Association of a promotional campaign for local dining facilities with the occurrence of COVID-19 in Asahikawa City, Japan, in November 2021.

Objectives: As social restrictions of COVID-19 are being eased worldwide, preventing SARS-CoV-2 transmission among staff members and customers in dining facilities is essential to continuously running business because restaurants and bars are high-risk locations for COVID-19 outbreaks. In 2021, COVID-19 outbreaks occurred at restaurants or bars in Asahikawa city, Japan two weeks after the launch of a promotional campaign for local dining facilities. We investigated this event to assess the association between the promotional campaign and the occurrence of SARS-CoV-2 infection. Study design: Cohort study. Methods: We assessed the association between the occurrence of COVID-19 cases in the restaurants and bars and their participation in the campaign by calculating risk ratio and 95% confidence interval. Results: Cases were identified among workers or customers in 4.0% (4/101) of the participating restaurants or bars and in 1.2% (39/3257) of the non-participating restaurants or bars. The risk ratio was 3.3 (95% confidence interval 1.2-9.0). Conclusion: The association between the occurrence of SARS-CoV-2 infection in the restaurants or bars and participation in the campaign is undeniable. Promotional campaigns to vitalize dining facilities should be accompanied by enhanced infection prevention measures, especially ventilation.

A novel application of hectorite nanoclay for preparation of colorectal cancer spheroids with malignant potential.

Three-dimensional (3D) cell culture, which provides an in vivo-like environment in vitro unlike the conventional two-dimensional (2D) cell culture, has attracted much attention from researchers. Although various 3D cell culture methods have been developed, information on a method using inorganic nanoclay is scant. Here, we report that hectorite, an inorganic layered silicate, can be used as an auxiliary material for 3D cell culture. Human colon cancer cell lines cultured in a medium containing 0.01% synthetic hectorite spontaneously formed 3D spheroids in an adherent plate. Morphologically, these spheroids were more dispersed in all directions than control spheroids generated in an ultralow adherent plate. Microarray analysis showed that FGF19, TGM2, and SERPINA3, whose expression is reportedly increased in colon cancer tissues and is related to tumorigenesis or metastasis, were upregulated in HT-29 spheroids formed using synthetic hectorite compared with those in control spheroids. Gene ontology analysis revealed upregulation of genes associated with morphogenesis, cytoskeleton, extracellular matrix, cellular uptake and secretion, signaling pathways, and gene expression regulation. Moreover, fluorescence-labeled hectorite particles were localized in the cytoplasm of individual cells in spheroids. These results suggest that the synthetic hectorite modified the physiological state of and gene expression within the cells, triggering spheroid formation with malignant characteristics. Our findings highlight a novel application of synthetic hectorite for 3D cell culture.

Characteristics of frequently attending children in hospital emergency departments: a systematic review.

OBJECTIVE: To summarise the literature on frequent attendances to hospital emergency departments (EDs) and describe sociodemographic and clinical characteristics of children who attend EDs frequently. SETTING: Hospital EDs. PARTICIPANTS: Children <21 years, attending hospital EDs frequently. PRIMARY OUTCOME MEASURES: Outcomes measures were defined separately in each study, and were predominantly the number of ED attendances per year. RESULTS: We included 21 studies representing 6 513 627 children. Between 0.3% and 75% of all paediatric ED users were frequent users. Most studies defined four or more visits per year as a 'frequent ED' usage. Children who were frequent ED users were more likely to be less than 5 years old. In the USA, patients with public insurance were more likely to be frequent attenders. Frequent ED users more likely to be frequent users of primary care and have long-term conditions; the most common diagnoses were infections and gastroenteritis. CONCLUSIONS: The review included a wide range of information across various health systems, however, children who were frequent ED users have some universal characteristics in common. Policies to reduce frequent attendance might usefully focus on preschool children and supporting primary care in responding to primary care oriented conditions.

Patient-initiated second medical consultations-patient characteristics and motivating factors, impact on care and satisfaction: a systematic review.

