[Duck hepatitis B virus (DHBV) and viral DNA in duck hepatocellular carcinoma and liver tissue].
The hybridization test for duck hepatitis B virus DNA was performed in 34 ducks with hepatoma from Qidong, Jiangsu province. Among the 34 hepatoma ducks, 18 were positive for DHBV DNA in the serum and 27 were positive in the tumor and/or liver tissue. Tissue sections were stained with Victoria blue nuclear fast red for detecting DHBV surface antigen. Victoria blue positive cells were found in 11 tumors and 15 paratumorous regions of 23 ducks with hepatocellular carcinoma. Although paratumorous regions were positively stained in 3 of 8 ducks with cholangiocarcinoma, all were negative within their tumors. All paratumorous regions and 2 tumor regions of 3 ducks with hepatocellular-cholangiocarcinoma were positive for Victoria blue. The results suggest that duck hepatocellular carcinoma be closely related to DHBV infection.


[Signaling mechanism of cardioprotective effects of opioids].
It has been established that G(i/o)-proteins are an intermediate link that provides intracellular signaling between opioid receptors and protein kinases. Our investigations have shown that protein kinase C is involved in realization of the anti-necrotic and anti-apoptotic effects of opioids. PI3 and Akt kinases are involved in the cardioprotective effect of opioids. MEK1/2, ERK1/2, Src and JAK2 kinases play an important role in the cardioprotective effect of opioids. Further study of the participation of JNK, p70s6K and GRK2 in the opioid-induced increase of cardiac tolerance to ischemia and reperfusion is required. NO-synthase plays an important role in the cardioprotective action of opioids. Transactivation of opioid and adenosine receptors is an important element in the development of cardiac tolerance to ischemia and reperfusion. Opioid transactivation of EGF receptor is a connecting link between opioid receptors and ERK1/2 and PI3 kinase cascades.


A Randomized Controlled Noninferiority Trial of Single Dose of Oral Dexamethasone Versus 5 Days of Oral Prednisone in Acute Adult Asthma.
Oral dexamethasone demonstrates bioavailability similar to that of oral prednisone but has a longer half-life. We evaluate whether a single dose of oral dexamethasone plus 4 days of placebo is not inferior to 5 days of oral prednisone in treatment of adults with mild to moderate asthma exacerbations to prevent relapse defined as an unscheduled return visit for additional treatment for persistent or worsening asthma within 14 days. Adult emergency department patients (aged 18 to 55 years) were randomized to receive either a single dose of 12 mg of oral dexamethasone with 4 days of placebo or a 5-day course of oral prednisone 60 mg a day. Outcomes including relapse were assessed by a follow-up telephone interview at 2 weeks. One hundred seventy-three dexamethasone and 203 prednisone subjects completed the study regimen and telephone follow-up. The dexamethasone group by a small margin surpassed the preset 8% difference between groups for noninferiority in relapse rates within 14 days (12.1% versus 9.8%; difference 2.3%; 95% confidence interval -4.1% to 8.6%). Subjects in the 2 groups had similar rates of hospitalization for their relapse visit (dexamethasone 3.4% versus prednisone 2.9%; difference 0.5%; 95% confidence interval -4.1% to 3.1%). Adverse effect rates were generally the same in the 2 groups. A single dose of oral dexamethasone did not demonstrate noninferiority to prednisone for 5 days by a very small margin for treatment of adults with mild to moderate asthma exacerbations. Enhanced compliance and convenience may support the use of dexamethasone regardless.


Primary structure of rat spermidine synthase: an example of refining the cDNA-derived amino acid sequence.
The primary structure of rat spermidine synthase having the N-terminal acetylated methionine and 98.7% homology with that of the mouse enzyme is presented using a limited amount of the homogeneous enzyme. The study strategy was principally to compare the molecular masses of liberated peptides determined by three specific cleavage methods with those expected from known cDNA-derived amino acid sequences of mouse and human enzymes using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF-MS). The cleavage methods involved two enzymatic methods using lysylendopeptidase and arginylendopeptidase, and a chemical method for cleaving at the cysteine residue using 2-nitro-5-thiocyanobenzoic acid. Their usefulness was clearly demonstrated. Column-switching semimicro reversed-phase HPLC, which permits application of the entire reaction mixture, was useful for collecting a small amount of peptides containing the N-terminal amino acid, to confirm acetylation of the N-terminal methionine by MALDI TOF-MS. It was necessary in this approach to examine the amino acid sequence of certain peptides. The Edman method was used for the sequence analysis, and this will be replaced by an improved MALDI TOF-MS now available in a few laboratories.


Differences in urinary arsenic metabolites between diabetic and non-diabetic subjects in Bangladesh.
Ingestion of inorganic arsenic (iAs) is considered to be related to the development of diabetes mellitus. In order to clarify the possible differences in the metabolism in diabetics, we measured urinary iAs metabolites in diabetic cases and non-diabetic control subjects in Faridpur, an arsenic-contaminated area in Bangladesh. Physician-diagnosed type 2 diabetic cases (140 persons) and non-diabetic controls (180 persons) were recruited. Drinking water and spot urine samples were collected. Mean concentrations of total arsenic in drinking water did not differ between cases (85.1 μg/L) and controls (85.8 μg/L). The percentage of urinary iAs (iAs%) was significantly lower in cases (8.6%) than in controls (10.4%), while that of dimethylarsinic acid (DMA%) was higher in cases (82.6%) than in controls (79.9%). This may have been due to the higher secondary methylation index (SMI) in the former (11.6) rather than the latter (10.0). Adjusting for matching factors (sex and unions), and the additional other covariates (age and water arsenic) significantly attenuated the differences in iAs%, SMI, and DMA%, respectively, though the difference in monomethylarsonic acid% was newly significant in the latter adjustment. Our study did not suggest any significant differences in urinary arsenic metabolites between diabetic and non-diabetic subjects.


How low can they go? Aerobic respiration by microorganisms under apparent anoxia.
Oxygen (O2) is the ultimate oxidant on Earth and its respiration confers such an energetic advantage that microorganisms have evolved the capacity to scavenge O2 down to nanomolar concentrations. The respiration of O2 at extremely low levels is proving to be common to diverse microbial taxa, including organisms formerly considered strict anaerobes. Motivated by recent advances in O2 sensing and DNA/RNA sequencing technologies, we performed a systematic review of environmental metatranscriptomes revealing that microbial respiration of O2 at nanomolar concentrations is ubiquitous and drives microbial activity in seemingly anoxic aquatic habitats. These habitats were key to the early evolution of life and are projected to become more prevalent in the near future due to anthropogenic-driven environmental change. Here, we summarize our current understanding of aerobic microbial respiration under apparent anoxia, including novel processes, their underlying biochemical pathways, the involved microorganisms, and their environmental importance and evolutionary origin.


Assessing midwives' breastfeeding knowledge: properties of the Newborn Feeding Ability questionnaire and Breastfeeding Initiation Practices scale.
There are few reliable and valid tools to assess lactation and infant feeding knowledge and practices. This study tested the psychometric properties of two new scales, the Newborn Feeding Ability (NFA) questionnaire and Breastfeeding Initiation Practices (BIP) scale to assess midwives' breastfeeding knowledge and practices specific to breastfeeding initiation. A national postal survey of Australian midwives (n = 3500) was conducted in October 2001. Reliability was determined through Cronbach's alpha coefficient and stability determined by a test-retest. Content validity was established through a critical review of literature and review by an expert panel. Construct validity was informed by an exploratory factor analysis and principle component analysis with varimax rotation. Correlations between NFA and BKQ knowledge subscale scores and BIP and BKQ practice subscale scores assessed criterion validity. A multiple hierarchical regression analysis determined predictive validity of the NFA and BIP. A response rate of 31.6% (n = 1107) was achieved. Adequate internal consistency was established for both instruments. Five factors on the NFA questionnaire were congruent with knowledge about effects of skin-to-skin contact, physiological stability, newborn innate abilities, work practices and effective breastfeeding. The BIP revealed three factors related to observing pre-feeding behavior, mother/baby care and attachment and positioning practices. Predictive validity of knowledge was moderate (r = 0.481, p < 0.01) and contributed to 31.5% of variance in reported practice. Midwives with high knowledge scores were more likely to report best practice when assisting mothers to initiate breastfeeding. Midwives with more personal breastfeeding experience scored higher on all scales. The Newborn Feeding Ability questionnaire and the Breastfeeding Initiation Practices scale can contribute to practice development by assessing lactation and infant feeding knowledge and practice deficits. Individual learning needs can be identified, and effectiveness of education interventions evaluated using these tools. Further testing is required with other samples of midwives and health professionals involved in the promotion of breastfeeding.


Tuftsin - Properties and Analogs.
Immunomodulation is one of the significant therapeutic strategies. It includes both stimulation and suppression of the immune system by a variety of substances called immunomodulators, designed to regulate the immune response of the organism against infections of varying etiology. An example of such a substance is tuftsin (TKPA) 3 (Fig. (1)). In this paper were included tuftsin derivatives, which were described over the years, their together with biological activity and clinical potential. We reviewed a bibliographic database to gather all the important information about the tuftsin peptide. We have delineated the significant information on the activity of the tetrapeptide itself and its derivatives. Analogs were divided because of their anti-tumor, anti-inflammatory, antimicrobial and anti-viral activity. This paper describes eighty-six documents. Thirty-two of them concern on activity of tuftsin in the human organism. The remaining fifty-four describe peptide analogues and their properties, including eleven papers about the tuftsin-based peptides contained in the vaccines, nine papers representing anticancer activity of the tuftsin derivatives, twenty-six about antiinflammatory compounds, and five papers describing the antitumor activity of the tuftsin analogs. The findings of this review confirm the importance of the tuftsin and their derivatives. Most of these substances showed anti-tumor, anti-inflammatory or antibacterial activities. A large amount of the compounds may find use in vaccines. Tuftsin can also be used to prepare fusion proteins in the treatment of cancer and as carriers of many biologically active substances.


