Generality of Post-Antimicrobial Treatment Persistence of Borrelia burgdorferi Strains N40 and B31 in Genetically Susceptible and Resistant Mouse Strains.

A basic feature of infection caused by Borrelia burgdorferi, the etiological agent of Lyme borreliosis, is that persistent infection is the rule in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable but noncultivable spirochetes persist following treatment with several different antimicrobial agents. The current study utilized the mouse model to evaluate if persistence occurs following antimicrobial treatment in disease-susceptible (C3H/HeJ [C3H]) and disease-resistant (C57BL/6 [B6]) mouse strains infected with B. burgdorferi strains N40 and B31 and to confirm the generality of this phenomenon, as well as to assess the persisters' clinical relevance. The status of infection was evaluated at 12 and 18 months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, as well as being noncultivable. The phenomenon of persistence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice and not unique to any particular B. burgdorferi strain. The results also demonstrate that, following antimicrobial treatment, both strains of B. burgdorferi, N40 and B31, lose one or more plasmids. The study demonstrated that noncultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection. The clinical relevance of persistent spirochetes beyond 18 months following antimicrobial treatment requires further studies in other animal models.

Clinical Validation of a Peritoneal Dialysis Prescription Model in the PatientOnLine Software.

Peritoneal transport characteristics and residual renal function require regular control and subsequent adjustment of the peritoneal dialysis (PD) prescription. Prescription models shall facilitate the prediction of the outcome of such adaptations for a given patient. In the present study, the prescription model implemented in the PatientOnLine software was validated in patients requiring a prescription change. This multicenter, international prospective cohort study with the aim to validate a PD prescription model included patients treated with continuous ambulatory peritoneal dialysis. Patients were examined with the peritoneal function test (PFT) to determine the outcome of their current prescription and the necessity for a prescription change. For these patients, a new prescription was modeled using the PatientOnLine software (Fresenius Medical Care, Bad Homburg, Germany). Two to four weeks after implementation of the new PD regimen, a second PFT was performed. The validation of the prescription model included 54 patients. Predicted and measured peritoneal Kt/V were 1.52 ± 0.31 and 1.66 ± 0.35, and total (peritoneal + renal) Kt/V values were 1.96 ± 0.48 and 2.06 ± 0.44, respectively. Predicted and measured peritoneal creatinine clearances were 42.9 ± 8.6 and 43.0 ± 8.8 L/1.73 m(2)/week and total creatinine clearances were 65.3 ± 26.0 and 63.3 ± 21.8 L/1.73 m(2) /week, respectively. The analysis revealed a Pearson's correlation coefficient for peritoneal Kt/V of 0.911 and Lin's concordance coefficient of 0.829. The value of both coefficients was 0.853 for peritoneal creatinine clearance. Predicted and measured daily net ultrafiltration was 0.77 ± 0.49 and 1.16 ± 0.63 L/24 h, respectively. Pearson's correlation and Lin's concordance coefficient were 0.518 and 0.402, respectively. Predicted and measured peritoneal glucose absorption was 125.8 ± 38.8 and 79.9 ± 30.7 g/24 h, respectively, and Pearson's correlation and Lin's concordance coefficient were 0.914 and 0.477, respectively. With good predictability of peritoneal Kt/V and creatinine clearance, the present model provides support for individual dialysis prescription in clinical practice. Peritoneal glucose absorption and ultrafiltration are less predictable and are likely to be influenced by additional clinical factors to be taken into consideration.

Methylation and gene expression responses to ethanol feeding and betaine supplementation in the cystathionine beta synthase-deficient mouse.