OBJECTIVES: To review the characteristics and motivations of patients seeking second opinions, and the impact of such opinions on patient management, satisfaction and cost effectiveness. DATA SOURCES: Embase, Medline, PsycINFO and Health Management Information Consortium (HMIC) databases. STUDY DESIGN: A systematic literature search was performed for terms related to second opinion and patient characteristics. Study quality was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. DATA COLLECTION/EXTRACTION METHODS: We included articles focused on patient-initiated second opinions, which provided quantitative data on their impact on diagnosis, treatment, prognosis or patient satisfaction, described the characteristics or motivating factors of patients who initiated a second opinion, or the cost-effectiveness of patient-initiated second opinions. PRINCIPAL FINDINGS: Thirty-three articles were included in the review. 29 studies considered patient characteristics, 19 patient motivating factors, 10 patient satisfaction and 17 clinical agreement between the first and second opinion. Seeking a second opinion was more common in women, middle-age patients, more educated patients; and in people having a chronic condition, with higher income or socioeconomic status or living in central urban areas. Patients seeking a second opinion sought to gain more information or reassurance about their diagnosis or treatment. While many second opinions confirm the original diagnosis or treatment, discrepancies in opinions had a potential major impact on patient outcomes in up to 58% of cases. No studies reported on the cost effectiveness of patient initiated second opinions. CONCLUSIONS: This review identified several demographic factors associated with seeking a second opinion, including age, gender, health status, and socioeconomic status. Differences in opinion received, and in the impact of change in opinion, varies significantly between medical specialties. More research is needed to understand the cost effectiveness of second opinions and identify patient groups most likely to benefit from second opinions.

Factors that facilitate multigenerational exchanges in regional locations: a cross-sectional study in Niigata City, Japan.

BACKGROUND: In the process of community building, it is important to create a place for multigenerational exchanges. To promote multigenerational exchanges in regional locations, it is essential to clarify whether such exchanges are related to government infrastructure, regional characteristics, and social capital, and how these exchanges contribute to community building. METHODS: A cross-sectional questionnaire study was conducted with representatives from 455 Chiiki no Cha-no-Ma (literal translation "community living room," and hereafter "Cha-no-Ma") in Niigata City, Japan. Responses were received from 405 representatives (response rate: 89.0 %), and 401 agreed to participate (4 declined). The survey details included basic information (e.g., date each location was established, frequency of meetings, number of caretakers and participants, qualifications of the representative), activities reflecting local culture, a social capital scale, the effects of the Cha-no-Ma implemented by the representative (12 items), challenges for management (16 items), and the implementation of multigenerational exchanges. RESULTS: Most of the age groups that participated in the Cha-no-Ma were elderly, and multigenerational exchanges took place in 125 locations (31.5 %). Items that had a significant connection to the implementation of multigenerational exchanges were "Frequency of meetings" (p < 0.001) and "Activities reflecting local culture" (p = 0.026). Binomial logistic regression analysis indicated that a high frequency of meetings was associated with the implementation of multigenerational exchanges (Odds ratio = 3.839). There was a significantly higher ratio of implementation of multigenerational exchanges when the effects were a "connection with the region" (p = 0.006) and "conversations with different generations" (p = 0.004), and when the challenge was "no support from residents" (p = 0.002). CONCLUSIONS: Cha-no-Ma participation is low among young people. The following ideas can be considered in order to increase multigenerational exchanges in regional locations. These exchanges may be promoted by increasing the frequency of meetings with qualified personnel and by adding activities that reflect local culture, such as festivals and making local foods. This community-based study clearly indicates that implementing multigenerational exchanges is an important activity for community building because it is related to connection within the community.

Lessons on the COVID-19 pandemic, for and by primary care professionals worldwide.