Building a fission machine--structural insights into dynamin assembly and activation.
Dynamin is a large multidomain GTPase that assembles into helical arrays around the necks of deeply invaginated clathrin-coated pits and catalyzes membrane fission during the final stages of endocytosis. Although it is well established that the function of dynamin in vivo depends on its oligomerization and its capacity for efficient GTP hydrolysis, the molecular mechanisms governing these activities have remained poorly defined. In recent years, there has been an explosion of structural data that has provided new insights into the architecture, organization and nucleotide-dependent conformational changes of the dynamin fission machine. Here, we review the key findings of these efforts and discuss the implications of each with regard to GTP hydrolysis, dynamin assembly and membrane fission.


Case Presentation: Monkeypox.
Monkeypox is a rare viral disease that initially appeared in West and Central Africa, and is primarily transmitted to humans from animals. It moved to the United States in 2003, which was the first time the disease had left the African continent. It is still uncommon in the United States and elsewhere, although outbreaks have occurred, especially in gay communities,1-3 causing it to be declared a health emergency in some areas. (SKINmed. 2022;20:410-411).


Construction of a cDNA clone corresponding to mouse alpha 1(IV) procollagen.
A new procedure for the synthesis of double stranded cDNA, based upon release of mRNA by "in vitro" translation, was used to clone type IV collagen. Collagen synthesizing polysomes selectively isolated from a mouse parietal yolk sac carcinoma (PYS-2) were used for translation in an heterologous cell-free system. Translation products were collagenase-sensitive and displayed an electrophoretic mobility correspondent to type IV collagen. Translation released mRNA was employed to construct a 100 base pairs long cDNA clone which hybridized to a 7,800 nucleotides long mRNA. Peptides synthesized by "in vitro" translation of hybrid selected mRNA displayed an electrophoretic mobility compatible with that of alpha 1 (IV) collagen, were sensitive to collagenase and were immunoprecipitated by anti-type IV collagen antibody.


[Axonal damage in multiple sclerosis].
The presence of axonal lesions in plaques of demyelination in patients with multiple sclerosis (MS) has been known for many years. Traditionally it was believed that axonal loss occurred in chronic lesions. However, demonstration of pathological degeneration in active plaques, use of new resonance techniques such as spectroscopy or the transfer of magnetization, showing axonal damage in white matter of apparently normal aspect, and the presence of axonal neurofilaments in the cerebrospinal fluid during the episode has made it necessary to reconsider the contribution made by axonal damage to the pathogenesis of MS. Besides, recent studies have shown that a factor present in the cerebrospinal fluid of patients with MS may contribute to the induction of neuronal apoptosis. These facts, apart from their pathogenic implications and consequent clinical repercussions, will affect investigation of alternative treatments for this disorder, and by means of clinico-immunoradiological correlation will help to define the prognosis of the course of the disorder in these patients.


Primary and Repeat Cesarean Deliveries: A Population-based Study in the United States, 1979-2010.
Despite the temporal increase in cesarean deliveries, the extent to which maternal age, period, and maternal birth cohorts may have contributed to these trends remains unknown. We performed an analysis of 123 million singleton deliveries in the United States (1979-2010). We estimated rate ratio (RR) with 95% confidence interval (CI) for primary and repeat cesarean deliveries. We examined changes in cesarean rates with weighted Poisson regression models across three time-scales: maternal age, year of delivery, and birth cohort (mother's birth year). The primary cesarean rate increased by 68% (95% confidence interval [CI]: 67%, 69%) between 1979 (11.0%) and 2010 (18.5%). Repeat cesarean deliveries increased by 178% (95% CI: 176, 179) from 5.2% in 1979 to 14.4% in 2010. Cesarean rates increased with advancing age. Compared with 1979, the RR for the period effect in primary and repeat cesarean deliveries increased up to 1990, fell to a nadir at 1993, and began to rise thereafter. A small birth cohort effect was evident, with women born before 1950 at increased risk of primary cesarean; no cohort effect was seen for repeat cesarean deliveries. Adjustment for maternal BMI had a small effect on these findings. Period effects in primary cesarean were explained by a combination of trends in obesity and chronic hypertension, as well as demographic shifts over time. Maternal age and period appear to have important contributions to the temporal increase in the cesarean rates, although the effect of parity on these associations remains undetermined.


[Rabies].
Rabies virus, a neurotropic lyssavirus responsible for unavoidable fatal encephalitis, is transmitted by saliva of infected animals through bite, scratch or licking of broken skin or a mucous membrane. Infection can be prevented by timely prevention (wash for several minutes, antisepsis and vaccination completed by antirabies immunoglobulins [Ig] according to the severity of exposure). The 55,000 human deaths estimated annually worldwide result mainly from uncontrolled canine rabies in enzootic countries (particularly in Africa and in Asia), attributable to a lack of resources or interest for this disease. Bat rabies, henceforth first cause of human's rabies in many countries in America, affects a very small number of individuals but seems more difficult to control. Shortened vaccine protocols, rationalized use of Ig and development of products of substitution should enhance access of exposed patients to prevention. Finally, research on the biological cycle, the pathogeny and on escape of virus-induced mechanisms from the immune system should continue to pave the way for presently unknown treatments of clinical rabies.


Trichinella spiralis cathepsin B bound and degraded host's intestinal type I collagen.
Trichinellosis is a zoonotic parasitic disease that poses threats to human health, the meat industry, food safety, and huge financial losses. The critical stage of Trichinella spiralis (T. spiralis) infection is the invasion of intestinal larvae into the host's intestinal epithelial cells (IECs). T. spiralis Cathepsin B (TsCB) specifically interacts with IECs to facilitate the invasion of larvae. This study aims to look at how TsCB affects mouse IECs. TsCB was successfully cloned, expressed, and characterized, demonstrating its natural cysteine protease hydrolysis activity. A total of 140 proteins that interact with rTsCB were identified by GST pull-down combined with LC-MS/MS, including type I collagen, an essential component of the host's intestinal epithelial barrier system and intimately related to intestinal epithelial damage. TsCB transcription and expression levels rise, whereas type I collagen in the host's intestinal mucosa decline when the T. spiralis larvae invaded. Besides, it was discovered that TsCB bound to and degraded type I collagen of the host's intestine. This research can serve as a foundation for clarifying how T. spiralis invades the host's intestinal barrier and might provide information on potential targets for the creation of novel treatments to treat parasite illnesses.


Healthcare professionals' hand hygiene knowledge and beliefs in the United Arab Emirates.
Hand hygiene at key moments during patient care is considered an important infection prevention and control measure to reduce healthcare-associated infections. While there is extensive research in Western settings, there is little in the United Arab Emirates where particular cultural and religious customs are thought to influence hand hygiene behaviour. To examine the hand hygiene knowledge and beliefs of health professionals at a tertiary care hospital in the United Arab Emirates. A mixed methods design employed a survey followed by focus groups with nurses and doctors. A total of 109 participants (13.6%) completed the survey: 96 nurses (88%) and 13 doctors (12%). Doctors' hand hygiene knowledge was slightly higher than that of nurses (78.5% versus 73.5%). There was no significant difference in scores on the hand hygiene beliefs scale between nurses (M = 103.06; SD = 8.0) and doctors (M = 99.00; SD = 10.53; t (80) = 1.55; p = 0.13, two-tailed). Seven categories emerged following transcript analysis. Hand hygiene knowledge scores suggest further hand hygiene education is required, especially on alcohol-based hand rub use. Addressing doctors' beliefs is particularly important given the leadership roles that doctors play in healthcare settings.


Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?
Bone marrow stem cells (BMSCs) may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. However, stem cells from older hosts exhibit decreased function during stress. We therefore hypothesized that (1) BMSCs derived from neonatal hosts would provide protection to ischemic myocardium, and (2) neonatal stem cells would enhance postischemic myocardial recovery above that seen with adult stem cell therapy. Female adult Sprague Dawley rat hearts were subjected to an ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). BMSCs were harvested from adult and neonatal mice and cultured through several passages under normal conditions (37 degrees C, 5% CO(2)/air). Immediately prior to ischemia, 1 million adult or neonatal BMSCs were infused into the coronary circulation. Cardiac functional parameters were continuously recorded. Pretreatment with adult BMSCs significantly increased postischemic myocardial recovery as noted by improved left ventricular developed pressure, end diastolic pressure, contractility, and rate of relaxation. Neonatal stem cells, however, did not cause any noticeable improvement in myocardial functional parameters following ischemia. Neonatal and adult BMSCs are distinctly different in the degree of beneficial tissue protection that they can provide. The data herein suggests that a critical age exists as to when stem cells become fully activated to provide their beneficial protective properties. Defining the genes that initiate these protective properties may allow for genetic amplification of beneficial signals, and the generation of "super stem cells" that provide maximum protection to ischemic tissues.


Self-inflicted burns in soldiers.
Self-inflicted burns are a multidisciplinary medical challenge. In contrast to the more common motive of attempted suicide in self-infliction of a burn, usually of a serious degree, a second motive is malingering. Motivation of this nature has been exhibited among Israeli soldiers who inflict on themselves low- to moderate-degree burns to obtain dismissal from mandatory military service. The purpose of our study is to investigate and define this phenomenon. A retrospective analysis was performed on a population of 75 soldiers admitted to our Medical Center during the year 2010 with the diagnosis of any sort of burn. We set up a database including all relevant information about the burns including date and time of occurrence, cause, body location, depth of burn injury, area and shape of burn, etiology, and prescribed treatment. The summer was found to be the season with the highest incidence of burns. As far as the day of the week was influential, we found that the greater percentage of burns occurred at the beginning of the week. Most of the burns involved a minor surface area on the dorsal aspect of the foot. Scalding with hot water was the most common cause of burn. Eighty-one percent of the burns were atypical, being well demarcated.Most of the burn cases happened at home with no witnesses to the event. Sixty-one percent of the patients were not admitted to the hospital and were conservatively treated. Israeli soldiers tend to inflict burns on themselves for ulterior motives. Such burns are almost always minor with a small trauma area and sharp demarcations, and hence can be differentiated from other self-inflicted burns described in the literature. We found that most of the burns occur when the soldiers are on vacation at home. This is probably because the privacy allows them to carry out their act undisturbed. It is important to raise the awareness of attending physicians to the characteristics of these burns. Such patients should be evaluated by medical teams including mental health professionals to help them psychologically and to eliminate this unfortunate problem.


