A multiarray electrode mapping method for percutaneous thermocoagulation as treatment of trigeminal neuralgia. Technical note on a series of 178 consecutive procedures.
We describe our method and mapping technique of the trigeminal nerve using a quadripolar electrode to minimize morbidity of percutaneous thermocoagulation as treatment of trigeminal neuralgia. Of 381 patients selected for postgasserian thermocoagulation, 178 consecutive procedures were carried out using, in most cases, our painless and ambulatory method and technique. All patients were preoperatively subjected to 3-dimensional constructive interference in steady-state magnetic resonance and magnetic resonance angiography. Transgasserian introduction of our quadripolar multiarray electrode under constant fluoroscopic monitoring is used with systematic recording of radiologic angles at, in front of, and behind the clivus profile, always below the selar floor. The individual's somatotopic map based on the verbal responses of 34 facial subsegments in lieu of the usual 3 is carefully established. Lesions are aimed at the trigger of pain and restricted to fibers with the lowest thresholds. Maximal lesions are one third the size used in conventional thermocoagulation. Lesions attempt to avoid damage to the first division, uninvolved fibers, and the motor division. Pre- and postoperatory thresholds demonstrate that trigger-aimed small lesions do not extend to unwanted subsegments. The described technique can minimize unnecessary complications from percutaneous thermocoagulation.


Gene Editing in Human Pluripotent Stem Cells: Recent Advances for Clinical Therapies.
The identification of human embryonic stem cells and reprogramming technology to obtain induced pluripotent stem cells from adult somatic cells have provided unique opportunity to create human disease models, gene editing strategies and cell therapy options.Development of pluripotent stem cells from somatic cells and genomic manipulation tools enabled to use site specific nucleases in the cell therapy research. Identification of efficient gene manipulation, safe differentiation and use will provide a novel strategy to treat many diseases in the near future. Current available registered clinical trials clearly indicate the need for pluripotent stem cell and gene therapy treatment options. Although gene editing based pluripotent stem cell research is a popular field for research worldwide, improvement of clinical approaches for treatment still remains to be investigated. In this review, we summarized the current situation of gene editing based pluripotent cell therapy developments and applications in clinics.


Therapeutic efficacy and safety of Kangfuxin in combination with rabeprazole in the treatment of peptic ulcer: A systematic review and meta-analysis.
Kangfuxin (KFX), a well-known Chinese patent medicine which extracted from Periplaneta americana, is widely used as an adjuvant in the treatment of peptic ulcers (PUs) with proton pump inhibitors (PPIs) such as rabeprazole, in China. However, no clear consensus has been reached on the efficacy for PU treatment. We searched in 7 electronic databases to find randomized controlled trials (RCTs) completed before May 31, 2020 to explore the clinical efficiency of KFX plus rabeprazole in the treatment of PU. Risk ratio (RR) corresponding to 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by both Egger's and Begg's tests. Statistical analyses were performed using RevMan 5.4 and Stata version 10.0. Twenty-five RCTs, comprising 2555 PU patients, were included in this study. Meta-analysis showed that, when compared with rabeprazole-based treatment alone, KFX plus rabeprazole significantly improved the healing rate (RR = 1.34, 95% CI 1.25-1.44) and overall response rate of ulcers (RR = 1.16, 95% CI 1.13-1.20), alleviated the clinical symptoms of PU (RR = 1.14, 95% CI 1.08-1.21), and reduced the recurrence of PU (RR = 0.38, 95% CI 0.24-0.61) without an increase in the occurrence of adverse events (RR = 0.92, 95% CI 0.66-1.28). Our study suggests that KFX combined with rabeprazole showed positive therapeutic effects and is safe for treating PU, which may provide more reliable evidence for the clinical use of KFX in the treatment of PU.


The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis.
The aortic calcification index (ACI), estimated on abdominal computed tomographic scans, has been associated with the extent of arteriosclerosis in hemodialysis patients. However, the contribution of biochemical markers to the progression of vascular calcification in patients undergoing hemodialysis is not fully understood. We examined the relationship between coronary risk factors; metabolic factors, including serum osteoprotegerin (OPG) concentration; and progression of vascular calcification in 26 dialysis patients. Mean patient age was 52.6 +/- 8.7 (SD) years, and mean duration of dialysis therapy was 7.7 +/- 5.8 years. ACI was measured twice in each patient, and the mean interscan period was 4.9 +/- 0.3 years. Mean ACI changed from 22.2 +/- 24.2 to 33.9 +/- 28.8 overall, and mean change in ACI (DeltaACI) was 12.0 +/- 9.9. Patients were divided into 2 groups: slow progressors, with DeltaACI of 4.1 +/- 3.2 (n = 13), and rapid progressors, with DeltaACI of 19.8 +/- 7.9 (n = 13). Serum fasting glucose and CRP levels of rapid progressors were high, and their serum albumin and intact parathyroid hormone levels were low. Multiple regression analyses showed that serum OPG levels were independently associated with vascular calcification in the hemodialysis patients studied. Rapid progression of vascular calcification was associated with dose of calcium carbonate prescribed and serum OPG concentration. The clinical significance of these observations remains to be determined.


[Potential organ donors at an Italian intensive care unit].
To determine evaluate the number and characteristics of the population diagnosed as being cerebrally dead and the reasons why organs were not donated. Retrospective study from 1.1.1990 to 31.5.1994. Intensive care ward at Arezzo Hospital. 46 patients diagnosed as being cerebrally dead owing to primary intracranial pathology. Of the 1256 patients admitted to intensive care, 46 were diagnosed as being cerebrally dead. Five became organ donors. The study examines the reasons why the organs of the remaining patients dwere not donated. In spite of the fact that the number of donors corpses was broadly in line with national figures (8 per million inhabitants versus 9.7 for the NITp average and 6 for the national average), it is worth underlining the high percentage of patients (26.8%) for whom it was not possible to identify the reasons why the commission for the ascertainment of cerebral death was not summoned. This emphasises the need for greater commitment in the early identification of cerebral death, the monitoring and maintenance of organ functions in potential donors, and likewise the need for increased clarity in the formulation of statutory requirements regarding cerebral death.


A hybrid bird cage resonator for sodium observation at 4.7 T.
A bird cage resonator operating at 52.9 MHz is described. The particularity of the presented design is due to fixed capacitors between conductors. Tuning is performed by adjusting a self-capacitance system without breaking the coil symmetry. This structure denoted as "hybrid" is suitable for biological lossy samples.


Immunohistochemical assessment of E-cadherin and beta-catenin in trichofolliculomas and trichoepitheliomas.
Trichofolliculomas and trichoepitheliomas are benign skin neoplasms originating from hair follicle cells. They result from defects in the signaling pathways that regulate hair follicle morphogenesis and regeneration. Thus they seem to be an excellent model of these processes. It is known that the E-cadherin/beta-catenin system of adhesion molecules plays a crucial role in the maintenance of tissue architecture. The aim of the present study was to investigate their involvement in benign hair follicle tumor development. Semiquantitative intensity of expression were examined in formalin-fixed and paraffin-embedded tissue sections of 53 trichoepitheliomas, 15 trichofolliculomas and 19 normal skin samples by indirect immunohistochemistry. The intensity of E-cadherin/beta-catenin expression in tumor cells did not differ from controls. However, normal hair follicles cells exhibited membranous E-cadherin/beta-catenin expression, whereas both types of tumors, particularly trichoepitheliomas, showed E-cadherin/beta-catenin expression with a predominantly cytoplasmic localization. We suggest that this dystopic distribution of the E-cadherin/beta-catenin complex in hair follicle tumor cells may be a marker of cell-cell adhesion disruption which may contribute to the tumor formation.


Suppression of calphobindin I (CPB I) production in carcinoma of uterine cervix and endometrium.
Calphobindin I (CPB I) is a member of the family of Ca(2+)-dependent phospholipid binding proteins collectively termed as annexins. CPB I (Annexin V) has recently been shown to be an endogenous inhibitor of protein kinase C, a key enzyme in the cellular signal transduction and its inhibition by CPB I is presumed to be related ultimately to carcinogenesis. We therefore examined the level of production of CPB I in uterine cancer cells. Immunohistochemical analysis, northern blot, and in situ hybridization showed that the production of CPB I was markedly suppressed at the level of transcription in both cervical and endometrial carcinoma cells when compared to their normal counterparts. Decrease in production of CPB I may lead to dysregulated activation of protein kinase C and, accordingly, may be involved in a disorder of cell differentiation, proliferation, and carcinogenesis.


Clinical implications of vascular dysfunction in acute and convalescent COVID-19: A systematic review.
Accumulating evidence suggests that endothelial dysfunction is implicated in the pathogenesis and severity of coronavirus disease 2019 (COVID-19). In this context, vascular impairment in COVID-19 might be associated with clinical manifestations and could refine risk stratification in these patients. This systematic review aims to synthesize current evidence on the frequency and the prognostic value of vascular dysfunction during acute and post-recovery COVID-19. After systematically searching the MEDLINE, clinicaltrials.gov and the Cochrane Library from 1 December 2019 until 05 March 2022, we identified 24 eligible studies with laboratory confirmed COVID-19 and a thorough examination of vascular function. Flow-mediated dilation (FMD) was assessed in 5 and 12 studies in acute and post-recovery phase respectively; pulse wave velocity (PWV) was the marker of interest in three studies in the acute and four studies in the post-recovery phase. All studies except for one in the acute and in the post-recovery phase showed positive association between vascular dysfunction and COVID-19 infection. Endothelial dysfunction in two studies and increased arterial stiffness in three studies were related to inferior survival in COVID-19. Overall, a detrimental effect of COVID-19 on markers of endothelial function and arterial stiffness that could persist even for months after the resolution of the infection and provide prognostic value was congruent across published studies. Further research is warranted to elucidate clinical implications of this association.