BACKGROUND: Alcoholic steatohepatitis (ASH) is caused in part by the effects of ethanol (EtOH) on hepatic methionine metabolism. METHODS: To investigate the phenotypic and epigenetic consequences of altered methionine metabolism in this disease, we studied the effects of 4-week intragastric EtOH feeding with and without the methyl donor betaine in cystathionine beta synthase (CßS) heterozygous C57BL/6J mice. RESULTS: The histopathology of early ASH was induced by EtOH feeding and prevented by betaine supplementation, while EtOH feeding reduced and betaine supplementation maintained the hepatic methylation ratio of the universal methyl donor S-adenosylmethionine (SAM) to the methyltransferase inhibitor S-adenosylhomocysteine (SAH). MethylC-seq genomic sequencing of heterozygous liver samples from each diet group found 2 to 4% reduced methylation in gene bodies, but not promoter regions of all autosomes of EtOH-fed mice, each of which were normalized in samples from mice fed the betaine-supplemented diet. The transcript levels of nitric oxide synthase (Nos2) and DNA methyltransferase 1 (Dnmt1) were increased, while those of peroxisome proliferator receptor-α (Pparα) were reduced in EtOH-fed mice, and each was normalized in mice fed the betaine-supplemented diet. DNA pyrosequencing of CßS heterozygous samples found reduced methylation in a gene body of Nos2 by EtOH feeding that was restored by betaine supplementation and was correlated inversely with its expression and positively with SAM/SAH ratios. CONCLUSIONS: The present study has demonstrated relationships among EtOH induction of ASH with aberrant methionine metabolism that was associated with gene body DNA hypomethylation in all autosomes and was prevented by betaine supplementation. The data imply that EtOH-induced changes in selected gene transcript levels and hypomethylation in gene bodies during the induction of ASH are a result of altered methionine metabolism that can be reversed through dietary supplementation of methyl donors.

Posterior Reversible Encephalopathy Syndrome (PRES) as a Complication of Immunosuppressive Therapy in Renal Transplantation in Children.

Although kidney transplantation is by far the best method of renal replacement therapy, organ receiver is still not spared of eventual toxic consequences of drugs that are in charge of keeping the transplanted kidney functional. Both calcineurin inhibitors, of which tacrolimus more often, occasionally lead to neurotoxic side effects, mostly mild and reversible and dose-dependent in nature, but they can also be very severe or even fatal. It is very important to be aware of possible neurotoxic effects, to confirm them radiologically, and to prevent or reduce drug effects on nervous system. Sometimes the reduction of dose or substitution with another drug with similar mechanism effect is sufficient to terminate the neurotoxic effects of the drug and still not jeopardize the function of transplanted organ.

The early dissemination defect attributed to disruption of decorin-binding proteins is abolished in chronic murine Lyme borreliosis.

The laboratory mouse model of Lyme disease has revealed that Borrelia burgdorferi differentially expresses numerous outer surface proteins that influence different stages of infection (tick-borne transmission, tissue colonization, dissemination, persistence, and tick acquisition). Deletion of two such outer surface proteins, decorin-binding proteins A and B (DbpA/B), has been documented to decrease infectivity, impede early dissemination, and, possibly, prevent persistence. In this study, DbpA/B-deficient spirochetes were confirmed to exhibit an early dissemination defect in immunocompetent, but not immunodeficient, mice, and the defect was found to resolve with chronicity. Development of disease (arthritis and carditis) was attenuated only in the early stage of infection with DbpA/B-deficient spirochetes in both types of mice. Persistence of the DbpA/B-deficient spirochetes occurred in both immunocompetent and immunodeficient mice in a manner indistinguishable from that of wild-type spirochetes. Dissemination through the lymphatic system was evaluated as an underlying mechanism for the early dissemination defect. At 12 h, 3 days, 7 days, and 14 days postinoculation, DbpA/B-deficient spirochetes were significantly less prevalent and in lower numbers in lymph nodes than wild-type spirochetes. However, in immunodeficient mice, deficiency of DbpA/B did not significantly decrease the prevalence or spirochete numbers in lymph nodes. Complementation of DbpA/B restored a wild-type phenotype. Thus, the results indicated that deficiency of DbpA/B allows the acquired immune response to restrict early dissemination of spirochetes, which appears to be at least partially mediated through the lymphatic system.

Dynamics of connective-tissue localization during chronic Borrelia burgdorferi infection.

