Ocular findings in leprosy patients in Nigeria.
An ophthalmic assessment of patients in four out of the five leprosy clinics in Anambra State, eastern Nigeria, showed that 63% had ocular disease and 43.5% had sight-threatening disorders. Most of the problems occurred in multibacillary leprosy patients. The blindness rate of (8.7%) is nearly 10 times higher than that within the general population in area. The causes of blindness were cataract, exposure keratopathy and uveitis. Some patients also had glaucoma and chorioretinal lesions. Eye health service within the leprosy control service in the area is non-existent. The importance of giving priority to blindness prevention in leprosy patients in the area is emphasised.


A novel insertion in the FOXL2 gene in a Chilean patient with blepharophimosis ptosis epicanthus inversus syndrome type I.
A novel insertion in the forkhead transcription factor 2 (FOXL2) was identified in a Chilean patient with blepharophimosis, ptosis, and epicanthus inversus syndrome associated with premature ovarian failure (BPES type I). A clinical and molecular characterization of a patient with BPES type I was performed. We present a 16-year-old adolescent girl with surgically treated blepharophimosis, ptosis, and epicanthus inversus that was associated with delayed puberty and secondary amenorrhea at the age of 15, indicators that suggested that the patient had BPES type I. The FOXL2 gene was analyzed by sequencing its coding region. The sequence analysis of the FOXL2 gene revealed a novel heterozygous mutation: an 11 bp duplication (c.901_911dup11) that was predicted to encode a truncated protein (p.Pro305Argfs*54). A novel out-of-frame duplication following the polyalanine domain in the FOXL2 gene was identified in a Chilean patient with BPES type I. This study characterized the molecular alterations in FOXL2 and confirmed the diagnosis, thereby providing information to allow for improved genetic counseling for the patient and her family.


Suppression of epidemic spreading in complex networks by local information based behavioral responses.
The interplay between individual behaviors and epidemic dynamics in complex networks is a topic of recent interest. In particular, individuals can obtain different types of information about the disease and respond by altering their behaviors, and this can affect the spreading dynamics, possibly in a significant way. We propose a model where individuals' behavioral response is based on a generic type of local information, i.e., the number of neighbors that has been infected with the disease. Mathematically, the response can be characterized by a reduction in the transmission rate by a factor that depends on the number of infected neighbors. Utilizing the standard susceptible-infected-susceptible and susceptible-infected-recovery dynamical models for epidemic spreading, we derive a theoretical formula for the epidemic threshold and provide numerical verification. Our analysis lays on a solid quantitative footing the intuition that individual behavioral response can in general suppress epidemic spreading. Furthermore, we find that the hub nodes play the role of "double-edged sword" in that they can either suppress or promote outbreak, depending on their responses to the epidemic, providing additional support for the idea that these nodes are key to controlling epidemic spreading in complex networks.


Interaction of external alkali metal ions with the Na-K pump of human erythrocytes: a comparison of their effects on activation of the pump and on the rate of ouabain binding.
The effects of external alkali metal ions on the rate of ouabain binding and on the rate of the Na-K pump were examined in human red blood cells. In Na-containing solutions, K, Cs, and Li decreased the rate of ouabain binding. For K and Cs, the kinetics of this effect were similar to those for their activation of the pump. In Na-free (choline-substituted) solutions the rate of ouabain binding was decreased by K whereas it was promoted by Cs and Li. External Na increased the rate of ouabain binding whether or not external K was present, and the kinetics of this effect were not the same as those for inhibition of the pump by Na. These findings are interpreted to mean that not only do the cations affect ouabain binding at the external loading sites on the pump from which ions are translocated inward, but that there are additional sites on the external aspect of the pump at which cations can promote ouabain binding, and that these sites can be occupied by Li, Na, and Cs. It is postulated that these latter sites are those from which Na is discharged after outward translocation by the pump.


Prevalence of impairments, disabilities, handicaps and quality of life in the general population: a review of recent literature.
To determine the prevalence rates of morbidity in the general population through bibliographic research. Articles relating to impairment, disability, handicap, quality of life and their prevalence in the general population, published between January 1990 and March 1998, were selected on the MEDLINE database. The 20 articles retained out of 433 used 41 different indicators. Indicators of impairment, disability, handicap and low quality of life showed prevalence rates of 0.1-92%, 3.6-66%, 0.6-56% and 1.8-26% respectively, depending on age and the accuracy of indicators. The heterogeneity of the conceptual framework and insufficient recognition of the importance of indicator accuracy, the age factor and the socioeconomic characteristics of the studied populations impede reliable international comparison. Further standardization of indicators is therefore required. The revision of the International Classification of Impairments, Disabilities and Handicaps may make it possible to resolve some of the difficulties encountered.


[Characteristics of the course and outcome of pregnancy in developmental anomalies of the uterus].
Ultrasonographic follow-up of 311 pregnant women with a history of habitual abortion has revealed uterine malformations in 61 (19.6%) women. An arcuate uterus was found in 25, bicornuate and duplex uterus in 20, septate uterus in 15 and unicornuate uterus in 1 women. The paper presents ultrasonographic criteria for the identification of uterine malformations and certain pregnancy complications. The study showed pregnancy outcomes to be correlated to malformation severity. The outcomes were satisfactory in the presence of the arcuate uterus and poor in the presence of the bicornuate and septate uterus. The findings suggest that all women with uterine malformations require a close follow-up throughout the pregnancy to make an earlier diagnosis and to remedy the abnormalities detected.


Immunohistochemical study of skin reinnervation by regenerative axons.
The time sequence of sensory and sudomotor nerve regeneration to the mouse footpad was studied between one and seven weeks after crush or section of the sciatic nerve. Protein gene product 9.5, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide were localized in thick sections by using indirect immunofluorescence techniques and imaged by confocal microscopy. Nerve regeneration was visually assessed in all nerves and quantified in sweat glands. After denervation, protein gene product 9.5 immunoreactivity remained as dim fluorescence within thick fibers of dermal nerve trunks, whereas thin nerve fibers to sweat glands and to epidermis disappeared. By 14 days postcrush and 35 days postsection, the first protein gene product 9.5 immunoreactive regenerating axons appeared in large nerve trunks, quickly extending to epidermis and sweat glands. Reinnervation of Meissner's corpuscles occurred nearly simultaneous with return of epidermal free nerve endings and sudomotor network. Calcitonin gene-related peptide, vasoactive intestinal peptide, and substance P immunoreactivity disappeared completely one week after denervation, then reappeared at 17-18 days postcrush and 35 days postsection. Fewer nerve fibers were immunoreactive to these peptides than to protein gene product 9.5. The overall density of reinnervation, although reduced, more closely resembled normal in the sweat glands and Meissner's corpuscles than in the epidermis. Reinnervation was more successful after crush than after nerve section. The time course for functional return of sweating paralleled the return of protein gene product 9.5 immunoreactivity, whereas appearance of vasoactive intestinal peptide was delayed by several days.


Minimum alveolar concentration threshold of sevoflurane for postoperative dream recall.
Many factors affect postoperative dream recall, including patient characteristics, type of anesthesia, timing of postoperative interview and stress hormone secretion. Aims of the study were to determine whether Bispectral Index (BIS)-guided anesthesia might decrease sevoflurane minimum alveolar concentration (MAC) when compared with hemodynamically-guided anesthesia, and to search for a MAC threshold useful for preventing arousal, dream recall and implicit memory. One hundred thirty patients undergoing elective thyroidectomy were enrolled. Anesthesia was induced with propofol 2 mg kg(-1), fentanyl 3 mcg kg(-1) and cis-atracurium 0.15 mg kg(-1). For anesthesia maintenance, patients were randomly assigned to one of two groups: a BIS-guided group in which sevoflurane MAC was adjusted on the basis of BIS values, and a hemodynamic parameters (HP)-guided group in which MAC was adjusted based on HP. An auditory recording was presented to patients during anesthesia maintenance. Dream recall and explicit/implicit memory were investigated upon awakening and approximately after 24 h. Mean sevoflurane MAC during auditory presentation was similar in the two groups (0.85 ± 0.16 and 0.87 ± 0.17 [P = 0.53] in BIS-guided and HP-guided groups, respectively). Frequency of dream recall was similar in the two groups: 27% (N. = 17) in BIS-guided group, 18% (N. = 12) in HP-guided group, P = 0.37. In both groups, dream recall was less probable in patients anesthetized with MAC values ≥ 0.9 (area under ROC curve = 0.83, sensitivity = 90%, and specificity = 49%). BIS-guided anesthesia was not able to generate different MAC values compared to HP-guided anesthesia. Independent of the guide used for anesthesia, a sevoflurane MAC over 0.9 was required to prevent postoperative dream recall.


Identification of Biofilm Inhibitors by Screening Combinatorial Libraries of Metal Oxide Thin Films.
With the rise in nosocomial infections worldwide, research on materials with an intrinsic ability to inhibit biofilm formation has been generating a great deal of interest. In the present work, we describe how thin film material libraries generated by pulsed laser deposition can be used for simultaneously screening several novel metal oxide mixtures that inhibit biofilm formation in a common human pathogen, Salmonella enterica serovar Typhimurium. We discovered that in a material library constructed using two metal oxides, the net effect on biofilm formation can be modeled as an addition of the activities of the individual oxides weighted to their relative composition at that particular point on the library. In contrast, for similar material libraries constructed using three metal oxides, there was a nonlinear relation between the amount of dominant metal oxide and the formation of Salmonella biofilms. This nonlinearity resulted in several useful metal oxide combinations that were not expected from the weighted average predictions. Our novel application will lead to the discovery of additional alternatives for creating antimicrobial surfaces.