Health and educational aspirations in adolescence: a longitudinal study in Finland.
The health selection hypothesis suggests that poor health leads to low educational attainment during the life course. Adolescence is an important period as poor health might prevent students from making the best educational choices. We test if health in adolescence is associated with educational aspirations and whether these associations persist over and above sociodemographic background and academic achievement. Using classroom surveys, a cohort of students (n = 5.614) from the Helsinki Metropolitan Region was followed from the 7th (12-13 years,) up to the 9th grade (15-16 years) when the choice between the academic and the vocational track is made in Finland. Health factors (Strengths and Difficulties Questionnaire (SDQ), self-rated health, daily health complaints, and long-term illness and medicine prescribed) and sociodemographic background were self-reported by the students. Students' educational aspirations (applying for academic versus vocational track, or both) and their academic achievement were obtained from the Joint Application Registry held by the Finnish National Agency for Education. We conducted multilevel multinomial logistic regression analyses, taking into account that students are clustered within schools. All studied health factors were associated with adolescents' educational aspirations. For the SDQ, daily health complaints, and self-rated health these associations persisted over and above sociodemographic background and academic achievement. Students with better health in adolescence were more likely to apply for the academic track, and those who were less healthy were more likely to apply for the vocational track. The health in the group of those students who had applied for both educational tracks was in between. Inconsistent results were observed for long-term illness. We also found robust associations between educational aspirations and worsening health from grade 7 to grade 9. Our findings show that selection by health factors to different educational trajectories takes place at early teenage much before adolescents choose their educational track, thus supporting the health selection hypothesis in the creation of socioeconomic health inequalities. Our findings also show the importance of adolescence in this process. More studies are needed to reveal which measures would be effective in helping students with poor health to achieve their full educational potential.


Rescue Retrieval of a Fully Deployed Low-Profile Intracranial Stent After Acute Occlusion.
The use of self-expandable stents for endovascular treatment of intracranial aneurysms has increased over time. Different types of stent malpositioning, such as stent migration, distortion, incomplete opening, and apposition, can occur as a complication of the stent deployment procedure. In this report, we present a successful retrieval of a low-profile stent after full deployment in a dissecting posterior-inferior cerebellar artery because of incomplete apposition and subsequent acute occlusion of the stent.


Bisphosphonates for preventing bone disease in kidney transplant recipients: a meta-analysis of randomized controlled trials.
An estimated 60% of kidney transplant recipients have mineral bone disease and about 0.5% break their hip within the first year after transplantation. We conducted a systematic review of benefits and harms of bisphosphonates in kidney transplant recipients. We searched CENTRAL (Issue 5, 2015) for randomized controlled trials in all languages and screened the reference list of an earlier Cochrane review. One reviewer identified the trials, extracted all data, and assessed risk of bias. Meta-analysis used a random effects model, with results expressed as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Bisphosphonates have uncertain effects on death (RR 0.45, CI 0.04-4.69) and vertebral fractures (RR 0.58, CI 0.24-1.43, I(2) 0%). Bisphosphonates moderately to importantly reduce the loss of vertebral bone mineral density (MD 5.98%, CI 3.77-8.18% change from baseline in g calcium/cm² at 12 months, I(2) 91%) and femoral bone mineral density (MD 5.57%, 3.12-8.01% change from baseline in g calcium/cm² at 12 months, I(2) 69%). At this stage, insufficient evidence exists to support routine use of bisphosphonates to reduce fracture risk after kidney transplantation. Data on important health outcomes are lacking, surrogate outcomes poorly reflect bone quality in kidney transplant recipients, and serious adverse events are not studied and reported systematically.


Phosphodeoxyribosyltransferases, designed enzymes for deoxyribonucleotides synthesis.
A large number of nucleoside analogues and 2'-deoxynucleoside triphosphates (dNTP) have been synthesized to interfere with DNA metabolism. However, in vivo the concentration and phosphorylation of these analogues are key limiting factors. In this context, we designed enzymes to switch nucleobases attached to a deoxyribose monophosphate. Active chimeras were made from two distantly related enzymes: a nucleoside deoxyribosyltransferase from lactobacilli and a 5'-monophosphate-2'-deoxyribonucleoside hydrolase from rat. Then their unprecedented activity was further extended to deoxyribose triphosphate, and in vitro biosyntheses could be successfully performed with several base analogues. These new enzymes provide new tools to synthesize dNTP analogues and to deliver them into cells.


Specific floater home ranges and prospective behaviour in the European starling, Sturnus vulgaris.
In many bird species, floaters are present on the breeding grounds in one or more years before they breed. There is increasing evidence that they have specific home ranges in which they search for information about current and future breeding opportunities. We investigated the role of prospecting in a migratory European starling (Sturnus vulgaris) population. Radio-tracking showed that male starling floaters use specific home range areas during the breeding period. Nest-box observations demonstrated that non-parental nest intrusion is common in the starling and that it is significantly more frequent during the nestling than during the incubation period. In addition, small groups of nest boxes were more likely to be occupied by starlings if they had been put up during the preceding breeding season. The results suggest that floaters try to acquire information about local breeding communities. One specific type of information may be the location of potential breeding sites.


[Meta-analysis of assisted music therapy for chronic schizophrenia].
To evaluate the effect of assisted music therapy for chronic schizophrenia. 11 articles including 603 chronic schizophrenia patients were meta-analyzed using fixed effect model or random effect model. 6 randomized controlled trials were synthesized, showing that the difference was significant in statistics between experimental group (patients with music and drugs therapy) and control group (patients with drugs therapy only). Both the scores of SANS and BPRS for the control group were higher than those for the experimental group (SANS, d = 0.68; 95%CI: 0.46-0.90 and BPRS, d = 0.44; 95%CI: 0.06-0.82). In addition, the scores of both SANS and BPRS for the pre-test were higher than those for the post-test (SANS, d = 1.17; 95%CI: 0.02-2.32 and BPRS, d = 2.05; 95%CI: 0.28-3.82). The short-term effect of assisted music therapy is positive for chronic schizophrenia, but the long-term effect is still to be further studied.


The impact of COVID-19 on the patterns of emergency department visits among pediatric patients.
This study aimed to investigate the patterns of pediatric patients visiting emergency departments (EDs) before and after the COVID-19 pandemic and evaluate the interactive effect between the COVID-19 outbreak and age groups. We performed a cross-sectional study using the nationwide emergency patient database in Korea from January 2019 to December 2020. Pediatric patients (≤18 years) who visited all 402 nationwide EDs were included. The age- and sex-standardized incidence rates of pediatric ED visits per 1,000,000 person-days were calculated, and the incidence rate ratio (IRR) was calculated. The adjusted odds ratio (aOR) and 95% confidence interval (CI) of in-hospital mortality were calculated by a multivariable logistic regression. Among 2,808,756 patients, 1,835,045 (65.3%) patients visited before COVID-19, and 973,711 (34.7%) patients visited after the COVID-19 period. The standardized incidence rates of ED visits per 1,000,000 person-days were 589.3 in the before COVID-19 group and 326.9 in the after COVID-19 group (IRR (95% CI): 0.55 (0.53-0.58)). By diagnosis, the IRRs (95% CI) of mental health disorders (0.84 (0.42-1.65)) and self-harm or suicidal attempts (0.99 (0.38-2.59) were not significant, while the incidence rate of infectious disease was significantly decreased (0.48 (0.42-0.54)). The aOR (95% CI) of in-hospital mortality after COVID-19 was 1.58 (1.44-1.73) compared to that before COVID-19. During the COVID-19 pandemic, the incidence of pediatric ED visits decreased, and these effects differed by age group. Age-specific policies are needed to ensure that children receive the care they need at the right time.


Electron Bifurcation Makes the Puzzle Pieces Fall Energetically into Place in Methanogenic Energy Conservation.
Elaborate arrays of iron-sulfur clusters link active sites via a flavin that bifurcates electrons through two energetically independent paths. The structure of the heterodisulfide reductase provides insight into how methanogens conserve energy through coupling hydrogen oxidation to coordinated exergonic heterodisulfide and endergonic ferredoxin reduction in an overall thermodynamically favorable reaction.


[Quality of life of living kidney donor: a national report].
The renal transplantation is nowadays the reference treatment of ESRD. Living donor kidney transplantation is less often performed in France than in other countries. Nevertheless, numerous French and international surveys have evidenced that it provides the recipients a longer life expectancy and a better quality of life. Donors themselves, what do they become? How are they? For the first time in France, a survey has been implemented to investigate the quality of life of living kidney donor to one of their close relations. This study has been undertaken by the Agency of the biomedecine and the service Clinical Epidemiology and Evaluation (EEC), of the University teaching hospital of Nancy. The main objective was to describe the quality of life of the living donors having given a kidney for more than a year and less than 5 years. The secondary objective was to contribute to the knowledge of the main factors associated to the living kidney donor quality of life, one year after the donation. Participants had to be living in France at the time of the donation which had taken place between June 30(th), 2005 and March 1(st), 2009. A folder gathering various self-administrated questionnaires was sent to the place of residence of the donor between March and April, 2010. These data were completed by medical data collected near the transplantation centres by the Agency of biomedecine within the framework of the register CRISTAL. They included the characteristics of the donation and of the donor at the very time of the donation, 3 months after the donation and at the last annual assessment. Three living donors in four, that is 501 persons, agreed to fully participate. They constituted a representative national sample of all the living donors of this period. The non participants were younger (4.5 years on average) and had a less adequate annual follow-up. The women were more represented (61 %) than men. The median age was 53 years. More of 2/3 were employed at the time of the survey. The three main categories of donors were ascendants (36 %), collateral (33 %) and spouses (26%). The donation decision was taken without hesitation (94 %) and at an early stage of the evolution of the recipient renal disease (64 %). The delivered information was considered globally satisfactory except for the painful consequences and for the scar. The living donors were, long after their donation, in an excellent physical health state according to the SF36 summarized physical score and this especially when they were old as compared to the same age and sex general population. This phenomenon highlights the drastic selection of the potential donors. The only factor influencing the level of long term physical health was the surgical technique: the 261 subjects having undergone a coelioscopy had less often presented post operative pain (OR=0.5; 0.3-0.8; P<0.002) and had more often recovered completely without any residual pain (OR=1.7; 1.2-2.5; P<0.004). The quality of life mental dimension according to the SF36 summarized mental score was very close to that of the same age and sex of the general population although a slightly lower. It is influenced by characteristics related to the way the donation had been lived, particularly the understanding of their donation by their circle of acquaintances (average score 74.2/100), the perception of a feeling of owing on behalf of the recipient (46.5 %) and the fact of having lived a competition to be retained as the donor (for 266 cases another potential donor did exist and 21 lived the donation as a strong competition). More than 84 % of the donors was still followed by a healthcare professional at the time of the survey. The main expressed complaints concern the quality of the medical follow-up (70 donors expressed themselves openly on this topic) and the pain and scar after effects of the intervention. In spite of the surgical complications, of the dissatisfactions regarding their medical follow-up, of dismissals or of necessary adjustments of their professional life (13 %), of their difficulties to carry heavy loads, of sometimes complex relations with the recipient (23 % positive, 10 % negative) or their circle of acquaintances, of expenses non reimbursement and of losses of salary (12 %), they would be 95 % to recommend the donation and if it was to be redone 98 % would do it again! Benefits brought to the recipient won largely over the encountered difficulties. This retrospective and cross-sectional study allows to state recommendations which have to be confirmed by the 2009-2012 longitudinal study: to favour the coelioscopy which offers an advantage in terms of less frequent pain and a better post operative recovery, to better understand the phenomena of competition between potential and donors recipients, to improve the information about the potential consequences of the donation on the pain and on the scar, to inform the donor about the importance to associate the proxies with the decisionmaking or at least with the discussion and finally to improve the society recognition of the donation.


