The Hypoxic Proteome and Metabolome of Barley (Hordeum vulgare L.) with and without Phytoglobin Priming.
Overexpression of phytoglobins (formerly plant hemoglobins) increases the survival rate of plant tissues under hypoxia stress by the following two known mechanisms: (1) scavenging of nitric oxide (NO) in the phytoglobin/NO cycle and (2) mimicking ethylene priming to hypoxia when NO scavenging activates transcription factors that are regulated by levels of NO and O2 in the N-end rule pathway. To map the cellular and metabolic effects of hypoxia in barley (Hordeum vulgare L., cv. Golden Promise), with or without priming to hypoxia, we studied the proteome and metabolome of wild type (WT) and hemoglobin overexpressing (HO) plants in normoxia and after 24 h hypoxia (WT24, HO24). The WT plants were more susceptible to hypoxia than HO plants. The chlorophyll a + b content was lowered by 50% and biomass by 30% in WT24 compared to WT, while HO plants were unaffected. We observed an increase in ROS production during hypoxia treatment in WT seedlings that was not observed in HO seedlings. We identified and quantified 9694 proteins out of which 1107 changed significantly in abundance. Many proteins, such as ion transporters, Ca2+-signal transduction, and proteins related to protein degradation were downregulated in HO plants during hypoxia, but not in WT plants. Changes in the levels of histones indicates that chromatin restructuring plays a role in the priming of hypoxia. We also identified and quantified 1470 metabolites, of which the abundance of >500 changed significantly. In summary the data confirm known mechanisms of hypoxia priming by ethylene priming and N-end rule activation; however, the data also indicate the existence of other mechanisms for hypoxia priming in plants.


Perception of male gender preference among pregnant igbo women.
Male gender preference is a dominant feature of Igbo culture and could be the reason behind women seeking fetal gender at ultrasound. The aim of this study is to investigate the perception of prenatal ultrasound patients of male gender preference in a patriarchal and gender sensitive society. The study was a cross-sectional survey, which targeted pregnant women who presented for prenatal ultrasound at four selected hospitals in Anambra State. A convenience sample size of 790 pregnant women constituted the respondents. The data collection instrument was a 13-item semi-structured self-completion questionnaire designed in line with the purpose of the study. Descriptive and inferential statistical analyses were carried out with statistical significance being considered at P < 0.05. Most of the women (88.4%, 698/790) were aware that fetal gender can be determined during the prenatal ultrasound while just over half of them (61.0%, 482/790) wanted fetal gender disclosed to them during prenatal ultrasound. More than half (58.6%, 463/790) of the women desired to have male babies in their present pregnancies while 20.1% (159/790) desired female babies and 21.3% (168/790) did not care if the baby was male or female. Some of the women (22.2%, 175/790) wanted to have male babies in their present pregnancies for various reasons predominant of which was protecting their marriages and cementing their places in their husbands' hearts. Male gender preference was strongly perceived. There was considerable anxiety associated with prenatal gender determination and moderate loss of interest in the pregnancy associated with disclosure of undesired fetal gender. Socio-demographic factors had significant influence on perception of male gender preference. Male gender preference is strongly perceived among Igbo women and its perception is significantly influenced by socio-demographic factors. Male gender preference may be responsible for Igbo women seeking fetal gender at ultrasound.


Genetic complementation of the Saccharomyces cerevisiae leu2 gene by the Escherichia coli leuB gene.
The leucine operon of Escherichia coli was cloned on a plasmid possessing both E. coli and Saccharomyces cerevisiae replication origins. This plasmid, pEH25, transformed leuA, leuB, and leuD auxotrophs of E. coli to prototrophy; it also transformed leu2 auxotrophs of S. cerevisiae to prototrophy. beta-Isopropylmalate dehydrogenase was encoded by the leuB gene of E. coli and the leu2 gene of yeast. Verification that the leuB gene present on pEH26 was responsible for complementing yeast leu2 was obtained by isolating in E. coli several leuB mutations that resided on the plasmid. These mutant leuB- plasmids were no longer capable of complementing leu2 in S. cerevisiae. We conclude that S. cerevisiae is capable of transcribing at least a portion of the polycistronic leu operon of E. coli and can translate a functional protein from at least the second gene of this operon. The yeast Leu+ transformants obtained with pEH25, when cultured in minimal medium lacking leucine, grew with a doubling time three to four times longer than when cultured in medium supplemented with leucine.


[Idiopathic chronic pancreatitis (with diffuse stenosis of Wirsung's duct) in ulcerative colitis].
We describe a case of chronic idiopathic pancreatitis associated with ulcerative colitis. Pancreatitis is a rare extra-intestinal manifestations of inflammatory bowel disease. Chronic idiopathic pancreatitis associated with ulcerative colitis are usually painless, without calcification, with stricture of the main pancreatic duct and with severe exocrine pancreatic insufficiency.


Haemostatic Profile of Patients with Chronic Liver Disease- its Correlation with Severity and Outcome.
The liver plays an important role in the haemostatic system as it synthesizes the majority of coagulation factors and fibrinolytic proteins. The present study was planned to determine the range of haemostatic defects in patients of chronic liver diseases. Test performed included Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), Thrombin Time (TT), Fibrinogen, Protein C, D Dimer and platelet count. Comparisons between groups frequencies and groups means were made using Chi-square test and Student's t-test, respectively. In cirrhosis group PT, aPTT, TT and D Dimer level were significantly increased compared to Chronic Hepatitis (CH) and control group (p<0.001 for all comparisons). Serum fibrinogen, Protein C and platelet count were significantly reduced in cirrhosis patients compared to CH and control group. (p<0.001 for all comparisons). All studied coagulation parameters were within normal limit in CH group. However, statistically significant difference was found in protein C and mean platelet count in CH group compared to control (p=0.03 and p<0.001 respectively). No evidence of bleeding or thrombosis was present in study group. In cirrhosis patients severe derangement in both anti and procoagulant factors occurs. Haemostatic profile in chronic hepatitis patient remains within normal limits.


[The underlying cause of kidney disease is often unknown in dialysis patients: a possible genomic approach].
As much as 16-17% European and American patients on renal replacement therapy do not have a conclusive diagnosis of the cause of their renal failure. This may have important implications on the types of morbidity they can develop in case of systemic diseases with extrarenal involvement, or recurrent renal diseases in transplanted patients. A better knowledge of the underlying disease can have important prognostic and therapeutic repercussions. In this study we evaluated the rate of uremic patients who can benefit from a genomic diagnostic approach. Patients liable to a future genomic diagnostic study were selected based on two criteria: (i) age of dialysis entry less or equal to 55 years, and (ii) presence of a non-conclusive diagnosis. Based on the data extracted from the REGDIAL registry, we analyzed 534 patients undergoing renal replacement therapy. We identified 300 patients with age of entry into replacement therapy <55 years (56.2% of the overall study population). Among these, we identified 107 patients with missing or inconclusive diagnosis, which was equal to 20% of the overall population. Of these patients, 32.8% reported a positive family history of kidney disease. This study confirms that a significant proportion of patients on renal replacement therapy do not have an etiological diagnosis and may be subject to a genomic evaluation. With the increasing availability of genomic sequencing technology and the falling of related costs, nephrologists will be increasingly inclined to incorporate clinical genetic testing into their diagnostic armamentarium. There is therefore a need for in-depth, multicenter studies aimed at developing evidence-based guidelines, clear indications and at confirming the usefulness of genetic testing in nephrology.


Role of calcium in cAMP-mediated effects in the elasmobranch rectal gland.
The effects of A23187 and verapamil on the vasomotor and secretory effects of adenosine 3',5'-cyclic monophosphate (cAMP) in the rectal gland were investigated in Scyliorhinus canicula and Squalus acanthias. A23187 was a potent vasoconstrictor in the gland and reversed the vasodilatory action of cAMP in glands constricted with norepinephrine. Verapamil, like cAMP, prevented the vasoconstriction induced in the gland by norepinephrine. A23187 had no effect on the secretory activity (measured as ouabain binding and ouabain-sensitive oxygen consumption) of the glands. Verapamil inhibited the stimulation of ouabain binding, ouabain-sensitive oxygen consumption, and sodium secretion rate induced by cAMP plus theophylline, but did not affect the stimulation of ouabain binding and ouabain-sensitive oxygen consumption induced by amphotericin B. These data indicate that it is the cAMP-induced stimulation of the sodium-chloride cotransport system that is verapamil sensitive, and it is suggested that this stimulation is a calcium-dependent process. This emphasizes the independent nature of the secretory and vasomotor effects of the nucleotide in the gland.


Work-related stress and psychosomatic medicine.
This article introduces key concepts of work-related stress relevant to the clinical and research fields of psychosomatic medicine. Stress is a term used to describe the body's physiological and/or psychological reaction to circumstances that require behavioral adjustment. According to the Japanese National Survey of Health, the most frequent stressors are work-related problems, followed by health-related and then financial problems. Conceptually, work-related stress includes a variety of conditions, such as overwork, unemployment or job insecurity, and lack of work-family balance. Job stress has been linked to a range of adverse physical and mental health outcomes, such as cardiovascular disease, insomnia, depression, and anxiety. Stressful working conditions can also impact employee well-being indirectly by directly contributing to negative health behaviors or by limiting an individual's ability to make positive changes to lifestyle behaviors, such as smoking and sedentary behavior. Over the past two decades, two major job stress models have dominated the occupational health literature: the job demand-control-support model and the effort-reward imbalance model. In both models, standardized questionnaires have been developed and frequently used to assess job stress. Unemployment has also been reported to be associated with increased mortality and morbidity, such as by cardiovascular disease, stroke, and suicide. During the past two decades, a trend toward more flexible labor markets has emerged in the private and public sectors of developed countries, and temporary employment arrangements have increased. Temporary workers often complain that they are more productive but receive less compensation than permanent workers. A significant body of research reveals that temporary workers have reported chronic work-related stress for years. The Japanese government has urged all employers to implement four approaches to comprehensive mind/body health care for stress management in the workplace: focusing on individuals, utilizing supervisory lines, enlisting company health care staff, and referring to medical resources outside the company. Good communications between occupational health practitioners and physicians in charge in hospitals/clinics help employees with psychosomatic distress to return to work, and it is critical for psychosomatic practitioners and researchers to understand the basic ideas of work-related stress from the viewpoint of occupational health.


