Immune checkpoint inhibitors-related pancreatitis with fulminant type 1 diabetes mellitus: case report and literature review.
Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of advanced human malignancies. ICIs-related adverse events, including pancreatitis and diabetes, have been individually characterized in the literature. The co-occurrence of ICIs-related pancreatitis with diabetes is rare and easily overlooked, but it is often severe or fatal. We present a patient with renal tumor resection who was treated with injection of the PD-L1 inhibitor toripalimab and eventually developed acute pancreatitis and fulminant type 1 diabetes mellitus. In addition, we conducted a literature review of ICIs-related pancreatitis with diabetes. The case in our report presented with paroxysmal abdominal pain and loss of appetite. Intravenous fluids and insulin infusion improved the patient's pancreatitis and explosive hyperglycemia. This article suggests that ICIs can affect endocrine and exocrine functions of the pancreas, while providing information and new perspectives for the diagnosis and treatment of this challenging rare disease, helping inspire clinicians for the early identification and effective management of similar cases.


Distribution of thoracic lymphadenopathy in sarcoidosis using computed tomography.
The authors used chest computed tomography to determine the distribution of pulmonary lymphadenopathy in 40 patients with sarcoidosis. Using the American Thoracic Society lymph node map, the number and distribution of significant lymph nodes was calculated. Overall, lymphadenopathy was identified in 39 of the 40 patients. Mediastinal adenopathy was present in 38 patients, and hilar adenopathy was present in 27. Commonly involved nodal stations were 4R, 5, 7, 10R, 11R, and 11L, and little involvement was seen in stations 1, 6, and 14. An understanding of the common sites of adenopathy in sarcoidosis is useful when assessing adenopathy in patients without a known diagnosis.


The Effect of Various Finish Line Configurations on the Marginal Seal and Occlusal Discrepancy of Cast Full Crowns After Cementation - An In-vitro Study.
The marginal fit of crowns is of clinical importance. It is found that marginal and occlusal discrepancies are commonly increased following cementation. The resistance of cementing materials is a factor that prevents cast restorations from being correctly seated. Different finish lines behave differently in facilitating the escape of the cement. When the escape path of the cement decreases, the crown fails to seat further. This study was planned with an aim to evaluate the effect of various finish lines on the marginal seal and occlusal seat of full crown preparations. Six stainless steel metal dies were machined to simulate molar crown preparations. The diameter was 10 mm and height was 6mm. The occlusal surface was kept flat and a small circular dimple was machined for reorientation of the wax pattern and metal copings, margins of various designs were machined accurately. The margins prepared were Group A- 90(0)C shoulder, Group B- Rounded shoulder, Group C- 45 degree sloped shoulder, Group D- Chamfer, Group E- Long chamfer, Group F- Feather edge. Full cast metal crowns of base metal alloy were fabricated over the metal dies. Zinc phosphate luting cement was used for the cementation. After twenty four hours, the cemented crown and die assembly were embedded in clear acrylic resin so as to hold the assembly together while sectioning. Twenty four hours later, all the samples were sectioned sagitally. The sectioned halves were focused under a stereomicroscope and the cement spaces were measured to the nearest micron. The cement thickness was measured at two points on the occlusal surface and one at each margin. Significant differences were observed in the occlusal seat and marginal seal of all the finish line configurations. The rounded shoulder had the best occlusal seat, followed by 90(0)C shoulder. The occlusal seat and marginal seal afforded by the shoulder finish lines were similar whereas there was a vast difference in the seating and sealing of long chamfer and feather edged preparations. They showed the worst occlusal seat. It was found that the finish lines like shoulder preparations which exhibit poor sealing prior to complete cementation allow good seating whereas margins which seal earlier do not allow escape of cement and hence do not seat completely.


The role of exercise parameters on small extracellular vesicles and microRNAs cargo in preventing neurodegenerative diseases.
Physical activity (PA), which includes exercise, can reduce the risk of developing various non-communicable diseases, including neurodegenerative diseases (NDs), and mitigate their adverse effects. However, the mechanisms underlying this ability are not yet fully understood. Among several possible mechanisms proposed, such as the stimulation of brain-derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), the possible involvement of particular vesicular structures enclosed in lipid membranes known as extracellular vesicles (EVs) has recently been investigated. These EVs would appear to exert a paracrine and systemic action through their ability to carry various molecules, particularly so-called microRNAs (miRNAs), performing a function as mediators of intercellular communication. Interestingly, EVs and miRNAs are differentially expressed following PA, but evidence on how different exercise parameters may differentially affect EVs and the miRNAs they carry is still scarce. In this review we summarized the current human findings on the effects of PA and different exercise parameters exerted on EVs and their cargo, focusing on miRNAs molecules, and discussing how this may represent one of the biological mechanisms through which exercise contributes to preventing and slowing NDs.


Candida albicans Hyphae: From Growth Initiation to Invasion.
Candida albicans is a commensal resident of the human gastrointestinal and genital tracts. Under conditions such as dysbiosis, host immune perturbances, or the presence of catheters/implanted medical devices, the fungus may cause debilitating mucosal or fatal systemic infections. The ability of C. albicans to grow as long filamentous hyphae is critical for its pathogenic potential as it allows the fungus to invade the underlying substratum. In this brief review, I will outline the current understanding regarding the mechanistic regulation of hyphal growth and invasion in C. albicans.


Real-time reverse transcription-PCR expression profiling of porcine troponin I family in three different types of muscles during development.
In this study, the expression profiling of three troponin I isoforms (TNNI1, TNNI2 and TNNI3) was investigated in two pig breeds differing in muscularity (Yorkshire and Meishan) at six stages (fetal 60 days and postnatal 3, 35, 60, 120, and 180 days) and three types of muscles (longissimus dorsi muscle, LD; semitendinosus, ST; cardiac muscle, CM) using relative real-time quantitative PCR. Significant differences of troponin I expression in three muscles were found between Yorkshire and Meishan breeds at some stages. The expression peak of TNNI1 and TNNI2 in LD and ST was at postnatal 35 or 60 days in Yorkshire and at postnatal 120 or 180 days in Meishan pigs, while it occurred in CM at postnatal 3 days in two pig breeds. The relative expression values of TNNI1 and TNNI2 were significantly higher in LD than ST at most of stages after birth. The expression ratio of TNNI2 versus TNNI1 favoured TNNI2 expression in ST and LD, but on the contrary in CM. The expression peak of TNNI3 occurred at postnatal 60 and 120 days in Yorkshire and Meishan pigs, respectively. TNNI1 and TNNI3 were co-expressed in CM during the fetal and earlier stages after birth.


Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.
A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 +/- 5.4/GP = 6.2 +/- 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe.


Specific inhibition of redox-linked proton pump activity of cytochrome oxidase by oleate hydroperoxide and involvement of ferrocytochrome c in the catabolism of hydroperoxide.
Both oleic acid and oleate hydroperoxide at concentrations below 200 nmol/mg asolectin remarkably depressed the proton pumping of cytochrome c oxidase reconstituted into liposomes but did not affect the respiratory control ratio. The inhibitory effect was comparable to that of N,N'-dicyclohexylcarbodiimide. Oleate hydroperoxide in the vesicles was reduced by ferrocytochrome c in the absence of cytochrome oxidase and converted to the hydroxy fatty acid. This non-enzymatic oxidation of ferrocytochrome c affected slightly the proton pumping and the cytochrome c oxidation by liposomal cytochrome oxidase. A physiological role of ferrocytochrome c in catabolism of the hydroperoxide of fatty acids is thus suggested.


A grounded theory study of the narrative behind Indian physiotherapists global migration.
It is estimated that an additional 6.4 million allied health professionals are required to address India's health challenges. Physiotherapy is amongst the largest of these professions. Over the last decade, thousands of Indian physiotherapists have sought to study and work overseas. In this study, 19 physiotherapists from across India were interviewed. Data were collected and analysed using construct+ivist grounded theory methods. The findings indicate that the Indian physiotherapy profession faces many political and clinical hierarchical challenges within the Indian healthcare infrastructure. The profession's education provision has developed, and the private clinical sector has grown, but there are significant disparities in quality and standards across the sector. The profession in India has variable autonomy, is not nationally regulated, is poorly paid, and the leadership has been divided. The political, educational, and clinical context in Indian physiotherapy impacts upon physiotherapists' ability to practise effectively to their professional satisfaction. Individual physiotherapists are frustrated by their workplace and travel overseas where they hear that the physiotherapy profession and practice is different. Whilst the disjunctures influencing these factors continue, and overseas physiotherapy practice is perceived as different and superior, Indian physiotherapists will continue to seek to migrate overseas, and facilitating their return will be challenging.


Bacterial communities in the small intestine respond differently to those in the caecum and colon in mice fed low- and high-fat diets.
Bacterial communities in the mouse caecum and faeces are known to be altered by changes in dietary fat. The microbiota of the mouse small intestine, by contrast, has not been extensively profiled and it is unclear whether small intestinal bacterial communities shift with dietary fat levels. We compared the microbiota in the small intestine, caecum and colon in mice fed a low-fat (LF) or high-fat (HF) diet using 16S rRNA gene sequencing. The relative abundance of major phyla in the small intestine, Bacteriodetes, Firmicutes and Proteobacteria, was similar to that in the caecum and colon; the relative abundance of Verrucomicrobia was significantly reduced in the small intestine compared to the large intestine. Several genera were uniquely detected in the small intestine and included the aerotolerant anaerobe, Lactobacillus spp. The most abundant genera in the small intestine were accounted for by anaerobic bacteria and were identical to those identified in the large intestine. An HF diet was associated with significant weight gain and adiposity and with changes in the bacterial communities throughout the intestine, with changes in the small intestine differing from those in the caecum and colon. Prominent Gram-negative bacteria including genera of the phylum Bacteroidetes and a genus of Proteobacteria significantly changed in the large intestine. The mechanistic links between these changes and the development of obesity, perhaps involving metabolic endotoxemia, remain to be determined.


