expression and proliferate in a distinct inflammatory environment.
Ocular adnexal marginal zone B-cell lymphomas (OAMZLs) arise in the connective tissues of the orbit or in the mucosa-associated lymphoid tissue of the conjunctiva. Here, we present the immunological and genetic analyses of 20 primary Chlamydia psittaci (Cp)-negative OAMZLs. Analysis of the immunoglobulin variable heavy chain (IgV(H)) gene usage demonstrated a significant preference for V(H)4-34. A combined analysis across all previously published OAMZLs confirmed that this is a general feature of OAMZL, in particular of the Cp-negative group. Our series of OAMZLs did not express the characteristic rheumatoid factor V(H)DJ(H) rearrangements that were previously found in salivary gland- and gastric-marginal zone B-cell lymphomas (MZBCLs). We did not detect the MZBCL-specific chromosomal translocations, t(11;18) API2-MALT1 (mucosa-associated lymphoid tissue1) and t(14;18) IgH/MALT1. Two cases contained a premature stop codon in the A20 gene (TNFAIP3) and one case harbored the activating MYD88 hotspot mutation L265P. Variable nuclear expression of BCL10, NFκB1 (p50) and NFκB2 (p52) suggests that other additional genetic abnormalities affecting the NFκB pathway exist within this group of lymphomas. OAMZL showed variable expression of the chemokine receptor CXCR3 and integrin α4β7 by the tumor B cells, and low interferon-γ and interlukin-4 mRNA levels in the tissue, indicative of an inflammatory environment with features in between those previously found in cutaneous and other extranodal MZBCL. The strongly biased usage of V(H)4-34 in Cp-negative OAMZLs suggests involvement of a particular stimulatory (auto-) antigen in their development.


Risk factors and strategies for prevention of depression, anxiety and eating disorders among adolescents during the coronavirus disease 2019 (COVID-19) pandemic: a review.
The purpose of this review is to identify prevalent trends and risk factors in depression, anxiety, and eating disorders in the adolescent population in the post coronavirus disease 2019 (COVID-19) scenario. We examined the literature published on adolescent mental health since the COVID-19 pandemic. We chose to summarize studies published from 2019 to 2022, using bibliographic search tools. We developed criteria for selecting articles for our review using diagnostic indicators and keywords. Mental health conditions such as depression, anxiety and eating disorders are commonly prevalent in this population and have shown increasing rates in the past three years. Some risk factors associated with these diagnoses include reduction in social interaction, increased workloads, routine shifts, sleep quality, social media usage and parental involvement. Routines, sleep cycles, physical activity, and social media should all be considered as a part of prevention in this population. Approaches that seem to be successful include maintaining social ties and avoiding negative social media usage with harmful content. Increased global public awareness, as well as parental awareness, through media campaigns, is critical to slowing the spread of mental health challenges in adolescents and teenagers in the post-COVID-19 era.


Radiofrequency Ablation for Prevention of Outflow Tract Obstruction in Percutaneous Mitral Valve-in-Valve Replacement.
Left ventricular outflow tract obstruction (LVOTO) can complicate percutaneous mitral valve replacement and may preclude patients considered high surgical risk from transcatheter therapies. We report a case of mitral valve-in-valve procedure in a patient at high risk for LVOTO. (Level of Difficulty: Advanced.).