A retrospective epidemiology study of contact eczema among the elderly attending a tertiary dermatology referral centre in Singapore.
The aim of this study was to examine the epidemiology of contact eczema in the elderly patients attending a skin clinic in Singapore. This is a retrospective study on patients attending our skin clinic at the National Skin Centre. All patients older than 49 years old attending our Contact and Occupational Dermatoses Clinic between 1990 and 1993 were included in the study. The prevalence of contact eczema among different age groups (50-59 years, 60-69 years, and 70-79 years) were compared. Diagnosis of contact dermatitis was based on the clinical history, physical examination and relevant patch test reactions. Demographic data of the patients were collected and analysed. Chi-square test was used for statistical analysis. Two hundred and one patients who were older than 49 years old, were included in the study. There was no significant difference in the prevalence of personal history of atopy among the 3 age groups. There was no significant difference in the racial distribution of the 3 age groups. The proportion of patients who were occupationally active decreased with age (50% vs 23% vs 0% respectively). There was no significant difference in the proportion of patients with positive patch test reactions in the 3 age groups although the proportion appears to increase with age (68% vs 75% vs 75% respectively). Similarly, the proportion of patients with allergic contact dermatitis was slightly higher in the older age group although the difference was not statistically significant among the 3 age groups (32% vs 45% vs 39% respectively). The face (54%) and hands (31%) were the commonest sites of eczema in the younger age group (50-59 years age group) whereas the lower limbs (41%) and the upper limbs (33.3%) were the commonest sites of eczema in the older patients (70-79 years age group). Nickel allergy was significantly more common in the younger age group (23% vs 17% vs 14% respectively). Medicament allergy (clioquinol-mix) and medicament related allergens e.g. balsam of Peru and fragrance-mix and para-phenylenediamine were slightly more prevalent in the older patients. The findings appear to indicate that the prevalence of allergic contact dermatitis is higher in older patients and that contact dermatitis tends to occur on the extremities in older patients than younger patients.


Outbreaks of the winter moth on Sitka Spruce in Scotland are not influenced by nutrient deficiencies of trees, tree budburst, or pupal predation.
Since the early 1980s, the winter moth, Operophtera brumata L. (Lepidoptera: Geometridae) has emerged as a serious pest of Sitka Spruce, Picea sitchensis Bong. plantations in southern Scotland. Outbreaks are characterised by susceptible sites within plantations which can occur immediately adjacent to resistant sites. We investigated the level of some nutrients in the trees, the date of budburst of the trees, and the numbers of some potential predators of winter moth pupae. None could satisfactorily explain outbreak patterns. Although foliage analysis demonstrated that many trees were marginal or deficient in phosphorus, nitrogen and potassium, these deficiencies were not related to the susceptibility of a site. Within sites, the numbers and weights of O. brumata were positively related to phosphorus content and negatively related to calcium content of foliage. Other evidence suggests, however, that these correlations may not represent direct effects of phosphorus and calcium on larval growth and survival. Date of budburst, which commonly determines susceptibility of deciduous hosts to O. brumata, was unrelated to density, and pupal predators were more, not less, abundant in susceptible sites. Although it is difficult to distinguish between factors that initiate outbreaks and those that maintain them, these data suggest that nutrient deficiencies of trees, budburst date, and the distribution of pupal predators of the winter moth cannot explain patterns of outbreak of the winter moth on spruce.


Mini-review: The market growth of diagnostic and therapeutic monoclonal antibodies - SARS CoV-2 as an example.
The emergence of novel viruses poses severe challenges to global public health highlighting the crucial necessity for new antivirals. Monoclonal antibodies (mAbs) are immunoglobulins that bind to a single epitope. Mouse mAbs are generated by classic hybridoma technology and are mainly used for immunodiagnostics. For immunotherapy, it is critical to use monoclonal antibodies in their human form to minimize adverse reactions. They have been successfully used to treat numerous illnesses, accordingly, an increasing number of mAbs, with high potency against emerging viruses is the target of every biopharmaceutical company. The diagnostic and therapeutic mAbs market grows rapidly into a multi-billion-dollar business. Biopharmaceuticals are innovative resolutions which revolutionized the treatment of significant chronic diseases and malignancies. Currently, a variety of therapeutic options that include antiviral medications, monoclonal antibodies, and immunomodulatory agents are available for the management of COVID-19. The invasion of mAbs in new medical sectors will increase the market magnitude as it is expected to generate revenue of about 300 billion $ by 2025. In the current mini-review, the applications of monoclonal antibodies in immune-diagnosis and immunotherapy will be demonstrated, particularly for COVID-19 infection and will focus mainly on monoclonal antibodies in the market.


99mTc-labeled annexin V fragments: a potential SPECT radiopharmaceutical for imaging cell death.
Annexin V is a protein that binds to phosphatidylserine exposed on dying cells. The phosphatidylserine-specific sequence is attributed to a chain on the N-terminal of annexin consisting of 13 amino acid sequence. Radiolabeled annexin V is used for imaging apoptosis. With an aim to synthesize a probe that can detect cell death akin to annexin V but smaller in size, annexin-13 fragments were derivatized to contain cysteine, cysteine-cysteine and histidine in their sequence at N terminal and were labeled with (99m)Tc via nitrido and carbonyl precursors. The (99m)Tc-labeled annexin-13 derivatives were characterized by HPLC and studied for their stability. In vitro and in vivo studies were carried out in apoptotic HL-60 cells and fibrosarcoma tumor-bearing Swiss mice, respectively. The (99m)Tc complexes were formed in high yields and were found to be stable. HPLC pattern of (99m)Tc nitrido complex of cysteine-cysteine-annexine 13 (CC-Anx13) and (99m)Tc carbonyl complex of histdine-annexin 13 (H-Anx13) revealed the formation of single species. In vitro cell uptake studies with (99m)Tc nitrido complex of cysteine-cysteine-annexin 13 fragment showed 6.5% uptake in apoptotic HL-60 cells. The uptake was found to be specific on testing with apoptotic HL-60 cells. Biodistribution studies of (99m)Tc nitrido complex with CC-Anx13 in fibrosarcoma tumor-bearing Swiss mice revealed optimum tumor uptake of 0.52 (0.17) %ID/g at 1 h pi. (99m)Tc(N)-CC-anx13 showed specific uptake in apoptotic tumor cells and warrants further evaluation.


Navigational guidelines and positional relationships of the human auditory ossicles from three-dimensional topography for ensuring safe and effective malleostapedotomy : Stereotactic topography of the auditory ossicles and its clinical implication.
The aims of the present study were to identify detailed positional relationship between the auditory ossicles and to provide theoretic navigational guidelines for optimal prosthesis adaptation and effective malleostapedotomy. Fifty sides of the temporal bone from donated cadavers were scanned by MicroCT and the malleus, incus, stapes and tympanic membrane were materialized three dimensionally using computer software. Dimensions between the auditory ossicles closely related to malleostapedotomy were measured twice. The grip site of malleus handle was mean 1.8 mm superior and mean 1.3 mm anterior, and linear distance between the grip site of malleus handle and the footplate of the stapes was mean 6.5 mm. The stapes was not parallel to the tympanic membrane and rotated mean 10.7° posteriorly relative to the tympanic membrane. Surgeons should start with at least 8.75 mm prosthesis to cover the upper limits of potential anatomy and then trim down to the individualization to the case. The ideal loop morphology has to be oval shape more than 1.4 mm in the long diameter and 1.0 mm in the short diameter. The wire of the prosthesis has to be bended at the two points: about 10° anteriorly at the most proximal point of the wire and about 50° superiorly at the stapes head point.


Methodological components and quality of evidence summaries: a scoping review protocol.
The objective of this review is to identify and map the available evidence related to evidence summary methodologies and indicators of quality. It can be challenging for clinicians and policy makers to keep up-to-date with current evidence and best practice. An evidence summary is a way to provide health care decision makers with the most recent, highest quality evidence available on a particular topic in an easily digestible format to facilitate evidence-based clinical decisions. However, objectively evaluating the methodological quality of these types of evidence reviews is challenging. Articles, papers, books, dissertations, reports and websites will be included if they evaluate, or describe the development or appraisal of, an evidence summary methodology. A three-step search strategy will be used to find both published and unpublished literature. The following databases will be searched: US National Library of Medicine Database (PubMed) Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, ProQuest Dissertations and Theses, and Embase. The gray literature search will include relevant government and university websites, the Health Evidence Network website, the World Health Organization (WHO) Health Evidence Network website, the McMaster Health Systems Evidence website, and relevant websites included in the Canadian Agency for Drugs and Technologies in Health (CADTH) Grey Matters Handbook. Sources published in English will be considered, with no date limitation.


