May Measurement Month 2018: an analysis of blood pressure screening results in South Africa.
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension (ISH) aimed at raising awareness of high BP and acting as a temporary solution to the lack of screening programmes worldwide. As part of MMM, screening in South Africa in 2017 revealed that 24.5% of adults (mean age = 31 years) have hypertension and only half of those with hypertension had controlled BP. These data highlight the need for continued screening and awareness campaigns. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2018. Blood pressure measurements, the definition of hypertension and statistical analyses followed the MMM protocol. The sites screened were general populations and university campuses in preference to hospitals and clinics, aiming to raise awareness and allow access to screening to those less likely to be aware of their BP. In total, 2965 individuals (age 40.5 ± 18.2 years) were screened. After multiple imputation for missing BP readings, 34.6% had hypertension, only 56.7% of those with hypertension were aware, 21.2% of those not receiving treatment for hypertension were hypertensive, and a large proportion (42.5%) of individuals receiving antihypertensive medication had uncontrolled BP. These results suggest that opportunistic screening campaigns can identify significant numbers with undiagnosed and uncontrolled hypertension. The high proportions of individuals with undiagnosed and treated uncontrolled hypertension highlight the need for hypertension awareness campaigns and more rigorous management of hypertension.


Prevalence and growth kinetics of Shiga toxin-producing Escherichia coli (STEC) in bovine offal products in Japan.
Recent epidemiological data suggest a link between the consumption of bovine offal products and Shiga toxin-producing Escherichia coli (STEC) infection in Japan. This study thus examined the prevalence of STEC in various types of these foods. PCR screened 229 bovine offal products for the presence of Shiga toxin (stx) gene. Thirty-eight (16·6%) samples were stx positive, of which eight were positive for rfbE(O157) and three were positive for wzy(O26). Four O157 and one O26 STEC isolates were finally obtained from small-intestine and omasum products. Notably, homogenates of bovine intestinal products significantly reduced the extent of growth of O157 in the enrichment process compared to homogenates of beef carcass. As co-incubation of O157 with background microbiota complex from bovine intestinal products in buffered peptone water, in the absence of meat samples, tended to reduce the extent of growth of O157, we reasoned that certain microbiota present in offal products played a role. In support of this, inoculation of generic E. coli from bovine intestinal products into the homogenates significantly reduced the extent of growth of O157 in the homogenates of bovine intestinal and loin-beef products, and this effect was markedly increased when these homogenates were heat-treated prior to inoculation. Together, this report provides first evidence of the prevalence of STEC in a variety of bovine offal products in Japan. The prevalence data herein may be useful for risk assessment of those products as a potential source of human STEC infection beyond the epidemiological background. The growth characteristic of STEC O157 in offal products also indicates the importance of being aware when to test these food products.


A Study Correlating the Tumor Site and Size with the Level of Axillary Lymph Node Involvement in Breast Cancer.
Breast cancer is the leading cancer in women. The most common histologic type of breast cancer is infiltrating ductal carcinoma. The mainstay of the treatment of breast cancer is surgery when the tumor is localized, followed by chemotherapy as well as radiotherapy (when indicated) and in estrogen receptor and progesterone receptor positive tumors, adjuvant hormonal therapy. The aim of this study is to correlate tumor site and size with the level of axillary lymph node involvement (ALNI) in early and locally advanced breast cancer. This prospective and observational study was conducted on fifty female patients of carcinoma breast with early and locally advanced breast cancer. The age distribution showed two peaks at 41-50 years and 51-60 years with 42 and 24 patients, respectively, in both the age groups. Preoperative lymph node positivity by ultrasonography matched with postoperative histopathological examination (HPE) report. Preoperative ultrasonographically determined tumor size was similar to the final histopathological T stage. As size of tumor increases, there is an increase in ALNI which suggests that nodal metastasis is indicative of tumor chronology. Ultrasonography is a good tool to objectively measure tumor size and lymph node involvement preoperatively. Quadrant of involvement can emerge as a clinically useful prognostic cancer in breast cancer as there is a higher incidence of lymph node positivity with increasing size of the breast tumor and for tumors located at the upper outer quadrant of the breast.


PERson-centredness in hypertension management using information technology (PERHIT): a protocol for a randomised controlled trial in primary health care.
Purpose: For primary health care (PHC), hypertension is the number one diagnosis for planned health care visits. The treatment of high blood pressure (BP) and its consequences constitutes a substantial economic burden. In spite of efficient antihypertensive medications, a low percentage of patients reach a well-controlled BP. The PERson-centredness in Hypertension management using Information Technology (PERHIT) Study is a multicentre randomised controlled trial. PERHIT is designed to evaluate the effect of supporting self-management on systolic blood pressure by the use of information technology in Swedish primary health care.Materials and Methods: After inclusion, 900 patients from 36 PHC centres are randomised to two groups. In the intervention group, patients are provided with a self-management support system including a home-BP monitor and further requested to perform self-reports and measure BP every evening for eight consecutive weeks. In the control group, patients receive treatment as usual.Results: The primary outcome will be the change in systolic blood pressure in patients with hypertension. In addition, person-centredness, daily life activities, awareness of risk and health care costs will also be evaluated.Conclusion: The results of this randomised controlled trial with assessment of blood pressure and same-day self-reports will provide patients a tool to understand the interplay between blood pressure and lifestyle applicable to primary health care. The self-management support system may be of importance for improved adherence to treatment and persistence to treatment recommendations.


Common denominators in death from pediatric back-over trauma.
Low-speed "back-over" injuries comprise a small number of pediatric automobile versus pedestrian (AVP) trauma, however these injuries tend to be more severe and have a higher rate of mortality. The objective of this study was to determine environmental, mechanistic, and demographic factors common in pediatric back-over injuries resulting in death. Patients were identified from the trauma registry of an urban Level I trauma center over a 15-year period. Charts for all pediatric AVP injuries in ages 4 years and younger were reviewed. Mortalities due to back-over injuries were identified. For the study period reviewed (1995-2010) we identified 535 cases of auto versus pedestrian injury in children less than 4-years-old. Of these, 31 (5.79%) were mortalities. Among those 31 mortalities, six (19.3%) were identified as resulting from back-over trauma. Mean age was significantly lower in back-over injuries as compared with non back-over AVP trauma (1.33 ± 0.23 years, vs 3.5 ± 1.0 years, P = 0.001). We noted a trend toward female gender (67%) and Hispanic ethnicity (67%). All sustained massive blunt head trauma as the cause of death. There were no significant differences in Injury Severity Score or Revised Trauma Score in the back-over group. Environmental analysis revealed that cars were the perpetrating vehicle 50 per cent of the time, and sport utility vehicles, vans, or trucks 50 per cent of the time. In all cases, the accidents occurred in the patient's own driveway and by either a family member (67%) or acquaintance (33%). These data suggest that key characteristics of back-over trauma resulting in mortality include very young age, massive head trauma, injury occurring in the patient's own driveway, and with a family member or acquaintance behind the wheel. This may help identify points of injury prevention to decrease the number of victims of back-over trauma in the pediatric population.


Counseling athletes on the risk of chronic traumatic encephalopathy.
Chronic traumatic encephalopathy (CTE) is a rare progressive neurologic disorder that can manifest as a combination of cognitive, mood and behavioral, and neurologic symptoms. Despite clinically apparent symptoms, there is no imaging or other diagnostic test that can confirm diagnosis in living subjects. Diagnosis can only be confirmed postmortem by specific histopathologic features within the brain tissue identified on autopsy. CTE represents a unique tauopathy that is distinct from other neurodegenerative diseases. PubMed was searched from 1990 to 2013 for sport concussion and chronic traumatic encephalopathy. Articles were also identified from bibliographies of recent reviews and consensus statements. Clinical review. Level 5. Although CTE is postulated to occur as a result of repetitive mild traumatic brain injury, the specific etiology and risk factors have not yet been elucidated, and postmortem diagnosis makes causality difficult to determine. When counseling athletes and families about the potential association of recurrent concussions and the development of CTE, discussion of proper management of concussion is cornerstone. Unfortunately, to date, there is no equipment that can prevent concussions; however, rule changes and legislation may decrease the risk. It is imperative that return to play is medically supervised by a provider trained in the management of concussion and begins only once symptoms have resolved. In addition, athletes with permanent symptoms should be retired from contact sport.


Pathophysiology of Childhood-Onset Myasthenia: Abnormalities of Neuromuscular Junction and Autoimmunity and Its Background.
The pathophysiology of myasthenia gravis (MG) has been largely elucidated over the past half century, and treatment methods have advanced. However, the number of cases of childhood-onset MG is smaller than that of adult MG, and the treatment of childhood-onset MG has continued to be based on research in the adult field. Research on pathophysiology and treatment methods that account for the unique growth and development of children is now desired. According to an epidemiological survey conducted by the Ministry of Health, Labour and Welfare of Japan, the number of patients with MG by age of onset in Japan is high in early childhood. In recent years, MG has been reported from many countries around the world, but the pattern of the number of patients by age of onset differs between East Asia and Western Europe, confirming that the Japanese pattern is common in East Asia. Furthermore, there are racial differences in autoimmune MG and congenital myasthenic syndromes according to immunogenetic background, and their pathophysiology and relationships are gradually becoming clear. In addition, treatment options are also recognized in different regions of the world. In this review article, I will present recent findings focusing on the differences in pathophysiology.