The etiologic agent of Lyme disease, Borrelia burgdorferi, localizes preferentially in the extracellular matrix during persistence. In chronically infected laboratory mice, there is a direct association between B. burgdorferi and the proteoglycan decorin, which suggests that decorin has a role in defining protective niches for persistent spirochetes. In this study, the tissue colocalization of B. burgdorferi with decorin and the dynamics of borrelial decorin tropism were evaluated during chronic infection. Spirochetes were found to colocalize absolutely with decorin, but not collagen I in chronically infected immunocompetent C3H mice. Passive immunization of infected C3H-scid mice with B. burgdorferi-specific immune serum resulted in the localization of spirochetes in decorin-rich microenvironments, with clearance of spirochetes from decorin-poor microenvironments. In passively immunized C3H-scid mice, tissue spirochete burdens were initially reduced, but increased over time as the B. burgdorferi-specific antibody levels waned. Concurrent repopulation of the previously cleared decorin-poor microenvironments was observed with the rising tissue spirochete burden and declining antibody titer. These findings indicate that the specificity of B. burgdorferi tissue localization during chronic infection is determined by decorin, driven by the borrelia-specific antibody response, and fluctuates with the antibody response.

Lymphoadenopathy during lyme borreliosis is caused by spirochete migration-induced specific B cell activation.

Lymphadenopathy is a hallmark of acute infection with Borrelia burgdorferi, a tick-borne spirochete and causative agent of Lyme borreliosis, but the underlying causes and the functional consequences of this lymph node enlargement have not been revealed. The present study demonstrates that extracellular, live spirochetes accumulate in the cortical areas of lymph nodes following infection of mice with either host-adapted, or tick-borne B. burgdorferi and that they, but not inactivated spirochetes, drive the lymphadenopathy. The ensuing lymph node response is characterized by strong, rapid extrafollicular B cell proliferation and differentiation to plasma cells, as assessed by immunohistochemistry, flow cytometry and ELISPOT analysis, while germinal center reactions were not consistently observed. The extrafollicular nature of this B cell response and its strongly IgM-skewed isotype profile bear the hallmarks of a T-independent response. The induced B cell response does appear, however, to be largely antigen-specific. Use of a cocktail of recombinant, in vivo-expressed B. burgdorferi-antigens revealed the robust induction of borrelia-specific antibody-secreting cells by ELISPOT. Furthermore, nearly a quarter of hybridomas generated from regional lymph nodes during acute infection showed reactivity against a small number of recombinant Borrelia-antigens. Finally, neither the quality nor the magnitude of the B cell responses was altered in mice lacking the Toll-like receptor adaptor molecule MyD88. Together, these findings suggest a novel evasion strategy for B. burgdorferi: subversion of the quality of a strongly induced, potentially protective borrelia-specific antibody response via B. burdorferi's accumulation in lymph nodes.

Influence of arthritis-related protein (BBF01) on infectivity of Borrelia burgdorferi B31.

BACKGROUND: Lyme borreliosis, caused by tick-borne Borrelia burgdorferi, is a multi-phasic, multi-system disease in humans. Similar to humans, C3H mice develop arthritis and carditis, with resolution and periodic bouts of recurrence over the course of persistent infection. Borrelia burgdorferi arthritis-related protein (Arp/BBF01), a highly conserved protein among B. burgdorferi s.s. isolates, has been shown to be antigenic in humans with Lyme borreliosis, and a target for antibody-mediated disease resolution in the mouse model. RESULTS: A mutant strain of B. burgdorferi s.s. deficient of the arp gene and a complemented version of that mutant were created and examined for phenotypic effects in mice compared to wild-type B. burgdorferi. Deletion of arp did not abolish infectivity, but did result in a higher infectious dose compared to wild-type B. burgdorferi, which was restored by complementation. Spirochete burdens in tissues of C3H-scid mice were lower when infected with the arp mutant, compared to wild-type, but arthritis was equally severe. Spirochete burdens were also lower in C3H mice infected with the arp mutant, but disease was markedly reduced. Ticks that fed upon infected C3H mice were able to acquire infection with both wild-type and arp mutant spirochetes. Arp mutant spirochetes were marginally able to be transmitted to naïve hosts by infected ticks. CONCLUSION: These results indicated that deletion of BBF01/arp did not abrogate, but diminished infectivity and limited spirochete burdens in tissues of both immunocompetent and immunodeficient hosts, and attenuated, but did not abolish the ability of ticks to acquire or transmit infection.

Pregnancy in renal transplantation.

