The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution method.The frequency of resistance(FoR)to MEM combined with InC58 was investigated.Mutants were sequenced and tested for cross resistance,fitness,and the stability of the resistance phenotype.Compared with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(P.aeruginosa)and OXA-23-carrying Acinetobacter baumannii(A.baumannii).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,respectively.The mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

3D printing of poly(ethyleneimine)-functionalized Mg-Al mixed metal oxide monoliths for direct air capture of CO_(2)

Direct air capture(DAC)of CO_(2)plays an indispensable role in achieving carbon-neutral goals as one of the key negative emission technologies.Since large air flows are required to capture the ultradilute CO_(2)from the air,lab-synthesized adsorbents in powder form may cause unacceptable gas pressure drops and poor heat and mass transfer efficiencies.A structured adsorbent is essential for the implementation of gas-solid contactors for cost-and energy-efficient DAC systems.In this study,efficient adsorbent poly(ethyleneimine)(PEI)-functionalized Mg-Al-CO_(3)layered double hydroxide(LDH)-derived mixed metal oxides(MMOs)are three-dimensional(3D)printed into monoliths for the first time with more than 90%adsorbent loadings.The printing process has been optimized by initially printing the LDH powder into monoliths followed by calcination into MMO monoliths.This structure exhibits a 32.7%higher specific surface area and a 46.1%higher pore volume,as compared to the direct printing of the MMO powder into a monolith.After impregnation of PEI,the monolith demonstrates a large adsorption capacity(1.82 mmol/g)and fast kinetics(0.7 mmol/g/h)using a CO_(2)feed gas at 400 ppm at 25℃,one of the highest values among the shaped DAC adsorbents.Smearing of the amino-polymers during the post-printing process affects the diffusion of CO_(2),resulting in slower adsorption kinetics of pre-impregnation monoliths compared to post-impregnation monoliths.The optimal PEI/MeOH ratio for the post-impregnation solution prevents pores clogging that would affect both adsorption capacity and kinetics.

Quercetin inhibits truncated isoform of dopamine-and cAMP-regulated phosphoprotein as adjuvant treatment for trastuzumab therapy resistance in HER2-positive breast cancer

Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression.To evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor tissues.We established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer assays.Instead,there is no response from the responder.Furthermore,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell migration.We found that quercetin effectively reduced t-DARPP expression in HER2+BC cells.In t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest.In conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.

3D bioprinting of in vitro porous hepatoma models:establishment,evaluation,and anticancer drug testing

Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma:A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.

Recent advances in RNA-targeting therapy for neurological diseases

Advances in sequencing and molecular technology now allow us to understand the genetic underpinnings of complex diseases such as neurological disorders.Genetic variations(or mutations) in the DNA sequence of single genes have been implicated in neurological diseases such as Huntington's disease and spinal muscular atrophy.As a result,the development of gene therapies for neurological diseases is now a feasible endeavor.

An Experimental Study of Composite Columns Filled with Eucalyptus nitens Timber under Axial Compression

Eucalyptus nitens(E.nitens)has been much used for producing paper but also shows promise for structural applications.In this study,static compressive tests were undertaken to examine its suitability to be used in an innovative composite column.The composite column was comprised of a rectangular steel tube with E.nitens timber infill.The nonlinear compressive behaviour of the composite column filled with E.nitens wood for both dry and wet conditions was examined.The same tests on rectangular steel tubes and bare dry and wet E.nitens samples were also undertaken as a comparison.For samples with different conditions,the ultimate capacity was evaluated and the effect of each condition on the compressive behaviour of the composite column was clarified.The steel tubes showed greater ductile behaviour,and more ductility was found in the wet samples.The steel tubes with E.nitens timber infill samples exhibited a greater linear elastic range connected with higher maximum loads,while the bare timber samples could support only lower maximum loads.The results from this research were promising for the use of rectangular steel tubes with E.nitens timber infill in structural applications.