The COVID-19 pandemic has modified organisation and processes of primary care. In this paper, we aim to summarise experiences of international primary care systems. We explored personal accounts and findings in reporting on the early experiences from primary care during the pandemic, through the online Global Forum on Universal Health Coverage and Primary Health Care. During the early stage of the pandemic, primary care continued as the first point of contact to the health system but was poorly informed by policy makers on how to fulfil its role and ill equipped to provide care while protecting staff and patients against further spread of the infection. In many countries, the creativity and initiatives of local health professionals led to the introduction or extension of the use of telephone, e-mail and virtual consulting, and introduced triaging to separate 'suspected' COVID-19 from non-COVID-19 care. There were substantial concerns of collateral damage to the health of the population due to abandoned or postponed routine care. The pandemic presents important lessons to strengthen health systems through better connection between public health, primary care, and secondary care to cope better with future waves of this and other pandemics.

Integration of sexual and reproductive health services in the provision of primary health care in the Arab States: status and a way forward.

Different approaches are used for integration of sexual and reproductive health (SRH) services at the primary health care (PHC) level, aiming at providing comprehensive services leaving no one behind. This paper aims to assess gaps in the delivery of SRH in PHC services, identifying challenges and proposing action towards universal health coverage in Arab countries. The United Nations Population Fund, Arab States Regional Office (UNFPA/ASRO), in partnership with Middle East and North Africa Health Policy Forum (HPF), launched an assessment of integration of SRH into PHC in 11 Arab countries in 2017-2018. Desk reviews were conducted, using published program reports and national statistics. Data from country reports were compiled to present a regional assessment, challenges and recommendations. SRH services are partially integrated in PHC. Family planning is part of PHC in all countries except Libya, where only counselling is provided. Only Morocco, Tunisia and Oman provide comprehensive HIV services at PHC level. Jordan, Libya and Saudi Arabia rely mainly on referral to other facilities, while most of the integrated family planning or HIV services in Sudan, Morocco and Oman are provided within the same facilities. Action is required at the policy, organisational and operational levels. Prioritisation of services can guide the development of essential packages of SRH care. Developing the skills of the PHC workforce in SRH services and the adoption of the family medicine/general practice model can ensure proper allocation of resources. A presented regional integration framework needs further efforts for addressing the actions entailed.

Primary care healthcare policy implementation in the Eastern Mediterranean region; experiences of six countries: Part II.

Background: Primary healthcare (PHC) is essential for equitable access and cost-effective healthcare. This makes PHC a key factor in the global strategy for universal health coverage (UHC). Implementing PHC requires an understanding of the health system under prevailing circumstances, but for most countries, no data are available.Objectives: This paper describes and analyses the health systems of Algeria, Kuwait, Morocco, Saudi Arabia, Jordan and Iraq to PHC.Methods: Data were collected during a workshop at the Wonca East Mediterranean Regional Conference in 2018. Academic family physicians (FP) presented their country; using the Wonca framework of 11 PowerPoint slides, with queries of the country demographics, main health challenges, and the position of PHC in the health system.Results: The six countries had achieved a significant improvement in populations' health but currently face challenges of health financing, a small number of certified FPs, difficulties in accessing services and bureaucratic procedures. Primary concerns were the absence of a family practice model, brain drain and immigration of FPs. Countries differed in building a coherent policy.Conclusion: Priorities should be focused on: developing PHC model in Eastern Mediterranean region with advocacy for community-based PHC to policymakers; capacity building for strengthening PHC-oriented health systems with FP specialty training and restrict practising to fully trained FPs; engage communities to improve understanding of PHC; adopt quality and accreditation policies for better services; validation of the referral and follow-up process; and, develop public-private partnership mechanisms to enhance PHC for UHC.

Primary care integration of sexual and reproductive health services for chlamydia testing across WHO-Europe: a systematic review.

