ABSTRACT
BACKGROUND: Replenishing the physician-scientist workforce constitutes a central mission of medical education, but the loss of qualified trainees to non-academic positions remains an ongoing threat. Among the barriers facing physician-scientists today is the game-like model of U.S. medical residency matching through the National Research Matching Program (NRPM), which applies several assumptions regarding the comparability of applicant qualifications, cohort size, and the institutional breadth of applicants' training needs. METHODS: The current report therefore summarizes the survey-based views and experiences of physician-scientist trainees obtained following the 2021-2022 application cycle for research-oriented residency programs, or physician-scientist training programs (PSTPs). From among this small cohort of applicants, we obtained survey-based feedback of 27 PSTP applicants across 17 U.S. medical universities, among whom 85% (23/27) matched into a PSTP. RESULTS: Among these PSTP applicants, 25/27 (93%) recognized "scientific community" as the most important feature of a postgraduate training program, with applicants identifying as female placing a higher value on the program's infrastructure of personal and/or family support. Most (18/27) respondents found "waiting for interviews" as the most stressful phase of their application cycle, and roughly half of all respondents encountered at least one NRMP policy violation through post-interview communication. Specifically, 93% (25/27) respondents were contacted by at least one PSTP following interviews, and 1/3 of them admitted to feeling pressured into sharing their ranking preferences. CONCLUSION: We highlight many previously unrecognized priorities among applicants to PSTPs, which include fostering community among its trainees and reinforcing structured mentoring. We uncover an inconsistency among PSTPs regarding the post-interview process, which represents an opportunity to better support applicants seeking to gauge programs according to their clinical, scientific, and academic interests as physician-scientists, while still adhering to NRMP policies.
Subject(s)
Education, Medical , Internship and Residency , Physicians , Humans , Female , Education, Graduate , Emotions , Surveys and QuestionnairesABSTRACT
A study was conducted to determine the seroprevalence and risks factors of Coxiella burnetii in zebu cattle from the northern regions of Cameroon. From a total of 2016 (1754 females and 262 males) sera sampled, 801, 762 and 453 were collected, respectively, from Adamawa, North and Far North, and screened for Coxiella burnetii using indirect enzyme-linked immunosorbent assay (iELISA). A total of 23.76% (479/2016) were serologically positive. The seroprevalence of Adamawa, North and Far North were 29.09% (233/801), 19.95% (152/762) and 20.75% (94/453); respectively. The seropositivity of male and female were 4.58% and 26.62%; respectively. Cattle from Adamawa region were more likely to have been exposed to C. burnetii than animals from Far North region (OR = 3.28; 95%CI: 1.13-7.85; p = 0.02). The Gudali breed was significantly more infected than Aku (OR =2.52; 95%CI: 1.06-5.99; p = 0.03), and animals aged of (6-9) years were 1.89 times more likely to have been infected to C. burnetii than young animals (p = 0.03). The seropositivity to this bacterium was significantly associated to pregnant cattle than non-pregnant (OR = 1.71; 95%CI: 1.01-2.90; p = 0.04). Female cattle were more likely to have been infected by C. burnetii than male and the rainy season were 1.66 more associated to this disease than dry season. The linear regression model indicated that C. burnetii seropositivity were positively correlated to the regions (0.09, CI: 0.04; 0.18; p = 0.007), age (0.01, CI: -0.01; 0.04; p = 0.02), sex (0.19, CI: 0.08-0.32, p = 0.001) and physiological status (0.11, CI: -0.04; 0.26; p = 0.006). This study revealed that C. burnetii infection is widespread among zebu cattle of Adamawa, North and Far North of Cameroon.