Accurate processing and secretion in the baculovirus expression system of an erythroid-cell-stimulating factor consisting of a chimaera of insulin-like growth factor II and an insect insulin-like peptide.
A synthetic gene encoding the signal peptide and the N-terminal sequence of bombyxin, an insect insulin-like peptide, and the 58 amino acids of the C-terminal sequence of human insulin-like growth factor II (IGF II) has been expressed using the baculovirus system. This synthetic chimaera was obtained by amplification of four overlapping oligonucleotides using Taq polymerase and cloning into the transfer vector pBluebac. The construct was integrated by homologous recombination into the Autographa californica nuclear polyhedrosis genome. Spodoptera frugiperda Sf9 insect cells infected with the recombinant baculovirus secreted an accurately processed peptide consisting of the ten N-terminal amino acids of bombyxin and the 58 C-terminal amino acids of IGF II. The N-terminal glutamine of bombyxin was changed to asparagine to facilitate sequencing of the synthetic peptide. The chimaera was five times more potent than human recombinant IGF II in its capacity to stimulate thymidine incorporation into erythroid cells of fetal bovine liver in a serum-free medium. It stimulated erythroid colony formation in the presence of 2 microunits/ml erythropoietin in cells cultured over a monolayer of stromal cells of fetal liver. Artificial chimaeras as described here may prove useful for the production of insulin, IGF I and other peptides as secreted proteins in insect cells.


Distinct signals conveyed by pheromone concentrations to the mouse vomeronasal organ.
In mammalian species, detection of pheromone cues by the vomeronasal organ (VNO) at different concentrations can elicit distinct behavioral responses and endocrine changes. It is not well understood how concentration-dependent activation of the VNO impacts innate behaviors. In this study, we find that, when mice investigate the urogenital areas of a conspecific animal, the urinary pheromones can reach the VNO at a concentration of approximately 1% of that in urine. At this level, urinary pheromones elicit responses from a subset of cells that are tuned to sex-specific cues and provide unambiguous identification of the sex and strain of animals. In contrast, low concentrations of urine do not activate these cells. Strikingly, we find a population of neurons that is only activated by low concentrations of urine. The properties of these neurons are not found in neurons responding to putative single-compound pheromones. Additional analyses show that these neurons are masked by high-concentration pheromones. Thus, an antagonistic interaction in natural pheromones results in the activation of distinct populations of cells at different concentrations. The differential activation is likely to trigger different downstream circuitry and underlies the concentration-dependent pheromone perception.


Design for an aging brain.
Vaillancourt and Newell (Neurobiol. of Aging 2001) show that although many aging systems decrease in complexity as anticipated by Lipsitz and Goldberger (JAMA 1992), other aging systems increase in complexity. Vaillancourt and Newell explain the discrepancy by proposing that systems with a point attractor decrease in complexity with age, whereas those with an oscillating attractor increase in complexity with age. Vaillancourt and Newell are certainly correct that no one direction fits all results. Aging and death sometimes follow from a system being too simple, or, too complex. A perspective, based on the work of W. Ross Ashby (1956 and http://pespmc1.vub.ac.be/ASHBBOOK.html) is used in this commentary to consider why some systems become apparently more simple and others more complex as they age. In this Ashby-inspired view the measured complexity of a system's Responses to Disturbances is proportional to the ratio D/R, where D and R are sets containing the variety of possible disturbances and responses. The model expands on Ashby's by proposing that D consists of two components, Dp and Du. Dp consists of disturbances that are a function of the system's perception. Responses to Dp are often anticipatory and the response itself dominates the outcome. Du are disturbances that are unavoidable. Outcomes decrease or increase in measured entropy as a function of changes in (Dp + Du)/R. The variety of elements in both Dp and R decrease with age. When D/R decreases with age, the system shows less complexity. Conversely when D/R increases with Age, the results become more entropic.


Molecular epidemiology in cancer risk assessment and prevention: recent progress and avenues for future research.
Molecular epidemiology is increasingly being applied in studies of cancer risks derived from exposure to environmental carcinogens of both endogenous and exogenous origins. Analytical methods have been developed that are capable of detecting and quantifying levels of covalent adducts of several important classes of carcinogens with cellular DNA and blood proteins. Methods of sufficient sensitivity and specificity to detect ambient levels of exposure are in current use. These are being used in studies related to tobacco use (polycyclic aromatic hydrocarbons, aromatic amines, tobacco-specific nitrosamines); dietary exposures (aflatoxins, N-nitrosamines, heterocyclic amines); medicinal exposures (cisplatin, alkylating agents, 8-methoxypsoralen, ultraviolet photoproducts); occupational exposures (aromatic amines, polycyclic aromatic hydrocarbons, oxides of ethylene and styrene, and vinyl chloride); and oxidative damage (8-hydroxyguanine, thymine glycol). Methodologic improvements together with their expanded use in feasibility studies continue to produce results that support the validity of this approach for detecting and quantifying exposure to carcinogens. Genetic markers are also being used to detect early biological responses in efforts to link carcinogen exposure to initiating events in the carcinogenesis process. These include, in addition to traditional cytogenetic markers (e.g., chromosomal aberrations, sister chromatid exchange, micronuclei), other alterations in chromosomal structure such as restriction fragment length polymorphisms, loss of heterozygosity, and translocation markers. Specific genetic changes have recently been identified as critical molecular events in the initiation and development of many cancers. Important among these are activation of oncogenes, especially those of the ras family, and inactivation of tumor-suppressor genes (e.g., p53 and Rb) by point mutations and/or chromosomal deletions and other structural changes. Although some of these changes are known to occur in chemically induced tumors of experimental animals, the possible role of chemical carcinogens in the induction of genetic abnormalities in human cancers has yet to be determined. Continuing investigations employing the methods of molecular epidemiology promise to provide further evidence concerning these relationships. Future investigations employing newly developed molecular biological methods, in particular those based on polymerase chain reaction amplification of DNA, to identify alterations in DNA and chromosomal structure, combined with methods for characterizing exposure to carcinogens and early effects, have great potential for further elucidating the role of genotoxic agents in the etiology of human cancers and also for the development of strategies for their prevention.


Palestinian strategies, guidelines, and challenges in the treatment and management of coronavirus disease-2019 (COVID-19).
Coronavirus disease-2019 (COVID-19) outbreak is a global concern and the World Health Organization (WHO) has declared it as a Public Health Emergency of International Concern. The Palestinian Authority (PA) has quickly and effectively responded to the outbreak of COVID-19, using an internationally and nationally coordinated, to contain the spread of the virus within the borders. The PA approaches are containment and suppression, which is designed to protect the citizens from infection while also mitigating the stress on the health care system. The PA immediately declared a State of Emergency when the first cases in Palestine were diagnosed on 5 March 2020 and launched robust national containment measures to encourage the citizens to protect themselves and follow the guidance. There is currently no vaccine or effective treatment for COVID-19, the treatment is either supportive and/ or the treatment of symptoms. Several strategies in the treatment of the disease were applied including medications. This review aims to summarize the different strategies, guidelines, challenges, and treatments used against COVID-19 worldwide and in Palestine. Different literature and guidelines among different databases were searched. Literature reviewing was conducted using the following search engines, Google Scholar, Medline, Pub Med, EMBASE, Web of Science, and Science Direct. Data also obtained from WHO and PA reports, and the published peer-reviewed articles of 2019-nCoV. The review focuses on the strategies, guidelines, therapeutics, challenges, and different approaches used in the treatment and management of the disease in Palestine and globally. The Palestinian Ministry of Health (MoH) strategies to end the COVID-19 pandemic were; slow and stop transmission; provide optimized care for patients; and minimize the impact of the epidemic on health systems, social services, and economic activity. Thus, proper management, right actions, and effective treatment of the disease should be considered to achieve these strategies. The biggest problem for PA to control and stop the outbreak of the disease is the different challenges which include; the Israeli military and economic control, uncontrol the borders, shortage of medical and financial resources, crowded cities and refugee camps, poverty, food insecurity, and the financial crisis. To date, there are no specific vaccines or medicines for COVID-19; and treatments are under investigation through clinical trials. However, an array of drugs approved for other indications, as well as multiple investigational agents, are being studied for the treatment of COVID-19; in several hundred clinical trials around the World. Treatment is essentially supportive and symptomatic.


The association between cannabis use and outcome in pharmacological treatment for opioid use disorder.
With the ongoing opioid crisis and policy changes regarding legalization of cannabis occurring around the world, it is necessary to consider cannabis use in the context of opioid use disorder (OUD) and its treatment. We aimed to examine (1) past-month cannabis use in patients with OUD, (2) self-reported cannabis-related side effects and craving, and (3) the association between specific characteristics of cannabis use and opioid use during treatment in cannabis users. Participants receiving pharmacological treatment for OUD (n = 2315) were recruited from community-based addiction treatment clinics in Ontario, Canada, and provided information on past-month cannabis use (self-report). Participants were followed for 3 months with routine urine drug screens in order to assess opioid use during treatment. We used logistic regression analysis to explore (1) the association between any cannabis use and opioid use during treatment, and (2) amongst cannabis-users, specific cannabis use characteristics associated with opioid use. Qualitative methods were used to examine responses to the question: "What effect does marijuana have on your treatment?". Past-month cannabis use was reported by 51% of participants (n = 1178). Any cannabis use compared to non-use was not associated with opioid use (OR = 1.03, 95% CI 0.87-1.23, p = 0.703). Amongst cannabis users, nearly 70% reported daily use, and half reported experiencing cannabis-related side effects, with the most common side effects being slower thought process (26.2%) and lack of motivation (17.3%). For cannabis users, daily cannabis use was associated with lower odds of opioid use, when compared with occasional use (OR = 0.61, 95% CI 0.47-0.79, p < 0.001) as was older age of onset of cannabis use (OR = 0.97, 95% CI 0.94, 0.99, p = 0.032), and reporting cannabis-related side effects (OR = 0.67, 95% CI 0.51, 0.85, p = 0.001). Altogether, 75% of cannabis users perceived no impact of cannabis on their OUD treatment. Past-month cannabis use was not associated with more or less opioid use during treatment. For patients who use cannabis, we identified specific characteristics of cannabis use associated with differential outcomes. Further examination of characteristics and patterns of cannabis use is warranted and may inform more tailored assessments and treatment recommendations.