One hundred consecutive pneumonectomies after induction therapy for non-small cell lung cancer: an uncertain balance between risks and benefits.
We sought to assess postoperative outcome after pneumonectomy after neoadjuvant therapy in patients with non-small cell lung cancer. This retrospective study included 100 patients treated from January 1989 through December 2003 for a primary lung cancer in whom pneumonectomy had been performed after an induction treatment. Surgical intervention had not been considered initially for the following reasons: N2 disease (stage IIIA, n = 79), doubtful resectability (stage IIIB [T4, N0], n = 19), and M1 disease (stage IV [T2, N0, M1, solitary brain metastasis], n = 2). All patients received a 2-drug platinum-based regimen with a median of 2.5 cycles (range, 2-4 cycles), and 30 had associated radiotherapy (30-45 Gy). There were 55 right and 45 left resections. Overall 30-day and 90-day mortality rates were 12% and 21%, respectively. At multivariate analysis, one independent prognostic factor entered the model to predict 30-day mortality: postoperative cardiovascular event (relative risk, 45.7; 95% confidence interval, 3.7-226.7; P = .001). Four variables predicted 90-day mortality: age of more than 60 years (relative risk, 5.06; 95% confidence interval, 1.47-17.48; P = .01), male sex (relative risk, 8.25; 95% confidence interval, 1.01-67.34; P = .049), postoperative respiratory event (relative risk, 3.64; 95% confidence interval, 1.14-9.37; P = .007), and postoperative cardiovascular event (relative risk, 7.84; 95% confidence interval, 3.12-19.71; P < .001). Estimated overall survivals in 90-day survivors were 35% (range, 29%-41%) and 25% (range, 19.3%-30.7%) at 3 and 5 years, respectively. At multivariate analysis, one independent prognostic factor entered the model: pathologic stage III-IV residual disease (relative risk, 1.89; 95% confidence interval, 1.09-3.26; P = .022). Pneumonectomy after induction therapy is a high-risk procedure, the survival benefit of which appears uncertain.


[Identification of Volatile Chemical Constituents from Hui Formula "Ha Hei Lili" by GC-MS].
The volatile components of the Hui formula "Ha Hei Lili" were extracted by steam distillation extraction (SD) and supercritical CO2 fluid extraction, and the structures were analyzed and identified by GC-MS. The GC-MS conditions were set as follows: Rxi-5Sil MS quartz capillary column (30 m x 0.25 mm, 0.25 μm), the initial temperature of 50 degrees C to keep 1 min, to 10 degrees C/min heating to 120 degrees C, maintained 3 min, then to 3 degrees C/min heating to 200 degrees C, maintained 3 min, and then to 5 degreesC/min heating to 290 degrees C, maintained until completion of analysis; helium as the carrier gas, column flow rate 1.0 ml/min, split ratio 25: 1, inlet temperature 250 degrees C, EI ionization source 70 eV, ion source temperature 230 degrees C, scan range of m/z 35 - 500. Yield of volatile oil were 0.21% and 5.44% extracted by SD and SFE methods, respectively; and for SD method, 36 kinds of compounds were identified, accounted for 87.02% of total mass of volatile oil; for SFE method, 38 kinds of constituents were identified, accounted for 97.47% of total mass of volatile oil. The type of constituents contained in the volatile oil extracted by SD and SFE methods are totally different; and GC-MS can be used to identify the structures and relative content of volatile components, the results of this study can provide an experimental basis for development and utilization of Hui formula "Ha Hei Lili".


Hypermetabolism in critically ill patients with COVID-19 and the effects of hypothermia: A case series.
We have observed that critically ill patients with COVID-19 are in an extreme hypermetabolic state. This may be a major contributing factor to the extraordinary ventilatory and oxygenation demands seen in these patients. We aimed to quantify the extent of the hypermetabolic state and report the clinical effect of the use of hypothermia to decrease the metabolic demand in these patients. Mild hypothermia was applied on four critically ill patients with COVID-19 for 48 h. Metabolic rates, carbon dioxide production and oxygen consumption were measured by indirect calorimetry. The average resting energy expenditure (REE) was 299% of predicted. Mild hypothermia decreased the REE on average of 27.0% with resultant declines in CO2 production (VCO2) and oxygen consumption (VO2) by 29.2% and 25.7%, respectively. This decrease in VCO2 and VO2 was clinically manifested as improvements in hypercapnia (average of 19.1% decrease in pCO2 levels) and oxygenation (average of 50.4% increase in pO2). Our case series demonstrates the extent of hypermetabolism in COVID-19 critical illness and suggests that mild hypothermia reduces the metabolic rate, improves hypercapnia and hypoxia in critically ill patients with COVID-19.