ABSTRACT
A cross-sectional survey was conducted to investigate the knowledge, attitudes, practices and zoonotic risk perception of Q fever among 484 selected cattle farmers (438) and veterinary personnel (46) in three northern regions of Cameroon. Data collection was conducted using questionnaires and responses were recoded into binary scale. An ANOVA test was used to assess significant differences in mean knowledge, attitude, practice and zoonotic risk perception (KAPP) scores between regions, while Linear regression was done to explore the relationship between demographic characteristic and KAPP. Overall, surveyed had low mean scores for knowledge (0.02 ± 0.11), desirable attitude (0.30 ± 0.16), appropriate practice (0.43 ± 0.13) and negative perception of zoonotic risks (0.05 ± 0.11). The means knowledge, attitude, practice and risks perception scores of cattle farmers were lower than those of veterinary personnel. The nature of respondent was negatively associated to knowledge and risks perception, while regions were negatively correlated to attitude and practice. These results revealed significant knowledge gaps, low levels of desired attitudes, and high-risk behavioral practices. To improve awareness, control programs are needed to update knowledge on medical personnel and to prevent animal-to-human transmission.
ABSTRACT
With aging worldwide population and the high incidence of cancer in the population of people over 75 years old, there is a need for oncologists and geriatricians to strengthen their collaboration to improve elderly patients care. Complexity of cancer and aging issues must be considered simultaneously to establish a personalized care plan. Thus, the G8 is a screening tool that allows to identify patients who should benefit from a geriatric assessment, which is a key step in the management process. This specific evaluation offers a multidisciplinary approach to functional, psychological, nutritional, cognitive and social status and has demonstrated its prognostic value in terms of choice of treatment but also in terms of patient survival. In nearly 20% of cases, the geriatric assessment leads to a change in the choice of treatment, and at one year the initial care plan is not carried out in a quarter of cases. The presence of malnutrition and functional impairment leading to dependence on basic activities of daily living had a significant impact on this change in therapeutic choice. Survival is not only impacted by malnutrition and functional impairment but also by the presence of severe comorbidities and thymic and neurocognitive impairment. The patient's choice must remain at the center of the elaboration of the care plan with the oncologists and geriatricians in order to propose the most appropriate treatment for his or her situation.
Subject(s)
Activities of Daily Living , Neoplasms , Aged , Aging , Comorbidity , Female , Geriatric Assessment , Geriatricians , Humans , Male , Neoplasms/complications , Neoplasms/diagnosis , Neoplasms/epidemiologySubject(s)
Anesthesia, Epidural/adverse effects , Anesthesia, Obstetrical/adverse effects , Blood Patch, Epidural/methods , Diplopia/etiology , Diplopia/therapy , Intracranial Hypotension/etiology , Adult , Cesarean Section , Diagnosis, Differential , Female , Humans , Intracranial Hypotension/diagnostic imaging , Intracranial Hypotension/therapy , Magnetic Resonance Imaging/methodsABSTRACT
BACKGROUND: Urinary tract infections (UTI) are the second cause of community-acquired bacterial infections in the elderly. Distinguishing symptomatic UTI from asymptomatic bacteriuria is problematic, as older adults are less likely to present with localized urinary symptoms. We evaluated characteristics of patients presenting UTI among elderly with sepsis. Moreover, we aimed to evaluate the sensibility and specificity of urine dipstick tests in the diagnosis of UTI in geriatric population. PATIENTS AND METHOD: We led a prospective, monocentric, observational study between April 2017 and January 2018. We included patients hospitalized in geriatric wards, who were prescribed urine culture for UTI symptoms or/and infection without primary sites for which a urine culture was prescribed. Dipstick urinalyses were performed for all patients. Clinical and biological characteristics of all patients were compared according to the final diagnosis of UTI. Moreover, results of dipstick tests were evaluated for the diagnosis of UTI in this population. RESULTS: Among 165 patients, 67 (40.6 %) had a UTI and 98 (59.4 %) had another diagnosis. These two groups were comparable for age and daily-living activities. In the UTI group, the proportion of women was higher than in the other group (P<0.05), and mean MMSE score was lower (P<0.05). Positive urine dipstick test for leukocytes and/or nitrites had high sensitivity (92 %), but low specificity (50 %). Negative predictive value of this test was high (91 %). CONCLUSION: For suspicion of UTI among elderly, few criteria are specific. Negative dipstick tests can suggest an absence of UTI due to its high negative predictive value.