An olecranon chondral flap and osteochondral coronoid fracture in a spontaneously reduced elbow dislocation in a child.
Elbow injuries in children are very common and radiographs are often difficult to interpret because of the radiolucency of the cartilaginous anlage and the progressive appearance of multiple secondary ossification centres. Elbow dislocations are rare injuries in children. Coronoid fractures can occur during dislocation or relocation of the elbow and can be the only hallmark of a severe injury. The understanding of the mechanics of these injuries has undergone considerable evolution over the past decade. Intra-articular chondral flap fractures are a traumatic elevation of the hyaline cartilage from the subchondral bone. They are also rare injuries in children but should be included in the differential when examining an injured joint. The infrequency of these injuries provides little opportunity to become accustomed to the radiographic signs. We present a case report of a 4-year-old boy with both an olecranon chondral flap and coronoid cartilaginous fracture after a joint dislocation. We present his plain radiography and MRI with illustrated photographic records of the operative findings. This injury has been little described in the literature and never with such imaging to aid understanding of both the pathology and the injury mechanism.


Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro.
Leptin, the product of ob gene, is an endocrine hormone that regulates adipose tissue mass. Recently, leptin has been found to generate a growth signal involving a tyrosine kinase-dependent intracellular pathway and promote angiogenic processes via activation of leptin receptor (Ob-R) in endothelial cells. However, it is not clear how leptin functions to promote multi-step processes involved in the neovascularization at the atherosclerotic plaque. We have examined the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and Ob-R in human atherosclerotic lesions, leptin-mediated angiogenesis in vivo and in vitro. Immunohistochemical analysis of human atherosclerotic aorta revealed an increased expression of Ob-R in the intima of neorevascularized regions and of both MMPs and TIMPs predominantly in the endothelial lining of intimal neovessels and macrophages/foam cells. In the rat corneal angiogenesis assay, leptin elicited a comparable sensitivity of angiogenic activity to those of vascular endothelial growth factor (VEGF). The immunohistological analysis of the leptin-treated rat cornea showed definitive rises in Ob-R, MMPs and TIMPs expression as well as those of VEGF receptor (VEGFR-1). Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) and elevation of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression in a dose-dependent manner. Leptin also induced increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery smooth muscle cells (HCASMCs). These findings suggest that leptin, a hormone with pluralistic properties including a mitogenic activity on vascular endothelial cells, plays a role in matrix remodeling by regulating the expression of MMPs and TIMPs. Taken together, our findings further provide evidences for leptin's role as an angiogenesis inducer in the normal organ (rat cornea) and in aberrant vasculature under duress like atherosclerosis.


Load Transfer Characteristics of Various Designs of Three-Implant-Retained Mandibular Overdentures.
Many different attachment systems (eg, bars, studs, magnets, telescopic copings) have been used to retain overdentures. The current study aimed to investigate the load transfer characteristics and to compare the stress levels of four attachment designs for mandibular overdentures retained by one central implant and two inclined distal implants. Photoelastic mandibular models fabricated with three screw-type implants (Tapered Screw-Vent, 3.75 × 13 mm) were placed in the parasymphyseal area. The center implant was vertically oriented to the midline, and the other implants were embedded in the canine areas with a 20-degree angulation relative to the center implant. Four overdentures with different attachment designs (bar, bar/ball, bar/distally placed Rk-1s, and Locators) were studied in the context of this model. Vertical loads (100 N) were applied to the central fossa of the right first molar area of each overdenture. Stress levels that developed in the denture-bearing areas and around the implants were observed photoelastically and evaluated visually. The studied attachment designs showed low and moderate stress levels. The greatest stress was found with the bar/ball design, while the lowest stress levels were observed with the Locator attachment design. Stresses were concentrated on the loaded side for each design. All tested designs experienced moderate stress around the posterior edentulous area. None of the designs experienced more than moderate stress. The lowest stress was noted with the Locator attachments, which transmitted little discernible stress around the implants.


Linking Self-Control, Hope, Positivity Ratio, Anxiety and Handwashing Habits during the Coronavirus Outbreak.
The novel COVID-19 is an infectious disease caused by the coronavirus. In the early stages of the pandemic, Israel struggled to contain its local outbreak through various measures that have virtually halted daily life and placed tens of thousands of people into quarantine. This study explored the role played by self-control and hope for obtaining two desired outcomes: (1) maintaining one's positivity ratio (having more positive than negative affect-an indicator of wellbeing) and (2) increasing one's contagion-preventing behavior (in this study-handwashing habits). Path analysis was conducted using survey data collected from 537 Israeli adults. Our findings suggest that self-control's association with the positivity ratio is mediated through hope and anxiety levels. Self-control positively correlates with hope levels and negatively correlates with anxiety levels. Higher hope levels correlate with a higher positivity ratio, while lower anxiety levels correlate with a higher positivity ratio. The relationship between self-control and handwashing habits was mediated by hope, anxiety, and existing handwashing habits. This study brings research a step forward in demonstrating the vital role of positive components in achieving desired psychological and behavioral outcomes during an anxiety-provoking epidemic outbreak. In addition to its theoretical innovation, the importance of this study lies in its practical value: We focus on variables that are influenced by policy, education, and communication.


Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers are still needed. Methylation of the death associated protein kinase (DAPK or DAPK1) gene and TP53 mutations are likely to have prognostic value in DLBCL. We have assessed TP53 mutations and allelic DAPK1 methylation patterns in a cohort of 119 DLBCL patients uniformly treated with R-CHOP-like regimens. We found that DAPK1 promoter methylation was associated with shorter overall survival (p=0.017) and disease-specific survival (p=0.023). In multivariate analyses DAPK1 methylation remained as an independent prognostic factor predicting disease-specific survival (p=0.038). When only considering individuals heterozygous for the rs13300553 SNP monoallelic methylation of the A-allele was associated with shorter overall- and disease-specific survival (p<0.001). Patients carrying both DAPK1 methylation and a TP53 mutation had an inferior survival compared to patients carrying only one of these molecular alterations, however, this was borderline statistically significant. Allele-specific DAPK1 methylation patterns were also studied in a cohort of 67 multiple myeloma patients, and all of the methylated multiple myeloma samples heterozygous for the rs13300553 SNP were methylated on both alleles.


Musculoskeletal problems and quality of life of elementary school teachers.
To investigate prevalence and anatomical distribution of musculoskeletal pain (MSP) and its impact on quality of life (QoL) in elementary school teachers working in Muğla town center. Physical, sociodemographic and occupational characteristics of 104 teachers were recorded. Onset, prevalence and consequences of MSP (Extended Nordic Musculoskeletal Questionnaire) and QoL (Short Form-36 Health Survey) of teachers with (n = 37) and without (n = 67) MSP during the last 12 months were compared. The prevalence of MSP was 77% for the lifelong period and 36% for the last 12 months. Physical and sociodemographic characteristics, daily employment period and length of standing and sitting were similar between groups (p > 0.05). The most common painful regions were the neck (39%) and the lower back (38%). MSP of these regions was the common reason for seeking healthcare, prevention from activities and taking sick leave. MSP had negative impact, especially on the physical components of QoL (p < 0.05). The results reveal high prevalence of MSP among teachers, as well as its negative impacts on QoL. Especially neck and lower back seem to be the most frequently affected regions of the body. These findings draw attention toward the need for developing strategies to prevent MSP among teachers.


Causes of cancer and cancer prevention.
Current understanding of the complex processes of cancer causation through a study of the mechanisms of carcinogenesis have documented that there are several major steps each, with distinct quantitative risk assessment factors. The first series of steps, defined by genotoxicity, deal with the assessment of the type of genotoxic carcinogen and its metabolism, leading to a DNA- and macromolecular-reactive species. A second area concerns the rate of cell duplication, important in leading to cell transformation to an early neoplastic state. The third key area explores agents that bear on a further development and growth of the transformed cells, an area that has quite distinct dose-response relationships from the first type. Therefore, modulation of the third area provides excellent means of control. In addition, of course, the optimal means is avoiding exposure to genotoxic carcinogens.


Trans-sodium crocetinate for treating hypoxia/ischemia.
Trans-sodium crocetinate (TSC) is a novel compound that offers promise as a treatment for conditions caused by hypoxia or ischemia. TSC was originally developed at the University of Virginia for hemorrhagic shock, as part of the battlefield casualty program sponsored by the US Office of Naval Research. Animal toxicology studies have demonstrated that high levels of TSC are well-tolerated, and a Phase I clinical study has shown that TSC is also safe in humans. The drug acts via a mechanism that has not been previously exploited in a pharmaceutical. TSC increases the rate of oxygen diffusion between the erythrocytes and the tissues by altering the 'structure' of water in blood plasma. It does this by causing additional hydrogen bonds to form among the water molecules. Further development of TSC for hemorrhagic shock and other hypoxic/ischemic conditions is being done by Diffusion Pharmaceuticals LLC.


RNA Helicase A Is an Important Host Factor Involved in Dengue Virus Replication.
Dengue virus (DENV) utilizes host factors throughout its life cycle. In this study, we identified RNA helicase A (RHA), a member of the DEAD/H helicase family, as an important host factor of DENV. In response to DENV2 infection, nuclear RHA protein was partially redistributed into the cytoplasm. The short interfering RNA-mediated knockdown of RHA significantly reduced the amounts of infectious viral particles in various cells. The RHA knockdown reduced the multistep viral growth of DENV2 and Japanese encephalitis virus but not Zika virus. Further study showed that the absence of RHA resulted in a reduction of both viral RNA and protein levels, and the data obtained from the reporter replicon assay indicated that RHA does not directly promote viral protein synthesis. RHA bound to the DENV RNA and associated with three nonstructural proteins, including NS1, NS2B3, and NS4B. Further study showed that different domains of RHA mediated its interaction with these viral proteins. The expression of RHA or RHA-K417R mutant protein lacking ATPase/helicase activity in RHA-knockdown cells successfully restored DENV2 replication levels, suggesting that the helicase activity of RHA is dispensable for its proviral effect. Overall, our work reveals that RHA is an important factor of DENV and might serve as a target for antiviral agents.IMPORTANCE Dengue, caused by dengue virus, is a rapidly spreading disease, and currently there are no treatments available. Host factors involved in the viral replication of dengue virus are potential antiviral therapeutic targets. Although RHA has been shown to promote the multiplication of several viruses, such as HIV and adenovirus, its role in the flavivirus family, including dengue virus, Japanese encephalitis virus, and emerging Zika virus, remains elusive. The current study revealed that RHA relocalized into the cytoplasm upon DENV infection and associated with viral RNA and nonstructural proteins, implying that RHA was actively engaged in the viral life cycle. We further provide evidence that RHA promoted the viral yields of DENV2 independent of its helicase activity. These findings demonstrated that RHA is a new host factor required for DENV replication and might serve as a target for antiviral drugs.