The cost of mental disorders: a systematic review.
To identify and synthesise the literature on the cost of mental disorders. Systematic literature searches were conducted in the databases PubMed, EMBASE, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to January 1980-May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses; (2) diagnosis of at least one mental disorder; (3) study population based on the general population; (4) outcome in monetary units. The systematic review was preregistered on PROSPERO (ID: CRD42019127783). In total, 13 579 potential titles and abstracts were screened and 439 full-text articles were evaluated by two independent reviewers. Of these, 112 articles were included from the systematic searches and 31 additional articles from snowball searching, resulting in 143 included articles. Data were available from 48 countries and categorised according to nine mental disorder groups. The quality of the studies varied widely and there was a lack of studies from low- and middle-income countries and for certain types of mental disorders (e.g. intellectual disabilities and eating disorders). Our study showed that certain groups of mental disorders are more costly than others and that these rankings are relatively stable between countries. An interactive data visualisation site can be found here: https://nbepi.com/econ. This is the first study to provide a comprehensive overview of the cost of mental disorders worldwide.


Mapping the landscape of cerebral amyloid angiopathy research: an informetric analysis perspective.
To quantitatively analyse the research output and major trends in the field of cerebral amyloid angiopathy (CAA) over six decades, from 1954 to 2014, using advanced informetrics methods, we systematically identified CAA-related articles from PubMed, collected metadata and performed productivity analysis, copublication analysis, and network and content analysis over defined time periods. Linear regression was used to investigate these relationships. Changes in CAA research themes (2000-2014) were defined using a topic modelling technique. A total of 2340 CAA papers were published between 1954 and 2014. The mean number (3.03; 95% CI 2.62 to 3.45; p<0.0001) and mean rate (0.13%; 95% CI 0.11% to 0.15%; p<0.0001) of CAA publications increased yearly. Analysis of copublication networks over 5-year periods from 1990 to 2014, revealed a great increase in the total number of connected investigators publishing on CAA (coefficient 16.74; 95% CI 14 to 19.49; p<0.0001) as well as the interactions between them (coefficient 73.53; 95% CI 52.03 to 89.03; p<0.0001). Further analysis of the network characteristics showed that in the past 15 years, copublication networks became not only larger, but also more connected and coherent. Content analysis identified 16 major CAA research themes and their differential evolution in the past 15 years, with the following main trends: (A) limited focus on vascular cognitive impairment; (B) a shift in emphasis towards neuroimaging, cerebral microbleeds and diagnostic aspects and away from pathological aspects; and (3) a reduced emphasis on basic biology apart from an increased focus on mouse models and perivascular drainage. Our study reveals the rapidly developing nature of the CAA research landscape, providing a novel quantitative and objective basis for identifying unmet needs and new directions. Our findings support the idea of a collaborative culture in the field, encouraging international research initiatives.


Head & neck cancer. Its impact on the history of mankind.
Squamous cell carcinoma is the most common head & neck malignancy, and its first descriptions date from the pharaonic era. It has impacted humanity by affecting labor, scientific and cultural productivity and, sometimes, it has influenced the course of history. Head & neck cancer is more common in economically impoverished countries and individuals; however, it can affect any socioeconomic stratum; it has been suffered by known, famous, economically powerful celebrities, intellectuals and artists. Head & neck cancer treatment has been controversial since its initial description up to the present day. Therapeutic decisions have been influenced not only by the stage but by the patient's environment and, sometimes, in an effort to reduce the morbidity resulting from the various oncological treatments, erroneous decisions have been made that have implied the loss of the patient's life. Unfortunately, currently we continue to see these behaviors. A synthesis of cases of renowned celebrities that suffered from this cancer is presented, and the impact this implied in the society of their times is described.


Influence of gender on outcomes after thoracic endovascular aneurysm repair.
Previous studies have shown that female gender is associated with increased morbidity and mortality after endovascular abdominal aortic aneurysm repair. The goal of this study was to assess the effect of gender on 30-day outcomes after thoracic endovascular aortic aneurysm repair (TEVAR) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. This was a review of the 2005 to 2011 ACS-NSQIP database to identify all patients who underwent TEVAR for nonruptured thoracic aortic aneurysms. Procedure and diagnosis codes were used to capture the study population. Patients were stratified according to gender. Baseline, operative, and outcomes data were compared in bivariate fashion. The primary outcome measure was 30-day mortality, and a risk-adjusted generalized linear model with Poisson distribution was used to identify relative risk. During the study period, 649 patients, 279 women (43%) and 370 men (57%), underwent TEVAR. Baseline demographics according to gender were similar; however, women were less likely to drink alcohol (1% vs 5%; P = .001) and to have a history of cardiac surgery (14% vs 27%; P < .001). More women required iliac artery exposure (18% vs 7%; P < .001). Operative times (173.6 ± 6.3 vs 159.8 ± 5.2 minutes; P = .03), transfusion rates (30% vs 17%, P = .001), and hospital length of stay (7.7 ± 0.5 vs 7.6 ± 0.5 days; P = .009) were increased in women compared with men. Overall, postoperative complications were similar, but unadjusted mortality was significantly greater in women (6% vs 3%; P = .03). On multivariable analysis, female gender was no longer a significant predictor of mortality (relative risk [RR], 2.30; 95% confidence interval [CI], 0.99-5.34; P = .053). Independent predictors of 30-day mortality included increasing age (RR, 1.05; 95% CI, 1.01-1.09; P = .02), emergency procedure (RR, 3.76; 95% CI, 1.79-7.87; P < .001), and iliac artery exposure (RR, 4.42; 95% CI, 2.07-9.44; P < .001). Thirty-day unadjusted mortality after TEVAR for nonruptured thoracic aortic aneurysms is increased in women compared with men, but this univariate finding did not persist after risk adjustment. Multivariable analysis showed need for iliac artery exposure, age, and emergency surgery were independently associated with higher mortality rates. These results suggest a need for decreased device delivery size and improvements in endovascular technology.


Preferential accumulation in vivo of 24R,25-dihydroxyvitamin D(3) in growth plate cartilage of rats.
Vitamin D(3) is metabolized in vivo through 25-(OH)D(3) (25D) to both 1α,25-(OH)(2)D(3) (1,25D) and 24R,25-(OH)(2)D(3) (24,25D). Whereas it is assumed that this metabolism occurs primarily in the kidney, recent studies show that there are extrarenal 1α-and 24R-hydroxylase activities as well, and in chondrocytes, these enzymes are regulated by hormones and growth factors. Furthermore, chondrocytes from the resting zone of growth plate cartilage are a target cell population for 24,25D action, suggesting that this vitamin D metabolite may be targeted to this tissue in vivo. To test this hypothesis, 30 normal male Sprague Dawley rats (120 ±20 g) were divided into three groups of eight animals each, and a control group of six animals, and fed ad libitum for 2 wk, a standard rat chow (Teklad LM-485), which contained 3 IU vitamin D(3)/g. The rats were then injected im daily at 9:00AM: , for 4 consecutive d, with 0.1 mL of either [(3)H]-25D, [(3)H]-1,25D or [(3)H]-24,25D. Each dose contained 13 pmol of hormone (0.36 μCi/dose). The distribution of these metabolites was assessed in tibial bone (B) following ablation of the bone marrow, articular cartilage from the tibia (AC), costochondral growth plate cartilage (GC), serum (S), small intestine (I), and kidney (K). The use of high specific activity tritiated vitamin D metabolites facilitated determining tissue localization and further metabolism without perturbation of the body pools of each major metabolite. Accumulation of [(3)H]-1,25D or [(3)H]-24,25D in each tissue was compared to circulating serum levels. In rats dosed with [(3)H]-25D, the tissue:serum ratios for 1,25D were 4.1 (AC), 35.4 (GC), 1.3 (B), 0.7 (K), and 3.0 (I); and tissue:serum ratios for 24,25D were 1.6 (AC), 9.9 (GC), 0.04 (B), 0.2 (K), and 0.4 (I). In rats dosed with [(3)H]-24,25D alone, GC was the only tissue to accumulate the administered metabolite at a concentration significantly higher than that of serum. Similarly, in rats dosed with [(3)H]-1,25D alone, GC was the only tissue to accumulate 1,25D at a concentration higher than that of serum. These results demonstrate, for the first time, that under in vivo conditions, GC specifically accumulates 24,25D and 1,25D. This suggests that growth plate may be a target organ for these two hormones.


Diagnosis and Therapeutic Strategies of Unusual Subglottic Pleomorphic Adenoma: A Rare Case Report and Literature Review.
Pleomorphic adenoma (PA) is primarily found in the salivary glands, and is extremely rare in the subglottic region. Here we present a subglottic PA that presented with symptoms of dry cough and dyspnea. A submucosal mass was found in the subglottic region under laryngoscopy, occluding approximately 40% of the lumen. The patient underwent the transoral endoscopic CO2 laser microsurgery under high-frequency jet ventilation for mass resection, and the pathology report supported the diagnosis of PA. At the 2-year follow-up, there was no evidence of recurrence, and the patient is currently under regular long-term monitoring. Dyspnea and dry cough are nonspecific respiratory symptoms. When no findings discovered in the regular site, it should be noted that the subglottic area is often a blind spot for both pulmonologists and otolaryngologists, and as such, requires careful examination. Transoral endoscopic CO2 laser microsurgery under high-frequency jet ventilation was found to be an effective and less invasive method for treating subglottic PA. This approach helped avoid tracheostomy and resulted in better postoperative recovery.


The transcriptional repressor REST/NRSF modulates hedgehog signaling.
The spatial and temporal control of gene expression is key to generation of specific cellular fates during development. Studies of the transcriptional repressor REST/NRSF (RE1 Silencing Transcription Factor or Neural Restrictive Silencing Factor) have provided important insight into the role that epigenetic modifications play in differential gene expression. However, the precise function of REST during embryonic development is not well understood. We have discovered a novel interaction between zebrafish Rest and the Hedgehog (Hh) signaling pathway. We observed that Rest knockdown enhances or represses Hh signaling in a context-dependant manner. In wild-type embryos and embryos with elevated Hh signaling, Rest knockdown augments transcription of Hh target genes. Conversely, in contexts where Hh signaling is diminished, Rest knockdown has the opposite effect and Hh target gene expression is further attenuated. Epistatic analysis revealed that Rest interacts with the Hh pathway at a step downstream of Smo. Furthermore, we present evidence implicating the bifunctional, Hh signaling component Gli2a as key to the Rest modulation of the Hh response. The role of Rest as a regulator of Hh signaling has broad implications for many developmental contexts where REST and Hh signaling act.