Subject(s)
Urinalysis/methods , Urinary Tract Infections/diagnosis , Aged, 80 and over , Bacteriuria/diagnosis , Female , Geriatrics , Humans , Male , Predictive Value of Tests , Prospective Studies , Sensitivity and SpecificityABSTRACT
INTRODUCTION: This work aims to evaluate selection criteria used during the cataract surgery scheduling visit, to choose whether or not there will be an anesthesiologist available during the surgery, depending upon the patient's comorbidities. MATERIALS AND METHODS: Retrospective study performed in 2016 in Angers university medical center. Two groups were established on the cataract surgery scheduling visit, based on patients' comorbidities and vital signs (blood pressure, heart rate). One group of patients were operated with topical anesthesia, with the anesthesia team, the other one only with blood pressure and heart rate monitoring, with, if needed, a written protocol of sedation or blood pressure control, which could be administrated by a circulating nurse. Those two groups were compared in terms of postoperative complications, intraoperative pain and postoperative visual acuity. RESULTS: 248 surgeries were performed on 185 individual patients, with 108 under stand-alone topical anesthesia, and 135 under anesthetist-monitored topical anesthesia. No significant difference was demonstrated between the two groups, in terms of complications, intraoperative pain or visual acuity outcomes. DISCUSSION: This study allows us to assess selection criteria used in our hospital to determine which patients can undergo cataract surgery under topical anesthesia without the anesthesia team. This procedure lowers organizational constraints while still insuring patient safety. Some patients still probably need an anesthesiologist present, such as those with an unstable disease or risk of agitation, in order to optimize the medications administered during surgery.
Subject(s)
Ambulatory Surgical Procedures/methods , Anesthesia, Local/methods , Anesthetics, Local/administration & dosage , Cataract Extraction/methods , Patient Selection , Administration, Topical , Aged , Aged, 80 and over , Ambulatory Surgical Procedures/adverse effects , Anesthesia, Local/adverse effects , Anesthesiologists , Anesthetics, Local/adverse effects , Cataract/diagnosis , Cataract/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Monitoring, Intraoperative/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Referral and Consultation , Retrospective StudiesABSTRACT
PURPOSE: Osteogenesis imperfecta (OI) predisposes to recurrent fractures. Patients with the moderate to severe forms of OI present with antenatal fractures, and the mode of delivery that would be safest for the fetus is not known. METHODS: We conducted systematic analyses of the largest cohort of individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared among individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates, including method of delivery, on fracture-related outcomes. RESULTS: When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean delivery (CD). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CD. CONCLUSION: Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI, shows that CD is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CD should be performed only for other maternal or fetal indications, not for the sole purpose of fracture prevention in OI.Genet Med 18 6, 570-576.