Dose-response effects of estrogenic mycotoxins (zearalenone, alpha- and beta-zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm.
The aim of this study was to investigate the in vitro effects of the Fusarium fungus-derived mycotoxin, zearalenone and its derivatives alpha-zearalenol and beta-zearalenol on motility parameters and the acrosome reaction of stallion sperm. Since the toxic effects of zearalenone and its derivatives are thought to result from their structural similarity to 17beta-estradiol, 17beta-estradiol was used as a positive control for 'estrogen-like' effects. Stallion spermatozoa were exposed in vitro to zearalenone, alpha-zearalenol, beta-zearalenol or 17beta-estradiol at concentrations ranging from 1 pM - 0.1 mM. After 2 hours exposure, motility parameters were evaluated by computer-assisted analysis, and acrosome integrity was examined by flow cytometry after staining with fluoroscein-conjugated peanut agglutinin. Mycotoxins affected sperm parameters only at the highest concentration tested (0.1 mM) after 2 hours exposure. In this respect, all of the compounds reduced the average path velocity, but only alpha-zearalenol reduced percentages of motile and progressively motile sperm. Induction of motility patterns consistent with hyperactivation was stimulated according to the following rank of potency: alpha-zearalenol > 17beta-estradiol > zearalenone = beta-zearalenol. The hyperactivity-associated changes observed included reductions in straight-line velocity and linearity of movement, and an increase in the amplitude of lateral head displacement, while curvilinear velocity was unchanged. In addition, whereas alpha- and beta- zearalenol increased the percentages of live acrosome-reacted sperm, zearalenone and 17beta-estradiol had no apparent effect on acrosome status. In short, alpha-zearalenol inhibited normal sperm motility, but stimulated hyperactive motility in the remaining motile cells and simultaneously induced the acrosome reaction. Beta-zearalenol induced the acrosome reaction without altering motility. Conversely, zearalenone and 17beta-estradiol did not induce the acrosome reaction but induced hyperactive motility albeit to a different extent. Apparently, the mycotoxin zearalenone has 17beta-estradiol-like estrogenic activity that enables it to induce hyperactivated motility of equine sperm cells, whereas the zearalenol derivatives induce premature completion of the acrosome reaction and thereby adversely affect stallion sperm physiology. The alpha form of zearalenol still possessed the estrogenic ability to induce hyperactivated motility, whereas its beta stereo-isomere had lost this property.


Social and early life determinants of survival from cradle to grave: A case study in wild baboons.
Field studies of natural mammal populations present powerful opportunities to investigate the determinants of health and aging using fine-grained observations of known individuals across the life course. Here, we synthesize five decades of findings from one such study: the wild baboons of the Amboseli ecosystem in Kenya. First, we discuss the profound associations between early life adversity, adult social conditions, and key aging outcomes in this population, especially survival. Second, we review potential mediators of the relationship between early life adversity and survival in our population. Notably, our tests of two leading candidate mediators-social isolation and glucocorticoid levels-fail to identify a single, strong mediator of early life effects on adult survival. Instead, early adversity, social isolation, and glucocorticoids are independently linked to adult lifespans, suggesting considerable scope for mitigating the negative consequences of early life adversity. Third, we review our work on the evolutionary rationale for early life effects on mortality, which currently argues against clear predictive adaptive responses. Finally, we end by highlighting major themes emerging from the study of sociality, development, and aging in the Amboseli baboons, as well as important open questions for future work.


Therapeutic targeting of alpha 4-integrins in chronic inflammatory diseases: tipping the scales of risk towards benefit?
Inhibition of leukocyte trafficking via alpha4-integrin antibody blockade has recently become a validated therapeutic approach for several inflammatory diseases, including multiple sclerosis, ulcerative colitis and Crohn's disease. In the midst of this recent success, 3 patients receiving chronic treatment with the anti-alpha4 antagonist natalizumab (Tysabri) for the treatment of multiple sclerosis or Crohn's disease, developed JC-virus related progressive multifocal leukoencephalopathy (PML). These unforeseen consequences suggest that long term blockade of alpha4-integrins might prevent trafficking of non-pathogenic lymphocytes that are essential for viral immunosurveillance. In the current issue of the European Journal of Immunology Bjursten and colleagues report that long term treatment with anti-alpha4-integrin antibodies results in exacerbation of the murine model of colitis induced by the targeted deletion of the heterotrimeric G protein subunit Galphai2. In order to properly evaluate the efficacy and safety of anti-alpha4-integrin therapy, the relationship between these observations in an immunologically altered animal model and human clinical disease needs to be carefully measured.


[A Method for Isolating Tumor Cells from Large Volume of Malignant Pleural Effusion and Its Efficacy Evaluation].
Malignant plural effusion (MPE) is one of the most common specimen for liquid biopsy gene detection. This study aims to explore a method for isolating tumor cells from large volume of MPE and evaluate its efficacy and application prospect in gene detection. Pleural effusions (>500 mL) from 20 advanced lung cancer patients were obtained by effusion drainage and used to isolate tumor cells with cell separation media Percoll and Ficoll. Cell number and purity were calculated. DNA was extracted from the supernatant (etDNA), total cells and isolated tumor cells of pleural effusion (ETC-DNA) to detect the mutation of tumor-related genes by next-generation sequencing. The median number of cells isolated from malignant pleural effusion was 8.50×10⁴ (interquel range: 9.25×10³-3.75×10⁵), 85.50%±5.80% of the cells were identified as tumor cells. The detection rates of epidermal growth factor receptor (EGFR) gene mutation of etDNA, total cell DNA and ETC-DNA were 70.00%, 50.00% and 70.00%, reseparately, while the median EGFR mutation abundance in 3 components was 16.05% (4.78%-43.06%), 1.09% (0.00%-2.39%), and 33.02% (18.50%-76.70%), respectively. ETC-DNA had good consistency with tissue DNA (P>0.999, kappa=1.000) and etDNA (P>0.999, kappa=1.000). ETC-DNA inclined to have higher EGFR mutation than etDNA, but the result was not statistically significant. Our method can isolate large amount of tumor cells from a large volume of malignant pleural effusion with high purity. Using ETC-DNA as specimen improves the efficacy of gene detection, thus is worth further study.


Jejunum versus colon for free oesophageal reconstruction: an experimental radiological assessment.
The reconstruction of the cervical oesophagus and the hypopharynx by revascularised bowel grafts has become a frequently described treatment option. Problems with the standard jejunal grafts have led us to suggest that the colon provides a suitable alternative. Experimental work in dogs demonstrates clear functional differences between colon and jejunum as free oesophageal grafts, and shows how structurally and functionally the colon integrates into the new position in the oesophagus better than the jejunum.


Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline: 5,6,7-Trimethoxyflavan derivatives as novel potential anticancer agents modulating hippo signaling pathway.
Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline afforded 5,6,7-trimethoxyflavan derivatives that were efficiently synthesized in four linear steps. As lung cancer is the most lethal cancer, twenty-three synthesized compounds were evaluated against a panel of lung cancer cells. Amongst, compounds 8q and 8e showed interesting activity. Hence, compounds 8q and 8e were evaluated against panels of diverse cancers. Compounds 8q and 8e showed broad spectrum anticancer activity. However, compound 8q was more effective and, hence, was advanced for potency evaluation and characterization. Compound 8q showed comparable potencies to gefitinib, and oxaliplatin against lung and colorectal cancers, respectively, and superior potencies to temozolomide, dacarbazine, cisplatin, enzalutamide, methotrexate, imatinib against brain, skin, ovary, prostate, breast, and blood cancers, respectively. Compound 8q increased cleaved PARP, caspase 3, and 7 inducing apoptosis. In addition, it inhibited cyclins A, B1, H and cdc25c, and increased p53 triggering cell cycle arrest in G2/M phase. Moreover, it decreased YAP and increased LATS1 and p-mob1/mob1 activating hippo signaling. Furthermore, it decreased p-PI3K/PI3k, p-mTOR/mTOR and p-P70S6K/P70S6K inhibiting PI3k pathway. Together, these findings present compound 8q as a potential anticancer lead compound for further development of potential agents.


Medication overuse headache in Europe and Latin America: general demographic and clinical characteristics, referral pathways and national distribution of painkillers in a descriptive, multinational, multicenter study.
Medication overuse headache (MOH) is a very disabling and costly disorder due to indirect costs, medication and healthcare utilization. The aim of the study was to describe general demographic and clinical characteristics of MOH, along with the national referral pathways and national painkillers distribution in several European and Latin American (LA) Countries. This descriptive cross-sectional observational study included 669 patients with MOH referred to headache-centers in Europe and LA as a part of the COMOESTAS project. Information about acute medication and healthcare utilization were collected by extensive questionnaires, supplemented with structured patient interviews. Triptans were overused by 31 % European patients and by 6 % in LA (p < 0.001), whereas ergotamines were overused by 4 % in Europe and 72 % in LA (p < 0.001). Simple analgesics were overused by 54 % in Europe and by 33 % in LA (p < 0.001), while combination-analgesics were more equally overused (24 % in Europe and 29 % in LA). More European patients (57 %) compared with LA patients (27 %) visited general practitioners (p < 0.001), and 83 % of European patients compared to 38 % in LA consulted headache specialists (p < 0.001). A total of 20 % in Europe and 30 % in LA visited emergency rooms (p = 0.007). There are marked variations between LA and Europe in healthcare pathways and in acute medication overuse regarding patients with MOH. This should be considered when planning prevention campaigns against MOH.


Orbital abscess: visual loss following extraction of a tooth--case report.
It is the purpose of this article to alert the general practitioner to the severe consequences that may result from a tooth extraction, including the loss of vision, despite the use of antibiotics. Early and aggressive treatment is critical in obstructing the spread of infection toward the orbits, the eyes, and eventually the brain.


Diabetes increases the risk of depression: A systematic review, meta-analysis and estimates of population attributable fractions based on prospective studies.
We aim to examine the relationship between diabetes and depression risk in longitudinal cohort studies and by how much the incidence of depression in a population would be reduced if diabetes was reduced. Medline/PubMed, EMBASE, PsycINFO, and Cochrane Library databases were searched for English-language published literature from January 1990 to December 2017. Longitudinal studies with criteria for depression and self-report doctors' diagnoses or diagnostic blood test measurement of diabetes were assessed. Systematic review with meta-analysis synthesized the results. Study quality, heterogeneity, and publication bias were examined. Pooled odds ratios were calculated using random effects models. Population attributable fractions (PAFs) were used to estimate potential preventive impact. Twenty high-quality articles met inclusion criteria and were analyzed. The pooled odds ratio (OR) between diabetes and depression was 1.33 (95% CI, 1.18-1.51). For the various study types the ORs were as follows: prospective studies (OR 1.34, 95% CI 1.14-1.57); retrospective studies (OR 1.30, 95% CI 1.05-1.62); self-reported diagnosis of diabetes (OR 1.37, 95% CI 1.17-1.60); and diagnostic diabetes blood test (OR 1.25, 95% CI 1.04-1.52). PAFs suggest that over 9.5 million of global depression cases are potentially attributable to diabetes. A 10-25% reduction in diabetes could potentially prevent 930,000 to 2.34 million depression cases worldwide. Our systematic review provides fairly robust evidence to support the hypothesis that diabetes is an independent risk factor for depression while also acknowledging the impact of risk factor reduction, study design and diagnostic measurement of exposure which may inform preventive interventions.


