[Epidemiologic and molecular genetic of suicidal behavior].
The current understanding of suicidal behaviors is that such behaviors are multidetermined and mental state and trait related. Genetic factors appear to be of great importance, as suggested by the findings of family, twin, and adoption studies. Whether these genetic factors are similar to those involved in the susceptibility to psychiatric disorders closely related to suicidal behavior (eg, manic depressive illness, schizophrenia or substance use disorders) is yet unknown. However, a genetic factor of susceptibility to suicide, independent or additive to the genetic transmission of the psychiatric disorders that are related to suicidal behavior, is strongly suggested by the data of the Copenhagen adoption study and a study of Amish families. Recently, new approaches have been proposed to identify the genetic component of such complex traits. Association studies between genetic markers and a disease phenotype has been successfully applied to several complex disease such as essential hypertension. One candidate gene for suicidal behaviors is the tryptophane hydroxylase (TPH) gene which is the first and possibly rate-limiting enzyme of the metabolic pathway for serotonin. Indeed, altered serotoninergic function in both completed suicide and suicide attempt has been one of the most replicated findings in modern biological psychiatry. In our knowledge, only two studies have tested the association between suicide attempt and the TPH gene and their authors found negative results. Despite these negative results, association studies that use candidate gene remain one of the methods of choice for studying the genetic component of suicidal behaviors.


Mutations of the coat protein gene of bacteriophage lambda that overcome the necessity for the Fl gene; the EFi domain.
The functions of most of the 10 genes involved in phage lambda capsid morphogenesis are well understood. The function of the FI gene is one of the exceptions. Mutants in FI fail to mature and package DNA. The gene product (gpFI) seems to act as a catalyst for the formation of an intermediate in capsid assembly called complex II, which contains a procapsid (an empty capsid precursor), terminase (the enzyme that cleaves the DNA precursor and packages it into the procapsid) and DNA. The mechanism for this stimulation remains unknown. It has also been reported that gpFI appeared to stimulate terminase-mediated cos cleavage, in the absence of procapsids, by increasing enzyme turnover. In comparison with other head-gene mutants, FI mutants are leaky, producing approx. 0.1 phage per infected cell. Some second-site revertants of FI- phages, called 'fin', that bypass the necessity for gpFI, have been isolated and found to harbour a mutation in the genes that code for the two subunits of terminase. In the course of mapping additional fin mutants, it was discovered that some mapped outside the terminase genes. To localize the mutations, restriction fragments of fin mutant DNAs were subcloned into plasmids and their ability to contribute to fin function was determined by marker-rescue analysis. The location of the fin mutation was further delineated by deletion analysis of a plasmid that was positive for fin. This showed that some fin mutations mapped to a region comprising genes E, D and a portion of C. The sequencing of this entire region in several fin isolates showed that the fin mutations are clustered in a small region of gene E corresponding to a portion of 26 amino acid residues of the coat protein (gpE). We have called this region of the protein the EFI domain. All the mutations result in an increase in positive charge relative to the wild-type protein. These results suggest that DNA maturation and packaging are in part controlled by an interaction between gpFI and capsid gpE.


Physical association with WWOX suppresses c-Jun transcriptional activity.
WWOX is a tumor suppressor that functions as a modular protein partner of transcription factors. WWOX contains two WW domains that mediate protein-protein interactions. In this report, we show that WWOX, via its first WW domain, specifically associates with the proline-rich motif of c-Jun proto-oncogene. Our data show that phosphorylation of c-Jun caused by overexpression of mitogen-activated protein kinase kinase kinase 1 (Mekk1), an upstream activator of c-Jun, enhances the interaction of c-Jun with WWOX. Furthermore, exposure of HaCaT keratinocytes to UVC radiation resulted in the association of endogenous WWOX and c-Jun. The WWOX-c-Jun complexes mainly occur in the cytoplasm. Expression of WWOX attenuates the ability of MEKK1 to increase the activity of a c-Jun-driven activating protein-1 (AP-1)-luciferase reporter plasmid. In contrast, a point mutation in the first WW domain of WWOX has no effect on transactivation of AP-1 when coexpressed with c-Jun protein. Our findings reveal a novel functional cross-talk between c-Jun transcription factor and WWOX tumor suppressor protein.


Wegener granulomatosis: a case report and update.
Wegener granulomatosis (WG) is a systemic disease of unknown etiology characterized by necrotizing granulomatous inflammation, tissue necrosis, and variable degrees of vasculitis in small and medium-sized blood vessels. The classic clinical pattern is a triad involving the upper airways, lungs and kidneys. Ninety percent of patients present with symptoms involving the upper and/or lower airways, and 80% will eventually develop renal disease. WG should be suspected in any patient with progressive or unresponsive sinus disease, glomerulonephritis, pulmonary hemorrhage, mononeuritis multiplex or unexplained multisystem disease. Before the routine use of glucocorticoids and cyclophosphamide, the one year mortality was 82%. However in 1973, Fauci and Wolf discovered that daily prednisone and cyclophosphamide induced complete remission in 75% of patients. The continued use of prednisone and cyclophosphamide for 1 year past remission leads to marked improvement in more than 90% of patients; however, is also associated with serious toxicities. Depending on the disease severity, current treatments employ induction with short-term cyclophosphamide followed by less toxic agents such as methotrexate to maintain disease remission. Although it is a rare disorder, it is pertinent to internists because it is a multisystem disease that presents in a variety of ways. We describe a 63-year-old white male with WG who presented with progressively worsening headaches, bilateral eye redness, epistaxis, hemoptysis and an unintentional 20 pound weight loss, and review the current treatment recommendations.


Evaluation of the DNA-damaging and mutagenic activity of oxolinic and pipemidic acids by the granuloma pouch assay.
The mutagenic and DNA-damaging activities of oxolinic acid and pipemidic acid were evaluated in the rat granuloma pouch assay. After oral administration at high doses both the chemicals produce DNA alkali-labile sites in granuloma tissue cells, and with oxolinic acid an increase of liver and kidney DNA elution rate was also observed. In contrast, after direct injection into the granuloma tissue, DNA damage was absent. This indicates that DNA lesions are induced by a stable intermediate presumably formed in liver and converted to the ultimate DNA-damaging species in extrahepatic tissues. The simultaneous analysis of 6-thioguanine-resistant cells in the granuloma tissue revealed no statistically significant mutation induction either after local treatment or oral administration. No clear dose-response curve was obtained. However, after oral application in some of the animals an enhanced mutation frequency was detected, and the cloning efficiency of cells exposed to the drugs was reduced even after culturing them for 6 days. The most likely explanation is that functional multilocus mutations are induced which cannot be recovered efficiently at the HGPRT locus.


Cytokine control of PMN phagocytosis: regulatory effects of hypoxemia and hypoxemia-reoxygenation.
We investigated the effects of hypoxemia and hypoxemia-reoxygenation (H/R) on interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), or IL-1beta stimulation of whole blood polymorphonuclear leukocyte (PMN) phagocytosis and bactericidal activity. Whole blood PMN were rendered hypoxemic (venous PO2 < 15 mmHg), normoxic (venous PO2 60-80 mmHg), or reoxygenated after hypoxemia (H/ R = venous PO2 150-200 mmHg) and were incubated with IL-8, TNF-alpha, or IL-1beta before sequential addition of serum-opsonized fluorescent microspheres and fluorescein isothiocyanate-conjugated mouse anti-human CD64, CD32w, CD16, CD35, or CD11b/CD18. Concomitant two-color flow cytometric analyses were then performed measuring mean channel fluorescence and the percentage of PMN positive for phagocytosis, with simultaneous subset receptor analysis on populations of PMN that exceeded control levels of phagocytosis. During hypoxemia, whole blood PMN phagocytosis in the presence of IL-8, TNF-alpha, or IL-1beta was increased compared with normoxia. Northern blot analyses revealed an increase in steady-state mRNA levels for CD32w during hypoxemia + IL-8 and CD64 during hypoxemia + IL-1beta. During reoxygenation, both whole blood PMN phagocytosis and bactericidal activity were reduced in the presence of IL-8, TNF-alpha, or IL-1beta, and in subsets of PMN with reduced phagocytosis H/R reduced CD64, CD32w, CD16, CD35, and CD11b/CD18 expression in the presence of each cytokine. Northern blot analyses revealed that H/R reduced mRNA levels for opsonic receptors primarily for IL-1beta-stimulated PMN. These results demonstrate a direct regulatory effect of hypoxemia and H/R on whole blood PMN phagocytosis, receptor expression, and steady-state mRNA levels of both Fc(gamma) and complement receptors.


Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model.
The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage. In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV. We demonstrate here that vaccination with ChAdOx2 CCHF induces both a humoral and cellular immune response in mice and 100% protection in a lethal CCHF challenge model. Delivery of the adenoviral vaccine in a heterologous vaccine regimen with a Modified Vaccinia Ankara vaccine (MVA CCHF) induces the highest levels of CCHFV-specific cell-mediated and antibody responses in mice. Histopathological examination and viral load analysis of the tissues of ChAdOx2 CCHF immunised mice reveals an absence of both microscopic changes and viral antigen associated with CCHF infection, further demonstrating protection against disease. There is the continued need for an effective vaccine against CCHFV to protect humans from lethal haemorrhagic disease. Our findings support further development of the ChAd platform expressing the CCHFV GPC to seek an effective vaccine against CCHFV. This research was supported by funding from the Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BB/R019991/1 and BB/T008784/1].


Multifocal Οsteomyelitis Localization after Pyomyositis in Children: Importance of Timely Response.
Pyomyositis is a rare bacterial infection that used to prevail in tropical areas for the past century. Nowadays though, more and more cases are reported in high-temperature climate areas. Diagnosis is often delayed due to the variance in clinical presentation, the challenging nature of physical examination of a child, and lack of specific laboratory investigating tools. When the diagnosis is delayed, the outcome may be unpredictable. Multifocal localization through hematogenous or direct spread that may affect the skeletal bone tissue is common. Timely diagnosis and response is a race against septic shock. We present a case series of seven children diagnosed with pyomyositis due to Staphylococcus aureus. High or less clinical suspicion has obviously affected the final outcome since two patients who were not treated in time were subjected to a life-threatening hazard. Five patients who were diagnosed and treated within the first three days after initiation of their symptoms had a predictable and good outcome without complications.