Anion exchange pathways for Cl- transport in rabbit renal microvillus membranes.
We evaluated the mechanisms of chloride transport in microvillus membrane vesicles isolated from the rabbit renal cortex. The presence of Cl-formate exchange was confirmed. Outward gradients of oxaloacetate, HCO3, acetate, lactate, succinate, sulfate, and p-aminohippurate (PAH) stimulated the rate of Cl uptake minimally (less than 25%) or not at all. However, an outward gradient of oxalate stimulated Cl uptake by 70%, and an outward Cl gradient induced uphill oxalate uptake, indicating Cl-oxalate exchange. Moreover, an outward formate gradient induced uphill oxalate uptake, indicating formate-oxalate exchange. Studies of inhibitor and substrate specificity indicated the probable operation of at least two separate anion exchangers in mediating Cl transport. The Cl-formate exchanger accepted Cl and formate as substrates, had little or no affinity for oxalate, was sensitive to inhibition by furosemide, and was less sensitive to inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The Cl (formate)-oxalate exchanger also accepted Cl and formate as substrates but had high affinity for oxalate, was highly sensitive to inhibition by DIDS, and was less sensitive to inhibition by furosemide. The Cl-formate exchanger was electroneutral, whereas the Cl (formate)-oxalate exchanger was electrogenic. We conclude that at least two separate anion exchangers mediating Cl transport are present on the luminal membrane of the rabbit proximal tubule cell. These exchangers may play important roles in mediating transtubular Cl and oxalate transport in this nephron segment.


The influence of a vibrotactile biofeedback system on postural dynamics during single-leg standing in healthy older adults.
The effectiveness of sensory substitution technology, such as haptic-based vibrotactile biofeedback (VBF), has been verified for balance training and rehabilitation. However, whether VBF training changes postural dynamics in older people remains unknown. This study investigated the influence of VBF training on postural dynamics during single-leg standing in older adults, using detrended fluctuation analysis (DFA). Twenty older adults participated in this study. Measurement of postural sway comprised three phases: first measurement session as a baseline test, postural training (day 1), and second measurement session (day 2). The BF group received BF training during the balance training session, while the control group practiced single-leg stance without BF. The center of pressure (CoP) trajectory was recorded in the first measurement session (pre) and second measurement session (post) at 50 Hz. DFA revealed the presence of two linear scaling regions in the CoP, indicating the presence of fast- and slow-scale fluctuations. For the BF group, slow-scale postural dynamics revealed more anti-persistent behavior after training in the anterior-posterior direction. However, the control group showed a change toward more random dynamics after training. These different influences suggest that the BF system might improve error correction strategies during single-leg standing for older adults, while single-leg standing training without the BF system might cause the loss of controllability in single-leg standing. Further, the results of the DFA are discussed in the context of balance training using VBF.


The cell biology of MHC class I antigen presentation.
MHC class I antigen presentation refers to the co-ordinated activities of many intracellular pathways that promote the cell surface appearance of MHC class I/beta2m heterodimers loaded with a spectrum of self or foreign peptides. These MHC class I peptide complexes form ligands for CD8 positive T cells and NK cells. MHC class I heterodimers are loaded within the endoplasmic reticulum (ER) with peptides derived from intracellular proteins. Alternatively, MHC class I molecules may be loaded with peptides derived from extracellular proteins in a process called MHC class I cross presentation. This pathway is less well defined but can overlap those pathways operating in classical MHC class I presentation and has recently been reviewed elsewhere (1). This review will address the current concepts regarding the intracellular assembly of MHC class I molecules with their peptide cargo within the ER and their subsequent progress to the cell surface.


Utilization and Determinants of Postnatal Care Services in Ethiopia: A Systematic Review and Meta-Analysis.
Postnatal care use is vital in saving mother and newborn lives which is a continuum of care for maternal, neonatal and child health. This review aimed to determine the utilization and determinants of postnatal care use in Ethiopia. PubMed, Scopus, Web of Science, and Embase databases were searched on June 25, 2017. The study screening, data extraction and quality assessment were done independently by two reviewers. Effect sizes were pooled using a random-effects model. Nine articles were included in the review. The pooled estimate for utilization of the service was 32% (95% CI: 21%, 43%). The pooled results of determinants of postnatal care use was statistically significant among those mothers who had ability to make decisions (1.89; 1.25, 2.54), had a history of antenatal care utilization (2.55; 1.42, 3.68), received more than two antenatal care visits (1.84; 1.28, 2.40), and received the service from skilled service provider (3.16; 1.62, 4.70). It was also found that mothers who gave birth in health faciliteis (2.13; 1.14, 3.12), had middle monthly income, richer, were from urban areas, and had knowledge of obstetric danger signs were significantly associated with increased odds of postnatal care use. Utilization of the services is low in Ethiopia. Antenatal care utilization, skilled service provider, being from urban area and delivery in health facility had a significant effect on postnatal care utilization. More rigorous studies are needed to identify determinant with the causal association to postnatal care utilization. The review was registered on PROSPERO CRD42017060266.


Targeting host calpain proteases decreases influenza A virus infection.
Influenza A viruses (IAV) trigger contagious acute respiratory diseases. A better understanding of the molecular mechanisms of IAV pathogenesis and host immune responses is required for the development of more efficient treatments of severe influenza. Calpains are intracellular proteases that participate in diverse cellular responses, including inflammation. Here, we used in vitro and in vivo approaches to investigate the role of calpain signaling in IAV pathogenesis. Calpain expression and activity were found altered in IAV-infected bronchial epithelial cells. With the use of small-interfering RNA (siRNA) gene silencing, specific synthetic inhibitors of calpains, and mice overexpressing calpastatin, we found that calpain inhibition dampens IAV replication and IAV-triggered secretion of proinflammatory mediators and leukocyte infiltration. Remarkably, calpain inhibition has a protective impact in IAV infection, since it significantly reduced mortality of mice challenged not only by seasonal H3N2- but also by hypervirulent H5N1 IAV strains. Hence, our study suggests that calpains are promising therapeutic targets for treating IAV acute pneumonia.


Rab11 regulates cell-cell communication during collective cell movements.
Collective cell movements contribute to development and metastasis. The small GTPase Rac is a key regulator of actin dynamics and cell migration but the mechanisms that restrict Rac activation and localization in a group of collectively migrating cells are unknown. Here, we demonstrate that the small GTPases Rab5 and Rab11 regulate Rac activity and polarization during collective cell migration. We use photoactivatable forms of Rac to demonstrate that Rab11 acts on the entire group to ensure that Rac activity is properly restricted to the leading cell through regulation of cell-cell communication. In addition, we show that Rab11 binds to the actin cytoskeleton regulator Moesin and regulates its activation in vivo during migration. Accordingly, reducing the level of Moesin activity also affects cell-cell communication, whereas expressing active Moesin rescues loss of Rab11 function. Our model suggests that Rab11 controls the sensing of the relative levels of Rac activity in a group of cells, leading to the organization of individual cells in a coherent multicellular motile structure.


[Tuberculous epiglotittis, an atypical form of laryngeal tuberculosis. Presentation of a case and revision of litterature].
An important arousal of tuberculosis has been observed in the last years, together with a change in it's clinical patterns, specially the extrapulmonar form, among wich is this laryngeal tuberculosis. This two facts and the marked polymorphism and mimetism proper of this condition may suggest that the Mycobacterium tuberculosis should be included in the differential diagnosis of any atypical lesion of the larynx, in order to obtain an earlier diagnosis excluding carcinoma and instaurate a chimotherapic protocol for minimizing or even avoiding any sequelae. Tuberculous epiglotittis is one of these atypical and unusual forms. The authors report a case of a 67 year-old male and provide a discussion on the diagnostic problems of this condition.


Histopathology of Red Tattoo Reactions.
Despite popularity of tattoos, complications may occur. In particular, red tattoo reactions due to allergic reactions are the most frequent chronic tattoo reactions. However, little is known about its histopathology and underlying pathomechanisms. The aim of this article is to analyze the histopathology of red tattoo reactions for diagnostic purposes and to acquire more insight into pathogenesis. A retrospective cross-sectional study was conducted by reviewing the histopathology of 74 skin biopsies of patients with allergic red tattoo reactions. Histopathological findings, such as inflammation patterns, inflammatory cells and pigment depth and color, were semi-quantified with an in-house validated scoring system by 2 independent senior investigators. Histiocytes and lymphocytes were both present in >93%. Histiocytes were the predominant inflammatory cells in 74.3%, but well-defined granulomas were mostly absent (78.0%). Eosinophils were uncommon (8.1%) The predominantly histiocytic reaction combined with interface dermatitis was the main inflammation pattern (37.9%). Most biopsies showed more than one reaction pattern. Interface involvement was observed in 64.8%, despite the intended depth of standard tattoo procedures, in which pigment is placed deeper, in the upper- and mid-dermis. Statistical analyses showed a significant association between inflammation severity and pigment depth (P = 0.024). In 6 cases (8.1%) pigments could not be retrieved histologically. In this cohort we demonstrated that cutaneous reactions to red tattoo ink are frequently characterized by the combination of dermal predominantly histiocytic infiltrates and epidermal interface dermatitis. Allergic reactions to red tattoo pigments probably represent a combination of a subtype IVa and IVc allergic reaction. Clinicians should be aware of the specific histopathology of these reactions and therefore the importance of taking a diagnostic skin biopsy.


