Characteristics of thoracic malignancies that occur after solid-organ transplantation.
Chronic immunosuppression after solid-organ transplantation is associated with increased risk of developing malignancies. The purpose of this study was to determine the clinical characteristics and the outcome of thoracic malignancies in patients who have undergone solid-organ transplantation. Among a cohort of 2831 patients who received a transplant at our institution and were followed between 1984 and 2009, 24 patients (0.85%) developed thoracic malignancies. Risk factors for lung cancer, as well as demographic, cancer, and transplantation characteristics, were analyzed. Survival data were also collected. Twenty-four patients were included (21 men, median age 61.7 years). Twenty-two patients were smokers. The most frequent histologic types were squamous cell carcinoma (n = 11, 46%) and adenocarcinoma (n = 9, 37%). The median time period between transplantation and diagnosis of lung cancer was 6.6 years. Ten lung malignancies occurred after kidney transplantation (0.5%), eight after liver transplantation (1.3%), and six after heart transplantation (2.8%). Seven patients underwent surgery, three had radiotherapy, four had chemotherapy, and six had multimodal treatment. The median survival time was 1.5 years, ranging from 6 months for stage IV to 3.7 years for stage I. Solid-organ transplantation is associated with a high risk of lung cancer and may have an important synergetic part with other risk factors for lung cancer (tobacco). However, survival rates from lung cancer in our study population are similar to those of nontransplanted patients. In addition, surgery can result in favorable survival results.


[Immune stratum of the population in relation to the causative agent of pseudotuberculosis].
The state of population immunity may be controlled by analyses of placental, abortion, and donor blood. The existence of a high direct correlation between the level of the immune stratum of the population and pseudotuberculosis morbidity has been revealed. Regression equations suitable for the prognostication of pseudotuberculosis morbidity have been obtained by means of computers.


Peptide transport in antigen presentation.
The TAP1/2 complex translocates peptides from the cytosol into the endoplasmic reticulum. In the rat, TAP polymorphism affects the pool of peptides presented by major histocompatibility complex class I molecules, whereas in mouse and humans the functional consequences of observed structural polymorphism have not yet been determined. Peptide binding to TAP precedes ATP binding, and ATP hydrolysis is required to release and translocate peptides. Cytosolic peptides entering the class I pathway via the TAP complex may differ significantly in size and sequence. Not all peptides that are able to bind to TAP can be translocated into the endoplasmic reticulum, and TAP-binding affinity does not directly correlate with antigenicity of the peptide. Most translocated peptides are released from the endoplasmic reticulum by an incompletely defined ATP-dependent mechanism. TAP interaction with class I molecules stimulates peptide binding and transport by TAP and may also facilitate efficient loading of class I with peptides. Pathogenic microorganisms, such as herpes simplex virus, may encode inhibitors of TAP-mediated peptide transport in order to evade immune surveillance.


Impact of Non-Tailored One-Way Automated Short Messaging Service (OASMS) on Glycemic Control in Type 2 Diabetes: A Retrospective Feasibility Study.
Short message service (SMS) is easily accessible and potentially an ideal platform for delivering patient-targeted messages. However, an effective SMS dosing strategy is not well established. Our purpose was to evaluate the impact of diabetes self-care promoting messages via non-tailored one-way automated SMS (OASMS) on glycemic control in type 2 diabetes (T2DM). The change in hemoglobin A1c (HbA1c) was compared between patients who received the service and those who did not. This retrospective quasi-experimental pre-post feasibility study was conducted at an academic medical center endocrinology clinic. English-speaking adults (≥18 years) with uncontrolled T2DM (HbA1c ≥ 8%) were included. A total of 69 patients (intervention n = 34; control n = 35) met the inclusion criteria. The mean (±SD) baseline HbA1c values were 10.2% (±1.9%) and 9.9% (±1.7%) in the intervention and control arms, respectively. Median follow-up was 3.3 months (IQR = 3-4.2). An ANCOVA model adjusted for baseline HbA1c and age showed an estimated HbA1c reduction difference of -0.97% (95% CI, -1.73 to -0.20%, p = 0.014), favoring the intervention arm. Inverse propensity score weighting confirmed the ANCOVA results. Our study suggests that adding diabetes self-care promoting messages via non-tailored OASMS to usual care improves glycemic control in poorly controlled T2DM. Larger and longer studies are needed to evaluate different features of the non-tailored OASMS strategy.


Core-shell Zn2GeO4 nanorods and their size-dependent photoluminescence properties.
Size-tunable crystalline core-crystalline shell Zn2GeO4 nanorods were synthesized via a facile hydrothermal reaction. High purity Zn2GeO4 nanorods were obtained at pH = 7. The length of Zn2GeO4 nanorods (L = 50-100 nm) can be controlled through a one-step process, while micro-sized nanorods with an aspect ratio of the length to the diameter of 10 were yielded in a two-step process. The single crystalline nature of Zn2GeO4 nanorods with a core-shell structure was verified by high resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) measurements. The Raman study revealed that there is no oxygen defect in Zn2GeO4 nanocrystals, suggesting that photoluminescence emission of Zn2GeO4 can be attributed to the presence of the interstitial Zn defect in Zn2GeO4 nanocrystals. As the diameter of nanorods decreased, the excitation and emission peaks appeared to be redshifted due to the quantum size effect.


Can antigen-specific regulatory T cells protect against graft versus host disease and spare anti-malignancy alloresponse?
Allogeneic hematopoietic cell transplantation provides effective control of hematopoietic malignancies, but with an associated risk of graft-versus-host disease (GVHD) related morbidity and mortality. Several advances in hematopoietic cell transplantation including high resolution HLA typing, development of reduced intensity conditioning regimens, infectious prophylaxis and treatment, and novel immunosuppressive agents have resulted in improved outcomes and improved access to transplantation, but GVHD remains a major obstacle. This clinico-pathological syndrome, mediated by donor alloreactive T cells, occurs often despite prophylactic immunosuppressive therapy. Regulatory T cells, a suppressive subset of the T-cell repertoire, may offer promise as a novel cellular therapy for more effective prevention of GVHD. While advances have been made in pre-clinical experimental animals, several challenges remain in the translation of this work to human trials. Strategies to effectively produce ex vivo expanded alloantigen-specific regulatory T cells specific for ubiquitous alloantigens but sparing hematopoietic- or tumor-associated antigens hold promise to prevent GVHD while allowing a preserved graft versus malignancy effect.


Sibling play therapy with homeless children: an opportunity in the crisis.
A shelter for the homeless in Hawaii uses the residential setting as an opportunity to provide on-site, flexibly scheduled, culturally sensitive play therapy to young children, specifically targeting siblings as a natural support system to counteract the restricted peer interaction and play experience of this population. Case examples illustrate how sibling groups use the playroom to manage family crises as they happen, resolve conflicts, and express difficult feelings, making sense of their unpredictable world and mastering crucial developmental tasks.


PHGDH as a mechanism for resistance in metabolically-driven cancers.
At the forefront of cancer research is the rapidly evolving understanding of metabolic reprogramming within cancer cells. The expeditious adaptation to metabolic inhibition allows cells to evolve and acquire resistance to targeted treatments, which makes therapeutic exploitation complex but achievable. 3-phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme of de novo serine biosynthesis and is highly expressed in a variety of cancers, including breast cancer, melanoma, and Ewing's sarcoma. This review will investigate the role of PHGDH in normal biological processes, leading to the role of PHGDH in the progression of cancer. With an understanding of the molecular mechanisms by which PHGDH expression advances cancer growth, we will highlight the known mechanisms of resistance to cancer therapeutics facilitated by PHGDH biology and identify avenues for combatting PHGDH-driven resistance with inhibitors of PHGDH to allow for the development of effective metabolic therapies.


PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development.
Wnt signalling in development operates via members of the Frizzleds, G-protein-coupled receptors that bind specific Wnt ligands and mediate signalling via distinct pathways. The Wnt/Ca(2+)/cGMP pathway mediated by Frizzled-2 was discovered recently. Activation of this pathway leads to increased intracellular concentrations of Ca(2+) and decreased intracellular concentrations of cGMP. The nature of the phosphodiesterase responsible for this Frizzled-2-mediated effect on cGMP levels was identified based on three separate criteria: (i) sensitivity to selective enzyme inhibitors, (ii) behaviour on chromatographic separation, and (ii) isolation by two-dimensional gels in tandem with direct mapping by MS of tryptic digests of the activity. On the basis of results from these three analyses, the cGMP-specific phosphodiesterase, PDE6, is demonstrated to be an effector for the Wnt/Ca(2+)/cGMP signalling pathway of development, which is mediated by Frizzled-2.


Factors of good outcome after discharge from support house (engoryou) for schizophrenia.
To restore mentally disabled persons to social activities, it is necessary to establish an appropriate facility and support system according to the severity of disorder. In the present study, in an attempt to obtain a guide to identifying conditions on which the use of the support house (engoryou) is effective, patients who had been discharged from the support house were divided into different groups by evaluation at discharge. The first group consisted of 30 patients who underwent continued social rehabilitation (recovery group); the second group consisted of 25 patients with discontinued social rehabilitation (the re-hospitalization group), and their demographic factors were compared. The findings are summarized as follows: (i) the recovery group had a significantly shorter total hospitalization period and a smaller number of hospitalizations before entry into the facility, as compared to the re-hospitalization group; (ii) the recovery group was significantly better than the re-hospitalization group in terms of the score of 'thought disorder', although there was no difference in total Brief Psychiatric Rating Scale (BPRS) score, at the time of entry into the facility; (iii) the recovery group was better than the re-hospitalization group in terms of the Rehabilitation Evaluation Hall and Baker (REHAB) items 'speech skills' and 'self-care' at the time of entry into the facility; (iv) the re-hospitalization group experienced relapse of symptoms, mainly positive ones, at the time of the discontinuation of the use of the facility or re-admission. These findings suggest that to make good use of the support house, the improvement of thought disturbance and self-care must be managed appropriately and the prolongation of hospital stay must be prevented before entry into the facility.


Using benchmarking data to determine vascular access device selection.
Benchmarking data has validated that patients with planned vascular access device (VAD) placement have fewer device placements, less difficulty with device insertions, fewer venipunctures, earlier assessment for placement of central VADs, and shorter hospital stays. This article will discuss VAD program planning, early assessment for VAD selection, and benchmarking of program data used to achieve positive infusion-related outcomes.