Determining the False-Negative Rate Using Fluorescence Image-Assisted Sentinel Lymph Node Biopsy in Cutaneous Melanoma.
Despite the advances in cutaneous melanoma management, the false-negative rates (FNRs) of sentinel lymph node biopsy (SLNB) are still high. These rates are dependent not only on the technique but also on definitional terms and percentage of head/neck melanoma (highest false-negative SLNB). Fluorescence imaging technology is well acquainted in plastic surgery and other specialties. Having demonstrated that fluorescence-assisted SLNB is effective in melanoma, we are interested in determining its FNR. We obtained institutional review board approval to follow up prospectively all patients with cutaneous melanoma who underwent radioisotope/fluorescence-assisted SLNB with the intent to capture 100 negative SLNB patients. Inclusion criteria were as follows: (1) National Comprehensive Cancer Network criteria; (2) an SLNB report; (3) at least 24 months of follow-up in the negative SLNB group. The outcome variables were FNR and adjusted FNR of SLNB, considering the criterion standard of assessing the accuracy of SNLB. The FNR was defined as the proportion of patients with false-negative SLNB to patients with true-positive and false-negative SLNB [false negative/(false negative + true positive)]. Adjusted FNR refers to the previously described false-negative SLNB, but in the absence of local/in-transit recurrence or distant metastases. Furthermore, false-negative incidence (false-negative/negative SLNB patients) was also calculated. Length of follow-up was date of surgery to the date of last follow-up/death. A total of 125 participants, with 52.0% being male and 48.0% being female, were included. One hundred patients had an SLNB negative for metastases, whereas the rest had positive SLNB results. Median follow-up time of the cohort and that of the negative SLNB group were 36.7 (2.6-58.5) and 37.9 (24.0-58.5) months, respectively. A relatively high number (24.8%) of head/neck melanoma were included. We identified 2 cases of false-negative SLNB, with one having in-transit metastases. Thus, the FNR and adjusted FNR were 7.4% and 3.7%, respectively. The false-negative incidence and adjusted false-negative incidence were 2.0% and 1.0%, respectively. This is the first prospective study examining the FNR of fluorescence-assisted SLNB for patients with cutaneous melanoma. Our study reveals that this technique has one of the lowest FNRs published, especially considering the large percentage of participants with head/neck melanoma involved.


Galiellalactone is a direct inhibitor of the transcription factor STAT3 in prostate cancer cells.
The transcription factor STAT3 is constitutively active in several malignancies including castration-resistant prostate cancer and has been identified as a promising therapeutic target. The fungal metabolite galiellalactone, a STAT3 signaling inhibitor, inhibits the growth, both in vitro and in vivo, of prostate cancer cells expressing active STAT3 and induces apoptosis of prostate cancer stem cell-like cells expressing phosphorylated STAT3 (pSTAT3). However, the molecular mechanism of this STAT3-inhibiting effect by galiellalactone has not been clarified. A biotinylated analogue of galiellalactone (GL-biot) was synthesized to be used for identification of galiellalactone target proteins. By adding streptavidin-Sepharose beads to GL-biot-treated DU145 cell lysates, STAT3 was isolated and identified as a target protein. Confocal microscopy revealed GL-biot in both the cytoplasm and the nucleus of DU145 cells treated with GL-biot, appearing to co-localize with STAT3 in the nucleus. Galiellalactone inhibited STAT3 binding to DNA in DU145 cell lysates without affecting phosphorylation status of STAT3. Mass spectrometry analysis of recombinant STAT3 protein pretreated with galiellalactone revealed three modified cysteines (Cys-367, Cys-468, and Cys-542). Here we demonstrate with chemical and molecular pharmacological methods that galiellalactone is a cysteine reactive inhibitor that covalently binds to one or more cysteines in STAT3 and that this leads to inhibition of STAT3 binding to DNA and thus blocks STAT3 signaling without affecting phosphorylation. This further validates galiellalactone as a promising direct STAT3 inhibitor for treatment of castration-resistant prostate cancer.


Effect of the Hofmeister anions upon the swelling of a self-assembled pH-responsive hydrogel.
We report the effect of a range of monovalent sodium salts on the molecular equilibrium swelling of a simple synthetic microphase separated poly(methyl methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate)-block-poly(methyl methacrylate) (PMMA(88)-b-PDEA(223)-b-PMMA(88)) pH-responsive hydrogel. Sodium acetate, sodium chloride, sodium bromide, sodium iodide, sodium nitrate and sodium thiocyanate were selected for study at controlled ionic strength and pH; all salts are taken from the Hofmeister series (HS). The influence of the anions on the expansion of the hydrogel was found to follow the reverse order of the classical HS. The expansion ratio of the gel measured in solutions containing the simple sodium halide salts (NaCl, NaBr, and NaI) was found to be strongly related to parameters which describe the interaction of the ion with water; surface charge density, viscosity coefficient, and entropy of hydration. A global study which also included nonspherical ions (NaAce, NaNO(3) and NaSCN) showed the strongest correlation with the viscosity coefficient. Our results are interpreted in terms of the Collins model, where larger ions have more mobile water in the first hydration cage immediately surrounding the gel, therefore making them more adhesive to the surface of the stationary phase of the gel and ultimately reducing the level of expansion.


Degeneration of cortical function in the Royal College of Surgeons rat.
The purpose of the current study was to determine the progress of cortical functional degeneration in the Royal College of Surgeons (RCS) rat. Cortical responses were measured with optical imaging of intrinsic signals using gratings of various spatial frequencies. Subsequently, electrophysiological recordings were also taken across cortical layers in response to a pulse of broad-spectrum light. We found significant degeneration in the cortical processing of visual information as early as 4 weeks of age. These results show that degeneration in the cortical response of the RCS rat starts before development has been properly completed.


Schwannoma of the pancreas: a report of two cases and a review of the literature.
Schwannoma of the pancreas is a rare neoplasm. It generally affects older adults (average age, 60 yr). The sex incidence is equal. These tumors vary considerably in size and approximately two-thirds are partially cystic, which can cause clinical confusion with epithelial neoplasms. Histologically, they are typical schwannomas, with Antoni A and Antoni B areas, and they do not cause undue diagnostic problems once adequate tissue is examined histologically.


[Breaking of distractors of the Harrington type after surgical treatment of scoliosis].
180 patients with scoliosis (aged 12-29 years) were subjected to the correction of deformation by means of the Harringtone type distractors and spondylodesis with utilization of osseous transplants. In 24 of them (13,3%) the distractor has been broken in different terms after the operation. The danger of the break increases with the age of the patients and abruptly increases in case of scoliosis of the V degree (in excess of 90 degrees) and in case of necessity to bend the distractor to correct the kyphoscoliosis. The distractor break is associated not with the material structure but with the rod design.


Estrogen regulates myogenic tone in hippocampal arterioles by enhanced basal release of nitric oxide and endothelial SK Ca channel activity.
Arteries and arterioles exhibit myogenic tone, a partially constricted state that allows further constriction or dilation in response to moment-to-moment fluctuations in blood pressure. The vascular endothelium that lines the internal surface of all blood vessels controls a wide variety of essential functions, including the contractility of the adjacent smooth muscle cells by providing a tonic vasodilatory influence. Studies conducted on large (pial) arteries on the surface of the brain have shown that estrogen lowers myogenic tone in female mice by enhancing nitric oxide (NO) release from the endothelium, however, whether this difference extends to the intracerebral microcirculation remains ambiguous. The existing incomplete picture of sex differences in cerebrovascular physiology combined with a deficiency in treatments that fully restore cognitive function after cerebrovascular accidents places heavy emphasis on the necessity to investigate myogenic tone regulation in the microcirculation from both male and female mice. We hypothesized that sex-linked hormone regulation of myogenic tone extends its influence on the microcirculation level, and sought to characterize it in isolated arterioles from the hippocampus, a major cognitive brain area. Using diameter measurements both in vivo (acute cranial window vascular diameter) and ex vivo (pressure myography experiments), we measured lower myogenic tone responses in hippocampal arterioles from female than male mice. By using a combined surgical and pharmacological approach, we found myogenic tone in ovariectomized (OVX) female mice matches that of males, as well as in endothelium-denuded arterioles. Interestingly, eNOS inhibition induced a larger constriction in female arterioles but only partially abolished the difference in tone. We identified that the remnant difference was mediated by a higher activity and expression of the small-conductance Ca 2+ -sensitive K + (SK) channels. Collectively, these data indicate that eNOS and SK channels exert greater vasodilatory influence over myogenic tone in female mice at physiological pressures.


Poly(malic acid) bearing Doxorubicin and N-Acetyl Galactosamine as a site-specific prodrug for targeting hepatocellular carcinoma.
In the past, several systems of drug delivery carriers have been designed with a high capacity to target specific cells and/or tissues and a reduced non-specific toxicity. In this context, we synthesized and characterized novel poly(malic acid) derivatives bearing Doxorubicin (Dox), Poly(ethylene glycol) (PEG) and/or N-Acetyl Galactosamine (NAcGal) for drug delivery. These poly(malic acid) derivatives were obtained by chemical modification of the carboxylic acid lateral groups of poly(malic acid) (PMLA). The resulting nanoplatforms were evaluated for their in vitro cytotoxicity using the human HepaRG hepatoma cell line. Results reveal that the PMLA nanoplatform modified with PEG and Dox has an IC50 of 936 nM corresponding to a Dox concentration of 47 nM, while the grafting of NAcGal onto the nanoplatform reduced the IC50 to 527 nM corresponding to a Dox concentration of 26 nM. The presence of the targeting moiety, NAcGal, thus improves the cellular toxicity of the Dox.