Conceptualizing resilience in adult mental health literature: A systematic review and narrative synthesis.
This review aims to identify how the term 'resilience' is conceptualized across adult mental health research due to ongoing criticism regarding the lack of consistency in its conceptualization. A systematic search, including hand searches of book chapters, was conducted using search terms ('resilien*') AND ('mental illness' OR 'mental health problem'). Papers were excluded if they did not meet the following criteria: written in English, provide a clear conceptualization of resilience, include only adults (aged 18 + ) in the sample, solely focus on individuals with a primary diagnosis of mental illness, and peer-reviewed. Data were extracted on conceptualizations of resilience, demographic, and diagnostic variables of the study population, publication year, and the research design used. Conceptualizations were combined and collapsed into overarching themes and then refined through joint discussion, consultation with a third reviewer, and input from a larger multidisciplinary team. Thirty-one texts (6 book chapters, 4 reviews, 2 appraisals/critical evaluations, 1 editorial, and 18 research projects) were included. Two broad understandings of resilience were identified: resilience as a process and resilience as a characteristic of an individual. Processes comprise three themes: 'immunity', 'bouncing back', and 'growth', whilst characteristics are captured in two themes 'personal resources' and 'social resources'. These findings suggest that resilience can be conceptualized in a clear and meaningful manner in adult mental health research. The five themes reflect distinct ways of using the term resilience. Whilst each one of them may have merit in future research, it appears beneficial to make clear in research which exact conceptualization of resilience has been adopted. When considering and reading about 'resilience', one should be aware that there are different concepts of it. The main difference is between resilience as a personal characteristic and resilience as a process. Therapy may address resilience as a personal characteristic by utilizing individual and social resources. The therapeutic process may be understood as resilience in form of bouncing back and personal growth.


Decreased uptake of exogenous substrates following graded muscle stimulation.
An exercising in vivo canine hindlimb model was used to assess the pattern of exogenous substrate delivery and uptake as a function of contraction frequency. The limb was stimulated to contract at 0, 4, 8, 12 8, 4, and 0 Hz for 10-min periods. Blood flow was proportional to stimulatory frequency. Oxygen consumption increased to a maximum at 12 Hz and subsequently declined. Glucose, free fatty acid, and lactate uptakes decreased despite increased deliveries and maintained arterial concentrations at 12 Hz. At this point there was a net release of glycerol and lactate from the muscle. Microvascular shunting was not the cause of decreased exogenous substrate uptake at 12 Hz. A switch from exogenous to endogenous muscle substrates occurred with the onset of decreased substrate uptake. The mechanism that facilitates this switch from exogenous to endogenous substrates remains unknown.


Aspermerodione, a novel fungal metabolite with an unusual 2,6-dioxabicyclo[2.2.1]heptane skeleton, as an inhibitor of penicillin-binding protein 2a.
Rising drug resistance limits the treatment options infected by methicillin-resistant Staphylococcus aureus (MRSA). A promising solution for overcoming the resistance of MRSA is to inhibit the penicillin-binding protein 2a (PBP2a). A novel terpene-polyketide hybrid meroterpenoid, aspermerodione (1), characterized by an unusual 2,6-dioxabicyclo[2.2.1]heptane core skeleton, and a new heptacyclic analogue, andiconin C (2), were isolated and identified from the liquid cultures of endophytic fungus Aspergillus sp. TJ23. The structures and their absolute configurations of all chiral centers were elucidated via extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations and determined via single-crystal X-ray diffraction analysis. Aspemerodione (1) was found to be a potential inhibitor of PBP2a, and work synergistically with the β-lactam antibiotics oxacillin and piperacillin against MRSA.


The prevalence of diabetes amongst young Emirati female adults in the United Arab Emirates: A cross-sectional study.
The prevalence of type 2 diabetes is rapidly increasing in the United Arab Emirates (UAE). The purpose of this study was to investigate the prevalence of prediabetes and diabetes using FPG and HbA1c and to examine their relationships with obesity and other risk factors in young female Emirati college students. In this cross-sectional study we recruited 555 female college students aged 17-25, enrolled at United Arab Emirates University in Al Ain, UAE. Anthropometric analysis, blood pressure, and various biochemical markers were measured using standard methods. Type 2 Diabetes, impaired fasting plasma glucose (FPG), and elevated HbA1c levels were examined in the study population as per the standards of medical care in diabetes, set out by the American Diabetes Association in 2020. Based on the HbA1c test, the prevalence of pre-diabetes and diabetes were 24% and 8.6%, respectively. Based on the FPG test, the prevalence of pre-diabetes and diabetes were 9.2% and 0.5%, respectively. The kappa statistic of concordance between HbA1c and FPG was 0.287, P < 0.001. Abnormal glycemic status was significantly associated with decreased high-density lipoprotein (HDL) level (< 50 mg/dl) (p = 0.002) and elevated high-sensitivity C-reactive protein (Hs-CRP) level (≥ 2.0 mg/L) (P < 0.001). Using FPG to evaluate glycemic control seems to underestimate the burden of undiagnosed diabetes which could have a significant impact on clinical practice. Our data indicates an association between abnormal glycemic status with HDL and Hs-CRP. Further evaluation is needed to assess the impact of using HbA1c as a diagnostic test for diabetes in the UAE.


Binding of gelatinases A and B to type-I collagen and other matrix components.
Matrix sequestration of matrix metalloproteinases may be important for the facilitation of remodelling events and the migration of cells through the extracellular matrix. Using an ELISA technique we studied the ability of pro and active forms of gelatinases A and B (GLA and GLB) to bind to matrix components and the contribution made by the different enzyme domains. Pro and active forms of GLA and GLB bound to type-I and type-IV collagens, gelatin and laminin films. Binding to collagens occurred exclusively via the N-terminal portion of the molecule in both of the gelatinases; deletion of the fibronectin-like domain in GLA abolished binding. Fibronectin was shown to compete with GLA, confirming that binding occurs through this domain. GLA and GLB competed for binding to collagen type I, whereas collagenase and stromelysin bound to different sites and could be co-localized with the gelatinases. We conclude that gelatinases have different binding specificities from those previously documented for stromelysin and collagenase, which bind through their C-terminal domains to collagen fibrils.


Protection from nitrosative stress: a central role for microbial flavohemoglobin.
Nitric oxide (NO) is an inevitable product of life in an oxygen- and nitrogen-rich environment. This reactive diatomic molecule exhibits microbial cytotoxicity, in large part by facilitating nitrosative stress and inhibiting heme-containing proteins within the aerobic respiratory chain. Metabolism of NO is therefore essential for microbial life. In many bacteria, fungi, and protozoa, the evolutionarily ancient flavohemoglobin (flavoHb) converts NO and O(2) to inert nitrate (NO(3)(-)) and undergoes catalytic regeneration via flavin-dependent reduction. Since its identification, widespread efforts have characterized roles for flavoHb in microbial nitrosative stress protection. Subsequent genomic studies focused on flavoHb have elucidated the transcriptional machinery necessary for inducible NO protection, such as NsrR in Escherichia coli, as well as additional proteins that constitute a nitrosative stress protection program. As an alternative strategy, flavoHb has been heterologously employed in higher eukaryotic organisms such as plants and human tumors to probe the function(s) of endogenous NO signaling. Such an approach may also provide a therapeutic route to in vivo NO depletion. Here we focus on the molecular features of flavoHb, the hitherto characterized NO-sensitive transcriptional machinery responsible for its induction, the roles of flavoHb in resisting mammalian host defense systems, and heterologous applications of flavoHb in plant/mammalian systems (including human tumors), as well as unresolved questions surrounding this paradigmatic NO-consuming enzyme.


Knowledge, attitudes, and practices (KAP) toward seasonal influenza vaccine among college students under the COVID-19 pandemic in South China.
The control measures of the coronavirus disease 2019 (COVID-19) pandemic had influenced the activity of the influenza virus, and we were wondering the knowledge, attitudes, and practices (KAP) toward seasonal influenza vaccine among college students were having at the context of the COVID-19 pandemic. Online questionnaire survey of the college students was conducted and the data was collected anonymously, cross-sectional study were used to describe the distribution of the KAP. There were 815 respondents in our study. Most participants have a high recognition of the effectiveness and safety of the influenza vaccine. However, a low awareness rate of influenza vaccine knowledge and vaccination rate (18%) against influenza was observed among college students. The education level and major would have a higher weight on the influence of KAP among the college students. Binary logistic regression analysis showed that the sex (OR = 2.163, p < .001), age (OR = 2.242, p < .001), heard of the influenza vaccine (OR = 2.655, p = .014), and "How necessary do you think vaccinating every year is?" (OR = 3.947, p < .001) of the college students were the main factors that affect the KAP on influenza vaccination. Our study provided an insight into the KAP of influenza vaccine among college students in South China. The vaccination rate and acceptability of influenza vaccine in college students are higher than that in the whole population.


Vaccination against Klebsiella aerogenes.
Klebsiella vaccine was prepared from strains of Klebsiella aerogenes with capsular types K1, K36, K44 and K Cross (a type which cross-reacts in vitro with sera from many klebsiella capsular types). The vaccine was extracted by dialysis and ultrafiltration from capsular material released during growth of the bacteria in a five-day batch culture. Mice given one dose of vaccine from K1a (1.0 microgram/mouse) survived lethal intraperitoneal challenge of 11/11 homologous klebsiella strains four days after vaccination; 14 days after vaccination protection against the same challenge strains had declined to 5/11 strains. Vaccines from K1a, b, c, K36, K44 and K Cross induced homologous protection and protected mice against different ranges of heterologous klebsiella capsular types. The protective response of the mice was greatly enhanced by administering three doses of the vaccines. Vaccines from K1, K36, K44 and K Cross protected mice against 14/20, 11/20, 10/20 and 9/20 homologous and heterologous klebsiella challenge strains respectively. None of the klebsiella vaccines was toxic for mice at the immunizing dose (1.0 microgram/mouse). Vaccine from K36 was the most lethal, killing mice at 10(3) immunizing doses. The least toxic vaccine was from K44, which killed mice at 10(4) immunizing doses.