Effect of oral hygiene maintenance on HbA1c levels and peri-implant parameters around immediately-loaded dental implants placed in type-2 diabetic patients: 2 years follow-up.
The aim of the present 2-year follow-up study was to assess the effect of oral hygiene maintenance on hemoglobin Alc (HbA1c) levels and peri-implant parameters around immediately-loaded dental implants placed in type-2 diabetic patients with varying glycemic levels. Ninety-one individuals were divided into three groups. In group 1, 30 systemically healthy individuals were included (HbA1c < 6%). Patients in group 2 and 3, comprised of 30 patients with T2DM (HbA1c 6.1-8%); and 31 patients with T2DM (HbA1c 8.1-10%) respectively. In all groups, patients received immediately loaded bone level implants. All participants were enrolled in a 6 monthly periodontal/peri-implant maintenance program. Peri-implant bleeding on probing (BOP), probing depth (PD), and marginal bone loss (MBL) were measured at 6, 12, and 24 months of follow-up. Mean preoperative HbA1c levels in patients in groups 1, 2, and 3 were 4.5%, 6.8%, and 8.7% respectively. In group-1, there was no significant difference in HbA1c levels at all follow-up durations. Among patients in groups 2 and 3, there was a significant decrease in HbA1c levels at 24-months follow-up than 6-months follow-up. At 6 months follow-up, BOP, PD, and MBL were significantly higher among patients in group-3 than group-1. At 12 and 24 months follow-up, there was no significant difference in BOP, PD, and MBL in all groups. Oral hygiene maintenance reduces hyperglycemia and peri-implant inflammatory parameters around immediately loaded dental implants placed in type 2 diabetic patients.


Insulin pump therapy started at the time of diagnosis: effects on glycemic control and pancreatic β-cell function in type 1 diabetes.
In the interest of preserving residual insulin secretory capacity present at the time of diagnosis with type 1 diabetes (T1D), we compared the efficacy of starting insulin pump therapy at diagnosis with standard multiple daily insulin injections (MDIs). We conducted a prospective, randomized, pilot trial comparing MDI therapy with continuous subcutaneous insulin therapy (pump therapy) in 24 patients, 8-18 years old, with newly diagnosed T1D. Subjects were evaluated at enrollment and 1, 3, 6, 9, and 12 months after initial diagnosis of T1D. Preservation of insulin secretion, measured by mixed-meal-stimulated C-peptide secretion, was compared after 6 and 12 months of treatment. Between-group differences in glycosylated hemoglobin (HbA1c), continuous glucose sensor data, insulin utilization, anthropometric measures, and patient satisfaction with therapy were also compared at multiple time points. Initiation of pump therapy within 1 month of diagnosis resulted in consistently higher mixed-meal tolerance test-stimulated C-peptide values at all time points, although these differences were not statistically significant. Nonetheless, improved glycemic control was observed in insulin pump-treated subjects (more time spent with normoglycemia, better mean HbA1c), and pump-treated subjects reported comparatively greater satisfaction with route of treatment administration. Initiation of insulin pump therapy at diagnosis improved glycemic control, was well tolerated, and contributed to improved patient satisfaction with treatment. This study also suggests that earlier use of pump therapy might help to preserve residual β-cell function, although a larger clinical trial would be required to confirm this.


The β-carboline Harmine improves the therapeutic benefit of anti-PD1 in melanoma by increasing the MHC-I-dependent antigen presentation.
Harmine is a dual-specificity tyrosine-regulated kinase 1A (DYRK1A) inhibitor that displays a number of biological and pharmacological properties. Also referred to as ACB1801 molecule, we have previously reported that harmine increases the presentation of major histocompatibility complex (MHC)-I-dependent antigen on melanoma cells. Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells. Treatment of mice bearing melanoma B16-F10 with ACB1801 inhibits the growth and weight of tumors and induces a profound modification of the tumor immune landscape. Strikingly, combining ACB1801 with anti-PD1 significantly improves its therapeutic benefit in B16-F10 melanoma-bearing mice. These results suggest that, by increasing the MHC-I, ACB1801 can be combined with anti-PD1/PD-L1 therapy to improve the survival benefit in cancer patients displaying a defect in MHC-I expression. This is further supported by data showing that i) high expression levels of TAP1, Tapasin and Lmp2 was observed in melanoma patients that respond to anti-PD1; ii) the survival is significantly improved in melanoma patients who express high MHC-I signature relative to those expressing low MHC-I signature; and iii) high expression of MHC-I signature in melanoma patients was correlated with increased expression of CD8 and NK cell markers and overexpression of proinflammatory chemokines involved in the recruitment of CD8+ T cells.


Novel approaches to immunotherapy for B-cell malignancies.
Immunotherapy for cancer refers to a wide array of novel therapeutic interventions that harness the immune system to target and eradicate malignant cells in the host. Advances in the understanding of how tumor cells evade host immune detection, coupled with improved gene transduction technologies, have enabled investigators to propose and test novel immune-based therapies for B-cell malignancies. As a result, more immunogenic vaccination strategies, able to elicit immune responses to otherwise poorly immunogenic tumor antigens, are being tested in early clinical trials. Furthermore, with the development of efficient T-cell transduction methodologies, investigators are able to generate autologous antitumor T-cell responses through the introduction of chimeric antigen receptors able to target tumor antigens. However, whether the promising preclinical and phase I clinical data presented here will ultimately translate into improved survival of patients with B-cell malignancies remains largely unknown.


Quality of life in mothers of preschoolers with high-functioning pervasive developmental disorders.
Parents of children with pervasive developmental disorders (PDD) are likely to experience serious distress. The aims of this study were to (i) assess distress among mothers of preschoolers with high-functioning PDD (HFPDD); and (ii) examine its relation to the child's behavioral characteristics. Participants were 30 mothers of preschoolers with HFPDD, and 30 mothers of a matched control group. Short Form 36 Health Survey Questionnaire (version 2), and the Strengths and Difficulties Questionnaire were used for assessment. The children's autistic traits were assessed using the total number of items for the DSM-IV-TR autistic disorder diagnosis. Mothers in the HFPDD group were more distressed mentally than physically. Neither physical nor mental distress in the group was related to the child's autistic traits, while their mental distress was significantly related to the child's behavior problems. Mothers in the HFPDD group were at increased risk of impaired mental wellbeing. Maternal mental distress in the group was significantly related to general behavior problems, but not to autistic traits in the child.


In situ caries models.
By using in situ models, we have the potential to study both fundamental aspects of the caries process as well as more applied research problems such as the effect of food on dental caries and the role of fluoride in caries prevention in human subjects without actually causing caries in the natural dentition. The key experimental parameters that need to be considered in the development of an in situ model are the characteristics of the subject panel, the physical design of the model, the type of hard tissue substrate and the method of assessing mineral status, and the study design and clinical protocol. Each parameter must be carefully considered in relation to the objectives of the research, study design requirements, ethical considerations, impact on clinical relevance, and impact on the control of variation. The major source of variation associated with in situ models should be of biological and not experimental origin. The design and conduct of proper in situ model studies require a clear understanding of the caries process, sound analytical support, and a knowledge of how to work with research subjects to achieve a high level of compliance. Given the complex nature of caries, a combination of hard tissue substrates--including sound, surface-softened lesions and subsurface lesions--may be necessary to model all aspects of caries progression and prevention successfully. Internal validation of in situ models using fluoride dose-response controls is considered to be necessary for studies evaluating the efficacy of new fluoride dentifrice formulations.


Association between convalescent plasma and the risk of mortality among patients with COVID-19: a meta-analysis.
Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Embase, PubMed, Web of Science, Cochrane and MedRix were searched for potentially relevant articles. All included papers were assessed for the quality using modified Jadad scale and Newcastle-Ottawa scale for randomized controlled trial (RCT) and non - RCT, respectively. We used a Q test and Egger test to assess the heterogeneity and publication bias among studies, respectively. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 12 papers consisting of three cross-sectional studies, one prospective study, five retrospective studies, and three RCT studies were included in our analysis. Of them, a total of 1,937 patients treated with CCP and 3,405 patients without CCP were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without CCP had a 1.32 times higher risk of mortality than those treated with CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, could reduce the mortality rate among COVID-19 patients.


[Observation of three anti-M. tuberculosis antibodies in children with tuberculosis during chemotherapy].
Earlobe blood from 122 children with tuberculosis and 187 healthy children were assayed for anti-OTIgG, anti-PPDIgG and anti-Ag6IgG by ABC-ELISA. We found that the mean levels and sensitivity of anti-OTIgG and anti-PPDIgG decreased significantly in patients receiving more than 3 months of chemotherapy, but the anti-Ag6IgG remained constant. 18 patients were followed up for 12 months. among them 6 patients had a conversion from negative of anti-Ag6IgG to positive results. It is suggested that IgG to various M. tuberculosis antigens changes differently during the chemotherapy.


A three-month longitudinal study of changes in day/night serum total antioxidant capacity in paranoid schizophrenia.
Free radicals and an oxidant/antioxidant imbalance have been involved in the schizophrenia pathophysiology. The total antioxidant capacity (TAC) is a measure of the antioxidant capacity of a system. Day/night changes are a biological characteristic of hormones such as melatonin or cortisol. There is little information about TAC day/night changes in schizophrenia patients. The aim of this research is to study if there are day/night changes in serum TAC levels of schizophrenia patients. Thirty-two DSM-IV schizophrenia paranoid patients were studied. Blood was sampled at 12:00 and 00:00 h at admission, discharge and three months after hospital discharge (TMAHD). TAC results are expressed as mmol of Trolox/L. Patients did not have day/night TAC differences at admission (12:00: 0.67±0.12 vs. 00:00: 0.61±0.14, p>0.14) or discharge (12:00: 0.65±0.15 vs. 00:00: 0.65±0.12, p>0.99). At TMHD, patients had significantly higher TAC levels at midday than midnight (12:00: 0.83±0.10 vs. 00:00: 0.74±0.12, p<0.006) as it has been reported in healthy subjects. There were no significant TAC differences at 12.00 and 00:00 between admission and discharge. At TMAHD, patients had significantly higher TAC levels than at admission and discharge, both at 12:00 and 00:00 h. In conclusion, the absence of day/night serum TAC changes when clinically relapsed and the normalization of day/night serum TAC changes at TMHD can be considered as a biological marker of schizophrenia evolution.


