Possible functions of adrenomedullin from the seminal fluid in the female reproductive tract of the rat

Adrenomedullin (ADM) is found in male accessory sex glands and is part of the seminal secretion. It plays an important role in protecting the sperm in the female reproductive tract. In this study, we investigated the roles of ADM in inflammation and oxidative stress in the endometrium and in leukocyte and macrophage infiltration in the endometrial stroma. The expression of the ADM gene in the ventral prostate, coagulating gland, and seminal vesicle was determined by real time PCR. The peptide levels in the tissue and secretion were measured using an EIA Kit. The highest ADM mRNA and peptide levels were found in the ventral prostate. Most of the ADM in the seminal vesicle was stored in the tissue while little was secreted. The expression of the IL-1β gene and the secretion of TNFα and IL-6 in uterine tissue decreased significantly after treatment with ADM for 4 hours. Using an immunostaining method, the levels of leukocyte and macrophage infiltration were found to be lower at 24 hours post coitus than 1.5 hours post coitus. The infusion of ADM receptor antagonist reduced the infiltration of leukocyte and macrophages in the endometrial stroma at 24 hours post coitus. As to the anti-oxidative effect of ADM in the female tract, the reactive oxygen species (ROS) level in isolated endometrial epithelial cells was significantly decreased after treatment with ADM or seminal fluid. Our findings demonstrated that ADM in the seminal secretion may modify the inflammatory responses, play an anti-oxidative role, and increase leukocyte and macrophage infiltration in the uterus.     

Arginine decreases Cryptosporidium parvum infection in undernourished suckling mice involving nitric oxide synthase and arginase

ObjectiveThis study investigated the role of L-arginine supplementation to undernourished and Cryptosporidium parvum–infected suckling mice.MethodsThe following regimens were initiated on the fourth day of life and injected subcutaneously daily. The C. parvum–infected controls received L-arginine (200 mmol/L) or phosphate buffered saline. The L-arginine–treated mice were grouped to receive NG-nitro-arginine methyl ester (L-NAME) (20 mmol/L) or phosphate buffered saline. The infected mice received orally 10⁶ excysted C. parvum oocysts on day 6 and were euthanized on day 14 at the infection peak.ResultsL-arginine improved weight gain compared with the untreated infected controls. L-NAME profoundly impaired body weight gain compared with all other groups. Cryptosporidiosis was associated with ileal crypt hyperplasia, villus blunting, and inflammation. L-arginine improved mucosal histology after the infection. L-NAME abrogated these arginine-induced improvements. The infected control mice showed an intense arginase expression, which was even greater with L-NAME. L-arginine decreased the parasite burden, an effect that was reversed by L-NAME. Cryptosporidium parvum infection increased urine NO₃^?/NO₂^? concentrations compared with the uninfected controls, which was increased by L-arginine supplementation, an effect that was also reversed by L-NAME.ConclusionThese findings show a protective role of L-arginine during C. parvum infection in undernourished mice, with involvement of arginase I and nitric oxide synthase enzymatic actions.     

Is the chronic use of Ferula harmonis to enhance mice erectile function effective and safe? A histopathological study

Abstract

Many studies are aimed towards a solution for erectile dysfunction which is a worldwide health problem. Medicinal and natural herbal medications have been prescribed but their long-term effects are not well known. This study aimed to investigate the impact of the chronic administration of F. hermonis root extract on the structure of the male mice reproductive organs and their fertility and to study the possible protective role of vitamin C. Sixty male albino mice were divided into 3 groups: the control, the experimental group that received F. hermonis root extract orally (6?mg/kg) for six weeks, and the treated group that received F. hermonis plus vitamin C for six weeks. Serum testosterone level and mice fertility were assessed. At the end of the experiment mice were sacrificed; testis, epididymis, and seminal vesicle were dissected and processed for routine histopathological and immunohistochemical examination. The chronic administration of F. hermonis extract significantly decreased the level of testosterone and partially impaired fertility. Histopathological degenerative changes and a significant reduction in estrogen receptor (ER)β expression were observed in testes, epididymis, and seminal vesicle. Vitamin C administration did not completely protect the testis from these harmful effects. Although F. hermonis roots are recommended to improve erectile and fertility problems, it should be used for short periods and with extreme caution. Further clinical studies to assess safety and efficacy are needed.     