Synthesis of 2-azulenyl-1,1,4,4-tetracyano-3-ferrocenyl-1,3-butadienes by [2+2] cycloaddition of (ferrocenylethynyl)azulenes with tetracyanoethylene.
1-, 2-, and 6-(Ferrocenylethynyl)azulene derivatives 10-16 have been prepared by palladium-catalyzed alkynylation of ethynylferrocene with the corresponding haloazulenes under Sonogashira-Hagihara conditions. Compounds 10-16 reacted with tetracyanoethylene (TCNE) in a [2+2] cycloaddition-cycloreversion reaction to afford the corresponding 2-azulenyl-1,1,4,4,-tetracyano-3-ferrocenyl-1,3-butadiene chromophores 17-23 in excellent yields. The redox behavior of the novel azulene chromophores 17-23 was examined by using cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed their multistep electrochemical reduction properties. Moreover, a significant color change was observed by visible spectroscopy under electrochemical reduction conditions.


Therapy and management of systemic AL (primary) amyloidosis.
The optimal treatment of immunoglobulin light chain amyloidosis (AL) patients requires early diagnosis, correct amyloid typing, effective treatment and careful supportive therapy. In the last few years the therapeutic arsenal for the management of AL has been considerably enriched. Cardiac dysfunction can be accurately monitored by measuring the serum concentration of natriuretic peptide type-B and cardiac troponins and the quantitative test for circulating free light chains allows an easy assessment of haematological response to chemotherapy. These new tools can be combined in order to maximise the improvement of organ dysfunction and minimise toxicity, adapting the intervention to each patient.


Judgement criteria for molar incisor hypomineralisation (MIH) in epidemiologic studies: a summary of the European meeting on MIH held in Athens, 2003.
This paper reviews the proceedings and conclusions of a meeting of experts concerned with the problem of hypomineralised incisors and molars (MIH). The aims of this meeting were to establish criteria for the judgement of MIH, to select representative cases and to discuss how the name of the condition was best described as hypomineralised, or hypomaturated, first permanent molars. There was not complete agreement as to the correct diagnosis and aetiology of the condition. A suggested list of definitions of the judgement criteria to be used in diagnosing Molar Incisor Hypomineralisation (MIH) for prevalence studies was agreed upon.


Frailty Attenuates the Impact of Metformin on Reducing Mortality in Older Adults with Type 2 Diabetes.
To determine whether the protective effect of metformin against death is modified by frailty status in older adults with type 2 diabetes. We conducted a cohort study during October 1, 1999-September 30, 2006 among veterans aged 65-89 years old with type 2 diabetes but without history of liver, renal diseases, or cancers, who had sulfonylureas or metformin as the sole antidiabetic drug for ≥180 days. The Cox proportional hazard model was used to compare hazard rates of all-cause mortality between the metformin and sulfonylurea users adjusting for the propensity score of metformin use and covariates: age, race/ethnicity, diabetes duration, Charlson comorbidity score, statin use, smoking status, BMI, LDL, and HbA1c. In this cohort of 2,415 veterans, 307 (12.7%) were metformin users, 2,108 (87.3%) were sulfonylurea users, the mean age was 73.7±5.2 years, the mean study period was 5.6±2.3 years, the mean HbA1c at baseline was 6.7±1.0%, 23% had diabetes for ≥10 years, and 43.6% (N=1,048) died during the study period. For patients with and without frailty, the adjusted hazard ratio (HR) of death for metformin vs. sulfonylurea use were 0.92 (95% CI=0.90-1.31, p-value=0.19) and 0.69 (95% CI = 0.60-0.79, p-value<0.001), respectively. Logistic regression analyses showed that metformin (vs. sulfonylurea) was significantly associated with a decreased odds of frailty (OR: 0.66, 95% CI: 0.61-0.71, p-value <.0001). Our study suggests that metformin could potentially promote longevity via preventing frailty in older adults with type 2 diabetes.


Update: Urinary stones, active component, U.S. Armed Forces, 2011-2015.
Urinary stones can cause debilitating morbidity that impairs the operational effectiveness of affected members of the U.S. Armed Forces. This report documents that, during the past 5 years, rates of incident diagnoses of urinary stones decreased by about 17% in the active component of the U.S. military. During the period, annual rates of inpatient diagnosed cases were low and relatively stable, while rates of outpatient diagnosed cases slightly decreased. Incidence rates were slightly higher among females than males in 2011; however, rates were very similar among males and females from 2012 through 2015. Rates of incident diagnoses among white, non-Hispanic and Native American/Alaska Native service members were consistently 80%-100% higher than among black, non-Hispanic and Asian/Pacific Islander service members and 35%-45% higher than among Hispanic and "other race/ethnicity" service members. During the 5-year period, a total of 3,350 service members received more than one incident diagnosis of urinary stones ("recurrent cases"); one-tenth (10.2%) of all incident cases during the period were recurrent cases. Service members with histories of urinary stones should be counseled and closely supervised to avoid dehydration and to adhere to diets that reduce the risk of stone formation.


ATP serves an anti-inflammatory role by enhancing β-defensin-2 response in acute pneumonia of rat.
The aim of the current study was to evaluate the effect of ATP on the expression of rat β-defensin-2 (rBD-2) in a time-dependent manner, as well as its therapeutic value in an acute pneumonia rat model. A total of 30 rats as a treatment group and 30 as a control group were treated with the same dose of ATP and normal saline, respectively, lung tissues were isolated from rat and expression of rBD-2 mRNA was assessed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) at 12, 24 and 36 h following treatment. Rats were divided into five groups: The control group treated with normal saline, the Pseudomonas aeruginosa (PA) infected group, group treated with ATP, group treated with cephalosporins, and the group treated with both ATP and cephalosporins. At 24 h following treatment, rat serum and lung tissues were collected for assessment of histological changes, and alterations to expression of the rBD-2 protein by immunohistochemistry, expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 proteins by ELISA. RT-qPCR results indicated that the expression of rBD-2 mRNA was upregulated in response to ATP stimulation in lung tissues of rat, reaching its highest peak at 24 h. Immunohistochemistry demonstrated that ATP treatment enhanced the expression of rBD-2 protein in rat lungs. Ceftazidime and ATP protected lungs from infection of PA and reduced the pathological damage of the lung. Overexpression of rBD-2 by ATP led to decreased protein expression of TNF-α and IL-6 in lung tissues and serum. ATP upregulates the expression of rBD-2 and serves an anti-inflammatory role in the acute pneumonia of a rat model.


Significance of donor transmitted disease in cardiac transplantation.
Infectious complications constitute a major cause of morbidity and mortality after heart transplantation. Those infections transmitted with the transplanted heart are potentially avoidable. Cytomegalovirus infections and toxoplasmosis occupy a prominent position in this category. The outcome of transplanting hearts from donors previously exposed to these infections depends largely on the existing immune status of the recipient. This paper is a retrospective study on the incidence of Toxoplasma gondii and cytomegalovirus infections in patients undergoing heart and heart-lung transplantation at Papworth Hospital, Cambridge.


Halogen Bonding Interactions for Aromatic and Nonaromatic Explosive Detection.
Improved sensing strategies are needed for facile, accurate, and rapid detection of aromatic and nonaromatic explosives. Density functional theory was used to evaluate the relative binding interaction energies between halogen-containing sensor model molecules and nitro-containing explosives. Interaction energies ranged from -18 to -14 kJ/mol and highly directional halogen bonding interactions were observed with bond distances ranging between 3.0 and 3.4 Å. In all geometry optimized structures, the sigma-hole of electropositive potential on the halogen aligned with a lone pair of electrons on the nitro-moiety of the explosive. The computational results predict that the strongest interactions will occur with iodine-based sensors as, of all the halogens studied, iodine is the largest, most polarizable halogen with the smallest electronegativity. Based on these promising proof-of-concept results, synthetically accessible sensors were designed using 1,4-dihalobenzene (X = Cl, Br, and I) with and without tetra-fluoro electron withdrawing groups attached to the benzene ring. These sensing molecules were embedded onto single walled carbon nanotubes that were mechanically abraded onto interdigitated array electrodes, and these were used to measure the responses to explosive model compounds cyclohexanone and dimethyl-dinitro-benzene in nitrogen gas. Amperometric current-time curves for selectors and control molecules, including concentration correlated signal enhancement, as well as response and recovery times, indicate selector responsiveness to these model compounds, with the largest response observed for iodo-substituted sensors.


Study of silver ion migration from melt-blended and layered-deposited silver polyethylene nanocomposite into food simulants and apple juice.
Colloidal silver nanoparticles were prepared via chemical reduction using polyethylene glycol (PEG) as a reducing agent, stabiliser and solvent. Silver polyethylene nanocomposites were produced via two methods, namely: melt blending and layer-by-layer (LBL) deposition of silver nanoparticles onto a polyethylene film. The silver ion release from either melt-blended or LBL-deposited nanocomposites into a food simulant and apple juice during 30 days at 4°C and 40°C was determined by atomic absorption spectroscopy. The effects of incorporating or coating of silver nanoparticles, silver concentration, contact media, temperature and time on silver ion migration were evaluated using factorial design. The diffusion coefficients of silver ions into the food simulants and apple juice were calculated using the Miltz model. The results indicated that the production method of nanocomposite, silver concentration, temperature, time and contact media showed a significant effect (p < 0.05) on silver ion migration. The quantity of silver ion migration from the nanocomposites into the food simulants and apple juice was less than the cytotoxicity-level concentration (10 mg kg(-1)) in all cases over 30 days. The coating of silver nanoparticles, higher silver concentration in the nanocomposite, higher temperature and acidic property of contact liquid all promoted the silver ion release from the nanocomposite films. The migration of silver ions from nanocomposites obeyed first-order diffusion kinetics.


Ontogenesis of gonadotropin-releasing hormone neurons: a model for hypothalamic neuroendocrine cell development.
The vertebrate hypothalamo-pituitary-gonadal axis is the anatomical framework responsible for reproductive competence and species propagation. Essential to the coordinated actions of this three-tiered biological system is the fact that the regulatory inputs ultimately converge on the gonadotropin-releasing hormone (GnRH) neuronal system, which in rodents primarily resides in the preoptic/hypothalamic region. In this short review we will focus on: (1) the general embryonic temporal and spatial development of the rodent GnRH neuronal system, (2) the origin(s) of GnRH neurons, and (3) which transcription - and growth factors have been found to be critical for GnRH neuronal ontogenesis and cellular fate-specification. Moreover, we ask the question whether the molecular and cellular mechanisms involved in GnRH neuronal development may also play a role in the development of other hypophyseal secreting neuroendocrine cells in the hypothalamus.