Effects of Treatment of Asymptomatic Hyperuricemia on Graft Survival and Mortality in Kidney Transplant Recipients.
BACKGROUND Hyperuricemia is very common after renal transplantation. It is associated with an increased risk of cardiovascular events and graft loss. To date, however, treatment is only recommended in symptomatic disease. MATERIAL AND METHODS We included 503 adult patients who underwent kidney transplantation at the Charité-Universitätsmedizin Berlin in this retrospective study. Patients were followed up for up to 120 months. All-cause mortality, graft survival, changes in level of serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were analyzed. RESULTS At 12 months post-transplantation, 225 patients had a serum uric acid (SUA) level >7 mg/dl: 52 patients were treated with allopurinol, 37 with benzbromarone, and 136 patients received no medication for hyperuricemia (control). At 12 months, eGFR did not differ between groups (p=0.15) but treated patients had higher SUA levels (p<0.001) compared to the control group. SUA-lowering treatment was associated with a lower risk of all-cause mortality (p=0.013) and graft loss (p=0.014) compared to controls. At 120 months, patients in the treatment group had lower SUA levels (p=0.001) and higher eGFR (p<0.001) compared to the control group. CONCLUSIONS Treatment of asymptomatic hyperuricemia was associated with a substantial benefit in patient and graft survival.


[The lymph and blood microcirculatory beds of the pancreas in the early period of experimental acute pancreatitis].
Results of the study evidence that in the early period of acute experimental pancreatitis (AEP)--from 10 minutes to 2 hours--changes in acino-capillary complex consist in compensatory-adaptive reaction and are related to metabolic disorders. Abortive interstitial oedema disappears in 20-30-minutes, dilated lymphatic vessels being visible macroscopically. Further progress of oedema with consequent focal haemorrhagic pancreonecrosis is possible in case of insufficient lymphatic drainage. The latter may be due both to destruction of lymphatic endotheliocytes and barrage of lymphatic ways with agglutinates. This indicates primacy of enzymatic alteration of pancreatocytes and secondary nature of vascular changes as well as necessity of early intensive care aimed at correction of lympho- and haemocirculation.


A study to assess and compare the peripheral blood neutrophil chemotaxis in smokers and non smokers with healthy periodontium, gingivitis, and chronic periodontitis.
Chronic periodontitis is the inflammation within the supporting tissues of the teeth resulting in attachment loss and bone loss. There are certain environmental factors such as smoking that can modify the host response to plaque organisms; hence can account for the aggressive progression of the disease. Smokers show a decreased expression of clinical inflammation even in the presence of abundant plaque accumulation. Neutrophils are the predominant host defense cells which protect the periodontal tissues from plaque organisms, deficiencies of neutrophil function, such as chemotaxis and phagocytosis, often result in increased susceptibility to periodontitis. Smoking can induce alteration in the neutrophil function; therefore, it is of importance to know the changes caused by smoking on neutrophil chemotaxis. This study will provide an essential basis for evaluating the role of nicotine in pathogenesis of periodontal disease by assessing the neutrophil activity. A total of 60 smokers and 60 non smokers were examined for this study. Both the groups included 20 subjects with gingivitis, periodontitis, and healthy periodontium. The periodontal status of the study subjects were assessed by gingival index, Russels periodontal index, sulcus bleeding index, and clinical attachment level. The blood sample was taken from each individual for the chemotactic analysis using agarose method. In this study, there was a significant decrease in the neutrophil chemotaxis in smokers with gingivitis, periodontitis, and healthy periodontium, compared to non smokers with similar findings. Delayed neutrophil chemotaxis was found in smokers compared to non smokers with same periodontal status.


Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer.
Abnormal lipid metabolism often occurs under hypoxic microenvironment, which is an important energy supplement for cancer cell proliferation and metastasis. We aimed to explore the lipid metabolism characteristics and gene expression features of pancreatic ductal adenocarcinoma (PDAC) related to hypoxia and identify biomarkers for molecular classification based on hypoxic lipid metabolism that are evaluable for PDAC prognosis and therapy. The multiple datasets were analyzed integratively, including corresponding clinical information of samples. PDAC possesses a distinct metabolic profile and oxygen level compared with normal pancreatic tissues, according to the bioinformatics methods. In addition, a study on untargeted metabolomics using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry(UPLC-MS) revealed lipid metabolites differences affected by oxygen. Analysis of PDAC gene expression profiling in The Cancer Genome Atlas (TCGA) revealed that the sphingolipid process correlates closely with HIF1α. According to the characters of HIF-1 and sphingolipid, samples can be clustered into three subgroups using non-negative matrix factorization clustering. In cluster2, patients had an increased survival time. Relatively high MUC16 mutation arises in cluster2 and may positively influence the cancer survival rates. This study explored the expression pattern of lipid metabolism under hypoxia microenvironment in PDAC. On the basis of metabolic signatures, we identified the prognosis subtypes linking lipid metabolism to hypoxia. The classifications may be conducive to developing personalized treatment programs targeting metabolic profiles.


Oral-facial clefts and associated malformations in the squirrel monkey (Saimiri sciureus).
Of the 414 squirrel monkey pregnancies recorded at this institution since 1977, seven (1.7%) have resulted in offspring with clefts of the lip and/or palate. Associated malformations include a ventricular septal defect, renal agenesis, anal atresia, axial skeletal anomalies, and craniorachischisis (anencephaly and spina bifida). Three of these infants are the result of consanguineous matings.


Risk Factors for Death Among Veterans Following Acute Kidney Injury.
Acute kidney injury is prevalent among hospitalized veterans, and associated with increased risk of death following discharge. However, risk factors for death following acute kidney injury have not been well defined. We developed a mortality prediction model using Veterans Health Administration data. This retrospective cohort study included inpatients from 2013 through 2018 with a creatinine increase of ≥0.3 mg/dL. We evaluated 45 variables for inclusion in our final model, with a primary outcome of 1-year mortality. Bootstrap sampling with replacement was used to identify variables selected in >60% of models using stepwise selection. Best sub-sets regression using Akaike information criteria was used to identify the best-fitting parsimonious model. A total of 182,683 patients were included, and 38,940 (21.3%) died within 1 year of discharge. The 10-variable model to predict mortality included age, chronic lung disease, cancer within 5 years, unexplained weight loss, dementia, congestive heart failure, hematocrit, blood urea nitrogen, bilirubin, and albumin. Notably, acute kidney injury stage, chronic kidney disease, discharge creatinine, and proteinuria were not selected for inclusion. C-statistics in the primary validation cohorts were 0.77 for the final parsimonious model, compared with 0.52 for acute kidney injury stage alone. We identified risk factors for long-term mortality following acute kidney injury. Our 10-variable model did not include traditional renal variables, suggesting that non-kidney factors contribute to the risk of death more than measures of kidney disease in this population, a finding that may have implications for post-acute kidney injury care.


Health Vulnerability Index for Disaster Risk Reduction: Application in Belt and Road Initiative (BRI) Region.
Despite the importance of health vulnerability in disaster risk assessment, most of the existing disaster vulnerability indicators only emphasize economic and social vulnerability. Important underlying health risks such as non-communicable disease are not included in vulnerability measures. A three-phase methodology approach was used to construct a disaster risk model that includes a number of key health indicators which might be missing in global disaster risk analysis. This study describes the development of an integrated health vulnerability index and explains how the proposed vulnerability index may be incorporated into an all-hazard based disaster risk index in the Belt and Road Initiative (BRI), also known as the "Silk Road Economic Belt", region. Relevant indicators were identified and reviewed in the published literature in PubMed/Medline. A two-stage dimension reduction statistical method was used to determine the weightings of relevant dimensions to the construction of the overall vulnerability index. The proposed final health vulnerability index included nine indicators, including the proportion of the population below 15 and above 65 years, under-five mortality ratio, maternal mortality ratio, tuberculosis prevalence, age-standardized raised blood pressure, physician ratio, hospital bed ratio, and coverage of the measles-containing-vaccine first-dose (MCV1) and diphtheria tetanus toxoid and pertussis (DTP3) vaccines. This proposed index, which has a better reflection of the health vulnerability in communities, may serve as a policy and implementation tool to facilitate the capacity-building of Health-Emergency Disaster Risk management (Health-EDRM).


Proteolytic cleavage of ras GTPase-activating protein during apoptosis.
p120-ras GTPase-activating protein (rasGAP) associates with Ras and negatively regulates Ras signaling by stimulating the intrinsic rate of Ras GTPase activity. rasGAP also associates with other cellular signaling proteins which suggest that rasGAP may play a role in coordinating other signal transduction pathways. Disruption of rasGAP in vivo results in extensive apoptosis. Fas-mediated apoptosis results in the activation of caspases that cleave cellular substrates which are important for maintaining cytoplasmic and nuclear integrity. We show here that rasGAP is proteolytically cleaved by caspases early in Fas-induced apoptosis of Jurkat cells. rasGAP was also cleaved by DNA-damaging chemotherapeutic agents and TNF-related apoptosis inducing ligand (TRAIL), also known as Apo2L. Based on the size of the products generated by cleavage of deletion mutants of rasGAP we predict that cleavage of rasGAP occurs in the hydrophobic region and between the SH2(2) and ras-p21 interacting domain which would leave an intact ras-p21 interacting domain. Interestingly, cleavage of rasGAP in vitro enhanced rasGAP hydrolysis activity. Our results demonstrate that diverse apoptotic stimuli cause caspase-mediated cleavage of rasGAP early in apoptosis.


The effects of a full-scale anaerobic side-stream reactor on sludge decay and biomass activity.
A full-scale anaerobic side-stream reactor (ASSR) for sludge reduction was monitored in terms of sludge production and compared with the previous conventional activated sludge configuration (CAS). A detailed solid mass balance was calculated on the whole full-scale plant to estimate the sludge reduction associated with the ASSR. The activity of the biomass, which undergoes alternation of aerobic and anaerobic conditions, was investigated by the respirometric test. The ASSR promoted a reduction of heterotrophic biomass activity and the substrate consumption rate in the activated sludge implemented with ASSR (AS + ASSR) was 36% smaller than in the CAS period. The solid mass balance indicated a sludge reduction of 28%. During the 270-day operation, the observed sludge yield passed from 0.438 kgTSS/kgCOD in the CAS to 0.315 in the AS + ASSR configuration. The solubilization of chemical oxygen demand (COD), NH4 +-N and orthophosphate were verified under anaerobic conditions. The results suggest that the possible mechanisms of sludge reduction were the increase of the system sludge retention time (SRT) by ASSR addition, and the reduction in heterotrophic biomass activity added to the organic compounds' hydrolysis.