Modulating effect of MgO-SiO2 nanoparticles on immunological and histopathological alterations induced by aflatoxicosis in rats.
AflatoxinB1 (AFB1) is well-known as a feed borne-hepatotoxic and immunosuppressive mycotoxin. This study was conducted to evaluate the efficacy of nanocomposite magnesium oxide and silicon oxide (MgO-SiO2) in reducing the toxic effects of AFB1on the immunity and histological alterations in liver, spleen and intestine of adult male rats. Animals were divided into a control (Gp1) and three experimental groups (Gps); Gp2 received feed contained 200 ppb AFB1, Gp3 received feed contained 200 ppb AFB1 and 0.5 g/kg MgO-SiO2 nanocomposite. While, rats of Gp4 received feed contained 0.5 g/kg MgO-SiO2 nano-composite. Cellular and humoral immune responses, as well as histopathological examination and caspase-3 expression in liver, spleen, and intestine, were all evaluated. Residual concentration of AFB1was determined in serum, liver and fecal samples. The obtained data were statistically analyzed. AFB1markedly reduced body weight gain and food and water consumption. Cellular immune response (total and differential leukocytes count, neutrophils' phagocytic activity, lymphocyte transformation, macrophage activity and serum lysozyme activity), serum total protein, and humoral immune response (fractions of protein as estimated by SDS- PAGE electrophoresis) were all severely reduced by AFB1. Moreover, AFB1induced marked histological alterations and apoptosis in liver, spleen, and intestine. These findings suggested that the nanocomposite MgO-SiO2 has high affinity to adsorb AFB1 and can effectively modulate its toxicity in rats. Nanocomposite MgO-SiO2 may offer a novel effective and cheap approach for the preventive management of aflatoxicosis in animals.


Benign Multicystic Peritoneal Mesothelioma Presenting as a Colonic Mass.
Benign multicystic peritoneal mesothelioma (BMPM) is a rare neoplasm of the abdominal mesothelium (i.e., peritoneum, mesentery, and omentum). We present the case of a 74-year-old male who presented with a right paracolic gutter fluid collection and cystic mass. The patient underwent diagnostic laparoscopy with resection of the mass. The final pathology revealed BMPM. The pathogenesis may have been related to longstanding diverticular disease, which could prove to be an underrecognized risk factor for the development of BMPM. Therefore, this case suggests a broadened differential diagnosis to include BMPM in specific cases of pre-operatively diagnosed colonic masses. The patient is disease-free 11 months post-operatively.


["Mobilize the masses to urgently go into action and overcome the drought"].
At present, the drought is serious. Urgently taking action and doing everything possible to overcome the drought and strive for a bumper autumn harvest is an extremely urgent combat task facing the people of our province. Since mid-June, it has rained in our province several times but it has not rained very evenly. It has not rained in many places during the past 1/2 year and more. By the end of July, autumn crops on 37.35 million mu of land have been affected by the drought, accounting for more than 1/3 of the total area of the autumn crops. The drought has greatly harmed the growth of autumn crops. If we do not act now the drought will seriously affect the autumn harvest. Mobilizing the masses to urgently go into action to overcome the drought and strive for a bumper autumn harvest is a major task which has a bearing on the livelihood of both the urban and rural people of our province and on the further development of the excellent situation. Therefore, party committees at all levels must pay attention to this, concentrate the forces to grasp it firmly and well, and not lower their guard. The party members, cadres, and masses must carry forward the spirit of fighting continuously and struggling hard, make full use of all water conservancy projects and antidrought machinery and tools, try their best to find new water resources, and use water reasonably and sparingly. All walks of life and trades must do everything possible to vigorously support the struggle against the drought and do well in supplying the oil and electricity needed for agricultural machinery and help to repair machinery and tools. We all must contribute toward the effort to achieve a bumper autumn harvest.


Compared to what? An analysis of the management of control groups in Cochrane reviews in neurorehabilitation.
Control groups are used in clinical trials to increase confidence that any improvements in patient outcomes are due the therapy under investigation and not to other factors. The reported effect size of any intervention is estimated from differences in outcomes achieved by intervention participants in comparison to control participants. Clinical heterogeneity in control groups across different studies can make the pooling of data from these studies in one meta-analysis questionable or reduce certainty in their results. The aim of this study was to evaluate: 1) the variability in the types of control groups used in studies that have been pooled in meta-analyses in Cochrane reviews on neurorehabilitation interventions; and 2) how authors of Cochrane reviews on neurorehabilitation interventions have taken information about control groups into consideration when making decisions to undertake meta-analyses and interpreting their results. We searched the Cochrane library for reviews on neurorehabilitation interventions published between 2012 and 2016 that included at least one meta-analysis involving a control group. We extracted data from included reviews on the review characteristics, the characteristics of the included meta-analyses, and any information on how the review authors managed control groups in the conduct and interpretation of meta-analyses. The 43 included reviews pooled data from 358 clinical trials, with an average of 5±5 clinical trials (range: 2-45) contributing to each meta-analysis. The majority of clinical trials involved a control group containing active treatments (61.7%; 221 of 358), often "treatment as usual" controls without any additional placebo or sham intervention. Over half (58.1%; 25 of 43) of the included meta-analyses involved pooling of data from studies with a mix of different types of control groups, with an additional 25.6% pooling data from studies where control participants had received a range of different active treatments. The influence of different control groups on the summary results from meta-analyses was not analyzed in 21 (48.8%) of the included reviews. Further work is needed to develop: standardized ways to categorize control conditions in rehabilitation trials; more guidance on reporting criteria for control groups in rehabilitation trials; and agreed methods for managing different control types in one meta-analysis.


[Study on the association of transporter associated with antigen processing gene with ankylosing spondylitis and HLA-B27 in Han nationality].
To investigate the association between transporter associated with antigen processing(TAP) gene and ankylosing spondylitis(AS) as well as HLA-B27. PCR-SSO was used to analyze the frequencies of TAP alleles and variant amino acids of TAP in 48 patients (B27(+)) with AS and 123 normal individuals (B27(+) or B27(-)). The phenotypes of Ile/Ile, Asp/Asp were over-presented for TAP1 and Val/Val, Ala/Thr, Stop/Stop for TAP2 in Han nationality. For each TAP there were four alleles: TAP1*0101, TAP1*0201, TAP1*0301, TAP1*0401, and TAP2*0101, TAP2*0102, TAP2*0201, TAP2*0202. In the research subjects, hybridization blanks accounted for 9.9%(17/171) of TAP1 and 15.8%(27/171) of TAP2. No difference was found in the distribution of TAP alleles between the AS patients(B27(+)) and normal controls(B27(+) or B27(-)). In the patients group the frequency of phenotype in codon of 333 (Val/Val) was significantly decreased as compared with that of the healthy controls(B27(+))(P<0.05). In addition, the frequency of phenotype Ala/Ala(665) was significantly decreased and that of Ala/Thr was significantly increased in normal controls(B27(-)), compared with those in normal controls(B27(+))(P<0.05). It is possible that there are new TAP alleles in Han nationality. No association was found between TAP alleles and AS. And the homozygosity for codon 333 which is Val/Val seems to offer resistance to AS among those HLA-B27(+) individuals. In normal individuals, negative correlation was found between heterozygote Ala/Thr and B27, and possibly there was positive correlation between phenotype Ala/Ala and B27.


Weight and body composition changes during oral contraceptive use in obese and normal weight women.
Oral contraceptive (OC) use seems to have little effect on weight change in normal weight women. Most previous studies have excluded obese women, so the effect of OC use on weight change in obese women is unknown. This analysis evaluates weight and body composition change with OC use among obese (body mass index [BMI] 30.0-39.9) and normal weight (BMI 19.0-24.9) women who were randomly assigned to two OC doses: 20 μg ethinyl estradiol (EE) and 100 μg levonorgestrel (LNG) OCs or 30 μg EE and 150 μg LNG OCs. Follow-up occurred after three to four OC cycles. Weight and body composition were measured at baseline and at follow-up using a bioelectrical impedance analyzer. Among 150 women (54 obese and 96 normal weight) who used OCs for 3 to 4 months, there were no clinically or statistically significant weight or body composition changes in the overall group or by BMI or OC formulation group. These findings add to evidence that EE/LNG OCs are not associated with short term weight or body composition change for normal weight women and suggest that OCs are also are not associated with short term weight or body composition change in obese women.


Mechanical Properties and Durability Performance of Concrete Containing Calcium Carbide Residue and Nano Silica.
Calcium carbide residue (CCR) is the end-product of production of acetylene gas for the applications such as welding, lighting, ripening of fruits, and cutting of metals. Due to its high pH value, disposing of CCR as a landfill increases the alkalinity of the environment. Therefore, due to its high calcium content, CCR is mostly blended with other pozzolanic materials, together with activators as binders in the cement matrix. In this study, cement was partially substituted using CCR at 0%, 7.5%, 15%, 22.5% and 30% by weight replacement, and nano silica (NS) was utilized as an additive by weight of binder materials at 0%, 1%, 2%, 3% and 4%. The properties considered were the slump, the compressive strength, the flexural strength, the splitting tensile strength, the modulus of elasticity, and the water absorption capacity. The microstructural properties of the concrete were also examined through FESEM and XRD analysis. The results showed that both CCR and NS increase the concrete's water demand, hence reducing its workability. Mixes containing up to 15% CCR only showed improved mechanical properties. The combination of CCR and NS significantly improved the mechanical properties and decreased the concrete's water absorption through improved pozzolanic reactivity as verified by the FESEM and XRD results. Furthermore, the microstructure of the concrete was explored, and the pores were refined by the pozzolanic reaction products. The optimum mix combination was obtained by replacing 15% cement using CCR and the addition of 2% NS by weight of cementitious materials. Therefore, using a hybrid of CCR and NS in concrete will result in reduction of cement utilization in concrete, leading to improved environmental sustainability and economy.