UNLABELLED: Pregnancy in kidney transplantation is, considering its numerous complications, listed in category of high-risk pregnancies. Complications occur as consequence of action of immunosuppressant drugs and mutual interactions of graft on pregnancy and pregnancy on graft. To asses conception it is necessary for female patient to fulfill conditions after which planning and management of pregnancy are carried out. Planning means a list of actions which altogether have as a goal to decrease risk factors for future mothers and for babies as much as possible. Pregnancy management is also procedural, including numerous hospitalizations, in which pregnancy, fetus and renal function are controlled, on-time identifying potentially dangerous complications and solving ones that might have already occurred. With all given precautions there is still no guarantee for successful pregnancy termination, although given measurements significantly improve possibilities of normal childbirth, like those in general population. KEYWORDS: renal transplantation, pregnancy.

A novel approach for simultaneous detection of the most common food-borne pathogens by multiplex qPCR.

Food contaminated with bacterial pathogens is a great threat to human health and food spoilage, having an impact on public health and the food industry. Research in food safety seeks to develop a practical, rapid, and sensitive detection technique for food-borne pathogens. In the past few decades, real-time quantitative polymerase chain reaction (qPCR) has been developed, and multiplex qPCR is a preferred feature. Multiplex qPCR enables the simultaneous amplification of many targets of interest in one reaction by using more than one pair of primers. In this study, we have developed and evaluated a hydrolysis (TaqMan) probe-based system for simultaneous detection of eight of the most common food-borne pathogens in a single-step procedure by multiplex qPCR. A multicolor combinational probe coding (MCPC) strategy was utilized that allows multiple fluorophores to label different probes in combinatorial manner. This strategy enabled simultaneous detection, identification, and quantification of targeted genes. The efficiency of the individual qPCR reactions for each target gene had values comparable to those established for multiplex qPCR, with detection limits of approximately < 10 copies of DNA per reaction. Pathogen load helps to predict bacteriological quality status in food products and serves to validate the efficiency of procedures to minimize or eliminate their presence, so newly developed multiplex qPCR was quantitative for each pathogen. During sample preparation, a step to concentrate the target organism from a relatively large sample size, remove all potential PCR inhibitors, and yield samples in a volume suitable for qPCR was incorporated.

Investigation of the EHV-1 Genotype (N752, D752, and H752) in Swabs Collected From Equids With Respiratory and Neurological Disease and Abortion From the United States (2019-2022).

Contemporary data on equine herpesvirus-1 (EHV-1) genotype (non-neuropathogenic or N752, neuropathogenic or D752 and new variant or H752) in clinically diseased equids is important in order to determine the frequency of these genotypes and their association with disease expression. A total of 297 EHV-1 qPCR-positive swabs collected from 2019 to 2022 from horses with respiratory disease (EHV-1), neurological disease (equine herpesvirus-1 myeloencephalopathy [EHM]) and abortion were tested for the three different EHV-1 genotypes (N752, D752 and H752) using qPCR allelic discrimination assays. All submissions originated from the United States and included 257 EHV-1 cases, 35 EHM cases and 5 cases of abortion. EHV-1 qPCR-positive cases were predominantly seen during winter and spring. N752 was the predominant genotype detected in EHV-1 cases (87.5%), EHM cases (74.3%) and abortions (80%). D752 was detected less frequently in EHV-1 cases (9.3%) and EHM cases (25.7%), while H752 was only detected in EHV-1 cases (3.1%). While the N752 genotype has remained the predominant genotype affecting horses with respiratory disease and abortion, it has also become a leading genotype in cases of EHM, when compared to historical data. The new H752 genotype, first reported in the United States in 2021, has remained confined to a cluster of geographically and temporally related outbreaks and the data showed no emerging spread of H752 since it was first reported. While the monitoring of EHV-1 genotypes is important from a diagnostic and epidemiological standpoint, it may also help establish medical interventions and preventive protocols to reduce the risk of severe complications associated with EHV-1 infection.

One hundred kidney transplantations in Tuzla.