Detection of Colorectal Carcinoma Based on Microbiota Analysis Using Generalized Regression Neural Networks and Nonlinear Feature Selection.
To obtain a screening tool for colorectal cancer (CRC) based on gut microbiota, we seek here to identify an optimal classifier for CRC detection as well as a novel nonlinear feature selection method for determining the most discriminative microbial species. In this study, the intestinal microflora in feces of 141 patients were modeled using general regression neural networks (GRNNs) combined with the proposed feature selection method. The proposed model led to slightly higher accuracy (AUC = 0.911) than previous studies . The results show that the Clostridium scindens and Bifidobacterium angulatum are indicators of healthy gut flora and CRC happens to reduce these bacterial species. In addition, Fusobacterium gonidiaformans was found to be closely correlated with the CRC. The occurrence of colorectal adenoma was not sufficiently discriminatory based on fecal microbiota implicating that the change of colonic flora happens in the advanced phase of CRC development rather than initial adenoma. Integrating the proposed model with fecal occult blood test (FOBT), the CRC detection accuracy remained nearly unchanged (AUC = 0.915). The performance of the proposed method is validated using independent cohorts from America and Austria. Our results suggest that the proposed feature selection method combined with GRNN is potentially an accurate method for CRC detection.


Fetus in Fetu: A Rare Congenital Anomaly Diagnosed Postnatally by Ultrasonography and MRI.
Fetus in fetu (FIF) is a rare congenital anomaly with two controversial theories regarding its embryogenesis. Although it is an extremely rare condition, it should be kept in mind as a differential diagnosis while evaluating children with abdominal calcification. Radiological findings on postnatal days 2 and 5 of a neonate with an antenatal scan showing an abdominal mass in the fetus are described here. Ultrasonography and magnetic resonance imaging (MRI) revealed the mass in which the contents favored a diagnosis of the FIF. Characteristic features of FIF on MRI have been less explored and knowledge regarding the same will be of immense help to the radiologist. Complete surgical excision followed by histopathology confirmed the diagnosis.


Choline acetyltransferase-immunoreactive patches overlap specific efferent cell groups in the cat superior colliculus.
Fibers containing acetylcholine (ACh) form distinct patches in the dorsal intermediate gray layer (IGL) of the cat superior colliculus (SC). Although these patches are known to overlap several afferent projections to SC, it is not known whether they are associated with specific postsynaptic cell groups. We have examined the relationship of these ACh fiber patches to specific efferent cell groups by combining retrograde transport of horseradish peroxidase (HRP) with choline acetyltransferase (ChAT) immunocytochemistry. Successful HRP injections were made into the predorsal bundle (PB), the tecto-pontine-bulbar pathway (TPB) and the cuneiform region (CFR), the inferior olive (IO), the dorsolateral pontine gray nucleus (PGD), and the pedunculopontine tegmental nucleus (PPTN). The distribution of HRP-labeled neurons which project to these targets was mapped by a computer-based microscope plotter. Distinct clusters of HRP-labeled neurons in the IGL were seen after three injections into the mesencephalic reticular formation that involved the caudal TPB and cuneiform region (CFR), and after one injection into the medial accessory nucleus of IO. As many as seven clusters of labeled neurons were found in some sections through the caudal one-half of SC after the TPB/CFR injections. Each cluster consisted of 3-20 cells, all of which were small to medium in size. In sections also tested for ChAT, the cell clusters in the TPB/CFR cases were found to overlap precisely the ACh patches in the IGL. In addition, SC neurons projecting to the IO formed clusters above the ChAT patches and in the intermediate white layer (IWL) of SC. None of the other HRP injections produced any obvious cell clusters in the deep layers of SC. These results are the first to show that specific cell groups, distinguished by size and projection site, form clusters that match the patch-like innervation of cholinergic afferents to SC. This modular organization may correspond to saccade-related cells that have also been reported to be organized into clusters in the cat SC.


Adolescent School Bullying and Life Skills: A Systematic Review of the Recent Literature.
The health consequences of being involved in bullying and cyberbullying are well described for adolescents, but many questions related to the role played by their life skills remain unanswered. Accordingly, this systematic review aims to provide a clear overview of research on the relationships between bullying involvement as a bully, victim, bully-victim or bystander, and adolescents' life skills. This article systematically reviewed 71 relevant empirical studies that met the inclusion criteria, extracted from the PubMed, PsycINFO, Scopus, Sage, Wiley, and SpringerLink databases. Their main findings were categorized according to the three types of life skills described by the World Health Organization: decision-making/problem-solving skills, interpersonal and communication skills, and self-management skills. Results showed relatively consensual outcomes for communication and interpersonal skills (empathy, moral disengagement) and skills for managing stress (coping strategies). Other decision-making or interpersonal skills, such as executive function or theory of mind, were poorly explored, and require further research, if we are to understand how life skills may be involved in bullying. Taken together, our findings highlight methodological heterogeneity and measurement problems in bullying studies that make their results difficult to interpret. Recommendations for prevention/education health researchers and professionals are provided, emphasizing the importance of considering the sociocognitive development of adolescents in bullying prevention.