Acculturation does not necessarily lead to increased physical activity during leisure time: a cross-sectional study among Turkish young people in the Netherlands.
Non-Western migrant populations living in Western countries are more likely to be physically inactive during leisure time than host populations. It is argued that this difference will disappear as they acculturate to the culture of the host country. We explored whether this is also true for migrants who experience contextual barriers such as having children, living in a less attractive neighbourhood, or having occupational physical activity. Cross-sectional data were obtained from the LASER-study (2003-2004) on health related behaviours in first and second generation Turkish young people living in the Netherlands. For this study we included 485 Turkish participants aged 15-30 years, who participated in a structured interview during a home visit. Acculturation was indicated by level of 'cultural orientation towards the Dutch culture' and 'social contacts with ethnic Dutch' with persons being low oriented towards the Dutch culture and having few social contacts with ethnic Dutch as reference group. The measured barriers were 'having children', 'occupational physical activity' and 'living in a less attractive neighbourhood'. Logistic regression analyses were used to assess the associations between acculturation and physical activity during leisure time, stratified by these contextual barriers. Greater cultural and social integration was associated with increased physical activity during leisure time. Odds ratio's were 1.85 (CI: 1.19-2.85) for 'cultural orientation' and 1.77 (CI: 1.15-2.71) for 'social contacts with ethnic Dutch'. However, these associations were not present or less strong among people who had children, or who were living in a less attractive neighbourhood or who engaged in occupational physical activity. Physical activity during leisure time increased with greater acculturation, however, this relationship was found only among participants without children, living in a attractive neighbourhood and having no occupational activity. Interventions aimed at migrant populations should not only focus on the least integrated. Instead, effectiveness might be enhanced when interventions are sensitive to the contextual barriers that might inhibit physical activity behaviours during leisure time.


Influence of Female Sex Hormones in Different Stages of Women on Periodontium.
The primary etiologic factor for periodontal diseases is "Dental plaque." Although pathogenic bacteria in dental plaque are required for the incidence of periodontal disease, a susceptible host is also very important. The susceptibility of the host can be modified by many systemic factors with hormones level being one. The periodontium shows an exaggerated inflammatory response to plaque modified by female sex hormones during puberty, pregnancy, in women taking oral contraceptives, and at the postmenopausal stage. This review provides an in detail analysis of how periodontium is influenced by the fluctuation in sex steroid hormones of females during different phases of their lifetime and to discuss how much the same hormone at different ages and stages shows an exaggerated gingival response to plaque.


Surgeon dependent variation in adenotonsillectomy costs in children.
To (1) identify the major expenses for same-day adenotonsillectomy (T&A) and the costs for postoperative complication encounters in a children's hospital and (2) compare differences for variations in costs by surgeon. Observational cohort study. Tertiary children's hospital. A standardized activity-based hospital accounting system was used to determine total hospital costs per encounter (not including professional fees for surgeons or anesthetists) for T&A cases at a tertiary children's hospital from 2007 to 2012. Hospital costs were subdivided into categories, including operating room (OR), OR supplies, postanesthesia care unit (PACU), same-day services (SDS), anesthesia, pharmacy, and other. Costs for postoperative complication encounters were included to identify a mean total cost per case per surgeon. The study cohort included 4824 T&As performed by 14 different surgeons. The mean cost per T&A was $1506 (95% confidence interval, $1492-$1519, with a range of $1156-$1828 for the lowest and highest cost per case per surgeon; P < .01). Including the cost for postoperative complications, the mean cost increased to $1599 ($1570-$1629). The largest cost categories included OR (31.9%), SDS (28.1%), and OR supplies (15.6%). A large portion of T&A expenses are due to OR and supply costs. Significant differences in costs between surgeons for outpatient T&A were identified. Studies to understand the reasons for this variation and the impact on outcomes are needed. If this variation does not affect patient outcomes, then reducing this variation may improve health care value by limiting waste.


Cell proliferation of the rat gastrointestinal mucosa after treatment with E2 prostaglandins and indomethacin.
The frequency of arrested mitoses after vincristine injection was studied in the gastrointestinal mucosa of rats treated with either natural prostaglandin E2 (0.2-5.0 mg X kg-1, b.d.), 15-R-15 methyl prostaglandin E2 (2 mg X kg-1, b.d.) or indomethacin (1.0-3.0 mg X kg-1, b.d.). In addition to the mitotic index, morphometric measurements including the mucosal thickness and the thickness of the proliferative and functional zones of the gastric corpus, antrum and jejunum were performed. Natural prostaglandin E2, at the highest dose range, reduced significantly the mitotic index in the gastric antrum. Normal values were found in the gastric corpus and jejunum and in the antrum with the lower doses. The mitotic index was unaffected by treatment with 15-R-15 methyl prostaglandin E2. Natural prostaglandin E2 produced trophic changes (i.e. increased thickness and/or hyperplasia) in the antrum, functional epithelial zone of the gastric corpus and in the jejunum. More pronounced trophic changes were observed in the mucosa of rats treated with the analogue. Indomethacin reduced the mucosal thickness in all examined epithelia and lowered the mitotic index in the jejunum. It is concluded that the trophic effects of E2 prostaglandins on gastrointestinal epithelia are not caused by increased production of new cells. The reduced mitotic index observed in the antral mucosa of prostaglandin-treated rats could be secondary to a negative feedback from the hyperplastic epithelium. The antitrophic effects of the prostaglandin-synthesis blocker (indomethacin) indicates that endogenous prostaglandins may participate in the epithelial cell regulation of the gastrointestinal tract.


Efficacy of Electrochemotherapy in the Treatment of Cutaneous Melanoma Metastases and Rare Non-melanoma Skin Cancer.
We aimed to verify the clinical efficacy and safety of the electrochemotherapy in melanoma metastases and in cases of rare non-melanoma tumors that were difficult to treat for the specific anatomical site or for patient comorbidities. We treated 68 patients (699 cutaneous nodules), 44 patients with metastatic melanomas and 24 patients with non-melanoma tumors, at the Melanoma & Skin Cancer Unit, Florence, Italy. We obtained an objective response of 89.7% (88.6% in melanomas and 91.7% in non-melanoma tumors), complete response 54.4% and partial response 35.3%. This study showed that electrochemotherapy is effective in the treatment of melanoma metastases and in rare types of non-melanoma tumors. In particular, we successfully treated rare tumors as angiosarcoma, pleomorphic sarcoma, myxofibrosarcoma, sarcoma di Kaposi, porocarcinoma, sebaceous carcinoma, Merkel cell carcinoma, malignant blue nevus, undifferentiated epitheliomorphic cell neoplasia and metastases from thyroid carcinoma. No serious adverse events were observed.


A lessons learned system in healthcare IT implementation.
In this paper, we adopted a Lesson learned (LL) approach to promote knowledge sharing and knowledge management in healthcare IT implementation processes. The goal of the LL system is to provide system implementation suggestions based on the similarities between a new case and previous known cases. By doing so the LL system might help prevent avoidable healthcare IT failures via reuse of knowledge gained through past experiences.


Reversal of clopidogrel-induced bleeding with rFVIIa in healthy subjects: a randomized, placebo-controlled, double-blind, exploratory study.
Clopidogrel (Plavix®) therapy, although effective for minimizing risk of thrombotic events, is also associated with potential bleeding risk. Recombinant activated FVII (rFVIIa, NovoSeven®) induces hemostasis in hemophilia patients with inhibitors (alloantibodies) and has been proposed as potential treatment for mitigating clopidogrel therapy-mediated bleeding. In this single-center, randomized, placebo-controlled, double-blind, dose-escalation, exploratory phase I trial, we assessed the safety and effects of rFVIIa in reversing clopidogrel-enhanced bleeding in an experimentally induced punch biopsy in healthy subjects. Efficacy assessments included the reversal of bleeding characteristics (bleed duration [BD], the primary end point and blood loss volume [BV] induced by punch biopsy, and thromboelastograph [TEG®] parameters) with rFVIIa or placebo after clopidogrel treatment. A significant number of subjects (56%) had limited response to clopidogrel (defined as ≤30% platelet aggregation inhibition) and were discontinued from study. The remaining subjects continued and had 4 biopsies. Of 40 subjects randomized, 37 were evaluated for efficacy. Clopidogrel treatment increased BD and BV compared with the baseline biopsy. Recombinant FVIIa (10 and 20 μg/kg) significantly mitigated the clopidogrel-induced effects on BV (P = 0.007 and P = 0.001, respectively). Early trial termination limited the evaluation of effects of higher rFVIIa doses. Subgroup analyses of subjects biopsied by the same physician demonstrated significant reduction of clopidogrel-induced BD with 20 μg/kg rFVIIa (P = 0.048). Ex vivo analysis of rFVIIa demonstrated clotting dynamics presented by parameters time to clot onset (TEG®-R) and clot angle (TEG®-A) (P < 0.005). In this clinical study, rFVIIa (10 and 20 μg/kg) reversed the effect of clopidogrel on blood loss.


Leading off-diagonal correction to the form factor of large graphs.
Using periodic-orbit theory beyond the diagonal approximation we investigate the form factor, K(tau), of a generic quantum graph with mixing classical dynamics and time-reversal symmetry. We calculate the contribution from pairs of self-intersecting orbits that differ from each other only in the orientation of a single loop. In the limit of large graphs, these pairs produce a contribution -2tau(2) to the form factor which agrees with random-matrix theory.


Long-term Clinical and Radiological Outcomes after Central Decompressive Laminoplasty for Lumbar Spinal Stenosis.
There are many technical modifications of decompressive lumbar laminectomy. The purpose of this study was to report long-term clinical and radiological outcomes of central decompressive laminoplasty (CDL), the corresponding author's own modification of lumbar laminectomy for lumbar spinal stenosis (LSS). Among 100 patients who underwent CDL by a single surgeon between December 2010 and March 2014, 68 patients were included in this study. Mean follow-up time was 37.7 months. Clinical and radiological data were gathered prospectively and reviewed retrospectively. Clinical outcome was measured by using visual analog scale (VAS) for back/buttock and leg, and the Oswestry Disability Index (ODI). Radiological outcome was measured by neutral slippage percentage, dynamic slippage percentage, and dynamic intervertebral angel on sagittal X-ray. Outcomes after CDL were assessed by changes of clinical and radiological parameters from the baseline. Mixed effect model with random patients' effect as used to test for differences in the repeated measured clinical and radiological data. The patients had no serious complications with an uneventful recovery during the early postoperative period. In the early postoperative period, VAS scores for back/buttock and leg improved significantly and were kept with time (p<0.001). ODI also improved significantly during the postoperative follow-up period (p<0.001). The radiologic parameters were well maintained and showed no progression of instability. During the follow-up, a case of herniated disc at same level recurrence was noted after lifting trauma, and 2 adjacent foraminal stenosis needed additional surgery. CDL provides long-term pain relief and functional restoration without progression of radiological instability.