Acetabular reconstruction in patients with low and high dislocation: 20- to 32-year survival of an impaction grafting technique (named cotyloplasty).
We report the results at a mean of 24.3 years (20 to 32) of 61 previously reported consecutive total hip replacements carried out on 44 patients with severe congenital hip disease, performed with reconstruction of the acetabulum with an impaction grafting technique known as cotyloplasty. The mean age of the patients at operation was 46.7 years (23 to 68) and all were women. The patients were followed post-operatively for a mean of 24.3 years (20 to 32), using the Merle d'Aubigné and Postel scoring system as modified by Charnley, and with serial radiographs. At the time of the latest follow-up, 28 acetabular components had been revised because of aseptic loosening at a mean of 15.9 years (6 to 26), and one at 40 days after surgery because of repeated dislocations. The overall survival rate for aseptic failure of the acetabular component at ten years was 93.1% (95% confidence interval (CI) 86.5 to 96.7) when 53 hips were at risk, and at 23 years was 56.1% (95% CI 49.4 to 62.8), when 22 hips remained at risk. These long-term results are considered satisfactory for the reconstruction of an acetabulum presenting with inadequate bone stock and circumferential segmental defects.


Effect of lower limb strength on falls and balance of the elderly.
To assess the effect of lower limb strength on falls and balance in community-dwelling elderly persons by a health status questionnaire, evaluation of lower limb strength and balance. A total of 86 subjects (age 69.8±5.3) were categorized into one of two groups, "Fallers" and "Non-fallers". Thirty one participants who had reported the experience of having fallen unexpectedly at least once in the past year were assigned into the group "Fallers", and the remaining 55 subjects having no fall history in the past year, "Non-fallers". A self-assessment questionnaire was taken. Lower limb strength was measured by a "Chair stand test". Balance was measured by the stability index of the fall risk test protocol of Balance System SD® (Biodex, New York, USA). The differences between the two groups were compared and the correlation between lower limb strength and balance were analyzed. The questionnaire demonstrated no significant differences between two groups. The "Chair stand test" showed a significantly less for the "Fallers" (p<0.05). The stability index was significantly greater in the "Fallers" group (p<0.05). There was a moderate negative correlation between the "Chair stand test" and the "Stability index" (R=-0.576, p<0.01). This study suggests that the "Chair stand test" is a useful screening process for lower limb strength which correlates to risk for falls and balance in the elderly.


Developing a Web-Based Cost Assessment Tool for Colorectal Cancer Screening Programs.
We developed a web-based cost assessment tool (CAT) to collect cost data as an improvement from a desktop instrument to perform economic evaluations of the Centers for Disease Control and Prevention's (CDC's) Colorectal Cancer Control Program (CRCCP) grantees. We describe the development of the web-based CAT, evaluate the quality of the data obtained, and discuss lessons learned. We developed and refined a web-based CAT to collect 5 years (2009-2014) of cost data from 29 CRCCP grantees. We analyzed funding distribution; costs by budget categories; distribution of costs related to screening promotion, screening provision, and overarching activities; and reporting of screenings for grantees that received funding from non-CDC sources compared with those grantees that did not. CDC provided 85.6% of the resources for the CRCCP, with smaller amounts from in-kind contributions (7.8%), and funding from other sources (6.6%) (eg, state funding). Grantees allocated, on average, 95% of their expenditures to specific program activities and 5% to other activities. Some non-CDC funds were used to provide screening tests to additional people, and these additional screens were captured in the CAT. A web-based tool can be successfully used to collect cost data on expenditures associated with CRCCP activities. Areas for future refinement include how to collect and allocate dollars from other sources in addition to CDC dollars.


Efficacy of a multiple diode laser system for body contouring.
Low-level laser therapy (LLLT) has been shown to induce cellular reactions in nonphotosynthetic cells however skepticism remains regarding efficacy at the clinical level. The purpose of this study was to evaluate the efficacy of LLLT independent of liposuction. Additionally, a weight loss supplement (Curva™, Santa Barbra Medical Innovations, Santa Barbra, CA) was evaluated. This clinical trial evaluates the effectiveness of the Erchonia EML Laser (Zerona™ System, Santa Barbra Medical Innovations) for non-invasive fat reduction and body contouring in a split-body clinical evaluation. Five subjects were enrolled and completed the study. Subjects had a body mass index (BMI) of less than or equal to 29 kg/m(2) and satisfied the set inclusion criteria. Participants were randomly assigned to receive low-level laser treatments on one side of the body three times per week for 2 weeks. One group took the weight loss supplement and was also treated with the laser. Subject satisfaction questionnaires, physician blinded photo evaluation, circumference measurements and ultrasound measurements were utilized to evaluate efficacy. Circumference measurements revealed no statistically significant reduction at either 7 days or 1 month post-treatment. One month following treatment the greatest circumference reduction overall was 0.5 ± 0.3 inches. Ultrasound measurements also did not reveal statistically significant reduction in fat layer thickness (P > 0.5). Evaluation by three blinded dermatologists resulted in average correct photo identification of 51.1%. Results reflect little clinical difference between post-treatment and baseline images. Three subjects recording a "dissatisfied" rating on satisfaction questionnaires and all subjects reported the effects of the treatment were less than expected. Subjects who took the weight loss supplement had no greater circumference reduction or identifiable clinical outcome. This small study demonstrates to the authors that there needs to be more evidence to show clinical circumferential reduction before LLLT can be recommended as an effective therapeutic option.


Neutralizing murine TGFβR2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis.
Elevated levels of TGFβ are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFβ pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFβ remains challenging because TGFβ has tumor suppressor functions in many epithelial malignancies, including pancreatic cancer. In fact, direct neutralization of TGFβ promotes tumor progression of genetic murine models of pancreatic cancer. Here, we report that neutralizing the activity of murine TGFβ receptor 2 using a monoclonal antibody (2G8) has potent antimetastatic activity in orthotopic human tumor xenografts, syngeneic tumors, and a genetic model of pancreatic cancer. 2G8 reduced activated fibroblasts, collagen deposition, microvessel density, and vascular function. These stromal-specific changes resulted in tumor cell epithelial differentiation and a potent reduction in metastases. We conclude that TGFβ signaling within stromal cells participates directly in tumor cell phenotype and pancreatic cancer progression. Thus, strategies that inhibit TGFβ-dependent effector functions of stromal cells could be efficacious for the therapy of pancreatic tumors. Cancer Res; 74(18); 4996-5007. ©2014 AACR.


Colloid cohydration and variable rate phenylephrine infusion effectively prevents postspinal hypotension in elective Cesarean deliveries.
Prevention of post-spinal hypotension in obstetric patients can be accomplished using intravenous fluid expansion and prophylactic use of sympathomimetic drugs. The affect of combination of colloids and phenylephrine infusion on maternal hemodynamics has not been widely studied and there is no consensus about the dosage required and time of starting its administration. This prospective, randomized, double-blind study enrolled 90 healthy term parturients undergoing elective Cesarean delivery under lumbar subarachnoid block (0.5% hyperbaric bupivacaine 10 mg with fentanyl 25 μg). Patients in Group A received prophylactic intravenous phenylephrine infusion (60 μg/minute) along with hydroxyl-ethyl-starch cohydration (6% HES 130/0.42;15 ml/kg) immediately after subarachnoid block. In Group B, patients received 6% HES cohydration and intermittent intravenous 50 μg boluses of phenylephrine. The efficacy of these in maintaining maternal SBP at 90-110% of baseline and neonatal well-being was evaluated. In Group B, 75.5% of patients required rescue phenylephrine boluses to maintain SBP while maternal hemodynamics were well maintained in Group A and rescue drug was not needed. Reactive hypertension occurred in one patient (2.2%) and bradycardia in two patients (4.4%) in Group A. Six patients complained of nausea in Group B (13.3%) compared to one in Group A. All the newborns had normal Apgar scores and Umbilical arterial pH > 7.2. A combination of colloid cohydration and prophylactic phenylephrine infusion initiated at 60 μg/minute maintained maternal hemodynamics and neonatal well-being during Cesarean deliveries requiring minimum interventions by the anesthesiologist.


Protocol for the PATHOME study: a cohort study on urban societal development and the ecology of enteric disease transmission among infants, domestic animals and the environment.
Global morbidity from enteric infections and diarrhoea remains high in children in low-income and middle-income countries, despite significant investment over recent decades in health systems and water and sanitation infrastructure. Other types of societal development may be required to reduce disease burden. Ecological research on the influence of household and neighbourhood societal development on pathogen transmission dynamics between humans, animals and the environment could identify more effective strategies for preventing enteric infections. The 'enteric pathome'-that is, the communities of viral, bacterial and parasitic pathogens transmitted from human and animal faeces through the environment is taxonomically complex in high burden settings. This integrated cohort-exposure assessment study leverages natural socioeconomic spectrums of development to study how pathome complexity is influenced by household and neighbourhood infrastructure and hygiene conditions. We are enrolling under 12-month-old children in low-income and middle-income neighbourhoods of two Kenyan cities (Nairobi and Kisumu) into a 'short-cohort' study involving repeat testing of child faeces for enteric pathogens. A mid-study exposure assessment documenting infrastructural, behavioural, spatial, climate, environmental and zoonotic factors characterises pathogen exposure pathways in household and neighbourhood settings. These data will be used to inform and validate statistical and agent-based models (ABM) that identify individual or combined intervention strategies for reducing multipathogen transmission between humans, animals and environment in urban Kenya. The protocols for human subjects' research were approved by Institutional Review Boards at the University of Iowa (ID-202004606) and AMREF Health Africa (ID-ESRC P887/2020), and a national permit was obtained from the Kenya National Commission for Science Technology and Innovation (ID# P/21/8441). The study was registered on Clinicaltrials.gov (Identifier: NCT05322655) and is in pre-results stage. Protocols for research on animals were approved by the University of Iowa Animal Care and Use Committee (ID 0042302).