[Comparative characteristics of cytosol glucocorticoid receptors from normal liver, the liver of tumor-bearing rats and hormone unresponsive Zajdela hepatoma].
Specific dexametasone (D) and cortisol (F) receptors have been found both in liver and Zajdela hepatoma. Rat liver cytosol receptors are characterized by the association constant (Kas) = 3,8 X 10(8) M-1 for D and 0,57 X 10(8) M-1 for F as well as by a number of binding sites (NBS)=4,9 X 10(-13) moles/mg protein and 4,06 X 10(-13) moles/mg protein, respectively. The receptors show stric specificity to glucocorticoids. Cytosol glucocorticoid-receptor complexes from liver and hepatoma sediment at 6-7S, when centrifuged in the buffer of a low ionic strength, and at 3-4S in the buffer of a high ionic strength (0,4 M KCl). The properties of cytosol receptors in the course of in vivo hepatoma growth were found to be gradually altering: Kas for D dropped whereas that for F increased; the NBS is decreased 3-4 fold as compared to normal liver cytosol--which may partially be accounted for by the unresponsiveness of the tumour to the hormones.


Backbone statistical potential from local sequence-structure interactions in protein loops.
Native proteins have been optimized by evolution simultaneously for structure and sequence. Structural databases reflect this interdependency. In this paper, we present a new statistical potential for a reduced backbone representation that has both structure and sequence characteristics as variables. We use information from structural data available in the Protein Coil Library, selected on the basis of resolution and refinement factor. In these structures, the nonlocal interactions are randomly distributed and, thus, average out in statistics, so structural propensities due to local backbone-based interactions can be studied separately. We collect data in the form of local sequence-specific phi-psi backbone dihedral pairs. From these data, we construct dihedral probability density functions (DPDFs) that quantify any adjacent phi-psi pair distribution in the context of all possible combinations of local residue types. We use a probabilistic analysis to deduce how the correlations encoded in the various DPDFs as well as in residue frequencies propagate along the sequence and can be cumulated in a statistical potential capable of efficiently scoring a loop by its backbone conformation and sequence only. Our potential is able to identify with high accuracy the native structure of a loop with a given sequence among possible alternative conformations from sets of well-constructed decoys. Conversely, the potential can also be used for sequence prediction problems and is shown to score the native sequence of a given loop structure among the most fit of the possible sequence combinations. Applications for both structure prediction and sequence design are discussed.


Angle of insertion and confirmation of angles measured after in vitro implantation during laminar vertebral stabilization in vertebral columns obtained from canine cadavers.
To determine angles of insertion for laminar vertebral fixation of L1 and L2 by use of a locking plate in dogs and to confirm screw placement by use of computed tomography (CT). Vertebral specimens harvested from 8 canine cadavers. The point of insertion and minimum and maximum insertion angles for laminar and facet screws for laminar vertebral stabilization were determined by use of CT. A precontoured locking plate was then placed by use of 1 locking screw in the lamina of each lumbar vertebra and 1 nonlocking screw in the facet joint. The position and angle of the screws were examined by use of CT, and penetration into the vertebral canal was recorded. Mean ± SD insertion angles for L1 and L2 were 18 ± 4° and 21 ± 5° toward the vertebral canal and 11 ± 4.4° and 10 ± 3° in a dorsal direction, respectively. Insertion angles for the facet joint were between 24 ± 4° ventrally and 12 ± 2° dorsally. Insertion of the screw did not penetrate the vertebral canal for 23 of 24 (96%) screws. For 23 of 24 inserted screws, the previously determined angle was maintained and purchase of bone and cortices was satisfactory. Placement of laminar and facet screws in canine vertebrae was possible and can be performed safely if angles of insertion determined pre-operatively via CT are maintained.


Elimination of ghosting artifacts from wavelength-shifting fiber neutron detectors.
Misassignment of neutron position (ghosting) produces artifacts which have been observed in wavelength-shifting (WLS) fiber detectors developed for time-of-flight (TOF) neutron powder diffraction. In position-sensitive detectors (PSDs) with WLS fiber encoding, thermal and cold neutrons interact with a monolithic (6)LiF/ZnS:Ag scintillator screen, and scintillation photons are generated and transported through the crossed fibers to photomultipliers (PMTs). The neutron position is determined by photon counts in the PMTs within a preset time window. Ghosting occurs when neutrons hit the group boundaries of two neighboring PMTs for x-position multiplexing, which is modeled as resulting from a long travel length (about 3-5 mm) of a small number of scintillation photons. This model is supported by the change observed in aperture images when the threshold number for photon-pulses was adjusted for neutron event determination. When the threshold number of photon-pulses was set above 10 for each PMT, the ghost peaks in the aperture images and TOF spectra of powder diffraction were strongly suppressed or completely eliminated, and the intrinsic background levels of the WLS detectors were significantly reduced. Our result indicates that WLS fiber detector is a promising alternative for (3)He PSDs for neutron scattering.


Entrapment of the flexor digitorum superficials in the radius fracture site.
Entrapment of the flexor tendon after fracture of both forearm bones is very rare. This report describes entrapment of the middle finger flexor digitorum superficialis (FDS) tendon alone in the radius fracture site. A 13-year-old boy fractured both forearms and had closed reduction and a long-arm cast. After the cast was removed he had full middle finger motion with the wrist flexed but was unable to extend the proximal interphalangeal or metacarpophalangeal joints and could extend only the distal interphalangeal joint of the middle finger with the wrist in the neutral or extension position. Entrapment of the middle finger FDS tendon was suspected. After surgical release of the FDS tendon at the fracture site the patient had good functional results.


Is Toothbrush Bristle Stiffness Associated with Erosive Tooth Wear in Adolescents? Findings from a Population-Based Cross-Sectional Study.
This population-based cross-sectional study investigated the association between toothbrush bristle stiffness and the occurrence of erosive tooth wear (ETW) among 15- to 19-year-old adolescents from southern Brazil. Data collection included the application of questionnaires and clinical examination. One questionnaire on sociodemographic information (sex, age, and socioeconomic status) was sent to the parents/legal guardians, while the other was applied to students and collected data regarding oral hygiene habits (toothbrushing frequency, toothbrushing after meals, and toothbrush bristle stiffness) and dietary habits (frequency of consumption of soft drinks, citric fruits, and fruit juice). After tooth cleaning and drying, all erupted permanent teeth were clinically assessed and classified according to the Basic Erosive Wear Examination (BEWE) by 2 calibrated examiners. The association between explanatory variables and ETW prevalence was assessed using Poisson regression models. Prevalence ratios (PRs) and their 95% confidence intervals (CIs) were estimated. A total of 1,197 adolescents were included (participation rate 72.3%). The overall prevalence of ETW was 57%. The final model showed that individuals who used toothbrushes with soft (PR = 1.28, 95% CI = 1.02-1.60) or medium (PR = 1.30, 95% CI = 1.01-1.69) bristles presented a higher ETW prevalence than those who used toothbrushes with extra-soft bristles, even after the adjustment for important cofactors. In conclusion, this study found a very weak but significant association between toothbrush bristle stiffness and ETW among Brazilian adolescents. Considering the cross-sectional design of this study and considering that some association was found even in such a young population, future studies using different designs and including different age-groups might elucidate the clinical relevance of this finding.


[A primary mucus-producing adenocarcinoma of the appendix with a bilateral Krukenberg tumor].
A patient is described with a primary mucous adenocarcinoma of the appendix with bilateral Krukenberg tumours. On the basis of the available literature the value of diagnosing a Krukenberg tumour of the ovaries is elucidated. Finally the question is raised whether this matter should influence policy as regards colorectal tumours.


Cloning of a novel monoamine oxidase cDNA from trout liver.
A trout liver monoamine oxidase (MAO) cDNA was cloned by screening a cDNA library with a human MAO-A cDNA probe. The trout MAO cDNA encodes 499 amino acids, with a molecular mass of 56.6 kDa. The deduced amino acid sequence of trout MAO shows 70% and 71% identity with those of human MAO-A and MAO-B, respectively. Trout MAO contains the pentapeptide sequence Ser-Gly-Gly-Cys-Tyr, to which the cofactor FAD is covalently bound. Transient expression of the cDNA in COS-7 cells shows that trout MAO oxidizes both serotonin [5-hydroxytryptamine (5-HT)] and beta-phenylethylamine (PEA), unlike human MAO-A and MAO-B, which oxidize only 5-HT and PEA, respectively. The Km for 5-HT is similar for trout MAO (130 +/- 17 mM) and human MAO-A (68 +/- 4 mM). The Km for PEA is similar for trout MAO (12.5 +/- 2.0 mM) and human MAO-B (1.5 +/- 0.2 mM). When 5-HT is used as a substrate, trout MAO is more sensitive to clorgyline (IC50, 2.8 +/- 0.2 x 10(-8) M) than deprenyl (IC50, 1.0 +/- 0.1 x 10(-6) M), a result similar to the inhibition selectivity of human MAO-A. However, trout MAO is less sensitive to clorgyline than is human MAO-A (IC50, 5.8 +/- 0.1 x 10(-10) M). Trout MAO is less sensitive to deprenyl (IC50, 4.6 +/- 0.3 x 10(-7) M) than is human MAO-B (IC50, 1.4 +/- 0.1 x 10(-9) M) when PEA is used as the substrate. These results indicate that trout MAO displays substrate and inhibitor selectivities that are not identical to those of either MAO-A and -B, and it therefore represents a novel type of MAO. The structure of trout MAO will provide insights into the substrate and inhibitor selectivities of the MAOs.


Transient Migration of Large Numbers of CD14(++) CD16(+) Monocytes to the Draining Lymph Node after Onset of Inflammation.
The dynamics of skin-draining cells following infection or vaccination provide important insight into the initiation of immune responses. In this study, the local recruitment and activation of immune cells in draining lymph nodes (LNs) was studied in calves in an adjuvant-induced inflammation. A transient but remarkably strong recruitment of monocytes was demonstrated after onset of inflammation, constituting up to 41% of live cells in the draining LNs after 24 h. Numerous CD14(+) cells were visualized in subcutaneous tissues and draining LNs, and the majority of these cells did not express dendritic cell-associated markers CD205 and CD11c. In the LNs, recruited cells were predominately of a CD14(++) and CD16(+) phenotype, consistent with an intermediate monocyte subset characterized to possess a high inflammatory potential. Moreover, monocytes from the draining LN showed a high expression of genes coding for pro-inflammatory cytokines, including IL-1β, IL-6, TNFa, and TGFβ. Shortly after their appearance in the LN cortical areas, the monocytes had moved into the medulla followed by an increase in peripheral blood. In conclusion, this study provides novel information on in vivo monocyte recruitment and migration after onset of inflammation.