Experimental evidence that mycorrhizal nitrogen strategies affect soil carbon.
Most land plants acquire nitrogen (N) through associations with arbuscular (AM) and ectomycorrhizal (ECM) fungi, but these symbionts employ contrasting strategies for N acquisition, which may lead to different stocks of soil carbon (C). We experimentally test this hypothesis with a mesocosm system where AM and ECM tree seedling roots, or their hyphae only, could access mineral soils with 13 C- and 15 N-enriched organic matter. We quantified loss of soil C and N, plant uptake of N and new inputs of plant C to soil. We found that AM, but not ECM, seedlings reduced soil C relative to controls. Soil C loss was greater in the presence of roots relative to hyphae only for both AM and ECM seedlings, but was correlated with plant N uptake for AM seedlings only. While new plant C inputs stimulated soil C loss in both symbioses, we detected plant C inputs more frequently and measured higher rates of decomposer activity in soils colonized by AM relative to ECM seedlings. Our study experimentally demonstrates how mycorrhizal strategies for N can affect soil C and C:N, even at the scale of an individual plant. Such effects may contribute to broad patterns in soil C across terrestrial ecosystems.


Double-Acting Soft Actuator for Soft Robotic Hand: A Bellow Pumping and Contraction Approach.
When compressing a soft bellow, the bellow will contract and pump out the fluid inside the bellow. Utilizing this property, we propose a novel actuation method called compressing bellow actuation (CBA), which can output fluidic power and tendon-driven force simultaneously. Based on the CBA method, a double-acting soft actuator (DASA) combining fluidic elastomer actuator (FEA) and tendon-driven metacarpophalangeal (MCP) joint is proposed for robotic finger design. The proposed DASA exhibits both compliance and adaptiveness of FEAs, and controllability and large output force of the tendon-driven methods. The fluid in the bellow can be either air or water or even integration of the two, thus constituting three different actuation modes. Mathematical modeling of the relationship between bellow compression displacement and DASA's bending angle is developed. Furthermore, experimental characterizations of DASA's bending angle and blocking force are conducted at different actuation modes. The double-acting method can availably promote the bending angle of an FEA by up to 155%, and the blocking force by up to 132% when the FEA is water-filled. A soft robotic hand with a forearm prototype based on the DASA fingers is fabricated for the demonstration of finger motion and gripping applications.


Rough Fresnel zone plates over metallic surfaces.
We analyze the focusing properties of Fresnel zone plates fabricated over steel tapes using laser ablation. Our intention is to implement the use of micro-optical elements when the use of conventional chrome-glass elements is not indicated. Because of the manufacture process, the surface presents a certain anisotropic roughness, which reduces the focusing properties. First, we develop numerical simulations by means of the Rayleigh-Sommerfeld approach, showing how roughness in both levels of the Fresnel zone plate affects the focalization of the lens. We also manufacture Fresnel zone plates over steel tape, and perform experimental verification that corroborates the numerical results.


[Spirometry, pulse oximetry, brochospasmolytic test. The pillars of COPD diagnosis].
In addition to case history and clinical examination, the basic diagnostic work-up of chronic obstructive pulmonary disease comprises in particular lung function testing by means of spirometry. In the event of an uncertain diagnosis, or in a search for underlying causes, an additional EKG, chest X-ray and bronchospasmolytic testing to determine the reversibility of the airways obstruction are employed. In COPD patients younger than 50, as well as in those with pulmonary edema largely confined to the basal fields, determination of the alpha-1-antitrypsin should be carried out. In the case of an exacerbation of the clinical presentation, the sputum should be cultured to determine the possible presence of pathogenic bacteria. Recurrent exacerbations or a rapid worsening of dyspnea necessitate hospitalization.


Emotional regularity: associations with personality, psychological health, and occupational outcomes.
Emotional regularity is the degree to which a person maintains and returns to a set of emotional states over time. The present investigation examined associations between emotional regularity and extant emotion measures as well as psychologically relevant dimensions of personality, health, and real-world occupational outcomes. Participants included 598 U.S. adults who provided daily experience sampling reports on their emotional states for approximately two months. Results suggest that emotional regularity was related to, but distinct from, well-established measures of emotion including emotional intensity, variability, covariation, inertia, granularity, and emodiversity. Furthermore, emotional regularity significantly predicted measures of personality, psychological health, and occupational outcomes even when accounting for extant emotion measures and sociodemographic covariates. Finally, it explained modest (7.5%) improvement (in terms of cross-validated RSq.) over baseline models containing emotional intensity, variability, and sociodemographic covariates. These findings suggest that emotional regularity may provide an important indicator of healthy emotional functioning and may be a promising area for further scientific discovery.


Granulocytic sarcoma: a systematic review.
Granulocytic sarcoma also called myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukemia and myelodysplastic syndromes. In some rare circumstances, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the granulocytic sarcoma is described as nonleukemic, primary or isolated. It is observed at any part of the body but the most common locations are soft tissues, bone, peritoneum and lymph nodes. Presenting signs or symptoms are mainly due to mass effect of the tumor and dysfunction of the organ, or the tissue that is affected. The diagnosis is performed by biopsy of the tumor. The tumor consists of immature granulocytic cells, which could be documented by H&E, immunohistochemistry, and flow cytometric methods. Fluorescence in-situ hybridization and molecular analysis are also performed. The optimal time and type of treatment is not clear. Surgery could be an option especially for tumors, which cause organ dysfunction and/or obstruction. Systemic treatment should be considered in all patients because without systemic treatment, relapses and progression to acute myeloid leukemia is the ultimate fate of the disease in many cases. Cytarabine-containing remission-induction chemotherapies have been the most applied therapeutic strategies, but it is not clear whether the consolidation therapies are required or not, and what kind of regimens are appropriate. The role of hematopoietic stem cell transplantation (HSC) as a consolidation regimen is not clear, but, after the relapse of the disease with or without bone marrow involvement, HSC transplantation should be considered in suitable patients after the reinduction performed by AML chemotherapies. There is only limited data about the role of radiotherapy in these patients. It could be used in patients with relapsed disease, organ dysfunction which should be quickly relieved and inadequate response to chemotherapy. The effect of radiotherapy on overall survival is not known. New prospective studies and clinical trials are needed to generate guidelines for the treatment of primary granulocytic sarcomas.


Development of the Japanese version of the Depression Literacy Scale.
Depression is a major social concern in Japan. It is therefore necessary to develop a scale in Japanese that can assess depression literacy. The present study aimed to develop the Japanese version of the Depression Literacy Scale (D-Lit-J), and examined its validity and reliability. Three groups were administered the D-Lit-J, including 117 first-year university English literature students, 112 first-year medical school students, and 53 psychiatrists. Among these, 112 (95.7%), 112 (100%), and 29 subjects (54.7%) returned completed questionnaires, respectively. The total D-Lit-J scores were compared between the three groups to assess known-group validity, and internal reliability was examined by calculating Cronbach's alpha coefficients. Medical students were asked to complete the questionnaire a second time, 3 weeks later (11 students did not respond), to assess the test-retest reliability using the intra-class correlation coefficient. The total D-Lit-J scores (mean ± SD) were 7.61 ± 4.18, 9.51 ± 4.37, and 17.7 ± 3.15, for English literature students, medical students, and psychiatrists, respectively, and there were significant differences between the three groups (p < .05). The Cronbach's alpha coefficients ranged from .800 to .834 in all students, and was .764 in psychiatrists, revealing a good internal consistency. The intra-class correlation coefficient of the scale was .769. The D-Lit-J showed a credible known-group validity, with good internal and test-retest reliabilities. Additional studies with a greater variety of subjects and that examine concurrent or discriminant validity will be necessary in the future.


[Multiple finger geodes in children].
Three pediatric patients with multiple geodes in the fingers are reported. This condition occurs mainly between one and three years and at seven years of age and is more common in winter. Affected fingers are swollen. Roentgenograms disclose several small lucent defects which are usually located in the middle phalanx. Several fingers are usually involved. The erythrocyte sedimentation rate is increased in virtually every case. Resolution occurs spontaneously within a few weeks or months. There is no tendency towards recurrence. Although the condition is inflammatory, exposure to cold is probably a precipitating factor.


A hybrid GaN/Ga2O3 structure anchored on carbon cloth as a high-performance electrode of supercapacitors.
A hybrid structure of GaN/Ga2O3 microrods was fabricated on carbon cloth (CC) using a hydrothermal process combined with a high-temperature nitridation followed by an air annealing process. By elevating the post-annealing temperature to 500 °C, both electron density (ND) and specific capacitance (Ca) of the composite electrode were significantly enhanced. Symmetric SCs assembled with GaN/CC-500 showed great potential in both 1 M H2SO4 aqueous solution and a PVA-H2SO4 gel-like electrolyte. The aqueous symmetric GaN/CC-500 SC exhibited an excellent capacitance (1301.20 mF cm-2, 0.5 mA cm-2), high rate capability (75.23% of capacitance retention at 10 mA cm-2), outstanding cycling stability (77.27% of capacitance retention after 20 000 cycles, 10 mA cm-2), and large energy storage capability (27.53 μW h cm-2 of energy density, 0.10 mW cm-2 of power density). All-solid-state symmetric GaN/CC-500 SC also manifested a high capacitance (1183.35 mF cm-2, 0.5 mA cm-2) and good rate capability (53.98% capacitance retention, 10 mA cm-2). The high electrochemical performance of the GaN/CC-500 electrode is attributed to the GaN/Ga2O3 hybrid structure, with α-Ga2O3 providing absorption/redox active sites on the surface, and the heavily oxygen-doped GaN enabling fast electron transport. The microrods with the GaN/Ga2O3 hybrid structure as the active material for solid SCs can deliver an energy density of 0.58 W h kg-1 (3.54 mW h cm-3) with a power density of 154 W kg-1 (0.94 W cm-3). The mechanism identified in this work would be helpful in designing GaN-based energy storage devices with better performances in the future.