Subject(s)
Cesarean Section/adverse effects , Fractures, Bone/physiopathology , Osteogenesis Imperfecta/physiopathology , Prenatal Diagnosis , Birth Weight/genetics , Female , Fractures, Bone/diagnosis , Fractures, Bone/etiology , Humans , Infant, Newborn , Logistic Models , Male , Osteogenesis Imperfecta/diagnosis , Osteogenesis Imperfecta/etiology , PregnancyABSTRACT
UNLABELLED: ESSENTIALS: Cancer patients are at high risk of venous thromboembolism (VTE). In this study, cases and controls were cancer patients who did or did not develop VTE. von Willebrand factor (VWF) levels were higher if compared with controls and correlated with cancer stage. VWF and ADAMTS-13 are associated with the occurrence of VTE in cancer. BACKGROUND: Patients with cancer are at high risk of venous thromboembolism (VTE). ADAMTS-13 regulates von Willebrand factor (VWF) activity, which plays a role in the development of cancer and in VTE. OBJECTIVES: The aim of this study was to search for an association between the levels of VWF and ADAMTS-13 and VTE in patients with cancer and to compare current scoring systems for prediction of VTE before and after addition of these parameters. PATIENTS/METHODS: In a case-control study, in which patients with recently diagnosed cancer were followed-up for 6 months, we compared 20 patients who developed VTE (cases) and 140 patients with cancer without VTE (controls), matched for sex, age, and type and stage of cancer. We measured VWF, ADAMTS-13 (activity and antigen), P-selectin, D-dimer and F1 + 2 levels at baseline, and calculated both the Khorana score and the Khorana score expanded after addition of P-selectin and D-dimer levels. RESULTS: VWF levels were significantly higher in cases when compared with controls (326 ± 185% vs. 242 ± 158%) and correlated with advanced stage of cancer: localized, 185 [142; 222]; locally advanced, 240 [146; 257]; metastatic, 267 [153; 324] (mean [interquartile range]). The addition of two biomarkers, ADAMTS-13 activity and F1 + 2 levels, to the Khorana score improved receiver operating curves. CONCLUSIONS: von Willebrand factor and ADAMTS-13 are associated with the occurrence of VTE in patients with cancer. Moreover, addition of ADAMTS-13 and F1 + 2 levels to the Khorana score considerably increases the predictive value for VTE.
Subject(s)
ADAMTS13 Protein/blood , Neoplasms/blood , Venous Thromboembolism/etiology , von Willebrand Factor/analysis , Aged , Area Under Curve , Biomarkers/blood , Case-Control Studies , Europe , Female , Humans , Male , Mexico , Middle Aged , Neoplasm Staging , Neoplasms/complications , Neoplasms/diagnosis , Peptide Fragments/analysis , Predictive Value of Tests , Prognosis , Prospective Studies , Prothrombin/analysis , ROC Curve , Risk Assessment , Risk Factors , Time Factors , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosisABSTRACT
Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.
Subject(s)
Bone Density , Collagen Type I/genetics , Osteogenesis Imperfecta/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Collagen Type I, alpha 1 Chain , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation , North America , Osteogenesis Imperfecta/diagnosis , Osteogenesis Imperfecta/physiopathologyABSTRACT
Reproductive biotechnologies are essential to improve the gene pool in small ruminants. Although embryo transfer (ET) and artificial insemination (AI) greatly reduce the risk of pathogen transmission, few studies have been performed to quantify this risk. The aim of this review is to contribute to the elements needed to evaluate the risk of lentivirus transmission in small ruminants (SRLV) during ET, from embryos produced in vitro or in vivo, and with the use of the semen destined for AI. The purpose is to consider the genetic possibilities of producing uninfected embryos from infected females and males or bearers of the SRLV genome. We have reviewed various studies that evaluate the risk of SRLV transmission through genital tissues, fluids, cells, and flushing media from female and male animals. We have only included studies that apply the recommendations of the International Embryo Transfer Society, to obtain SRLV-free offspring from infected female animals using ET, and the justification for using healthy male animals, free from lentivirus, as semen donors for AI. As such, ET and AI will be used as routine reproductive techniques, with the application of the recommendations of the International Embryo Transfer Society and World Organization for Animal Health.