Epidemiology, Diagnosis and Survival of Breast Cancer: Data from the Population-Based Cancer Registry of the City of Parakou from 2017 to 2021

Background: Breast cancer mortality remains high in the majority of developing countries. The Ministry of Health has established two population-based cancer registries in Benin: the first one in Cotonou in 2014 and the second one in Parakou in 2017. However, there is a scarcity of data on breast cancer survival and prognosis in Benin Republic. Objective: This study sought to investigate epidemiological, diagnostic, and survival aspects of breast cancer in Parakou, based on data from its population-based cancer registry from 2017 to 2021. Method: For descriptive and analytical purposes, we used a retrospective cohort design. From January 24, 2022 to August 31, 2022, data were collected in all health facilities covered by the Parakou population-based cancer registry using an individual questionnaire. Survival and prognosis analysis were performed using KAPLAN MEIER method and David COX proportional hazard model respectively. Result: A total of 81 patients have been included in this study. The incidence rate of breast cancer in Parakou was 17.5 per 100,000 person-years with a mortality rate of 2.76 per 100,000 person-years. The median age at diagnosis was 44.50 years with extremes ranging from 19 to 76 years and a predominance of 40 - 50 years age group. The median survival time was estimated at 30 months with an overall 5-year survival of 47%. Young age at diagnosis (p-value = 0.002) and advanced stage at diagnosis (p-value = 0.000) had a negative impact on survival in women. The combination of surgery and chemotherapy improved survival (p-value = 0.018). Conclusion: Breast cancer is still a public health issue in Parakou. It comes out mandatory that resources be made available to make screening, early diagnosis and appropriate treatment of breast cancer affordable.

Surveillance of Surgical Site Infections: A Public Health Emergency in a Regional Hospital of Northern Benin. A Prospective Observational Pilot Study

Background: Surgical site infections (SSIs) are considered as result of the healthcare quality in hospitals. Objective: to study SSI at Saint Jean de Dieu Hospital Tanguieta (SJDHT), prior to the implementation of a permanent monitoring system. Method: transversal, and descriptive study with prospective data collection was performed from 1 July to 31 janvier 2017 in the department of general surgery of SJDHT. The hospital lacks in a microbiology unit. All patients who underwent surgery during this period were included and the monitoring lasted one month. SSIs diagnostic was carried out according to WHO criteria as described in the Practical Guide for the Prevention of Nosocomial Infections published in 2002. Statistical tests (χ-square and Student’s t-test) were applied and p 0.05 were statistically significant. Results: Of 343 patients recorded, 105 (30.6%) had SSI. Their age averaged 40.3 years and the sex-ratio (men/women) was 2.8. The emergency surgery resulted in a 50.0% rate of SSI (p = 0.00). The SSI rate for clean and clean-contaminated surgery was 6.3% against 94.6% for infected surgery (p = 0.00). The SSI rates were 100% and 66.7% for NNISS = 2 and NNISS = 1 (p = 0.00), respectively. Superficial SSI rate was 13.3%, while deep SSI and organ/space SSI were 46.7% and 40%, respectively. The hospital stay of patients with SSI was three times longer than the length of patients without SSI (p = 0.00). Conclusion: SSIs are real burden at SJDHT. Appropriate measures must be adopted to reduce its prevalence.

Relationship between vitamin D deficiency and cardiovascular disease

Epidemiological studies have found that low 25-hydroxyvitamin D levels may be associated with coronary risk factors and adverse cardiovascular outcomes.Additionally,vitamin D deficiency causes an increase in parathyroid hormone,which increases insulin resistance and is associated with diabetes,hypertension,inflammation,and increased cardiovascular risk.In this review,we analyze the association between vitamin D supplementation and the reduction in cardiovascular disease.The role of vitamin D deficiency in cardiovascular morbidity and mortality is still controversial,and larger scale,randomized placebo controlled trials are needed to investigate whether oral vitamin D supplementation can reduce cardiovascular risk.Given the low cost,safety,and demonstrated benefit of higher 25-hydroxyvitamin D levels,vitamin D supplementation should become a public health priority for combating common and costly chronic cardiovascular diseases.

Resistance Evaluation of Some Chinese Leading Rice Maintainer, Restorer lines and Their Hybrids to Magnaporthe grisea

Six isolates of Magnaporthe grisea were selected to inoculate on 10 Chinese leading maintainer lines (B-lines), 14 restorer lines (R-lines) and their F1 hybrid plants. In the tested rice materials, R-lines were proved to be more resistant to blast than B-lines. The resistance frequency of about 25% F1 hybrid plants was less than their parents. In addition, 26 isolates of M. grisea collected from different rice growing areas of China were inoculated on 13 new improved hybrid rice combinations. The resistance frequencies of 5 improved hybrids were better than those of the controls and leading varieties in rice production of China.