Glycoprotein isolated from Solanum nigrum L. modulates the apoptotic-related signals in 12-O-tetradecanoylphorbol 13-acetate-stimulated MCF-7 cells.
Solanum nigrum L. (SNL) has been used in folk medicine for its anti-inflammatory activity. We isolated only the SNL glycoprotein from SNL and found that it was cytotoxic at low concentration. With respect to cytotoxicity, we investigated whether purified SNL glycoprotein is able to regulate protein kinase C (PKC) alpha activation and nuclear factor (NF)- kappaB activities in 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced tumor promotion, and whether it has an apoptosis-inducing effect in MCF-7 cells using western blot analysis. In addition, to elucidate the relationship between PKCalpha and NF-kappaB, inhibitory studies were performed with staurosporine (an inhibitor of phospholipid/calcium-dependent protein kinase) and pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB activation). To verify induction of apoptosis by the SNL glycoprotein, we performed DNA fragmentation and nuclear staining assays using ethidium bromide and bisbenzamide H33342. The results in this study indicated that SNL glycoprotein induces apoptosis through modulation of PKCalpha and NF-kappaB activity in MCF-7 cells. In fact, SNL glycoprotein interfered with PKCalpha membrane translocation and inhibited NF-kappaB (p50) protein activity in MCF-7 cells stimulated with TPA (61.68 ng/mL, 100 nM) dose-dependently. Regarding the apoptotic-inducing effect, nucleosomal DNA fragmentation and nuclear staining by SNL glycoprotein in MCF-7 cells were shown. Collectively, the data demonstrate that SNL glycoprotein is a potential natural anticancer agent because of its ability to induce apoptosis in MCF-7 cells.


Posthumanism: beyond humanism?
The focal point of posthumanism consists not as such in an a-critical acceptance of the technological promises - like there is for transhumanism - but in a total contamination and hybridization of human beings with other living beings and machines (these are the two main forms of contamination). The change of perspective untaken by posthumanism would be, thus, a paradigmatic shift in anthropology. As with ecologism, posthumanism, in order to obtain total contamination and man's openness to otherness, proposes the elimination and the fluidification of boundaries, thus even denying man's identity, and, with it, the very possibility of openness. However, by denying the identity, one denies the condition of possibility of thought, just as it has been manifested in history until now: hence we understand how, primarily, posthumanism is not configured as an adequate philosophical reflection, but as a narrative that takes origin from certain requirements, which are eminently human, and that discloses its deeply anthropogenic roots.


Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin.
Previous studies on mouse models have indicated that interleukin (IL)-17 and IL-17-producing T-helper (Th) cells are important for pulmonary host defence against Gram-negative bacteria. Human correlates to these findings have not yet been demonstrated. The aim of the present study was to determine whether or not IL-17-producing Th cells are present and whether IL-17 and other Th17-associated cytokines are involved in the immunological response to endotoxin in human airways. Segmental exposure to endotoxin and contralateral exposure to vehicle were performed in the lungs of healthy volunteers, with subsequent bronchoalveolar lavage 12 or 24 h after exposure to study local changes in cytokines and inflammatory cells. Endotoxin exposure increased concentrations of IL-17, IL-22 and their downstream effector molecules, human β-defensin-2 and IL-8/CXC chemokine ligand 8, in bronchoalveolar lavage fluid. Th cells with the capacity to produce IL-17 were found among the bronchoalveolar lavage cells, and expression of IL-17 mRNA correlated with expression of the transcription factor, retinoic-acid-receptor-related orphan receptor C variant 2. Moreover, endotoxin increased the numbers of neutrophils, macrophages and IL-17-producing T-cells, as well as the concentration of the Th17-regulating cytokines, IL-21 and IL-23. In conclusion, IL-17-producing Th cells are present, and IL-17, as well as other Th17-associated cytokines, is involved in the immunological response to endotoxin in human airways.


Air pollution accountability research: Moving from a chain to a web.
Air pollution accountability studies examine the relationship(s) between an intervention, regulation, or event and the resulting downstream impacts, if any, on emissions, exposure, and/or health. The sequence of events has been schematically described as an accountability chain. Here, we update the existing framework to capture real-life complexities and to highlight important factors that fall outside the linear chain. This new "accountability web" is intended to convey the intricacies associated with conducting an accountability study to various audiences, including researchers, policy makers, and stakeholders. We also identify data considerations for planning and completing a robust accountability study, including those relevant to novel and innovative air pollution and exposure data. Finally, we present a series of recommendations for the accountability research community that can serve as a guide for the next generation of accountability studies.


Study of nitrogen implantation in Ti surface using plasma immersion ion implantation & deposition technique as biocompatible substrate for artificial membranes.
The present investigation reports the modification of Ti substrates by a plasma technique to enhance their physio-chemical properties as biocompatible substrates for the deposition of artificial membranes. For that purpose, nitrogen ions are implanted into Ti substrate using the plasma immersion ion implantation & deposition (PIII&D) technique in a capacitively coupled radio frequency plasma. The plasma was characterized using optical emission spectroscopy, together with radio frequency compensated Langmuir probe, while the ion current towards the substrate was measured during the implantation process using an opto-electronic device. X-ray photoelectron spectroscopy (XPS) was used for chemical analysis of the surface, confirming the presence of δ-TiN. The penetration depth of the nitrogen ions into the Ti substrate was measured using secondary ions mass spectroscopy (SIMS) while the morphological changes were observed using atomic force microscopy (AFM). A calorimetric assay was used to prove that the TiN samples maintain the biocompatibility of the untreated Ti surface with its native oxide layer. The ion implantation increases the load bearing ability of Ti surface by the formation of α-Ti(N) and δ-TiN phases on the sub-surface of Ti, and maintains the bio compatibility of Ti surface. After the plasma treatment a thin layer of chitosan (CH) was deposited in order to provide a moisturizing matrix for the artificial membrane of 1,2-dipalmitoyl-sn-3- phosphor glycerocholine (DPPC). The CH and subsequently the DPPC were deposited on the plasma deposited TiN substrate by using physical vapor deposition. The formation of artificial membranes was confirmed by AFM, measuring the topography at different temperatures and performing force curves.


Molecular insights into the anti-inflammatory activity of fermented pineapple juice using multimodal computational studies.
Pineapple has been recognized for its potential to enhance health and well-being. This study aimed to gain molecular insights into the anti-inflammatory properties of fermented pineapple juice using multimodal computational studies. In this study, pineapple juice was fermented using Lactobacillus paracasei, and the solution underwent liquid chromatography-mass spectrometry analysis. Network pharmacology was applied to investigate compound interactions and targets. In silico methods assessed compound bioactivities. Protein-protein interactions, network topology, and enrichment analysis identified key compounds. Molecular docking explored compound-receptor interactions in inflammation regulation. Molecular dynamics simulations were conducted to confirm the stability of interactions between the identified crucial compounds and their respective receptors. The study revealed several compounds including short-chain fatty acids, peptides, dihydroxyeicosatrienoic acids, and glycerides that exhibited promising anti-inflammatory properties. Leucyl-leucyl-norleucine and Leu-Leu-Tyr exhibited robust and stable interactions with mitogen-activated protein kinase 14 and IκB kinase β, respectively, indicating their potential as promising therapeutic agents for inflammation modulation. This proposition is grounded in the pivotal involvement of these two proteins in inflammatory signaling pathways. These findings provide valuable insights into the anti-inflammatory potential of these compounds, serving as a foundation for further experimental validation and exploration. Future studies can build upon these results to advance the development of these compounds as effective anti-inflammatory agents.


Blending Gelatin and Cellulose Nanofibrils: Biocomposites with Tunable Degradability and Mechanical Behavior.
Many studies show how biomaterial properties like stiffness, mechanical stimulation and surface topography can influence cellular functions and direct stem cell differentiation. In this work, two different natural materials, gelatin (Gel) and cellulose nanofibrils (CNFs), were combined to design suitable 3D porous biocomposites for soft-tissue engineering. Gel was selected for its well-assessed high biomimicry that it shares with collagen, from which it derives, while the CNFs were chosen as structural reinforcement because of their exceptional mechanical properties and biocompatibility. Three different compositions of Gel and CNFs, i.e., with weight ratios of 75:25, 50:50 and 25:75, were studied. The biocomposites were morphologically characterized and their total- and macro- porosity assessed, proving their suitability for cell colonization. In general, the pores were larger and more isotropic in the biocomposites compared to the pure materials. The influence of freeze-casting and dehydrothermal treatment (DHT) on mechanical properties, the absorption ability and the shape retention were evaluated. Higher content of CNFs gave higher swelling, and this was attributed to the pore structure. Cross-linking between CNFs and Gel using DHT was confirmed. The Young's modulus increased significantly by adding the CNFs to Gel with a linear relationship with respect to the CNF amounts. Finally, the biocomposites were characterized in vitro by testing cell colonization and growth through a quantitative cell viability analysis performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, the cell viability analysis was performed by the means of a Live/Dead test with Human mesenchymal stem cells (hMSCs). All the biocomposites had higher cytocompatibility compared to the pure materials, Gel and CNFs.


The genetic basis of a species-specific character in the Drosophila virilis species group.
The genetic basis of the species-specific dorsal abdominal stripe of Drosophila novamexicana was examined. The dorsal stripe is present in D. novamexicana and absent in all other members of the Drosophila virilis species group. Interspecific crosses between D. novamexicana and genetically marked D. virilis revealed that all four of the autosomes (except the tiny dot chromosome, which was not marked) and the sex chromosomes (the X and Y chromosome effects could not be disentangled) showed a significant effect on the width of the dorsal stripe. All the autosomes act approximately additively; only minor interactions were detected among them. No significant maternal effects were found. This means that a minimum of five loci are involved in the character difference between the two species, and this is the maximum number that this technique could discern. These results suggest that, based on the number of factors involved in the character difference, the inheritance of this character should be considered polygenic, but because chromosome 2 (the largest chromosome in the species) contributed over half of the variance toward the character difference, it is best to consider the inheritance oligogenic based on effect. The implications of these findings are discussed in light of the importance of macromutation in speciation and the sex chromosome theory of speciation.