Elder Mistreatment in an Italian Population: Prevalence and Correlates.
This study aimed to examine the prevalence of elder mistreatment (EM) in an Italian population and to determine the risk factors. The sample consisted of 393 older adults (Mage = 77.07; standard deviation = 9.45) of whom 60.1% were females. The prevalence of EM was of 20.1%. Older elders who were separated, divorced, with a poor state of health, and problems of autonomy were more likely to experience EM. The most common forms of EM were physical/sexual (9.9%) and emotional mistreatment (9.9%). The most common perpetrators were paid caregivers and members of the victim's family. A path analysis model suggested that limited autonomy and poor perceived health status appeared to be predictors of EM. We conclude that the results of this study have important implications in terms of reducing mistreatment of older adults. Understanding EM is essential to promoting equality, tolerance, and supportive attitudes and developing better prevention policies and practices.


Transcriptome Profiles Reveal the Growth-Promoting Mechanisms of Paenibacillus polymyxa YC0136 on Tobacco (Nicotiana tabacum L.).
Paenibacillus polymyxa is an important member of the plant growth-promoting rhizobacteria. P. polymyxa YC0136 inoculation had beneficial effect on growth promotion and biological control of tobacco (Nicotiana tabacum L.) under field conditions. This study aimed to reveal the growth-promoting mechanisms of strain YC0136. In growth-promotion assays, tobacco plant height was increased by 8.42% and 8.25% at 60 and 90 days, respectively, after inoculation with strain YC0136. Strain YC0136 also promoted the accumulation of tobacco biomass in varying degrees. Following inoculation with strain YC0136, 3,525 and 4,368 tobacco genes were up-regulated and down-regulated, respectively. Strain YC0136 induced the expression of plant hormone-related genes in tobacco, including auxin, cytokinin, and gibberellin, as well as transcription factors related to stress resistance such as WRKY and MYB. In addition, strain YC0136 induced the up-regulation of genes in the phenylpropanoid biosynthesis pathway by 1.51-4.59 times. Interaction with tobacco also induced gene expression changes in strain YC0136, with 286 and 223 genes up-regulated and down-regulated, respectively. Tobacco interaction induced up-regulation of the ilvB gene related to auxin biosynthesis in strain YC0136 by 1.72 times and induced expression of some nutrient transport genes. This study contributes to our understanding of the growth-promoting mechanisms of strain YC0136 on tobacco and provides a theoretical basis for the application of P. polymyxa YC0136 as a biological fertilizer.


[Minimally invasive non-endoscopic thyroid resections].
The interest in the application of the minimally invasive procedures in the thyroid surgery vastly increased in recent years. To present our experience with the application of minimally invasive nonendoscopic resections in the thyroid surgery. 145 patients with various thyroid diseases were operated on with minimally invasive open approach for the period from 1 Janyary 2003 to 30 June 2004 in our institution. Nodular thyroid pathology has dominated. All patients were females, mean age 28.5 years. An preoperative ultrasonographic assessment of thyroid volume, nodular count, size and localization was performed in all cases. The mean thyroid lobe volume was 11.2 ml the size of the removed thyroid nodules was 9 to 33mm (21 +/- 12 mm). The incision length was measured at the beginning, at the end and one week after the operation. The extent of thyroid resection was as follows: partial thyroid resection of a lobe in 28 patients; bilateral partial thyroid resection in 16 patients; subtotal lobectomy in 35 patients; lobectomy in 50 patients; lobectomy with partial thyroid resection of the other lobe in 8 patients; subtotal thyroidectomy in 5 patients; thyroidectomy in 3 patients. The incision length at the end of operation was 3.0 +/- 0.5 cm. Mean operative time was 41.5 +/- 8.4 min. The postoperative hospital stay was 24 +/- 6 hours. Postoperative complications were not observed, except a little haematoma in one case at the beginning of the study, that did not required any additional intervention. The early and late postoperative cosmetic results we have observed, were undoubtedly better. Our experience demonstrates that miniinvasive nonendoscopic thyroid resections represent a simple, safe and feasible surgical procedure in selected patients with small to middle-size thyroid nodules.


Challenges for Quality Assurance of Target Volume Delineation in Clinical Trials.
In recent years, new radiotherapy techniques have emerged that aim to improve treatment outcome and reduce toxicity. The standard method of evaluating such techniques is to conduct large scale multicenter clinical trials, often across continents. A major challenge for such trials is quality assurance to ensure consistency of treatment across all participating centers. Analyses from previous studies have shown that poor compliance and protocol violation have a significant adverse effect on treatment outcomes. The results of the clinical trials may, therefore, be confounded by poor quality radiotherapy. Target volume delineation (TVD) is one of the most critical steps in the radiotherapy process. Many studies have shown large inter-observer variations in contouring, both within and outside of clinical trials. High precision techniques, such as intensity-modulated radiotherapy, image-guided brachytherapy, and stereotactic radiotherapy have steep dose gradients, and errors in contouring may lead to inadequate dose to the tumor and consequently, reduce the chance of cure. Similarly, variation in organ at risk delineation will make it difficult to evaluate dose response for toxicity. This article reviews the literature on TVD variability and its impact on dosimetry and clinical outcomes. The implications for quality assurance in clinical trials are discussed.


Orthogonal interactions of CO molecules on a one-dimensional substrate.
We investigate the chemisorption structure of CO molecules on the quasi-one-dimensional Cu(110)-(2 × 1)-O surface by low-temperature scanning tunneling microscopy and density functional theory. Contrary to flat metal surfaces, where CO molecules adsorb in an upright geometry and interact through repulsive intermolecular interactions, we find the most stable adsorption structure of single CO molecules to be at Cu atoms of substrate Cu-O- chains with the Cu-CO unit bent by ~±45° in two equivalent structures at low coverages. At higher coverages, CO molecules combine in the same structure into highly ordered single-molecule-wide rows perpendicular to the substrate chains in an approximately 8 × 1 full monolayer structure. First-principles calculations attribute the unprecedented chemisorption behavior of CO molecules to lifting of the host Cu atoms by 1 Å from the surface Cu-O- chains, in order to optimize the bonding and reduce the repulsive interactions with the substrate. This structural distortion enables short-range intermolecular dipole-dipole attraction and creates orthogonal long-range surface-mediated repulsion leading to unusual self-assembly of CO molecules into coherent nanometer scale molecular grating structures.


Influence of curve morphology and location on the efficacy of rigid conservative treatment in patients with adolescent idiopathic scoliosis.
The aim of the present study was to answer the question whether curve morphology and location have an influence on rigid conservative treatment in patients with adolescent idiopathic scoliosis (AIS). We retrospectively analyzed AIS in 127 patients with single and double curves who had been treated with a Chêneau brace and physiotherapeutic specific exercises (B-PSE). The inclusion criteria were the presence of structural major curves ≥ 20° and < 50° (Risser stage 0 to 2) at the time when B-PSE was initiated. The patients were divided into two groups according to the outcome of treatment: failure (curve progression to ≥ 45° or surgery) and success (curve progression < 45° and no surgery). The main curve type (MCT), curve magnitude, and length (overall, above and below the apex), apical rotation, initial curve correction, flexibility, and derotation by the brace were compared between the two groups. In univariate analysis treatment failure depended significantly on: 1) MCT (p = 0.008); 2) the apical rotation of the major curve before (p = 0.007) and during brace treatment (p < 0.001); 3) the initial and in-brace Cobb angles of the major (p = 0.001 and p < 0.001, respectively) and minor curves (p = 0.015 and p = 0.002); 4) major curve flexibility (p = 0.005) and the in-brace curve correction rates (major p = 0.008, minor p = 0.034); and 5) the length of the major curve (LoC) above (p < 0.001) and below (p = 0.002) the apex. Furthermore, MCT (p = 0.043, p = 0.129, and p = 0.017 in MCT comparisons), LoC (upper length p = 0.003, lower length p = 0.005), and in-brace Cobb angles (major p = 0.002, minor p = 0.027) were significant in binary logistic regression analysis. Curve size, location, and morphology were found to influence the outcome of rigid conservative treatment of AIS. These findings may improve future brace design and patient selection for conservative treatment. Cite this article: Bone Joint J 2021;103-B(2):373-381.


Hyperthermia and radiotherapy in bladder cancer.
Hyperthermia represents a unique, safe, and advantageous methodology for improving therapeutic strategies in the management of bladder cancer. This modality has shown promise in contributing to treatment regimens for both superficial and muscle-invasive disease. Especially in conjunction with intravesical chemotherapy, systemic therapy, and radiotherapy, hyperthermia shows particular synergistic benefit. As such, it should be explored further through clinical use and clinical trial in conjunction with currently available techniques and emerging technologies. However, to conceptualise the way forward, it is particularly important to understand the current challenges to widespread use of non-invasive, bladder-sparing approaches and the current state of bladder cancer care. As such, in the following article, we have focused on not only the rationale for concurrent radiotherapy and hyperthermia, but also the clinical landscape in bladder cancer as a whole.


Leg ulcers in the primary antiphospholipid syndrome. Report of a case with a peculiar proliferative small vessel vasculopathy.
Leg ulcers are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus. They may also occur in patients with primary antiphospholipid syndrome(PAPS). Histopathologic findings at the edges of the ulcers may give insight into their pathogenesis. In a patient with PAPS and a leg ulcer, a biopsy of the ulcer's edge revealed a peculiar small vessel nodular proliferation in the upper and lower dermis. There was mild mixed inflammatory infiltrate in the surrounding connective tissue, a few vessels with fibrin thrombi, and some with fibrin deposition within their walls. A review of the literature revealed similar findings in other skin ulcers associated with lupus anticoagulants. This suggests peculiar pathogenetic mechanisms that may be akin to those responsible for antiphospholipid arterial vasculopathy.


What an endoscopist should know about immunoglobulin-G4-associated disease of the pancreas and biliary tree.
Autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC) are the recently recognized pancreatobiliary manifestations of IgG4-associated systemic disease (ISD). Clinically, ISD of the pancreas and/or biliary tree may mimic pancreatic cancer, sclerosing cholangitis, or cholangiocarcinoma. Patients often present with abdominal pain, weight loss, jaundice, itch, and biochemical signs of pancreatitis and cholestasis. Tomography may reveal enlargement of the pancreas or may mimic malignant pancreatic lesions, and cholangiopancreatography may disclose irregularities of the pancreatic duct and stenoses of the distal and/or proximal common bile duct and intrahepatic bile ductules. Serum immunoglobulin G4 (IgG4) is elevated in most patients but, unlike tissue IgG4-loaded plasma cell infiltrates, is not diagnostic of the disease. The application of consensus diagnostic criteria for laboratory investigations, imaging, and histologic findings can identify patients who qualify for corticosteroid treatment. The excellent response to immunosuppressive therapy suggests an immune-mediated etiology of the disease, but the exact pathophysiological mechanisms are still under investigation. Relapse may occur after tapering down of corticosteroids, which supports the rationale of maintenance immunosuppression after remission has been induced.