Familial retrocecal appendicitis.
A family pedigree containing sixteen individuals with acute appendicitis is presented. In all but one the position of the appendix was retrocecal. In two other members explored for abdominal pain wherein acute appendicitis was not the cause, the appendix was also found to be retrocecal. The anatomic retrocecal location of the appendix in this pedigree shows a degree of uniformity that implies a common predisposing factor inherited as a simple, dominant unit-character.


The antibacterial effect of Plectranthus scutellarioides (L.) R.Br. leaves extract against bacteria associated with peri-implantitis.
The present study investigates Plectranthus scutellarioides (L.) R.Br. as potential antibacterial oral rinse against bacteria associated with peri-implantitis to prevent the initial infection as well as disease progression. Phytochemical screening was done on P. scutellarioides lyophilized extract to identify the presence of chemical constituent by using mass-based identification. The extract was screened for its antibacterial activity against 4 Gram-positive aerobes (early colonizer) and 5 Gram-negative facultative anaerobes as well as obligate anaerobes (late colonizer) using disc diffusion method. The extract was tested for minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), its cytotoxicity effects on human gingival fibroblast cell (HnGF) as well as bacteria morphological changes by scanning electron microscopy (SEM). Four flavonoid compounds were identified namely quercetin-3-glucoside, quercitrin, quercetin 3-(6″-acetylglucoside) and quercetin 3-O-acetyl-rhamnoside. The sensitivity test revealed that P. scutellarioides extract was effective against all the bacteria tested. MIC concentrations for the Gram-positive aerobes were in the range of 1.56-12.50 mg/mL, and the MBC concentrations were within 3.13-12.50 mg/mL. For Gram-negative obligate anaerobes, the MIC concentration were within 3.13-12.50 mg/mL and MBC within 6.25-200.00 mg/mL. The ethanolic extract did not have any cytotoxic effect on HnGF cells at the tested concentrations. SEM images showed bacterial cell wall disruption for all the bacteria tested. The results showed that P. scutellarioides extract exerts its antibacterial property by disrupting the cell wall of all the bacteria tested. Hence, P. scutellarioides may benefit from further investigations on its safety for oral use as an adjunctive treatment for peri-implantitis.


Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4.
Correct localization of membrane proteins is essential to all cells. Chaperone cascades coordinate the capture and handover of substrate proteins from the ribosomes to the target membranes, yet the mechanistic and structural details of these processes remain unclear. Here we investigate the conserved GET pathway, in which the Get4-Get5 complex mediates the handover of tail-anchor (TA) substrates from the cochaperone Sgt2 to the Get3 ATPase, the central targeting factor. We present a crystal structure of a yeast Get3-Get4-Get5 complex in an ATP-bound state and show how Get4 primes Get3 by promoting the optimal configuration for substrate capture. Structure-guided biochemical analyses demonstrate that Get4-mediated regulation of ATP hydrolysis by Get3 is essential to efficient TA-protein targeting. Analogous regulation of other chaperones or targeting factors could provide a general mechanism for ensuring effective substrate capture during protein biogenesis.