Subject(s)
Lentivirus Infections/etiology , Lentivirus Infections/transmission , Lentiviruses, Ovine-Caprine , Reproductive Techniques, Assisted/veterinary , Ruminants/virology , Animals , Biotechnology/methods , Biotechnology/standards , Female , Goats/embryology , Goats/virology , Lentiviruses, Ovine-Caprine/pathogenicity , Lentiviruses, Ovine-Caprine/physiology , Male , Models, Biological , Pregnancy , Reproductive Techniques, Assisted/standards , Review Literature as Topic , Risk Factors , Sheep/embryology , Sheep/virologyABSTRACT
Rift Valley Fever (RVF) is a zoonotic arbovirosis. Among animals, it mainly affects ruminants, causing abortions in gravid females and mortality among young animals. In humans, RVF virus infection is usually asymptomatic or characterized by a moderate fever. However, in 1 to 3% of cases, more severe forms of the disease (hepatitis, encephalitis, retinitis, hemorrhagic fever) can lead to the death of infected individuals or to major sequels. The RVF virus (Bunyaviridae, genus Phlebovirus) was identified for the first time in the 1930s in Kenya. It then spread over almost all African countries, sometimes causing major epizootics/epidemics. In 2000, the virus was carried out of Africa, in the Middle East Arabian Peninsula. In 2007-2008, Eastern-African countries, including Madagascar, reported significant episodes of RVF virus, this was also the case for the Comoros archipelago and the French island of Mayotte. This ability to spread associated with many vectors, including in Europe, and high viral loads in infected animals led the health authorities worldwide to warn about the potential emergence of RVF virus in areas with a temperate climate. The awareness has increased in recent years with climate changes, which may possibly modify the vector distribution and competence, and prompted many RVF virus-free countries to better prepare for a potential implantation of RVF.
Subject(s)
Disease Outbreaks , Rift Valley Fever/epidemiology , Aedes/virology , Africa/epidemiology , Animal Husbandry , Animals , Antibodies, Viral/blood , Cattle , Cattle Diseases/epidemiology , Cattle Diseases/virology , Culex/virology , Hemorrhage/etiology , Humans , Indian Ocean Islands/epidemiology , Insect Vectors/virology , Meningoencephalitis/etiology , Occupational Diseases/epidemiology , Occupational Diseases/virology , Population Surveillance , RNA, Viral/blood , Retinitis/etiology , Retinitis/mortality , Rift Valley Fever/complications , Rift Valley Fever/diagnosis , Rift Valley Fever/prevention & control , Rift Valley Fever/transmission , Rift Valley Fever/veterinary , Rift Valley fever virus/genetics , Rift Valley fever virus/immunology , Rift Valley fever virus/isolation & purification , Risk Factors , Viral Vaccines , ZoonosesABSTRACT
Maedi Visna virus (MVV) causes progressive degenerative inflammatory disease in multiple organs including the lungs (pneumonia, 'maedi'), mammary gland, joints and nervous system (meningoencephalomyelitis, 'visna') in sheep. Maedi Visna Virus has been detected in macrophages of several tissues and epithelial cells in vivo: bone marrow, cells of the central nervous system, lung and bronchial tissues, milk epithelial cells recovered from milk samples and epithelial cells of mammary tissue. However, the presence of MVV in the genital tracts of naturally infected ewes has not previously been studied. The aim of this study was to use nested-PCR, targeting the gag gene, to determine whether genital tissues (ovaries, oviducts and uterus) from 83 ewes originating from various breeding herds in the South-East of France were positive for MVV-proviral DNA. Peripheral blood mononuclear cells (PBMC) tested positive for MVV-proviral DNA, using nested-PCR analysis, in 57.8% of ewes (48/83). The provirus was also identified in 47% (78/166) of the ovaries, 38.6% (64/166) of the oviducts and 45.8% (38/83) of the uteri sampled. These findings clearly demonstrate, for the first time, that tissue samples from the genital tract of ewes (ovary, oviduct and uterus) can be infected with MVV. This suggests that there is a risk of vertical and/or horizontal transmission of MVV during embryo transfer from embryos produced in vivo or in vitro.