Malnutrition, and anthropometric and biochemical abnormalities in end-stage renal disease patients.
To detect and compare the degree of malnutrition as well as the anthropometric and biochemical abnormalities among male and female patients with end-stage renal disease (ESRD). A cross-sectional study was carried out at hemodialysis units in 7 Jordanian hospitals, between 2004 - 2005. Two hundred and seventeen ESRD outpatients who underwent hemodialysis were recruited using the convenience-sampling technique. A subjective global assessment (SGA) was used to assess the degree of malnutrition in both male and female patients. Anthropometric and biochemical measurements were also assessed in all patients. The SGA suggested that 50% of females were well nourished while 75% of the males were moderately to severely malnourished. The measured anthropometric variables showed a significant decrease in both male and female patients, except for triceps skinfold thickness. The hemoglobin as well as blood creatinine level were lower among females. In the biochemical parameters, there was a significant decrease in hemoglobin, albumin, and total protein blood levels in male patients. However, a significant decrease in hemoglobin only was detected in female patients with advanced malnutrition. The nutritional status determined by SGA indicated a higher proportion of male patients with moderate to severe malnutrition as compared to female patients. Most of the anthropometric parameters could be used to assess the nutritional status of hemodialysis patients. The noticeable hemoglobin reduction, which increased with malnutrition degree, was significant in both male and female patients, while serum albumin and total protein reduction was significant among male patients only.


Synthesis and in situ atomic force microscopy characterization of temperature-responsive hydrogels based on poly(2-(dimethylamino)ethyl methacrylate) prepared by atom transfer radical polymerization.
Well-defined copolymers of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and benzophenone methacrylate (BPMA) with different compositions were synthesized via atom transfer radical polymerization. The molecular weights of these copolymers were Mn approximately 30 000 g/mol, while the BPMA content varied from 2.5 to 10 mol %. The copolymers with a low content of BPMA (2.5 and 5 mol %) exhibited a sharp thermal transition at 33-36 degrees C in aqueous solution. A hydrogel was immobilized and patterned on a silicon wafer via UV treatment of the spin-coated polymer layer using a photomask technique. The thermoresponsive behavior of the patterned polymer gel was quantitatively investigated by variable temperature in situ contact mode atomic force microscopy, which revealed the presence of two lower critical solution temperature regions. One region was between 25 and 30 degrees C, corresponding to the topmost layer of the hydrogel film, and the other region, around 40 degrees C, corresponded to the bulk of the hydrogel. Concurrent lateral force microscopy measurements revealed that, just above the transition temperature, the bulk region exhibited enhanced friction.


Problems reported by people who request cosmetic surgery.
In a questionnaire, a sample of cosmetic surgery patients were asked to describe the five most important areas or activities of their life affected by their condition or feature. Their answers indicate that people who request cosmetic surgery experience a wide range of problems.


An automated Computerized Severity Index.
The Computerized Severity Index (CSI) is a commercially available scoring system for hospital inpatients. Trained abstractors review the patient's paper medical record and enter the diagnoses and relevant physiological attributes. The HELP (Health Evaluation through Logical Processing) System at LDS Hospital stores patient data in discrete codes. This paper describes the development of an automatic interface between the standalone, personal-computer-based severity system and the mainframe-based hospital information system. The interface scores patient severity without the need for manual chart review. Severity scores from the automated and manual methods were identical for 70% of 222 general medical patients scored retrospectively. An evaluation of the causes for differing scores between the two methods is presented.


Biochemical and molecular identification of Gram-positive isolates with β-hemolysis activity isolated from the nasal swab of pigs during the human meningitis outbreak in Badung Regency, Bali-Indonesia.
The nasal cavity of a pig serves as an entry point and a habitat for the colonization of commensal microbes and pathogenic bacteria. Based on biochemical and serological tests, Streptococcus b-hemolytic Group C was identified as the Gram-positive bacteria, which resulted in the 1994 outbreak and death of thousands of pigs in Bali. Furthermore, this agent is zoonotic and frequently results in the development of meningitis lesions in the infected pig. Recently, a meningitis outbreak in humans was also reported after the consumption of pig-derived foods at Sibang Kaja, Badung-Bali. This study aimed to identify and characterize Gram-positive β-hemolytic organisms collected from nasal swab of pigs from the outbreak area, as well as to compare API Kit and 16S rRNA gene analysis methods. This study commenced with the cultivation of two isolates, Punggul Swab Nasal (PSN) 2 and PSN 19, which were characterized by β-hemolysis activity. These samples were then conventionally and molecularly identified using Kit API 20 Strep and 16S ribosomal RNA (rRNA) gene primers, respectively. Using the Kit API 20 Strep, both isolates were identified as Enterococcus faecium, which was previously classified as Group D Streptococci. Based on the 16S rRNA gene sequencing, PSN 2 and PSN 19 were molecularly confirmed to have 99 and 98.1% similarities with E. faecium (NR042054), respectively. Furthermore, both isolates share the same clade in the phylogenetic tree analysis. Using Kit API 20 Strep and 16S rRNA gene analysis, the PSN 2 and PSN 9 Gram-positive isolates with β-hemolysis activity from pig nasal swabs were identified as E. faecium.


HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase.
Inactivation of the von Hippel-Lindau tumor suppressor protein (pVHL) is the signature lesion in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). pVHL loss causes the transcriptional activation of hypoxia-inducible factor (HIF) target genes, including many genes that encode histone lysine demethylases. Moreover, chromatin regulators are frequently mutated in this disease. We found that ccRCC displays increased H3K27 acetylation and a shift toward mono- or unmethylated H3K27 caused by an HIF-dependent increase in H3K27 demethylase activity. Using a focused short hairpin RNA library, as well as CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) and a pharmacological inhibitor, we discovered that pVHL-defective ccRCC cells are hyperdependent on the H3K27 methyltransferase EZH1 for survival. Therefore, targeting EZH1 could be therapeutically useful in ccRCC.


Physico-chemical and sensory evaluation of potato (Solanum tuberosum L.) after irradiation.
This work evaluated the effects of ionizing radiation on the physico-chemical and sensory characteristics of the potato cultivar Ágata (Solanum tuberosum L.), including budding and deterioration, with the end goal of increasing shelf life. For this, four groups of samples were harvested at the maturation stage. Three of them were separately exposed to a Co-60 source, receiving respective doses of 0.10, 0.15 and 2.00 kGy, while the non-irradiated group was kept as a control. All samples were stored for 35 days at 24 °C (± 2) and at 39% relative humidity. The following aspects were evaluated: budding, rot, loss of weight, texture, flesh color, moisture, external and internal appearance, aroma, soluble solids, titratable acidity, vitamin C, protein, starch and glucose. The results indicated that 0.15 kGy was the most effective dose to reduce sprouting and post-harvest losses, under the conditions studied.


Syntheses of the 47 electron clusters [(Cp*Fe)3(mu3-X)2] (X = S, Se) and the First Fe/Sn/Se Heterocubane Cluster [(CpFe)3(SnCl3)(mu3-Se)4] x DME by the use of chalcogenostannate salts.
By reacting 1-aminoethylammonium (H2NCH2CH2NH3+ = enH+) salts of [Sn2E6]4- anions (E = S, Se), [enH]4[Sn2S6] (1) and [enH]4[Sn2Se6] x en (2), with FeCl2/LiCp, three novel (partly) oxidized, Cp* ligated iron chalcogenide clusters were synthesized. Two of them, [(CpFe)3(mu3-S)2] (3) and [(Cp*Fe)3(mu3-Se)2] (4), contain formally 47 valence electrons. [(Cp*Fe)3(SnCl3)(mu3-Se)4] x DME (5) represents the first known mixed metal Fe/Sn/Se heterocubane type cluster. Compounds 3-5 were structurally characterized by single-crystal X-ray diffraction, and the odd valence electron number of the [Fe3E2] clusters (E = S, Se) was confirmed by density functional (DFT) investigations, mass spectrometry, cyclic voltammetry and a susceptibility measurement of 3.


Human epididymis protein 4 reference intervals in a multiethnic asian women population.
Ovarian cancer is ranked as the fifth most common cause of cancer death in women. In Malaysia, it is the fourth most common cancer in females. CA125 has been the tumor marker of choice in ovarian cancer but its diagnostic specificity in early stages is only 50%. Hence, there is a critical need to identify an alternative tumor marker that is capable of detecting detect ovarian cancer at an early stage. HE4 is a new tumor marker proposed for the early diagnosis of ovarian cancer and disease recurrence. Currently, none of the normal ranges of HE4 quoted in the literature are based on data for a multiethnic Asian population. Therefore, the aim of this study was to determine reference intervals for HE4 in an Asian population presenting in University Malaya Medical Centre, a tertiary reference hospital. 300 healthy women were recruited comprising 150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to a pelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levels were determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The reference intervals were determined following CLSI guidelines (C28-A2) using a non-parametric method. The upper limits of the 95th percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L, and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was noted to increase with age especially in women who were more than 50 years old. We also noted that our proposed reference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4 vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study also showed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels of HE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between the Malays and Chinese ethnic groups. More data are needed to establish a reference interval that will better represent the multiethnic Malaysian population. Probably a larger sampling size of equal representation of the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidence on whether genetics plays a role in reference interval determination.


Treadmill training in Parkinson's patients after deep brain stimulation: Effects on gait kinematic.
The purpose of this study was to evaluate the effect of treadmill training with body weight support on gait kinematics parameters in patients with PD using DBS. Twelve patients completed the protocols (age: 60.9±10.6 years; disease duration: 20±7 years; and time since DBS surgery: 20±4 months). The same set of patients underwent two trainings protocols and four gait analyses (before and after each training). They received eight weeks of treadmill training without body weight support (16 sessions) in conjunction with physiotherapy program followed by six weeks of wash out period, followed by eight weeks of body-weight-supported treadmill training in conjunction with a same physiotherapy program. The Gait Kinematic Analysis involved eight infrared cameras that detected 19 reflective spherical markers attached in limb lower of patients. Statistical analysis used the Wilcoxon test (p≤0.05). Both the training no showed significant differences in linear variables. As the angular variables, only training with support showed significant increase of ranges of motion: pelvis tilt, obliquity and rotation amplitude; hip adduction-abduction and rotation amplitude; percentage of peak flexion in swing phase; foot progression amplitude. The body weight supported treadmill training may promote increase of mobility of lower limbs during gait and it could be a targeted intervention for PD patients treated with DBS.