OBJECTIVE: To identify current uptake of chlamydia testing (UCT) as a sexual and reproductive health service (SRHS) integrated in primary care settings of the WHO European region, with the aim to shape policy and quality of care. DESIGN: Systematic review for studies published from January 2001 to May 2018 in any European language. DATA SOURCES: OVID Medline, EMBASE, Maternal and Infant Care and Global Health. ELIGIBILITY CRITERIA: Published studies, which involved women or men, adolescents or adults, reporting a UCT indicator in a primary care within a WHO European region country. Study designs considered were: randomised control trials (RCTs), quasi-experimental, observational (eg, cohort, case-control, cross-sectional) and mixed-methods studies as well as case reports. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the sources and validated the selection process. The BRIGGS Critical Appraisal Checklist for Analytical Cross-Sectional Studies, the Mixed Methods Appraisal Tool 2011 and Critical Appraisal Skills Programme (CASP) checklists were considered for quality and risk of bias assessment. RESULTS: 24 studies were finally included, of which 15 were cross-sectional, 4 cohort, 2 RCTs, 2 case-control studies and 1 mixed-methods study. A majority of the evidence cites the UK model, followed by the Netherlands, Denmark, Norway and Belgium only. Acceptability if offered test in primary healthcare (PHC) ranged from 55% to 81.4% in women and from 9.5% to 70.6% when both genders were reported together. Men may have a lower UCT compared with women. When both genders were reported together, the lowest acceptability was 9.5% in the Netherlands. Denmark presented the highest percentage of eligible people who tested in a PHC setting (87.3%). CONCLUSIONS: Different health systems may influence UCT in PHC. The regional use of a common testing rate indicator is suggested to homogenise reporting. There is very little evidence on integration of SRHS such as chlamydia testing in PHC and there are gaps between European countries.

Cardiovascular risk and fruit and vegetable consumption among women in KSA; A cross-sectional study.

OBJECTIVES: This study aims to assess fruit and vegetable consumption among Saudi women to identify perceived benefits and barriers associated with a healthy diet in cardiovascular disease (CVD) risk prevention and to correlate Framingham risk scores (FRSs) with the perceived barriers. METHODS: A questionnaire adapted from the Health Beliefs Related to Cardiovascular Disease Scale was administered to women attending a primary care centre in KSA. In addition to descriptive statistics, a chi-square test and multiple linear regression analysis were used to determine the association between perceptions of benefit and barriers with FRS categories and between mean FRS and perceived barriers. RESULTS: A total of 503 women were included in this study, and 75% of the women were older than 45 years. More than 60% of women were obese, and 97% consumed 1-3 fruit and vegetable servings per day, whereas only 1.4% consumed fruits and vegetables 5 or more times per day. The majority of women were aware of the benefits of a healthy diet in CVD prevention. No significant difference between FRS and perceived benefits or barriers was observed. Barriers across the low- to high-risk groups included a lack of knowledge about a 'healthy diet', insufficient time to cook, food affordability, and having more important problems. Women who disagreed on barriers had negative beta coefficients for the mean FRS (p < 0.03). CONCLUSIONS: In this study cohort, fruit and vegetable intake was lower than the recommended guidelines. Despite awareness of the benefits of a healthy diet in CVD prevention, very few women understood the true meaning of 'healthy diet'. A direct association between FRS and perceptions/barriers could not be validated. Perceived barriers could be addressed by integrating innovative educational campaigns to existing models of the Healthy Food Plan.

[Gender-based relations and mistreatment in medical schools: A pending agenda in Mexico and the world]. / Las relaciones de género y el maltrato en las escuelas de medicina: una agenda pendiente en México y el mundo.

The purpose of this review is to describe and analyze the status of gender violence in medical schools around the world, and its consequences in undergraduate students' health and academic development, mainly on female students. The different modalities reported in the literature are presented: gender discrimination, sexism, and sexual harassment, among others. The increase of women in medical schools has not transcendentally improved their condition in these institutions, where androcentrism and gender regimes that favor gender violence reproduce. This type of violence is a public health, human rights, and academic problem.

Quantitative transcriptomic profiling of branching in a glycosphingolipid biosynthetic pathway.