Impaired bacteriological responses in babies after maternal iron dextran infusion.
The effect of a total dose infusion of iron dextran in pregnancy on 15 mothers and their babies was compared with 19 controls. The bacteriostatic effect and opsonising ability of the sera, of babies born to the treated mothers, were considerably impaired. This was associated with a significantly lower transferrin concentration in these mothers. Although these in vitro tests were not associated with an increase in overt infection during the perinatal period, they suggest the need for caution in the use of total dose infusions in pregnancy.


Penetrating keratoplasty after epikeratophakia for keratoconus.
Seven patients underwent penetrating keratoplasty after epikeratophakia for keratoconus. All seven patients achieved clear grafts and 20/40 or better best corrected visual acuity after penetrating keratoplasty. Three of the seven patients had one or more episodes of rejection after penetrating keratoplasty; all were treated successfully. No grafts were lost. The results in terms of graft clarity and visual acuity are comparable with those in patients undergoing penetrating keratoplasty for keratoconus with no previous ocular surgery. Whether the relatively high rate of rejection episodes (three [43%]) seen in this small number of patients indicates some relationship between previous epikeratophakia and subsequent rejection after penetrating keratoplasty remains to be seen.


[Clinical practice of hereditary motor neuropathy (HMN) and hereditary sensory and autonomic neuropathy (HSAN)].
Inherited neuropathy is a genetically and clinically heterogeneous group of neuropathies, the main category becomes Charcot-Marie-Tooth neuropathy (CMT), also known as hereditary motor and sensory neuropathy (HMSN), distal hereditary motor neuropathy (dHMN), and hereditary sensory autonomic neuropathy (HSAN). At least 80 genes have been associated with CMT, HMN or HSAN, a precise molecular diagnosis is often needed to make a clinical diagnosis accurately, enable genetic counseling of the patient and understanding of their molecular mechanisms. To identify the mutation in each patient, using a high-throughput NGS, we established a diagnostic procedure involving screening of disease causing genes in CMT, HMN or HSAN.


DEC1 coordinates with HDAC8 to differentially regulate TAp73 and ΔNp73 expression.
P73, a member of the p53 family, plays a critical role in neural development and tumorigenesis. Due to the usage of two different promoters, p73 is expressed as two major isoforms, TAp73 and ΔNp73, often with opposing functions. Here, we reported that transcriptional factor DEC1, a target of the p53 family, exerts a distinct control of TAp73 and ΔNp73 expression. In particular, we showed that DEC1 was able to increase TAp73 expression via transcriptional activation of the TAp73 promoter. By contrast, Np73 transcription was inhibited by DEC1 via transcriptional repression of the ΔNp73 promoter. To further explore the underlying mechanism, we showed that DEC1 was unable to increase TAp73 expression in the absence of HDAC8, suggesting that HDAC8 is required for DEC1 to enhance TAp73 expression. Furthermore, we found that DEC1 was able to interact with HDAC8 and recruit HDAC8 to the TAp73, but not the ΔNp73, promoter. Together, our data provide evidence that DEC1 and HDAC8 in differentially regulate TAp73 and ΔNp73 expression, suggesting that this regulation may lay a foundation for a therapeutic strategy to enhance the chemosensitivity of tumor cells.


Identification of a tetrameric assembly domain in the C terminus of heat-activated TRPV1 channels.
Transient receptor potential (TRP) channels as cellular sensors are thought to function as tetramers. Yet, the molecular determinants governing channel multimerization remain largely elusive. Here we report the identification of a segment comprising 21 amino acids (residues 752-772 of mouse TRPV1) after the known TRP-like domain in the channel C terminus that functions as a tetrameric assembly domain (TAD). Purified recombinant C-terminal proteins of TRPV1-4, but not the N terminus, mediated the protein-protein interaction in an in vitro pulldown assay. Western blot analysis combined with electrophysiology and calcium imaging demonstrated that TAD exerted a robust dominant-negative effect on wild-type TRPV1. When fused with the membrane-tethered peptide Gap43, the TAD blocked the formation of stable homomultimers. Calcium imaging and current recordings showed that deletion of the TAD in a poreless TRPV1 mutant subunit suppressed its dominant-negative phenotype, confirming the involvement of the TAD in assembly of functional channels. Our findings suggest that the C-terminal TAD in TRPV1 channels functions as a domain that is conserved among TRPV1-4 and mediates a direct subunit-subunit interaction for tetrameric assembly.


The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions.
Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT.


Myostatin and muscle atrophy during chronic kidney disease.
Chronic kidney disease (CKD) patients often exhibit a low muscle mass and strength, leading to physical impairment and an increased mortality. Two major signalling pathways control protein synthesis, the insulin-like growth factor-1/Akt (IGF-1/Akt) pathway, acting as a positive regulator, and the myostatin (Mstn) pathway, acting as a negative regulator. Mstn, also known as the growth development factor-8 (GDF-8), is a member of the transforming growth factor-β superfamily, which is secreted by mature muscle cells. Mstn inhibits satellite muscle cell proliferation and differentiation and induces a proteolytic phenotype of muscle cells by activating the ubiquitin-proteasome system. Recent advances have been made in the comprehension of the Mstn pathway disturbance and its role in muscle wasting during CKD. Most studies report higher Mstn concentrations in CKD and dialysis patients than in healthy subjects. Several factors increase Mstn production in uraemic conditions: low physical activity, chronic or acute inflammation and oxidative stress, uraemic toxins, angiotensin II, metabolic acidosis and glucocorticoids. Mstn seems to be only scarcely removed during haemodialysis or peritoneal dialysis, maybe because of its large molecule size in plasma where it is linked to its prodomain. In dialysis patients, Mstn has been proposed as a biomarker of muscle mass, muscle strength or physical performances, but more studies are needed in this field. This review outlines the interconnection between Mstn activation, muscle dysfunction and CKD. We discuss mechanisms of action and efficacy of pharmacological Mstn pathway inhibition that represents a promising treatment approach of striated muscle dysfunction. Many approaches and molecules are in development but until now, no study has proved a benefit in CKD.


Bone Mass Loss and Sarcopenia in Ecuadorian Patients.
To study the association between osteoporosis and sarcopenia and determine the prevalence of osteosarcopenia in patients who attended a rheumatology center in Ecuador. A cross-sectional study was conducted in a population of patients who had a densitometric study. The diagnosis of sarcopenia was determined by the DXA standard gold test, screening, and conventional methods (bioimpedance, anthropometric measurements, SARC-F, muscle function, and gait test). A total of 92 patients were studied. The median age was 66 ± 10, 90% females. Using the criteria of SMI, 65% had sarcopenia of which 9% had only sarcopenia and 56% had osteosarcopenia; 22% had only osteopenia/osteoporosis; and 13% none of these conditions. The prevalence of sarcopenia according to handgrip strength was 60%, gait speed 45%, and SARC-F score 40%. The prevalence of osteosarcopenia according to handgrip strength was 51%, gait speed 34%, and SARC-F score 32%. Osteoporosis was associated with a higher prevalence of sarcopenia using the criteria of SMI since 40% had sarcopenia in the normal DXA group, 64% in the osteopenia group, and 76% in the osteoporosis group (p=0.017). Of the women, 69% had sarcopenia compared to 33% of the men (p=0.034). The BMI was lower in the group with sarcopenia (25.1 ± 4.1 kg/m2) compared to the group without sarcopenia (29.4 ± 4.1 kg/m2, p < 0.001). Patients with osteosarcopenia and sarcopenia had lower BMI, handgrip strength, ASM, SMI, and total-body skeletal muscle mass than those with osteopenia/osteoporosis or normal patients. 65% of the studied population had sarcopenia. It is clear that the prevalence of sarcopenia is higher in patients with greater loss of bone mass. Identifying pathways that affect both bone and muscle could facilitate the development of treatments that simultaneously improve osteoporosis and sarcopenia.


Three alternative promoters of the rat gamma-glutamyl transferase gene are active in developing lung and are differentially regulated by oxygen after birth.
The rat gamma-glutamyl transferase mRNA transcripts I, II, and III are derived from three alternative promoters, P(I), P(II), and P(III). In the adult only mRNA III is expressed in the lung. We show that mRNA III gene expression is developmentally regulated in the fetal lung; it is first expressed in gestation. In contrast to the adult lung, the fetal lung expresses mRNA I, II, and III. The switch from the fetal to the adult pattern of gammaGT mRNA expression begins within the first 24 h of birth and is complete by 10 d of age. gammaGT mRNA II disappears within 24 h, mRNA I disappears by 10 d leaving mRNA III as the sole transcript. Alveolar epithelial type 2 cells (AT2) isolated from the adult lung express only mRNA III. When cultured in 21% O2 mRNA III is maintained, but when cultured in 3% O2 the fetal pattern of mRNA I, II and III expression is induced. When AT2 cells in hypoxia are exposed to carbon monoxide, mRNA II is suppressed suggesting that a heme-binding protein (responsive to oxygen) may suppress mRNA II expression and may be responsible for the decrease in lung mRNA II seen after birth. A reporter gene under the control of DNA sequences from the gammaGT P(III) promoter is activated in transient transfection studies in response to hyperoxia, while a deletion construct retaining an antioxidant responsive element is not. Oxygen appears to regulate each of the alternative promoters of the gammaGT gene, such that P(II) is rapidly repressed by a heme-dependent mechanism, P(I), is more gradually repressed by a nonheme mechanism and P(III) is activated by a putative oxygen response element. We hypothesize that similar oxygen-dependent mechanisms regulate other genes in the developing lung at birth.