Subject(s)
DNA, Viral/isolation & purification , Genitalia, Female/virology , Lentivirus Infections/veterinary , Proviruses/genetics , Sheep Diseases/virology , Visna-maedi virus/genetics , Animals , Fallopian Tubes/virology , Female , Lentivirus Infections/virology , Ovary/virology , Polymerase Chain Reaction/veterinary , Sheep , Uterus/virologyABSTRACT
The objective of this study was to determine whether MVV can be transmitted by ovine embryos produced in vitro and whether the zona pellucida (ZP) provides any protection against MVV infection. Zona pellucida (ZP)-intact and ZP-free embryos, produced in vitro, at the 8-16 cell stage, were cocultured for 72h in an insert over an ovine oviduct epithelial cell (OOEC)-goat synovial membrane (GSM) cell monolayer that had been previously infected with MVV (K1514 strain). The embryos were then washed and transferred to either direct contact or an insert over a fresh GSM cell monolayer for 6 h. The presence of MVV was detected using RT-PCR on the ten washing fluids and by the observation of typical cytopathic effects (CPE) in the GSM cell monolayer, which was cultured for 6 weeks. This experiment was repeated 4 times with the same results: MVV viral RNA was detected using RT-PCR in the first three washing media, while subsequent baths were always negative. Specific cytopathic effects of MVV infection and MVV-proviral DNA were detected in GSM cells that were used as a viral indicator and cocultured in direct contact or as an insert with MVV-exposed ZP-free embryos. However, no signs of MVV infection were detected in cells that were cocultured with exposed ZP-intact or non-exposed embryos. This study clearly demonstrates that (i) in vitro, ZP-free, early ovine embryos, which had been exposed to 10(3) TCID(50)/m MVV in vitro, are capable of transmitting the virus to susceptible GSM target cells, and that (ii) the IETS recommendations for handling in vivo produced bovine embryos (use of ZP-intact embryos without adherent material and performing ten washes) are effective for the elimination of in vitro MVV infection from in vitro produced ovine embryos. The absence of interaction between ZP-intact embryos and MVV suggests that the in vitro produced embryo zona pellucida provides an effective protective barrier.
Subject(s)
Embryo, Mammalian/virology , Fertilization in Vitro , Pneumonia, Progressive Interstitial, of Sheep/transmission , Visna-maedi virus/isolation & purification , Visna/transmission , Animals , Embryo Culture Techniques , Goats/virology , Pneumonia, Progressive Interstitial, of Sheep/virology , RNA, Viral/analysis , Sheep/embryology , Synovial Membrane/virology , Visna/virology , Visna-maedi virus/genetics , Zona Pellucida/physiologyABSTRACT
Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants, caused by a Phlebovirus (Bunyaviridae). It is widespread in Africa and has recently spread to Yemen and Saudi Arabia. RVF epidemics are more and more frequent in Africa and the Middle East, probably in relation with climatic changes (episodes of heavy rainfall in eastern and southern Africa), as well as intensified livestock trade. The probability of introduction and large-scale spread of RVF in Europe is very low, but localized RVF outbreaks may occur in humid areas with a large population of ruminants. Should this happen, human cases would probably occur in exposed individuals: farmers, veterinarians, slaughterhouse employees etc. Surveillance and diagnostic methods are available, but control tools are limited: vector control is difficult to implement, and vaccines are only available for ruminants, with either a limited efficacy (inactivated vaccines) or a residual pathogenic effect. The best strategy to protect Europe and the rest of the world against RVF is to develop more efficient surveillance and control tools and to implement coordinated regional monitoring and control programmes.
Subject(s)
Rift Valley Fever/epidemiology , Europe/epidemiology , Humans , Public Health , Rift Valley Fever/diagnosis , Rift Valley Fever/etiology , Rift Valley Fever/physiopathology , Rift Valley Fever/prevention & control , Rift Valley Fever/transmissionABSTRACT
The outcome of patients with cirrhosis and chronic kidney disease treated with combined liver-kidney transplantation (CLKT) is not well known because most series of patients treated with CLKT include not only patients with cirrhosis but also patients with inherited diseases without cirrhosis. To evaluate to what extent the combined kidney transplantation impairs posttransplantation outcome compared to liver transplantation (LT) alone, the outcome of patients with cirrhosis and chronic kidney disease treated with CLKT (n = 20) was compared to that of a group of patients with cirrhosis without chronic kidney disease treated with LT alone matched by age, sex, year of transplantation and severity of cirrhosis (n = 60). The primary end point of the study was survival, and secondary end points were outcome of renal function and complications within 6 months of transplantation. Patients with CLKT had a higher incidence of bacterial infections and transfusion requirements compared to LT patients. The incidence of acute renal failure during the first 6 months was similar, yet the severity of renal failure was greater in patients with CLKT. Hospital and intensive care unit (ICU) stays were longer in the CLKT group. One- and three-year survival probabilities in patients treated with CLKT were 80 and 75% compared to 97 and 88%, respectively, in patients treated with LT. In conclusion, CLKT for patients with cirrhosis and chronic kidney disease is associated with a relatively high frequency of postoperative complications that moderately impairs short-term survival. However, 3-year survival of patients with cirrhosis treated with CLKT is excellent.