Low birth weight as cardiometabolic risk in Japanese high school girls.
To examine the relationships between birth weight and metabolic syndrome (MS) risk factors in healthy Japanese high school girls. After obtaining informed consent, we carried out health surveys for the Food Educational Program (FEP) in 2007 and 2008 in 243 healthy Japanese high school girls aged 16.4 ± 1.4 years and examined anthropometric measurements, including abdominal circumference, systolic and diastolic blood pressures (SBP and DBP, respectively), triglycerides (TG), high-density lipoprotein cholesterol (HDL), insulin, and blood glucose to calculate insulin resistance after fasting for 3 hours after lunch. Birth weight was checked by maternity record book, and food customs were recorded using a questionnaire. We analyzed the prevalence of MS risk factors by Bonferroni test following 1-way analysis of variance and their relationships with birth weight by correlation analyses. According to criteria for MS risk factors in Japanese children and adults, the prevalence of obesity, high blood pressure, dyslipidemia, and high blood glucose was 7.4%, 9.1%, 7.0%, and 16.0%, respectively, and MS was detected in only 1 girl who had obesity and 2 more risks (high SBP and TG). Among 180 subjects who reported their birth weights, birth weights were significantly inversely related with SBP (p = 0.007), DBP (p = 0.033), TG (p = 0.009), insulin level (p = 0.047), insulin resistance ( p= 0.050), and number of metabolic risk factors (p = 0.022). Thirteen girls (7.2%) whose birth weights were lower than 2500 g had significantly higher SBP (p = 0.037), DBP (p = 0.032), TG (p = 0.011), insulin level (p=0.037), and insulin resistance (p = 0.043), than 31 girls (17.2%) with birth weights equal to or more than 3400 g. The association of low birth weight could be detected to be significant with such risks of MS as SBP, DBP, TG, insulin level, and insulin resistance even in healthy Japanese high school girls, indicating the importance of follow-up and FEP for children with low birth weight for the prevention of MS in the later life.


Estimating Transitional Probabilities with Cross-Sectional Data to Assess Smoking Behavior Progression: A Validation Analysis.
New analytical tools are needed to advance tobacco research, tobacco control planning and tobacco use prevention practice. In this study, we validated a method to extract information from cross-sectional survey for quantifying population dynamics of adolescent smoking behavior progression. With a 3-stage 7-path model, probabilities of smoking behavior progression were estimated employing the Probabilistic Discrete Event System (PDES) method and the cross-sectional data from 1997-2006 National Survey on Drug Use and Health (NSDUH). Validity of the PDES method was assessed using data from the National Longitudinal Survey of Youth 1997 and trends in smoking transition covering the period during which funding for tobacco control was cut substantively in 2003 in the United States. Probabilities for all seven smoking progression paths were successfully estimated with the PDES method and the NSDUH data. The absolute difference in the estimated probabilities between the two approaches varied from 0.002 to 0.076 (p>0.05 for all) and were highly correlated with each other (R2 =0.998, p<0.01). Changes in the estimated transitional probabilities across the 1997-2006 reflected the 2003 funding cut for tobacco control. The PDES method has validity in quantifying population dynamics of smoking behavior progression with cross-sectional survey data. The estimated transitional probabilities add new evidence supporting more advanced tobacco research, tobacco control planning and tobacco use prevention practice. This method can be easily extended to study other health risk behaviors.


[Hyponatremia in children: from pathophysiology to therapy].
This present review analyzes the etiology, diagnostics and management of conditions associated with hyponatremia. Excess water and/or sodium wasting lead to the development of hyponatremia in children. There are diverse etiologies associated with hyponatremia, correct diagnosis is based on detailed history, physical examination and basic laboratory tests. Symptomatic hyponatremia can be a life threatening emergency and thus requires fast and vigorous management. Inappropriate treatment may cause fatal consequences.


[The surgical treatment of renovascular hypertension in subjects with a single kidney].
Renovascular hypertension in subjects with a solitary kidney, though an infrequent condition, requires surgical direct revascularization procedures either to reduce the hypertensive state and, more important, to preserve renal function. This paper reports a series of six surgically treated cases between 1982 and 1990, with at least two years follow-up. Preoperative renal function, as evaluated by BUN and blood creatinine, was reduced in 5 cases, the remaining one being normal. All subjects were hypertensive at admission: in four cases drug therapy was ineffective for restoring normal pressure values. All subjects had previously undergone surgical nephrectomy: in 3 cases for shrunk kidney, in 2 for failure of a previous attempt of renal revascularization, and one for renal tuberculosis. 3 subjects were concomitantly affected with abdominal aortic aneurysm, and one had previously undergone aortobifemoral bypass. Treatment of the concomitant aortic lesion and renal artery revascularization were carried out at the same operation. Operations performed were TEA of residual renal artery in 3 cases, prosthetic reconstruction in 2 and intraoperative transluminal angioplasty by Gruentzig balloon catheter in one. Over a two-year follow-up renal function remained good in 4 cases, while one subject required a second surgical revascularization due to late acute thrombosis of a previous aortorenal saphenous vein graft. Acute early postoperative renal failure occurred in one case and permanent haemodialysis was instituted. No deaths were recorded in this series.


Plasma insulin and growth hormone concentrations in pregnant sheep I: diurnal variations in mid- and late pregnancy.
Two or three foetal lambs regularly result in a varying degree of carbohydrate shortage in mother ewes in late pregnancy. We have investigated the correlation between plasma insulin, growth hormone and energy substrate concentrations in ewes 8 and 1 weeks before lambing. Plasma growth hormone was fairly constant (2-3 ng/ml) throughout the 24-h cycle 8 weeks before parturition. Seven weeks later higher average levels and increased diurnal fluctuations were observed in 3 out of 4 multiparous ewes. The average post-absorptive insulin levels were reduced by 50 per cent during the same interval. Simultaneously decreased post-absorptive sugar and increased acetoacetate levels were observed. It is concluded that the hormonal adaptations to the increasing carbohydrate deficit in late pregnancy, especially among multiparous ewes, include: a) reduced post-absorptive plasma insulin levels, b) reduced insulin responses to feeding, and c) increased levels of growth hormone in the plasma.


Does low-level laser therapy affect the survival of patients with head and neck cancer?
Low-level laser therapy (LLLT) is used in patients with head and neck cancer (HNC) for treatment-related mucositis. There is conflicting evidence as to whether LLLT leads to the proliferation of tumor cells and whether it interferes with the tumoricidal effect of radiotherapy or chemoradiotherapy, if the tumor lies within the LLLT field. Using fuzzy matching, 126 HNC patients who had received LLLT including the tumor region and 126 matching HNC patients without LLLT (controls) treated at the Department of Otorhinolaryngology, Head & Neck Surgery, Medical University of Innsbruck, were identified. The overall survival was compared using the Kaplan-Meier analysis. Fuzzy matching yielded 2 patient samples well comparable in terms of risk of death. The survival did not significantly differ between patients with and without LLLT (p = 0.18). An increased risk of death in HNC patients who received LLLT covering the tumor region was not observed in our study.


Cryptococcus infection in a non-HIV patient: a case report.
Cryptococcal infections are fungal infections most commonly seen in immunocompromised patients. Chronic high-dose steroid may precipitate such an immunocompromised state and thus create susceptibility to fungal infections. Cryptococcus neoformans is a saprophyte usually found in soil contaminated with pigeon droppings. Suspicion to diagnose begins with clinical symptoms that can be non-specific such as fevers, cough, and headaches. We present a case of steroid-induced cryptococcal infection in a non-HIV-infected person.


A new elevating metatarsal osteotomy: geometrical design and applications.
For metatarsalgia and lesser toe deformities, a commonly performed procedure is the Weil osteotomy, which inevitably depresses the metatarsal head, changing the intrinsic muscle axis and generating phalanx extension. The objective of this study is to present a new metatarsal osteotomy that shortens or lengthens and elevates the metatarsal head, the elevating metatarsal osteotomy (EMO), with its geometrical analysis and possible applications. A geometrical model was designed, planning an oblique subcapital osteotomy with slice resection and distal displacement. A trigonometric analysis was done to calculate how to shorten, elevate, or lengthen the metatarsal head. The EMO elevates the head in one-third of the width of the resected slice. Distal and dorsal displacement of the metatarsal head results in an elevation and lengthening of the metatarsal bone (60% elevation and 65% lengthening). Performing an elevating metatarsal osteotomy will lengthen and elevate the metatarsal head, which sometimes is necessary when treating toe deformities and instability.


Electrophysiological properties of a new permanent endocardial lead for uni- and bipolar pacing.
Unipolar and bipolar electrode systems were compared for electrogram amplitudes and slew rates, signal source impedance, and myocardial stimulation threshold and resistance in 15 consecutive patients who received a new endocardial electrode (Cordis 325-161). The bipolar electrograms showed the highest amplitude in nine of the patients (60%). The unipolar and bipolar electrograms were equal in four patients (26.7%), whereas the unipolar electrograms were highest in only two patients (13.3%). The difference in mean amplitude between bipolar (11.1 mV) and unipolar (10.1 mV) electrograms was statistically significant (p 0.05). Mean slew rates were almost equal (1.7 versus 1.6 V/s; p greater than 0.1). The bipolar electrode system always gave somewhat higher signal source impedance than the unipolar system (p 0.001). The current threshold was significantly lower during bipolar pacing (0.59 mA) in constant current pacing mode, than during unipolar pacing (0.65 mA) (p less than 0.05). No significant differences were found during constant voltage pacing. Stimulation resistance was highest in the bipolar electrode system (p less than 0.001). We conclude that the bipolar electrode system is as good as, or better than, the unipolar system both for ventricular sensing and for pacing.