Regional variations in glia and neuropil within the hypothalamic ventromedial nucleus.
The normal fine structure of glia and neuropil in the various regional subdivisions of the hypothalamic ventromedial nucleus in the adult male albino rat is described in this report. Although most HVM astrocytes throughout the nucleus appear ordinary in cytology, certain astrocytes found in the posterior ventrolateral subdivision of the nucleus appear somewhat reactive, in that they contain numerous thick fascicles of gliofibrils and pleomorphic dense bodies. The processes of these reactive astrocytes elaborate multiple, concentric lamellae which encapsulate small, round, pyknotic masses (probably degenerate axonal elements). These degenerate profiles, which are greatly outnumbered by normal HVM boutons, may represent synaptic contacts that deteriorate spontaneously in the normal adult HVM. Other signs of spontaneous degeneration occurring within this neuropil include the occasional presence of large masses of necrotic debris which appear engulfed by microglia. These findings suggest the presence in the normal adult HVM neuropil of a low-grade degenerative process with attendant gliosis, which is topographically centered about the posterior ventrolateral region of the nucleus. Regions of neuropil containing degenerate boutons also contain altered neuronal processes, some of which may be growth cones. The topographic proximity of the degenerating boutons to possible signs of axonal or dendritic regeneration indicates that certain synaptic circuits in the normal adult HVM may be plastic, and subject to spontaneous remodelling.


Phosphine-mediated enantioselective [1 + 4]-annulation of Morita-Baylis-Hillman carbonates with 2-enoylpyridines.
This work describes a phosphine-catalyzed asymmetric [1 + 4] annulation of Morita-Baylis-Hillman carbonates with 2-enoylpyridines for constructing the enantiomerically enriched 2,3-dihydrofuran motif. In the presence of (-)-1,2-bis[(2R,5R)-2,5-dimethylphospholano]benzene, a series of Morita-Baylis-Hillman carbonates reacted with 2-enoylpyridines smoothly to afford a wide range of optically active 2,3-dihydrofurans featuring pyridine motifs in high yields with excellent asymmetric induction.


Increased expression of HIV co-receptor CXCR4 on CD4+ T-cells in patients with active visceral leishmaniasis.
Enhanced expression of the human immunodeficiency virus (HIV) co-receptor CXCR4 renders T-lymphocytes more susceptible for infection with HIV. We demonstrate that patients with active visceral leishmaniasis have a higher proportion of circulating CD4+ T-cells expressing CXCR4 than healthy controls, suggesting that Leishmania may facilitate HIV infection of CD4+ lymphocytes.


Susceptibility of human isolates of Salmonella typhimurium DT 104 to antimicrobial agents used in human and veterinary medicine.
Multiple antibiotic resistance is frequently observed among strains of Salmonella typhimurium DT104. We examined the antibiotic resistance patterns of 240 human isolates submitted from central and northern Alberta to our laboratory for confirmatory testing during 1996-1999. Broth microdilution MIC panels included antibiotics proposed by the Canadian National Enteric Disease Surveillance Committee for human and animal isolates. Seven different susceptibility patterns were observed. The two most common patterns accounted for 83% of isolates; 48% were susceptible to all antibiotics tested and 35% were resistant to ampicillin, tetracycline, chloramphenicol and amoxicillin-clavulanate. All strains were susceptible to enrofloxacin and trovafloxacin with variable resistance to kanamycin and chloramphenicol. There were more susceptible isolates observed in 1996 and 1997 than in 1998 and 1999, but multiple resistant isolates were found throughout the study period.


[Use of new non-nephrotoxic immunosuppressive drugs in kidney transplantation, especially after ischemia-reperfusion injury].
Medium- and long-term renal graft survival depends on 4 main factors: the quality of the harvested graft, ischemia-reperfusion injury during harvesting and re-implantation, rejection, and the nephrotoxicity of certain drugs (especially immunosuppressants) used in this setting. The most nephrotoxic immunosuppressive drugs are the anticalcineurins (cyclosporine A and tacrolimus), a class discovered in the late 1970s and currently representing a basic component of all immunosuppressive protocols for solid organ graft recipients. The renal tubular and vascular toxicity of anticalcineurins is due to their immunosuppressive mechanism: they block the calcineurin pathway and thereby prevent transmission of the first signal from the T cell receptor to the nucleus, which normally triggers cytokine synthesis, New non-nephrotoxic immunosuppressants are therefore needed, especially for grafts of poor quality or subject to severe ischemia-reperfusion injury. Attention is turning to "old " molecules such as anti-thymocyte globulins, but exciting new immunosuppressants are now appearing. Alefacept is a fusion protein that binds to the immunological synapse-associated molecule CD2, which normally interacts with LFA-3. Belatacept, another fusion protein, blocks the T cell second signal CD 28-B7.1/B7.2. Finally, new chemical agents are being developed, such as sautrasporine, a tyrosine kinase inhibitor, and tofacitinib, a Jak inhibitor.