Role of uric acid in hypertension, renal disease, and metabolic syndrome.
Hyperuricemia has long been known to be associated with cardiovascular disease, and it is particularly common in people with hypertension, metabolic syndrome, or kidney disease. Most authorities have viewed elevated uric acid as a secondary phenomenon that is either innocuous or perhaps even beneficial, since uric acid can be an antioxidant. However, recent experiments have challenged this viewpoint. In this paper we argue that uric acid is a true risk factor for cardiovascular disease. Furthermore, we suggest that the recent increased intake in the American diet of fructose, which is a known cause of hyperuricemia, may be contributing to the current epidemic of obesity and diabetes.


[Seroprevalence of the human cytomegalovirus among blood donors and AIDS patients in Bamako].
Our aim was to study the prevalence of the human cytomegalovirus (HCMV) among blood donors and AIDS patients and to examine a clinical correlation between AIDS and HCMV seroprevalence in Bamako (Mali, West Africa). We have used Elisa kits for detecting HIV and HCMV specific antibodies. The HCMV seroprevalence was 89% among AIDS patients, 71% among HIV-infected blood donors and 58% among HIV-uninfected blood donors. The HCMV seroprevalence rate was higher among AIDS patients than among HIV-uninfected blood donors (p=0.0000007) and than among HIV-infected blood donors (p=0.00146). There was no significant difference between the HCMV seroprevalence among HIV-infected blood donors and among HIV-uninfected blood donors (p=0.0547). There was no relationship between HCMV seroprevalence and sex or age among AIDS patients and blood donors. There was a significant difference on pneumonia among HCMV-infected AIDS patients and among HCMV-uninfected AIDS patients (40% versus 0%; p=0.005). Buccal and phaiyngal candidosis, dermatosis, Kaposi's sarcoma and nervous system diseases had the same frequency among HCMV-infected and HCMV-uninfected AIDS patients.


"Ain't Necessarily So!": The Brake Industry's Impact on Asbestos Regulation in the 1970s.
Canada is proposing a ban on asbestos, and the US Environmental Protection Agency has listed it among the first 10 materials it is investigating under the new Toxic Substances Control Act revisions. However, this effort is currently running up against enormous industry and political opposition. Here, we detail the activities in the early 1970s of the Friction Materials Standards Institute, an industry trade association, to stifle earlier attempts to regulate asbestos use in brake linings, one of the oldest and most obvious sources of asbestos exposure to mechanics, among others. (Am J Public Health. 2017: 1395-1399. doi: 10.2105/AJPH.2017.303901).


Structural determination of unknown subsidiary colors in commercial food red Nos. 2 and 102.
Major subsidiary colors A (Sub A) and B (Sub B) in commercial Food Red No. 102, and colors C (Sub C) and D (Sub D) in commercial Food Red No.2 were isolated. These structures were characterized by physicochemical evidence. The structures of Sub A, B, and C are trisodium salt of 7-hydroxy-8-(6-sulfonaphthyl-2-azo)-1,3-naphthalenedisulfonic++ + acid, disodium salt of 4-amino-3-(4-sulfonaphthyl-1-azo)-1-naphthalenesulfonic acid and trisodium salt of 3-hydroxy-4-(6-sulfonaphthyl-2-azo)-2,7-naphthalenedisulfonic++ + acid, respectively. Sub D was identified as Sub B.


The relationship of weight suppression to treatment outcomes during behavioral weight loss.
Many adults enter behavioral weight loss (BWL) programs at a weight below their highest lifetime weight. The discrepancy between highest lifetime weight and current weight is known as weight suppression (WS). Research has yet to characterize WS during BWL or investigate its relation to weight loss outcomes or treatment acceptability. Adults (N = 272) in a 12-month BWL program were assessed. WS was calculated by subtracting measured baseline weight from self-reported highest lifetime weight. Participants with higher WS lost significantly less weight than those with lower WS during treatment, although they still had clinically meaningful weight losses (e.g., participants with WS above the median: 7.8 kg; participants with WS below the median: 12.0 kg). WS was unrelated to weight losses at 24-month follow-up. Controlling for weight loss, treatment acceptability was unrelated to WS. BWL appears appropriate for those with high WS, but future research should aim to improve outcomes in this group.


Diversity and community structure of cyanobacteria and other microbes in recycling irrigation reservoirs.
Recycling irrigation reservoirs (RIRs) are emerging aquatic environments of global significance to crop production, water conservation and environmental sustainability. This study characterized the diversity and population structure of cyanobacteria and other detected microbes in water samples from eight RIRs and one adjacent runoff-free stream at three ornamental crop nurseries in eastern (VA1 and VA3) and central (VA2) Virginia after cloning and sequencing the 16S rRNA gene targeting cyanobacteria and chloroplast of eukaryotic phytoplankton. VA1 and VA2 utilize a multi-reservoir recycling irrigation system with runoff channeled to a sedimentation reservoir which then overflows into transition and retention reservoirs where water was pumped for irrigation. VA3 has a single sedimentation reservoir which was also used for irrigation. A total of 208 operational taxonomic units (OTU) were identified from clone libraries of the water samples. Among them, 53 OTUs (358 clones) were cyanobacteria comprising at least 12 genera dominated by Synechococcus species; 59 OTUs (387 clones) were eukaryotic phytoplankton including green algae and diatoms; and 96 were other bacteria (111 clones). Overall, cyanobacteria were dominant in sedimentation reservoirs, while eukaryotic phytoplankton and other bacteria were dominant in transition/retention reservoirs and the stream, respectively. These results are direct evidence demonstrating the negative impact of nutrient-rich horticultural runoff, if not contained, on natural water resources. They also help in understanding the dynamics of water quality in RIRs and have practical implications. Although both single- and multi-reservoir recycling irrigation systems reduce the environmental footprint of horticultural production, the former is expected to have more cyanobacterial blooming, and consequently water quality issues, than the latter. Thus, a multi-reservoir recycling irrigation system should be preferred where feasible.


Acute asthma: under attack.
The burden of asthma (death, disability, and an increasing prevalence) makes it a major public health problem worldwide. In an effort to decrease this burden, investigators are studying many aspects of this disease. The role of race, ethnicity, infections, and pollutants as triggers, as well as the risk factors are now being defined. Research into methods to decrease acute exacerbations and improve emergency and in-hospital management, using standardized protocols and incentives for follow-up care, has yielded valuable information but has met with limited success. Adherence to the national guidelines has been poor and to some extent can be attributed to the lack of a practical method of measuring the degree of lung inflammation and cumbersome treatment protocols. Exhaled nitric oxide is a noninvasive marker of inflammation and may provide a rational method to titrate corticosteroid and leukotriene receptor antagonist therapy. The best route and dosing regimen for corticosteroid administration (oral vs intramuscular vs nebulized) are the subject of several studies, with no clear-cut winner. The burden of asthma in developing countries with limited financial resources has also triggered a search for simpler, cheaper, and practical methods for beta-agonist delivery using indigenous spacers. Recent research in asthma has unveiled our incomplete knowledge of the disease but has also provided a sense of where efforts should be expended. Research into the genetics and pharmacogenetics of asthma and into the societal factors limiting the delivery of optimal care is likely to yield useful and practical information.


miR-142 inhibits the migration and invasion of glioma by targeting Rac1.
Increasing evidence has shown that aberrant microRNAs (miRNAs) are implicated in tumorigenesis and tumor progression by regulating oncogenes or tumor suppressors. Dysregulation of miR-142 has been reported in multiple tumors. However, its clinical roles and underlying mechanism in glioma remain to be elucidated. In the present study, we found that the expression of miR-142 was significantly downregulated in both glioma tissues and cell lines by qRT-PCR. Clinical analysis revealed that decreased miR-142 was markedly associated with advanced World Health Organization (WHO) grade. Moreover, we disclosed that miR-142 was a novel independent prognostic marker in the prediction of the 5-year survival of glioma patients. The ectopic overexpression of miR-142 inhibited cell migration, invasion and invasion‑related gene expression. Notably, miR-142 modulated Rac1 by directly binding to its 3'-untranslated (3'-UTR) region, leading to the suppression of the expression of matrix metalloproteinases (MMPs). In glioma clinical samples, miR-142 was inversely correlated with Rac1 expression, and played positive roles in glioma migration and invasion. Alteration of Rac1 expression at least partially abolished the migration, invasion and MMP expression of miR-142 in glioma cells. In the present study, we identified Rac1 as a functional target of miR-142 in glioma. In conclusion, our data indicated that miR-142 inhibited the migration, invasion and MMP expression of glioma by targeting Rac1, and may represent a novel potential therapeutic target and prognostic marker for glioma.


Building the house around the plumbing.
Signaling between growing blood vessels and the tissues that they innervate has traditionally been viewed as a one-way conversation, with organs and tissues supplying important cues for the growth and anatomical patterning of the blood vessels supplying them, but not vice-versa. Two recent papers now provide evidence that blood vessels can have an important role in promoting the assembly of organs and tissues. These papers show that proper formation of the pancreas and liver and induction of endocrine and hepatic cell types in these endodermal organs requires inductive signals from blood vessels.


Measuring Survival of Hematopoietic Cancer Cells with the Colony-Forming Assay in Soft Agar.
Colony-forming assays measure the ability of cells in culture to grow and divide into groups. Any cell that has the potential to form a colony may also have the potential to cause cancer or relapse in vivo. Colony-forming assays also provide an indirect measurement of cell death because any cell that is dead or dying will not continue to proliferate. The proliferative capacity of adherent cells such as fibroblasts can be determined by growing cells at low density on culture dishes and counting the number of distinct groups that form over time. Cells that grow in suspension, such as hematopoietic cells, cannot be assayed this way because the cells move freely in the media. Assays to determine the colony-forming ability of hematopoietic cells must therefore be performed in solid matrices that restrict large-scale movement of the cells. One such matrix is soft agar. This protocol describes the use of soft agar to compare the colony-forming ability of untreated hematopoietic cells to the colony-forming ability of hematopoietic cells that have been treated with a cytotoxic agent.