Effects of soil type, moisture content, redox potential and methyl bromide fumigation on Kd values of radio-selenium in soil.
Understanding the processes that determine the solid-liquid partitioning (K(d) value) of Se is of fundamental importance in assessing the risk associated with the disposal of radio-selenium-containing waste. Using a mini-column (rather than batch) approach, K(d) values for (75)Se were determined over time in relation to soil moisture content (field capacity or saturated), redox potential and methyl bromide fumigation (used to disrupt the soil microbial population) in three contrasting soil types: clay loam, organic and sandy loam. The K(d) values were generally in the range 50-500 L kg(-1), with mean soil K(d) increasing with increasing organic matter content. Saturation with water lowered the measured redox potentials in the soils. However, only in the sandy loam soil did redox potential become negative, and this led to an increase in (75)Se K(d) value in this soil. Comparison of the data with the Eh-pH stability diagram for Se suggested that such strong reduction may have been consistent with the formation of the insoluble Se species, selenide. These findings, coupled with the fact that methyl bromide fumigation had no discernible effect on (75)Se K(d) value in the sandy loam soil, suggest that geochemical, rather than microbial, processes controlled (75)Se partitioning. The inter-relations between soil moisture content, redox potential and Se speciation should be considered in the modelling and assessment of radioactive Se fate and transport in the environment.


Growth of Li x La y Sr z MnO3 thin films by pulsed laser deposition: complex relation between thin film composition and deposition parameters.
Li x La y Sr z MnO3 thin films of various compositions (x,y,z) have been grown using pulsed laser deposition. The compositions of the films have been studied as a function of deposition temperature, target-to-substrate distance and deposition pressure with respect to different cation ratios of the targets by inductively coupled plasma mass spectrometry. When growing multi-elemental oxide thin films containing lithium (with its large mass difference to other elements), lithium loss is most probably inevitable. But the desired thin film composition can be achieved by selecting specific growth conditions and different target compositions. The experiments also elucidate some of the mechanisms behind the incongruent lithium transfer from the targets to thin films.


Predicting drug-disease associations via sigmoid kernel-based convolutional neural networks.
In the process of drug development, computational drug repositioning is effective and resource-saving with regards to its important functions on identifying new drug-disease associations. Recent years have witnessed a great progression in the field of data mining with the advent of deep learning. An increasing number of deep learning-based techniques have been proposed to develop computational tools in bioinformatics. Along this promising direction, we here propose a drug repositioning computational method combining the techniques of Sigmoid Kernel and Convolutional Neural Network (SKCNN) which is able to learn new features effectively representing drug-disease associations via its hidden layers. Specifically, we first construct similarity metric of drugs using drug sigmoid similarity and drug structural similarity, and that of disease using disease sigmoid similarity and disease semantic similarity. Based on the combined similarities of drugs and diseases, we then use SKCNN to learn hidden representations for each drug-disease pair whose labels are finally predicted by a classifier based on random forest. A series of experiments were implemented for performance evaluation and their results show that the proposed SKCNN improves the prediction accuracy compared with other state-of-the-art approaches. Case studies of two selected disease are also conducted through which we prove the superior performance of our method in terms of the actual discovery of potential drug indications. The aim of this study was to establish an effective predictive model for finding new drug-disease associations. These experimental results show that SKCNN can effectively predict the association between drugs and diseases.


Correlation of exosomal microRNA clusters with bone metastasis in non-small cell lung cancer.
20-40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) when symptom develops. Novel biomarkers with higher prediction value of BM are needed. Plasma-derived exosomal microRNAs had been isolated and sequenced of total 30 non-small cell lung cancer (NSCLC) patients including 16 with bone metastasis and 14 without bone metastasis. Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients with (BM +) or without (BM-) BM. Weight Co-expression network of miRNAs (WGCNA) analyses identified three consensus clusters (A, B, C) of highly correlated miRNAs, among which cluster B (144 miRNAs) showed significantly differential expression in lung cancer patients, especially in BM + group. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. Three differentially expressed miRNAs between BM + and BM- patients within cluster B were identified as miR-574-5p, a suppressor of Wnt/β-catenin pathway, was down-regulated, while miR-328-3p and miR-423-3p, two activators of the same pathway, were up-regulated in BM + patients. Cluster A miRNAs (n = 49) also showed trend of upregulation in BM + patients. Interestingly, pathway analysis indicated that 43 of them are associated with chromosome14, which has been suggested to promote epithelial-mesenchymal transition (EMT) and bone metastasis.


Characteristics and Effectiveness of Postoperative Rehabilitation Strategies in Ankle Fractures: A Systematic Review.
To explore the characteristics and to report on the effectiveness of postoperative rehabilitation strategies for people with an ankle fracture. PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL were searched to identify studies published from January 2010 to November 2021. Studies that described or evaluated postoperative rehabilitation strategies for surgically repaired ankle fractures were included. Data on postoperative rehabilitation were extracted in accordance with the Template for Intervention Description and Replication guide. Quality was assessed using the National Heart, Lung, and Blood Institute's Study Quality Assessment Tools. Meta-analysis was planned to look at the effectiveness of postoperative rehabilitation strategies. Forty studies described postoperative rehabilitation strategies without evaluating effectiveness, whereas 15 studies focused on evaluating effectiveness. Because of the large variety in postoperative strategies and outcomes, narrative synthesis was deemed most suitable to answer our aims. Characteristics of postoperative rehabilitation strategies varied widely and were poorly described in a way that could not be replicated. Most of the studies (48%) used a late weight-bearing approach, although definitions and details around weight-bearing were unclear. Late weight-bearing has been the most common postoperative approach reported in the past 10 years. The variety of definitions around weight-bearing and the lack of details of rehabilitation regimens limit replication and affect current clinical practice. The authors propose to adopt consistent definitions and terminology around postoperative practices such as weight-bearing to improve evidence for effectiveness and ultimately patient outcomes. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Turner's syndrome and carbohydrate metabolism. II. Parotid salivary insulin concentration in normal subjects and in patients with gonadal dysgenesis.
Ten children with XO gonadal dysgenesis and ten control siblings (CS) had sequential IV tolbutamide and IM glucagon tests to ascertain serum and salivary insulin concentrations, to confirm the presence of parotid salivary insulin and to determine if these concentrations were of diagnostic value in the diagnosis of insulin deficiency. After tolbutamide, peak serum insulin concentrations were lower in the patients with Turner's syndrome (TS) than in control siblings (58 +/- 10 vs 90 +/- 15 microU/ml) and fractional areas under insulin curves were significantly lower in the patients with Turner's syndrome at 10 to 15 minutes (TS: 240 +/- 16 microUmin/ml; CS: 340 +/- 46 microU-min/ml, P less than 0.05) and at 15 to 30 minutes (TS: 562 +/- 62 microU-min/ml; CS: 884 +/- 128 microU-min/ml, P less than 0.05). After glucagon, peak serum insulin concentrations were significantly lower in Turner's syndrome than in control siblings(P less than 0.02, at 45 minutes) and fractional areas under insulin curves were also lower in TS than in siblings at 30 to 45 minutes (TS: 1,062 +/- 185 microU-min/ml; CS: 2,189 +/- 402 microU-min/ml, P less than 0.02). Basal salivary immunoreactive insulin (IR) concentrations were similar in both groups: TS: 4.8 +/- 2.1 microU/min; CS: 2.1 +/- 0.4 microU/min. Peak salivary IRI concentrations after tolbutamide were 13.8 +/- 4.7 microU/min in Turner's syndrome and 8.8 +/- 1.8 microU/ml in control siblings. Peak salivary IRI values in Turner's syndrome and in control siblings after glucagon were 26.8 +/- 10.1 and 13.4 +/- 2.1 microU/min, respectively. While significant differces in insulin secretion in serum were detected in the two patient groups, no differences were noted between groups when salivary insulin concentrations were compared. These data confirm serum insulin deficiency in gonadal dysgenesis, the presence of immunoreactive insulin in parotid saliva, and suggest the possibility that extrapancreatic insulin synthesis could occur in the parotid gland.


5-HT(2C) receptor agonists and the control of appetite.
The role of serotonin (5-HT) in appetite control is well recognised. 5-HT drugs reduce food intake in rodents in a manner consistent with an enhancement of satiety. In humans, they have been shown to reduce caloric intake, an effect associated with reduced hunger and increased satiety. These effects appear to be mediated, at least in part, by the 5-HT(2C) receptor subtype. 5-HT-acting drugs such as fenfluramine, d-fenfluramine, and sibutramine have provided effective anti-obesity treatments in the past. However, more selective agents are needed that produce the same changes in eating behaviour and induce weight loss without unacceptable side effects. Lorcaserin, a selective 5-HT(2C) receptor agonist, is a novel anti-obesity agent that reduces both energy intake and body weight. The effects of lorcaserin on eating behaviour remain to be characterised as does its behavioural specificity.


Intra-aortic balloon pump for hemodynamic support in hepatobiliary surgery: report of a case.
The intra-aortic balloon pump (IABP) can be used transiently to improve cardiac function mechanically, in patients with severe cardiomyopathy and heart failure refractory to medical therapy. In the field of surgery, the IABP is most commonly used for patients with myocardial infarction, congestive heart failure, or other chronic cardiac conditions, who are undergoing cardiac surgery. Conversely, it is rarely used in hepatobiliary surgery, with only two reports found in the literature, excluding cases of emergency cholecystectomy. We describe how we used an IABP successfully during surgery to repair a transected bile duct in a patient with peripartum cardiomyopathy.