Role of offending out-door aero-allergen and CD14 C(-159)T polymorphism in development and severity of asthma in a Kolkata patient population.
Present study involved identification of offending out-door aero-allergens and associated genetic pathway in nasso-bronchial asthma among Kolkata population. Skin-prick test was done among 950 asthmatic patients against 11 common aero-allergens and total serum IgE concentration was measured. PCR-RFLP was done in patients and non-asthmatic control (n=220 in each) to characterize functional polymorphism, C(-159)T, of CD14, a positional candidate gene for allergy. Association of genetic polymorphisms was made with clinico-pathological conditions. We identified Cocos nucifera as the most common aero-allergen sensitizer among atopic patients in Kolkata. Patients with childhood-onset asthma were significantly more sensitive towards aero-allergens and had significantly higher serum IgE level than those of adult-onset (p< 0.0001). No significant difference was found in distribution of SNP genotypes of CD14 among case and control (p=0.178). However among patients, frequency of C allele is significantly higher in childhood-onset group than that of adult-onset and concordantly in former CC genotype was associated with significant higher level of serum IgE than CT and TT. In Kolkata, pollen is a common out-door aero-allergen and Cocos nucifera is predominant among pollens. Childhood-onset and adult-onset of asthma showed significant difference in allergen sensitivity as well as genetic background with respect to CD14 polymorphism.


Measuring the depth of invasion in vulvar squamous cell carcinoma: interobserver agreement and pitfalls.
The depth of invasion is an important prognostic factor for patients with vulvar squamous cell carcinoma (SCC). The threshold of 1 mm distinguishes between FIGO stages IA and ≥IB disease and guides the need for groin surgery. Therefore, high interobserver agreement is crucial. The conventional and the alternative method are described to measure the depth of invasion. The aims of this study were to assess interobserver agreement for classifying the depth of invasion using both methods and to identify pitfalls. Fifty slides of vulvar SCC with a depth of invasion approximately 1 mm were selected, digitally scanned and independently assessed by 10 pathologists working in a referral or oncology centre and four pathologists in training. The depth of invasion was measured using both the conventional and alternative method in each slide and categorised into ≤1 and >1 mm. The percentage of agreement and Light's kappa for multi-rater agreement were calculated, and 95% confidence intervals were calculated by bootstrapping (1000 runs). The agreement using the conventional method was moderate (κ = 0.57, 95% confidence interval = 0.45-0.68). The percentage of agreement among the participating pathologists using the conventional method was 85.0% versus 89.4% using the alternative method. Six pitfalls were identified: disagreement concerning which invasive nest is deepest, recognition of invasive growth and where it starts, curved surface, carcinoma situated on the edge of the tissue block, ulceration and different measurement methods. Pathologists reached only moderate agreement in determining the depth of invasion in vulvar SCC, without a notable difference between the two measurement methods.


Factors Driving Citizen Engagement With Government TikTok Accounts During the COVID-19 Pandemic: Model Development and Analysis.
During the COVID-19 pandemic, growth in citizen engagement with social media platforms has enabled public health departments to accelerate and improve health information dissemination, developing transparency and trust between governments and citizens. In light of these benefits, it is imperative to learn the antecedents and underlying mechanisms for this to maintain and enhance engagement. The aim of this study is to determine the factors and influencing mechanisms related to citizen engagement with the TikTok account of the National Health Commission of China during the COVID-19 pandemic. Using a web crawler, 355 short videos were collected from the Healthy China account on TikTok (with more than 3 million followers throughout China), covering the period from January 21, 2020, to April 25, 2020. The title and video length, as well as the number of likes, shares, and comments were collected for each video. After classifying them using content analysis, a series of negative binomial regression analyses were completed. Among the 355 videos, 154 (43.4%) related to guidance for clinicians, patients, and ordinary citizens, followed by information concerning the government's handling of the pandemic (n=100, 28.2%), the latest news about COVID-19 (n=61, 17.2%), and appreciation toward frontline emergency services (n=40, 11.3%). Video length, titles, dialogic loop, and content type all influenced the level of citizen engagement. Specifically, video length was negatively associated with the number of likes (incidence rate ratio [IRR]=0.19, P<.001) and comments (IRR=0.39, P<.001). Title length was positively related to the number of shares (IRR=24.25, P=.01), likes (IRR=8.50, P=.03), and comments (IRR=7.85, P=.02). Dialogic loop negatively predicted the number of shares (IRR=0.56, P=.03). In comparison to appreciative information, information about the government's handling of the situation (IRR=5.16, P<.001) and guidelines information (IRR=7.31, P<.001) were positively correlated with the number of shares, while the latest news was negatively related to the number of likes received (IRR=0.46, P=.004). More importantly, the relationship between predictors and citizen engagement was moderated by the emotional valence of video titles. Longer videos with positive titles received a higher number of likes (IRR=21.72, P=.04) and comments (IRR=10.14, P=.047). Furthermore, for short videos related to government handling of the pandemic (IRR=14.48, P=.04) and guidance for stakeholders (IRR=7.59, P=.04), positive titles received a greater number of shares. Videos related to the latest news (IRR=66.69, P=.04) received more likes if the video title displayed higher levels of positive emotion. During the COVID-19 pandemic, videos were frequently published on government social media platforms. Video length, title, dialogic loop, and content type significantly influenced the level of citizen engagement. These relationships were moderated by the emotional valence of the video's title. Our findings have implications for maintaining and enhancing citizen engagement via government social media.


Comparison of inducers of crisis forms in Plasmodium falciparum in vitro.
A variety of known or suspected inducers of crisis form parasites in cultivated Plasmodium falciparum were examined. Sera from Sudanese residents of malaria-endemic areas, sera from American tuberculosis patients, and rabbit sera containing tumor necrosis factor were assayed in vitro for cytotoxic activities against P. falciparum and mouse L-M cell cultures. Inhibition was determined by measurement of incorporation of radiolabeled nucleic acid precursors. When compared to normal serum, parasites grown in the presence of a 1:4 dilution of rabbit sera containing tumor necrosis factor, TB patient sera, or Sudanese sera were metabolically inhibited 73%, 75%, and 95%, respectively. However, only the rabbit sera containing tumor necrosis factor were cytotoxic to L-M cells, inhibiting radiolabel incorporation by 80% at a 1:1,000 serum dilution. These findings suggest that tumor necrosis factor is apparently not responsible for the induction of parasite crisis forms by the inhibitory human sera tested. In addition, human gamma-interferon had no effect on parasite growth.


Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS.
We report data on a group of 37 VCFS patients with specific reference to their intelligence, behaviour, and social competence. Fifty five percent of the children had a borderline to normal IQ. Mental retardation (defined as IQ < 70 or > -2 SD below the mean) was found in 45%. In the majority, the mental retardation was mild (38%) and only two patients had moderate mental retardation. Severe mental retardation seems to be rare in VCFS. The present study shows also that the incidence of mental retardation is much higher in the familial than the de novo group. Intelligence is not correlated with the presence or absence of a heart defect. Significantly higher verbal IQs than performance IQs (probably related to deficits in visuospatial-perceptual functioning) were found. Problems in social-emotional functioning and attention were also found. Further longitudinal studies are necessary to provide an accurate prognosis and appropriate intervention for VCFS children.


Successful cultivation of a potentially pathogenic coccoid organism with trophism for gastric mucin.
We have devised a procedure that permits the cultivation of a gram-positive coccoid species from biopsy material obtained from the antrum of the stomachs of patients with gastric disorders. Antibodies directed against surface proteins obtained from the coccoid isolates were detected in all patients with gastric disorders examined in this study, including both Helicobacter pylori-infected and H. pylori-uninfected patients. Several of these isolates, including a prototype designated strain SL100, have been characterized in some detail. Strain SL100 exhibits urease and exceptionally high catalase activities and assumes a variety of spherical morphologies as detected by electron microscopy. This isolate expresses an adhesin that binds to gastric mucin. The adhesin activity was detected only after the isolate was exposed to an acidic pH, suggesting that in the natural process of infection, the low pH of the stomach unmasks a cell surface component with adhesin activity. Strain SL100 grows best under a microaerophilic conditions (10% CO2, 5% O2, 85% N2), but it also grows quite well under aerobic conditions. Thus, this organism would be expected to proliferate outside of the human host as well as in the gastric mucosa. Oral infection of newborn piglets resulted in colonization of the gastric antrum and growth retardation. Preliminary taxonomic classification indicates similarity to the Staphylococcus DNA homology groups containing S. cohnii and S. xylosus. One of us (C.K.) apparently became infected with this organism as indicated by gastric symptoms and the subsequent presence of strain-specific antisera not present in other workers in the laboratory.


Optical spectrum of bottom-up graphene nanoribbons: towards efficient atom-thick excitonic solar cells.
Recently, atomically well-defined cove-shaped graphene nanoribbons have been obtained using bottom-up synthesis. These nanoribbons have an optical gap in the visible range of the spectrum which make them candidates for donor materials in photovoltaic devices. From the atomistic point of view, their electronic and optical properties are not clearly understood. Therefore, in this work we carry out ab-initio density functional theory calculations combine with many-body perturbation formalism to study their electronic and optical properties. Through the comparison with experimental measurements, we show that an accurate description of the nanoribbon's optical properties requires the inclusion of electron-hole correlation effects. The energy, binding energy and the corresponding excitonic transitions involved are analyzed. We found that in contrast to zigzag graphene nanoribbons, the excitonic peaks in the absorption spectrum are a consequence of a group of transitions involving the first and second conduction and valence bands. Finally, we estimate some relevant optical properties that strengthen the potential of these nanoribbons for acting as a donor materials in photovoltaic.