INTRODUCTION: Kidney transplantation assures considerably better quality of life than the treatment of end-stage renal disease patients with dialysis. GOAL: Authors intended to present results of kidney transplantations that were performed for over 13 years in UCC Tuzla. EXAMINEES AND METHODS: Total of 100 transplantations have been done over 13 years. The gender and age structure have been presented, as well as number of transplantations per year, type of transplantation (living related donor, living unrelated donor, deceased donor), number and percentage of donors and results of transplantations expressed as survival of both the patient and transplanted kidney/ renal graft. We also wanted to presented other important events such as dates of introduction of certain drugs, dates of first cadaver transplantation, transplantation with desensitization protocols and dates of first living unrelated (spousal/emotional) transplantation. RESULTS: The survival of patients and renal grafts were demonstrated by Kaplan-Meier curve, and obtained results were fully in range of results recommended in other literature and by other authors. One-year survival of graft is 94%, with five-year survival being 75%. One-year survival of patients is 95%, and five-year survival of patients was 84%. DISCUSSION: Our results have been compared to those from other studies, gaining suggestions for transplantation improvement. CONCLUSION: Among all modifications of renal replacement therapy transplantation is by far the method of choice because, its well known advantages aside, it also has an economical advantage over chronic treatment with dialysis and it should therefore become interesting to healthcare systems.

Relationship between depression and quality of life after myocardial infarction.

Aim To examine the prevalence of depression in patients after acute myocardial infarction (AMI), as well as the relationship between the depression and quality of life. Methods The survey was conducted via sociodemographic questionnaire, Beck Depression Inventory (BDI), and Short Form 36 Health Survey questionnaire (SF-36). The result of SF-36 is expressed in subscales that make up the health status profile, i.e. physical functioning, physical role, emotional role, social functioning, mental health, vitality, pain and general health. Results The study included 120 patients, of which 70 males and 50 females aged between 41 and 88 years (mean 64.73±11.218). All patients were hospitalized at the Clinical Centre of the University of Sarajevo, Clinic for Cardiovascular Disease and Rheumatism, due to complications caused by AMI. After AMI 59 (49.17%) patients had depression. Depression was negatively associated with physical functioning, physical role, emotional role, social functioning, mental health, vitality, pain and general health. Physical functioning (r= -0.701; p<0.01) and physical role (r = -0.538; p<0.01) had the highest correlation with depression. Conclusion The evaluation of depressive symptoms after AMI is imperative, because the appearance of symptoms could have an effect on the patient's quality of life.

Frequency of Detection of Respiratory Pathogens in Clinically Healthy Show Horses Following a Multi-County Outbreak of Equine Herpesvirus-1 Myeloencephalopathy in California.

Actively shedding healthy horses have been indicated as a possible source of respiratory pathogen outbreak, transmission, and spread. Using nasal swabs from clinically healthy sport horses submitted for qPCR testing after an outbreak of equine herpesvirus-1 (EHV-1) myeloencephalopathy (EHM) in the spring of 2022, this study aimed to identify the rate of clinically healthy horses shedding common and less characterized respiratory pathogens within the sport horse population to better understand their role in outbreaks. Swabs were collected during a required quarantine and testing period, according to the United States Equestrian Federation (USEF), and showed return-to-competition requirements. Common respiratory pathogens, such as equine influenza virus (EIV), EHV-4, and equine rhinitis B virus (ERBV), were found at low but stable frequencies within previously reported ranges, whereas EHV-1 and Streptococcus equi subspecies equi (S. equi) were found at or above previously reported frequencies. Less characterized respiratory pathogens, such as EHV-2, EHV-5, and S. equi subspecies zooepidemicus (S. zooepidemicus), were found within previously reported ranges. Common respiratory pathogens, especially EHV-1 following the multiple EHM outbreaks, were found to be circulating in clinically healthy sport horse populations, reflecting their silent transmission. The strategy of quarantine and EHV-1 qPCR testing of clinically healthy horses was successful at eliminating additional EHM outbreaks and facilitating safe return to competition with no reported respiratory disease outbreaks following the subsequent shows in California.

Prevalence and geographic distribution of Babesia conradae and detection of Babesia vogeli in free-ranging California coyotes (Canis latrans).