[Pulse therapy (high doses of venous methylprednisolone) in children with rheumatic carditis. Prospective study of 40 episodes].
To use corticosteroids in a shorter period to treat rheumatic carditis, keeping the patient in the hospital; and verify the time interval of normalization of rheumatic activity tests with this method. In 36 patients (40 episodes) intravenous methyl-prednisolone (1g/day) was administered. The number of series ranged from two to four, according to severity of the disease. The ages ranged from 6 to 17 years old, all of them fulfilled the criteria of Jones for diagnosis of rheumatic fever. They were submitted to treatment to eradicate the streptococcus, worms, PPD and dental focus extraction, before use of corticosteroids. In all patients the signals and symptoms of heart failure improved. In six cases occurred complications during pulse therapy that were easily controlled with clinical measures. Two series of methylprednisolone were used in 10 children, three in nine and four in 21 episodes. Eight patients were sent to valve replacement. The interval of time that laboratory tests of rheumatic activity became negative was 41.2 +/- 13.3 days. Using this IV corticotherapy it was possible decrease the amount of days of this medication, keeping the patient in the hospital. In this way we eliminate the problem of interruption of the treatment. There was not significative difference between oral and IV corticotherapy in order to the laboratory tests become negative.


Specificity and biological role of cathepsin D.
The purity of cathepsin D has been increased from 150 units/mg to over 200 units/mg. Peptides such as Ala-Phe-NH2, His-Phe-NH2 and Phe-Phe were split by impure enzyme and activity was blocked by pepstatin and diazoacetylnorleucine methyl ester. Pure preparations no longer digested these peptides. This points to the presence of a second peptidase activity similar to cathepsin D in specificity and inhibition properties, but distinct from it . Cathepsin D splits the peptides Leu-Phe-NH2, Leu-Tyr-NH2, Ac-Phe-TyrI2, and Ala-Leu-Tyr-Leu upon overnight incubation. More rapid splitting is found with phenyl sulfite, Glu-Ala-Leu-Tyr-Leu-Val, and Bz-Arg-Gly-Phe-Phe-Leu-4-methoxy-beta-naphthylamide. Digestion of bovine hemoglobin and human serum albumin by ruptured rat liver tritosomes was studied over the pH range 2.5-6.5. The combined action of cathepsin D and thiol proteinases accounted for most of the digestion. Cathepsin D accounted for 75% of the hemoglobin digestion at pH 3 and 45% at pH 5. Thiol proteinase accounted for 85% of the albumin digestion at pH 5. The role of cathepsin D in the development of embryonic limbs and skin, in uterine involution, and in cartilage degradation was reviewed. The activity of cathepsin D on cartilage matrix proteoglycans is limited to acid pH values. Human articular cartilage also contains metalloproteases active at pH 4.5 and 5.7.


Exposure to low-intensive superhigh frequency electromagnetic field as a factor of carcinogenesis in experimental animals.
Inbred albino mice and C57Bl/6 mice were exposed to nonthermal radiation of 37 GHz frequency in order to detect delayed effects caused by repeated irradiation. The detected pathomorphological changes and the dynamics of their formation suggest that these factors are responsible for delayed formation of immunodeficiency provoking mutagenic and carcinogenic effects.


Computed tomography in the evaluation of the optic chiasm.
Computed tomography (CT) is the procedure of choice for initial evaluation of patients suspected of having chiasmal or perichiasmal lesions. Over 1000 patients were examined with high resolution CT, using axial and coronal scans, contrast enhancement, multiplanar reformations, and, when indicated, metrizamide CT cisternography. The normal anatomic appearance of the chiasm and neighboring structures are: (1) symmetric or asymmetric enlargement of the chiasm; (2) areas of abnormal density, without or with contrast enhancement, in the chiasm or perichiasmal region; (3) alteration of the suprasellar cistern; and (4) distortion of the anterior-inferior third ventricle.


Methane production in a bioelectrochemistry integrated anaerobic reactor with layered nickel foam electrodes.
Towards the regulation and enhancement of inter-species electron transfer in sludge anaerobic digestion system, microbial electrolysis technology has become one of the effective ways to accelerate both fermentation and methanogenesis. In this study, the reactor performances and microbial activities related to biocathode formation are evaluated when the role of biocathode is regulated by series of layered cathodes. The results show the abundance of the cathodic methanogens decreased when enlarges the cathode area due to the lower current density. The biocathode evolution is directly related to the spatial methane distribution, which can further determine 25% increase of methane production rate compared to control without biocathode. Ultimately, the maximum methane production yield of 145.79 mL·d-1 is achieved by the optimal cathode area with a current density of 5.3 mA/cm3. The spatially methanogens distribution in suspended sludge and electrodes regulated by the layered cathodes is regarded to be the key to increase methanogenesis.


Significant life experiences in an adult sample.
This study sought to focus on the significant life experiences of an adult sample (n = 45, ages 30-60); in particular, stress, traumas, and trauma-resolved experiences were examined and compared to like experiences of an undergraduate sample. The results for the adults revealed that two-thirds of the sample were able to convert traumas into strens, and the ability seemed to be dependent more on the person than the specific event. Success at converting, if it occurred at all, usually occurred while in subjects were in their 20s; once it occurred, subsequent events were more likely to be coped with in a more positive manner. The implications for primary and early secondary prevention are discussed.


Socialisation of new graduate nurses to practising nurses.
The aim of this study was to explore the socialisation experiences of new graduate baccalaureate nurses to practising nurses. How nurses contend with the stress of their professional role has been of interest to both researchers and healthcare administrators over the past 30 years. Work stress of clinical nurses comes mainly from organisational and professional factors. However, few studies have explored the professional and organisational socialisation experiences of new graduate nurses. A qualitative descriptive approach was adopted. Participants were graduates of a baccalaureate nursing programme and employed full time at four medical centres in Taiwan, their first full-time work experience. Data were collected through semi-structured, open-ended, in-depth interviews, which were transcribed verbatim and analysed by content analysis. Three themes were identified: overwhelming chaos, learning by doing and being an insider. Although the professional socialisation process was hard for the new graduate nurses, they needed much time to increase their knowledge and clinical skills to fulfil clinical needs. However, the hardest work was the organisational socialisation process, which involved fitting into the bureaucratic system, such as maintaining interpersonal relationships with colleagues and familiarising themselves with the ward rules and culture. Neophyte nurse participants were also frustrated by the conflict between professional and organisational values. The study findings show that the transition from new graduate nurse to practising nurse was stressful for these participants, particularly due to the clash between the professional value of patient-oriented nursing care and the organisational value of task-oriented nursing. Senior clinical nurses can consider this study's descriptions of new graduate nurses' experiences to help them become insiders and provide quality care.


Targeting proliferating tumor cells via the transcriptional control of therapeutic genes.
We have previously reported the construction of a cell cycle-regulated HSV-1 amplicon vector (denoted as pC8-36) that confers luciferase reporter gene activities dependent on cellular divisions. However, luciferase reporter gene is well known for its relatively high sensitivity, thus, it is crucial to evaluate the therapeutic efficacy of a transcriptional targeted vector. In this report, we have engineered the FasL and FADD genes into pC8-36 and demonstrated their efficacy for the treatment of human gliomas in vitro and in vivo. Using trypan blue dye exclusion and TUNEL assay, FasL expression mediated by pC8-36 was shown to induce a significantly higher percentage of cell death in proliferating cells than those observed in the G(1)-arrested cells. The observed cell killing effect correlated well with the level of FasL protein expression when analyzed by ELISA assay. Furthermore, the incorporation of both FasL and FADD into pC8-36 resulted in the enhancement of apoptosis in the target glioma cells both in vitro and in vivo. Targeting proliferating tumor cells via the transcriptional control of therapeutic genes could potentially improve the safety and efficacy of cancer gene therapy, and thus would allow the development of strategies for more effective anticancer therapies.


Minimally and Non-invasive Approaches to Rejection Identification in Vascularized Composite Allotransplantation.
Rejection is common and pernicious following Vascularized Composite Allotransplantation (VCA). Current monitoring and diagnostic modalities include the clinical exam which is subjective and biopsy with dermatohistopathologic Banff grading, which is subjective and invasive. We reviewed literature exploring non- and minimally invasive modalities for diagnosing and monitoring rejection (NIMMs) in VCA. PubMed, Cochrane, and Embase databases were queried, 3125 unique articles were reviewed, yielding 26 included studies exploring 17 distinct NIMMs. Broadly, NIMMs involved Imaging, Liquid Biomarkers, Epidermal Sampling, Clinical Grading Scales, and Introduction of Additional Donor Tissue. Serum biomarkers including MMP3 and donor-derived microparticles rose with rejection onset. Epidermal sampling non-invasively enabled measurement of cytokine & gene expression profiles implicated in rejection. Both hold promise for monitoring. Clinical grading scales were useful diagnostically as was reflection confocal microscopy. Introducing additional donor tissue showed promise for preemptively identifying rejection but requires additional allograft tissue burden for the recipient. NIMMs have the potential to dramatically improve monitoring and diagnosis in VCA. Many modalities show promise however, additional research is needed and a multimodal algorithmic approach should be explored.


Unusual Cerebral Emboli.
The heart and the carotid arteries are the most common sites of origin of embolic disease to the brain. Clots arising from these locations are the most common types of brain emboli. Less common cerebral emboli include air, fat, calcium, infected vegetations, and tumor cells as well as emboli originating in the venous system. Although infarcts can be the final result of any type of embolism, described herein are the ancillary and sometimes unique imaging features of less common types of cerebral emboli that may allow for a specific diagnosis to be made or at least suspected in many patients.


Suitability of control materials in the differential inhibition assay for human pancreatic and salivary amylase.
We investigated the behavior of 26 quality-control sera with the inhibitor method for differential amylase (EC 220.127.116.11) assay. We also studied the sensitivity to the wheat-derived inhibitor of pancreatic amylases from 10 different animals in comparison with human pancreatic and salivary amylase. The results indicate that only control materials containing human amylases can be measured accurately. The animal amylases (bovine, equine, porcine) used in many quality control sera are relatively insensitive to the inhibitor as compared with human pancreatic and salivary amylase.