Electrodiagnostic studies: are they useful in clinical practice?
Electrodiagnostic testing (electromyography [EMG] and nerve conduction studies [NCS]) may result in some patient discomfort. The justification for such testing should be based on the expectation that the results will affect patient management. This study was conducted to determine how frequently the results of EMG/NCS change the clinical management of the patient. One investigator (MB) spoke to each referring physician after EMG/NCS to determine if any management decisions were altered by the test. One hundred forty consecutive EMG/NCS records were obtained. Follow-up was available on 100 patients. Of 78 patients with abnormal findings on EMG/NCS, 29 (37%) had a diagnosis different from the referring diagnosis. For 43 of the 78 (55%), the physician reported that additional diagnostic testing was undertaken or treatment plans were altered. EMG/NCS are useful, informative, and diagnostic in the management of various neurologic disorders.


Response properties of lateral hypothalamic neurons during ingestive behavior with special reference to licking of various taste solutions.
Activity of 58 single neurons in the lateral hypothalamic area (LHA) was recorded while Wistar male rats were drinking water and various taste solutions in a test box. A cue tone was presented before opening of a shutter for access to a drinking spout. Except 8 neurons which were non-responsive in the present experimental paradigm, 50 neurons were classified into 3 types according to their response properties: (1) 10 neurons changed their activity with arousal state or circadian rhythm, (2) 10 neurons responded to specific sensory stimuli, i.e. 2 were classified as taste-responsive neurons, which responded excitatory to sodium salts, 3 neurons responded to olfactory stimulation, 5 to somatosensory stimulation applied to the perioral region, and (3) the remaining 30 decreased their activity during licking of liquids regardless of their qualities. Besides this classification, activity of 28 of 58 LHA neurons was altered after onset of the cue tone (or before start of licking), i.e. 24 increased their activity (learned anticipatory response), and 3 modulated their tonic activity into burst discharges corresponding to sniffing, and 1 increased its activity in relation to stepping toward the drinking spout. These data suggest that about half of the LHA neurons increased their activity in anticipatory (searching or approaching) periods just before ingestion, and decreased activity in rewarding periods during ingestion of water or sapid solutions.


Adrenal cortical carcinoma.
A review of 28 cases of adrenal cortical carcinoma provides some insights into the natural history of this disease and suggests modifications in current techniques of diagnosis and management. Our patients ranged in age from 1 to 69 years but it is notable that all of our male patients were more than 39 years old. In addition the men tended to have high stage tumors that were nonfunctional. Female patients, on the other hand, were more evenly distributed in terms of stage, function and age at diagnosis. Staging was extremely important and is discussed in some detail. A dismayingly large number of patients were found to have stage 3 or 4 tumor at initial diagnosis, suggesting that aggressive and rapid evaluation and a high index of suspicion are important to optimize survival. Function is helpful but non-function is common and should not dissuade one from the diagnosis. Excretory urography with tomography followed by angiography frequently will provide the diagnosis. Endocrinologic evaluation should be done with alacrity. Survival with high stages of disease is poor and lengthy evaluation should not be allowed to delay prompt and, hopefully, curative surgery. Surgical resection is the key to cure; chemotherapy and radiotherapy provided relatively poor results in our hands although mitotane has shown a 34 to 54 per cent response rate.


Subdiaphragmatic vagotomy increases the sensitivity of lumbar Aδ primary afferent neurons along with voltage-dependent potassium channels in rats.
Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) ) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing I(A) currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV.


Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells.
Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 degrees C with ketone bodies (acetoacetate, beta-hydroxybutyrate). Acetoacetate, but not beta-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by beta-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes.