Serum trace elements levels in preeclampsia and eclampsia: correlation with the pregnancy disorder.
Preeclampsia and eclampsia are fatal medical complications of pregnancy accounting for 20-80 % of increased maternal death in developing countries. Their aetiologies are still under investigation. Serum trace elements have been suggested to be involved in the pathogenesis of preeclampsia. Aim of this study was to address the correlation of serum trace elements with preeclampsia and eclampsia. It was a comparative cross-sectional study conducted on conveniently recruited 44 preeclampsia, 33 eclampsia and 27 normotensive pregnant patients. Atomic absorption spectrometry was employed to analyse serum concentrations of Ca, Mg, Cu, Zn and Fe. Data were analysed by Student's t test, one-way analysis of variance and multinomial logistic and binary regression analyses. p < 0.05 was considered as a level of significance. In preeclampsia, the serum Ca and Mg were significantly lower than those in eclampsia, while Cu and Zn values were higher. Significant changes of Ca, Mg and Cu were noted among preeclampsia, eclampsia and pregnant control. Serum Ca and Mg indicated a positive association, and Cu gave a negative association in preeclampsia. Cu/Fe ratio was high in eclampsia. Significant correlations of Mg with Zn in eclampsia and Mg with Fe in preeclampsia and eclampsia were predicted. Significant changes in serum trace element levels were present in preeclampsia and eclampsia that may have a link with the pathogenesis of pregnancy disorder.


Resilience from coastal protection.
Coastal areas are important residential, commercial and industrial areas; but coastal hazards can pose significant threats to these areas. Shoreline/coastal protection elements, both built structures such as breakwaters, seawalls and revetments, as well as natural features such as beaches, reefs and wetlands, are regular features of a coastal community and are important for community safety and development. These protection structures provide a range of resilience to coastal communities. During and after disasters, they help to minimize damages and support recovery; during non-disaster times, the values from shoreline elements shift from the narrow focus on protection. Most coastal communities have limited land and resources and few can dedicate scarce resources solely for protection. Values from shore protection can and should expand to include environmental, economic and social/cultural values. This paper discusses the key aspects of shoreline protection that influence effective community resilience and protection from disasters. This paper also presents ways that the economic, environmental and social/cultural values of shore protection can be evaluated and quantified. It presents the Coastal Community Hazard Protection Resilience (CCHPR) Index for evaluating the resilience capacity to coastal communities from various protection schemes and demonstrates the use of this Index for an urban beach in San Francisco, CA, USA.


Beautiful stranger: Voices from the front lines of community practice in Israel.
Over the past few decades, economic, political and cultural forces have altered the development of social policies and affected the life circumstances of oppressed communities in many countries. In response, calls for greater understanding and awareness of macro practice skills and interventions have been increasing within many of the social care professions. These calls have been particularly strong within the social work profession. A major field in macro social work is community practice, which aims to help people organise, plan and act for change. To date, there has been a dearth of studies examining social workers' involvement in community practice at the ground level. Drawing on in-depth interviews with 26 community social workers in public social services in Israel, this qualitative study examines community social workers' everyday experiences of community practice and the meanings they attribute to it. Findings highlight three main themes: (a) the elusive and unbounded nature of community practice; (b) the tense relations that community social workers maintain with various actors within the profession; and (c) the complex relations they maintain with the communities in which they work. We discuss these findings in light of Georg Simmel's concept of 'the stranger'. Implications to community practice are outlined.


Improving self-sufficiency in organ transplantation in Korea.
After attaining a qualified medical capacity in organ transplantation, Korea has been struggling to increase the number of deceased organ transplants to reach self-sufficiency. As one of these efforts, Korea revised the organ transplantation law in 2010 by adding three articles the mandatory reporting based on the recommendation of the 3rd Global Consultation on Organ Transplantation of Madrid in 2010. Along with the new constitution, considerable efforts have been initiated to upgrade the deceased organ transplantation system while maintaining the virtues of fairness, justice, and transparency. The Korean Society of Transplantation played a critical role in revising the law as well as in establishing organizations such as the Korean Organ Donation Agency (KODA; 2009), the Vitallink (2009), and the Korean Organ Transplantation Registry (KOTRY; 2010). By the activities of these professional organizations, Korea could implement fundamental programs such as mandatory reporting and could develop various education programs for organ donation for students and the general population. As a result, the number of deceased donors increased from 1.08 p.m.p. (2000) to 9.23 p.m.p.(2020). Further efforts are needed to increase the number of organ donor cardholders and family consent rates by well-designed, target-specific education programs to overcome traditional negative cultural barriers toward organ donation. The community atmosphere of honoring and thanking donors and their families should be nurtured by national and regional activities of life-sharing weeks linked with organ donor memorial parks.


Fasting plasma glucose and lipid profiles of diabetic patients improve with aerobic exercise training.
This study presents the effects of aerobic exercise training on fasting plasma glucose and lipid profiles (FPG/LP) of diabetic patients in Kumasi. A randomised experimental with control design. The study was conducted at the diabetic unit of KATH in Kumasi, Ghana. Twelve diabetic patients [grouped into intervention (IG) and control (CG)] attending the diabetic unit of KATH with diabetes diagnosis durations less than fifty years, ambulant status/age of 20-68years, sedentary and free from complications. Eight weeks aerobic exercise training between August 2015 and March 2016. Body weight (BW), Body mass index (BMI), fasting plasma glucose (FPG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (T) and total cholesterol (TC). Body weight (4.85kg, 7.0%), body mass index (4.08kg/m2, 7.3%), FPG (5.28mmol/L, 43.5%), LDL-C (.33mmol/l, 11.9%), TC (.47 mmol/l, 5.3%) and T (.48mmol/l, 29.4%) profiles of the patients in IG declined while HDL-C (.11mmol/l, 7.1%) increased. IG patients improved significantly in FPG [6.27 ± 0.91 < 8.00 ± 0.96; t=-52.00, P = 0.000], BW [58.60 ± 15.34 < 75.35 ± 22.00; t= 3.29, P = 0.040] and BMI [23.45 ±5.03<27.04 ±4.78, t=4.24, P = .050] compared to CG. Patients in IG, in addition to conventional care, experienced non-significant decline in LDL-C, TC, T, increase in HDL-C and significant reduction in FPG, BW, and BMI over those receiving conventional care only. Exercise Scientists are recommended to handle exercise sessions for healthcare prevention and management routines of diabetic patients. Not declared.


Suboptimal T-cell Therapy Drives a Tumor Cell Mutator Phenotype That Promotes Escape from First-Line Treatment.
Antitumor T-cell responses raised by first-line therapies such as chemotherapy, radiation, tumor cell vaccines, and viroimmunotherapy tend to be weak, both quantitatively (low frequency) and qualitatively (low affinity). We show here that T cells that recognize tumor-associated antigens can directly kill tumor cells if used at high effector-to-target ratios. However, when these tumor-reactive T cells were present at suboptimal ratios, direct T-cell-mediated tumor cell killing was reduced and the ability of tumor cells to evolve away from a coapplied therapy (oncolytic or suicide gene therapy) was promoted. This T-cell-mediated increase in therapeutic resistance was associated with C to T transition mutations that are characteristic of APOBEC3 cytosine deaminase activity and was induced through a TNFα and protein kinase C-dependent pathway. Short hairpin RNA inhibition of endogenous APOBEC3 reduced rates of tumor escape from oncolytic virus or suicide gene therapy to those seen in the absence of antitumor T-cell coculture. Conversely, overexpression of human APOBEC3B in tumor cells enhanced escape from suicide gene therapy and oncolytic virus therapy both in vitro and in vivo Our data suggest that weak affinity or low frequency T-cell responses against tumor antigens may contribute to the ability of tumor cells to evolve away from first-line therapies. We conclude that immunotherapies need to be optimized as early as possible so that, if they do not kill the tumor completely, they do not promote treatment resistance.


[The experience of enteral feeding with nasojejunal tube in children in critical state].
The article deals with the experience of setting and use of jejunal tube in children in critical state. The terms and procedure of jejunal tube with the purpose of satisfaction of plastic and energy needs and prevention of the multiple organ failure development.


Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition.
A white female, now age 40 and receiving total parenteral nutrition for more than 5 years, developed unexpected 15% weight loss after 3 1/2 years of regimen, together with peripheral neuropathy confirmed by nerve conduction measurements. An intravenous glucose tolerance test showed that the fractional rate (K) had decreased to 0.89%/min (normal greater than 1.2). There was observed during this glucose infusion a borderline normal insulin response with a fall in plasma free fatty acids and in plasma leucine. During daily infusion of well over 400 g of glucose, the respiratory quotient was 0.66. Chromium balance was negative. Chromium levels were, in blood 0.55 ng/ml (normal 4.9 to 9.5) and in hair 154 to 175 ng/g (normal greater than 500). Regular insulin daily (45 micron) in the infusate nearly maintained euglycemia but despite this, and even with further glucose intake to restore weight loss, intravenous glucose tolerance test (K) and respiratory quotient were unchanged. Administration of insulin was then stopped and 250 microng of Cr added to the daily total parenteral nutrition infusate for 2 weeks. After this the intravenous glucose tolerance test (K) and respiratory quotient became normal (1.35 and 0.78, respectively). Over the next 5 months insulin was not needed and glucose intake had to be reduced substantially to avoid overweight. In this period nerve conduction and well-being returned to normal. With a maintenance addition of chromium to the total parenteral nutrition infusate (tentatively this addition is 20 microng/day) the patient has remained well for 18 months (to July 1976). These results suggest that relatively isolated chromium deficiency in man, hitherto poorly documented, causes 1) glucose intolerance, 2) inability to utilize glucose for energy, 3) neuropathy with normal insulin levels, 4) high free fatty acid levels and low respiratory quotient and, 5) abnormalities of nitrogen metabolism.