Asymmetric cell division and Notch signaling specify dopaminergic neurons in Drosophila.
In Drosophila, dopaminergic (DA) neurons can be found from mid embryonic stages of development till adulthood. Despite their functional involvement in learning and memory, not much is known about the developmental as well as molecular mechanisms involved in the events of DA neuronal specification, differentiation and maturation. In this report we demonstrate that most larval DA neurons are generated during embryonic development. Furthermore, we show that loss of function (l-o-f) mutations of genes of the apical complex proteins in the asymmetric cell division (ACD) machinery, such as inscuteable and bazooka result in supernumerary DA neurons, whereas l-o-f mutations of genes of the basal complex proteins such as numb result in loss or reduction of DA neurons. In addition, when Notch signaling is reduced or abolished, additional DA neurons are formed and conversely, when Notch signaling is activated, less DA neurons are generated. Our data demonstrate that both ACD and Notch signaling are crucial mechanisms for DA neuronal specification. We propose a model in which ACD results in differential Notch activation in direct siblings and in this context Notch acts as a repressor for DA neuronal specification in the sibling that receives active Notch signaling. Our study provides the first link of ACD and Notch signaling in the specification of a neurotransmitter phenotype in Drosophila. Given the high degree of conservation between Drosophila and vertebrate systems, this study could be of significance to mechanisms of DA neuronal differentiation not limited to flies.


A Rare Case of Early Onset Multiple Myeloma in a 20-Year-Old Female With Factor X Inhibitor.
Multiple myeloma is plasma cell neoplasm affecting persons over the age 60. Less than 2% of the cases occur below the age 40. In this case report we discuss a young 20-year-old female presenting with 90% plasma cells on bone marrow biopsy and presence of factor X inhibitor.


[Orthopaedic management of long bones metastasis].
The recent progress in oncologic management of patients with metastatic disease has permitted a significant improvement of their life expectancy. Many of these patients will suffer from complications related to bone metastasis. Unfortunately an orthopaedic treatment is seldom offered to them, mainly because of the misconception that this would not bring them any benefice. However these patients are often good candidates for an orthopaedic management, which objectives are to relieve pain and to re-establish their quality of life. The available surgical techniques are well described and the management protocols are clearly defined, as are the expectable complications and the errors that must not be done.


Immunohistochemical detection of soluble immunoglobulins in living mouse small intestines using an in vivo cryotechnique.
Some morphological changes are inevitable during immersion- or perfusion-fixation and following alcohol-dehydration for tissue preparations. Common immunostaining techniques for these specimens have some limitations to capture accurate localizations of soluble proteins in cells and tissues. In this study, to examine in situ distributions of immunoglobulins (Igs), small intestinal tissues of living mice were prepared with our "in vivo cryotechnique" (IVCT). Thin sections were first stained with hematoxylin-eosin for morphology, and then some immunostainings were performed on serial sections for IgA, Ig kappa light chain, IgG1 heavy chain (IgG1), and IgM. Living morphological states of small intestinal tissues, including flowing erythrocytes and opening blood vessels, were observed on paraffin sections prepared with IVCT. IgA was immunolocalized in many plasma cells of the lamina mucosa propria, intestinal matrices, and also in epithelial cells of the intestinal villi and crypts. Both IgG1 and IgM immunoreactivities were mainly detected in blood vessels, whereas only IgG1 was also immunolocalized in interstitial matrices of mucous membranes. By perfusion-fixation and alcohol-dehydration, however, IgA immunoreactivity was observed in plasma cells, but not in epithelial cells or the lamina mucosa propria. Thus, IVCT was more useful to examine in vivo immunolocalizations of soluble Igs in small intestines.


[Detection of clinical diagnosis and different symptoms of Sjogren's syndrome by traditional chinese medicine (TCM)]
OBJECTIVE:To search for the appropriate diagnostic criteria of SS and confirm the differentiation of SS.METHODS:The European di agnostic criteria has been used in clinic work for about two years,and differentiated the symptoms of SS by TCM. The specialty and relationship between them was made an inquiry.RESULTS:The European criteria set for SS offers the clinic work a practical method to correctly classify the patients suspected of having this disorder. It refers to the signs and symptoms caused by the insufficiency of spleen-qi with deficiency of liver-yin and kidney-yin.CONCLUSION:It has been further proved for easy to make up the diagnostic of SS and its treatment using traditional chinese medicine.


Dentoskeletal changes induced by the Jasper jumper and cervical headgear appliances followed by fixed orthodontic treatment.
INTRODUCTION The objective of this controlled clinical study was to compare the dentoskeletal effects of the Jasper jumper with those of cervical headgear, when both are used with edgewise appliances to correct Class II Division 1 malocclusion. Lateral cephalograms of 75 patients were divided into 3 groups of 25. The control group included untreated Class II children with an initial mean age of 11.82 years (range, 9.35-14.84 years); they were followed without treatment for a mean period of 1.95 years (range, 0.90-3.95 years). The Jasper jumper group had an initial mean age of 11.86 years (range, 9.45-14.94 years); they were treated for a mean period of 1.96 years (range, 0.93-3.98 years). The cervical headgear group had an initial mean age of 12.29 years (range, 9.95-15.24 years); they were treated for an average of 1.88 years (range, 0.95-3.95 years). Comparison of the initial measurements showed that the 3 groups were similar at pretreatment, thus allowing direct comparisons. Analysis of variance (ANOVA) and the Tukey test were applied for comparison of the groups. Different appliances yielded specific effects on several components (skeletal and dentoalveolar) evaluated. Anterior maxillary growth was significantly restricted by the cervical headgear. Mandibular growth was similar in all 3 groups, although it was slightly greater in the Jasper jumper group. The experimental groups had similar improvements in maxillomandibular relationshipd. The pattern of craniofacial growth was not significantly different between groups. The most significant effect on the maxillary dentoalveolar component was retrusion of the maxillary incisors by the cervical headgear. The effects observed for the Jasper jumper group were primarily related to the mandibular dentoalveolar component, including labial tipping and protrusion of the mandibular incisors, and mesial movement and extrusion of the mandibular molars compared with the control group. The headgear appliance corrected the Class II malocclusion mostly by anterior maxillary restriction and maxillary dentoalveolar effects. Correction of the Class II malocclusion with the Jasper jumper appliance was largely due to mandibular dentoalveolar effects rather than skeletal effects.


Experimental Caryospora bigenetica (Apicomplexa: Eimeriidae) infections in swine (Sus scrofa).
Two Hampshire-Landrace crossbred pigs were found to contain developmental stages of Caryospora bigenetica following oral inoculation with 1 x 10(8) oocysts. One pig was given intramuscular injections of methylprednisolone acetate. Both pigs displayed clinical signs of dermal coccidiosis from 3 to 10 days after inoculation, including swollen jowls and hocks, bilateral ocular discharges, generalized erythema, and lethargy. Meronts and gamonts were observed histologically in numerous tissues including jowl, ear, footpad, tongue, and lung at 10 days postinoculation. The present study is the first report of C. bigenetica infections in swine.


Soil water availability influences the temperature response of photosynthesis and respiration in a grass and a woody shrub.
Seedlings of the shrub kānuka (Kunzea ericoides var. ericoides (A. Rich) J. Thompson) and the pasture grass brown top (Agrostis capillarus L.) were grown in intact soil cores in climate-controlled cabinets to analyse the thermal response of leaf-level carbon exchange at four levels of volumetric soil water content (θ). The objective was to resolve the combined effects of relatively rapid and short-term changes in θ and temperature on the thermal responses of both photosynthesis and respiration in these two contrasting plant types. Results showed that θ had a greater effect on the short-term temperature response of photosynthesis than the temperature response of respiration. The optimum value of θ for net photosynthesis was around 30% for both plants. The photosynthetic capacity of kānuka and the grass declined significantly when θ fell below 20%. The temperature sensitivity of photosynthesis was low at low soil water content and increased at moderate to high soil water content in both plant types. Statistical analysis showed that the temperature sensitivity of photosynthetic parameters was similar for both plant types, but the sensitivity of respiratory parameters differed. Respiratory capacity increased with increasing soil water content in kānuka but declined significantly when θ fell below 15%. There was no significant influence of soil water content on respiratory capacity in the grass. Collectively, our results indicate that θ influenced the temperature sensitivity of photosynthesis and respiration, and altered the balance between foliar respiration and photosynthetic capacity in both plant types.


Distinct Local and Global Functions of Aβ Low-Threshold Mechanoreceptors in Mechanical Pain Transmission.
The roles of Aβ low-threshold mechanoreceptors (LTMRs) in transmitting mechanical hyperalgesia and in alleviating chronic pain have been of great interest but remain contentious. Here we utilized intersectional genetic tools, optogenetics, and high-speed imaging to specifically examine functions of Split Cre labeled Aβ-LTMRs in this regard. Genetic ablation of Split Cre -Aβ-LTMRs increased mechanical pain but not thermosensation in both acute and chronic inflammatory pain conditions, indicating their modality-specific role in gating mechanical pain transmission. Local optogenetic activation of Split Cre -Aβ-LTMRs triggered nociception after tissue inflammation, whereas their broad activation at the dorsal column still alleviated mechanical hypersensitivity of chronic inflammation. Taking all data into consideration, we propose a new model, in which Aβ-LTMRs play distinctive local and global roles in transmitting and alleviating mechanical hyperalgesia of chronic pain, respectively. Our model suggests a new strategy of global activation plus local inhibition of Aβ-LTMRs for treating mechanical hyperalgesia.