Serogroup B invasive meningococcal disease (IMD) outbreak at a Japanese high school dormitory: An outbreak investigation report from the first IMD outbreak in decades

PurposeThe first outbreak of invasive meningococcal disease (IMD) in decades occurred in a high school dormitory in 2011. This report aims to describe the results of the IMD outbreak investigation and to discuss current issues of IMD in Japan.MethodsWe conducted an epidemiological and microbiological investigation against the IMD outbreak of serogroup B among students and staff in a high school dormitory. Information on patients was collected to analyze risk factors for IMD. Control measures and public health actions were summarized.ResultsThree cases of meningitis and two cases of bacteremia were identified. Freshmen (15–16 years old) living in the dormitory with preceding cough were high-risk populations in this outbreak. Pulsed-field gel electrophoresis, multilocus sequence typing, and porA gene sequencing results revealed that all isolates were closely related to each other and had deep similarities to the domestic circulating meningococcal strain. The outbreak was terminated after promptly implementing control measures. Based on the results of our investigation, from April 2013, national infectious disease surveillance started to target meningococcal bacteremia as part of IMD, in addition to meningococcal meningitis, which was newly designated as a category II school infectious disease under the School Health and Safety Act.ConclusionsThis outbreak has enhanced public health measures against IMD in Japan. The development of national guidelines for appropriate public health interventions on the IMD outbreak response including chemoprophylaxis is still needed.     

Epidemiology and economic burden of meningococcal disease in Germany: A systematic review

IntroductionInvasive meningococcal disease (IMD) is a notifiable disease in Germany and other European countries. Due to the high lethality of the disease and the risk of long-term consequences, IMD prevention is of high public health relevance despite the low number of cases in the population. This study aims to describe key epidemiological and economic parameters of IMD in Germany to support national decision-making processes for implementing enhanced prevention measures.MethodsBased on a systematic literature review in PubMed and EMBASE, all publications on the burden of disease and costs of IMD published up to May 2020 were evaluated. Additionally, notification data were used to report the annual case numbers and incidence of IMD in Germany until the end of 2019.ResultsThirty-six studies were included, of which 35 reported data on the epidemiological burden of disease and three reported data on economic aspects of IMD. The type of reported endpoints and results on the incidence of IMD differed widely by reporting year, population, and data source used. Most of the data are reported without specific information about a serogroup. Data on the economic burden of disease and healthcare resource use are scarce. Based on mandatory notification data, a decrease in the incidence of notified IMD cases has been observed since 2004. Currently, the nationwide annual incidence in Germany is at 0.3 cases per 100,000 persons and has gradually decreased. While the overall decline is mainly attributable to MenB, cases with MenY and MenW are the only ones that have increased on a low level in recent years.ConclusionWhile IMD is a rare disease, high direct and indirect costs illustrate the relevance of the disease for patients, caregivers, as well as for the health care system. Future research should concentrate on quantifying the long-term economic burden and indirect costs of meningococcal disease. Integrated IMD surveillance with isolate characterisation remains crucial to inform public health policies.     

Meningococcal disease burden and transmission in crowded settings and mass gatherings other than Hajj/Umrah: A systematic review

BackgroundMass gatherings (MGs) such as the Hajj and Umrah pilgrimages are known to amplify the risk of invasive meningococcal disease (IMD) due to enhanced transmission of the organism between attendees. The burden of IMD at MGs other than Hajj and Umrah has not previously been quantified through a systematic review.MethodsA systematic search for relevant articles in PubMed and Embase was conducted using MeSH terms; this was buttressed by hand searching. Following data abstraction, a narrative synthesis was conducted to quantify the burden of IMD at MGs and identify potential risk factors and mitigation measures.ResultsThirteen studies reporting occurrence of IMD at MGs or similar crowded settings were identified. Eight studies reported cases or outbreaks in MGs of ≥1000 people; five others reported IMD in other crowded settings; all occurred between 1991 and 2015. All age groups were involved in the identified studies; however the majority of cases (∼80%) were young people aged 15–24 years. The number of affected people ranged from one to 321 cases and the overall crude estimate of incidence was calculated as 66 per 100,000 individuals. Serogroups A, C, B and W were identified, with serogroups A and C being most common. Of 450 cases of IMD reported in non-Hajj/Umrah MGs, 67 (14.9%) had fatal outcomes.ConclusionIMD outbreaks at non-Hajj/Umrah MGs are generally much smaller than Hajj-related outbreaks and affect mainly young people. Health education and vaccination should be considered for attendees of high risk non-Hajj/Umrah MGs, especially those involving adolescents and young adults.     