Family outcomes from a randomized control trial of relapse prevention therapy in first-episode psychosis.
We have previously reported that our combined individual and family cognitive-behavioral therapy (CBT) relapse prevention therapy (RPT) was effective in reducing relapse rates compared to treatment as usual (TAU) within a specialist program for young, first-episode psychosis patients who had reached remission on positive symptoms. Here, we report the outcomes for family participants of DSM-IV-diagnosed first-episode psychosis patients recruited between November 2003 and May 2005 over a 2.5-year follow-up period. The primary hypothesis was that, compared to family members receiving TAU, family participants who received RPT would have significantly improved appraisals of stressors related to caregiving. Secondary hypotheses were that RPT would be associated with reduced expressed emotion and improved psychological distress. Family members were assessed at baseline and at 7-month, 12-month, 18-month, 24-month, and 30-month follow-up on appraisal of caregiving, expressed emotion, and psychological distress using the Experience of Caregiving Inventory, The Family Questionnaire, and the General Health Questionnaire of 28 Items, respectively. The family component of RPT was based on family behavioral therapy for schizophrenia with a specific focus on psychoeducation and CBT for relapse prevention. Thirty-two families received RPT, and 31 families received TAU. There were significant group effects for aspects of the appraisal of caregiving, including negative symptoms, positive personal experiences, and total positive score on the Experience of Caregiving Inventory. Time effects were evident for emotional overinvolvement and for aspects of the appraisal of caregiving. There were no significant effects for psychological distress. The relatives of patients who received RPT perceived less stress related to their relative's negative symptoms and an increase in perceived opportunities to make a positive contribution to the care of their relative compared to carers in the TAU condition. Cognitive-behavioral therapy for relapse prevention showed promise in improving the experience of caregiving for family members of first-episode psychosis patients over a 2.5-year follow-up period. anzctr.org.au Identifier: ACTRN12605000514606.


Postnatal development of depth-dependent collagen density in ovine articular cartilage.
Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Adult AC is characterised by a depth-dependent composition and structure of the extracellular matrix that results in depth-dependent mechanical properties, important for the functions of adult AC. Collagen is the most abundant solid component and it affects the mechanical behaviour of AC. The current objective is to quantify the postnatal development of depth-dependent collagen density in sheep (Ovis aries) AC between birth and maturity. We use Fourier transform infra-red micro-spectroscopy to investigate collagen density in 48 sheep divided over ten sample points between birth (stillborn) and maturity (72 weeks). In each animal, we investigate six anatomical sites (caudal, distal and rostral locations at the medial and lateral side of the joint) in the distal metacarpus of a fore leg and a hind leg. Collagen density increases from birth to maturity up to our last sample point (72 weeks). Collagen density increases at the articular surface from 0.23 g/ml ± 0.06 g/ml (mean ± s.d., n = 48) at 0 weeks to 0.51 g/ml ± 0.10 g/ml (n = 46) at 72 weeks. Maximum collagen density in the deeper cartilage increases from 0.39 g/ml ± 0.08 g/ml (n = 48) at 0 weeks to 0.91 g/ml ± 0.13 g/ml (n = 46) at 72 weeks. Most collagen density profiles at 0 weeks (85%) show a valley, indicating a minimum, in collagen density near the articular surface. At 72 weeks, only 17% of the collagen density profiles show a valley in collagen density near the articular surface. The fraction of profiles with this valley stabilises at 36 weeks. Collagen density in articular cartilage increases in postnatal life with depth-dependent variation, and does not stabilize up to 72 weeks, the last sample point in our study. We find strong evidence for a valley in collagen densities near the articular surface that is present in the youngest animals, but that has disappeared in the oldest animals. We discuss that the retardance valley (as seen with polarised light microscopy) in perinatal animals reflects a decrease in collagen density, as well as a decrease in collagen fibril anisotropy.


[Acquired hemophilia complicated with multiple muscle abscess by Nocardia].
An 82-year-old man was referred to our hospital because of bilateral leg swelling and ecchymosis. A hemostatic study showed prolonged aPTT, <1% factor VIII coagulant activity, and a high titer (30.4 Bethesda Units/ml) of factor VIII inhibitor. The diagnosis of acquired hemophilia A (AHA) was made, and treatment with prednisolone (PSL) was started. Within one month of treatment, the hemorrhagic symptom disappeared, aPTT levels returned to normal, and his factor VIII inhibitor was eradicated; however, factor VIII inhibitor was detected again when PSL was decreased to 10 mg/day. We then added cyclosporine A (CyA) to PSL as a second line salvage therapy. CyA therapy resulted in the resolution of AHA with marked and prolonged efficacy; however, hot, red tumors appeared in his right arm and left thigh. Needle aspiration of the tumors revealed muscle abscess, and Nocardia brasiliensis was isolated. We started treatment with sulfamethoxazole-trimethoprim, and the abscess healed promptly without recurrence.


The localization of nuclear DNA helicase II in different nuclear compartments is linked to transcription.
Nuclear DNA helicase II (NDH II) is a member of the DEAH superfamily of helicases and functions as a pre-mRNA- and mRNA-binding protein in human cells. Here we report for the first time that human NDH II is associated with the nucleolus of transformed and nontransformed cells as shown by immunofluorescence and by ultrastructural studies. When RNA polymerase II (POL II) transcription is inhibited, NDH II highly accumulates in the nucleolus and shows predominant association with subdomains in DFC and in a portion of GC attached to DFC. Furthermore, these subdomains completely co-localize with mRNA-binding protein TLS. In addition, we show that nucleolar accumulation of NDH II is closely related to G(0)-phase growth arrest in human fibroblasts. Thus, the nucleolar localization of NDH II depends upon the metabolic state of the cell. Based on the data we propose that NDH II operates in both nucleoplasmic and nucleolar mode, and that its redistribution reflects accumulations indicating a possible cycling of NDH II between nucleoplasm and the nucleolus. The nucleolus can serve as a temporary storage or recycling center for NDH II. Possible functions of NDH II in pre-rRNA biogenesis, or in nucleolar mRNA metabolism, are also discussed.


A multiphase CFD model of DAF process.
A Eulerian-Eulerian multiphase CFD model is employed for the air/water flow. A 3D structure grid is used to incorporate the air nozzle and tank geometry. The fixed frictionless wall boundary approximating the free surface acts as a sink to allow the air bubbles to escape. The air/water volume fraction in the flotation tank is evaluated to determine the effective air/water fluid density. The floc particle is then introduced and is tracked in the air/water fluid using a disperse Lagrangean model. Fate of these flocs depends on their sizes and density. Flocs therefore can either escape through the top water surface, settles in the main tank or breakthrough under the outlet weir. The CFD model is developed for a full scale DAF tank to predict the flow dynamic, particle removal and settled solid profile. The general flow pattern is compared with flow visualisation using the underwater camera. Comparison of average fluid velocities is carried out using acoustic Doppler velocimetry ADV measurement.


High-Temperature Induced Chlorophyll Fluorescence Rise in Plants at 40-50 degrees C: Experimental and Theoretical Approach.
We studied the temperature dependence of chlorophyll fluorescence intensity in barley leaves under weak and actinic light excitation during linear heating from room temperature to 50 degrees C. The heat-induced fluorescence rise usually appearing at around 40-50 degrees C under weak light excitation was also found in leaves treated with 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU) or hydroxylamine (NH(2)OH). However, simultaneous treatment with both these compounds caused a disappearance of the fluorescence rise. We have suggested that the mechanism of the heat-induced fluorescence rise in DCMU-treated leaves is different than that in untreated or NH(2)OH-treated leaves. In DCMU-treated leaves, the heat-induced fluorescence rise reflects an accumulation of Q(A) (-) even under weak light excitation due to the thermal inhibition of the S(2)Q(A) (-) recombination as was further documented by a decrease in the intensity of the thermoluminescence Q band. Mathematical model simulating this experimental data also supports our interpretation. In the case of DCMU-untreated leaves, our model simulations suggest that the heat-induced fluorescence rise is caused by both the light-induced reduction of Q(A) and enhanced back electron transfer from Q(B) to Q(A). The simulations also revealed the importance of other processes occurring during the heat-induced fluorescence rise, which are discussed with respect to experimental data.


A clinical trial testing the safety and efficacy of a standardized Eucommia ulmoides Oliver bark extract to treat hypertension.
A tea made from Eucommia ulmoides leaves and bark is part of the Japanese diet. Eucommia is an herbal medicine that, by increasing nitric oxide, reduced blood pressure (BP) in rats and humans in an uncontrolled clinical trial. A controlled clinical trial was conducted to evaluate an aqueous bark extract of Eucommia standardized to eight percent pinoresinol di-beta-D-glucoside (PG) for BP reduction in humans. Study 1: Twenty-four healthy adult subjects with a BP between 120-160/80-100 mmHg were randomized to Eucommia extract 500 mg three times daily for eight weeks. Automatic 24-hour ambulatory blood pressure monitoring (24-h ABPM) was utilized at baseline and after eight weeks. Study 2: The effect of the Eucommia extract on isoproterenol-stimulated lipolysis was evaluated in a human fat cell assay to determine whether Eucommia was a beta-adrenergic blocker. Study 3: Thirty healthy adult subjects with a BP between 120-160/80-100 mmHg were randomized to 1 g Eucommia extract three times daily for two weeks with 24-h ABPM at baseline and after two weeks. Study 1: There was no toxicity or any difference in BP between the two groups. Study 2: Eucommia at 0.5% w/v reduced isoproterenol-stimulated lipolysis from 2.67 to 1.4 times the buffer control (P<0.001). Study 3: The Eucommia extract was well-tolerated and reduced BP by an average of 7.5/3.9 mmHg (P<0.008). The standardized Eucommia extract reduced BP and has beta-adrenergic blocking activity. Eucommia may be an appropriate nutraceutical intervention for prehypertension.