Ethical evaluation of compulsory measles immunisation as a benchmark for good health management in the European Union.
The results of the study Benchmarking Regional Health Management II suggest that compulsory measles immunisation is a good practice in public health management. Yet, the potential achievement of the desired health outcome alone is not a sufficient reason to make the immunisation obligatory. Rather, compulsory measles immunisation is a morally challenging measure. In this article, compulsory measles immunisation is critically evaluated from a public health ethics point of view. For this evaluation, a set of ethical criteria is proposed: respect for autonomy, health maximisation, efficiency, proportionality and social justice. The authors suggest it should not be taken for granted that compulsory measles immunisation should be championed, rather, health policy makers in the European Union should try to raise immunisation rates with non-compulsory means.


Indirect electrochemiluminescence detection of lysine and histidine separated by capillary electrophoresis based on charge displacement.
Indirect electrochemiluminescence (ECL) detection was applied for the analysis of lysine (Lys) and histidine (His) separated by capillary electrophoresis (CE). With the most effective electrophoretic buffer system, which contained 15 mM phosphate buffer (pH = 5.8) and 0.5 mM Tripropylamine (TPA), fast separation of the two basic amino acids could be performed within 7 min. The linear ranges were 10-35 μM, 35-150 μM for Lys; and 5-35 μM, 35-150 μM for His. The detection limits (S/N = 3) were 0.3 μM for Lys and 1.0 μM for His, respectively. The proposed method was also successfully used for the determination of Lys in the oral pharmaceutical formulations.


Food grade microemulsion systems: canola oil/lecithin:n-propanol/water.
In this study, the capability of a natural surfactant, lecithin, and the influence of ionic strength, pH, and temperature on some properties of a food grade microemulsion system were evaluated. For this purpose, the pseudoternary phase diagrams of canola oil/lecithin:n-propanol/water microemulsions in the presence of different salts (NaCl and CaCl2), ionic strengths, pHs, and temperatures were constructed. Our findings showed that the presence of salts slightly increased the W/O areas on the phase diagrams, whereas pH variation was not effective on the microemulsion formation. The expansion of microemulsion areas with temperature indicated the greater triglycerides solubilization capacity of lecithin based microemulsions at higher temperatures. These findings revealed the efficiency of lecithin-based microemulsion system for solubilization of triglycerides which can potentially be used for extraction of edible vegetable oils particularly canola oil.


The factor structure of major depression symptoms: a test of four competing models using the Patient Health Questionnaire-9.
Little research has examined the underlying symptom structure of major depressive disorder (MDD) symptoms based on DSM-IV criteria. Our aim was to analyze the symptom structure of major depression, using the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 was administered to a sample of 2615 Army National Guard soldiers from Ohio. A one-factor model of depression and three separate two-factor models previously established in the literature were evaluated using confirmatory factor analysis. Results demonstrated greater support for the two-factor models of depression than for the one-factor model. The best fitting model was the two-factor model of somatic and non-somatic symptoms supported previously by Krause et al. (2010) and Richardson and Richards (2008). Implications for understanding the components and mechanisms of MDD are discussed.


Estimation of the phase distribution in dental amalgam with the electron microprobe.
The phase distributions of several dental amalgams have been determined by two methods: calculation from elemental analysis data obtained with the microprobe, and measurement of phase areas on backscattered electron photographs with the image analyzer. The results of these methods agree, in general, with the distributions predicted by the stoichiometric equations.


Reconstruction of postburn female breast deformity.
Postburn breast deformity is a sequelae of severe scar contraction of the burned chest. During the past four years, 6 female patients with such a deformity required reconstruction, and the surgery was performed in our department. Three different types of breast reconstruction were undertaken, each one achieving a satisfactory aesthetic result.


Immunohistochemical demonstration of equine herpesvirus-1 antigen in neurons and astrocytes of horses with acute paralysis.
Equine herpesvirus-1 (EHV-1) infection in a few widely scattered neurons and astrocytes plus endothelial cells in brain and spinal cord of two horses with naturally occurring paralytic disease was demonstrated by use of an immunoperoxidase technique. These horses were euthanatized less than 48 hours after the onset of clinical signs. No staining for EHV-1 was demonstrated in brain or spinal cord of three horses that had a longer duration of clinical disease or in two uninfected horses.


Mean platelet volume changes before and after glycated hemoglobin (HbA1c) improvement in a large study population.
Diabetes mellitus (DM) is a metabolic disorder associated with both microvascular and macrovascular complications. Mean platelet volume (MPV) is a marker of platelet activity, which plays a major role in the development of vascular complications of DM. The aim of this study is to compare the MPV levels before and after the decrease of glycated hemoglobin (HbA1c) levels in a large diabetic population. This was a retrospective study conducted on type 2 diabetic patients from the outpatient clinic for 1 year between 2014 and 2015 with the participation of 595 diabetic patients. When we compared the basal and post-treatment values, a significant decrease of MPV and HbA1c levels was found (HbA1c: 9.41 ±1.98% vs. 7.43 ±1.29%, p < 0.001; MPV: 9.11 ±1.42 vs. 8.17 ±1.04, p < 0.001). There was also a positive correlation between the mean changes of MPV and HbA1c levels after the treatment (ΔMPV: 0.93 ±0.96 vs. ΔHbA1c: 1.96 ±1.43; p = 0.005, r = 0.115). When the participants were divided into two groups according to their basal HbA1c levels (group A: HbA1c ≤ 6.5% and group B: HbA1c > 6.5%), it was clearly seen that improvement of glucose levels led to a significant decrease in MPV levels in both groups. The results of this study show that better glycemic control is associated with a significant decrease of MPV levels, regardless of whether the treatment modality is insulin or oral antidiabetic.


Diagnostic Evaluation of the Knee in the Office Setting Using Small-Bore Needle Arthroscopy.
Arthroscopy is currently the gold standard for diagnosing intra-articular knee pathology. Magnetic resonance imaging (MRI) can be a clinical adjunct for diagnosis; however, it is not without its shortcomings. Although highly accurate, even advanced imaging misdiagnoses the condition in 1 in 14 patients with regard to anterior cruciate ligament pathology. Previous studies have indicated that MRI fails to identify meniscal pathology when one exists in 1 of every 10 cases, and diagnoses pathology when pathology truly does not exist in 1 of every 5 patients. In-office arthroscopy offers an alternative to formal diagnostic arthroscopy, with reduced cost and risk of complications. This is a technique article that discusses the use of small-bore needle arthroscopy in the office setting.


Influence of pumpkin seed cake and extruded linseed on milk production and milk fatty acid profile in Alpine goats.
The aim was to determine the effect of substituting pumpkin seed cake (PSC) or extruded linseed (ELS) for soya bean meal in goats' diets on milk yield, milk composition and fatty acids profile of milk fat. In total, 28 dairy goats were divided into three groups. They were fed with concentrate mixtures containing soya bean meal (Control; n=9), ELS (n=10) or PSC (n=9) as main protein sources in the trial lasting 75 days. Addition of ELS or PSC did not influence milk yield and milk gross composition in contrast to fatty acid profile compared with Control. Supplementation of ELS resulted in greater branched-chain fatty acids (BCFA) and total n-3 fatty acids compared with Control and PSC (P<0.05). Total n-3 fatty acids were accompanied by increased α-linolenic acid (ALA, C18:3n-3; 0.56 g/100 g fatty acids) and EPA (C20:5n-3; 0.12 g/100 g fatty acids) proportions in milk of the ELS group. In contrast, ELS and PSC resulted in lower linoleic acid (LA, C18:2n-6; 2.10 and 2.28 g/100 g fatty acids, respectively) proportions compared with Control (2.80 g/100 g fatty acids; P<0.05). Abovementioned resulted in lower LA/ALA ratio (3.81 v. 7.44 or 6.92, respectively; P<0.05) with supplementation of ELS compared with Control or PSC. The PSC diet decreased total n-6 fatty acids compared with the Control (2.96 v. 3.54 g/100 g fatty acids, P<0.05). Oleic acid (c9-C18:1), CLA (c9,t11-18:2) and t10-,t11-C18:1 did not differ between treatments (P⩾0.08), although stearic acid (C18:0) increased in ELS diets compared with Control (12.7 v. 10.2 g/100 g fatty acids, P<0.05). Partially substituted soya bean meal with ELS in hay-based diets may increase beneficial n-3 fatty acids and BCFA accompanied by lowering LA/ALA ratio and increased C18:0. Pumpkin seed cake completely substituted soya bean meal in the diet of dairy goats without any decrease in milk production or sharp changes in fatty acid profile that may have a commercial or a human health relevancy.


Toward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing.
Precision/personalized medicine in oncology has two key pillars: molecular profiling of the tumors and personalized reporting of the results in ways that are clinically contextualized and triangulated. Moreover, neurosurgery as a field stands to benefit from precision/personalized medicine and new tools for reporting of the molecular findings. In this context, glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Precision/personalized medicine has emerged as a promising approach for personalized therapy in GBM. In this study, we performed whole exome sequencing of tumor tissue samples from six newly diagnosed GBM patients and matched nontumor control samples. We report here the genetic alterations identified in the tumors, including single nucleotide variations, insertions or deletions (indels), and copy number variations, and attendant mutational signatures. Additionally, using a personalized cancer genome-reporting tool, we linked genomic information to potential therapeutic targets and treatment options for each patient. Our findings revealed heterogeneity in genetic alterations and identified targetable pathways, such as the PI3K/AKT/mTOR pathway. This study demonstrates the prospects of precision/personalized medicine in GBM specifically, and neurosurgical oncology more generally, including the potential for genomic profiling coupled with personalized cancer genome reporting. Further research and larger studies are warranted to validate these findings and advance the treatment options and outcomes for patients with GBM.