Voltage-induced dependence of Raman-active modes in single-wall carbon nanotube thin films.
We report on electrical Raman measurements in transparent and conducting single-wall carbon nanotube (SWNT) thin films. Application of external voltage results in downshifts of the D and G modes and in reduction of their intensity. The intensities of the radial breathing modes increase with external electric field related to the application of the external voltage in metallic SWNTs, while decreasing in semiconducting SWNTs. A model explaining the phenomenon in terms of both direct and indirect (Joule heating) effects of the field is proposed. Our work rules out the elimination of large amounts of metallic SWNTs in thin film transistors using high field pulses. Our results support the existence of Kohn anomalies in the Raman-active optical branches of metallic graphitic materials.


Modification of iron status in young overweight/mildly obese women by two dietary interventions designed to achieve weight loss.
To determine the modification of iron status in a group of overweight/mildly obese women following two different weight control programs. The study subjects were 57 women who were assigned to one of two slightly hypocaloric diets: V (increased consumption of vegetables), or C (increased consumption of cereals, especially breakfast cereals). All data were determined at the start of the study and at 2 and 6 weeks into the dietary intervention period. Both diets led to a reduction in body weight and heme iron intake, and an increase in the intake of total and non-heme iron, at 2 and 6 weeks. At 6 weeks, a reduction in transferrin levels was seen in C subjects. Subjects with the worst initial iron status (hemoglobin <P25: 12.6 g/l) following C diet showed an increase of mean corpuscular hemoglobin concentration at 2 and 6 weeks and improved hemoglobin levels at 6. Also at 6 weeks, the C subjects had more erythrocytes than similar V subjects (only considering women with hemoglobin <P25: 12.6 g/l). A well-designed hypocaloric diet need not entail a risk of iron deficiency. Breakfast cereals are an important source of non-heme iron and could help to improve iron status, especially in women with poor initial iron levels.


Endothelial protection by pentaerithrityl trinitrate: bilirubin and carbon monoxide as possible mediators.
Pentaerithrityl tetranitrate (PETN) is a long-acting donor of nitric oxide (NO) and has recently been characterized as an antianginal agent that, in contrast with other nitric acid esters, does not induce oxidative stress and is therefore free of tolerance. Moreover, animal experiments have revealed that PETN actively reduces oxygen radical formation in vivoand specifically prevents atherogenesis and endothelial dysfunction. Because heme oxygenase-1 (HO-1) has been described as an antiatherogenic and cytoprotective gene in the endothelium, our aim was to investigate the effect of the active PETN metabolite pentaerithrityl trinitrate (PETriN) on HO-1 expression and catalytic activity in endothelial cells. Endothelial cells derived from human umbilical vein were incubated with PETriN (0.01-1 mM) for 8 hr. PETriN increased HO-1 mRNA and protein levels in a concentration-dependent fashion up to 3-fold over basal levels. Elevation of HO-1 protein was accompanied by a marked increase in catalytic activity of the enzyme as reflected by enhanced formation of both carbon monoxide and the endogenous antioxidant, bilirubin. Pretreatment of endothelial cells with PETriN or bilirubin at low micromolar concentrations protected endothelial cells from hydrogen peroxide-mediated toxicity. HO-1 induction and endothelial protection by PETriN were not mimicked by isosorbide dinitrate, another long-acting nitrate. The present study demonstrates that the active PETN metabolite, PETriN, stimulates mRNA and protein expression as well as enzymatic activity of the antioxidant defense protein, HO-1, in endothelial cells. Increased HO-1 expression and ensuing formation of bilirubin and carbon monoxide may contribute to and explain the specific antioxidant and antiatherogenic actions of PETN.


Consumption of alcoholic beverages, driving vehicles, a balance of dry law, Brazil 2007-2013.
The study analyzes the trend in frequency of adults who drive under the influence of alcohol in major Brazilian cities after the passing of laws, which prohibit drunk driving. Data from the Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey (VIGITEL) between 2007 and 2013 were analyzed. The frequency of adults who drove after abusive alcohol consumption was reduced by 45.0% during this period (2.0% in 2007 to 1.1% in 2013). Between 2007 and 2008 (-0.5%) and between 2012 and 2013 (-0.5%), significant reductions were observed in the years immediately after the publication of these laws that prohibit drunk driving. These improvements towards the control of drunk driving show a change in the Brazilian population's lifestyle.


Nitrogen metabolism of two portunid crabs, carcinus maenas and necora puber, during prolonged air exposure and subsequent recovery: a comparative study
Carcinus maenas and Necora puber were exposed to air for 72 h and 18 h, respectively, at 18 degreesC. Nitrogen excretion, blood and muscle ammonia content and blood urate and lactate content were recorded throughout the experimental emersion and following reimmersion (recovery period). During emersion, the rate of ammonia excretion was strongly reduced in both species, while urea and amine excretion were not enhanced. Blood and muscle ammonia content increased steadily, reaching 1.3 and 10.4 mmol l-1, respectively, after an 18 h emersion in N. puber. In contrast, in C. maenas, blood ammonia levels increased slightly during the first 12 h and then remained at this level (approximately 0.12 mmol l-1) until the end of emersion. Muscle ammonia content showed a non-significant increase at 12 h, after which values returned to control values (3.3 mmol l-1) for the next 60 h. Blood urate and lactate content increased in emersed N. puber, indicating strong internal hypoxia, but urate content did not increase in C. maenas until the third day of emersion. Upon reimmersion, both species released large amounts of ammonia within a few minutes. Two different patterns of ammonia release then were observed: ammonia excretion was enhanced for a further 3 h in N. puber, whereas raised ammonia excretion rates were observed for a further 24 h in C. maenas. These patterns, the recovery of blood and muscle ammonia levels and the calculated nitrogen balance between emersed and control crabs indicated that specific processes were used to manage the nitrogen overload induced by air exposure. Whereas N. puber shows little or no ability to limit ammonia accumulation in its body, C. maenas exhibits strong regulation of its nitrogen metabolism. The probability that amino acid synthesis is involved in this regulation and whether these species use metabolic depression as a survival strategy are discussed.


Using the "Frontalis-Free Orbital Septum-Complex Flap" in the Correction of Unilateral Congenital Ptosis.
Congenital ptosis has deleterious effects on the appearance and vision-related function. Patients need timely and effective treatments. A new surgical practice was performed using the discarded fibrous and thickened orbital septum to prolong the advanced frontalis muscular flap and reduce iatrogenic injuries in the frontalis. A 5-year-old boy with severe unilateral congenital ptosis was enrolled and got satisfactory surgical effects without complication. The "frontalis-free orbital septum-complex flap" is a new and relatively ideal method. The purpose of this paper is to demonstrate this surgical practice and provide a new idea for correcting congenital ptosis with the thickened and fibrotic orbital septum.


The frequency and reasons for vaginal examinations in labour.
Vaginal examinations (VEs) in labour are a routine part of intrapartum care. Current U.K. guidelines recommend that VEs are offered to women at regular intervals of not less than 4h and only performed when justifiably necessary. However, justification may be interpreted differently by different midwives. This study aimed to investigate (i) the number of VEs performed in relation to length of labour and (ii) the reasons given by midwives for performing the VE. This study recruited a group of women (n=144) admitted in either spontaneous labour or for induction of labour from one NHS hospital in Scotland. The number of VEs performed, the reason provided by the midwife for its need and the length of labour were all recorded. The number of VEs carried out (mean 2.9, SD 1.5, range 1-7) increased as length of time in labour in hospital increased. Approximately half the sample (52%) had 3 or more VEs during labour. Almost 70% of women had more VEs than expected when the criteria of 4 hourly VEs was applied. The most common reason given by midwives for performing a VE was to assess labour progress and to assess the commencement of labour. Despite maternity care policy to limit interventions in normal labour, we found that a substantial number of women received more VEs than was consistent with adherence to guidelines. However, until further research is conducted to validate other measures of labour progress, the number of VEs undertaken during labour is unlikely to decrease.


How to make a living by exhaling methane.
Methane produced in the biosphere is derived from two major pathways. Conversion of the methyl group of acetate to CH(4) in the aceticlastic pathway accounts for at least two-thirds, and reduction of CO(2) with electrons derived from H(2), formate, or CO accounts for approximately one-third. Although both pathways have terminal steps in common, they diverge considerably in the initial steps and energy conservation mechanisms. Steps and enzymes unique to the CO(2) reduction pathway are confined to methanogens and the domain Archaea. On the other hand, steps and enzymes unique to the aceticlastic pathway are widely distributed in the domain Bacteria, the understanding of which has contributed to a broader understanding of prokaryotic biology.


An experimental analysis of the contribution of 228Ra progeny to the gross alpha-particle activity of water samples.
The contribution of 228Ra progeny to the gross alpha-particle activity of water samples by EPA Method 900.0 is investigated as a function of residue mass and geometry and time between sample collection and analysis. It is shown that these factors can cause the contribution of 228Ra progeny to gross alpha-particle activity to be up to 2.2 times the initial 228Ra activity for grab samples and up to 3.5 times the initial 228Ra activity for quarterly composite samples when samples are held for the maximum 6-mo holding time. Thus, under some conditions, 228Ra, by itself, can cause a gross alpha-particle violation (>0.55 Bq L(-1)). Since 228Ra activity is already regulated, a gross alpha-particle activity violation that only exists because of the presence of 228Ra can be considered to be a false positive violation.


Cascade Screening for Familial Hypercholesterolemia: PCR Methods with Melting-Curve Genotyping for the Targeted Molecular Detection of Apolipoprotein B and LDL Receptor Gene Mutations to Identify Affected Relatives.
A key objective of the UK National Institute for Health and Care Excellence (NICE) pathway for diagnosis of familial hypercholesterolemia (FH) is the identification of affected relatives of index cases through cascade screening. At present, there is no systematic appraisal of available methodological options to identify the appropriate diagnostic testing protocol that would allow cost-effective cascade genetic screening. The majority of FH-causing mutations identified in the LDL receptor (LDLR) or apolipoprotein B (APOB) genes are single-nucleotide changes. This pattern of mutations suggests that PCR methods using melting curve-based genotyping might offer a convenient methodological approach for screening relatives. We developed and validated one-tube PCR methods for the mutations APOB c.10580G>A (p.Arg3527Gln), LDLR c.1474G>A (p.Asp492Asn), and c.2054C>T (p.Pro685Leu) and 3 novel LDLR mutations identified in the Coventry and Warwickshire population: LDLR c.1567G>C (p.Val523Leu), c.487dupC (p.Gln163Profs17), and c.647G>C (p.Cys216Ser). These methods successfully amplified target sequence from genomic DNA extracted from either peripheral blood or saliva. They also demonstrated acceptable analytical performance characteristics (specificity of amplification, repeatability, and reproducibility) over a wide range of DNA concentrations and purity. This approach was used for cascade testing of relatives of index FH cases with confirmed mutations and identified family members with high plasma LDL cholesterol as heterozygous for disruptive alleles. Our study generates proof-of-concept evidence of methods suitable for detecting single nucleotide substitutions and insertions that can deliver reliable, easy, low-cost, and rapid family screening of FH patients and can be adopted by nonspecialist molecular diagnostic laboratories.


PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target.
Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies. PI3K-Akt-mTOR signaling pathway plays a vital role in regulating the infection course of many viruses. In this study, we have dissected the effects of PI3K-Akt-mTOR signaling pathway on rotavirus infection using both conventional cell culture models and a 3D model of human primary intestinal organoids. We found that PI3K-Akt-mTOR signaling is essential in sustaining rotavirus infection. Thus, blocking the key elements of this pathway, including PI3K, mTOR and 4E-BP1, has resulted in potent anti-rotavirus activity. Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. This effect involves 4E-BP1 mediated induction of autophagy, which in turn exerts anti-rotavirus effects. These results revealed new insights on rotavirus-host interactions and provided new avenues for antiviral drug development.


Potassium channel blockade amplifies cardiac instability numerical studies of torsades de pointes.
Suppression of responses to premature stimulation has been the guiding principle in managing many cardiac arrhythmias. Recent clinical trails revealed that sodium channel blockade increased the incidence of re-entrant cardiac arrhythmias resulting in sudden cardiac death, although the physiologic mechanism remains uncertain. Potassium channel blockade offers an alternative mechanism for suppressing responses to premature stimuli. We have developed a simple model of a 2D sheet of excitable cells. We can initiate re-entrant activation with stimuli timed to occur within a period of vulnerability (VP). Reducing the Na conductance increases the VP while reducing the K conductance increases the collective instability of the array, and arrhythmias similar to torsades de pointes seen in patients subjected to K channel blocked can be readily initiated. Thus, while K channel blockade may suppress excitability by prolonging the action potential duration, it appears to simultaneously exhibit proarrhythmic properties that result in complex re-entrant arrhythmias.


Disruption of prostate epithelial differentiation pathways and prostate cancer development.
One of the foremost problems in the prostate cancer (PCa) field is the inability to distinguish aggressive from indolent disease, which leads to difficult prognoses and thousands of unnecessary surgeries. This limitation stems from the fact that the mechanisms of tumorigenesis in the prostate are poorly understood. Some genetic alterations are commonly reported in prostate tumors, including upregulation of Myc, fusion of Ets genes to androgen-regulated promoters, and loss of Pten. However, the specific roles of these aberrations in tumor initiation and progression are poorly understood. Likewise, the cell of origin for PCa remains controversial and may be linked to the aggressive potential of the tumor. One important clue is that prostate tumors co-express basal and luminal protein markers that are restricted to their distinct cell types in normal tissue. Prostate epithelium contains layer-specific stem cells as well as rare bipotent cells, which can differentiate into basal or luminal cells. We hypothesize that the primary oncogenic cell of origin is a transient-differentiating bipotent cell. Such a cell must maintain tight temporal and spatial control of differentiation pathways, thus increasing its susceptibility for oncogenic disruption. In support of this hypothesis, many of the pathways known to be involved in prostate differentiation can be linked to genes commonly altered in PCa. In this article, we review what is known about important differentiation pathways (Myc, p38MAPK, Notch, PI3K/Pten) in the prostate and how their misregulation could lead to oncogenesis. Better understanding of normal differentiation will offer new insights into tumor initiation and may help explain the functional significance of common genetic alterations seen in PCa. Additionally, this understanding could lead to new methods for classifying prostate tumors based on their differentiation status and may aid in identifying more aggressive tumors.


Target meta-awareness is a necessary condition for physiological responses to masked emotional faces: Evidence from combined skin conductance and heart rate assessment.
Much heated debate surrounds the extent to which we can process emotional stimuli without awareness. In particular the extent to which masked emotional faces can elicit changes in physiology measurements, such as heart rate and skin conductance responses, has produced controversial findings. In the present study, we aimed to determine whether briefly presented faces can elicit physiological changes and, specifically, whether this is due to unconscious processing. We measured and adjusted for individual differences in the detection threshold using both receiver operating characteristics and hit rates. For this we also used a strict Bayesian assessment of participant thresholds. We then measured physiological responses to threshold adjusted emotional faces and for hits, misses and post-binary subdivisions of target meta-awareness. Our findings based on receiver operating characteristics revealed that, when faces were successfully masked there were no significant physiological differences in response to stimuli with different emotional connotations. In contrast, when targets were masked based on hit rates we did find physiological responses to masked emotional faces. With further analysis we found that this effect was specific to correct detection of angry and fearful faces and that increases in experienced arousal were associated with higher confidence ratings for correct detection of these stimuli. Collectively, our results do not support the notion of unconscious processing when using markers of physiological processes. Rather they suggest that target meta-awareness is a necessary condition for - and possibly determined by - physiological changes in response to masked emotional faces.


M1 and M2a polarization of human monocyte-derived macrophages inhibits HIV-1 replication by distinct mechanisms.
The capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines and other extracellular stimuli. In this study, we demonstrate that cytokine-induced polarization of human monocyte-derived macrophage (MDM) into either classical (M1) or alternatively activated (M2a) MDM is associated with a reduced capacity to support productive CCR5-dependent (R5) HIV-1 infection. M1 polarization was associated with a significant down-regulation of CD4 receptors, increased secretion of CCR5-binding chemokines (CCL3, CCL4, and CCL5), and a >90% decrease in HIV-1 DNA levels 48-h postinfection, suggesting that the inhibition occurred at an early preintegration step in the viral life cycle. In contrast, M2a polarization had no effect on either HIV-1 DNA or protein expression levels, indicating that inhibition occurred at a late/postintegration level in the viral life cycle. M2a inhibition was sustained for up to 72-h postinfection, whereas M1-effects were more short-lived. Most phenotypic and functional changes were fully reversible 7 days after removal of the polarizing stimulus, and a reciprocal down-regulation of M1-related chemokines and cytokines was observed in M2a MDM and vice versa. Since reversion to a nonpolarized MDM state was associated with a renewed capacity to support HIV replication to control levels, M1/M2a polarization may represent a mechanism that allows macrophages to cycle between latent and productive HIV-1 infection.


Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma.
We describe molecular convergence between BMI1 and CHD7 in the initiation of medulloblastoma. Identified in a functional genomic screen in mouse models, a BMI1High;CHD7Low expression signature within medulloblastoma characterizes patients with poor overall survival. We show that BMI1-mediated repression of the ERK1/2 pathway leads to increased proliferation and tumor burden in primary human MB cells and in a xenograft model, respectively. We provide evidence that repression of the ERK inhibitor DUSP4 by BMI1 is dependent on a more accessible chromatin configuration in G4 MB cells with low CHD7 expression. These findings extend current knowledge of the role of BMI1 and CHD7 in medulloblastoma pathogenesis, and they raise the possibility that pharmacological targeting of BMI1 or ERK may be particularly indicated in a subgroup of MB with low expression levels of CHD7.


The effect of capsaicin on expression patterns of CGRP in trigeminal ganglion and trigeminal nucleus caudalis following experimental tooth movement in rats.
The aim of this study was to explore the effect of capsaicin on expression patterns of calcitonin gene-related peptide (CGRP) in the trigeminal ganglion (TG) and trigeminal subnucleus caudalis (Vc) following experimental tooth movement. Male Sprague-Dawley rats were used in this study and divided into small-dose capsaicin+force group, large-dose capsaicin+force group, saline+force group, and no force group. Closed coil springs were used to mimic orthodontic forces in all groups except for the no force group, in which springs were inactivated. Capsaicin and saline were injected into periodontal tissues. Rats were euthanized at 0 h, 12 h, 1 d, 3 d, 5 d, and 7 d following experimental tooth movement. Then, TG and Vc were obtained for immunohistochemical staining and western blotting against CGRP. Immunohistochemical results indicated that CGRP positive neurons were located in the TG, and CGRP immunoreactive fibers were distributed in the Vc. Immunohistochemical semiquantitative analysis and western blotting analysis demonstrated that CGRP expression levels both in TG and Vc were elevated at 12 h, 1 d, 3 d, 5 d, and 7 d in the saline + force group. However, both small-dose and large-dose capsaicin could decrease CGRP expression in TG and Vc at 1 d and 3 d following experimental tooth movement, as compared with the saline + force group. These results suggest that capsaicin could regulate CGRP expression in TG and Vc following experimental tooth movement in rats.


[Clinical and morphofunctional characteristics of hydatid liver echinococcosis].
To examine the levels of aspartate aminotransferase (AsAT) and alaninaminotransferase (AlAT) in homogenates of hepatic biopsies from patients with echinococcosis. Clinical, biochemical examinations, ultrasonic examination of the liver were made in 49 patients with hydatid echinococcosis of the liver and 5 control patients operated on for extrahepatic pathology. Morphological picture of the liver was examined with light microscopy. AsAT and AlAT activity in hepatic tissue were estimated with 2,4-dinitrophenilhydrazin method. There were marked cellular and extracellular disorders and significant lowering of transaminases in the pericystic zone of hepatic tissue vs such indices for far from the echynococcal cyst sites of the liver. In hepatic echinococcosis hepatic tissue undergoes diffuse alteration associated with severe morphofunctional disorders which require adequate preoperative preparation of the patients, in postoperative period adequate intensive therapy is needed.