Penetration of Sandimmune (cyclosporin A) in rat skin in vitro. Effects of penetration enhancers and solvents.
The effect of various fatty acids or alcohols on the penetration rates and skin concentrations of cyclosporin A (Sandimmune; CyA) was evaluated in an in vitro model using skin of hairless rats. The influence of chain length, number and position of double bonds and branching of the carbon chain of the enhancer were investigated. In addition the penetration dependency of CyA on the concentration of both enhancer and CyA was studied. CyA was quantitated by high-performance liquid chromatography. The penetration rates of CyA through rat skin decreased with increasing number of double bonds of the enhancer and decreasing CyA concentrations in the donor solution, and increased with increasing chain length of the enhancer. Enhancers increase penetration rates by a factor of up to 20-90 in alcoholic vs. maximally 5-fold in oily compositions. Enhancers increase skin concentrations of CyA by a factor of up to 10-25 in alcoholic and about 4-20 in oily compositions.


[An edentulous case with articulation disorder and severe bone resorption].
A 71-year-old man complained of articulation disorder caused by poor retention of the upper and lower complete dentures. Both maxillary and mandibular residual ridges showed severe resorption. The dentures had short base borders and poor retentions, and were sway with mandibular functional movement. First, I planned to improve the retention and mandibular position of his dentures by repairing his dentures. When I confirmed to make a good retention and an appropriate mandibular position, I started to make new dentures, and then set them. Evaluation before and after treatment showed recovery of articular function. The new denture, which has suitable tongue space, made the tongue movement area during speaking wider. This might result from the patient acclimatizing to a new condition. New dentures showing stable retention and good articular function were not sway during functioning or articulation, and the patients articulation became clear.


On the intermediates in chiral bis(oxazoline)copper(II)-catalyzed enantioselective reactions--experimental and theoretical investigations.
The intermediates in the chiral bis(oxazoline)copper(II)-catalyzed reactions have been investigated by means of experimental and theoretical investigations. It is shown that the absolute configuration of the hetero-Diels-Alder adduct obtained from the reaction of ethyl glyoxylate with 1,3-cyclohexadiene in the presence of the chiral bis(phenyloxazoline)copper(II) is dependent on the solvent. In this case, a linear relationship between the enantiomeric excess (ee) and the dielectric constant of the solvent was observed. However, the enantiomeric excess for the adduct obtained with the chiral bis(tert-butyloxazoline)copper(II) complex is independent of the solvent. The addition of different coordinating solvents to the chiral catalysts was investigated and no effect on the enantioselectivity of the reaction was observed. A series of chiral bis(tert-butyloxazoline)-, bis(phenyloxazoline)-, and bis(indaneoxazoline)copper(II) complexes has been prepared and characterized by X-ray analysis, and the similarity between the structures is discussed. For comparison, two related chiral bis(tert-butyloxazoline)- and bis(phenyloxazoline)zinc(II) complexes were also prepared and characterized. A series of chiral bis(oxazoline)copper(II)-substrate (the substrate being glyoxal or methyl glyoxylate) complexes was investigated by means of ab initio calculations. Calculation of the total energy of the optimized structure of 17-, 19-, and 21-electron bis(oxazoline)copper(II)-substrate complexes give the 17-electron complex as the most stable and the most reactive complex, while the 21-electron complex is less stable and also much less reactive. The optimized structures of both the 17-electron bis(tert-butyloxazoline)- and bis(phenyloxazoline)copper(II)-substrate complexes show that the plane of the substrate molecule is twisted by approximately 40-45 degrees out of the bis(oxazoline)copper(II) plane, in agreement with the X-ray structures. On the basis of the experimental results, X-ray structures, and ab initio calculations, the structure of the intermediate(s) and reactivity of the chiral bis(oxazoline)copper(II)-substrate complexes are discussed.


Comparative evaluation of urolithiasis management options in patients with horseshoe kidney: A systematic review and meta-analysis.
Horseshoe kidney is a rare congenital anomaly commonly complicated by urolithiasis. Extracorporeal shockwave lithotripsy (ESWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL) are treatment options for horseshoe kidney stones. The aim of this systematic review is to compare the benefits and risks of these management options. MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to February 2022. A total of 516 nonduplicate studies were screened against the inclusion and exclusion criteria. Studies comparing at least 2 interventions with ≥10 patients per intervention were included. Nine retrospective observational studies published from 2007 to 2021 with a total of 565 patients were included. Reported mean ± SD or mean (range) stone sizes ranged between 17.90 ± 2.43 mm and 27.9 ± 8.6 mm for PCNL, 8.4 (2-25) mm and 22.3 ± 9.1 mm for URS, and 11.9 ± 2.0 mm and 16.8 ± 4.4 mm for ESWL. There was no difference in single-session and overall stone-free rate (SFR) between PCNL and URS, with a risk ratio of 1.04 (95% confidence interval, 0.95-1.13; I2 = 20.63%). Ureteroscopy had better stone clearance than ESWL, with an overall SFR risk ratio of 1.38 (95% confidence interval, 1.04-1.82; I2 = 0%). There was no statistically significant difference in overall SFR between PCNL and ESWL. Most patients who underwent URS and ESWL experienced Clavien-Dindo (CD) grade I-II complications. Percutaneous nephrolithotomy was associated with the highest complication rates, including 5 CD grade III and 3 CD grade IV complications and a mean postoperative hemoglobin drop of 0.47 to 1.83 g/dL. There were no CD grade V complications across all studies. There was no difference in SFR between PCNL and URS. Ureteroscopy was associated with a smaller stone burden and fewer and less severe complications. Ureteroscopy was found to be more effective than ESWL with a higher SFR and comparable safety profile. Further large-scale randomized controlled trials are needed to confirm these findings.


Perceptions of Oncology Providers and Cancer Survivors on the Role of Nutrition in Cancer Care and Their Views on the "NutriCare" Program.
Cancer patients and survivors can experience treatment related side effects that impact nutrition status, as well as unwanted weight loss, weight gain and poor dietary quality. Therefore, they are a group that would benefit from nutrition intervention. A qualitative study was conducted online (six focus groups and two interviews) with 12 oncology providers and 12 survivors in the United States. Participants were asked about the role of nutrition in survivors' health, appropriate components of nutrition care for cancer patients, and strategies to integrate nutrition into oncology care. Feedback on a proposed program, "NutriCare", was also sought. Focus groups were recorded, transcribed verbatim, and analyzed for themes. Four main themes emerged: (1) nutrition is an important component of oncology care and source of empowerment for cancer patients; (2) in the NutriCare program, the prescription pad component was viewed as a critical aspect, and there was also a preference for dealing with patients and survivors separately; (3) for implementation, the most appropriate time for providers to talk to patients about nutrition is during the development of the treatment plan. Reinforcement of key nutrition messages by providers was also highlighted; (4) major barriers included lack of time and motivation by providers. Survivors were interested in and providers supportive of integrating nutrition into oncology care.


Role of pRIFLE Criteria in Early Diagnosis of Severity Staging of Neonatal AKI and its Impact on Management.
Mortality is high among sick neonates who have concomitant acute kidney injury (AKI). This observational study was done at Special Care Baby Unit (SCABU) of Dhaka Medical College Hospital (DMCH), Bangladesh from October 2013 to March 2014 to find out the role of pRIFLE criteria in prediction of severity stages of AKI in neonate and early intervention to see the immediate outcome. A total of 44 neonates with AKI were included, all were treated conservatively and with intermittent peritoneal dialysis (IPD) as needed. The neonate of ≤7 days old comprised the main bulk (n=28) and M: F = 21: 23. The diagnosis was based on eCCL criteria of pRIFLE showed that 40.9% neonates were at risk of AKI, 20.5% have had already injured. Higher proportions of neonates were classified as failure (38.6%). The distribution of biochemical parameters among three stages of AKI showed serum potassium was significantly higher in failure group (p<0.001). The serum creatinine both at baseline and at next evaluations were significantly raised in the failure group (p<0.001). However, failure group had a significantly longer hospital stay compared to risk and injury group (p<0.001). Multiorgan failure was found to be lower in the risk group compared to other two groups (p=0.026). Majority of the failure group needed dialysis as compared to the risk and injury group (p<0.001). The mortality was progressively higher from risk to failure groups (p=0.106). Overall 27% of the neonates diagnosed AKI by pRIFLE were died of the disease. The study concluded that pRIFLE staging in AKI is useful and sensitive in the diagnosis and management of AKI in neonates.


The consequence of level of nutrition on heifer ovarian and mammary development.
Replacing cows in the herd is second only to nutrition as the single greatest input cost in cow/calf beef production. The increased availability of cereal grains for feeding livestock has allowed replacement heifers to enter the production system at younger ages. Many heifer development programs feed to ensure heifers reach puberty before the time that they are mated to calve at 2 yr of age. Nutrition level during development has been associated with altered milk production and stayability. We hypothesized that heifers exposed to a lower nutrition level during the peripubertal period would have less methylation of the DNA in the mammary gland and ovarian cortex. We also hypothesized that the ovarian reserve would decrease in heifers fed for rapid growth compared to heifers fed for slow growth during puberty. At 257±1 d of age, heifers in the Stair-Step treatment (n=6) received 157 kcal ME/BW kg0.75 for 84 d and heifers in the Conventional treatment (n=6) were offered 228 kcal ME/BW kg0.75. At d 84, heifers were fed for an additional 83 d. Stair-Step heifers were offered 277 kcal ME/BW kg0.75, and heifers on the Conventional treatment received 228 kcal ME/BW kg0.75. Mammary weights (P=0.43), capillary area density (P=0.74), and capillary surface density (P=0.18) did not differ between treatments and neither did alveolar number (P=0.55) and alveolar density (P=0.49). Reproductive tract weights (P=0.69) and ovarian weight (P=0.68) and ovarian size (P>0.75) did not differ between treatments. In histological sections, Stair-Step heifers had more primordial follicles than Conventional heifers (P=0.02), but primary (P=0.59) and secondary (P=0.15) follicles did not differ. Global methylation of parenchymal tissue (P=0.82), mammary fat pad (P=0.45), and ovarian cortex (P=0.14) did not differ between treatments. Anterior pituitary weight did not differ between treatments (P=0.16). Our hypothesis that modifying peripubertal nutrition modifies global methylation of the mammary and ovary is not supported; however, our hypothesis that it modifies the ovarian reserve is supported.