Toward 7T breast MRI clinical study: safety assessment using simulation of heterogeneous breast models in RF exposure.
To facilitate assessment of RF power deposition and temperature rise within the breast, we present a method to seamlessly join heterogeneous breast models with standard whole-body models and demonstrate simulations at 7 T. Finite-difference time-domain electromagnetic and bioheat simulations are performed to analyze the specific absorption rate (SAR) and temperature rise distributions in 36 Breast Imaging Reporting and Data System (BI-RADS) categorized breast models fused to 2 female whole-body models while transmitting from a 7T breast volume coil. The breast models are uncompressed in the prone position and feature heterogeneous tissue contents; fusion with human models uses affine transformation and the level-set method. The fusion method produces a continuous transient from the chest region to the posterior portion of breast models while preserving the original volume and shape of breast models. Simulation results of both Ella and Hanako models indicate that the maximum local SAR, partial body SAR, and local tissue temperature rise are positively correlated with both breast density and the highest BI-RADS density classification. Additionally, maximum local tissue temperature rise is positively correlated with maximum 10-g SAR values. Fibroglandular tissue content plays an important role in the distribution of SAR and temperature rise within breast tissue. The combined body-breast models preserve the integrity of breast models while concurrently exhibiting the loading of whole-body human models. The procedures presented in this simulation study facilitate safety assessments for breast MRI across the population at both clinical and ultrahigh field strengths.


Vaso-active therapy can improve 6-min walk distance in patients with pulmonary hypertension and fibrotic interstitial lung disease.
Dyspnea and functional limitation in interstitial lung diseases (ILD) are not always adequately explained by the degree of compromise in pulmonary function alone. Pulmonary hypertension (PH) is felt to be a major contributor to morbidity and mortality in these patients. It is not clear whether treatment with newer vaso-active agents benefits patients with PH in the setting of moderate or severe ILD. Medical records of patients followed at our institution between July 2001 and June 2005 were reviewed to identify patients with moderate or severe fibrotic ILD and PH. Data regarding demographics, hemodynamics, and clinical characteristics at baseline and during follow-up were collected. We identified 19 patients who met our inclusion criteria and in whom vaso-active therapy [epoprostenol (N=10), bosentan (N=9)] was initiated. Most patients [(15/19(79%)] showed an initial positive response to therapy and improved their 6-min walk distance (6MWD) by >50m (responders) and 12/15 (80%) improved by at least 1 WHO functional class. At 1-year follow-up, 7 of 15 (47%) 'responders' had deteriorated significantly. None of the patients died during 1 year of follow-up. Epoprostenol and bosentan produced short-term functional benefit in our patients with PH and moderate or severe restrictive ILD. The generalizability of these results awaits the results of larger, prospective, randomized trials in such patients.


Role of integrins in mouse eyelid development: studies in normal embryos and embryos in which there is a failure of eyelid fusion.
Eyelid fusion normally occurs between E15.5 and E16.5 of mouse embryonic development and results from the migration of a population of periderm-derived epithelial cells over the corneal surface. Cell migration is known to depend on extracellular matrix receptors of the integrin family and to be regulated by growth factors. We were therefore interested that a failure of eyelid fusion has been reported in mice that are homozygous null for the transforming growth factor alpha (TGF-alpha) gene and in mice (invalpha5beta1) in which a transgenic alpha5beta1 integrin under the control of the involucrin promoter is misexpressed in differentiating keratinocytes. We examined expression of the alpha2beta1, alpha3beta1, alpha5beta1 and alpha6beta4 integrins during eyelid fusion in wild-type embryos and found selective upregulation of the alpha5beta1 integrin and its ligand, fibronectin, in the migrating eyelid tip cells. In TGF-alpha null embryos, the failure of eyelid fusion was correlated with a failure to upregulate the alpha5beta1 integrin and fibronectin in the tip cells. Using beta-galactosidase as a reporter gene in transgenic mice, we observed specific activity of the involucrin promoter in the eyelid tip cells. In invalpha5beta1 mice the transgenic human integrin was overexpressed not only in the tip cells but throughout the eyelid epidermis. In contrast, the endogenous, murine, alpha5beta1 integrin was only weakly expressed in the tip cells. We speculate that selective and coordinated expression of the alpha5beta1 integrin and fibronectin in eyelid tip cells is required for eyelid fusion and may be under the control of growth factors that include TGF-alpha.


Radiation Therapy for Benign Disease: Keloids, Macular Degeneration, Orbital Pseudotumor, Pterygium, Peyronie Disease, Trigeminal Neuralgia.
Although the use of ionizing radiation on malignant conditions has been well established, its application on benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, when the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the present use of radiation therapy for some of the most common benign conditions.