Changing epidemiology of Infant Meningococcal Disease after the introduction of meningococcal serogroup C vaccine in Italy, 2006–2014

BackgroundIn Italy, the incidence of Invasive Meningococcal Disease (IMD) was around 0.28 per 100,000 over the last years. Since the risk IMD is usually high among infants aged less than 1 year, we decided to evaluate the trend of IMD cases reported between 2006 and 2014 in this age group. In particular, the study aim was to describe the main characteristics of IMD cases in infants following the introduction of MCC vaccine (2005) and to estimate the number of cases which are potentially preventable through early vaccination.MethodsThe National Surveillance System of Bacterial Meningitis was established in 1994 and in 2007 was extended to all invasive bacterial diseases. Clinical data and isolates and/or clinical samples are collected from hospitalized patients throughout the country. IMD cases are reported by clinicians to the local health authorities, and samples are sent to the Reference Laboratory at the Istituto Superiore di Sanità for further characterization and storage at −80 °C. In particular, serogroup identification is obtained by agglutination with commercial antisera or by multiplex PCR.ResultsThe annual incidence for infants <1 year old remained rather stable of 3.6 per 100,000, with several upward and downward oscillations and a peak in 2010. The incidence of IMD among infants was more than 10 times higher than the overall rate of IMD observed in Italy. Finally, serogroup B was more frequently detected among infants aged <1 year, accounting for 65% of the total (p < 0.01).ConclusionsDuring the study period, IMD incidence reported among infants aged less than one year old was 10 times higher than the overall rate, and serogroup B was the most commonly detected over time. The long-term impact of meningococcal C conjugate vaccine and the effect of the introduction of meningococcal B vaccination among infants need to be evaluated.     

Cost-Effectiveness of 4CMenB Infant Vaccination in England: A Comprehensive Valuation Considering the Broad Impact of Serogroup B Invasive Meningococcal Disease

ObjectivesThis cost-effectiveness analysis (CEA) of 4CMenB infant vaccination in England comprehensively considers the broad burden of serogroup B invasive meningococcal disease (MenB IMD), which has not been considered, or was only partially considered in previous CEAs.MethodsA review of previous MenB vaccination CEAs was conducted to identify aspects considered in the evaluation of costs and health outcomes of the disease burden of MenB IMD. To inform the model structure and comprehensive analysis, the aspects were grouped into 5 categories. A stepwise analysis was conducted to analyze the impact of each category, and the more comprehensive consideration of disease burden, on the incremental cost-effectiveness ratio (ICER).ResultsMenB IMD incidence decreased by 46.0% in infants and children 0-4 years old within 5 years after introduction of the program. Stepwise inclusion of the 5 disease burden categories to a conventional narrow CEA setting reduced the ICER from £360 595 to £18 645—that is, considering the impact of all 5 categories, 4CMenB infant vaccination is cost-effective at a threshold of £20 000 per QALY gained.ConclusionsWhen considering comprehensively the MenB IMD burden, 4CMenB infant vaccination can be cost-effective, a finding contrary to previous CEAs. This analysis allows policy decision-makers globally to infer the impact of current disease burden considerations on the cost-effectiveness and the comprehensive assessment necessary for MenB IMD. Although this comprehensive CEA can help inform decision making today, it may be limited in capturing the full disease burden and complex interactions of health and economics of MenB IMD.     

Risk of invasive meningococcal disease in university students in England and optimal strategies for protection using MenACWY vaccine