Climate and meteorological processes of the East Antarctic ice sheet between Zhongshan and Dome-A

The 1228 km over-snow traverse route between the Chinese Zhongshan Station, on the coast of Prydz Bay, and Dome-A, at 4091 m elevation the highest point of the East Antarctic ice sheet, has been the focus of CHINARE surface meteorological and climate studies since 2002. A network of seven Automatic Weather Stations has been deployed along this section, including at Dome-A itself, and some of these have now provided nearly-hourly data for over a decade. Atmospheric boundary layer turbulence and radiation observations have been made over the near-coastal ice sheet inland of Zhongshan and surface turbulence measurements using an ultrasonic anemometer system have also been made in the deep interior of the ice sheet. Summer GPS radiosonde soundings of the atmospheric boundary layer have been made at Kunlun Station, near Dome-A. In this paper these observations are combined to provide a comprehensive overview of the meteorological regime of this region of the ice sheet, its climate variability, and as a reference for future study of climate change. This includes investigation of the variation of surface climate features with elevation and distance from the coast, the height and structure of the boundary layer over the ice sheet, and seasonal and regional changes in ice/snow-air interactions, including turbulent and radiative energy fluxes. The air temperature and snow temperature between the coastal Zhongshan and Dome-A on the inland plateau have not changed significantly in the past decade compared with the inter-annual variability.

The influence of defects in a plasma photonic crystal on the characteristics of microwave transmittance

Plasma photonic crystals(PPCs) have been a hot research topic in the band gap(BG) material field in recent years due to their unique advantages, such as the feasibility of changing the parameters and hence the properties of the materials with respect to traditional photonic crystals(PCs). In this paper,we focus mainly on the effects of some types of defects introduced in PPCs on the changes in BG characteristics of microwave(MW) transmittance. The research is carried out using numerical simulation with a one-dimensional finite-difference time-domain(FDTD) method, and six types of defects, including a lattice-constant defect, radii-ratio defect, additional-column defect, column-width defect, plasma-frequency defect, and electron-collision-frequency defect, are concerned. It transpires that introducing a defect in a PPC in different manners may realize the symmetric change, alternative change, shifting, generating, transforming, disappearing, and attenuating of BGs in transmittance spectra, which has great potential for the manufacture of spatiotemporal-controllable MW materials and devices with more feasible modulating functions.

Alkali metal cation effects on electrocatalytic CO_(2)reduction with iron porphyrins

The electrocatalytic CO_(2)reduction reaction(CO_(2)RR)has attracted increasing attention in recentyears.Practical electrocatalysis of CO_(2)RR must be carried out in aqueous solutions containing electrolytesof alkali metal cations such as sodium and potassium.Although considerable efforts havebeen made to design efficient electrocatalysts for CO_(2)RR and to investigate the structure–activityrelationships using molecular model complexes,only a few studies have been investigated the effectof alkali metal cations on electrocatalytic CO_(2)RR.In this study,we report the effect of alkali metalcations(Na^(+)and K^(+))on electrocatalytic CO_(2)RR with Fe porphyrins.By running CO_(2)RR electrocatalysisin dimethylformamide(DMF),we found that the addition of Na^(+)or K^(+)considerably improves thecatalytic activity of Fe chloride tetrakis(3,4,5‐trimethoxyphenyl)porphyrin(FeP).Based on thisresult,we synthesized an Fe porphyrin^(N)18C6‐FeP bearing a tethered 1‐aza‐18‐crown‐6‐ether(^(N)18C6)group at the second coordination sphere of the Fe site.We showed that with the tethered^(N)18C6 to bind Na^(+)or K^(+),^(N)18C6‐FeP is more active than FeP for electrocatalytic CO_(2)RR.This workdemonstrates the positive effect of alkali metal cations to improve CO_(2)RR electrocatalysis,which isvaluable for the rational design of new efficient catalysts.