Percentile growth charts for biomedical studies using a porcine model.
Increasing rates of obesity and heart disease are compromising quality of life for a growing number of people. There is much research linking adult disease with the growth and development both in utero and during the first year of life. The pig is an ideal model for studying the origins of developmental programming. The objective of this paper was to construct percentile growth curves for the pig for use in biomedical studies. The body weight (BW) of pigs was recorded from birth to 150 days of age and their crown-to-rump length was measured over the neonatal period to enable the ponderal index (PI; kg/m3) to be calculated. Data were normalised and percentile curves were constructed using Cole's lambda-mu-sigma (LMS) method for BW and PI. The construction of these percentile charts for use in biomedical research will allow a more detailed and precise tracking of growth and development of individual pigs under experimental conditions.


Response of liver metastases after treatment with yttrium-90 microspheres: role of size, necrosis, and PET.
Yttrium-90 radioembolization is an emerging treatment for liver malignancies. The purpose of this study was to evaluate the imaging response of liver metastases to 90Y microspheres based on size and necrosis criteria using CT and comparing the results to PET and to describe imaging features related to 90Y therapy. We reviewed the imaging studies of 42 patients with unresectable liver metastases treated with lobar radioembolization with 90Y. CT response was determined using traditional size criteria (World Health Organization [WHO] and Response Evaluation Criteria in Solid Tumors [RECIST]), necrosis criteria, and combined criteria (RECIST and necrosis). We compared the response on CT with the response on PET. Complications of treatment were assessed. The response rate was 19% (8/42) by WHO criteria, 24% (10/42) by RECIST, 45% (19/42) by necrosis criteria, and 50% (21/42) by combined criteria. Stabilization of lesion size occurred in 50% of patients. Necrosis and combined criteria identified responders earlier than RECIST and WHO criteria. Seven responders by combined criteria had an increase in lesion size on initial follow-up and would have been considered nonresponders. PET scans were obtained in 23 patients (33 treated lobes). PET detected significantly more responses to treatment (21/33, 63%) than CT using RECIST (2/33, 6%) or combined criteria (8/33, 24%) (p < 0.05, McNemar test). Complications of treatment included radiation cholecystitis (10 patients, 23%) and liver edema (18 patients, 42%). The use of necrosis and size criteria on CT and correlation with PET may improve the accuracy of assessment of response to 90Y treatment in patients with liver metastases and detect response earlier than standard size criteria.


A laminar cortical model for 3D perception of slanted and curved surfaces and of 2D images: development, attention, and bistability.
A model of laminar visual cortical dynamics proposes how 3D boundary and surface representations arise from viewing slanted and curved 3D objects and 2D images. The 3D boundary representations emerge from non-classical receptive field interactions within intracortical and intercortical feedback circuits. Such non-classical interactions within cortical areas V1 and V2 contextually disambiguate classical receptive field responses to ambiguous visual cues using cells that are sensitive to colinear contours, angles, and disparity gradients. Remarkably, these cell types can all be explained as variants of a unified perceptual grouping circuit whose most familiar example is a 2D colinear bipole cell. Model simulations show how this circuit can develop cell selectivity to colinear contours and angles, how slanted surfaces can activate 3D boundary representations that are sensitive to angles and disparity gradients, how 3D filling-in occurs across slanted surfaces, how a 2D Necker cube image can be represented in 3D, and how bistable 3D Necker cube percepts occur. The model also explains data about slant aftereffects and 3D neon color spreading. It shows how chemical transmitters that habituate, or depress, in an activity-dependent way can help to control development and also to trigger bistable 3D percepts and slant aftereffects. Attention can influence which of these percepts is perceived by propagating selectively along object boundaries.


Towards exposure of elusive metabolic mixed-culture processes: the application of metaproteomic analyses to activated sludge.
Protein expression is a direct reflection of specific microbial activities in any ecosystem. In order to assess protein expression in mixed microbial communities, the feasibility of applying proteomic techniques to activated sludge samples has recently been demonstrated. We report the application of metaproteomics to two activated sludges from a laboratory-scale sequencing batch reactor with dissimilar phosphorus removal performances. Fluorescence in situ hybridization (FISH) revealed that the sludge with good enhanced biological phosphorus removal performance (EBPR) was dominated by Betaproteobacteria (65% of EUBMIX binding cells) and gave positive signals for the Rhodocyclus-type PAO specific probe (59%). The non-EBPR sludge was dominated by tetrad-forming Alphaproteobacteria (75%). With regard to the proteomic investigation, 630 individual protein spots were matched across the replicate groups of the anaerobic and aerobic phases of the EBPR sludge with 9.4% of all spots being statistically different between the two phases. The non-EBPR metaproteomic maps exhibited 590 matched spots with 14.7% statistical differences between the two phases. Overall, the non-EBPR sludge expressed around 30% more significant differences than the EBPR sludge. The comparison of protein expression in the two sludges showed that their metaproteomes were substantially different and this was reflected in their microbial community structures and metabolic transformations.


Molecularly imprinted polymers for the determination of a pharmaceutical development compound in plasma using 96-well MISPE technology.
The use of molecularly imprinted polymers (MIPs) as sorbents for the solid phase extraction (SPE) of a pharmaceutical compound in development, prior to quantitative analysis was investigated. Three MIPs were synthesised using a structural analogue as the template molecule. Each polymer was prepared with different monomers and porogens. The MIPs were then tested for their performance both in organic and aqueous environments, the final aim being to load plasma directly onto the polymers. At an early development stage, there is a limited amount of compound available. Due to this limitation, reducing the amount of template required for imprinting was investigated. A MIP capable of extracting the analyte directly from plasma was produced. The specificity of the polymer allowed the method to be validated at a lower sensitivity than a more conventional SPE assay. For the first time, MIPs were packed into 96-well blocks enabling high throughput analysis. The analytical method was fully validated for imprecision and inaccuracy down to 4 ng/ml in plasma.


Safety and security in small-scale recovery housing for people with severe mental illness: an inner-city case study.
The authors examined the lived experience of residents with severe mental illness in a small-scale recovery-housing building in the inner city. They attempting to identify and understand factors that influenced adjustment and stability. Four focus groups with 17 residents and participant observation with residents, case managers, and supervisory staff were conducted longitudinally over a two-year period. Data were analyzed according to the tenets of qualitative content analysis. Safety and security was the most prominent issue raised by residents. Serious concerns about this issue could be divided into three categories: threats raised by the behavior of other residents (and their associates), threats raised by strangers, and threats related to loss of self-control. A related theme involved ongoing tension between residents' desire for communal connections and their conflicting desire for a bounded private life. Ongoing attention to the issue of safety and security should be a key component of recovery-oriented housing in inner-city residential areas. Further research may need to compare the experience of safety and security among residents living in recovery housing with the experience of those in independent scatter-site housing and traditional congregate housing.


TLR-7 Stress Signaling in Differentiating and Mature Eosinophils Is Mediated by the Prolyl Isomerase Pin1.
The response of eosinophils (Eos) to respiratory virus has emerged as an important link between pulmonary infection and allergic asthmatic exacerbations. Eos activate innate immune responses through TLR signaling. In this study, using mouse and human Eos and mice lacking the prolyl isomerase Pin1 selectively in Eos, we show that Pin1 is indispensable for eosinophilopoiesis in the bone marrow (BM) and mature cell function in the presence of TLR7 activation. Unbiased in vivo analysis of mouse models of allergic airway inflammation revealed that TLR7 activation in knockout mice resulted in systemic loss of Eos, reduced IFN production, and an inability to clear respiratory viruses. Consistent with this finding, BM mouse Eos progenitors lacking Pin1 showed markedly reduced cell proliferation and survival after TLR7 activation. Mechanistically, unlike wild-type cells, Pin1 null mouse Eos were defective in the activation of the endoplasmic reticulum stress-induced unfolded protein response. We observed significant reductions in the expression of unfolded protein response components and target genes, aberrant TLR7 cleavage and trafficking, and reduced granule protein production in knockout Eos. Our data strongly suggest that Pin1 is required for BM Eos generation and function during concurrent allergen challenge and viral infection.


Amundsen Sea Mollusca from the BIOPEARL II expedition.
Information regarding the molluscs in this dataset is based on the epibenthic sledge (EBS) samples collected during the cruise BIOPEARL II / JR179 RRS James Clark Ross in the austral summer 2008. A total of 35 epibenthic sledge deployments have been performed at five locations in the Amundsen Sea at Pine Island Bay (PIB) and the Amundsen Sea Embayment (ASE) at depths ranging from 476 to 3501m. This presents a unique and important collection for the Antarctic benthic biodiversity assessment as the Amundsen Sea remains one of the least known regions in Antarctica. Indeed the work presented in this dataset is based on the first benthic samples collected with an EBS in the Amundsen Sea. However we assume that the data represented are an underestimation of the real fauna present in the Amundsen Sea. In total 9261 specimens belonging to 6 classes 55 families and 97 morphospecies were collected. The species richness per station varied between 6 and 43. Gastropoda were most species rich 50 species followed by Bivalvia (37), Aplacophora (5), Scaphopoda (3) and one from each of Polyplacophora and Monoplacophora.


ORFeus: a computational method to detect programmed ribosomal frameshifts and other non-canonical translation events.
In canonical protein translation, ribosomes initiate translation at a specific start codon, maintain a single reading frame throughout elongation, and terminate at the first in-frame stop codon. However, ribosomal behavior can deviate at each of these steps, sometimes in a programmed manner. Certain mRNAs contain sequence and structural elements that cause ribosomes to begin translation at alternative start codons, shift reading frame, read through stop codons, or reinitiate on the same mRNA. These processes represent important translational control mechanisms that can allow an mRNA to encode multiple functional protein products or regulate protein expression. The prevalence of these events remains uncertain, due to the difficulty of systematic detection. We have developed a computational model to infer non-canonical translation events from ribosome profiling data. ORFeus identifies known examples of alternative open reading frames and recoding events across different organisms and enables transcriptome-wide searches for novel events.