Cellular biosynthesis of macromolecules often involves highly branched enzyme pathways, thus cellular regulation of such pathways could be rather difficult. To understand the regulatory mechanism, a systematic approach could be useful. We genetically analyzed a branched biosynthetic pathway for glycosphingolipid (GSL) GM1 using correlation index-based responsible enzyme gene screening (CIRES), a novel quantitative phenotype-genotype correlation analysis. CIRES utilizes transcriptomic profiles obtained from multiple cells. Among a panel of B cell lines, expression of GM1 was negatively correlated with and suppressed by gene expression of CD77 synthase (CD77Syn), whereas no significant positive correlation was found for enzymes actually biosynthesizing GM1. Unexpectedly, a GM1-suppressive phenotype was also observed in the expression of catalytically inactive CD77Syn, ruling out catalytic consumption of lactosylceramide (LacCer) as the main cause for such negative regulation. Rather, CD77Syn seemed to limit other branching reaction(s) by targeting LacCer synthase (LacCerSyn), a proximal enzyme in the pathway, because they were closely localized in the Golgi apparatus and formed a complex. Moreover, turnover of LacCerSyn was accelerated upon CD77Syn expression to globally change the GSL species expressed. Collectively, these data suggest that transcriptomic assessment of macromolecule biosynthetic pathways can disclose a global regulatory mechanism(s) even when unexpected.

Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment.

The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

Allergic reactions to oxaliplatin in a single institute in Japan.

Allergic reactions to oxaliplatin can be severe and are an important cause of discontinuation of treatment. A retrospective review was performed for 105 patients who received FOLFOX regimens between May 2005 and June 2007. Twenty-five cases (23.8%) of allergic reactions were identified, including 9 late onset reactions (8.6%) and 16 immediate reactions (15.2%). Severe allergy (Grades 3 and 4) occurred in seven patients (6.7%). Re-introduction of FOLFOX was attempted for seven immediate onset patients with a severity grade of 1 or 2, and three of these patients (42.9%) showed relapse of allergy. In approximately 10% of the patients, FOLFOX had to be discontinued due to allergy before the disease became refractory to the regimen. Our experience indicates that allergy to oxaliplatin may be a significant concern and that methods are required for suppression of this allergy.

Wheat germ agglutinin stains dispersed post-golgi vesicles after treatment with the cytokinesis inhibitor psychosine.

The galactosylsphingosine psychosine (Psy) is one of the sphingolipids and induce the formation of multinuclear cells in several cell lines by inhibiting cytokinesis. In the present report, we show that intracellular organelles, including wheat germ agglutinin (WGA)-positive vesicles and early endosomes, are selectively dispersed by Psy. WGA is a conventional Golgi marker and WGA-positive vesicles appeared to co-localize with the Golgi apparatus in untreated cells. Psy treatment induced the dispersal of WGA-positive vesicles without affecting the structure of the Golgi apparatus, resulting in discrimination of WGA-positive vesicles from the Golgi apparatus. In sharp contrast to this effect of Psy, WGA-positive vesicles were not affected by brefeldin A treatment, which induced the disappearance of the Golgi apparatus. Immunostaining with anti-TGN46 antibodies revealed that a large portion of the WGA-positive vesicles were derived from the trans-Golgi network. Notably, the dispersed WGA-positive vesicles did not stain with anti-syntaxin 6, another marker of the trans-Golgi network. During cytokinesis, WGA-positive vesicles in the cytoplasm decreased, and WGA staining accumulated at the cleavage furrow, which was apparently inhibited by the presence of Psy. These data suggest that the transport of WGA-positive vesicles to the cleavage furrow is associated with the progression of cytokinesis.

Prostaglandin E1 improves survival rate after 95% hepatectomy in rats.