Antimicrobial and cytotoxicity activities of the medicinal plant Primula macrophylla.
Primula macrophylla (Primulaceae) is reported as to be useful in asthma, restlessness, insomnia and fish poisoning. Antifungal and toxic activities of crude extract, fractions and a pure isolated compound exhibited statistically significant activities. Excellent antifungal activity was found in the crude extract, benzene and ethyl acetate fractions against T. longifusis and against M. canis with different MIC values. Antileishmanial activity (IC(50) = 50ug/mL) was observed as compared to standard drug Amphotericin B, and cytotoxic activity (LD(50) = 47.919microg/mL) was also found in the chloroform fraction. While pure compound 2-phenylchromone (Flavone) isolated from the chloroform fraction showed good activity (IC(50) = 25microg/mL) against Leishmania and cytotoxicity (LD(50) = 2.0116 microg/mL) in Brine Shrimp experiments. From antileishmanial and cytotoxic activity it can be concluded that 2-phenylchromone is the major compound responsible for these activities.


Proteomic tools for environmental microbiology--a roadmap from sample preparation to protein identification and quantification.
The steadily increasing amount of (meta-)genomic sequence information of diverse organisms and habitats has a strong impact on research in microbial physiology and ecology. In-depth functional understanding of metabolic processes and overall physiological adaptation to environmental changes, however, requires application of proteomics, as the context specific proteome constitutes the true functional output of a cell. Considering the enormous structural and functional diversity of proteins, only rational combinations of various analytical approaches allow a holistic view on the overall state of the cell. Within the past decade, proteomic methods became increasingly accessible to microbiologists mainly due to the robustness of analytical methods (e.g. 2DE), and affordability of mass spectrometers and their relative ease of use. This review provides an overview on the complex portfolio of state-of-the-art proteomics and highlights the basic principles of key methods, ranging from sample preparation of laboratory or environmental samples, via protein/peptide separation (gel-based or gel-free) and different types of mass spectrometric protein/peptide analyses, to protein identification and abundance determination.


[Tigecycline for treatment of pneumonia].
Tigecyclin represents an important contribution for treatment of difficult-to-treat infections caused by polymicrobial or resistant flora. Its characteristics destinate it for use beyond the registered indications. Authors submit two case reports documenting its promising effect in patients with complicated pulmonary infection in whom standard treatment was not successful.


Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors.
Evidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development. The renal effects of the selective antagonist to AT1R, ZD 7155 and to AT2R, PD 1233319 were evaluated in two groups of conscious chronically instrumented lambs aged ~ one week (N = 8) and ~ six weeks (N = 10). Two experiments were carried out in each animal and consisted of the assessment of renal variables including glomerular and tubular function, for 30 min before (Control) and 60 min after infusion of ZD 7155 and PD 123319, respectively. Statistical significance was determined using parametric testing (Student t-test, analysis of variance ANOVA) as appropriate. ZD 7155 infusion was associated with a significant decrease in glomerular filtration rate and filtration fraction at one but not six weeks; urinary flow rate decreased significantly in older animals, whereas sodium excretion and free water clearance were not altered. There was an age-dependent effect on potassium handling along the nephron, potassium excretion decreasing after ZD 7155 infusion in younger but not in older lambs. PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group. These results provide evidence to support an important role for AT1Rs in mediating the renal effects of angiotensin II during postnatal maturation in conscious developing animals. In contrast to a role for AT2Rs later in life, there appears to be no role for AT2Rs in influencing the renal effects of Angiotensin II in the postnatal period.


[Electrolaser therapy on the Iarilo device in patients with chronic chlamydial prostatitis].
Multiple-modality treatment (antibiotics, immunocorrectors, vascular medication, physiotherapy) for chronic chlamydial prostatitis (CCP) was conducted in 141 patients. They were assigned to two groups which differed only by physical methods applied. Group 1 patients (n = 84) were exposed to electrolaser radiation (Yarilo unit), group 2 patients (n = 57) were treated by conventional physiotherapeutic methods. The advantages were reported in the group treated simultaneously with He-Ne laser introduced into the urethra, infrared laser, electrostimulation (Yarilo unit). Perineal pain and dysuria ceased in 58.9 and 9.8%, 62.1 and 13.2% of patients from group 1 and 2, respectively. Erection recovered in 90% of group 1 patients. In group 2 this percentage was 50%.


Phenotypic Variability of Dystrophinopathy Symptomatic Female Carriers.
Dystrophinopathies are X-linked muscular dystrophies characterized by pathogenic mutations in the dystrophin gene. Symptomatic dystrophinopathy female carriers may present with limb-girdle weakness. The diagnosis may be challenging in the absence of affected male relatives. We aimed to describe the phenotypic variability in a series of molecular-confirmed female dystrophinopathy patients. This is a retrospective analysis of medical records from 1997 to 2015. Ten female dystrophinopathy patients were selected, two with unusual phenotypes: one with early joint contractures muscular dystrophy and the other with very late onset myopathy. Muscle imaging studies demonstrated predominant asymmetric fat replacement. Muscle biopsy immunohistochemistry demonstrated clear mosaic pattern in two cases and only subtle reduction of dystrophin intensity in three. Adequate diagnosis is fundamental for genetic counseling and cardiologic follow-up. Female patients with dystrophinopathy may present unusual phenotypes such as early contractures and very late onset myopathy.


Dissolution of dental enamel in soft drinks.
A high percentage of the population consumes a variety of soft drinks on a daily basis. Many of these soft drinks contain sugar and various additives and have a low pH. This study compares enamel dissolution from both regular and diet beverages.


[Effects of oleic acid on expression of adiponectin and its PPARgamma mechanism in 3T3-L1 adipocytes].
To explore the effects of oleic acid on the gene and protein expression of adiponectin and its PPARgamma mechanism in 3T3-l1 adipocytes. L1 adipocytes were incubated with different concentration (25, 50, 100, 200, 400 micromol/L) for 24h, and the mRNA expression of adiponectin and PPARgamma was determined by real-time PCR (relative quantity). And then the 3T3-L1 adipocytes were treated for OA at concentration of 100 micromol/L for 24h with/without the affect of PPARgamma inhibitor GW9662, to determine the gene and protein expression of adiponectin. The protein expression changes of adiponectin were detected by immunoblotting. The mRNA expression of adiponectin and PPARgamma increased at the dosages of 25, 50, and 100micromol /L. With the increase of OA, the mRNA expression of adiponectin and PPARgamma decreased in a dose-dependent manner. Incubating with GW9662 and OA, decreases in the mRNA and protein expression of adiponectin were 77% and 78.01% (P < 0.05), compared with the control respectively. OA could increase the gene expression of adiponectin and PPARgamma mRNA in dose-dependent manner in 3T3-L1 adipocytes,which could be specifically blocked by GW9662, OA indues the expression of adiponectin mRNA and protein in 3T3-L1 adipocytes, possibly by a mechanism involving PPARgamma.


Coronary artery calcium score scan at 100 kVp with tin filtration (Sn100 kVp) prior to coronary computed tomography angiography for overall radiation dose reduction: a prospective cohort study.
Reducing radiation dose is a global concern in coronary computed tomography angiography (CCTA). We aimed to investigate whether a coronary artery calcium score (CACS) scan would lead to an overall reduction of radiation dose in CCTA examination and determine its necessity in routine CCTA imaging. A total of 297 patients with suspected coronary heart disease were consecutively enrolled in this prospective cohort study between March 1, 2021, and September 1, 2021. All patients were scanned using a prospective electrocardiogram-triggered sequence acquisition mode on a dual-source computed tomography (CT) scanner. The first 1-150 patients (group A, n=150) were scanned with CACS using tin filtration with low voltage (Sn100 kVp) to guide the CCTA scanning range, whereas the subsequent 151-297 patients (group B, n=147) were scanned using a scout view for the CCTA range. Participant characteristics, number of scans, scan length, actual heart length, CT dose index (CTDIvol), dose-length product (DLP), effective dose (ED), and qualitative analysis were statistically analyzed between the groups. There was no significant difference in sex, age, height, weight, body mass index (BMI), or heart rate between the 2 groups. The number of scans and scan length (149 of 3 scans at 10.35 cm, 1 of 4 scans at 13.80 cm; P<0.001), CTDIvol of CCTA (16.13 mGy; P<0.04), DLP of CCTA (166.90 mGy*cm; P<0.001), ED of CCTA (4.34 mSv; P<0.001), and overall ED (4.57 mSv; P<0.001) of group A showed significant differences compared with group B (36 of 3 scans at 10.35 cm, 109 of 4 scans at 13.80 cm, 2 of 5 scans at 17.25 cm; CTDIvol of CCTA at 18.30 mGy; DLP of CCTA at 235.60 mGy*cm; ED of CCTA at 6.13 mSv; overall ED at 6.13 mSv); meanwhile, actual heart length, qualitative analysis, and diagnostic CT reports were similar between the groups. The CACS scan with Sn100 kVp prior to CCTA imaging on dual-source CT could reduce overall radiation dose.


Interhemispheric Paracallosal Approach for an Arteriovenous Malformation of the Atrium: A Novel Technique.
Background: Intraventricular lesions present a surgical challenge because of the complexity of the ventricular anatomy, various perforating arteries, and eloquent brain areas surrounding the system. The ventricular atrium is particularly challenging because of the cingulate gyrus, corpus callosum, optic pathways, and significant vascular structures. We present the case of a patient for whom we used a new surgical approach to reach a lesion in the ventricular atrium. Case Report: A 26-year-old male presented with an intraventricular hemorrhage, acute hydrocephalus, and a grade III arteriovenous malformation (AVM) in the atrium of the left lateral ventricle. We approached the AVM through a posterior parietooccipital paracallosal interhemispheric approach. Instead of transecting the cingulate cortex as is traditionally done, we gently retracted the cingulate gyrus and made a small paracallosal incision to reach the atrium of the left lateral ventricle. The surgery was uneventful. The patient recovered well and was discharged home on postoperative day 3 without any deficits. Conclusion: This case illustrates a novel variation to an established approach to the ventricular atrium. With this technique, the surgeon minimizes disruption of brain tissue and thereby avoids the associated postoperative deficits associated with traditional approaches (transcortical, transcingulate, and conventional transcallosal). Tractography studies and a large cohort of patients are necessary to ensure the reproduction of good outcomes.