Babesia species are intraerythrocytic piroplasms that can result in disease characterized by hemolytic anemia and thrombocytopenia. Of the 5 species that are known to infect canids in the United States, Babesia conradae is most frequently diagnosed in California, and Babesia vogeli is prevalent in the US. Despite the recent re-emergence of B. conradae, the mechanism of transmission is not known. Coyotes (Canis latrans) have been a proposed reservoir of disease, and previous work has shown that dogs with known aggressive interactions with coyotes are at greater risk for infection. This study aimed to determine the prevalence of B. conradae in wild coyote populations in California to assess the viability of coyotes as a potential source of infection for domestic dogs. Four hundred and sixty-one splenic samples were obtained during post-mortem examination of coyote carcasses from Southern California, Fresno, and Hopland. Demographic data including age, sex, cause of death, and urbanity were collected for each coyote. DNA was extracted from samples and amplified using real-time PCR with primers specific for the B. conradae ITS-2 gene. The 18S gene was amplified and sequenced using conventional PCR primers specific to the Babesia genus from any coyotes positive for B. conradae. In total, 22 coyotes tested positive for B. conradae in Fresno (n = 15), Orange (n = 4), San Bernardino (n = 1), and Los Angeles counties (n = 1) with an overall prevalence of 4.8%. Coyotes from Fresno (P<.01) and rural coyotes (P<.01) were significantly more likely to be infected with B. conradae. Ten of 14 samples sequenced were 99-100% homologous to B. conradae, and 4 samples were 100% homologous with B. vogeli DNA indicating co-infection with both pathogens. This study demonstrates that coyotes can become infected and harbor B. conradae and B. vogeli and should be investigated as a possible source of infection in domestic dogs.

Challenges in navigating molecular diagnostics for common equine respiratory viruses.

Equine respiratory viruses remain a leading cause of equine morbidity and mortality, with the resurgence of certain infections, an increasing population of elderly, more susceptible horses, the growth of international equine commerce, and an expansion in geographic distribution of pathogens. The focus of rapid diagnosis of infectious diseases has also shifted recently, with the appearance and increasing importance of nucleic acid amplification-based techniques, primarily polymerase chain reaction (PCR), at the expense of traditional methods such as clinical microbiology. While PCR is fast, reliable, cost-effective, and more sensitive than conventional detection methods, careful interpretation of diagnostic test results is required, taking into account the clinical status of the patient, sample type, assay used and biological relevance of the detected viruses. The interpretation of common equine respiratory viruses such as influenza virus (EIV), alpha herpesviruses (EHV-1, EHV-4), arteritis virus (EAV) and rhinoviruses (ERAV, ERBV) is straight forward as causality can generally be established. However, the testing of less-characterized viruses, such as the gamma herpesviruses (EHV-2, EHV-5), may be confusing, considering their well-established host relationship and frequent detection in both diseased and healthy horses. For selected viruses, absolute quantitation (EHV-1 and EHV-4) and genotyping (EIV and EHV-1) has allowed additional information to be gained regarding viral state and virulence, respectively. This information is relevant when managing outbreaks so that adequate biosecurity measures can be instituted and medical interventions can be considered. The goal of this review is to help the equine practitioner navigate through the rapidly expanding field of molecular diagnostics for respiratory viruses and facilitate the interpretation of results.

Detection of Cephalosporin and Fluoroquinolone Resistance Genes via Novel Multiplex qPCR in Fecal Salmonella Isolates From Northern Californian Dairy Cattle, 2002-2016.