Facile synthesis of functionalizated carbon nanospheres for determination of Cu2+.
In this research, quantities of carbon nanospheres (CNSs) were prepared with a convenient and low cost method at atmospheric pressure and functionalized with the xanthate group in a simple way. The materials were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectra (FT-IR), and X-ray photoelectron spectroscopy (XPS). In addition, the carbon nanospheres (CNSs) xanthate was applied to fabricate a modified carbon paste electrode (CPE) for the selective and sensitive determination of Cu(2+). Also, the xanthate with a -CS2 group was applied as a chelating agent to enrich Cu(2+) in the determination of Cu(2+) ions. In square wave stripping voltammetry (SWSV), the carbon nanospheres xanthate-modified CPE displayed linear response to Cu(2+) in the concentration range of 8.0 × 10(-8) M to 2.2 × 10(-6) M with a detection limit (S/N = 3) of 3.55 × 10(-8) M. The modified electrode exhibited excellent analytical performance in terms of high repeatability. Finally, it was applied to detect Cu(2+) in the wastewater samples with high accuracy and good recovery, indicating its promising application in the routine analysis of metal ions.


Screening of Deoxynivalenol Producing Strains and Elucidation of Possible Toxigenic Molecular Mechanism.
In this study, seven strains of Fusarium graminearum were isolated from wheat, of which six were identified to produce deoxynivalenol and the production of deoxynivalenol was assessed. F. graminearum strain Fg1 was noted to produce 1.0 μg/g deoxynivalenol during the incubation period in the Czapek yeast broth, while none was detected in F. graminearum strain Fg2. Hence, the differences in proteomes and transcriptomes of Fg1 and Fg2 were compared to analyze the mechanism underlying deoxynivalenol production. Among the 66 significantly differentially expressed proteins in Fg1, 39 and 27 were more or less abundant expressed. Functional analysis suggested that the enzymes involved in the methylerythritol 4-phosphate and mevalonate pathways, which provide a substrate for biosynthesis of farnesyl pyrophosphate, a precursor of DON, were activated in Fg1. The transcriptomics data demonstrated that the expression level of a majority of genes, including trichothecene biosynthetic genes, protein kinases, and transcription factors, involved in trichothecene biosynthesis was higher in Fg1 than in Fg2. The results also revealed differential expression profiles of deoxynivalenol biosynthesis genes in strains Fg1 and Fg2, which emphasized their deoxynivalenol producing ability and the underlying mechanism.


supG and supL in Escherichia coli code for mutant lysine tRNAs+.
We have determined the nucleotide sequences of lysine tRNAs isolated from strains containing one or the other of two Escherichia coli ochre suppressors, supG and supL. Each strain, besides producing wild-type lysine tRNA, has a mutant lysine tRNA species that apparently can read the polypeptide chain termination codons UAA and UAG. The mutant tRNAs from supG and supL strains are identical. In each case the suppressor tRNA has an A36 for U36 nucleotide substitution. Furthermore, the hypermodified nucleoside at position 37 has been changed from t6A to ms2i6A.


[Cognitive development and risk factors in bilingual pre-school children from an immigrant background].
A sample of N=126 preschool children ages 57 to 72 months were examined to explore whether bilingual children from an immigrant background have a higher risk of developing specific developmental problems of educational ability and whether specific precursors could be identified. 63 children with bilingualism and immigrant background were compared to 63 controls matched for age, sex and length of stay in kindergarten. All children were tested with the BASIC-Preschool, a screening tool which assesses specific and non-specific precursors of school problems. Significantly higher risks for developing specific educational problems were found for children growing up bilingually. The subgroup of children with a Turkish background showed the poorest results. Not only language-based subtests of the BASIC-Preschool, but numeracy and visual spatial subtests were affected as language is necessary to understand and/or solve the tasks. For children with immigration background a differentiated analysis of individual resources and risk factors including the consideration of their primary language is required and no universal interventions can be recommended.


Effects of pressurization on structure, water distribution, and sensory attributes of cured ham: can pressurization reduce the crucial sodium content?
This study investigated the replacement of tumbling (intermittent vacuum tumbling for 6 h) with pressure treatment (7 MPa for 4 s) in the production of a cured ham product with the aim of elucidating if the pressure treatment could reduce the amount of salt added to obtain a satisfactory product. Confocal laser scanning microscopy (CLSM) revealed a pressure-induced loosening of the meat structure, and proton nuclear magnetic resonance (NMR) relaxometry revealed that this structural modification of the meat had an impact on water properties and water distribution in both cooked and cooked/fried products. Three salt levels (0.6, 1.1, and 1.7% w/w) were investigated, and sensory profiling revealed that the pressured-cooked meat obtained a significantly higher juiciness score at low and medium salt levels. In addition, sensory profiling assessments revealed that at the lowest salt concentration the pressured product was perceived to be saltier compared with the tumbled product; however, the difference was not significant and was absent upon frying. In contrast, in sensory time intensity analysis the maximum intensity and the total salt taste were significantly higher in the pressured samples at the low and medium salt levels in the cooked samples. In conclusion, the present study showed strong evidence that the structure and biophysical characteristics of cured ham is altered by pressurization and suggested that pressurization may reduce the critical amount of salt required in a ham product.


The direct field boundary impedance of two-dimensional periodic structures with application to high frequency vibration prediction.
Large sections of many types of engineering construction can be considered to constitute a two-dimensional periodic structure, with examples ranging from an orthogonally stiffened shell to a honeycomb sandwich panel. In this paper, a method is presented for computing the boundary (or edge) impedance of a semi-infinite two-dimensional periodic structure, a quantity which is referred to as the direct field boundary impedance matrix. This terminology arises from the fact that none of the waves generated at the boundary (the direct field) are reflected back to the boundary in a semi-infinite system. The direct field impedance matrix can be used to calculate elastic wave transmission coefficients, and also to calculate the coupling loss factors (CLFs), which are required by the statistical energy analysis (SEA) approach to predicting high frequency vibration levels in built-up systems. The calculation of the relevant CLFs enables a two-dimensional periodic region of a structure to be modeled very efficiently as a single subsystem within SEA, and also within related methods, such as a recently developed hybrid approach, which couples the finite element method with SEA. The analysis is illustrated by various numerical examples involving stiffened plate structures.


Isolation and Barcoding of Trace Pollen-free DNA for Authentication of Honey.
Adulteration and mislabeling of honey to mask its true origin have become a global concern. Pollen microscopy, the current gold standard for identifying honey's geographical and plant origins, is laborious, requires extensive training, and fails to identify filtered honey and honey spiked with pollen from a more favorable plant to disguise its origins. We successfully isolated pollen-free DNA from filtered honey using three types of adsorbents: (i) anti-dsDNA antibodies coupled to magnetic microspheres; (ii) anion-exchange adsorbent; and (iii) ceramic hydroxyapatite. The internal transcribed spacer 2 region of the captured pollen-free DNA was polymerase chain reaction-amplified and subjected to next-generation sequencing. Using an in-house bioinformatics pipeline, initial experiments showed that anion exchange had the greatest capacity to capture trace pollen-free DNA, and it was successfully applied to isolate DNA from five honey samples. Enrichment of trace pollen-free DNA from filtered honey samples opens a new approach for identifying the true origins of honey.


Differences in embryonic gene expression and quality indicate the benefit of epidermal growth factor receptor inhibitor during prematuration to improve competence in bovine oocytes.
The epidermal growth factor receptor (EGFR) pathway is directly involved in oocyte meiotic resumption induced by a gonadotropic stimulus. Here, we used an EGFR inhibitor (AG1478) to inhibit spontaneous meiosis resumption in bovine oocytes (EGFR- group) during 8 hr prematuration and assessed the competence of such oocytes for embryonic development, apoptosis and gene expression in comparison with Control group which was not prematured. Data are presented as mean ± SEM. Blastocysts rate on day 7 (40.81%, averaged) and hatching rate on day 9 (77.35%, averaged) were unaffected by treatment (p > 0.05). Similarly, treatment did not affect (p > 0.05) the total cell number on day 7 (119.05, averaged) and on day 9 (189.5, averaged). Apoptosis was reduced (p < 0.05) in EGFR- group day 7-embryos compared to Control group (3.7% ± 1.0 vs. 5.2% ± 0.8). Abundance of several transcripts was upregulated (p < 0.05) in EGFR- group, including genes related to embryo development and quality (NANOG and RPLP0), epigenetic regulation (H2AFZ), apoptosis (BID) and stress response (GPX4 and HIF1A). Taken together, the results presented here demonstrated a reduction in the apoptosis index and upregulation of NANOG, H2AFZ and RPLP0 mRNA levels, which are related to embryonic development. Our data suggest that temporary meiosis blockage with EGFR inhibitor during prematuration culture of bovine oocytes may be an interesting strategy to improve embryo quality.


Isolation of Antibodies to Heparan Sulfate on Glypicans by Phage Display.
Heparan sulfate (HS) plays an important role in development and disease. It interacts with many growth factors, chemokines, and other ligands known to be important for cell growth, motility, and differentiation. However, isolating an antibody to HS in mice, rabbits, or humans is difficult due to the poor immunogenicity of HS. Phage display is a major antibody engineering technology that allows the selection of antibodies for poorly immunogenic or highly conserved antigens. This protocol contains detailed procedures for HS antigen preparation and isolation of a phage displayed human single-chain Fv (HS20) that binds HS on glypican-3 (GPC3), and analysis of the selected phage antibody. It is conceivable that the procedures described in this protocol may be applicable to the isolation of antibodies for a variety of HS molecules. © 2018 by John Wiley & Sons, Inc.


Repopulation in radiation oncology: perspectives of clinical research.
Cellular repopulation is one of the most important biological determinants of the clinical outcome of fractionated radiation therapy. A number of randomized controlled trials of altered dose-fractionation have been conducted in patients with squamous cell carcinoma of the head and neck (HNSCC) and the main biological lessons from these are summarised. Data for other tumour histologies are relatively sparse. Further progress in radiotherapy for HNSCC is unlikely to result from altered fractionation alone, but a number of novel strategies for overcoming or exploiting repopulation are being researched. In the next 5 years, the top priorities for clinical and translational research in this field should be the development of clinically applicable predictive assays, functional imaging as an aid to optimize the dose distribution, optimization of combined modality therapies and novel biological strategies specifically targeting tumour cell proliferation.


[Coincidental finding in a man with a painful knee].
A 40-year-old man presented to the emergency department with a painful right knee. Conventional radiography and a CT-scan coincidentally found an asymptomatic intraosseous ganglion. The patient was treated conservatively, with success. Intraosseous ganglia are benign lesions of the metaphyseal area of the long bones. Treatment of asymptomatic lesions is not necessarily unless cortical bone is involved.