BACKGROUND/AIM: Prostaglandin E1 (PGE1) has a wide-ranging effect on cytoprotection. Overproduction of heat shock protein 70 (HSP70) in the liver protects hepatocytes under various pathologic conditions. In this study, we examined the effect of a nontoxic HSP-inducer, PGE1, on acute liver failure after 95% hepatectomy in rats. METHODS: PGE1 or vehicle was intravenously administered to rats 30 min before and during hepatectomy. RESULTS: Nine of 30 rats pretreated with PGE1 survived, whereas all 20 rats pretreated with vehicle died within 96 h after operation. During the 24-h postoperative period, PGE1 significantly suppressed the release of alanine aminotransferase and elevation of hyaluronic acid. Histological examination showed that the vacuolized hepatocytes and round hepatocytes with pyknotic nuclei are frequently seen in rats pretreated with vehicle, whereas active regeneration is seen in rats pretreated with PGE1. During the first 24 h after surgery, HSP70 induction was absent in the residual livers of vehicle-treated rats. In contrast, PGE1 stimulated the HSP accumulation within 24 h, and viable hepatocytes contained abundant HSP70 in their nuclei. CONCLUSION: Our results suggest that PGE1 may prevent acute liver failure after massive hepatectomy, at least in part, by enhancing HSP70 production in the residual liver.

Correlation index-based responsible-enzyme gene screening (CIRES), a novel DNA microarray-based method for enzyme gene involved in glycan biosynthesis.

BACKGROUND: Glycan biosynthesis occurs though a multi-step process that requires a variety of enzymes ranging from glycosyltransferases to those involved in cytosolic sugar metabolism. In many cases, glycan biosynthesis follows a glycan-specific, linear pathway. As glycosyltransferases are generally regulated at the level of transcription, assessing the overall transcriptional profile for glycan biosynthesis genes seems warranted. However, a systematic approach for assessing the correlation between glycan expression and glycan-related gene expression has not been reported previously. METHODOLOGY: To facilitate genetic analysis of glycan biosynthesis, we sought to correlate the expression of genes involved in cell-surface glycan formation with the expression of the glycans, as detected by glycan-recognizing probes. We performed cross-sample comparisons of gene expression profiles using a newly developed, glycan-focused cDNA microarray. Cell-surface glycan expression profiles were obtained using flow cytometry of cells stained with plant lectins. Pearson's correlation coefficients were calculated for these profiles and were used to identify enzyme genes correlated with glycan biosynthesis. CONCLUSIONS: This method, designated correlation index-based responsible-enzyme gene screening (CIRES), successfully identified genes already known to be involved in the biosynthesis of certain glycans. Our evaluation of CIRES indicates that it is useful for identifying genes involved in the biosynthesis of glycan chains that can be probed with lectins using flow cytometry.

PAI-1 plays an important role in liver failure after excessive hepatectomy in the rat.

BACKGROUND/AIMS: Well-organized turnover of the extracellular matrix is important in liver regeneration, which is regulated by the plasminogen activating system. The aim of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) after excessive hepatectomy and to ascertain whether angiotensin-converting enzyme (ACE) inhibitors, which are PAI-1 inhibitors as well, successfully improve the survival rate of rats that have undergone 95% partial hepatectomy (PHx). METHODS: Using liver tissues sampled after 90% or 95% PHx, the expression of PAI-1 mRNA was evaluated using reverse transcription polymerase chain reaction. Hepatic PAI-1 protein and urokinase-type plasminogen activator (uPA) levels were determined by enzyme-linked immunosorbent assay. Survival study and cytodynamic analysis by 5-bromo-2'-deoxyuridine staining were performed to evaluate the effects of ACE inhibition. RESULTS: The levels of PAI-1 mRNA and hepatic PAI-1 protein in the 95% PHx group peaked and were then maintained. By contrast, the uPA level fell relative to the 90% PHx group. Additionally, the hepatic PAI-1 protein level decreased and the survival rate improved in the 95% PHx rats that had undergone ACE inhibition. CONCLUSIONS: Our experimental results suggest that PAI-1 plays a role in the occurrence of liver failure after excessive hepatectomy via accelerated maturation of pro-uPA and fibrinolytic factors. These are potential molecular therapeutic targets for liver failure after excessive hepatectomy.