NMDA Receptors in the Central Nervous System.
NMDA-type glutamate receptors are ligand-gated ion channels that mediate a major component of excitatory neurotransmission in the central nervous system (CNS). They are widely distributed at all stages of development and are critically involved in normal brain functions, including neuronal development and synaptic plasticity. NMDA receptors are also implicated in the pathophysiology of numerous neurological and psychiatric disorders, such as ischemic stroke, traumatic brain injury, Alzheimer's disease, epilepsy, mood disorders, and schizophrenia. For these reasons, NMDA receptors have been intensively studied in the past several decades to elucidate their physiological roles and to advance them as therapeutic targets. Seven NMDA receptor subunits exist that assemble into a diverse array of tetrameric receptor complexes, which are differently regulated, have distinct regional and developmental expression, and possess a wide range of functional and pharmacological properties. The diversity in subunit composition creates NMDA receptor subtypes with distinct physiological roles across neuronal cell types and brain regions, and enables precise tuning of synaptic transmission. Here, we will review the relationship between NMDA receptor structure and function, the diversity and significance of NMDA receptor subtypes in the CNS, as well as principles and rules by which NMDA receptors operate in the CNS under normal and pathological conditions.


Breeding for Bio-ethanol Production in Lolium perenne L.: Association of Allelic Variation with High Water-Soluble Carbohydrate Content.
Increasing the extractable sugar yield from perennial crops is one strategy to generate renewable fuels such as bio-ethanol. Lolium perenne L. (perennial ryegrass) can contain significant (>30% dry matter) water-soluble sugars in the form of polymeric fructan which is readily extracted, broken down and fermented to bio-ethanol. A population of L. perenne generated from four parents which differed in water-soluble carbohydrate (WSC) content was subjected to multiple rounds of selection and recombination on the basis of early spring WSC content to produce a high WSC, and a low WSC population. A control population was generated by selecting the same number of plants at random. The alleles present at six candidate gene loci were analysed before and after selection and correlated to WSC content. Significant differences in the allele frequency of L. perenne soluble-acid invertase1:4 were observed between the three populations with one haplotype significantly associated with the high WSC C2S+ population (after three rounds of selection and two rounds of recombination). Moreover, WSC content was also associated with biomass accumulation. Thus, in addition to a 2.84-fold increase in WSC yield, the C2S+ population also had 1.48-fold more biomass per plant, resulting in 3.9-fold higher WSC yield per plant than the control population.


Effect of ozone and diode laser (635 nm) in reducing orthodontic pain in the maxillary arch-a randomized clinical controlled trial.
The effect of ozone, diode laser irradiation, and presence of teeth crowding/spacing on pain perception in orthodontic patient was tested. Overall, 76 patients [55 women and 21 men; age 35.1(6.4) years] who met the inclusion criteria participated in the study. Immediately after fixed orthodontic appliance placement, the patients were exposed to a pain relief treatment (one single session) using either 635-nm diode laser (SmartM, Lasotronix, Warsaw, Poland) or ozone therapy (OzoneDTA, Apoza, New Taipei City, Taiwan) by placing the handpieces in the area of each teeth apex and interdental papillae, from the maxillary right first molar to the maxillary left first molar. Subjects were divided into three groups: control group (G1, n = 26), ozone (G2, n = 26, exposed to ozone therapy, generator probe type 3, working time per point 5 s, 23 points, application time 1 min and 55 s), and laser group (G3, n = 25, exposed to continuous mode diode laser, 400 mW, handpiece diameter 8 mm, spot area 0.5024 cm2, power density per second 1.59 W/cm2, dose 2 J per point, time: 5 s per point, 23 points, total energy per session 46 J, application time 1 min and 55 s). The level of teeth crowding was assessed using the Lundstrom indicator. The patients received a questionnaire for pain assessment (the Numeric Rating Scale, NRS-11, grade level 0-10) and recorded at 7 time points (1 h, 6 h, and 1, 2, 3, 4, and 5 days ) after the fixed orthodontic appliance placement. The mean pain values for the diode laser, ozone, and control group were 3.6 (1.31) (95% CI, 2.95-4.25), 5.25 (3.37) (95% CI, 3.52-6.98), and 5.75 (2.40) (95% CI, 4.69-6.81), respectively. We observed lower pain values in the diode laser group compared to the control group (p = 0.0237). The use of ozone in this study did not result in significant pain reduction in comparison to control (p = 0.8040) and laser groups (p = 0.1029). There were no differences in pain perception between patients with crowded teeth and non-crowded teeth in each group (G1, p = 0.66, G2, p = 0.86, G3, p = 0.24). The use of 635-nm diode laser led to decreased pain perception; however, ozone and presence of teeth crowding/spacing did not affect the pain perception in orthodontic patients during the first 5 days after the fixed orthodontic appliance placement.


Gastroesophageal Reflux Disease in the Neonatal Intensive Care Unit Infant: Who Needs to Be Treated and What Approach Is Beneficial?
Gastroesophageal reflux (GER) and GER disease (GERD) pertaining to infants in the neonatal intensive care unit (NICU) are reviewed, based on research in this specific population. The developmental biology of the gastroesophageal junction, physiology of GER, and pathophysiology of GERD in this setting are summarized, and risk factors for GER and GERD identified. The epidemiology, economic burden, and controversies surrounding GERD in NICU infants are addressed, and an approach to GER and GERD in these patients formulated. Recent advancements in individual assessment of GER and GERD in the NICU infant are examined, and evidence-based guidelines for their adoption provided.


Development of a real-time bioprocess monitoring method for docosahexaenoic acid production by Schizochytrium sp.
Oxygen uptake rate (OUR) and respiratory quotient (RQ) are key respiratory parameters for docosahexaenoic acid (DHA) production by Schizochytrium sp. HX-308 under dissolved oxygen limited conditions. To investigate the relationship of OUR and RQ with culture status, three independent cultures with different aeration rates were performed in a 50L bioreactor. OUR was found to be positively correlated with the aeration rate, which reflected the oxygen supply level in each culture. The highest biomass, reaching 124.5g/L, was achieved under the highest OUR. DHA content was found to be highly correlated with the RQ value, and the highest DHA content (44.85% in total fatty acids, w/w) was achieved in the highest RQ level, which implies that the polyketide synthase pathway was more active. OUR and RQ, which reflect the physiological state of microorganisms, are suggested as synergistic real-time bioprocess monitoring parameters for DHA fermentation.


A Critical Sociocultural Understanding of Evidence-Based Research and Practice Paradigm in Contemporary Psychology.
The paper aims to develop a critical sociocultural understanding on the epistemological and historical analysis of evidence-based (EB) paradigm in contemporary psychological knowledge-production (research) and knowledge-application (practice). It firstly retraces the emergence of EB in medical disciplines, its paradigmatic status, and its subsequent adoption by mainstream psychological sciences. The description of EB historical roots and key concepts leads to the second part, where the paper reflects on key epistemological criticalities scholars have raised toward the EB paradigm. Then, we develop our sociocultural perspective to enrich the epistemological analysis and critique of EB. Specifically, we propose a hermeneutic and interpretative understanding which frames EB as a re-enactment of the positivist scientific research ambition to reach for a complete formalization of biological/psychological phenomena (endo-genetical dynamics), and of new socioeconomic, political, and individual needs posed by contemporary Western societal institutions to scientific knowledge (exo-genetical dynamics). Furthermore, building on such understanding, we suggest that EB works as a contemporary epistemic indicator and threshold, serving two functions: selective filtering and exclusion. Finally, we speculate that EB endo-genetical and exo-genetical developmental dynamics can be interpreted as an expression of the contemporary presentist regime of temporality and as a shift towards the regime of performative techniques instead of context-specific and future-oriented relational competences, also tracing a determining factor that has directed, directs and will continue to direct scientific research in psychology.


Effect of exogenous histidine on restoration of electron transfer on the donor side of photosystem II depleted of Mn.
It is shown that restoration of photoinduced electron flow with added Mn2+ (measured by photoreduction of DCPIP and photoinduced change of chlorophyll fluorescence yield) in Mn-depleted Photosystem II (PS II) membrane fragments isolated from spinach chloroplasts, is considerably increased by exogenous histidine (His). The stimulating effect of His is not observed if other electron donors (NH2OH or diphenylcarbazide) are used instead of Mn2+. His added alone does not induce electron transfer in Mn-depleted PS II preparations. Investigation of pH dependence of the stimulating effect of 2 mM His shows that the effect is observed only at pH > 5.0, it gives a 50% activation around pH 6.0 and saturates at pH 7.0-7.5. Nearly 200 microM His is required for a 50 effect at pH 7.0. It is suggested that the added His can be involved in stimulation of electron transfer on the donor side of PS II through direct interaction of Mn2+ with deprotonated form(s) of His resulting in formation of Mn-His complexes capable of efficient electron donation to PS II (though it is not excluded that His serves as a base that takes part in proton exchange coupled with redox reactions on the donor side of PS II or as an electron donor to the oxidized Mn).


Burden, depression and anxiety in primary caregivers of children and adolescents in renal replacement therapy.
Chronic kidney disease (CKD) is rare in children, but it causes repercussions in several aspects of life, because the disease and treatment cause great changes in the daily lives of the child and his family, increasing the burden on caregivers. To evaluate the burden of primary caregivers of children and adolescents who undergo renal replacement therapy (RRT). Cross-sectional, observational study performed at the Pediatric Renal Unit of a school hospital in the Northeast. Forty-nine primary caregivers of pediatric patients with CKD in RRT followed up in our clinic participated in the study. We used validated instruments to assess burden, depression and anxiety. We ran some tests to analyze the findings of burden, depression and anxiety in the sample. Most of the caregivers are the mothers of these children (89.8%), aged between 36 and 45 years (46.9%), have Elementary School education only (55.1%) and reported feeling pain in the body (69.4%), but they did not have chronic disease. The majority of the children have been in RRT from 1 to 3 years (40.8%), aged from 9 to 11 years (30.6%), are male (55.1%), and under hemodialysis (38.8%). The caregivers had a moderate level of burden (2.10), a high prevalence of moderate to severe depression (18.4%) and anxiety (47%), and a strong correlation between burden, depression and anxiety. Caring for a child with CKD is an intense experience, with negative consequences, due to uncertainties about the future and the very care these children require. We need to do something to help these caregivers better manage care, as well as cope with their own feelings.