Subject(s)
Graft Survival/physiology , Kidney Diseases/surgery , Kidney Transplantation/physiology , Liver Cirrhosis/surgery , Liver Transplantation/physiology , Adult , Chronic Disease , Female , Humans , Kidney Diseases/mortality , Kidney Transplantation/mortality , Liver Cirrhosis/mortality , Liver Transplantation/mortality , Male , Middle Aged , Postoperative Complications/epidemiology , Prevalence , Renal Insufficiency/epidemiology , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Staphylococcus aureus is recognized worldwide as a major pathogen causing clinical or subclinical intramammary infections in lactating sheep, goats and cows. The present study was carried out to compare 65 S. aureus isolates mainly obtained from nasal carriage and subclinical mastitis in dairy sheep and 43 isolates obtained from subclinical mastitis from 22 goats and 21 cows. A DNA microarray, containing probes against 190 true or putative virulence factors, was used to detect the presence of the virulence genes. Their presence/absence was independently assessed by PCR for the genes of interest. Sheep isolates obtained from the nostrils or the udders did not show any significant tissue specific virulence factor. The dominant pulse-field electrophoresis profile (OV/OV'), associated with spa clonal complex spa-CC 1773, matched mainly with the agr group III and was only found in ovine and caprine isolates. This clone was more specifically characterized by the prevalence of the following virulence genes: lpl4, ssl6, bsaA1, bsaB, bsaP, SAV0812. Moreover, seven virulence-associated genes (lpl1, sel, sec, tst, lukF-PV-like component, lukM, SAV0876) were associated with isolates from small ruminants, while the egc cluster, fhuD1, abiF and SAV2496 with bovine isolates. This genomic study suggests the existence of lineage- and host-specific genes leading to the development of host-specific pathogenic traits of S. aureus isolates.
Subject(s)
Mastitis/veterinary , Oligonucleotide Array Sequence Analysis/veterinary , Staphylococcal Infections/veterinary , Staphylococcus aureus/genetics , Virulence Factors/genetics , Animals , Cattle , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Female , Goat Diseases/microbiology , Goats , Mastitis/microbiology , Mastitis, Bovine/microbiology , Oligonucleotide Array Sequence Analysis/methods , Sheep , Sheep Diseases/microbiology , Species Specificity , Staphylococcal Infections/microbiologyABSTRACT
To determine whether systemic immunization with plasmid DNA and virus vector against visna/maedi virus (VMV) would induce protective immune responses, sheep were immunized with VMV gag and/or env sequences using particle-mediated epidermal bombardment and injection of recombinant modified vaccinia Ankara. The results showed that immunization induced both humoral and cell-mediated responses prior to and after virus challenge. The vaccination protocol did not prevent infection, but immunization with the gag gene or a combination of gag and env genes resulted in significantly reduced provirus loads in blood and mediastinal lymph node, respectively. Provirus loads in lung and draining lymph node were unaffected, but p25 expression was undetectable in lungs of animals immunized with a combination of gag and env genes. Analysis of target tissues for lesions at post-mortem showed that immunization with the env gene caused a significant increase in lesion score, while the gag gene or a combination of gag and env genes had no effect. Inclusion of the ovine interferon-gamma gene in the initial priming mixture had minimal effect on immune responses, provirus load, or lesion development, although it resulted in a decreased p25 expression in the lung. The results thus show that systemic immunization with gag or a combination of gag and env genes reduces provirus load in blood and lymphoid tissue, respectively whereas env immunization has no effect on provirus load but increased lesion development.