Strain solitons and topological defects in bilayer graphene.
Bilayer graphene has been a subject of intense study in recent years. The interlayer registry between the layers can have dramatic effects on the electronic properties: for example, in the presence of a perpendicular electric field, a band gap appears in the electronic spectrum of so-called Bernal-stacked graphene [Oostinga JB, et al. (2007) Nature Materials 7:151-157]. This band gap is intimately tied to a structural spontaneous symmetry breaking in bilayer graphene, where one of the graphene layers shifts by an atomic spacing with respect to the other. This shift can happen in multiple directions, resulting in multiple stacking domains with soliton-like structural boundaries between them. Theorists have recently proposed that novel electronic states exist at these boundaries [Vaezi A, et al. (2013) arXiv:1301.1690; Zhang F, et al. (2013) arXiv:1301.4205], but very little is known about their structural properties. Here we use electron microscopy to measure with nanoscale and atomic resolution the widths, motion, and topological structure of soliton boundaries and related topological defects in bilayer graphene. We find that each soliton consists of an atomic-scale registry shift between the two graphene layers occurring over 6-11 nm. We infer the minimal energy barrier to interlayer translation and observe soliton motion during in situ heating above 1,000 °C. The abundance of these structures across a variety of samples, as well as their unusual properties, suggests that they will have substantial effects on the electronic and mechanical properties of bilayer graphene.


Optimality in a partitioned task performed by social insects.
Biologists have long been aware that adaptations should not be analysed in isolation from the function of the whole organism. Here, we address the equivalent issue at the scale of a social insect colony: the optimality of component behaviours in a partitioned sequence of tasks. In colonies of Atta colombica, a leaf-cutting ant, harvested leaf tissue is passed from foragers to nest workers that distribute, clean, shred and implant the tissue in fungal gardens. In four laboratory colonies of A. colombica, we found that the highest colony-wide rate of leaf tissue processing in the nest was achieved when leaf fragment sizes were suboptimal for individual delivery rate by foragers. Leaf-cutting ant colonies appear to compromise the efficiency of collecting leaf tissue in order to increase their ability to handle the material when it arrives in the nest. Such compromise reinforces the idea that behavioural adaptations, like adaptations in general, must be considered within the context of the larger entity of which they are a part.


A Mild and Direct Site-Selective sp2 C-H Silylation of (Poly)Azines.
A base-mediated protocol that allows for the site-selective sp2 C-H silylation of azines is described. This method is distinguished by its mild conditions, simplicity and excellent site-selective modulation for a diverse set of azines, even in the context of late-stage functionalization, while exhibiting orthogonal reactivity with classical silylation reactions.


Transmission comb of a distributed Bragg reflector with two surface dielectric gratings.
The transmission behaviour of a distributed Bragg reector (DBR) with surface dielectric gratings on top and bottom is studied. The transmission shows a comb-like spectrum in the DBR band gap, which is explained in the Fano picture. The number density of the transmission peaks increases with increasing number of cells of the DBR, while the ratio of the average full width at half maximum to the corresponding average free spectral range, being only few percent for both transversal electric and magnetic waves, is almost invariant. The transmission peaks can be narrower than 0.1 nm and are fully separated from each other in certain wavebands. We further prove that the transmission combs are robust against randomness in the heights of the DBR layers. Therefore, the proposed structure is a candidate for an ultra-narrow-band multichannel filter or polarizer.


Evidence for the multifocal origin of bilateral and advanced human serous borderline ovarian tumors.
Borderline ovarian tumors (BOTs), or ovarian tumors of low malignant potential, represent a distinct category of epithelial ovarian neoplasms that have a clinically more favorable outcome than invasive epithelial ovarian cancer. Histologically, BOTs and invasive ovarian carcinomas both show cellular proliferation and pleomorphism, but unlike invasive ovarian carcinomas, BOTs lack stromal invasion. Although serous BOTs are frequently confined to a single ovary at the time of diagnosis, bilateral or extra-ovarian spread occurs in 30-40% of cases. The purpose of this study is to determine whether bilateral or extraovarian serous borderline lesions are metastatic sites from the original tumor, or represent separate primary tumors. DNA specimens from multiple tumor sites and normal tissue controls were obtained in eight women with bilateral or extra-ovarian serous borderline tumors. The pattern of loss of heterozygosity at the androgen receptor locus on the X chromosome was evaluated in the multiple tumor sites. In addition, the pattern of X-chromosome inactivation was determined using HpaII restriction endonuclease digestion, followed by PCR amplification of the androgen receptor locus. Multifocality was determined when alternate patterns of X-chromosome inactivation occurred. In two of the eight patients, the left and right ovarian tumor sites had different androgen receptor alleles inactivated, indicating that the bilateral tumors derived independently. In a third patient, the X inactivation pattern in the left ovarian tumor differed from the two peritoneal implants, suggesting that the implants were separate primary tumors, and not metastatic, from the left ovarian tumor. The remaining five patients had the same pattern of loss of heterozygosity and X inactivation in the tumor sites studied. These results suggest that bilateral and advanced stage serous BOTs may be multifocal in origin. This result is in contrast to invasive epithelial ovarian cancer, which has been shown to be unifocal in origin.


Effects of rumen-protected pantothenate supplementation on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows.
Lactation performance of dairy cow has considerably increased with animal breeding and management improvement in recent years. Ruminal net synthesised pantothenic acid is insufficient to meet the requirement of high producing dairy cows. The objective was to investigate the effects of rumen-protected pantothenate (RPP) on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows. Dry matter (DM) intake tended to increase, whereas milk yields, milk fat percentage and yield, body condition score (BCS) changes and net energy output except for maintenance increased linearly with increasing RPP supplementation. Ruminal pH and ammonia N concentration tended to decrease, total VFA tended to increase, while acetate-to-propionate ratio increased linearly with increasing RPP supplementation. Digestibilities of DM, organic matter and crude protein increased linearly, but neutral detergent fibre and acid detergent fibre digestibility tended to increase. Blood glucose, total protein, non-esterified fatty acids, pantothenic acid, pantothenate kinase, succinyl CoA, acyl carrier protein and acetyl CoA also increased linearly with increasing RPP supplementation. The results indicated that supplementary RPP improved lactation performance, nutrient digestion and blood parameters in a dose-dependent manner, and the optimal dose was 12 g RPP per cow per day in the current study. © 2017 Society of Chemical Industry.


A comprehensive sediment dynamics study of a major mud belt system on the inner shelf along an energetic coast.
Globally mud areas on continental shelves are conduits for the dispersal of fluvial-sourced sediment. We address fundamental issues in sediment dynamics focusing on how mud is retained on the seabed on shallow inner shelves and what are the sources of mud. Through a process-based comprehensive study that integrates dynamics, provenance, and sedimentology, here we show that the key mechanism to keep mud on the seabed is the water-column stratification that forms a dynamic barrier in the vertical that restricts the upward mixing of suspended sediment. We studied the 1000 km-long mud belt that extends from the mouth of the Changjiang (Yangtze) River along the coast of Zhejiang and Fujian Provinces of China and ends on the west coast of Taiwan. This mud belt system is dynamically attached to the fluvial sources, of which the Changjiang River is the primary source. Winter is the constructive phase when active deposition takes place of fine-grained sediment carried mainly by the Changjiang plume driven by Zhe-Min Coastal Currents southwestward along the coast.


trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing.
The regulation of polymorphonuclear leukocyte (PMN) function by mechanical forces encountered during their migration across restrictive endothelial cell junctions is not well understood. Using genetic, imaging, microfluidic, and in vivo approaches, we demonstrated that the mechanosensor Piezo1 in PMN plasmalemma induced spike-like Ca2+ signals during trans-endothelial migration. Mechanosensing increased the bactericidal function of PMN entering tissue. Mice in which Piezo1 in PMNs was genetically deleted were defective in clearing bacteria, and their lungs were predisposed to severe infection. Adoptive transfer of Piezo1-activated PMNs into the lungs of Pseudomonas aeruginosa-infected mice or exposing PMNs to defined mechanical forces in microfluidic systems improved bacterial clearance phenotype of PMNs. Piezo1 transduced the mechanical signals activated during transmigration to upregulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4, crucial for the increased PMN bactericidal activity. Thus, Piezo1 mechanosensing of increased PMN tension, while traversing the narrow endothelial adherens junctions, is a central mechanism activating the host-defense function of transmigrating PMNs.


Alteration of Nrf2 and Glutamate Cysteine Ligase expression contribute to lesions growth and fibrogenesis in ectopic endometriosis.
The redox-sensitive nuclear factor erythroid-derived 2-like 2 (NRF2) controls endogenous antioxidant enzymes' transcription and protects against oxidative damage which is triggered by inflammation and known to favor progression of endometriosis. Glutamate Cysteine Ligase (GCL), a target gene of NRF2, is the first enzyme in the synthesis cascade of glutathione, an important endogenous antioxidant. Sixty-one patients, with thorough surgical examination of the abdominopelvic cavity, were recruited for the study: 31 with histologically-proven endometriosis and 30 disease-free women taken as controls. Expressions of NRF2 and GCL were investigated by quantitative RT-PCR and immunohistochemistry in eutopic and ectopic endometria from endometriosis-affected women and in endometrium of disease-free women. Ex vivo stromal and epithelial cells were extracted and purified from endometrial and endometriotic biopsies to explore expression of NRF2 and GCL in both stromal and epithelial compartments by western blot. Finally, in order to strengthen the role of NRF2 in endometriosis pathogenesis, we evaluated the drop of NRF2 expression in a mouse model of endometriosis using NRF2 knockout (NRF2-/-) mice. The mRNA levels of NRF2 and GCL were significantly lower in ectopic endometria of endometriosis-affected women compared to eutopic endometria of disease-free women. The immunohistochemical analysis confirmed the decreased expression of both NRF2 and GCL in ectopic endometriotic tissues compared to eutopic endometria of endometriosis-affected and disease-free women. Immunoblotting revealed a significant decreased of NRF2 and GCL expression in epithelial and stroma cells from ectopic lesions of endometriosis-affected women compared to eutopic endometria from controls. Using a murine model of endometriosis, NRF2-/- implants were more fibrotic compared to wild-type with an increased weight and volume. These findings indicate that expression of the transcription factor NRF2 and its effector GCL are both profoundly deregulated in endometriotic lesions towards increased growth and fibrogenetic processes.