Heart rate variability during long truck driving work.
We recorded ambulatory electrocardiograms of 6 long distance truck drivers during their work period in order to observe the affect of autonomic nervous function and symptoms while doing their work. We also recorded their work patterns every minute. The RR50 value and the LFP/HFP ratio were calculated every two minutes based on R-R interval data. RR50 was significantly higher during taking naps than during other periods of work shifts, while, the LFP/HFP ratio showed significantly lower during taking naps than during other periods of work shifts. RR50 in the morning was significantly higher than that in the afternoon. On the contrary, the LFP/HFP ratio showed opposite tendency. Only on the times of driving, RR50 was significantly higher in the morning than that in the afternoon. On the other hand, the LFP/HFP ratio showed an opposite tendency. These results show that the parasympathetic nervous activities were more dominant than sympathetic nervous activities in the morning during the subjects were doing long distance truck driving including midnight work. Driving while in high parasympathetic nervous activity levels may add to cardiovascular stress and lead to drowsiness. And this may result in disrupted attention. It is necessary to decrease work time and improve working conditions of truck drivers working long-hour shifts.


Anti-mitochondrial M2 Antibodies Enhance the Risk of Supraventricular Arrhythmias in Patients with Elevated Hepatobiliary Enzyme Levels.
Objective Supraventricular arrhythmias are commonly detected in patients with anti-mitochondrial antibody M2 (AMA-M2)-associated myopathy. However, the prevalence of supraventricular arrhythmias in unselected AMA-M2-positive patients and the impact of AMA-M2 on supraventricular arrhythmias have yet to be fully investigated. Methods We analyzed 384 patients (116 men; age, 60 [48-69] years), who underwent AMA-M2 testing following the detection of elevated hepatobiliary enzymes. Supraventricular arrhythmias involving atrial fibrillation, atrial flutter, atrial tachycardia, sick sinus syndrome, and atrial standstill were confirmed by a 12-lead electrocardiogram, 24-hour ambulatory monitoring, and physician-assigned diagnoses within the three years before and two years after the AMA-M2 test. Results Seventy-seven (20%) patients were positive for AMA-M2. The prevalence of supraventricular arrhythmias among AMA-M2-positive patients was higher than that among AMA-M2-negative patients (14% vs. 6%, p=0.008). A univariate analysis showed that supraventricular arrhythmias were associated with AMA-M2 positivity, aging, congestive heart failure, and the CHADS2 score. The multivariate analysis determined that AMA-M2 positivity was an independent risk factor for supraventricular arrhythmias (odds ratio 3.52, p=0.011). Among the AMA-M2-positive patients, the AMA-M2 titer did not differ to a statistically significant extent, regardless of the presence or absence of supraventricular arrhythmias. Multiple supraventricular arrhythmias with extremely low atrial deflections was a characteristic finding in AMA-M2-positive patients with supraventricular arrhythmias. Conclusion AMA-M2 enhances the risk of supraventricular arrhythmias, indicating the possible involvement of the atrial myocardium and the formation of an arrhythmogenic substrate. The results highlight the need for clinical attention to supraventricular arrhythmias in AMA-M2-positive patients.


Extracellular neuraminidase production of streptococci associated with acute nephritis.
The possibility that streptococcal neuraminidase has a pathogenic role in acute poststreptococcal glomerulonephritis is reviewed. Experimental and clinical evidence suggesting autologous immune phenomena and anti-Ig reactivity in this disease is discussed. Neuraminidase may also induce sialic acid depletion that would be expected to result in changes of the electrical charge in the immune complex as well as in the glomerular polyanion filtration barrier. The nature of these changes will facilitate penetrability of material with nephritogenic potential. Neuraminidase production was detected in the majority of streptococcal isolates obtained from patients with glomerulonephritis and the best substrate for screening purposes appears to be bovine submaxillary gland mucin. On the basis of available evidence, it is suggested that the development of glomerulonephritis after streptococcal infection probably does not depend on neuraminidase production by the bacteria; however, this enzyme may be responsible for the anti-Ig reactivity demonstrated in some patients and thereby influence the course of the disease.


Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population.
A missense polymorphism in the NRG1 gene, Val>Leu in exon 11, was reported to increase the risk of schizophrenia in selected families from the Central Valley region of Costa Rica (CVCR). The present study investigated the relationship between three NRG1 genetic variants, rs6994992, rs3924999, and Val>Leu missense polymorphism in exon 11, in cases and selected controls from an isolated population from the CVCR. Isolated populations can have less genetic heterogeneity and increase power to detect risk variants in candidate genes. Subjects with bipolar disorder (BD, n=358), schizophrenia (SZ, n=273), or unrelated controls (CO, n=479) were genotyped for three NRG1 variants. The NRG1 promoter polymorphism (rs6994992) was related to altered expression of NRG1 Type IV in other studies. The expression of NRG1 type IV in the dorsolateral prefrontal cortex (DLPFC) and the effect of the rs6994992 genotype on expression were explored in a postmortem cohort of BD, SZ, major depressive disorder (MDD) cases, and controls. The missense polymorphism Val>Leu in exon 11 was not significantly associated with schizophrenia as previously reported in a family sample from this population, the minor allele frequency is 4%, thus our sample size is not large enough to detect an association. We observed however an association of rs6994992 with NRG1 type IV expression in DLPFC and a significantly decreased expression in MDD compared to controls. The present results while negative do not rule out a genetic association of these SNPs with BD and SZ in CVCR, perhaps due to small risk effects that we were unable to detect and potential intergenic epistasis. The previous genetic relationship between expression of a putative brain-specific isoform of NRG1 type IV and SNP variation was replicated in postmortem samples in our preliminary study.


Application of DNA Barcoding in the Classification of Grasshoppers (Orthoptera: Acridoidea)-A Case Study of grasshoppers from Hebei Province, China.
Grasshoppers (Orthoptera: Acridoidea) are the main pests in agriculture, animal husbandry and forestry, and some species of grasshoppers can cause serious disaster. Taxonomy is the basis of pest control. Traditional morphological identification is time-consuming and laborious. It may be due to the existence of cryptic species or the limited number of morphologists, making the identification extremely unstable. In recent years, with the development of molecular systematics, DNA barcoding technology has been applied to environment, ecology, quarantine and so on. This study focuses on testing the feasibility of DNA barcoding in the species identification for superfamily Acridoidea. Sequences of the cox1 gene were obtained from 245 individuals of 43 species of Acridoidea and one species of Tetrigoidea as outgroup from Hebei Province. Phylogenetic, genetic distance and sequence difference threshold analyses using the Maximum Likelihood (ML), Automatic Barcode Gap Discovery (ABGD) and Molecular Defined Operational Taxonomic Units (MOTU) methods, respectively, were performed for obtained sequences and the 139 additional sequences of 21 species downloaded from GenBank. The results have shown that 40, 33, and 35 species among the 48 species are consistent with the traditional morphological classification based on the phylogenetic tree, ABGD and MOTU results, respectively and the DNA barcoding technology is very efficient and helpful for identifying the species of the superfamily Acridoidea; however, the morphological approach is still playing a key role in the species identifications. It also indicates that the cox1 gene is suitable for the phylogeny of genera and species level, but it is not suitable for the phylogenetic relationship of the advanced taxa such as families.


Phase-separation transition in one-dimensional driven models.
A class of models of two-species driven diffusive systems which is shown to exhibit phase separation in d=1 dimensions is introduced. Unlike previously studied models exhibiting similar phenomena, here the relative density of the two species is fluctuating within the macroscopic domain of the phase separtated state. The nature of the phase transition from the homogeneous to the phase-separated state is discussed in view of a recently introduced criterion for phase separation in one-dimensional driven systems.


Magnetic resonance imaging of myocardial perfusion and viability using a blood pool contrast agent.
A comprehensive cardiac magnetic resonance (MR) examination should comprise imaging of myocardial perfusion, viability, and the coronary arteries. Blood pool contrast agents (BPCAs) improve coronary MR angiography, whereas their potential for imaging of perfusion and viability is unknown. The abilities to noninvasively image myocardial perfusion and viability using the BPCA P792 (Guerbet, France) were tested in a closed-chest model of nonreperfused myocardial infarction in 5 pigs. Two to 3 days after instrumentation, myocardial perfusion imaging with a saturation-recovery steady-state free precession technique and viability imaging with an inversion-recovery fast low-angle shot sequence were conducted on a 1.5-T MR scanner using the extracellular contrast agents (ECCA) Gd-DOTA (0.1 mmol Gd/kg) and blood pool contrast agent (BPCA) P792 (0.013 mmol Gd/kg). Perfusion defects were visualized in all pigs with good correlation between the ECCA and the BPCA (1.77 +/- 1.16 cm2 vs. 1.80 +/- 1.19 cm2, r = 0.959, P < 0.01). Reduced myocardial perfusion was detected using the ECCA up to 80 seconds after injection. In contrast, BPCA administration enabled visualization of perfusion defects on equilibrium perfusion imaging in all cases for 10 minutes. The size of myocardial infarction detected with viability MR imaging correlated well between the standard method (ECCA) and delayed-enhancement imaging with the BPCA (5.40 +/- 3.16 versus 5.52 +/- 3.13 cm3, r = 0.994, P < 0.002). The BPCA investigated in this study allows both reliable detection of perfusion defects on first pass and equilibrium perfusion imaging and characterization of viability after myocardial infarction. Thus, this contrast agent is suitable for a comprehensive cardiac MR examination.


Radicals, radical pairs and triplet states in photosynthesis.
The investigation of radical ions, radical pairs, and triplet states that occur in the primary processes of photosynthesis by various EPR techniques is described. The determination of the valence electron spin density distribution by ENDOR/TRIPLE spectroscopy is demonstrated for the primary electron donor. In combination with site-directed mutagenesis, these studies show that the spin distribution in the chlorophyll donor is strongly affected by the protein environment, and a link is established with the donor's oxidation potential and function in the electron transfer process. Similarities and differences between electron donors in anoxygenic (bacterial) and oxygenic photosynthesis are briefly discussed. Application of transient and pulse EPR techniques give information also on short-lived intermediates, such as radical pairs and triplet states, and allow the determination of distances and relative orientations of these species. The extension to time-resolved pulse ENDOR spectroscopy opens the possibility to resolve the electron-nuclear hyperfine structure of these reaction intermediates, even on a very short time scale.


Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model.
Although animal models of Alzheimer's disease (AD) recapitulate beta-amyloid-dependent hippocampal synaptic and cognitive dysfunctions, it is poorly understood how cortex-dependent remote memory stabilization following initial hippocampal coding is affected. Here, we systematically analyzed biophysical and behavioral phenotypes, including remote memory functions, of 5XFAD APP/PS1 transgenic mice containing five familial AD mutations. We found that 5XFAD mice show hippocampal dysfunctions as observed by reduced levels of baseline transmission and long-term potentiation at Schaffer collateral-CA1 synapses. Hippocampus-dependent memory tested 1 day after contextual fear conditioning was also impaired age-dependently in 5XFAD mice, as correlated with the onset of hippocampal synaptic failures. Importantly, remote memory stabilization during 30 days after training significantly declined in 5XFAD mice at time well before the onset of hippocampal dysfunctions. Our results indicate that 5XFAD mice provide a useful model system to investigate the mechanisms and therapeutic interventions for multiple synaptic and memory dysfunctions associated with AD.


Psoriatic skin inflammation is promoted by c-Jun/AP-1-dependent CCL2 and IL-23 expression in dendritic cells.
Toll-like receptor (TLR) stimulation induces innate immune responses involved in many inflammatory disorders including psoriasis. Although activation of the AP-1 transcription factor complex is common in TLR signaling, the specific involvement and induced targets remain poorly understood. Here, we investigated the role of c-Jun/AP-1 protein in skin inflammation following TLR7 activation using human psoriatic skin, dendritic cells (DC), and genetically engineered mouse models. We show that c-Jun regulates CCL2 production in DCs leading to impaired recruitment of plasmacytoid DCs to inflamed skin after treatment with the TLR7/8 agonist Imiquimod. Furthermore, deletion of c-Jun in DCs or chemical blockade of JNK/c-Jun signaling ameliorates psoriasis-like skin inflammation by reducing IL-23 production in DCs. Importantly, the control of IL-23 and CCL2 by c-Jun is most pronounced in murine type-2 DCs. CCL2 and IL-23 expression co-localize with c-Jun in type-2/inflammatory DCs in human psoriatic skin and JNK-AP-1 inhibition reduces the expression of these targets in TLR7/8-stimulated human DCs. Therefore, c-Jun/AP-1 is a central driver of TLR7-induced immune responses by DCs and JNK/c-Jun a potential therapeutic target in psoriasis.


Effects of oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs.
To determine the effects of short-term oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs. Thirty-two healthy adult Abyssinian guinea pigs were used in this study. One day before the start of the trial, the pretreatment baseline phenol red thread test (PRTT) values were recorded. Sixteen guinea pigs in the treated group received 25 mg/kg trimethoprim-sulfamethoxazole orally twice a day for 14 days. The other sixteen guinea pigs were used as untreated controls and received a placebo during the study. All the ophthalmic tests were performed without chemical restraint. PRTT values were evaluated in both eyes of all the guinea pigs using a commercial PRTT strip of a single lot number on days 0 (baseline), 15, and 21 after starting the trial. The pretreatment baseline mean ± SD PRTT values for the treatment and control groups were 11.12 ± 3.82 mm/15 s and 11.93 ± 2.73 mm/15 s, respectively. After 14 days of drug administration, the mean ± SD PRTT values for the treatment and control groups were 10.87 ± 3.11 mm/15 s and 13.00 ± 2.47 mm/15 s, respectively. On Day 21, the mean ± SD PRTT values for the treatment and control groups were 12.62 ± 4.05 mm/15 s and 12.87 ± 2.99 mm/15 s, respectively. Significant decreases in the PRTT values, compared with the pretreatment baseline values, were not observed in the treatment group on Day 15 (P = 0.14) and Day 21 (P = 0.31). Trimethoprim-sulfamethoxazole did not decrease tear production in the guinea pigs in this study.


galaxieEST: addressing EST identity through automated phylogenetic analysis.
Research involving expressed sequence tags (ESTs) is intricately coupled to the existence of large, well-annotated sequence repositories. Comparatively complete and satisfactory annotated public sequence libraries are, however, available only for a limited range of organisms, rendering the absence of sequences and gene structure information a tangible problem for those working with taxa lacking an EST or genome sequencing project. Paralogous genes belonging to the same gene family but distinguished by derived characteristics are particularly prone to misidentification and erroneous annotation; high but incomplete levels of sequence similarity are typically difficult to interpret and have formed the basis of many unsubstantiated assumptions of orthology. In these cases, a phylogenetic study of the query sequence together with the most similar sequences in the database may be of great value to the identification process. In order to facilitate this laborious procedure, a project to employ automated phylogenetic analysis in the identification of ESTs was initiated. galaxieEST is an open source Perl-CGI script package designed to complement traditional similarity-based identification of EST sequences through employment of automated phylogenetic analysis. It uses a series of BLAST runs as a sieve to retrieve nucleotide and protein sequences for inclusion in neighbour joining and parsimony analyses; the output includes the BLAST output, the results of the phylogenetic analyses, and the corresponding multiple alignments. galaxieEST is available as an on-line web service for identification of fungal ESTs and for download / local installation for use with any organism group at http://galaxie.cgb.ki.se/galaxieEST.html. By addressing sequence relatedness in addition to similarity, galaxieEST provides an integrative view on EST origin and identity, which may prove particularly useful in cases where similarity searches return one or more pertinent, but not full, matches and additional information on the query EST is needed.


Steroid sensitivity of thymocyte subpopulations during intrathymic differentiation. Effects of 17 beta-estradiol and dexamethasone on subsets expressing T cell antigen receptor or IL-2 receptor.
We have studied the effects of the steroid hormones, 17 beta-estradiol and dexamethasone, on the relative proportion of thymocyte expression of CD4 (L3T4), CD8 (Ly-2), TCR and IL-2R, used to identify different stages of thymocyte differentiation. After short-term in vivo steroid treatment, a significant decrease in the number and proportion of the CD4+/CD8+, double positive subpopulation was observed in parallel with a proportional increase in the percentage of the CD4+/CD8- single positive, of the CD4-/CD8-, double negative and, to a lesser extent, of the CD8+/CD4- subsets. Either steroid treatment increased the proportion of cells expressing either the epsilon-chain of the CD3 complex and/or the beta-chain of the TCR (beta-TCR) (TCR+/CD3+) and the 55 kDa protein of the IL-2R (IL-2R+), related to the increase of CD4+ SP thymocytes and of DN cells, respectively. Furthermore, the increased proportion of CD3+ cells could also be partially related to the increase of both the CD4+ and DN subsets. A decrease of the effect on either DN/IL-2R+ cells or CD4+ SP cells was selectively observed after long-term treatments with 17 beta-estradiol or DEX, respectively. It is concluded that after short-term administration, different steroid hormones mediate a similar selective depletion of DP, TCR-/CD3-, IL2R- cells presumably in an intermediate stage of differentiation. However, either steroid effects evolve differently in long-term treatment schedules, resulting in different effects on early (DN/IL2R+) and late (SP/IL2R-) steps of thymocyte differentiation.


Increased arterial stiffness in children treated with anthracyclines for malignant disease.
Survivors of childhood cancer have a significantly higher late morbidity and mortality from cardiovascular diseases. The aim of this study was to determine whether anthracyclines used in childhood could increase arterial stiffness, a well-known independent predictor of cardiovascular diseases. The study included 53 children and adolescents aged 6-20 years having completed anthracycline treatment for a malignant disease according to various protocols at least a year before. The patients were free from clinical or laboratory signs of the underlying disease or cardiac disease. Control group consisted of 45 age- and sex-matched healthy children. Arterial stiffness was determined by measuring aortic pulse wave velocity (PWVao) using oscillometric method (Arteriograph TensioMed device). PWVao value was significantly increased (6.24 +/- 1.34 m/s vs. 5.42 +/- 0.69 m/s; p < 0.001) in patients having received anthracyclines as compared to control group. Increased arterial stiffness was present irrespective of the following parameters: age, sex, body mass index, systolic and diastolic blood pressure, mean arterial pressure and heart rate. It is possible that the effect of anthracycline on increased cardiovascular morbidity and mortality in long-term childhood cancer survivors is associated not only with cardiotoxicity, but also with increased arterial stiffness.


Homology modeling and molecular docking studies on Type II diabetes complications reduced PPARγ receptor with various ligand molecules.
Peroxisome proliferator-activated receptor gamma (PPARγ), a type II nuclear receptor present in adipose tissue, colon and macrophages. It reduces the hyperglycemia associated metabolic syndromes. Particularly, type II diabetes-related cardiovascular system risk in human beings. The fatty acid storage and glucose metabolism are regulated by PPARγ activation in human body. According to recent reports commercially available PPARγ activating drugs have been causing severe side effects. At the same time, natural products have been proved to be a promising area of drug discovery. Recently, many studies have been attempted to screen and identify a potential drug candidate to activate PPARγ. Hence, in this study we have selected some of the bio-active molecules from traditional medicinal plants. Molecular docking studies have been carried out against the target, PPARγ. We Results suggested that Punigluconin has a efficient docking score and it is found to have good binding affinities than other ligands. Hence, we concluded that Punigluconin is a better drug candidate for activation of PPARγ gene expression. Further studies are necessary to confirm their efficacy and possibly it can develop as a potential drug in future.


Real Scenario of Oral Cancer Awareness Sessions-A Narrative Viewpoint.
Oral cancer is one of the most common forms of cancer seen in Southeast Asia. Tobacco, betel nut, and slaked lime are the important constituents of betel quid; this is regularly consumed by the youth and elderly as their regular practice. To curb this oral cancer menace, there are numerous policies and pathways, which are adopted by government, local authorities, and institutions. Among the various policies, one of the easiest ways to reach out to masses is in form of screening camps and sessions. Oral cancer screening forms the most vital part of any dental check-up camps. Due to ignorance or lack of adequate knowledge about the deadly results of cancer, people often neglect these screening camps. This may attribute to various reasons that lead to such ignorance and failure of such free screening sessions.