Effect of Postmortem Ageing on Quality Parameters,Contents of Proteins,Lipids and 25-Hydroxyvitamin D and Oxidative Stability in the Camel Meat during Cold Storage

The effect of ageing was evaluated on quality parameters(pH,electrical conductivity(EC),osmolality,drip loss(DL)and cooking loss(CL)),proteins,fat and 25-hydroxyvitamin D(25-OH-D)total levels and antioxidant status(malondialdehyde(MDA)and catalase(CAT)activity)in meat of camels during storage at 4±1°C.Samples were taken from the brachial triceps muscle(triceps barchii)and were stored at 4±1°C for 10 d.Quality parameters,chemical composition and antioxidant status were assessed at 3 h and 24 h postslaughter and 5,7 and 10 d postmortem during cold storage.CAT activity significantly decreased while osmolality,EC,DL,CL and MDA contents significantly increased,from the 5th or 7th postmortem day of cold storage of the camel meat.However,proteins,lipids and 25-OH-D total contents showed no significant differences during all period of ageing.In conclusion,in the dromedary camel,ageing time of triceps muscle influenced significantly its quality characteristics and antioxidant status from the 5th or 7th postmortem day of refrigerated storage,without any variation of proteins,fat and 25-OH-D contents.

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab

AIM:To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.METHODS:We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts:(1) the AGITG MAX trial(Phase Ⅲ randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine,bevacizumab and mitomycin C);(2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer(TRACC) registry(any first-line regimen ± bevacizumab);and(3) two cancer centres in New South Wales,Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre(NSWCC) from January 2005 to Decenber 2012,(any first-line regimen ± bevacizumab).For the AGITG MAX trial capecitabine was compared to the other two arms(capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycin C).In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases.Secondary endpoints included progression-free survival,chemotherapy duration,and overall survival.Time-toevent outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS:Eighty-four MAX,179 TRACC and 69 NSWCC patients had peritoneal disease.There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts.Of the patients without peritoneal disease in the MAX trial,4/300(1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123(0.8%) in the capecitabine alone arm.In the TRACC registry 3/126(2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53(1.9%) in the chemotherapy alone arm.In a further analysis of patients without peritoneal metastases in the TRACC registry,the rate of gastrointestinal perforations was 9/369(2.4%) in the chemotherapy/bevacizumab group and 5/177(2.8%) in the chemotherapy alone group.The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts:MAX 6.9 m vs 4.9 m,HR = 0.64(95%CI:0.42-1.02);P = 0.063;TRACC 9.1 m vs 5.5 m,HR = 0.61(95%CI:0.37-0.86);P = 0.009;NSWCC 8.7 m vs 6.8 m,HR = 0.75(95%CI:0.43-1.32);P = 0.32.Chemotherapy duration was similar across the groups.CONCLUSION:Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.

Au/CuO_x-TiO₂Catalysts for CO Oxidation at Low Temperature

A series of Au/CuOx-TiO2 with various Cu/Ti ratios were prepared. CuOx/TiO2 was prepared by incipient-wetness im- pregnation with aqueous solution of copper nitrate. Au catalysts were prepared by deposition-precipitation method at pH 7 and 338 K. The catalysts were characterized by inductively-coupled plasma-mass spectrometry, temperature pro- gramming reduction, X-ray diffraction, transmission electron microscopy, high-resolution transmission electron mi- croscopy and X-ray photoelectron spectroscopy. The reaction was carried out in a fixed bed reactor with a feed con- taining 1% CO in air at WHSV of 120,000 mL/h·g. High gold dispersion and narrow size distribution was obtained. The addition of CuOx in Au/TiO2 enhanced the activity on CO oxidation significantly. CuOx was in amorphous state which could stabilize the Au nanoparticles. Cu was in Cu1+ state. Cu donated partial electrons to Au. The interactions among Au, Cu1+ and TiO2 account for the high catalytic activity for CO oxidation. The significant promotional effect of CuOx on CO oxidation at low temperature was demonstrated.

Bending Stresses of Steel Web Tapered Tee Section Cantilevers

Although commonly used, no design method is available for steel web tapered tee section cantilevers. This paper investigates the bending stresses of such beams. Relationships between the maximum compressive stress and the degree of taper were investigated. An analytical model is presented to determine the location of the maximum stress when subjected to a uniformly distributed load or a point load at the free end and was validated using finite element analysis and physical tests. It was found that the maximum stress always occurs at the support when subjected to a uniformly distributed load. When subjected to a point load at the free end and the degree of taper is up to seven, it was found that Miller＇s equation could be used to determine the location of the maximum stress. However, it is shown that when the degree of taper is greater than seven, Miller＇s equation does not accurately predict the location and the analytical model should be used. It was also found that the location of the maximum stress was solely dependent on the degree of taper, while a geometric ratio, fl was required to determine the magnitude of the maximum stress. A simple method that predicts the magnitude of the maximum stress is proposed. The average error in the prediction of the magnitude of the maximum stress is found to be less than 1.0%.