An exploration of adolescent facial shape changes with age via multilevel partial least squares regression.
Multilevel statistical models represent the existence of hierarchies or clustering within populations of subjects (or shapes in this work). This is a distinct advantage over single-level methods that do not. Multilevel partial-least squares regression (mPLSR) is used here to study facial shape changes with age during adolescence in Welsh and Finnish samples comprising males and females. 3D facial images were obtained for Welsh and Finnish male and female subjects at multiple ages from 12 to 17 years old. 1000 3D points were defined regularly for each shape by using "meshmonk" software. A three-level model was used here, including level 1 (sex/ethnicity); level 2, all "subject" variations excluding sex, ethnicity, and age; and level 3, age. The mathematical formalism of mPLSR is given in an Appendix. Differences in facial shape between the ages of 12 and 17 predicted by mPLSR agree well with previous results of multilevel principal components analysis (mPCA); buccal fat is reduced with increasing age and features such as the nose, brow, and chin become larger and more distinct. Differences due to ethnicity and sex are also observed. Plausible simulated faces are predicted from the model for different ages, sexes and ethnicities. Our models provide good representations of the shape data by consideration of appropriate measures of model fit (RMSE and R2). Repeat measures in our dataset for the same subject at different ages can only be modelled indirectly at the lowest level of the model at discrete ages via mPCA. By contrast, mPLSR models age explicitly as a continuous covariate, which is a strong advantage of mPLSR over mPCA. These investigations demonstrate that multivariate multilevel methods such as mPLSR can be used to describe such age-related changes for dense 3D point data. mPLSR might be of much use in future for the prediction of facial shapes for missing persons at specific ages or for simulating shapes for syndromes that affect facial shape in new subject populations.


Skin biopsy as an aid to diagnosis of disorders of the nervous system without cutaneous manifestations.
There are several neurological diseases wherein skin biopsy is useful for diagnosis, even in the absence of skin involvement. Skin biopsy is especially relevant in diseases in which the metabolic error is unknown or has no available diagnostic biochemical test. Skin biopsy, being relatively noninvasive, obviates the need for an invasive procedure such as a brain biopsy. These disorders wherein skin biopsies are particularly useful include the progressive myoclonic epilepsies, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), neuroaxonal dystrophy, and small fiber neuropathies (SFN). We review the role of skin biopsy in such conditions with notes on preferred sites and techniques.


An Advanced but Traditional Technique of Transurethral Resection of the Prostate in Order not to Overlook Stage T1 Prostate Cancer.
A little deeper resection was done during transurethral resection of the prostate (TURP) for benign prostate hyperplasia (BPH) to fill the disparities of reported prevalence rates between latent and incidental prostate cancer, as well as in order not to overlook clinically significant incidental cancer. We performed TURP in 995 patients who were diagnosed to have BPH. With a routine TUR setup, first most of the transition and central zones were resected. Then a slightly deeper resection of the residual adenoma and the peripheral zone than in the usual TURP was made. Pathological specimens were collected from 6 different parts. Incidental cancer was diagnosed in 226 patients (22.7%). Gleason scores were distributed as follows: 6 or less in 150 cases (66.4%), 7 in 68 cases (30.1%), and 8 in 8 cases (3.5%). Even in the patients with lower prostate specific antigen (PSA), patients with incidental cancer and Gleason scores of 7 or more were 142 (21.2%) and 41 (28.9%) respectively at 0 < PSA < 4.0 ng/ml, and 95 (18.7%) and 26 (27.4%) respectively at 0 < PSA < 2.5 ng/ml. Multifocal/diffuse cancer was detected in 84 (37.2%) patients. With our method of advanced TURP, we detected incidental cancer at almost the same rate as reported in latent cancer. When TURP is performed, incidental cancer as well as to relieve voiding difficulties must not be overlooked, because there must be a considerable number of clinically significant incidental cancer of higher Gleason scores, and of multifocal/diffuse lesions.


The Subjective Postural Vertical Determined in Patients with Pusher Behavior During Standing.
The subjective postural vertical (SPV), i.e., the perceived upright orientation of the body in relation to gravity, is disturbed in patients with pusher behavior. So far, the SPV has been measured only when these patients were sitting, and the results were contradictory as regards the side of the SPV deviation. The objective was to investigate the SPV in patients with different degrees of severity of pusher behavior while standing. Eight stroke patients with pusher behavior, ten age-matched stroke patients without pusher behavior, and ten age-matched healthy control subjects were included. The SPV (SPV error, SPV range) was assessed in the pitch and the roll planes. Pusher behavior was classified with the Burke Lateropulsion Scale (BLS). In the pitch plane, the SPV range was significantly larger in pusher patients than in patients without pusher behavior or healthy controls. The SPV error was similar for groups. In the roll plane, the SPV error and the SPV range were significantly larger and more ipsilesionally tilted in the pusher group than in the other two groups. There was a significant correlation between the SPV error in the roll plane and the BLS score. The study revealed that patients with pusher behavior had an ipsilesional SPV tilt that decreased with decreasing severity of the behavior. The large uncertainty in verticality estimation in both planes indicates that their sensitivity for the perception of verticality in space is generally disturbed. These findings emphasize the importance of specific rehabilitation approaches to recalibrate the impaired inner model of verticality.


DA-EPOCH-R therapy for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements in a patient with renal dysfunction.
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double-hit lymphoma, has been reported as refractory to R-CHOP therapy and requires more intensive regimens. However, intensive and safe regimens for patients with renal dysfunction are unknown. Herein, we report the successful use of DA-EPOCH-R therapy for double-hit lymphoma in a 64-year-old man with renal dysfunction. The patient had lymphoma-induced bilateral ureteral obstruction. Although renal dysfunction remained after removing the obstruction using R-CHOP therapy, we completed six cycles of DA-EPOCH-R therapy without any major adverse events. DA-EPOCH-R therapy may be a safe regimen for renal dysfunction patients.


Multiclass classification of microarray data with repeated measurements: application to cancer.
Prediction of the diagnostic category of a tissue sample from its gene-expression profile and selection of relevant genes for class prediction have important applications in cancer research. We have developed the uncorrelated shrunken centroid (USC) and error-weighted, uncorrelated shrunken centroid (EWUSC) algorithms that are applicable to microarray data with any number of classes. We show that removing highly correlated genes typically improves classification results using a small set of genes.


Diabetes induces apoptosis in lymphocytes.
The occurrence of DNA fragmentation in lymphocytes obtained from alloxan-induced diabetic rats and diabetic patients was investigated. A high proportion of apoptotic lymphocytes in diabetic states may explain the impaired immune function in poorly controlled diabetic patients. Rat mesenteric lymph node lymphocytes were analysed for DNA fragmentation by using flow cytometry and agarose gel, and for chromatin condensation by Hoescht 33342 staining under different situations. Immediately after being obtained, the proportion of lymphocytes with fragmented DNA was twofold higher in alloxan-induced diabetic rats than in cells from control rats. After 48 h in culture, the occurrence of DNA fragmentation was also higher (81%) in cells from diabetic rats. Hoescht staining and fragmented DNA visualized in agarose gel were also higher in lymphocytes from alloxan-induced diabetic rats than in control cells. To investigate if this phenomenon also occurs in humans, blood lymphocytes from 14 diabetic subjects were examined. Similar results to those of rat lymphocytes were found in cells from diabetic patients immediately after being obtained and after 48 h in culture. The high occurrence of apoptosis in lymphocytes was accompanied by a reduced number of blood-circulating lymphocytes in diabetic patients. The involvement of low insulinaemia for the occurrence of apoptosis in lymphocytes was also examined. Insulin treatment markedly reduced the proportion of lymphocytes with fragmented DNA in alloxan-induced diabetic rats.


ICON: 3D reconstruction with 'missing-information' restoration in biological electron tomography.
Electron tomography (ET) plays an important role in revealing biological structures, ranging from macromolecular to subcellular scale. Due to limited tilt angles, ET reconstruction always suffers from the 'missing wedge' artifacts, thus severely weakens the further biological interpretation. In this work, we developed an algorithm called Iterative Compressed-sensing Optimized Non-uniform fast Fourier transform reconstruction (ICON) based on the theory of compressed-sensing and the assumption of sparsity of biological specimens. ICON can significantly restore the missing information in comparison with other reconstruction algorithms. More importantly, we used the leave-one-out method to verify the validity of restored information for both simulated and experimental data. The significant improvement in sub-tomogram averaging by ICON indicates its great potential in the future application of high-resolution structural determination of macromolecules in situ.


Platelet expression of PKCepsilon oncoprotein in myelofibrosis is associated with disease severity and thrombotic risk.
Myelofibrosis (MF) is the most aggressive Philadelphia-negative chronic myeloproliferative neoplasm (MPN) with high morbidity and mortality due to thrombo-hemorrhagic complications and leukemic transformation. MF is characterized by profound alterations of megakaryocytopoiesis, with consequent abnormalities in platelet number and function. We recently showed that the overexpression of the oncoprotein PKCepsilon plays a key role in the aberrant differentiation of MF megakaryocyte clone and that its levels correlate with disease burden. Moreover, our group previously demonstrated that PKCepsilon is over-expressed in platelets from patients with acute myocardial infarction (MI) and accounts for their increased reactivity. On these bases, we investigated here the activation state and PKCepsilon expression of MF platelets, testing potential correlations with thrombotic risk and disease aggressiveness. Platelets were isolated from peripheral blood samples of MF patients and healthy donors (HDs). Patients were stratified according to the IPSS/DIPSS risk category and history of cardiovascular events. Platelet activation was assessed by flow cytometry. PKCepsilon mRNA and protein levels were determined by real time-PCR and western blot. MF platelets circulate in an activated status and display significantly higher levels of PKCepsilon compared to HDs. In MF patients, PKCepsilon platelet levels were associated with high-risk disease as well as with a positive history of major cardiovascular events. PKCepsilon is configuring as the common denominator of neoplastic transformation and thrombus formation in MF. Overall, our data pinpoint PKCepsilon as a potential novel biomarker of disease aggressiveness and thrombotic risk in this hematologic neoplasm.