PurposeIn August 2015, in response to increasing group W invasive meningococcal disease (IMD) nationally, a MenACWY vaccine programme was introduced in the UK for 13–18 year olds. We reviewed the epidemiology of IMD in young adults and university-associated cases in England during 2014–15 academic year and assessed the potential impact of different immunisation strategies.MethodsPublic Health England national enhanced surveillance data were used to describe the epidemiology of IMD cases in 15–24 year olds in England during 2014/15. Relative risks for IMD were calculated overall and by capsular group in students compared with non- student peers for 2014 and 2013 school leavers. Assuming stable future incidence and vaccine efficacy of 90% for five years, we estimated cases averted and numbers needed to vaccinate (NNV) for different MenACWY immunisation programmes: school-based adolescent, GP-based school leaver, and targeting freshers.ResultsBetween July 2014 and June 2015, 112 IMD cases were diagnosed in those born between 01/09/1991 and 31/08/2001 (∼15 to 24 year-olds). During the 2014/15 academic year (September to June), 49 IMD cases were reported among students attending English universities, including 22 among 2014 school leavers. In this cohort, the relative risk of IMD was higher among students compared to non-students for all capsular groups (RR 11.6; 95% CI 4.7–28.7) and for groups A/C/W/Y (RR 14.8; 95% CI, 4.3–51.5). A school-based programme could potentially have averted 14 cases in 2014/15 and 24 cases over five years with a lower NNV (18,000) than other programmes.ConclusionsUniversity students, particularly first years entering direct from school, are at higher risk for IMD than non-students. With high vaccine coverage and timely completion, an adolescent school-based MenACWY programme has the greatest potential to prevent cases with the lowest NNV, but population impact through indirect (herd) protection could take longer.     

Cost-effectiveness of meningococcal polysaccharide serogroups A,C, W-135 and Y conjugate vaccine in Australian adolescents

ObjectivesThe incidence of invasive meningitis disease (IMD) is increasing in Australia. A conjugate vaccine of meningococcal polysaccharide serogroups A, C, W and Y (MenACWY) is currently indicated for infants aged 12 months on the Australian National Immunisation Program. This study sought to determine the cost-effectiveness of a broader MenACWY vaccination program for Australians aged 15 to 19 years.MethodsA Markov model was constructed to simulate the incidence and consequences of IMD in Australians aged 0–84 years, with follow up until age 85 years. The model comprised four health states: ‘Alive with no previous IMD’, ‘Alive, post IMD without long-term complications’, ‘Alive, post IMD with long-term complications’ and ‘Dead’. Decision analysis compared the clinical consequences and costs of a vaccination program versus no vaccination from the perspective of the Australian health care system. Age-specific incidence of IMD and fatality rates were derived from Australian surveillance data. Vaccine coverage, vaccine efficacy and herd immunity were based on published data. The total cost for MenACWY vaccination was AU$56 per dose. Costs and health outcomes were discounted by 5% per annum (in the base-case analysis).ResultsCompared to no vaccination, a MenACWY vaccination program targeted at Australians aged 15–19 years was expected to prevent 1664 IMD cases in the Australian population aged 0–84 years followed up until age 85 years. The program would lead to 1131 life years (LYs) and 2058 quality adjusted life years (QALYs) gained at a total cost of AU$115 million (all discounted values). These equated to incremental cost-effectiveness ratios of AU$101,649 per LY gained and AU$55,857 per QALY gained. A probabilistic sensitivity analysis demonstrated a likelihood of cost-effectiveness of 34.6%, assuming a willingness to pay threshold of AU$50,000 per QALY gained.ConclusionThe likelihood of this program being cost-effective under a willingness to pay threshold AU$50,000 per QALY gained is 35%.     

The epidemiology of invasive meningococcal disease in EU/EEA countries, 2004–2014

BackgroundInvasive meningococcal disease (IMD) is a major cause of bacterial meningitis and septicaemia although infection by some serogroups may be prevented through vaccination. We aimed to describe the epidemiology of IMD in EU/EEA countries during 2004–2014 to monitor serogroup- and age-specific trends, and compare country trends by the period of meningococcal C conjugate (MCC) vaccine introduction.MethodsWe analysed IMD surveillance data by age, gender, serogroup, country and outcome. We estimated the percentage change in annual notification rate (NR), using linear regression analysis of the log of the annual NR. We grouped countries by the year they introduced MCC vaccination into their routine immunisation programmes.ResultsThe overall NR was 0.9/100 000 population, and decreased 6.6% (95%CI: −8.0%;−5.1%) annually. Infants had the highest NR (16.0/100 000), and there were decreasing trends in all age groups <50 years. Serogroup B (SgB) caused 74% of all cases, and the majority of cases in all age groups. There were decreasing trends in SgB and serogroup C (SgC) and an increasing trend in serogroup Y. Countries that introduced MCC vaccination before, and between 2004 and 2014, had decreasing trends in NR of SgC, but not countries without routine MCC vaccination.ConclusionsOur findings support evidence that routine MCC vaccination was the driving force behind the decreasing SgC trend. Vaccinating against SgB in the first year of life could help reduce the burden of IMD due to this serogroup. Changing serogroup-specific NR trends highlight the need for high-quality surveillance data to accurately assess the changing epidemiology of IMD, the effectiveness and impact of implemented vaccines, and the need for future vaccines.     