Controlled protein dimerization through hybrid coordination motifs.
Protein homodimerization is the simplest form of oligomerization that is frequently utilized for the construction of functional biological assemblies and the regulation of cellular pathways. Despite its simplicity, dimerization still poses an enormous challenge for protein engineering and chemical manipulation, owing to the large molecular surfaces involved in this process. We report here the construction of a hybrid coordination motif--consisting of a natural (His) and a non-natural ligand (quinolate)--on the alpha-helical surface of cytochrome cb(562), which (a) simultaneously binds divalent metals with high affinity, (b) leads to a metal-induced increase in global protein stability, and importantly, (c) enables the formation of a discrete protein dimer, whose shape is dictated by the inner-sphere metal coordination geometry and closely approximates that of the DNA-binding domains of bZIP family transcription factors.


Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy.
The rates of fibrosis progression in chronic hepatitis C are significantly different between males and females. The antifibrogenic effect of oestrogen has been proposed, possibly via inhibition of stellate cells. The aim of this study was to evaluate the severity of chronic hepatitis C in women, in relation to the menopause, steatosis and hormone replacement therapy (HRT). From November 2003 to October 2004, women with chronic hepatitis C were enrolled prospectively. A questionnaire was completed prospectively and a blood sample was obtained on the day of biopsy. We identified characteristics associated with moderate/severe fibrosis using univariate and multivariate analysis. 251 women were included in the study. 122 women (52%) were menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe fibrosis (F2-F4, Metavir score) had a longer known duration of infection (>15 years), a higher body mass index and presented with steatosis more frequently than 190 (76%) women with mild fibrosis (F0-F1). Women with F2-F4 were more often menopausal (67% v 47%). The probability of fibrosis F2-F4 was lower for menopausal women receiving HRT (p = 0.012). Steatosis was more frequent and more severe in menopausal women. Severity of fibrosis was associated with a longer duration of infection (>15 years), a higher body mass index, advanced steatosis and the menopause. Menopausal women receiving HRT presented with a lower stage fibrosis. These results reinforce the hypothesis of a protective role of oestrogens in the progression of fibrosis. Steatosis may be implicated in the progression of fibrosis after the menopause.


Analysis of errors in following the rapid maxillary expansion activation protocol: An observational study.
The aim of this study is to analyse the correspondence between the reported number of activations and the number of prescribed activations. A total of 114 subjects with constricted maxillary arches (58 males, 56 females; mean age 10.26 ± 1.92 years) were enrolled in the study. The subjects underwent RME and all the parents were provided with a screw activations report form in order to remind them the number of prescribed activations. At the removal of the expander, the screw was turned back in order to count the effective number of activations applied. In 46 cases, out of a total of 114 patients, an involuntary error during the activation procedure was presumably made. A slight statistically significant correlation between the number of activations prescribed, and the number of incorrect activations was found. The errors consisted in added or missed activations, compared to the prescribed number but more frequently in missed activations with statistical significance. Errors in following the rapid palatal expansion activation protocol are not uncommon. These errors could consist in missed or added activations to the number prescribed by the orthodontist, more often in missed ctivations.


Aspiration cytodiagnosis of amyloid from vitreous fluid.
Amyloidosis of the vitreous body is a rare disorder that causes progressive visual loss. In this report, a 36-yr-old female with familial amyloidosis is described in whom a progressive reduction of vision in both eyes over the last 4 yr was ascribed to vitreous opacities due to amyloid. A left pars plana vitrectomy was performed and an aspirated sample of the vitreous on cytologic examination showed vitreous strands admixed with abundant dense, pink, globular material which was intensely positive on Congo red staining and exhibited yellowish-green birefringence indicative of amyloid. This was further confirmed ultrastructurally, which showed the classical appearance of amyloid fibrils. The case is of interest not only in view of the rarity of the condition but also in view of the fact that as far as we are aware the cytodiagnosis of amyloid from an aspirate sample from the vitreous has not been previously described in the literature.


Insulin receptor substrate-1 deficiency promotes apoptosis in the putative intestinal crypt stem cell region, limits Apcmin/+ tumors, and regulates Sox9.
Reduced apoptosis of crypt stem/progenitor cells and elevated insulin and IGFs are linked to colon cancer risk. Insulin receptor substrate-1 (IRS-1) mediates the actions of insulin, IGF-I, and IGF-II, but the role of endogenous IRS-1 in crypt apoptosis and cancer is undefined. Using IRS-1(-/-), IRS-1(+/-), and IRS-1(+/+) mice, we tested the hypothesis that reduced IRS-1 expression increases apoptosis of intestinal crypt cells and protects against Apc(min/+) (Min)/beta-catenin-driven intestinal tumors. Expression of Sox9, a transcriptional target of Tcf/beta-catenin and putative biomarker of crypt stem cells, was assessed in intestine of different IRS-1 genotypes and cell lines. Irradiation-induced apoptosis was significantly increased in the crypts and crypt stem cell region of IRS-1-deficient mice. Tumor load was significantly reduced by 31.2 +/- 14.6% in IRS-1(+/-)/Min and by 64.1 +/- 7.6% in IRS-1(-/-)/Min mice, with more prominent reductions in tumor number than size. Compared with IRS-1(+/+)/Min, IRS-1(-/-)/Min mice had fewer Sox9-positive cells in intestinal crypts and reduced Sox9 mRNA in intestine. IRS-1 overexpression increased Sox9 expression in an intestinal epithelial cell line. We conclude that even small reductions in endogenous IRS-1 increase apoptosis of crypt stem or progenitor cells, protect against beta-catenin-driven intestinal tumors, and reduce Sox9, a Tcf/beta-catenin target and putative stem/progenitor cell biomarker.


Preparation of mesostructured siloxane-organic hybrid films with ordered macropores by templated self-assembly.
Novel hierarchically ordered siloxane-based hybrid films with well-defined macropores and mesostructured pore walls have been prepared by the self-assembly process using oligomeric siloxane precursors bearing alkyl chains (CnH2n+1Si(OSi(OMe)3)3) in the presence of polystyrene opal films as a template. Either a two-dimensional (2D) hexagonal structure or a lamellar structure was formed depending on the alkyl chain length of the precursors (n = 10 and 16, respectively). In both of the films, the mesostructures were oriented along the spherical surface of the template and were retained after removal of the template. Calcination of the 2D hexagonal hybrid produced ordered porous silica with both macro- and microporosities. The lamellar hybrid film exhibited a unique property of accommodating alkyl alcohols with an expansion of the interlayer spacings. These results provide a new concept for designing hierarchical hybrid materials that are potentially applicable as adsorbents, catalysts, sensors, and photonic crystals.


Illuminating Iron: Mesoionic Carbenes as Privileged Ligands in Photochemistry.
The new iron age: The stabilization of an iron(III) complex with mesoionic carbenes has been shown to lead to record-breaking excited-state lifetimes and an unprecedented spin-allowed radiative decay from a 2 LMCT state. These results set the stage for a sustainable future in the new "iron age".


Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study.
Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats' model. 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining. There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS.


Analysis of genetic markers in forensic DNA samples using the polymerase chain reaction.
The ability to extract and type DNA from forensic evidentiary samples has revolutionized the field of forensic serology. Previously, genetic marker typing was limited to the analysis of blood group markers and soluble polymorphic protein markers. Because the number of suitable markers expressed in particular fluids and tissues is relatively small, and because mixtures of fluids cannot be separated for conventional genetic marker typing, a suspect frequently cannot be included or excluded as a fluid donor in a case. However, the development of methods to extract DNA from virtually all biological specimens has greatly expanded the potential for individual identification. Of particular importance was the ability to extract mixtures of sperm cells and epithelial cells found in sexual assault cases such that the DNA from the sperm cells could be typed independently of the DNA from the victim's epithelial cells. Restriction fragment length polymorphism (RFLP) analysis was the first DNA-based method applied to problems of individual identification. This method, while powerful in its ability to differentiate individuals, is limited by the quantity and quality of DNA required for an unambiguous result and by the amount of time it takes to obtain a result. Despite these limitations, several laboratories are using RFLP analysis successfully for the detection of polymorphisms in forensic DNA case samples. While the field of forensic serology was being revolutionized by the prospect of DNA analysis, the field of molecular biology was being revolutionized by the invention of the polymerase chain reaction (PCR), which ultimately has had an impact on every area of biological science. The PCR DNA amplification technology is ideally suited for the analysis of forensic DNA samples in that it is sensitive and rapid and not as limited by the quality of DNA as the RFLP method. The focus of this article is the use of the PCR for typing genetic markers, and we will address specifically the special considerations that arise from applying DNA amplification and typing technology to forensic materials.


Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood.
The platelet glycoproteins (GPs) Ib, integrin alpha(2)beta(1), and GPVI are considered central to thrombus formation. Recently, their relative importance has been re-evaluated based on data from murine knockout models. To examine their relationship during human thrombus formation on collagen type I fibers at high shear (1000 s(-1)), we tested a novel antibody against GPVI, an immunoglobulin single-chain variable fragment, 10B12, together with specific antagonists for GPIb alpha (12G1 Fab(2)) and alpha(2)beta(1) (6F1 mAb or GFOGER-GPP peptide). GPVI was found to be crucial for aggregate formation, Ca(2+) signaling, and phosphatidylserine (PS) exposure, but not for primary adhesion, even with more than 97% receptor blockade. Inhibiting alpha(2)beta(1) revealed its involvement in regulating Ca(2+) signaling, PS exposure, and aggregate size. Both GPIb alpha and alpha(2)beta(1) contributed to primary adhesion, showing overlapping function. The coinhibition of receptors revealed synergism in thrombus formation: the coinhibition of adenosine diphosphate (ADP) receptors with collagen receptors further decreased adhesion and aggregation, and, crucially, the complete eradication of thrombus formation required the coinhibition of GPVI with either GPIb alpha or alpha(2)beta(1). In summary, human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with alpha(2)beta(1) mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation.


Fluorescent Calixarene Scaffolds for NO Detection in Protic Media.
We present the first fluorescent water-soluble conjugated calixarene scaffolds that are capable of NO gas detection. Two different scaffolds, one based on a 5,5'-bicalixarene structure and its isomer bearing two distantly conjugated calixarene moieties, were synthesized. While the fluorescence of both isomers is quenched upon either passing of NO gas or generating it in situ from diethylamine NONOate, the bicalixarene-based scaffold showed a significantly stronger response. We also present an example of a dye encapsulation strategy to achieve the detection of NO at longer wavelengths than in the parent calixarene host. Finally, a conjugated polymer bearing a 5,5'-bicalixarene scaffold has also been prepared and demonstrated enhanced sensitivity compared to the monomer due to the molecular wire effect.


An estimate of the size of the metacyclic variable antigen repertoire of Trypanosoma brucei rhodesiense.
A group of 27 variable antigen type (VAT)-specific monoclonal antibodies (McAbs) have been made against metacyclic forms of a cloned stock of Trypanosoma brucei rhodesiense. In combination, these labelled in immunofluorescence 99.3% of trypanosomes in salivary probes from tsetse flies. The 0.7% of unlabelled trypanosomes were believed to be uncoated forms. The ability of a mixture of antibodies to kill metacyclics in vitro by complement-mediated lysis, thus neutralizing their infectivity for mice, was tested. The antibody mixture consisted of 24 McAbs plus 3 VAT-specific rabbit antisera. In 12 replicate experiments this mixture of antibodies prevented infection of mice. Parallel controls showed that neutralization was probably antibody-mediated and VAT specific. However, we have not been able to repeat these results on a long-term basis; this may be due to a loss of neutralizing activity by one of the McAbs. The successful neutralization experiments indicate that the number of VATs in the metacyclic repertoire of one stock of T. b. rhodesiense is limited to at most 27.


High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.
A number of sequencing studies identified the prognostic impact of somatic mutations in myelodysplastic syndrome (MDS). However the majority of them focused on methylation regulation, apoptosis and proliferation genes. Despite the number of experimental studies published on the role of micro-RNA processing and checkpoint genes in the development of MDS, the clinical data about mutational landscape in these genes is limited. We performed a pilot study which evaluated mutational burden in these genes and their association with common MDS mutations. High prevalence of mutations was observed in the genes studied: 54% had mutations in DICER1, 46% had mutations in LAG3, 20% in CTLA4, 23% in B7-H3, 17% in DROSHA, 14% in PD-1 and 3% in PD-1L. Cluster analysis that included these mutations along with mutations in ASXL1, DNMT3A, EZH2, IDH1, RUNX1, SF3B1, SRSF2, TET2 and TP53 effectively predicted overall survival in the study group (HR 4.2, 95%CI 1.3-13.6, p = 0.016). The study results create the rational for incorporating micro-RNA processing and checkpoint genes in the sequencing panels for MDS and evaluate their role in the multicenter studies.


[The future of PET in cardiology].
Positron emission tomography (PET) is an intrinsically quantitative method that provides an approach for the clinical cardiologist and cardiovascular researchers to evaluate the heart noninvasively. The ability to label biomolecules with positron-emiting radioisotopes, without disturbing their physiological properties, offers the opportunity to prove and quantify coronary blood flow, myocardial metabolism, and the alterations that occur with disease states. However, the major drawback prohibiting implementation of PET imaging in clinical routine is the limited availability of PET equipment and its greater cost per study. In order to enhance cost savings and resource efficiency in clinical practice, PET studies should be limited to those patients with equivocal studies by other imaging modalities or to define areas of potential viability and improve decisions for recommending coronary bypass grafting or cardiac transplantation. The combined data of multiple investigators suggest that 18-FDG-SPECT imaging may become the protocol of choice for determining myocardial viability because of its increased availability and cost-effectiveness as compared to PET.


Proteome and transcriptome analysis of retinoic acid-induced differentiation of human acute promyelocytic leukemia cells, NB4.
Acute promyelocytic leukemia (APL) is characterized by a translocation t(15:17) that fuses the retinoic acid receptor gene with the promyelocytic gene, which blocks differentiation to normal granulocytes. NB4 cells, derived from human acute promyelocytic leukemia, display this genotype and phenotype. All trans-retinoic acid (ATRA) induces differentiation of NB4 cell cultures in vitro and APL in vivo, although resistance to differentiation therapy frequently develops. To identify genes involved in differentiation, we compared gene expression at the mRNA and protein levels using microarray analyses and two-dimensional (2D) difference gel electrophoresis (DIGE), plus MALDI-TOF-TOF mass spectrometry. Differentially expressed transcripts were identified using oligonucleotide-based microarrays with targets representing almost 14 000 genes. Real time PCR was performed on a subset of genes whose products were shown to be differentially expressed using proteomic and/or genomic approaches. Our analyses identified 46 genes that were differentially expressed in NB4 +/- ATRA; 22 were identified using 2D-DIGE and 24 using microarray analysis. All but four of these genes were expressed at higher levels in differentiated cells, and several controlled cell structure (internal and cytoskelatal) or signal transduction. We observed that proteome analysis with DIGE and silver-stained 2D gel electrophoresis analyses revealed significant differences between the two measurement approaches. Furthermore, our data showed significant discordance between gene expression at the protein and transcript levels.


EVOLUTION OF INCOMPATIBILITY-INDUCING MICROBES AND THEIR HOSTS.
In many insect species, males infected with microbes related to Wolbachia pipientis are "incompatible" with uninfected females. Crosses between infected males and uninfected females produce significantly fewer adult progeny than the other three possible crosses. The incompatibility-inducing microbes are usually maternally transmitted. Thus, incompatibility tends to confer a reproductive advantage on infected females in polymorphic populations, allowing these infections to spread. This paper analyzes selection on parasite and host genes that affect such incompatibility systems. Selection among parasite variants does not act directly on the level of incompatibility with uninfected females. In fact, selection favors rare parasite variants that increase the production of infected progeny by infected mothers, even if these variants reduce incompatibility with uninfected females. However, productivity-reducing parasites that cause partial incompatibility with hosts harboring alternative variants can be favored once they become sufficiently abundant locally. Thus, they may spread spatially by a process analogous to the spread of underdominant chromosome rearrangements. The dynamics of modifier alleles in the host are more difficult to predict, because such alleles will occur in both infected and uninfected individuals. Nevertheless, the relative fecundity of infected females compared to uninfected females, the efficiency of maternal transmission and the mutual compatibility of infected individuals all tend to increase under within-population selection on both host and parasite genes. In addition, selection on host genes favors increased compatibility between infected males and uninfected females. Although vertical transmission tends to harmonize host and parasite evolution, competition among parasite variants will tend to maintain incompatibility.


Open-source Web Portal for Managing Self-reported Data and Real-world Data Donation in Diabetes Research: Platform Feasibility Study.
People with diabetes and their support networks have developed open-source automated insulin delivery systems to help manage their diabetes therapy, as well as to improve their quality of life and glycemic outcomes. Under the hashtag #WeAreNotWaiting, a wealth of knowledge and real-world data have been generated by users of these systems but have been left largely untapped by research; opportunities for such multimodal studies remain open. We aimed to evaluate the feasibility of several aspects of open-source automated insulin delivery systems including challenges related to data management and security across multiple disparate web-based platforms and challenges related to implementing follow-up studies. We developed a mixed methods study to collect questionnaire responses and anonymized diabetes data donated by participants-which included adults and children with diabetes and their partners or caregivers recruited through multiple diabetes online communities. We managed both front-end participant interactions and back-end data management with our web portal (called the Gateway). Participant questionnaire data from electronic data capture (REDCap) and personal device data aggregation (Open Humans) platforms were pseudonymously and securely linked and stored within a custom-built database that used both open-source and commercial software. Participants were later given the option to include their health care providers in the study to validate their questionnaire responses; the database architecture was designed specifically with this kind of extensibility in mind. Of 1052 visitors to the study landing page, 930 participated and completed at least one questionnaire. After the implementation of health care professional validation of self-reported clinical outcomes to the study, an additional 164 individuals visited the landing page, with 142 completing at least one questionnaire. Of the optional study elements, 7 participant-health care professional dyads participated in the survey, and 97 participants who completed the survey donated their anonymized medical device data. The platform was accessible to participants while maintaining compliance with data regulations. The Gateway formalized a system of automated data matching between multiple data sets, which was a major benefit to researchers. Scalability of the platform was demonstrated with the later addition of self-reported data validation. This study demonstrated the feasibility of custom software solutions in addressing complex study designs. The Gateway portal code has been made available open-source and can be leveraged by other research groups.


Epidemiology, etiology, diagnosis and treatment of prostate cancer.
Prostate cancer is more common in men over the age of 65 years. There are 15% cases with positive family history of prostate cancer Worldwide. Prostate cancer is the second leading cause of death among the U.S. men. Prostate cancer incidence is strongly related to age with the highest rates in older man. Globally millions of people are suffering from this disease. This study aims to provide awareness about prostate cancer as well as an updated knowledge about the epidemiology, etiology, diagnosis and treatment of prostate cancer.