Complications and quality of life in elderly patients with several comorbidities undergoing cutaneous ureterostomy with single stoma or ileal conduit after radical cystectomy.
To compare peri-operative outcomes and quality of life (QoL) in a series of elderly patients with high comorbidity status who underwent single stoma cutaneous ureterostomy (CU) or ileal conduit (IC) after radical cystectomy (RC). The clinical records of patients aged >75 years with an American Society of Anesthesiologists (ASA) score >2 who underwent RC at a single institution between March 2009 and March 2014 were retrospectively analysed. After RC, all patients included in the study received an IC urinary diversion or a CU with single stoma urinary diversion. Preoperative clinical characteristics as well as intra- and postoperative outcomes were evaluated and compared between the two groups. In addition, the Bladder Cancer Index (BCI) was used to assess QoL. A total of 70 patients were included in the final comparative analyses. Of these, 35 underwent IC diversion and 35 CU single stoma diversion. The two groups were similar with regard to age, gender, ASA score, type of indication and pathological features. Operating times (P < 0.001), estimated blood loss (P < 0.001), need for intensive care unit stay (P = 0.01), time to drain removal (P < 0.001) and length of hospital stay (P < 0.001) were significantly higher in patients undergoing IC diversion. The number of patients with intra- (P = 0.04) and early postoperative (P = 0.02) complications was also significantly higher among those undergoing IC diversion. Interestingly, the mean BCI scores were overlapping in the two groups. The present results show that CU with a single stoma can represent a valid alternative to IC in elderly patients with relevant comorbidities, reducing peri-operative complications without a significant impairment of QoL.


Spontaneous cortical slow-potential shifts and choice reaction time performance.
EEGs from Fz, Cz and Pz locations (reference--right mastoid) were obtained from 36 adults. For experimental trials the Fz slow potentials (SP) were determined for a pretask interval of: a 3 sec baseline, followed by a 2.5 sec SP shift, in either negative (3.5 microV) or positive (1.5 microV) direction, and maintenance at this level for another 2.5 sec. When this criterion was met the stimuli for a choice RT task were presented (potential-related event, PRE), which required a button-press response with the right or left hand for differing stimulus configurations. During subsequent control sessions subjects were tested without pretask criterion SP shifts, with yoked pretask intervals from the experimental sessions. For the experimental conditions the mean RTs were significantly faster and less variable with the negative than with the positive SP shift condition. For the control conditions mean RTs were somewhat faster for the positive than for the negative criterion, which might be attributed to the more variable pretask intervals during the latter polarity condition. For confirmation of the cortical localization of this effect, the experimental session was replicated with corresponding negative and positive SP shift criteria from Pz. No significant differences among means and standard deviations of RTs were found. SP shifts from criterion electrodes (Fz or Pz) were significantly greater in mean amplitude than the concomitant SP shifts from the other electrodes. The present findings demonstrate the feasibility of the PRE methodology for investigations of human brain functions.


[The Nursing School of Ribeirao Preto of the University of Sao Paulo: four decades].
The purpose of this article is to present the history of the College of Nursing, University of São Paulo at Ribeirão Preto Campus, since the management of its founders, ex-deans and the actual dean, emphasizing these administrations principal conquests.


Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum-based chemotherapy in advanced nonsmall-cell lung cancer patients.
Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum-based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p = 0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short-term period (HR 1.718, p = 0.003; HR 1.691, p = 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short-term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA+AA) had higher risk of hematologic toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and p = 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1-141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum-based chemotherapy.


El Niño Southern Oscillation as an early warning tool for malaria outbreaks in India.
Risks of malaria epidemics in relation to El Niño and Southern Oscillation (ENSO) events have been mapped and studied at global level. In India, where malaria is a major public health problem, no such effort has been undertaken that inter-relates El Niño, Indian Summer Monsoon Rainfall (ISMR) and malaria. The present study has been undertaken to find out the relationship between ENSO events, ISMR and intra-annual variability in malaria cases in India, which in turn could help mitigate the malaria outbreaks. Correlation coefficients among 'rainfall index' (ISMR), '+ winter ONI' (NDJF) and 'malaria case index' were calculated using annual state-level data for the last 22 years. The 'malaria case index' representing 'relative change from mean' was correlated to the 4 month (November-February) average positive Oceanic Niño Index (ONI). The resultant correlations between '+ winter ONI' and 'malaria case index' were further analysed on geographical information system platform to generate spatial correlation map. The correlation between '+ winter ONI' and 'rainfall index' shows that there is great disparity in effect of ENSO over ISMR distribution across the country. Correlation between 'rainfall index' and 'malaria case index' shows that malaria transmission in all geographical regions of India are not equally affected by the ISMR deficit or excess. Correlation between '+ winter ONI' and 'malaria case index' was found ranging from -0.5 to + 0.7 (p < 0.05). A positive correlation indicates that increase in El Niño intensity (+ winter ONI) will lead to rise in total malaria cases in the concurrent year in the states of Orissa, Chhattisgarh, Jharkhand, Bihar, Goa, eastern parts of Madhya Pradesh, part of Andhra Pradesh, Uttarakhand and Meghalaya. Whereas, negative correlations were found in the states of Rajasthan, Haryana, Gujarat, part of Tamil Nadu, Manipur, Mizoram and Sikkim indicating the likelihood of outbreaks in La Nina condition. The generated map, representing spatial correlation between ' + winter ONI' and 'malaria case index', indicates positive correlations in eastern part, while negative correlations in western part of India. This study provides plausible guidelines to national programme for planning intervention measures in view of ENSO events. For better resolution, district level study with inclusion of IOD and 'epochal variation of monsoon rainfall' factors at micro-level is desired for better forecast of malaria outbreaks in the regions with 'no correlation'.


From awareness to action: NIPD's engagement in the control of food-borne clonorchiasis.
Clonorchiasis is caused by ingestion of raw freshwater fish containing infective larvae of Clonorchis sinensis. China harbours the largest number of people with C. sinensis infection. During the past three decades, the National Institute of Parasitic Diseases, affiliated to the Chinese Center for Disease Control and Prevention (NIPD) conducted many studies to facilitate the control on clonorchiasis. Three national surveys have shown the updated epidemiology of clonorchiasis in China. Recently, a national surveillance system has also been established, which will enable the production of high-resolution map. The evaluation of the disease burden has enhanced the awareness on clonorchiasis. Diverse diagnosis techniques including rapid screening by questionnaire, serological tests, faecal examination and a molecular method have been developed or evaluated. The NIPD also participated in the early evaluation of praziquantel against clonorchiasis, which enhanced its application in China. Also, the NIPD has verified the efficacy of tribendimidine against clonorchiasis. A new sustainable strategy is also being explored. However, more research is expected to further facilitate control of clonorchiasis in China, as well as international cooperation in fighting human liver fluke infections in Asia.


Serum creatinine-to-cystatin C ratio as an indicator of sarcopenia in hemodialysis patients.
In hemodialysis patients, sarcopenia is common and related to morbidity and mortality. In non-dialysis patients, the serum creatinine-to-cystatin C (Cre/Cys-C) ratio is a marker of sarcopenia. Its clinical utility in hemodialysis populations, however, is still unknown. Our study aimed to determine whether sarcopenia could be detected using the Cre/Cys-C ratio in hemodialysis patients. This retrospective cross-sectional study included 85 hemodialysis patients whose handgrip strength (HGS) and bioimpedance analysis-estimated skeletal muscle index (SMI) were assessed. Sarcopenia was diagnosed as a combination of reduced muscle strength (women: HGS <18 kg; men: HGS <28 kg) and decreased muscle mass volume (women: SMI <5.7 kg/m2; men: SMI <7.0 kg/m2). Sarcopenia was observed in 33 (38.8%) patients. Patients with sarcopenia had a significantly lower Cre/Cys-C ratio than those without (1.3 ± 0.2 vs 1.7 ± 0.3, respectively; p < 0.0001). The Cre/Cys-C ratio was independently associated with HGS (β = 0.303, p = 0.011) and SMI (β = 0.376, p = 0.0007). After adjustment for sex and age, the C-statistic of the Cre/Cys-C ratio that predicted sarcopenia was 0.898 (95% CI [0.827, 0.969], p < 0.0001). Moreover, as Cre/Cys-C ratios increased, the risk of sarcopenia significantly decreased (adjusted OR: 0.665 for each 0.1 increase in the Cre/Cys-C ratio) (95% CI [0.501, 0.857], p = 0.0002). The Cre/Cys-C ratio may be a helpful prediction tool for sarcopenia in patients receiving hemodialysis.


Changes in depressed mood associated with 10 weeks of moderate cardiovascular exercise in formerly sedentary adults.
Two groups of adults classified with depressed mood (10% highest scores on the Profile of Mood States-Short Form Depression scale) were contrasted on changes in POMS Depression scores over 10 weeks. The exercise group (n = 26) was given a moderate cardiovascular exercise program of 3x/week for 20 to 30 min. per session. The control group (n=24) did not participate in exercise. Significant reductions in POMS Depression scores over 10 weeks were noted for the exercise group in between-group (d=-.88) and within-group (d=-1.32) analyses. Significantly more participants in the exercise group scored in the normal range at Week 10 (62%) than in the control group (29%). Neither changes in cardiorespiratory function (VO2 max) nor initial POMS Depression scores were significantly correlated with changes in POMS Depression scores after 10 weeks. Methodological improvements, limitations, and practical application of findings after replication were discussed.


Duplication cyst of the duodenum in the adult.
A duodenal duplication cyst in a 45-year-old male is reported. A hypotonic duodenography showed a smooth spherical defect in the descending portion of the duodenum. A fiberoptic duodenoscopy disclosed a smooth well-defined tumor which was located orally from the ampulla of Vater. A retrograde pancreatocholangiography indicated the tumor was not in communication with the pancreatic duct or biliary tract. At operation, a cystic spherical mass, 3 cm in diameter, was located in the posterior wall of the duodenum corresponding to the above described diagnosis. The combination of a greater awareness of this condition as well as improved X-ray and endoscopic techniques has made preoperative diagnosis more accurate.