Case fatality rates of invasive meningococcal disease by serogroup and age: A systematic review and meta-analysis

IntroductionInvasive meningococcal disease (IMD) is uncommon but still causes considerable public health burden due to its high mortality and morbidity. This review aims to quantitatively synthesise all published evidence pertinent to mortality caused by IMD and assess the effect of age and serogroup on case fatality rates (CFRs).MethodsThe PubMed and Embase databases, and the Cochrane Library were searched. Articles reporting national CFRs and published in English between January 2000 and May 2018 were eligible. The studies reporting mortality resulting from a specific symptom of IMD (e.g. meningococcal meningitis) were excluded. Mixed-effects logistic regression with a restricted cubic spline was used to analyse CFRs as a function of age. Random-effects meta-analyses were performed to estimate an overall CFR and CFRs by serogroup.ResultsAmong 48 eligible studies reporting national CFRs, 40 studies were included in meta-analyses representing 163,758 IMD patients. CFRs ranged from 4.1% to 20.0% with the pooled overall CFR of 8.3% (95% confidence interval (CI): 7.5–9.1%). Serogroup B was associated with a lower pooled CFR (6.9% (95%CI: 6.0–7.8%)) than other serogroups (W: 12.8% (95%CI: 10.7–15.0%); C: 12.0% (95%CI: 10.5–13.5%); Y: 10.8% (95%CI: 8.2–13.4%)). The meta-analysis was not performed for serogroup A (MenA) cases due to a small number of MenA patients who were enrolled in eligible studies. For laboratory confirmed IMD cases, the predicted CFR was 9.0% in infants, gradually decreased to 7.0% in 7-year olds, subsequently increased to 15.0% in young adults aged 28 years, stabilised between 15 and 20% in mid-aged adults and reached a high in elderly people.ConclusionsOur findings can provide useful information for better understanding the mortality risks, and quantifying the burden associated with IMD mortality.     

The burden of invasive meningococcal disease in the Netherlands, 2011–2020

IntroductionRepresentative information on disease course and outcome of invasive meningococcal disease (IMD) is important because of the shift in meningococcal epidemiology that recently occurred in the Netherlands. With this study, we update earlier research on the burden of IMD in the Netherlands.Material and methodsWe performed a retrospective study using Dutch surveillance data on IMD from July 2011 to May 2020. Clinical information was collected from hospital records. The effect of age, serogroup, and clinical manifestation on disease course and outcome was assessed in multivariable logistic regression analyses. Grouping of infecting isolates was performed by Ouchterlony gel diffusion or by PCR.ResultsClinical information was collected for 278 IMD cases of which the majority had IMD-B (55%), followed by IMD-W (27%), IMD-Y (13%), and IMD-C (5%). Most patients presented with meningitis (32%) or sepsis (30%). Hospitalisation for ≥ 10 days was most frequent among 24–64 year olds (67%). ICU admission was highest among 24–64 year olds (60%), and in case of sepsis (70%), or sepsis plus meningitis (61%). Sequelae at discharge was lower for patients with mild meningococcaemia compared to patients with sepsis plus meningitis (OR: 0.19, 95% CI: 0.07–0.51). The overall case fatality rate was 7%, and was highest for IMD-Y (14%) and IMD-W (13%) patients.ConclusionsIMD remains a disease with high morbidity and mortality. Sepsis (with or without meningitis) is associated with a more severe disease course and outcome compared to other clinical manifestations. The high disease burden can be partly prevented by meningococcal vaccination.     