Local outbreak of hepatitis E: a rare cause of viral hepatitis in Australia.
Hepatitis E is a not uncommon cause of viral hepatitis globally but is relatively rare in Australia. Here, we report a case of acute hepatitis E that was acquired in Sydney and was part of a cluster believed to be infected locally. This is to our knowledge the first known outbreak of locally acquired hepatitis E in Australia. We discuss pathogenesis, clinical features and means by which further spread of infection can be limited.


The Neural Representation of Visually Evoked Emotion Is High-Dimensional, Categorical, and Distributed across Transmodal Brain Regions.
Central to our subjective lives is the experience of different emotions. Recent behavioral work mapping emotional responses to 2,185 videos found that people experience upward of 27 distinct emotions occupying a high-dimensional space, and that emotion categories, more so than affective dimensions (e.g., valence), organize self-reports of subjective experience. Here, we sought to identify the neural substrates of this high-dimensional space of emotional experience using fMRI responses to all 2,185 videos. Our analyses demonstrated that (1) dozens of video-evoked emotions were accurately predicted from fMRI patterns in multiple brain regions with different regional configurations for individual emotions; (2) emotion categories better predicted cortical and subcortical responses than affective dimensions, outperforming visual and semantic covariates in transmodal regions; and (3) emotion-related fMRI responses had a cluster-like organization efficiently characterized by distinct categories. These results support an emerging theory of the high-dimensional emotion space, illuminating its neural foundations distributed across transmodal regions.


Effect of Germination and Extrusion on Physicochemical Properties and Nutritional Qualities of Extrudates and Tortilla from Wheat.
Wheat is the most common grain in the temperate region. Modifying its constituent through food processing improves its functionality and nutrient access. In this study, the combined effect of germination and extrusion on physicochemical properties and nutritional qualities of extrudates and tortilla from wheat was evaluated. Results showed that germination significantly increased (P <0.05) the γ-aminobutyric acid content in germinated whole wheat (GW) and extruded germinated whole wheat (EGW) as compared to the control of whole wheat (WW). Germination also significantly increased the protein content, reducing sugar and total soluble sugar content in GW, while extrusion had much increasing impact on reducing sugar content in extruded samples. Specific mechanical energy during extrusion was reduced as feed moisture content increased from 20 to 30%. Higher extruder screw speed (350 rpm) led to better expansion ratio at low moisture content (20%) as compared to low screw speed (200 rpm). Extrusion significantly increased the starch digestibility but decreased the protein digestibility in extrudates. Tortilla made from 100% WW had about the same physical characteristics, namely color and rollability, with tortilla made from 85% WW with 15% GW, 85% WW with 15% extruded whole wheat (EW), and 85% WW with 15% EGW. Tortilla made from 85% WW with 15% GW showed the largest diameter, thinnest thickness and least extensibility. A 15% extruded germinated wheat (350 rpm) addition in 85% WW showed significant increase of γ-aminobutyric acid content in tortilla compared to the control (100% WW).


Human immunodeficiency virus infection, Bcl-2, p53 protein, and Ki-67 analysis in ocular surface squamous neoplasia.
To determine the age and human immunodeficiency virus (HIV) status of patients with ocular surface squamous neoplasia (OSSN), and to analyze tumor proliferation, Bcl-2, and p53 oncoprotein expression in OSSN. Only patients with histologically proved neoplasia were included in this study. The HIV status was obtained only with informed consent. Monoclonal antibodies to p53 and Bcl-2 protein were used after microwave antigen retrieval to enhance immunohistochemical staining of the sections. Proliferation was assessed by means of Ki-67 antigen expression. Positive staining in each specimen was expressed as a percentage and graded accordingly. Forty-one eyes in 40 black patients with a mean age of 37 years were found to have OSSN. Of the 41 lesions, 35 represented in situ or invasive carcinoma. The remaining 6 had mild or moderately dysplastic lesions. Seventeen patients agreed to an HIV test and, of these, 12 (70.6%) were HIV positive. All 12 were younger than 50 years, and 11 had either carcinoma in situ or invasive lesions. Twenty-two of 40 lesions expressed significant (greater than 50% of neoplastic cells) p53 positivity, while Bcl-2 expression was detected in 10. Ki-67 expression was low, even in the HIV-positive lesions. At our institution, OSSN occurs in young patients, many of whom are HIV positive. Expression of p53 is a common finding, whereas Bcl-2 immunoexpression occurs in the minority of cases. Ki-67 analysis showed that OSSN is a slow-growing tumor, even in the presence of HIV infection.


Concerted evolution of duplicated control regions within an ostracod mitochondrial genome.
The luminescent marine ostracod Vargula hilgendorfii comprises distinct populations around the Japanese islands. Its mitochondrial DNA is unusual, with duplicated control regions (CRs; CR#1 and CR#2). We determined the sequences of ostracod CRs in 7 different populations. The sequences of CR#1 and CR#2 within any population were extremely similar, above 99.7%; moreover, their derived evolutionary tree indicates that the pairs of CRs have evolved in concert within each mitochondrial genome. These results suggest that an exact replication mechanism controls the concerted evolution of CRs.


Computational design of one-dimensional nonlinear photonic crystals with material dispersion for efficient second-harmonic generation.
A computational study of the second-harmonic generation in one-dimensional photonic crystals made of GaAs and AlAs with quadratic optical nonlinearity and material dispersion is presented. The computational approach uses a shooting method to solve nonlinear wave equations for coupled fundamental and second-harmonic fields and the invariant imbedding method to obtain the linear transmittance and group index spectra. The photonic crystal is built with an elementary cell consisting of four sublayers whose thicknesses are systematically varied. Doubly-resonant second harmonic generation with high conversion efficiency is achieved by choosing the geometrical parameters of the elementary cell optimally and controlling the band structure.


NF-κB downstream miR-1262 disturbs colon cancer cell malignant behaviors by targeting FGFR1.
Despite substantial advancements in screening, surgery, and chemotherapy, colorectal cancer remains the second most lethal form of the disease. Nuclear factor kappa B (NF-κB) signaling is a critical driver facilitating the malignant transformation of chronic inflammatory bowel diseases. In this study, deregulated miRNAs that could play a role in colon cancer are analyzed and investigated for specific functions in vitro using cancer cells and in vivo using a subcutaneous xenograft model. miRNA downstream targets are analyzed, and predicted binding and regulation are verified. miR-1262, an antitumor miRNA, is downregulated in colon cancer tissue samples and cell lines. miR-1262 overexpression suppresses colon cancer malignant behaviors in vitro and tumor development and metastasis in a subcutaneous xenograft model and a lung metastasis mouse model in vivo. miR-1262 directly targets fibroblast growth factor receptor 1 (FGFR1) and inhibits FGFR1 expression. FGFR1 overexpression shows oncogenic functions through the regulation of cancer cell proliferation, invasion, and migration; when cotransfected, lv-FGFR1 partially attenuates the antitumor effects of agomir-1262. NF-κB binds to the miR-1262 promoter region and inhibits transcription activity. The NF-κB inhibitor CAPE exerts antitumor effects; miR-1262 inhibition partially reverses CAPE effects on colon cancer cells. Conclusively, miR-1262 serves as an antitumor miRNA in colon cancer by targeting FGFR1. The NF-κB/miR-1262/FGFR1 axis modulates colon cancer cell phenotypes, including proliferation, invasion, and migration.


Combining brains: a survey of methods for statistical pooling of information.
More than one subject is scanned in a typical functional brain imaging experiment. How can the scientist make best use of the acquired data to map the specific areas of the brain that become active during the performance of different tasks? It is clear that we can gain both scientific and statistical power by pooling the images from multiple subjects; furthermore, for the comparison of groups of subjects (clinical patients vs healthy controls, children of different ages, left-handed people vs right-handed people, as just some examples), it is essential to have a "group map" to represent each population and to form the basis of a statistical test. While the importance of combining images for these purposes has been recognized, there has not been an organized attempt on the part of neuroscientists to understand the different statistical approaches to this problem, which have various strengths and weaknesses. In this paper we review some popular methods for combining information, and demonstrate the surveyed techniques on a sample data set. Given a combination of brain images, the researcher needs to interpret the result and decide on areas of activation; the question of thresholding is critical here and is also explored.


Evoked otoacoustic emissions: a fundamental and clinical survey.
Evoked otoacoustic emissions (EOAEs) hold some promise as a fast, objective and noninvasive procedure to study the cochlea at the outer hair cell level. This paper summarizes the fundamental aspects of EOAEs, in particular their relationship with the active biomechanical properties of the cochlea. The properties of EOAEs are analyzed in normally hearing ears, in ears with sensorineural hearing loss, especially in Ménière's disease, in acoustic neuromas and in central deafness; the properties of EOAEs were also evaluated as to their suitability for screening auditory dysfunction in infants.


Antigen-presenting capacity of rheumatoid synovial fibroblasts.
In normal, healthy joints, synovial fibroblasts do not express major histocompatibility complex (MHC) class II molecules. However, in inflamed joints of rheumatoid arthritis (RA) patients, synovial fibroblasts show an abundant expression of MHC class II. Does this increase in expression have functional consequences for antigen presentation to T cells? To date, the precise role of synovial fibroblasts in antigen presentation has not been documented. Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells. First, the antigen-presenting cell (APC) function of synovial fibroblasts was studied in an autologous model. From synovial tissue of a RA patient both a fibroblast cell line and a tetanus toxoid (TT)-specific CD4+ T-cell line were generated. A dose-dependent TT response was observed only when TT was presented by IFN-gamma-pretreated synovial fibroblasts. As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts. The response was DR4Dw4-restricted and could be inhibited by monoclonal antibody (mAb) to HLA-DR. In addition, the lymphokine secretion pattern of the synovial T-cell clone did not differ qualitatively upon antigen-specific stimulation using peripheral blood mononuclear cells (PBMC) or synovial fibroblasts as APC. In order to provide evidence for intracellular antigen processing we next examined the response of a M. leprae-specific T-cell clone with known epitope specificity. Our data suggest that synovial fibroblasts are not passive bystanders, but can become active participants in the development and maintenance of chronic inflammation.