Tracing the trans-pacific evolutionary history of a domesticated Seaweed (Gracilaria chilensis) with archaeological and genetic data.
The history of a domesticated marine macroalga is studied using archaeological, phylogeographic and population genetic tools. Phylogeographic and population genetic analyses demonstrated that the cultivated red alga Gracilaria chilensis colonised the Chilean coast from New Zealand. Combining archaeological observations with phylogeographic data provided evidence that exchanges between New Zealand and Chile have occurred at least before the Holocene, likely at the end of the Last Glacial Maximum (LGM) and we suggest that migration probably occurred via rafting. Furthermore, the remarkably low microsatellite diversity found in the Chilean populations compared to those in New Zealand is consistent with a recent genetic bottleneck as a result of over-exploitation of natural populations and/or the process of domestication. Therefore, the aquaculture of this seaweed, based essentially on clonal propagation, is occurring from genetically depressed populations and may be driving the species to an extinction vortex in Chile.


Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects.
The number of mouse mutants and strains with neural tube closure defects (NTDs) now exceeds 190, including 155 involving known genes, 33 with unidentified genes, and eight "multifactorial" strains. The emerging patterns of mouse NTDs are considered in relation to the unknown genetics of the common human NTDs, anencephaly, and spina bifida aperta. Of the 150 mouse mutants that survive past midgestation, 20% have risk of either exencephaly and spina bifida aperta or both, parallel to the majority of human NTDs, whereas 70% have only exencephaly, 5% have only spina bifida, and 5% have craniorachischisis. The primary defect in most mouse NTDs is failure of neural fold elevation. Most null mutations (>90%) produce syndromes of multiple affected structures with high penetrance in homozygotes, whereas the "multifactorial" strains and several null-mutant heterozygotes and mutants with partial gene function (hypomorphs) have low-penetrance nonsyndromic NTDs, like the majority of human NTDs. The normal functions of the mutated genes are diverse, with clusters in pathways of actin function, apoptosis, and chromatin methylation and structure. The female excess observed in human anencephaly is found in all mouse exencephaly mutants for which gender has been studied. Maternal agents, including folate, methionine, inositol, or alternative commercial diets, have specific preventative effects in eight mutants and strains. If the human homologs of the mouse NTD mutants contribute to risk of common human NTDs, it seems likely to be in multifactorial combinations of hypomorphs and low-penetrance heterozygotes, as exemplified by mouse digenic mutants and the oligogenic SELH/Bc strain.


Human handedness and the concept of developmental stability.
A model is proposed to explain the etiology of pathological handedness. Developmental instability, caused by elevated genotypic homozygosity, environmental disturbances, or their interaction, overrides programmed laterality and handedness in the same way that it perturbs the bilaterally symmetrical expression of morphological and metric traits. The model predicts that pathological handedness should be elevated among individuals with higher than average homozygosity and individuals who have developed under unfavorable uterine environments. Suggestions are offered for specific populations in which the predictions may be tested.


[CD14++CD16- and CD14+CD16+ human monocytes adhesion to endothelial cells].
Two subsets of monocytes were identified in humans and other mammals blood based on different levels of CD14 and CD16 expression. These subsets have different patterns of adhesion molecules and chemokine receptors, which suggest different modes of interaction with endothelium and tissue traffic. Here, we investigated the ability of CD14+CD16+ and CD14++CD16- monocytes to adhesion to endothelial cells monolayer in presence and in the absence of pro- and anti-inflammatory cytokines. We demonstrated that CD14+CD16+ monocytes had higher level of adhesion to intact endothelial cells monolayer than CD14++CD16- monocytes. Significant increase in adhesion of CD14++CD16- and CD14+CD16+ monocytes subpopulations was observed in the presence of both TNF alpha and TNF alpha combinations with other cytokines. IFN gamma and IL-4 showed no independent effects on adhesion of monocytes. These results have demonstrated that both CD14++CD16- and CD14+CD16+ monocytes can be recruited to inflamed endothelium, but, in the absence of inflammation, CD14+CD16+ monocytes adhere to endothelial cells two times stronger than CD14++CD16- monocytes.


[Antituberculous in vitro activity of Helichrýsum arenárium extract].
Bacteriostatic and bactericidal activity of aqueous solution (50 mg/mL) of alcoholic extract of Helichrýsum arenárium (L.) dried flowers, prepared by a special technique so as to increase the yield of flavonoids, was studied in vitro with respect to Mycobacterium tuberculosis (MBT) strains possessing varying degrees of drug resistance, as characterized by replacements Ser R Leu (modification of b-subunit RNA-polymerase of MBT) and Ser R Thr (inactivation of MBT catalase-peroxidase enzyme). The mechanism of this drug action is clearly distinguished from that of the first-line drugs, since strains resistant to these reference drugs have proved susceptible to extract H. arenárium extract. This extract can be recommended for preclinical and clinical studies in the search for new antituberculous drugs and for studying new mechanisms of drug action on MBT. It may also be an effective drug for the treatment of multidrug-resistant MBT strains.


Y-profile evidence: Close paternal relatives and mixtures.
We recently introduced a new approach to the evaluation of weight of evidence (WoE) for Y-chromosome profiles. Rather than attempting to calculate match probabilities, which is particularly problematic for modern Y-profiles with high mutation rates, we proposed using simulation to describe the distribution of the number of males in the population with a matching Y-profile, both the unconditional distribution and conditional on a database frequency of the profile. Here we further validate the new approach by showing that our results are robust to assumptions about the allelic ladder and the founder haplotypes, and we extend the approach in two important directions. Firstly, forensic databases are not the only source of background data relevant to the evaluation of Y-profile evidence: in many cases the Y-profiles of one or more relatives of the accused are also available. To date it has been unclear how to use this additional information, but in our simulation-based approach its effect is readily incorporated. We describe this approach and illustrate how the WoE that a man was the source of an observed Y-profile changes when the Y-profiles of some of his male-line relatives are also available. Secondly, we extend our new approach to mixtures of Y-profiles from two or more males. Surprisingly, our simulation-based approach reveals that observing a 2-male mixture that includes an alleged contributor's profile is almost as strong evidence as observing a matching single-contributor evidence sample, and even 3-male and 4-male mixtures are only slightly weaker.


Debunking the lethal triad and delineating damage control surgery.
The last three decades of literature in trauma have been erroneously hammered by the belief the lethal triad (LT) of acidosis, hypothermia and coagulopathy was, as claimed originally, the statutory rationale underlying for the application of damage control surgery (DCS) strategy. As a matter of fact, the LT is not all lethal: only acidosis is lethal and a reliable hard sign for DCS, indicating severe levels of hypoxemia and tissues hypoxia. The mainstream flow of events leading to exitus in hemorragic shock pass through macro and microcirculation dynamics, oxygen, acidosis, and ischemia-reperfusion toxemia. It is solely by interfering or manipulating these variables dynamics that we can decrease morbidity and mortality. A solid synoptic list of the indications and timing of DCS has been elaborated.


Flow cytometry identifies an early stage of platelet apoptosis produced by agonists of the P2X1 and P2X7 receptors.
Platelets express P2X1 receptors and our data also show the expression of P2X7 receptors. We studied the role of both receptors in platelet apoptosis by incubation of PRP with P2X agonists, then centrifuged to remove viable platelets, and analyzed the supernatant by flow cytometry to identify a sparse platelet-derived population that stained with MitoTracker dyes and CD41. BzATP, a potent agonist of P2X receptors, and ABT737, an activator of intrinsic apoptosis, produced altered platelets that stained moderately for annexin V and corresponded to an early stage apoptotic platelet (ESAP). Over a range of BzATP concentrations, we observed a dose-dependent formation of ESAPs between 5 and 500 uM BzATP, together with a variable formation of ESAPs at nanomolar ATP or BzATP (50-200 nM). Production of ESAPs occurred with αβ-meATP, while responses with either BzATP or αβ-meATP showed desensitization at a higher agonist concentration. Formation of ESAPs by either 100 nM or 0.5 mM BzATP was inhibited by preincubation of platelets with latrunculin A, an inhibitor of the actin cytoskeleton that prevents apoptosis. ESAP production was totally inhibited by preincubation of platelets with methyl-beta-cyclodextrin, which removes cholesterol from lipid rafts. Our data show that both P2X1 and P2X7 receptors are localized in platelet lipid rafts where P2X-agonists act to produce early stage apoptotic platelets.


Is a modular dual mobility acetabulum a viable option for the young, active total hip arthroplasty patient?
Modular dual mobility (DM) prostheses in which a cobalt-chromium liner is inserted into a titanium acetabular shell ( vs a monoblock acetabular component) have the advantage of allowing supplementary screw fixation, but the potential for corrosion between the liner and acetabulum has raised concerns. While DM prostheses have shown improved stability in patients deemed 'high-risk' for dislocation undergoing total hip arthroplasty (THA), their performance in young, active patients has not been reported. This study's purpose was to assess clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) in young, active patients receiving a modular DM acetabulum and recently introduced titanium, proximally coated, tapered femoral stem design. This was a prospective study of patients between 18 and 65 years of age, with a body mass index (BMI) < 35 kg/m2 and University of California at Los Angeles (UCLA) activity score > 6, who received a modular cobalt-chromium acetabular liner, highly crosslinked polyethylene mobile bearing, and cementless titanium femoral stem for their primary THA. Patients with a history of renal disease and metal hardware elsewhere in the body were excluded. A total of 43 patients (30 male, 13 female; mean age 52.6 years (sd 6.5)) were enrolled. All patients had a minimum of two years' clinical follow-up. Patient-reported outcome measures, whole blood metal ion levels (ug/l), and periprosthetic femoral BMD were measured at baseline, as well as at one and two years postoperatively. Power analysis indicated 40 patients necessary to demonstrate a five-fold increase in cobalt levels from baseline (alpha = 0.05, beta = 0.80). A mixed model with repeated measures was used for statistical analysis. Mean Harris Hip Scores improved from 54.1 (sd 20.5) to 91.2 (sd 10.8) at two years postoperatively (p < 0.001). All patients had radiologically well-fixed components, no patients experienced any instability, and no patients required any further intervention. Mean cobalt levels increased from 0.065 ug/l (sd 0.03) preoperatively to 0.30 ug/l (sd 0.51) at one year postoperatively (p = 0.01) but decreased at two years postoperatively to 0.16 ug/l (sd 0.23; p = 0.2). Four patients (9.3%) had a cobalt level outside the reference range (0.03 ug/l to 0.29 ug/l) at two years postoperatively, with values from 0.32 ug/l to 0.94 ug/l. The mean femoral BMD ratio was maintained in Gruen zones 2 to 7 at both one and two years postoperatively using this stem design. At two years postoperatively, mean BMD in the medial calcar was 101.5% of the baseline value. Use of a modular DM prosthesis and cementless, tapered femoral stem has shown encouraging results in young, active patients undergoing primary THA. Elevation in mean cobalt levels and the presence of four patients outside the reference range at two years postoperatively demonstrates the necessity of continued surveillance in this cohort. Cite this article: Bone Joint J 2019;101-B:365-371.