Lifetime costs of invasive meningococcal disease: A Markov model approach

IntroductionInvasive meningococcal disease (IMD) is an uncommon but life-threatening infectious disease associated with high sequelae rates in young children and an increased risk of mortality in adolescents and young adults. Funding decisions to reject inclusion of new meningococcal serogroup B vaccines on national immunisation schedules have been criticised by IMD patients, their families, paediatricians and charity organisations. We aim to estimate the lifetime costs of IMD with the best available evidence to inform cost-effectiveness analyses.MethodsA Markov model was developed taking healthcare system and societal perspectives. A range of data including age-specific mortality rates, and probabilities of IMD-related sequelae were derived from a systematic review and meta-analysis. All currencies were inflated to year 2017 prices by using consumer price indexes in local countries and converted to US dollars by applying purchasing power parities conversion rates. Expert panels were used to inform the model development process including key structural choices and model validations.ResultsThe estimated lifetime societal cost is US$319,896.74 per IMD case including the direct healthcare cost of US$65,035.49. Using a discount rate of 5%, the costs are US$54,278.51 and US$13,968.40 respectively. Chronic renal failure and limb amputation result in the highest direct healthcare costs per patient. Patients aged < 5 years incur the higher healthcare expenditure compared with other age groups. The costing results are sensitive to the discount rate, disease incidence, acute admission costs, and sequelae rates and costs of brain injuries and epilepsy.ConclusionsIMD can result in substantial costs to the healthcare system and society. Understanding the costs of care can assist decision-making bodies in evaluating cost-effectiveness of new vaccine programs.     

Search filters can find some but not all knowledge translation articles in MEDLINE: an analytic survey

ObjectiveAdvances from health research are not well applied giving rise to over- and underuse of resources and inferior care. Knowledge translation (KT), actions and processes of getting research findings used in practice, can improve research application. The KT literature is difficult to find because of nonstandardized terminology, rapid evolution of the field, and it is spread across several domains. We created multiple search filters to retrieve KT articles from MEDLINE.Study Design and SettingAnalytic survey using articles from 12 journals tagged as having KT content and also as describing a KT application or containing a KT theory.ResultsOf 2,594 articles, 579 were KT articles of which 201 were about KT applications and 152 about KT theory. Search filter sensitivity (retrieval efficiency) maximized at 83%–94% with specificity (no retrieval of irrelevant material) approximately 50%. Filter performances were enhanced with multiple terms, but these filters often had reduced specificity. Performance was higher for KT applications and KT theory articles. These filters can select KT material although many irrelevant articles also will be retrieved.ConclusionKT search filters were developed and tested, with good sensitivity but suboptimal specificity. Further research must improve their performance.     

Sociodemographic predictors of variation in coverage of the national shingles vaccination programme in England, 2014/15

IntroductionIn September 2013, England introduced a shingles vaccination programme to reduce incidence and severity of shingles in the elderly. This study aims to assess variation in vaccine coverage with regards to selected sociodemographic factors to inform activities for improving equity of the programme.MethodsEligible 70 year-olds were identified from a national vaccine coverage dataset in 2014/15 that includes 95% of GPs in England. NHS England Local Team (LT) and index of multiple deprivation (IMD) scores were assigned to patients based on GP-postcode. Vaccine coverage (%) with 95% confidence intervals (CIs), were calculated overall and by LT, ethnicity and IMD, using binomial regression.ResultsOf 502,058 eligible adults, 178,808 (35.6%) had ethnicity recorded. Crude vaccine coverage was 59.5% (95%CI: 59.3–59.7). Coverage was lowest in London (49.6% coverage, 95%CI: 49.0–50.2), and compared to this coverage was significantly higher in all other LTs (+6.3 to +10.4, p < 0.001) after adjusting for ethnicity and IMD. Coverage decreased with increasing deprivation and was 8.2% lower in the most deprived (95%CI: 7.3–9.1) compared with the least deprived IMD quintile (64.1% coverage, 95%CI: 63.6–64.6), after adjustment for ethnicity and LT. Compared with White-British (60.7% coverage, 95%CI: 60.5–61.0), other ethnic groups had between 4.0% (Indian) and 21.8% (Mixed: White and Black African) lower coverage. After adjusting for IMD and LT, significantly lower coverage by ethnicity persisted in all groups, except in Mixed: Other, Indian and Bangladeshi compared with White-British.ConclusionsAfter taking geography and deprivation into account, shingles vaccine coverage varied by ethnicity. White-British, Indian and Bangladeshi groups had highest coverage; Mixed: White and Black African, and Black-other ethnicities had the lowest. Patients' ethnicity and IMD are predictors of coverage which contribute to, but do not wholly account for, geographical variation coverage. Interventions to address service-related, sociodemographic and ethnic inequalities in shingles vaccine coverage are required.     

Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats

ObjectiveLiver fibrosis and subsequent cirrhosis is a major cause of death worldwide, but few effective antifibrotic therapies are reported. Whey-hydrolyzed peptide (WHP), a major peptide component of bovine milk, exerts anti-inflammatory effects in experimental models. A WHP-enriched diet is widely used for immunomodulating diets (IMD) in clinical fields. However, the effects of WHP on liver fibrosis remain unknown. The aim of this study was to investigate the antifibrotic effects of WHP in a rat cirrhosis model.MethodsProgressive liver fibrosis was induced by repeated intraperitoneal administration of dimethylnitrosamine (DMN) for 3 wk. Rats were fed either a WHP-enriched IMD (WHP group) or a control enteral diet (control group). The degree of liver fibrosis was compared between groups. Hepatocyte-protective effects were examined using hepatocytes isolated from rats fed a WHP diet. Reactive oxygen species and glutathione in liver tissue were investigated in the DMN cirrhosis model.ResultsMacroscopic and microscopic progression of liver fibrosis was remarkably suppressed in the WHP group. Elevated serum levels of liver enzymes and hyaluronic acid, and liver tissue hydroxyproline content were significantly attenuated in the WHP group. Necrotic hepatocyte rates with DMN challenge, isolated from rats fed a WHP-enriched IMD, were significantly lower. In the DMN cirrhosis model, reactive oxygen species were significantly lower, and glutathione was significantly higher in the WHP group’s whole liver tissue.ConclusionA WHP-enriched IMD effectively prevented progression of DMN-induced liver fibrosis in rats via a direct hepatocyte-protective effect and an antioxidant effect through glutathione synthesis.     

Cost of illness of invasive meningococcal disease caused by serogroup B Neisseria meningitidis in Spain

IntroductionInvasive meningococcal disease (IMD) is a severe infectious disease, mainly affecting children under 5 years, associated with long-term physical, neurological and psychological sequelae. In Spain, most IMD cases are caused by meningococcal serogroup B (MenB). This study estimates its economic burden from a societal perspective in Spain.MethodsA previously published bottom-up, model-based incidence costing approach by Scholz et al. (2019) to estimate the economic burden of MenB in Germany was adapted to the Spanish setting. Diagnosis and age-related costs for a hypothetical Spanish cohort were calculated over a lifetime horizon. Official Spanish databases, literature and expert opinion were used as data sources. The costs were updated to 2019 prices, and a 3% discount rate was applied. Direct costs related to the acute IMD phase, long-term sequelae, rehabilitation and public health response were considered. Indirect costs included productivity losses and premature mortality and were calculated using the human-capital approach (HCA) and friction-cost approach (FCA). Deterministic and probabilistic sensitivity analyses were also performed.ResultAt base-case, the total cost for a cohort of 142 patients (2017–2018 period) was €4.74 million (€33,484/case) using the FCA and €13.14 million (€92,768/case) using the HCA. Direct costs amounted to €4.65 million (€32,765/case). Sequelae costs represented 62.46% of the total cost using the FCA and 77.63% using the HCA. Deterministic sensitivity analysis showed that variation of ± 20% in the input parameter values (population, epidemiology, productivity, costs) had the greatest influence on the base-case results, and the probabilistic sensitivity analysis showed the probability of fitting base-case estimates was > 99%, both for FCA and HCA.DiscussionMenB IMD is an uncommon but severe disease, with a high economic burden for Spanish society. The elevated costs per IMD case reflect its severity in each patient suffering this disease, especially due to the development of sequelae.     

精浆一氧化氮与精液主要参数之间关系探讨

目的:探讨精浆一氧化氮与精液主要参数之间关系。方法:应用精子质量自动分析系统(CASA)检测精液主要参数,采用分光光度比色法检测精浆一氧化氮含量。结果:精浆一氧化氮含量与精液白细胞浓度呈低度正相关关系(r=0·294,P≤0·05),与精液量呈低度负相关关系(r=-0·33,P≤0·05);与a,b级精子百分率、精子密度、形态正常精子百分率均无显著相关性(P>0·05);精液参数正常组与异常组精浆一氧化氮含量比较差异无显著性(P>0·05);精液白细胞浓度、a,b级精子百分率、精液量、精子密度、形态正常精子百分率正常组与其对应的异常组比较,精浆NO含量差异亦均无显著性(P>0·05)。结论:精浆一氧化氮与精液主要参数无明显密切关系。