Subject(s)
Biolistics , Genes, env/genetics , Genes, gag/genetics , Pneumonia, Progressive Interstitial, of Sheep/prevention & control , Vaccines, DNA , Vaccinia virus/genetics , Animals , Antibodies, Viral/blood , Epidermis/virology , Female , Genes, env/immunology , Genes, gag/immunology , Immunization , Male , Pneumonia, Progressive Interstitial, of Sheep/virology , Proviruses/isolation & purification , Sheep , T-Lymphocytes/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Vaccinia virus/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/genetics , Viral Vaccines/immunology , Virion/genetics , Virion/immunology , Visna-maedi virusABSTRACT
Sheep were immunized against Visna/Maedi virus (VMV) gag and/or env genes via the nasopharynx-associated lymphoid tissue (NALT) and lung using polyethylenimine (PEI)-DNA complexes and modified vaccinia Ankara, and challenged with live virus via the lung. env immunization enhanced humoral responses prior to but not after VMV challenge. Systemic T cell proliferative and cytotoxic responses were generally low, with the responses following single gag gene immunization being significantly depressed after challenge. A transient reduction in provirus load in the blood early after challenge was observed following env immunization, whilst the gag gene either alone or in combination with env resulted in significantly elevated provirus loads in lung. However, despite this, a significant reduction in lesion score was observed in animals immunized with the single gag gene at post-mortem. Inclusion of IFN-gamma in the immunization mixture in general had no significant effects. The results thus showed that protective effects against VMV-induced lesions can be induced following respiratory immunization with the single gag gene, though this was accompanied by an increased pulmonary provirus load.
Subject(s)
Gene Products, env/immunology , Gene Products, pol/immunology , Pneumonia, Progressive Interstitial, of Sheep/prevention & control , Vaccines, DNA/immunology , Viral Vaccines/immunology , Visna-maedi virus/immunology , Animals , Antibodies, Viral/blood , Cell Proliferation , Cytotoxicity Tests, Immunologic , Female , Gene Products, env/genetics , Gene Products, pol/genetics , Genetic Vectors , Leukocytes, Mononuclear/immunology , Lung/immunology , Lung/pathology , Lung/virology , Male , Nasopharynx/immunology , Proviruses/isolation & purification , Severity of Illness Index , Sheep , T-Lymphocytes, Cytotoxic/immunology , Vaccines, DNA/administration & dosage , Vaccinia virus/genetics , Viral Load , Viral Vaccines/administration & dosageABSTRACT
The aim of this study was to demonstrate that embryo transfer can be used to produce CAEV-free kids from CAEV-infected biological mothers when appropriate procedure is implemented. Twenty-eight goats that had tested positive for CAEV using PCR on vaginal secretions were used as embryo donors. Embryos with intact-ZP were selected and washed 10 times; they were then frozen and used for transfer into CAEV-free recipient goats. Nineteen of the 49 recipient goats gave birth, producing a total of 23 kids. Three blood samples were taken from each recipient goat, 10 days before, during, and 10 days after parturition; these were tested for CAEV antibodies using ELISA and for CAEV proviral DNA using PCR. The mothers were then euthanized. Tissue samples were taken from the lungs, udder, and retromammary and prescapular lymph nodes. The kids were separated from their mothers at birth. Seven of them died. At 4 months of age, 16 kids were subjected to drug-induced immunosuppression. Blood samples were taken every month from birth to 4 months of age; samples were then taken on days 15, 21, and 28 after the start of the immunosuppressive treatment. The kids were then euthanized and tissue samples taken from the carpal synovial membrane, lung tissue, prescapular lymph nodes, inguinal and retromammary lymph nodes, and uterus. All samples from the 19 recipient goats and 23 kids were found to be negative for CAEV antibodies and/or CAEV proviral DNA. Under acute conditions for infection this study clearly demonstrates that embryo transfer can be safely used to produce CAEV-free neonates from infected CAEV donors.