Exploration of cuprotosis-related genes for predicting prognosis and immunological characteristics in acute myeloid leukaemia based on genome and transcriptome.
Acute myeloid leukemia (AML) is a common hematologic malignancy with a generally unfavorable prognosis. Cuprotosis as a new form of programmed cell death has been shown to play an important role in tumorigenesis and progression; However, the relationship between cuprotosis and the prognosis of AML patients remains unclear. Transcriptomic and genomics data, along with clinical information, were obtained from the TCGA and GEO databases. Especially, unsupervised clustering and machining learning were used to identify molecular subtypes and cuprotosis-related risk scores respectively. Kaplan-Meier analysis, univariate and multivariate Cox regression, and Receiver Operator Characteristic curve (ROC) were performed to assess the prognosis based on cuprotosis-related genes (CRGs). Moreover, multiple algorithms were used to evaluate immunological heterogeneity among patients with different risk scores. For in vitro analysis, the expression of genes involved in CRGs was detected by Quantitative Reverse Transcription Polymerase (qRT-PCR) in AML patients. Transcriptomic and genome data indicated the immense heterogeneity in the CRGs landscape of normal and tumor samples. Cuprotosis subtype A and cuprotosis regulatory subtype B in the genomics map and biological characteristics were significantly different from the other groups. Furthermore, these two subtypes had lower risk scores and longer survival times compared to other groups. Cox analyses indicated that risk score was an independent prognostic factor for AML patients. In addition, our risk score could be an indicator of survival outcomes in immunotherapy datasets. Our study demonstrates the potential of CRGs in guiding the prognosis, treatment, and immunological characteristics of AML patients.


Serum transaminase levels should be measured immediately prior to dosing in early phase I clinical trials.
Observations of predose spikes in transaminases from a phase I study prompted our review of other clinical trials, including 250 healthy participants from 4 studies at 3 sites. Six of these participants (2.4%) displayed elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels immediately predose despite normal values <48 hours previously, including one with ALT/AST = 237/175 IU/L (previously 41/29 IU/L). Testing immediately prior to dosing can exonerate a study drug and avoid unnecessary, expensive delays in early clinical trials.


Scalpel versus electrosurgery for abdominal incisions.
Scalpels or electrosurgery can be used to make abdominal incisions. The potential benefits of electrosurgery include reduced blood loss, dry and rapid separation of tissue, and reduced risk of cutting injury to surgeons, though there are concerns about poor wound healing, excessive scarring, and adhesion formation. To compare the effects on wound complications of scalpel and electrosurgery for making abdominal incisions. We searched the Cochrane Wounds Group Specialised Register (searched 24 February 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2); Ovid MEDLINE (1950 to February Week 3 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 23 February 2012); Ovid EMBASE (1980 to 2012 Week 07); and EBSCO CINAHL (1982 to 17 February 2012). We did not apply date or language restrictions. Randomised controlled trials (RCTs) comparing the effects on wound complications of electrosurgery with scalpel use for the creation of abdominal incisions. The study participants were patients undergoing major open abdominal surgery, regardless of the orientation of the incision (vertical, oblique, or transverse) and surgical setting (elective or emergency). Electrosurgical incisions included those in which the major layers of abdominal wall, including subcutaneous tissue and musculoaponeurosis (a strong sheet of fibrous connective tissue that serves as a tendon to attach muscles), were made by electrosurgery, regardless of the techniques used to incise the abdominal skin and peritoneum. Scalpel incisions included those in which all major layers of abdominal wall including skin, subcutaneous tissue, and musculoaponeurosis, were incised by a scalpel, regardless of the techniques used on the abdominal peritoneum. We independently assessed studies for inclusion and risk of bias. One review author extracted data which were checked by a second review author. We calculated risk ratio (RR) and 95% confidence intervals (CI) for dichotomous data, and difference in means (MD) and 95% CI for continuous data. We examined heterogeneity between studies. We included nine RCTs (1901 participants) which were mainly at unclear risk of bias due to poor reporting. There was no statistically significant difference in overall wound complication rates (RR 0.90, 95% CI 0.68 to 1.18), nor in rates of wound dehiscence (RR 1.04, 95% CI 0.36 to 2.98), however both these comparisons are underpowered and a treatment effect cannot be excluded. There is insufficient reliable evidence regarding the effects of electrosurgery compared with scalpel incisions on blood loss, pain, and incision time. Current evidence suggests that making an abdominal incision with electrosurgery may be as safe as using a scalpel. However, these conclusions are based on relatively few events and more research is needed. The relative effects of scalpels and electrosurgery are unclear for the outcomes of blood loss, pain, and incision time.


A supertypic HLA-DR specificity (DR4+5) defined by murine monoclonal antibody.
The hybridoma technique was used to produce a monoclonal antibody specific for a polymorphic determinant on human la antigens. BALB/c mice were immunized with a B-lymphoblastoid cell line derived from an HLA-DR3/DR4 positive donor. Hybridoma culture supernates were screened in two stages by means of the microcytotoxicity assay. Supernates were first tested against the la-positive immunizing cell line and against la-negative cells. Cultures identified as producing antibody cytoxic for the immunizing cell line but not for la-negative cells were subcultured and the supernates then tested against a selected panel of HLA-D homozygous cell lines (HCL). In this manner, it was possible to identify a microwell of hybrid cells producing an antibody that reacted with a polymorphic HLA-DR determinant. Cells from this culture, designated 17.15, were cloned twice by limiting dilution. Specificity was evaluated with a panel of 39 HCL and B cells from 70 normal donors. Antibody 17.15 recognized a supertypic DR "4 + 5" specificity, which was also present on DRw9 and some DR7 positive cells. These findings suggest that the cross-reactivity groups DR "4 + 5" (MB-3) and DR "4 + 7" (MT-3) defined by alloantisera may share a common supertypic specificity that is recognized by monoclonal antibody 17.15.


Quality of life in children with Type 1 diabetes: a comparison of general and diabetes-specific measures and support for a unitary diabetes quality-of-life construct.
To assess the factor structure of the Pediatric Quality of Life Inventory (PedsQL) Diabetes Module and to compare the PedsQL general and diabetes-specific quality of life (QOL) measures regarding psychometric properties and relations to relevant outcomes. The instruments were completed by 447 children age 9 to 15.5 years with Type 1 diabetes > 1 year from four US paediatric diabetes clinics; parents completed the parallel parent-proxy measures. Principal components factor analysis was used to examine the factor structure of the PedsQL diabetes module. Analyses of the generic and diabetes QOL measures included psychometric properties, parent-child correlations and correlations with depression, adherence and glycated haemoglobin (HbA(1c)). The factor structure of the PedsQL diabetes module did not support the original five subscales. Both one- and two-factor models were supported; however, parallel parent and child subscales did not emerge. While the generic and diabetes-specific measures of QOL were moderately to highly correlated with each other, the constructs were differentially associated with relevant diabetes outcomes. Generic QOL was more highly associated with depression than diabetes QOL. Conversely, diabetes QOL was more highly associated with adherence and HbA(1c), although this was seen to a greater extent for parent-proxy report than for child report. Factor analysis of the PedsQL diabetes module supports the use of a total diabetes QOL score. Findings regarding the associations of the generic and diabetes modules with diabetes outcomes underscore the unique contribution provided by both generic and diabetes QOL.


Apical bleeding: a rare cause of blindness after orbital decompression.
Orbital decompression is widely performed for the management of proptosis for cosmetic and functional cases of Graves orbitopathy. The main side effects include dry eye, diplopia, and numbness. Blindness after orbital decompression is extremely rare. The mechanisms of vision loss after decompression are not well described in the literature. Considering the devastating effect and rarity of this complication, this study presented two cases of blindness after orbital decompression. In both cases, vision loss was provoked by slight bleeding in the orbital apex.


The concept of inner cerebral trauma.
The pattern of "inner cerebral trauma" is a morphological and functional-pathological correlate of biomechanical conditions at the event of severe closed craniocerebral injury of acceleration-type, if the traumatizing forces act in the direction of the longest diameter of the skull. The lesions are characteristically localized in the "centro-axial" regions of the brain involving most frequently: corpus callosum, septum pellucidum, fornix, tela chorioidea, peri- and para-ventricular zone, infundibulobasal region and cingulum; this pattern also includes lesions of the hippocampal area, upper brainstem, pontocerebellar complex, and parasagittal areas of the cerebrum. This pattern includes lesions, which are from the onset "primary irreversible" as well as "primary reversible" lesions, which spread apart from the "epicentres" of the primary irreversible damage and are in principle more diffuse but still within the basic pattern of the main predilection. This is the basis of the process of "traumatic cerebral disease". The final size and scope of the pathological process of the "traumatic cerebral disease" depend on a number of secondary factors, which may allow the normal process of healing to keep the tissue changes within the initial scope of "primary irreversible damage", or may enhance a progressive process of turning the "reversible" traumatic damage into the irreversible lesions.


The effect of stereotypes and prejudices regarding gender roles on the relation between nurses and "Muslim fathers" in health institutions within the Community of Madrid (Spain).
Modern Western societies are characterized by a considerable cultural and ethnic diversity whereby different groups and minorities live side by side. However, not all people are viewed in the same light by the autochthonous population. This is particularly true in the case of Muslim immigrants, who are often prone to negative stereotyping and prejudice. This has become increasingly apparent since the 2001 terrorist attacks in New York and the subsequent attacks in various Western countries. This study seeks to analyze the relation between female nurses and those labeled by nurses as "Muslim fathers," as part of a research project on the care of immigrant children in Madrid (Spain). The findings promote reflection on the effects of nurses' stereotypes and prejudices regarding the gender roles of "Muslim fathers" and the relations between these groups. These prejudices can lead to situations of cultural imposition and/or discrimination. Self-reflection regarding stereotypes and prejudices is necessary in order to provide culturally competent care. The anthropobiological approach by Marie Françoise Collière may be useful for extending this type of care universally, not only to immigrant groups, as everyone, including nurses, patients, and family members, belong to part of a specific sociocultural context.