Retinol is specifically required during midgestation for neonatal survival.
Previous work has demonstrated that vitamin A-deficient, retinoic acid-supplemented pregnant rats cannot complete gestation without the administration of retinol. As little as 2 micrograms administered on day 10 of gestation is sufficient to prevent the characteristic fetal resorption that begins at day 15 of gestation. This single dose of retinol supports continued development through day 20 of gestation. However, if gestation is allowed to proceed to parturition, the newborn pups die within a few minutes of being severed from the umbilical cord. The pups are born with a pink and healthy skin tone, but within seconds of umbilical separation, they begin to gasp for air, become cyanotic in appearance, and die within several minutes from an apparent inability to obtain oxygen. Histological examination of these neonates demonstrates delayed pulmonary development. Branching and scalloping of ducts and saccule and subsaccule formation are decreased. This phenotype is consistent with that observed in respiratory distress syndrome seen in some premature human infants.


Mechanical response of collagen molecule under hydrostatic compression.
Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.


Synergistic effect of nickel and temperature on gene expression, multiple stress markers, and depuration: an acute toxicity in fish.
Aquatic animals are prone to extinction due to metal pollution and global climate change. Even though the fish and their products are also unsafe for human consumption, their exports have been rejected due to inorganic and organic contaminants. Nickel (Ni) is a metal that induces toxicity and accumulates in the aquatic ecosystem, posing health threats to humans, animals, and fish. In light of the above, our present investigation aimed to determine the median lethal concentration (96 h-LC50) of nickel alone and concurrent with high temperature (34 °C) (Ni + T) using static non-renewable bioassay toxicity test in Pangasianodon hypophthalmus. The groups treated under exposure to Ni reared under control condition (25-28.9 °C) and Ni + T exposure group reread under 34 °C. In this study, chose the definitive dose of Ni and Ni + T as 17, 18, 19, and 20 mg L-1 after the range finding test. The median lethal concentration of Ni and Ni + T was determined as 19.38 and 18.75 mg L-1, respectively at 96 h. Oxidative stress viz. catalase (CAT), superoxide dismutase (SOD), glutathione-s-transferase (GST), and glutathione peroxidase (GPx) in the liver, gill, and kidney were noticeably elevated with Ni and Ni + T during 96 h. Whereas, the CAT, GPx, and SOD gene expressions were significantly upregulated with Ni and Ni + T. Trilox equivalent anti-oxidant capacity (TEAC), cupric reducing anti-oxidant capacity (CUPRIC), ferric reducing ability of plasma (FRAP), ethoxy resorufin-O-deethylase (EROD), and acetylcholine esterase (AChE) were reduced due to exposure to Ni and Ni + T. Cellular metabolic stress and lipid peroxidation were highly affected due to Ni and Ni + T exposure. The immunological status, as indicated by total protein, albumin, globulin, A:G ratio, and nitro blue tetrazolium chloride (NBT), was severely affected by the toxicity of Ni and Ni + T. Moreover, the gene expression of interleukin (IL), tumor necrosis factor (TNFα), toll-like receptor (TLR), and total immunoglobulin (Ig) was remarkably downregulated following exposure to Ni and Ni + T. HSP 70, iNOS expression, ATPase, Na + /K + -ATPase, cortisol, and blood glucose was significantly elevated with Ni and Ni + T in P. hypophthalmus. The bioaccumulation of Ni in fish tissues and experimental water was determined. The kidney and liver tissues were highly accumulated with Ni, whereas DNA damage was reported in gill tissue. Interestingly, depuration study revealed that at the 28th day, the Ni bioaccumulation was below the maximum residue limit (MRL) level. Therefore, the present study revealed that Ni and Ni + T led to dysfunctional gene and metabolic regulation affecting physiology and genotoxicity. The bioaccumulation and depuration results also indicate higher residual occurrence of Ni in water and aquatic organisms for longer periods.


Pain and disability reported in the year following a distal radius fracture: a cohort study.
Distal radius fractures are a common injury that cause pain and disability. The purpose of this study was to describe the pain and disabilities experienced by patients with a distal radius fracture in the first year following fracture. A prospective cohort study of 129 patients with a fracture of the distal radius was conducted. Patients completed a Patient-rated Wrist Evaluation at their baseline clinic visit and at 2, 3, 6 and 12 months following their fracture. The frequency/severity of pain and disabilities reported was described at each time point. The majority of patients experienced mild pain at rest and (very) severe high levels of pain with movement during the first two-months following distal radius fracture. This time is also associated with (very) severe difficulty in performing specific functional activities and moderate to severe difficulty in four domains of usual activity. The majority of recovery occurred within six-months, but symptoms persisted for a small minority of patients at one-year following fracture. Patients had the most difficulty with carrying ten pounds and pushing up from a chair. Resumption of usual personal care and household work preceded, and was more complete, than work and recreational participation. This study demonstrated that the normal course of recovery following a distal radius fracture is one where severe symptoms subside within the first two-months and the majority of patients can be expected to have minimal pain and disability by six-months following fracture. This information can be used when planning interventions and assessing whether the progress of a patient is typical of other patients.


Assessing three soil removal methods for environmental DNA analysis of mock forensic geology evidence.
Soil is useful in criminal investigations as it is highly variable and readily transferred. Forensic geologists use several different techniques to removal soil from evidence prior to the analysis of inorganic components. There has been recent interest from the forensic science community to analyze environmental deoxyribonucleic acid (eDNA) associated with soil to augment existing forensic analyses. Notably however, limited research has been conducted to compare commonly used soil removal methods for downstream eDNA analysis. In this study, three soil removal methods were assessed: picking/scraping, sonication, and swabbing. Three mock evidence types (t-shirts, boot soles, and trowels) were sampled in triplicate with each removal method (n = 27). Soil samples underwent DNA isolation, quantification, and amplification of four genomic barcode regions: 16S for bacteria, ITS1 for fungi, ITS2 for plants, and COI for arthropods. Amplicons were prepared into libraries for DNA sequencing on an Illumina® MiniSeq. DNA concentrations were highest in picked/scraped samples and were statistically significant compared with swabbed and sonicated samples. Amplicon sequence variants (ASVs) were identified, and removal methods had no impact on the recovery of the total number of target ASVs. Additionally, when assessing each sample in multidimensional space, picked/scraped samples tended to cluster separately from swabbed and sonicated samples. The soil core used a reference in this study also clustered with the picked/scraped samples, indicating that these samples may be more reflective of the communities collected from soil cores. Based on these data, we identified that picking/scraping is an acceptable soil removal method for eDNA analysis.


Sonographically Occult Abscesses of the Buttock and Perineum in Children.
Ultrasound (US) is used to differentiate abscess from cellulitis. At our institution, we observed children who had purulent fluid obtained after a negative abscess US. We sought to determine the incidence of sonographically occult abscess (SOA) of the buttock and perineum, and identify associated clinical and demographic characteristics. Retrospective chart review including children younger than 18 years old presenting to pediatric emergency department with soft tissue infection of the buttock or perineum and diagnostic radiology US read as negative for abscess. We defined SOA as wound culture growing pathogenic organism obtained within 48 hours of the US. Clinical and demographic characteristics included age, sex, race, ethnicity, fever, history of spontaneous drainage, duration of symptoms, previous methicillin resistant Staphylococcus aureus (MRSA) infection, or previous abscess. We used univariate and multivariate logistic regression to assess correlation between these characteristics and SOA. A total of 217 children were included. Sixty-one (28%) children had SOA; 33 of 61 (54%) had incision and drainage within 4 hours of the US. Of children with SOA, 49 (80%) grew MRSA and 12 (20%) grew methicillin-sensitive S. aureus. In univariate analysis, a history of MRSA, symptom duration 4 days or less, age of younger than 4 years, and Hispanic ethnicity increased the odds of having SOA. In multivariate analysis, history of MRSA and duration of 4 days or less were associated with SOA. Twenty-eight percent of children in our institution with US of the buttock and perineum negative for abscess had clinical abscess within 48 hours, most within 4 hours. History of MRSA and shorter symptom duration increased the odds of SOA.


Correlation between poliovirus type 1 Mahoney replication in blood cells and neurovirulence.
Poliovirus (PV) is not often described as a monocyte- or macrophage-tropic virus; however, previous work indicated that neurovirulent PV type 1 Mahoney [PV(1)Mahoney] can productively infect primary human monocytes. To determine whether this replication has a functional role in pathogenesis, primary human mononuclear blood cells were infected with pairs of attenuated and neurovirulent strains of PV. Two neurovirulent strains of PV, PV(1)Mahoney and PV(2)MEF-1, replicated faster and to higher titers than attenuated counterparts PV(1)Sabin and PV(2)W-2, respectively, in primary human monocytes, suggesting that this replication may contribute to pathogenesis. PV(3)Leon grew weakly, while PV(3)Sabin, PV(2)Sabin, and PV(2) P712 did not replicate in these cells, perhaps because of their slow replication cycle. In U937 cells, a monocytelike cell line, PV(1)Mahoney replicated but PV(1)Sabin did not, while both grew well in HeLa cells. When molecular recombinants of PV(1)Mahoney and PV(1)Sabin were assessed, a correlation between neurovirulence and the ability to replicate in primary human mononuclear blood cells was found. Surprisingly, infectious centers assays with primary human mononuclear blood cells and U937 cells indicated that despite the lower overall viral yield, more cells are initially infected with the attenuated viruses. These results indicate that there are virulence-specific differences in the ability of PV(1)Mahoney to replicate in monocytes and suggest that there may be factors in monocytes that virulent strains of PV require.