Objective image quality assessment based on support vector regression.
Objective image quality estimation is useful in many visual processing systems, and is difficult to perform in line with the human perception. The challenge lies in formulating effective features and fusing them into a single number to predict the quality score. In this brief, we propose a new approach to address the problem, with the use of singular vectors out of singular value decomposition (SVD) as features for quantifying major structural information in images and then support vector regression (SVR) for automatic prediction of image quality. The feature selection with singular vectors is novel and general for gauging structural changes in images as a good representative of visual quality variations. The use of SVR exploits the advantages of machine learning with the ability to learn complex data patterns for an effective and generalized mapping of features into a desired score, in contrast with the oft-utilized feature pooling process in the existing image quality estimators; this is to overcome the difficulty of model parameter determination for such a system to emulate the related, complex human visual system (HVS) characteristics. Experiments conducted with three independent databases confirm the effectiveness of the proposed system in predicting image quality with better alignment with the HVS's perception than the relevant existing work. The tests with untrained distortions and databases further demonstrate the robustness of the system and the importance of the feature selection.


Cloning of cellulase gene using metagenomic approach of soils collected from Wadi El Natrun, an extremophilic desert valley in Egypt.
Wadi El Natrun microorganisms have been considered as a new resource for natural products due to its extreme condition of salinity and alkalinity. Therefore, this study was devoted to generate metagemic library from soils collected from such an extreme environment in order to clone a novel cellulase for physique industrial applications. Total soil-DNA was successfully extracted, and then digested by different restriction enzymes. Purified fragments ranged ~ 200-6500 bp were ligated and were cloned into plasmid cloning vector (pUC19) by using Escherichia coli DH5α (E. coli) host cells. A constructed metagenomic library composed of 270 clones was screened on carboxymethylcellulose (CMC) agar plate where the active clones had been characterized by the formation of the yellowish halo zone. Thereafter, clone 1 was selected as the most active as being based on cellulase activity quantification (19 μ/ml). Plasmid related to clone 1 encoded cellSNSY gene of approximately 1.5 kb was subjected to molecular characterization; the obtained partial sequence of 861 bps encoded 287 amino acids showing 76% similarity to the endoglucanase gene of Bacillus amyloliquefaciens. The recombinant cellSNSY was expressed under lacz promoter at 1 mM of isopropyl β-d-1-thiogalactopyranoside (IPTG), giving 21 μ/ml cellulase after ~ 27 h. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and an activity staining of the recombinant cellSNSY which revealed an active band with a molecular mass ~ 59 kDa appeared in the induced sample. The maximum enzyme activity of crude cellSNSY was observed at 45 °C and for a pH of 8.5. Interestingly, the enzyme activity was slightly inhibited by ethylenediamine tetraacetic acid (EDTA) and methanol. It showed high resistance to the tested heavy metals and the surfactant which ordered Zn> (SDS,Fe)>Mn>Cu. This study established an easy and a skillful way to clone/express a new found cellulase gene(s) under lacZ promoter. The isolated recombinant cellSNSY showed 76% similarity to endoglucanase gene, and the enzyme showed tolerance to the mostly tested agents including heavy metals, surfactant, solvents, and EDTA. Additionally, the studied recombinant showed a high stability up to 55 °C and for alkaline pH 8.5. These features make it an ample and viable for many applications.


Leprosy in Myanmar, epidemiological and operational changes, 1958-92.
The registered caseload and prevalence of leprosy have declined in Myanmar from a peak of 86.2 per 10,000 population (95% CI 85.43-86.97) in 1973-77 to 26.82 (95% CI 18.46-35.18) in 1988-92. The new case detection rates have also declined from 7.41 per 10,000 (95% CI 6.3- 8.52) in 1968-72 to 1.96 (95% CI 1.43-2.52) in 1988-92. The increase in the multibacillary proportion of new cases from 11.85% (95% CI 11.84-11.86) in 1968-72 to 40.54% (95% CI 37.2-43.88) in 1988-92 and the decline in proportion of new cases under 14 years of age from 26.81% (95% CI 26.8-26.82) in 1968-72 to 11.22% (95% CI 10.92-11.52), coupled with the finding of declining detection rates among school children and in mass village surveys could mean that the incidence of leprosy may be declining.


Inorganic supramolecular host architectures: [(M@18c6)2][TlI4].2H2O, M=0.5 Tl, (NH4,NH3), (H3O,H2O).
The compounds [(M@18c6)2][TlI4].2H2O, M=Tl, (NH4,NH3), (H3O,H2O) (cubic, Fd; a=1481.00 pm, for M=0.5 Tl, a=1304.65 pm for M=(NH4,NH3), a=1313.67 pm for M=(H3O,H2O)) can be obtained from solution in the presence of traces of transition metal halides (like copper and mercury halides). Apparently the transition metal cations work as a template in the form of tetrahedral [MX4] units during the synthesis of the supramolecular host architecture. That the compounds are versatile host lattices for tetrahedrally coordinated transition metal units becomes obvious by the large group of known host-guest complex compounds, [(MIIX4)(MI@18c6)4][TlX4]2.nH2O (MII=Cu, Co, Zn, Mn; MI=NH4+, Rb, Tl; X=Cl, Br).


Multimodal imaging of pigmented paravenous retinochoroidal atrophy.
To describe the multimodal imaging findings of pigmented paravenous retinochoroidal atrophy. A 23-year-old female presented to us for a routine ocular examination. She had a best-corrected visual acuity of 6/6 in both eyes. Anterior segment examination was unremarkable. Fundus examination showed pigmentary changes along the retinal vasculature extending from mid periphery to post-equatorial retina suggesting a diagnosis of pigmented paravenous retinochoroidal atrophy. Swept-source optical coherence tomography of the macula showed choriocapillaris thinning at the mid periphery whereas coherence tomography angiography at the mid periphery showed a relatively normal choriocapillaris vasculature in the early stage of the disease. A relatively normal choriocapillaris structure was seen on ocular coherence tomography angiography which could have been due to a milder form of the disease in a young patient.


Acute epiploic appendagitis at the tip of the appendix mimicking acute appendicitis: A rare case report with literature review.
Acute epiploic appendagitis of the appendix (AEAA) is a rare self-limiting inflammatory disorder of the epiploic appendages (EA) close to the vermiform appendix, which often times mimicking the presentation of acute appendicitis (AA). To date, very few cases of AEAA have been reported. We report a case of a 52-year old man with the clinical suspicion of AA, but post-operative specimen examination confirmed AEAA as the final diagnosis. A 52-year-old morbidly obese man presented to the emergency department with a 1-d history of the right lower quadrant (RLQ) abdominal pain. Physical examination revealed localized RLQ tenderness mimicking AA. The computed tomography abdomen was inconclusive, and a decision was made to perform laparoscopic appendectomy (LA). During the LA, an infarcted epiploic appendage at the tip of appendix and adherent to the abdominal wall was found, which was entirely excised. Final pathology showed congested and hemorrhagic epiploic appendage without any accompanied acute inflammatory changes in the wall of the appendix. Postoperative course was uneventful and he was doing well at seven months follow-up. The possibility of AEAA should be considered in patients clinically suspected of having AA. Surgery is considered for those refractory to conservative management, with inconclusive diagnosis or develop complications at presentation.


[Social status, psychological stress and myocardial infarction risk among 35-64-year-old women].
We examined the association between social status, assessed by education and occupational categories and risk of myocardial infarction. We conducted a case-control study among 35-64 year-old women of Kaunas. Cases were 191 women with first myocardial infarction treated in hospitals in 1997-2000, and controls were 482 women in the same age group, randomly selected, without ischemic heart disease. We used multiple logistic regression to estimate the adjusted odds ratios of developing myocardial infarction in relation to social status and psychological stress. The study results indicated that stress, arterial hypertension, smoking, overweight and low education increased the risk of first myocardial infarction among 35-64 years old women. Managers and service, market sales workers had about twice higher risk for myocardial infarction than associate professionals (OR = 2.64; 95% CI 1.17-6.62 and OR = 2.18; 95% CI 1.03-4.63 correspondingly).


Effect of thyroid hormone on the pre- and post-natal development of the rat testis.
The relationship between thyroid function and testicular development in the rat was investigated. Hypothyroidism was induced during fetal or post-natal life by adding methimazole (MMI) to the drinking water of pregnant or lactating mothers. A group of newborn rats was treated with MMI and i.p. injections of L-tri-iodothyronine (L-T3). Hypothyroidism was shown by the reduced serum levels of total T3 and of total thyroxine (T4) in pregnant mothers and in pubertal rats. Testes were studied using light microscopy at 18 and 21 days post coitum or during puberty (21, 35 and 50 days after birth); serum levels of gonadotrophins were also evaluated in pubertal rats. Hypothyroidism had no effect on testicular development during fetal life and when induced in newborn rats it was associated at puberty with reduced serum levels of FSH and LH and with delayed maturation of the testis compared with control rats. The delay in maturation consisted of a reduction in the diameter of seminiferous tubules, and a reduction in the number of germ cells per tubule; this was associated with increased degeneration and arrested maturation of germ cells. In addition, Sertoli cells demonstrated retarded development, as indicated by a delay in the appearance of cytoplasmic lipids and in the development of a tubule lumen. Hormonal and morphological abnormalities were absent in rats treated with MMI plus L-T3. In conclusion, hypothyroidism occurring soon after birth caused reduced levels of gonadotrophins in the serum and a delay in pubertal spermatogenesis, possibly due to retarded differentiation of the Sertoli cells.


Establishing clinical pharmacist telehealth services during the COVID-19 pandemic.
After community transmission of the novel virus that causes coronavirus disease 2019 (COVID-19) was detected in the State of Washington in February 2020, innovative measures, such as telehealth appointments, were needed to safely continue to provide optimal pharmaceutical care for patients with chronic conditions and cancer. Prior to the COVID-19 pandemic, federal regulations limited the scope of telehealth pharmacist services. However, enactment of the Coronavirus Preparedness and Response Supplemental Appropriations Act, followed by guidance by the Centers for Medicare and Medicaid Services and the Department of Health and Human Services, allowed currently credentialed providers (including pharmacists) to continue to provide patient care services via telehealth with fewer restrictions. Our health system has numerous credentialed pharmacists across multiple ambulatory care clinics. In this article, we highlight our process of expediting the implementation of telehealth services. This process included obtaining authorization for the credentialed pharmacists to provide telehealth services, completion of training modules, implementation of new technology platforms, development of new workflows, and utilization of resources for providers and patients to facilitate successful completion of telehealth visits. We also highlight the consent and documentation components crucially important to the telehealth visit and share some of our successes, as well as identified limitations, in providing pharmacist services via telehealth. In the setting of the COVID-19 pandemic, our institution was able to swiftly implement clinical pharmacist telehealth services for many patients, offering a safe and effective way to continue providing a high level of care. This article discusses our experience with and potential limitations of telehealth to assist other pharmacists seeking to implement and/or expand their telehealth services.