Importance of Viral Disease in Dairy Cow Fertility

Many viral diseases are endemic in cattle populations worldwide. The ability of many viruses to cross the placenta and cause abortions and fetal malformations is well understood. There is also significant evidence that viral infections have additional actions in dairy cows, which are reflected in reduced conception rates. These effects are, however, highly dependent on the time at which an individual animal first contracts the disease and are less easy to quantify. This paper reviews the evidence relating to five viruses that can affect fertility, together with their potential mechanisms of action. Acute infection with non-cytopathic bovine viral diarrhea virus (BVDV) in mid-gestation increases abortion rates or causes the birth of persistently infected calves. BVDV infections closer to the time of breeding can have direct effects on the ovaries and uterine endometrium, which cause estrous cycle irregularities and early embryo mortality. Fertility may also be reduced by BVDV-induced immunosuppression, which increases the susceptibility to bacterial infections. Bovine herpesvirus (BHV)-1 is most common in pre-pubertal heifers, and can slow their growth, delay breeding, and increase the age at first calving. Previously infected animals subsequently show reduced fertility. Although this may be associated with lung damage, ovarian lesions have also been reported. Both BHV-1 and BHV-4 remain latent in the host following initial infection and may be reactivated later by stress, for example associated with calving and early lactation. While BHV-4 infection alone may not reduce fertility, it appears to act as a co-factor with established bacterial pathogens such as Escherichia coli and Trueperella pyogenes to promote the development of endometritis and delay uterine repair mechanisms after calving. Both Schmallenberg virus (SBV) and bluetongue virus (BTV) are transmitted by insect vectors and lead to increased abortion rates and congenital malformations.BTV-8 also impairs the development of hatched blastocysts;furthermore, infection around the time of breeding with either virus appears to reduce conception rates. Although the reductions in conception rates are often difficult to quantify, they are nevertheless sufficient to cause economic losses, which help to justify the benefits of vaccination and eradication schemes.

Incidence and mortality of acute and chronic pancreatitis in the Netherlands:A nationwide record-linked cohort study for the years 1995-2005

AIM:To analyze trends in incidence and mortality of acute pancreatitis(AP) and chronic pancreatitis(CP) in the Netherlands and for international standard populations.METHODS:A nationwide cohort is identified through record linkage of hospital data for AP and CP,accumulated from three nationwide Dutch registries:the hospital discharge register,the population register,and the death certificate register.Sex-and age-group specific incidence rates of AP and CP are defined for the period 2000-2005 and mortality rates of AP and CP for the period 1995-2005.Additionally,incidence and mortality rates over time are reported for Dutch and international(European and World Health Organization) standard populations.RESULTS:Incidence of AP per 100000 persons per year increased between 2000 and 2005 from 13.2(95%CI:12.6-13.8) to 14.7(95%CI:14.1-15.3).Incidence of AP for males increased from 13.8(95%CI:12.9-14.7) to 15.2(95%CI:14.3-16.1),for females from 12.7(95%CI:11.9-13.5) to 14.2(95%CI:13.4-15.1).Irregular patterns over time emerged for CP.Overall mean incidence per 100000 persons per year was 1.77,for males 2.16,and for females 1.4.Mortality for AP fluctuated during 1995-2005 between 6.9 and 11.7 per million persons per year and was almost similar for males and females.Concerning CP,mortality for males fluctuated between 1.1(95%CI:0.6-2.3) and 4.0(95%CI:2.8-5.8),for females between 0.7(95%CI:0.3-1.6) and 2.0(95%CI:1.2-3.2).Incidence and mortality of AP and CP increased markedly with age.Standardized rates were lowest for World Health Organization standard population.CONCLUSION:Incidence of AP steadily increased while incidence of CP fluctuated.Mortality for both AP and CP remained fairly stable.Patient burden and health care costs probably will increase because of an ageing Dutch population.