Psychosis and Psychotic-Like Symptoms Affect Cognitive Abilities but Not Motivation in a Foraging Task.
Goal-directed behavior is a central feature of human functioning. It requires goal appraisal and implicit cost-benefit analyses, i.e., how much effort to invest in the pursuit of a certain goal, against its value and a confidence judgment regarding the chance of attainment. Persons with severe mental illness such as psychosis often struggle with reaching goals. Cognitive deficits, positive symptoms restricting balanced judgment, and negative symptoms such as anhedonia and avolition may compromise goal attainment. The objective of this study was to investigate to what degree symptom severity is related to cognitive abilities, metacognition, and effort-based decision-making in a visual search task. Two studies were conducted: study 1: N = 52 (healthy controls), and study 2: N = 46 (23 patients with psychosis/23 matched healthy controls). Symptoms were measured by the CAPE-42 (study 1) and the PANSS (study 2). By using a visual search task, we concomitantly measured (a) accuracy in short-term memory, (b) perceived accuracy by participants making a capture area or confidence interval, and (c) effort by measuring how long one searched for the target. Perseverance was assessed in trials in which the target was omitted and search had to be abandoned. Higher levels of positive symptoms, and having a diagnosis of psychosis, were associated with larger errors in memory. Participants adjusted both their capture area and their search investment to the error of their memory. Perseverance was associated with negative symptoms in study 1 but not in study 2. By simultaneously assessing error and confidence in one's memory, as well as effort in search, we found that memory was affected by positive, not negative, symptoms in healthy controls, and was reduced in patients with psychosis. However, impaired memory did not concur with overconfidence or less effort in search, i.e., goal directed behavior was unrelated to symptoms or diagnosis. Metacognition and motivation were neither affected by cognitive abilities nor by negative symptoms. Clinically, this could indicate that struggles with goal directed behavior in psychosis may not solely be dependent on primary illness factors.


Gastrointestinal stromal tumors: a comprehensive review.
Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. Most GISTs present asymptomatically. They are best identified by computed tomography (CT) scan and most stain positive for CD117 (C-Kit), CD34, and/or DOG-1. There have been many risk stratification classifications systems which are calculated based on tumor size, mitotic rate, location, and perforation. The approaches to treating GISTs are to resect primary low-risk tumors, resect high-risk primary or metastatic tumors with imatinib 400 mg daily for 12 months, or if the tumor is unresectable, neoadjuvant imatinib 400 mg daily followed by surgical resection is recommended. Sunitinib is required for KIT exon 9, 13, and 14 mutations, while ponatinib is used for exon 17 mutations and regorafenib for highly refractory tumors. High-risk tumors should be monitored for recurrence with serial abdominal CT scans. Radiofrequency ablation has shown to be effective when surgery is not suitable. Newer therapies of ipilimumab, nivolumab, and endoscopic ultrasound alcohol ablation have shown promising results. This report addresses the epidemiology, clinical presentation, diagnostic imaging, histologic diagnosis, classification and risk stratification, staging and grading, surgical treatment, adjuvant treatment, and metastasis of GISTs.


Situs Inversus Totalis and Schizophrenia Comorbidity.
The comorbidity of structural or genetic diseases with schizophrenia is seen as an opportunity to understand the formation of schizophrenia. This case report presents a patient with comorbidity of schizophrenia, tetralogy of Fallot (TOF) and total situs inversus. TOF is a cyanotic heart disease, which can be linked to 22q11 deletion and trisomy 21. Situs inversus totalis (SIT) is a congenital condition in which the major visceral organs, including the heart, are positioned in a mirror image from normal conditions. The comorbidity of TOF and SIT is quite rare. In our case report, schizophrenia is added to this rare comorbidity. This case report discussed the comorbidity and probable causal relationships. Furthermore, the research method of how transposition in internal organs is reflected in brain lateralization is also presented.


Demyelinated axons and motor function are protected by genetic deletion of perforin in a mouse model of multiple sclerosis.
Axon injury is a major determinant of the loss of neurological function in patients with multiple sclerosis. It is unclear, however, whether damage to axons is an obligatory consequence of demyelination or whether it is an independent process that occurs in the permissive environment of demyelinated lesions. Previous investigations into the role of CD8 T cells and perforin in the Theiler murine encephalomyelitis virus model of multiple sclerosis have used mouse strains resistant to Theiler murine encephalomyelitis virus infection. To test the role of CD8 T cells in axon injury, we established a perforin-deficient mouse model on the H-2 major histocompatibility complex background thereby removing confounding factors related to viral biology in this Theiler murine encephalomyelitis virus-susceptible strain. This permitted direct comparison of clinical and pathological parameters between perforin-competent and perforin-deficient mice. The extent of demyelination was indistinguishable between perforin-competent and perforin-deficient H-2 mice, but chronically infected perforin-deficient mice exhibited preservation of motor function and spinal axons despite the presence of spinal cord demyelination. Thus, demyelination is necessary but insufficient for axon injury in this model; the absence of perforin protects axons without impacting demyelination. These results suggest that perforin is a key mediator of axon injury and lend additional support to the hypothesis that CD8 T cells are primarily responsible for axon damage in multiple sclerosis.


Typhoid fever cases in the U.S. military.
Salmonella enterica, serovar Typhi (S. Typhi), a causative agent of enteric fever (typhoid fever), predominately affects populations in developing regions with poor access to clean food and water. In addition, travelers to these regions are at risk of exposure. We report the epidemiological characteristics of S. Typhi cases among active duty United States military personnel from 1998 to 2011 using data obtained from the Defense Medical Surveillance System. Cases were identified based on International Classification for Disease Ninth Edition - Clinical Modification codes. We identified a total of 205 cases S. Typhi for an incidence of 1.09 per 100,000 person-years. Cases were on average 31.7 years old, predominately married (n = 129, 62.9 %), Caucasian (n = 142, 69.3 %), male (n = 176, 85.9 %), and had a high school education (n = 101, 49.3 %). Of the identified cases, 122 had received a Typhoid vaccination within 4 years of diagnosis. This study provides an overview of enteric fever in the United States military. The incidence was similar to the general U.S. population except for increased incidence from 1998 to 2000, perhaps attributable to operational deployments in that period. Given that vaccination is an effective primary prevention measure against typhoid fever, active monitoring of pre-deployment vaccine history is warranted.


Auxiliary KCNE subunits modulate both homotetrameric Kv2.1 and heterotetrameric Kv2.1/Kv6.4 channels.
The diversity of the voltage-gated K(+) (Kv) channel subfamily Kv2 is increased by interactions with auxiliary β-subunits and by assembly with members of the modulatory so-called silent Kv subfamilies (Kv5-Kv6 and Kv8-Kv9). However, it has not yet been investigated whether these two types of modulating subunits can associate within and modify a single channel complex simultaneously. Here, we demonstrate that the transmembrane β-subunit KCNE5 modifies the Kv2.1/Kv6.4 current extensively, whereas KCNE2 and KCNE4 only exert minor effects. Co-expression of KCNE5 with Kv2.1 and Kv6.4 did not alter the Kv2.1/Kv6.4 current density but modulated the biophysical properties significantly; KCNE5 accelerated the activation, slowed the deactivation and steepened the slope of the voltage-dependence of the Kv2.1/Kv6.4 inactivation by accelerating recovery of the closed-state inactivation. In contrast, KCNE5 reduced the current density ~2-fold without affecting the biophysical properties of Kv2.1 homotetramers. Co-localization of Kv2.1, Kv6.4 and KCNE5 was demonstrated with immunocytochemistry and formation of Kv2.1/Kv6.4/KCNE5 and Kv2.1/KCNE5 complexes was confirmed by Fluorescence Resonance Energy Transfer experiments performed in HEK293 cells. These results suggest that a triple complex consisting of Kv2.1, Kv6.4 and KCNE5 subunits can be formed. In vivo, formation of such tripartite Kv2.1/Kv6.4/KCNE5 channel complexes might contribute to tissue-specific fine-tuning of excitability.


Functional insights from the distribution and role of homopeptide repeat-containing proteins.
Expansion of "low complex" repeats of amino acids such as glutamine (Poly-Q) is associated with protein misfolding and the development of degenerative diseases such as Huntington's disease. The mechanism by which such regions promote misfolding remains controversial, the function of many repeat-containing proteins (RCPs) remains obscure, and the role (if any) of repeat regions remains to be determined. Here, a Web-accessible database of RCPs is presented. The distribution and evolution of RCPs that contain homopeptide repeats tracts are considered, and the existence of functional patterns investigated. Generally, it is found that while polyamino acid repeats are extremely rare in prokaryotes, several eukaryote putative homologs of prokaryote RCP-involved in important housekeeping processes-retain the repetitive region, suggesting an ancient origin for certain repeats. Within eukarya, the most common uninterrupted amino acid repeats are glutamine, asparagines, and alanine. Interestingly, while poly-Q repeats are found in vertebrates and nonvertebrates, poly-N repeats are only common in more primitive nonvertebrate organisms, such as insects and nematodes. We have assigned function to eukaryote RCPs using Online Mendelian Inheritance in Man (OMIM), the Human Reference Protein Database (HRPD), FlyBase, and Wormpep. Prokaryote RCPs were annotated using BLASTp searches and Gene Ontology. These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling.