Sub-chronic concomitant ingestion of L-arginine and monosodium glutamate improves feed efficiency, lipid metabolism and antioxidant capacity in male Wistar rats.
The use of L-arginine (ARG) is common in supplements, whereas, Monosodium Glutamate (MSG) is widely used as flavor enhancing food additive. Thus, ARG and MSG may be present together in human diets, warranting this study aimed at investigating the effect of concomitant ingestion of ARG and MSG on some biochemical indices in male rats. Twelve male albino rats were grouped into three (n = 4) and concomitantly exposed to 0:0, 20:5 and 60:15 mg kg(-1) of ARG:MSG. Exposure was peroral and every twenty four h for 28 days. ARG plus MSG treatment caused a significant (p < or = 0.05) increase in Feed Efficiency (FE) (Low dose: 5.23 +/- 22%; High dose: 5.60 +/- 11%), whereas, it decreased (p < or = 0.05) the serum Total Cholesterol (T-Chol) (low dose: 80.83 +/- 0.11 mg/100 mL, high dose: 92.55 +/- 0.14 mg/100 mL), triacylglycerol (TAG) (low dose: 179.91 +/- 0.09 mg/100 mL, high dose: 119.77 +/- 0.32 mg/100 mL) and malondialdehyde (MDA) (low dose: 5.00 +/- 0.07 mg/100 mL, high dose: 24.36 +/- 0.10 mg/100 mL) concentrations of the rats in a dose dependent manner. However, (at the high dose) the increase in Body Weight (BW) (0.08 +/- 0.07 kg), Feed Intake (FI) (0.40 +/- 0.03 kg) and Water Intake (WI) (0.65 +/- 0.18 L) induced by ARG plus MSG exposure was not significant (p < or = 0.05), suggesting non treatment related effect on these routine parameters. However, exposure to ARG plus MSG may significantly improve feed efficiency, lipid metabolism and antioxidant capacity in the male rats.


Engineering of vitamin prototrophy in Clostridium ljungdahlii and Clostridium autoethanogenum.
Clostridium autoethanogenum and Clostridium ljungdahlii are physiologically and genetically very similar strict anaerobic acetogens capable of growth on carbon monoxide as sole carbon source. While exact nutritional requirements have not been reported, we observed that for growth, the addition of vitamins to media already containing yeast extract was required, an indication that these are fastidious microorganisms. Elimination of complex components and individual vitamins from the medium revealed that the only organic compounds required for growth were pantothenate, biotin and thiamine. Analysis of the genome sequences revealed that three genes were missing from pantothenate and thiamine biosynthetic pathways, and five genes were absent from the pathway for biotin biosynthesis. Prototrophy in C. autoethanogenum and C. ljungdahlii for pantothenate was obtained by the introduction of plasmids carrying the heterologous gene clusters panBCD from Clostridium acetobutylicum, and for thiamine by the introduction of the thiC-purF operon from Clostridium ragsdalei. Integration of panBCD into the chromosome through allele-coupled exchange also conveyed prototrophy. C. autoethanogenum was converted to biotin prototrophy with gene sets bioBDF and bioHCA from Desulfotomaculum nigrificans strain CO-1-SRB, on plasmid and integrated in the chromosome. The genes could be used as auxotrophic selection markers in recombinant DNA technology. Additionally, transformation with a subset of the genes for pantothenate biosynthesis extended selection options with the pantothenate precursors pantolactone and/or beta-alanine. Similarly, growth was obtained with the biotin precursor pimelate combined with genes bioYDA from C. acetobutylicum. The work raises questions whether alternative steps exist in biotin and thiamine biosynthesis pathways in these acetogens.


The renoprotective effect of combined antihypertensive drugs.
In recent years, a target blood pressure (BP) of at least 125/75 mmHg has been sought in order to reduce the rate of progression of chronic renal failure (CRF) and cardiovascular mortality. Some antihypertensive agents, such as ACE inhibitors, calcium channel blockers and angiotensin receptor antagonists (and perhaps endothelin converting enzyme inhibitors and endothelin antagonists), may also reduce CRF progression because they block some of the pathogenetic mechanisms involved in renal damage. Although this effect seems to be partially independent of BP reduction, it is still not clear whether these drugs are really superior to other antihypertensive agents when low BP is achieved. However, the possibility that combination treatments with some of these drugs may confer additive or even synergistic renoprotective effects other than BP control is not only fascinating, but also important because multidrug antihypertensive regimens are required anyway to manage BP adequately in the majority of patients with CRF.


ALK-positive anaplastic large cell lymphoma of skeletal muscle masquerading as soft tissue sarcoma.
Anaplastic large cell lymphoma (ALCL) is a subtype of T cell non-Hodgkin's lymphoma and can present as an extranodal disease. Primary ALCL of skeletal muscle is rare. We report a case of ALK-positive ALCL involving the left thigh and anterior chest wall in a 12-year-old male child. The fine needle aspiration cytology from the lesion showed cellular smears with singly scattered and occasional clusters of large pleomorphic atypical cells. A diagnosis of poorly differentiated malignant neoplasm was rendered. On core biopsy, the histomorphological features posed a diagnostic challenge with a myriad of morphological mimickers. The diagnosis was established by excluding specific entities by relevant immunostains and confirming the diagnosis by strong expression of CD30 and ALK on immunohistochemistry. Fluorescence in-situ hybridisation confirmed the characteristic t(2:5) translocation. Presentation of ALCL with skeletal muscle involvement is uncommon, and the diagnosis relies on broadening the diagnostic possibilities and judicious use of immunohistochemical markers.


Primary ciliary dyskinesia with transverse colon carcinoma.
Primary ciliary dyskinesia, characterized by chronic airway infection, impaired fertility, and situs inversus in half the number of cases, was detected in a 58-year-old Japanese woman, along with carcinoma of the transverse colon. She was of complete situs inversus and subfertile and had chronic bronchitis and nasal polyposis. Ultrastructurally, the cilia of the nasal mucosa lacked dynein arms. This is the first documentation of this disease coupled with cancer.


Caspr2 autoantibodies target multiple epitopes.
To better understand the mechanisms of autoantibodies to the axonal protein contactin-associated protein-like 2 (Caspr2) by studying their target epitopes. A plasmid for expressing Caspr2 was modified so that the various extracellular subdomains were deleted individually and in groups. Cultured cells were transfected to express these constructs and assayed by immunofluorescence staining with a commercial Caspr2 antibody and a panel of patient sera known to react with Caspr2. Western blotting was also performed. The role of glycosylation in immunogenicity was tested with tunicamycin and PNGase F treatment. Patient antibodies bound to the extracellular domain of Caspr2. Neither native protein structure nor glycosylation was required for immunoreactivity. Caspr2 constructs with single or multidomain deletions were expressed on the plasma membrane. All deletion constructs were recognized by patients' sera, although reactivity was significantly reduced with deletion of the discoidin-like subdomain and strongly reduced or abolished with larger deletions of multiple N-terminal subdomains. Caspr2 with all subdomains deleted except the discoidin-like domain was still recognized by the antibodies. Caspr2 autoantibodies recognize multiple target epitopes in the extracellular domain of Caspr2, including one in the discoidin-like domain. Reactivity for some epitopes is not dependent on glycosylation or native protein structure.


TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair cells.
Aminoglycoside ototoxicity involves the accumulation of antibiotic molecules in the inner ear hair cells and the subsequent degeneration of these cells. The exact route of entry of aminoglycosides into the hair cells in vivo is still unknown. Similar to other small organic cations, aminoglycosides could be brought into the cell by endocytosis or permeate through large non-selective cation channels, such as mechanotransduction channels or ATP-gated P2X channels. Here, we show that the aminoglycoside antibiotic gentamicin can enter mouse outer hair cells (OHCs) via TRPA1, non-selective cation channels activated by certain pungent compounds and by endogenous products of lipid peroxidation. Using conventional and perforated whole-cell patch clamp recordings, we found that application of TRPA1 agonists initiates inward current responses in wild-type OHCs, but not in OHCs of homozygous Trpa1 knockout mice. Similar responses consistent with the activation of non-selective cation channels were observed in heterologous cells transfected with mouse Trpa1. Upon brief activation with TRPA1 agonists, Trpa1-transfected cells become loaded with fluorescent gentamicin-Texas Red conjugate (GTTR). This uptake was not observed in mock-transfected or non-transfected cells. In mouse organ of Corti explants, TRPA1 activation resulted in the rapid entry of GTTR and another small cationic dye, FM1-43, in OHCs and some supporting cells, even when hair cell mechanotransduction was disrupted by pre-incubation in calcium-free solution. This TRPA1-mediated entry of GTTR and FM1-43 into OHCs was observed in wild-type but not in Trpa1 knockout mice and was not blocked by PPADS, a non-selective blocker of P2X channels. Notably, TRPA1 channels in mouse OHCs were activated by 4-hydroxynonenal, an endogenous molecule that is known to be generated during episodes of oxidative stress and accumulate in the cochlea after noise exposure. We concluded that TRPA1 channels may provide a novel pathway for the entry of aminoglycosides into OHCs.


New insights into the oxygen reduction reaction mechanism on Pt(111): a detailed electrochemical study.
The oxygen reduction reaction (ORR) is undoubtedly the most important fuel-cell cathodic reaction. In this work, a detailed electrochemical analysis of the ORR on Pt(111) in nonadsorbing electrolytes was performed, which included the high-potential region Eup =1.15 V while ensuring the electrode surface structure stability. Our results suggest that the reduction of a soluble intermediate species formed during the ORR is the rate-determining step in the whole reaction mechanism. This species does not undergo any other electrochemical reaction at E>0.9 V and may accumulate close to the electrode surface. Together with dissolved O₂, this intermediate may modify the oxide-growth dynamics on Pt(111). Hence, both species interact with the electrode surface through complex catalytic networks. Under certain experimental conditions, oxygenated species from the oxidation of Pt(111) may enhance the overall ORR current. These results propose an alternative to explain the current state of the art for this fundamental process.


Lipids, lipid metabolism and Kaposi's sarcoma-associated herpesvirus pathogenesis.
Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi's sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.