Signs and symptoms of the myofascial pain syndrome: a national survey of pain management providers.
The goal of this study was to assess clinical consensus regarding whether myofascial pain syndrome (MPS) is a legitimate and distinct diagnosis as well as the signs and symptoms characterizing MPS. A standardized mailed survey with return postage provided. A total of 1,663 American Pain Society members in medically related disciplines listed in the 1996/1997 directory. A standardized survey assessing clinical opinion regarding whether MPS is a legitimate diagnosis, whether MPS is a clinical entity distinct from fibromyalgia, and the signs and symptoms believed to be "essential to," "associated with," or "irrelevant to" to the diagnosis of MPS. Of the 403 surveys returned, 88.5% respondents reported that MPS was a legitimate diagnosis, with 81% describing MPS as distinct from fibromyalgia. The only signs and symptoms described as essential to the diagnosis of MPS by greater than 50% of the sample were regional location, presence of trigger points, and a normal neurologic examination. Regarding the signs and symptoms considered to be essential or associated with MPS, more than 80% of respondents agreed on regional location, trigger points, normal neurologic examination, reduced pain with local anesthetic or "spray and stretch," taut bands, tender points, palpable nodules, muscle ropiness, decreased range of motion, pain exacerbated by stress, and regional pain described as "dull," "achy," or "deep." Sensory or reflex abnormalities, scar tissue, and most test results were considered to be irrelevant to the diagnosis of MPS by a large proportion of the respondents. There was general agreement across specialties that MPS is a legitimate diagnosis distinct from fibromyalgia. There was a high level of agreement regarding the signs and symptoms essential or associated with a diagnosis of MPS. Differences across specialties are discussed. This survey provides a first step toward the development of consensus-based diagnostic criteria for MPS, which can then be validated empirically.


Addition of poly(A) and heteropolymeric 3' ends in Bacillus subtilis wild-type and polynucleotide phosphorylase-deficient strains.
Polyadenylation plays a role in decay of some bacterial mRNAs, as well as in the quality control of stable RNA. In Escherichia coli, poly(A) polymerase I (PAP I) is the main polyadenylating enzyme, but the addition of 3' tails also occurs in the absence of PAP I via the synthetic activity of polynucleotide phosphorylase (PNPase). The nature of 3'-tail addition in Bacillus subtilis, which lacks an identifiable PAP I homologue, was studied. Sizing of poly(A) sequences revealed a similar pattern in wild-type and PNPase-deficient strains. Sequencing of 152 cloned cDNAs, representing 3'-end sequences of nontranslated and translated RNAs, revealed modified ends mostly on incomplete transcripts, which are likely to be decay intermediates. The 3'-end additions consisted of either short poly(A) sequences or longer heteropolymeric ends with a mean size of about 40 nucleotides. Interestingly, multiple independent clones exhibited complex heteropolymeric ends of very similar but not identical nucleotide sequences. Similar polyadenylated and heteropolymeric ends were observed at 3' ends of RNA isolated from wild-type and pnpA mutant strains. These data demonstrated that, unlike the case of some other bacterial species and chloroplasts, PNPase of Bacillus subtilis is not the major enzyme responsible for the addition of nucleotides to RNA 3' ends.


BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications.
Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved during the last decades, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with poor clinical outcomes. Several studies found that germline or acquired DNA damage repair (DDR) defects affect a high percentage of mCRPC patients. Among DDR defects, BRCA mutations show relevant clinical implications. BRCA mutations are associated with adverse clinical features in primary tumors and with poor outcomes in patients with mCRPC. In addition, BRCA mutations predict good response to poly-ADP ribose polymerase (PARP) inhibitors, such as olaparib, rucaparib, and niraparib. However, concerns still remain on the role of extensive mutational testing in prostate cancer patients, given the implications for patients and for their progeny. The present comprehensive review attempts to provide an overview of BRCA mutations in prostate cancer, focusing on their prognostic and predictive roles.


Assessment of plant biomass and nitrogen nutrition with plant height in early-to mid-season corn.
The physiological basis for using non-destructive high-resolution measurements of plant height through plant height sensing to guide variable-rate nitrogen (N) applications on corn (Zea mays L.) during early (six-leaf growth stage, V6) to mid (V12) season is largely unknown. This study was conducted to assess the relationships of plant biomass and leaf N with plant height in early- to mid-season corn under six different N rate treatments. Corn plant biomass was significantly and positively related to plant height under an exponential model when both were measured at V6. This relationship explained 62-78% of the variations in corn biomass production. Leaf N concentration was, in general, significantly and positively related to plant height when both were measured at V6, V8, V10 and V12. This relationship became stronger as the growing season progressed from V6 to V12. The relationship of leaf N with plant height in early- to mid-season corn was affected by initial soil N fertility and abnormal weather conditions. The relationship of leaf N concentration with plant height may provide a physiological basis for using plant height sensing to guide variable-rate N applications on corn.


Relation between cell size and response characteristics of vestibulospinal neurons to labyrinth and neck inputs.
(1) The activity of 136 Deiters' neurons projecting to lumbosacral segments of the spinal cord has been recorded in decerebrate, partially cerebellectomized cats, and their response characteristics to sinusoidal stimulation of labyrinth and neck receptors have been related to cell size inferred from the conduction velocity of the corresponding axons. (2) Vestibulospinal neurons with faster conduction velocity and, by inference, having thicker axons and larger cell bodies differed from those neurons having lower axonal conduction velocity by displaying (i) a relatively irregular interspike interval distribution; (ii) a lower resting discharge rate; (iii) a periodically modulated response to the labyrinth input elicited by sinusoidal tilt around the animal's longitudinal axis (0.026 Hz, 10 degrees) characterized by an increase in firing rate during side-down roll tilt; (iv) an increase in gain (impulses per sec per degree) and phase lag relative to the displacement of the labyrinth response to increasing angular acceleration; (v) a greater gain in labyrinth than neck input, the latter elicited by sinusoidal neck rotation (0.026 Hz, 5 or 10 degrees); and (vi) due to the imbalance of the gains of the separate labyrinth and neck responses and their predictable vectorial summation, a response to both inputs elicited by head rotation resembling that obtained by labyrinth stimulation alone. (3) These findings are discussed in terms of the reciprocal distribution of synaptic contacts of vestibular and neck afferents on vestibulospinal neurons as a function of cell size. The evidence indicates that, in addition to intrinsic neuronal properties related to cell size, the quantitative and qualitative organization of synaptic inputs represents the critical factor controlling the responsiveness of vestibulospinal neurons.


Evolution of novel small-molecule therapeutics targeting sickle cell vasculopathy.
A 34-year-old African American woman with sickle cell disease and history of relatively severe hemolysis, chronic leg ulcers, and mild pulmonary hypertension presented with a new ischemic stroke. Recent research has suggested a syndrome of hemolysis-associated vasculopathy in patients with sickle cell disease, which features severe hemolytic anemia and leads to scavenging of nitric oxide and its biochemical precursor l-arginine. This diminished bioavailability of nitric oxide promotes a hemolysis-vascular dysfunction syndrome, which includes pulmonary hypertension, cutaneous leg ulceration, priapism, and ischemic stroke. Additional correlates of this vasculopathy include activation of endothelial cell adhesion molecules, platelets, and the vascular protectant hemeoxygenase-1. Some known risk factors for atherosclerosis are also associated with sickle cell vasculopathy, including low levels of apolipoprotein AI and high levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. Identification of dysregulated vascular biology pathways in sickle vasculopathy has provided a focus for new clinical trials for therapeutic intervention, including inhaled nitric oxide, sodium nitrite, L-arginine, phosphodiesterase-5 inhibitors, niacin, inhaled carbon monoxide, and endothelin receptor antagonists. This article reviews the pathophysiology of sickle vasculopathy and the results of preliminary clinical trials of novel small-molecule therapeutics directed at abnormal vascular biology in patients with sickle cell disease.


Biochemical characterization of trans-sialidase TS1 variants from Trypanosoma congolense.
Animal African trypanosomiasis, sleeping sickness in humans and Nagana in cattle, is a resurgent disease in Africa caused by Trypanosoma parasites. Trans-sialidases expressed by trypanosomes play an important role in the infection cycle of insects and mammals. Whereas trans-sialidases of other trypanosomes like the American T. cruzi are well investigated, relatively little research has been done on these enzymes of T. congolense. Based on a partial sequence and an open reading frame in the WTSI database, DNA sequences encoding for eleven T. congolense trans-sialidase 1 variants with 96.3% overall amino acid identity were amplified. Trans-sialidase 1 variants were expressed as recombinant proteins, isolated and assayed for trans-sialylation activity. The purified proteins produced α2,3-sialyllactose from lactose by desialylating fetuin, clearly demonstrating their trans-sialidase activity. Using an HPLC-based assay, substrate specificities and kinetic parameters of two variants were characterized in detail indicating differences in substrate specificities for lactose, fetuin and synthetic substrates. Both enzymes were able to sialylate asialofetuin to an extent, which was sufficient to reconstitute binding sites for Siglec-4. A mass spectrometric analysis of the sialylation pattern of glycopeptides from fetuin revealed clear but generally similar changes in the sialylation pattern of the N-glycans on fetuin catalyzed by the trans-sialidases investigated. The identification and characterization of a trans-sialidase gene family of the African parasite T. congolense has opened new perspectives for investigating the biological role of these enzymes in Nagana and sleeping sickness. Based on this study it will be interesting to address the expression pattern of these genes and their activities in the different stages of the parasite in its infection cycle. Furthermore, these trans-sialidases have the biotechnological potential to be used for enzymatic modification of sialylated glycoconjugates.


Twelve month follow-up on a randomised controlled trial of relaxation training for post-stroke anxiety.
To follow up participants in a randomised controlled trial of relaxation training for anxiety after stroke at 12 months. Twelve month follow-up to a randomised controlled trial, in which the control group also received treatment. Community. Fifteen of twenty one original participants with post-stroke anxiety participated in a one year follow-up study. A self-help autogenic relaxation CD listened to five times a week for one month, immediately in the intervention group and after three months in the control group. Hospital Anxiety and Depression Scale-Anxiety subscale and the Telephone Interview of Cognitive Status for inclusion. Hospital Anxiety and Depression Scale-Anxiety subscale for outcome. All measures were administered by phone. Anxiety ratings reduced significantly between pre and post-intervention, and between pre-intervention and one year follow-up ( χ2(2) = 22.29, p < 0.001). Reductions in anxiety in stroke survivors who received a self-help autogenic relaxation CD appear to be maintained after one year.