First Report of Southern Blight of Swiss Chard (Beta vulgaris subsp. cicla) Caused by Sclerotium rolfsii in California.
In June 2013, a commercial organic planting of Swiss chard (Beta vulgaris subsp. cicla) in Monterey County, CA, showed symptoms of a soilborne disease. Early symptoms consisted of delayed and stunted growth, with wilting of foliage during the warmer times of the day. Initially, a light brown discoloration developed on stems at the soil line. As disease progressed, a dark brown necrosis extended up the main stem and down along the upper portion of the taproot. In advanced cases, the plants collapsed and died. Extensive white cottony mycelium and numerous brown, spherical sclerotia, approximately 1 mm in diameter, developed externally on the lower stem, crown, and adhering adjacent soil. For this particular planting, approximately 10% of the 0.4 ha was lost. Sequentially planted sets of chard placed in other parts of the farm were unaffected. Isolations from necrotic plant tissues, sclerotia, and white mycelium all resulted in recovery of the same white fungus that in culture produced identical sclerotia but no other reproductive structures. Based on white mycelium, sclerotia morphology, and the presence of clamp connections at hyphal septa, the fungus was identified as Sclerotium rolfsii (1). Pathogenicity was tested by growing isolates on potato dextrose agar, drying the resulting sclerotia for 48 h, then burying 5 to 8 sclerotia adjacent to the crowns of healthy Swiss chard plants grown in pots. Three isolates were tested using 24 plants per isolate. Six control plants were inoculated with sterilized sand. All plants were incubated in a greenhouse at 22 to 25°C. After 8 days, inoculated plants began to wilt. By 14 days after inoculation, 100% of the inoculated plants showed symptoms identical to those observed in the field. One half of the plants were used for re-isolations, from which S. rolfsii was recovered from all necrotic crown and stem tissues. The other half of the plants were maintained in the greenhouse; these plants later supported the development of sclerotia. Sand-inoculated control plants did not develop any disease symptoms. The experiment was repeated and the results were the same. To our knowledge, this is the first report of southern blight of Swiss chard in California. Southern blight has not previously been found in this cooler, western part of the county adjacent to the Pacific Ocean; southern blight has been documented on other crops such as pepper, tomato, and chives (3) in the warmer eastern and southern parts of Monterey County. S. rolfsii has been reported on Swiss chard in Louisiana, South Carolina, and Cuba (2). References: (1) K. H. Domsch et al. Compendium of Soil Fungi, 2nd edition. IHW-Verlag, Eching, Germany, 2007. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab. Online publication, ARS, USDA. Retrieved July 26, 2013. (3) S. T. Koike et al. Plant Dis. 78:208, 1994.


Efficacy of graded activity versus supervised exercises in patients with chronic non-specific low back pain: protocol of a randomised controlled trial.
Low back pain is a relevant public health problem, being an important cause of work absenteeism worldwide, as well as affecting the quality of life of sufferers and their individual functional performances. Supervised active physical routines and of cognitive-behavioral therapies are recommended for the treatment of chronic Low back pain, although evidence to support the effectiveness of different techniques is missing. Accordingly, the aim of this study is to contrast the effectiveness of two types of exercises, graded activity or supervised, in decreasing symptoms of chronic low back pain. Sample will consist of 66 patients, blindly allocated into one of two groups: 1) Graded activity which, based on an operant approach, will use time-contingent methods aiming to increase participants' activity levels; 2) Supervised exercise, where participants will be trained for strengthening, stretching, and motor control targeting different muscle groups. Interventions will last one hour, and will happen twice a week for 6 weeks. Outcomes (pain, disability, quality of life, global perceived effect, return to work, physical activity, physical capacity, and kinesiophobia) will be assessed at baseline, at treatment end, and three and six months after treatment end. Data collection will be conducted by an investigator blinded to treatment allocation. This project describes the randomisation method that will be used to compare the effectiveness of two different treatments for chronic low back pain: graded activity and supervised exercises. Since optimal approach for patients with chronic back pain have yet not been defined based on evidence, good quality studies on the subject are necessary. NCT01719276.


Enhancing quality midwifery care in humanitarian and fragile settings: a systematic review of interventions, support systems and enabling environments.
Women and children bear a substantial burden of the impact of conflict and instability. The number of people living in humanitarian and fragile settings (HFS) has increased significantly over the last decade. The provision of essential maternal and newborn healthcare by midwives is crucial everywhere, especially in HFS. There is limited knowledge about the interventions, support systems and enabling environments that enhance midwifery care in these settings. The aim of this paper is to identify the factors affecting an enabling environment for midwives in HFS and to explore the availability and effectiveness of support systems for midwives. A structured systematic review was undertaken to identify peer-reviewed primary research articles published between 1995 and 2020. In total, 24 papers were included from Afghanistan, Bangladesh, Nigeria, Democratic Republic of Congo, South Sudan and Sudan, Ethiopia, Pakistan, Uganda and Liberia. There were two broad themes: (1) the facilitators of, and barriers to, an enabling environment, and (2) the importance of effective support systems for midwives. Facilitators were: community involvement and engagement and an adequate salary, incentives or benefits. Barriers included: security and safety concerns, culture and gender norms and a lack of infrastructure and supplies. Support systems were: education, professional development, supportive supervision, mentorship and workforce planning. More efforts are needed to develop and implement quality midwifery services in HFS. There is an urgent need for more action and financing to ensure better outcomes and experiences for all women, girls and families living in these settings. CRD42021226323.


Complete Genome Sequence of Lactobacillus plantarum subsp. plantarum Strain LB1-2, Isolated from the Hindgut of European Honeybees, Apis mellifera L., from the Philippines.
Lactobacillus plantarum subsp. plantarum strain LB1-2, isolated from the hindgut of European honeybees in the Philippines, is active against Paenibacillus larvae and has broad activity against several Gram-positive and Gram-negative bacteria. The complete genome sequence reported herein contains gene clusters for multiple bacteriocins and extensive gene inventories for carbohydrate metabolism.


Microsatellite Instability Status and the Expression of p16 and Cyclin D1 Proteins in Uterine Adenosarcoma and Their Clinicopathological Significance.
Uterine adenosarcoma has low malignant potential, except in cases with sarcomatous overgrowth (SOG) and a high-grade morphology. We here point out the prognostic clinicopathological and immunohistochemical features as well as the microsatellite instability (MSI) status of high- and low-grade adenosarcomas. In this study, DNA mismatch repair proteins, p16, cyclin D1, ER, PR, and CD10 were examined in uterine adenosarcoma cases using immunohistochemistry. The association between these proteins and clinicopathological parameters was also evaluated. ER, PR and CD10 expressions were lower and weaker in high-grade adenosarcomas with SOG compared to low-grade adenosarcomas without SOG (p < 0.05). p16 positivity was more frequent in high-grade adenosarcomas than low-grade adenosarcomas (p < 0.05). There was no statistically significant difference between cyclin D1 positivity, MSI, and other clinicopathological parameters (p ≥ 0.05). Cyclin D1 positivity and loss of CD10 expression were associated with shorter disease-free survival (DFS). Loss of ER and CD10 expression was associated with shorter overall survival (OS) (p < 0.05). MSI was not associated with DFS or OS (p ≥ 0.05). These results suggested that p16 positivity, and loss of ER, PR, and CD10 expression were predictors of high-grade morphology. Additionally, the current study showed that cyclin D1-positive tumors had high recurrence rates; however, no significant relationships were found between MSI and DFS or OS in patients with uterine adenosarcoma. Further investigations are required to determine the importance of p16, cyclin D1, and MSI in uterine adenosarcomas.


Tips and tricks in the dermoscopy of pigmented lesions.
Dermoscopy is a useful, widely used tool for examining pigmented lesions, especially helpful in cases of an uncertain nature. Nevertheless, doctors may experience diagnostic difficulties while using this method. An example of this may be found in the examination of subcorneal hematoma, dark nevi with black lamella or lesions of acral volar skin. In such cases, a few diagnostic tricks have proven to be helpful in achieving diagnostic accuracy. This paper reviews various methods of performing dermoscopy, suggesting a number of simple, yet helpful tests. These include the adhesive tape test, the skin scraping test and the ink furrow test. The adhesive tape test is helpful in differentiating between dark melanocytic nevi and melanoma. Hematoma may be more easily differentiated with the use of the so-called skin scraping test. The confirmation of benign and melanocytic lesions of acral volar skin, on the other hand, is more accurate when using the ink furrow test. These methods have been discussed here based upon a series of literature reviews, the authors' own experience and, also, iconography. The present article describes novel methods used in dermoscopy, helping to bring about a faster, more accurate diagnostics of those lesions which have proven to be more difficult to recognize. Helpful tricks, such as have been known to professional literature, as well as the authors' own experience (for instance, applying urea cream to hyperkeratotic lesions or using photographs of skin lesions taken with the aid of a mobile phone camera--all prior to surgery) will surely be considered beneficial to the practitioner, be it dermatologist or any other physician.


[The fight against malnutrition of the medical community between 1860 and 1940].
The aim of this manuscript is to highlight the contribution of the first two generations of physicians who faced malnutrition in Chile, between the end of nineteenth century and the first decades of the twentieth century. In the history of Chilean medicine, there is a paucity of research about the role of these physicians in the fight against malnutrition. The main interest was centered in the forties of the twentieth century and the first policies and actions for the working class feeding have been overlooked. The existence of two pioneering groups that have common elements and differences to face the problem of under nutrition is established.