[Prevalence of anaemia in schoolchildren in the Amazon area of Ecuador].
To determine the prevalence of anemia in rural school-age children in the Amazon region of Ecuador. We carried out a cross-sectional study during May to October 2000 in two cantons of the province of Orellana, in northeastern Ecuador, involving 626 children from 17 schools. Demographic and anthropometric data (weight and height) were collected, values for hemoglobin and for zinc erythrocyte protoporphyrin were determined, and feces samples were analyzed to check for infestation by parasites. The general prevalence of anemia was 16.6% among the schoolchildren; of the affected children, 75.5% of them had iron-deficiency anemia. The prevalence of moderate chronic undernutrition was 28.8% and that of serious chronic undernutrition was 9.3%. There was also a prevalence of moderate acute undernutrition of 8.4% and of severe acute undernutrition of 3.4%. Parasitic infections were very frequent (82.0%). The most common parasites were Entamoeba coli (30.3%) and Ascaris lumbricoides (25.0%). There were no relationships between the prevalence of either anemia or of iron-deficiency anemia and any of the indicators of nutrition or of parasitic infection. Anemia is not a serious public health problem in the population studied. Nevertheless, the high prevalence of chronic undernutrition among the children points to the need to improve their diets. The lack of association between the prevalence of undernutrition and anemia could be due to low iron bioavailability or absorption rather than insufficient intake. Studies are needed to evaluate the customary diet of this population.


Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation.
Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.


Providing palliative and end-of-life care in the community: the role of the home-care worker.
Home-care workers play a vital role in enabling patients to be cared for in their own homes; however, there is a lack of research on their role. The aim of this study was to explore the role of home-care workers in palliative and end-of-life care in the community. A mixed methods approach was used with two key phases. Phase one comprised a cross-sectional survey to home-care workers and phase two involved a focus group with community nurses. It was found that home-care workers considered palliative and end-of-life care as an important part of their role, and that while it was more stressful than routine work, it was nevertheless very rewarding. While the home-care workers demonstrated that their role incorporated a genuine caring dimension, they identified the need for additional support in the provision of end-of-life care, specifically during out-of-hours. Various restricting factors such as training deficits, need for support and supervision and communication issues were also identified.


Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study.
The objective of this study was to compare the effects of teneligliptin-based regimens and other gliptin-based regimens with respect to insulin resistance and glycemic control in patients with type 2 diabetes mellitus (T2DM). We enrolled T2DM subjects, inadequately controlled with metformin and glimepiride and taking one of the gliptins, and divided them into two groups, i.e. group 1 (teneligliptin-based regimens) and group 2 (other gliptin-based regimens). Fasting plasma insulin, adiponectin levels, homeostatic model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were measured and compared. Costs of different gliptins were noted, and mean cost of per day therapy was compared. Eighty-six subjects participated in this study (43 each in group 1 and group 2). No significant differences were observed in FBG, HbA1c, insulin levels, and HOMA-IR, but the trend was in favor of teneligliptin-based regimens. A significantly higher number of subjects achieved HbA1c target in group 1 (P < 0.001). Teneligliptin had significantly lower cost of per day therapy as compared to other dipeptidyl peptidase-4 inhibitors. Teneligliptin seems to be cost-effective and safer option in T2DM subjects who were not adequately controlled with metformin and sulfonylureas. However, further prospective studies are needed.


[Structure of the cell wall polysaccharide in the food protein yeast Candida spec. H. IV. Structure of the alkali labile oligosaccharide in the mannan-protein-phosphate complex].
Mild alkaline degradation of the proteophosphomannan (PPM) under conditions that effect beta-elimination of the residues, O-glycosidically bound on serine and threonine, release mainly mannose, glucose, mannobioses and mannotrioses with the same structures as those obtained by acetolysis of the polysaccharide component of the PPM. Methylation analysis and paper chromatography demonstrated the structural heterogeneity of the tetra-, penta- and hexasaccharide fractions containing 1,2- and 1,6-linked and 1,2,6-branched manno-oligosaccharides. Methylation analysis and acetolysis, paper chromatography and analysis of the carbohydrate composition of the oligosaccharide fractions DP 7-12 and DP 15-19 demonstrated inner core region like structures containing 1,2- and 1,6-linked mannose, 1,2,6- and 1,3,6-branchpoints and N-acetyl-D-glucosamine.


[Possiblities of craniofacial identification from incomplete and damaged skulls].
With the aim of development criteria for assessment of results of personal identification with the use of the method of photo superposition of incomplete and damaged skulls at initial stages of our work, the frequency of submission of such skulls to examination was determined. Main groups of skull defects were determined, and identification results subject to each defect were estimated; which gave conclusion that presence or absence of one or another defect did not impede photo superposition. Signs, which most frequently were crucial for final result of identification, were determined. Analysis of obtained data show that the more number of crucial signs will be taken into account at personal identification, all the more with incomplete skulls, the more valid result will be obtained.


NOTCH1 mutations in individuals with left ventricular outflow tract malformations reduce ligand-induced signaling.
Congenital aortic valve stenosis (AVS), coarctation of the aorta (COA) and hypoplastic left heart syndrome (HLHS) are congenital cardiovascular malformations that all involve the left ventricular outflow tract (LVOT). They are presumably caused by a similar developmental mechanism involving the developing endothelium. The exact etiology for most LVOT malformations is unknown, but a strong genetic component has been established. We demonstrate here that mutations in the gene NOTCH1, coding for a receptor in a developmentally important signaling pathway, are found across the spectrum of LVOT defects. We identify two specific mutations that reduce ligand (JAGGED1) induced NOTCH1 signaling. One of these mutations perturbs the S1 cleavage of the receptor in the Golgi. These findings suggest that the levels of NOTCH1 signaling are tightly regulated during cardiovascular development, and that relatively minor alterations may promote LVOT defects. These results also establish for the first time that AVS, COA and HLHS can share a common pathogenetic mechanism at the molecular level, explaining observations of these defects co-occurring within families.


Assessment of the Visual Analogue Score in the Evaluation of the Pruritus of Cholestasis.
Background and Aims: A visual analogue score (VAS), based on application of a visual analogue scale, has been widely used to assess pruritus in clinical studies of patients with cholestatic liver disease. A VAS is a numerical score of the severity of the perception of pruritus, and, hence, is inherently subjective. The objective of this study was to assess the reliability of a VAS as an index of pruritus in cholestatic patients. Methods: In 8 patients with chronic pruritus due to primary biliary cholangitis, values for a VAS of pruritus were compared with corresponding measurements of scratching activity, which were generated by a monitoring system specifically designed to quantitate this activity. The relationship between individual values for the VAS and corresponding values for scratching activity during a specific interval immediately preceding the recording of the VAS was examined by determining the Spearman's rank correlation coefficient. Results: The mean Spearman's rank correlation coefficient between individual values for the VAS and corresponding mean values for scratching activity was 0.072; the range of these coefficients was -0.04 to 0.26. A VAS of pruritus is an unreliable index of scratching activity, and, hence, of the pathophysiological process responsible for the pruritus of cholestasis. Conclusions: It is concluded that the use of a VAS as a primary quantitative endpoint in trials of the efficacy of potential therapies for the pruritus of cholestasis may be inappropriate.


Anti-inflammatory treatment of traumatic brain injury with Rabeximod reduces cerebral antigen presentation in mice.
A major component of the damaging effect after traumatic brain injury (TBI) is activation of the inflammatory system. In particular, chemokines and chemokine-regulated factors become activated in resident brain cells and signal to different invading immune cells. For evaluation of the effect on invading cells 3 days after injury, mice were treated with a single initial dose of the anti-inflammatory agent Rabeximod in an experimental TBI model. For comparison, mice subjected to TBI were similarly injected with cyclophosphamide. TBI resulted in reduced body weight, an effect further enhanced by administration of Rabeximod, without obvious influence on motor performance. As revealed by quantitative RT-PCR, microglial upregulation of chemokine Ccl3 in response to TBI was unaffected by Rabeximod. Also, injury-induced expression of Cxcl10 in plasmacytoid dendritic cells (DCs) and endothelial expression of platelet selectin (Selp) were uninfluenced by Rabeximod. In contrast, Rabeximod robustly reduced the H2-Aa transcript characteristic for classical DCs defined by CD11c/Itgax in the injured brain. In addition, the expression of lysozyme 2 in large phagocytic cells was impaired by Rabeximod. These results show that Rabeximod exerts a selective and potent inhibition of cells serving cortical antigen presentation after brain trauma.


How much is enough? Effects of technical and biological replication on metabarcoding dietary analysis.
DNA metabarcoding is increasingly used in dietary studies to estimate diversity, composition and frequency of occurrence of prey items. However, few studies have assessed how technical and biological replication affect the accuracy of diet estimates. This study addresses these issues using the European free-tailed bat Tadarida teniotis, involving high-throughput sequencing of a small fragment of the COI gene in 15 separate faecal pellets and a 15-pellet pool per each of 20 bats. We investigated how diet descriptors were affected by variability among (a) individuals, (b) pellets of each individual and (c) PCRs of each pellet. In addition, we investigated the impact of (d) analysing separate pellets vs. pellet pools. We found that diet diversity estimates increased steadily with the number of pellets analysed per individual, with seven pellets required to detect ~80% of prey species. Most variation in diet composition was associated with differences among individual bats, followed by pellets per individual and PCRs per pellet. The accuracy of frequency of occurrence estimates increased with the number of pellets analysed per bat, with the highest error rates recorded for prey consumed infrequently by many individuals. Pools provided poor estimates of diet diversity and frequency of occurrence, which were comparable to analysing a single pellet per individual, and consistently missed the less common prey items. Overall, our results stress that maximizing biological replication is critical in dietary metabarcoding studies and emphasize that analysing several samples per individual rather than pooled samples produce more accurate results.