Disclosing the Interfacial Electrolyte Structure of Na-Insertion Electrode Materials: Origins of the Desolvation Phenomenon.
Among a variety of promising cathode materials for Na-ion batteries, polyanionic Na-insertion compounds are among the preferred choices due to known fast sodium transfer through the ion channels along their framework structures. The most interesting representatives are Na3V2(PO4)3 (NVP) and Na3V2(PO4)2F3 (NVPF), which display large Na+ diffusion coefficients (up to 10-9 m2 s-1 in NVP) and high voltage plateaux (up to 4.2 V for NVPF). While the diffusion in the solid material is well-known to be the rate-limiting step during charging, already being thoroughly discussed in the literature, interfacial transport of sodium ions from the liquid electrolyte toward the electrode was recently shown to be important due to complex ion desolvation effects at the surface. In order to fill the blanks in the description of the electrode/electrolyte interface in Na-ion batteries, we performed a molecular dynamics study of the local nanostructure of a series of carbonate-based sodium electrolytes at the NVP and the NVPF interfaces along with careful examination of the desolvation phenomenon. We show that the tightness of solvent packing at the electrode surface is a major factor determining the height of the free energy barrier associated with desolvation, which explains the differences between the NVP and the NVPF structures. To rationalize and emphasize the remarkable properties of this family of cathode materials, a complementary comparative analysis of the same electrolyte system at the carbon electrode interface was also performed.


[Optimal duration of anticoagulant treatment of venous thromboembolism].
RECURRENT THROMBOSIS VERSUS ANTICOAGULANT-RELATED BLEEDING: The optimal duration of anticoagulation for venous thromboembolism depends on the balance between the risk of thrombosis if anticoagulation is stopped, and the risk of bleeding if patients remain on treatment. In the past decade, five large well designed trials have been completed which have compared different durations of anticoagulation for the treatment of various categories of patients with venous thrombosis. In conjunction with the findings of a number of other prospective studies, these trials have helped to identify risk factors for recurrent venous thrombosis and anticoagulant-related bleeding, and have led to a better understanding of the optimal duration of therapy for individual patients. RISK OF RECURRENT THROMBOSIS: The risk of recurrent thrombosis is low if thrombosis was precipitated by a major reversible risk factor such as surgery. Patients with idiopathic thrombosis (no apparent risk factor) and those with persistent risk factors (e.g., cancer), have a high risk of recurrence. Some hereditary (e.g., protein C, S or antithrombin deficiency) and acquired (e.g., antiphospholipid antibodies) thrombophilic states are risk factors for recurrence independently of whether thrombosis was, or was not, provoked by a major risk factor. DURATION OF THERAPY: Patients with a low risk of recurrence should be anticoagulated for three months. Others should be treated from 6 months to indefinitely, depending on the balance between the risk of recurrence and the risk of bleeding in each individual patient.


The Need for Nicotine De-addiction Services among Newly Diagnosed Tobacco-Related Head and Neck Cancer Patients, South India.
This study aimed to determine the proportion of tobacco-related head and neck cancer patients in need of nicotine de-addiction services at the time of diagnosis and factors associated with it. Facility-based cross-sectional study was conducted in a tertiary care center. Tobacco-related head and neck cancer patients with a past and present history of tobacco usage registered in cancer clinic from March 2016 to February 2017 were recruited. Participants were interviewed using a pretested and semi-structured questionnaire to gather information on the socio-demographic, clinical characteristics, and tobacco usage. Data were entered in EpiData v3.1 and analyzed using STATA v14. Among 220 participants recruited in the study, 83% were males, 47% were >60 years of age, and 40% had no formal education. Around 49% were smoking tobacco during the treatment period, 41% used smokeless tobacco, and 10% used both smoking and smokeless. The majority (56%) of them had stage T4 tumors. Around 71% of participants required de-addiction services. Those of age more than 70 years (aRR (95%CI) 1.43 (1.1-1.9)), currently employed (aRR (95%CI) 1.5 (1.2-1.9)), living alone (aRR (95%CI) 1.6 (1.0-2.5)) or in a nuclear family (aRR (95%CI) 1.5 (1.2-2)), who initiated tobacco use at a younger age (aRR (95%CI) 1.5 (1.0-2.2) were in higher need of de-addiction services. The majority of tobacco-related head and neck cancer patients required nicotine de-addiction treatment. Hence de-addiction services should be established as an integral unit of cancer clinics.


Nutrigenes, functional genomics and systems biology.
Traditionally, the classic reductionist approach attributes functions to individual genes. For instance, this has involved the analysis of motifs or the amino acid sequences of single gene products. It is unclear how the products of particular collections genes act together to provide higher order functionality in health and disease. To address this higher order problem, the function of collections of genes, as opposed to "one gene at a time" has to be studied. Accordingly, a model system is needed to test systems biology. In our studies, we used the homocysteine-folate metabolism as a model system.


Anti-angiogenesis therapies: their potential in cancer management.
Angiogenesis plays an important role in normal animal growth and development. This process is also vital for the growth of tumors. Angiogenesis inhibitors have a different mechanism of action to traditional chemotherapy agents and radiation therapy. The angiogenesis inhibitors can act synergistically with conventional treatments and tend to have non-overlapping toxicities. There are four drugs which have a proven role in treating cancer patients. Bevacizumab is a humanized monoclonal antibody that binds to and neutralizes vascular endothelial growth factor (VEGF). Sunitinib and sorafenib inhibit multiple tyrosine kinase receptors that are important for angiogenesis. Thalidomide inhibits the activity of basic fibroblast growth factor-2 (bFGF). The licensed indications and the supporting evidence are discussed. Other drugs are currently being tested in clinical trials and the most promising of these drugs are discussed. Aflibercept, also known as VEGF-trap, is a recombinant fusion protein that binds to circulating VEGF. The vascular disrupting agents act by targeting established blood vessels. These exciting new treatments have the potential to transform the management of cancer.


Prospects of Gene Knockouts in the Functional Study of MAMP-Triggered Immunity: A Review.
Plants depend on both preformed and inducible defence responses to defend themselves against biotic stresses stemming from pathogen attacks. In this regard, plants perceive pathogenic threats from the environment through pattern recognition receptors (PRRs) that recognise microbe-associated molecular patterns (MAMPs), and so induce plant defence responses against invading pathogens. Close to thirty PRR proteins have been identified in plants, however, the molecular mechanisms underlying MAMP perception by these receptors/receptor complexes are not fully understood. As such, knockout (KO) of genes that code for PRRs and co-receptors/defence-associated proteins is a valuable tool to study plant immunity. The loss of gene activity often causes changes in the phenotype of the model plant, allowing in vivo studies of gene function and associated biological mechanisms. Here, we review the functions of selected PRRs, brassinosteroid insensitive 1 (BRI1) associated receptor kinase 1 (BAK1) and other associated defence proteins that have been identified in plants, and also outline KO lines generated by T-DNA insertional mutagenesis as well as the effect on MAMP perception-and triggered immunity (MTI). In addition, we further review the role of membrane raft domains in flg22-induced MTI in Arabidopsis, due to the vital role in the activation of several proteins that are part of the membrane raft domain theory in this regard.


TumorNext: A comprehensive tumor profiling assay that incorporates high resolution copy number analysis and germline status to improve testing accuracy.
The development of targeted therapies for both germline and somatic DNA mutations has increased the need for molecular profiling assays to determine the mutational status of specific genes. Moreover, the potential of off-label prescription of targeted therapies favors classifying tumors based on DNA alterations rather than traditional tissue pathology. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext, which can detect single nucleotide variants, small insertions and deletions in 142 genes that are frequently mutated in somatic and/or germline cancers. TumorNext also detects gene fusions and structural variants, such as tandem duplications and inversions, in 15 frequently disrupted oncogenes and tumor suppressors. The assay uses a matched control and custom bioinformatics pipeline to differentiate between somatic and germline mutations, allowing precise variant classification. We tested 170 previously characterized samples, of which > 95% were formalin-fixed paraffin embedded tissue from 8 different cancer types, and highlight examples where lack of germline status may have led to the inappropriate prescription of therapy. We also describe the validation of the Affymetrix OncoScan platform, an array technology for high resolution copy number variant detection for use in parallel with the NGS panel that can detect single copy amplifications and hemizygous deletions. We analyzed 80 previously characterized formalin-fixed paraffin-embedded specimens and provide examples of hemizygous deletion detection in samples with known pathogenic germline mutations. Thus, the TumorNext combined approach of NGS and OncoScan potentially allows for the identification of the "second hit" in hereditary cancer patients.


[The microcirculatory bed within the brain stem in the acute period of severe craniocerebral trauma].
The authors studied changes of the intrastem microcirculatory channel in 72 patients who died in various terms of the acute period of severe craniocerebral trauma. According to the mechanism of the injury, an acceleration trauma had occurred in all cases. The microcirculatory channel was studied by filling it with an indicator mass (gelatin + india ink) and subsequent measurement of the length of the capillary network per 1 mm3 in various parts of the brain stem by the method suggested by S. M. Blinkov and G. D. Moiseev. As a control, a similar study was conducted in 20 individuals who died from extracranial injuries. Significant changes were revealed in the microcirculatory channel of the brain stem in the early period of craniocerebral trauma, and their periodization was established.


Mechanisms of ATPases--a multi-disciplinary approach.
ATPases are important molecular machines that convert the chemical energies stored in ATP to mechanical actions within the cell. ATPases are among the most abundant proteins with diverse functions involved in almost every cellular pathway. The well characterised ATPases include the various motor proteins responsible for cargo transfers, cell motilities, and muscle contractions; the protein degradation machinery - the proteasome; the ATP synthase, F-ATPase; and the chaperone systems. Other ATPases include DNA helicases and DNA replication complex; proteins responsible for protein/complex disassembly; and certain gene regulators. It is beyond the scope of this review to cover the complete range of ATPases. Instead, we will focus on a few representative ATPases, chosen based on their diverse mechanisms and properties. Furthermore, this review is by no means trying to cover comprehensively the literature for each ATPase nor the historical aspects in each field. We will focus on describing the various techniques being employed to derive the mechanisms and properties of the chosen ATPases. Among them, high and low resolution structural studies combined with biochemical assays seem to be the dominant technical advances adapted to reveal mechanisms for most of the ATPases except the bacterial sigma54 activators, whose mechanism of action is mostly derived from large amount of biochemical studies. A number of them, especially the F-ATPase and motor proteins, have been studied successfully by various single molecule and imaging techniques. We will therefore discuss them in greater details in order to describe the wide range techniques being utilised.