The objectives of this study were to evaluate the prevalence of extended spectrum ß-lactamase (ESBL) genes, AmpC-type ß-lactamase (ACBL) genes, and plasmid mediated quinolone resistance (PMQR) genes in Salmonella isolated at a Veterinary Medical Teaching Hospital microbiology laboratory, examine trends in presence of these resistance genes, and to explore the correlation between phenotypic resistance and presence of specific genes. The presence of ESBL, ACBL, and PMQR genes were detected using a single, novel multiplex qPCR. Only the genes bla CMY-2 and bla TEM were detected in the 110 Salmonella isolates tested. PMQR genes were not detected in isolates screened. Of 94 third-generation cephalosporin resistant isolates, representing eight serotypes, 48% (n = 45) were positive for bla CMY-2 only and 50% (n = 47) were simultaneously positive for bla CMY-2 and bla TEM. Two third-generation cephalosporin resistant isolates were tested negative for all ß-lactamase genes in our qPCR assay and likely house ESBL genes not screened for by our qPCR assay. A logistic regression model revealed that for serotype Dublin isolates (n = 38) the odds ratio for testing positive for bla TEM when compared to all other serotypes was 51.6 (95% CI: 4.01-664.03, p = 0.0029). For serotype Typhimurium (n = 9) the odds ratio for testing positive for bla TEM when compared to all other serotypes was 43.3 (95% CI: 1.76-1000, p = 0.0216). Overall, our results suggest that the prevalence of resistance to cephalosporins and fluoroquinolones due to ESBLs, ACBLs, and PMQR genes present in bovine nontyphoidal Salmonella enterica isolates has remained relatively constant in the isolates screened over a 14-year period.

Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.

The effectiveness of a new first-in-class antibiotic, tigecycline (glycylcycline), was evaluated during the early dissemination (1 week), early immune (3 weeks), or late persistent (4 months) phases of Borrelia burgdorferi infection in C3H mice. Mice were treated with high or low doses of tigecycline, saline (negative-effect controls), or a previously published regimen of ceftriaxone (positive-effect controls). Infection status was assessed at 3 months after treatment by culture, quantitative ospA real-time PCR, and subcutaneous transplantation of joint and heart tissue into SCID mice. Tissues from all saline-treated mice were culture and ospA PCR positive, tissues from all antibiotic-treated mice were culture negative, and some of the tissues from most of the mice treated with antibiotics were ospA PCR positive, although the DNA marker load was markedly decreased compared to that in saline-treated mice. Antibiotic treatment during the early stage of infection appeared to be more effective than treatment that began during later stages of infection. The viability of noncultivable spirochetes in antibiotic-treated mice (demonstrable by PCR) was confirmed by transplantation of tissue allografts from treated mice into SCID mice, with dissemination of spirochetal DNA to multiple recipient tissues, and by xenodiagnosis, including acquisition by ticks, transmission by ticks to SCID mice, and survival through molting into nymphs and then into adults. Furthermore, PCR-positive heart base tissue from antibiotic-treated mice revealed RNA transcription of several B. burgdorferi genes. These results extended previous studies with ceftriaxone, indicating that antibiotic treatment is unable to clear persisting spirochetes, which remain viable and infectious, but are nondividing or slowly dividing.

[Hypertension and age of the donor in living-related kidney transplantation]. / Hipertenzija i dob darivatelja u zivoj srodnoj transplantaciji bubrega.

INTRODUCTION: Post-transplantation hypertension is one of the most important factors with negative influence on survival of a graft and a patient. The objective of this study was to evaluate the influence of donor's age on hypertension and the outcome in living-related transplantation of the kidney. METHODS: The research included 52 recipients of the graft, 30 women and 22 men who received living-related kidney graft in the time period of 1999 to 2004. In the while control group consisted of recipients of graft who's donors were younger than 55. Age and sex of the donor, glomerular filtration rate of the donated kidney, dialysis treatment, kidney disease and number of months after transplantation were monitored. Blood pressure was measured once a day and average monthly value was assessed. Creatinine clearance was evaluated once in six months period. Functional kidney graft after 60 months was considered the one with serum creatinine < or = micromol/l. Statistical analysis included t test, Fisher's exact test, chi-square test, Kaplan - Meier curve and multivariate logistic regression. RESULTS: Experimental group included 23 examinees who received grafts from donors 55 years old and above (18 men and 5 women, average age 34.86 +/- 6.54, who have been treated for 35.33 +/- 37.59 months) while control group included 29 examinees (16 men and 13 women, average age 31.69 +/- 10.5, who have been treated for 21.03 +/- 25.59 months). Average age of the donors in the experimental group was 62.43 +/- 4.10 and 45.31 +/- 5.24 in control group. Mean creatinine clearance of the donated kidneys was 47.87 +/- 10.5 ml/min in experimental group and 51.19 +/- 10.1 ml/min in the control (p = 0.005). Sixty months after transplantation graft was functional in 32.69% recipients of the experimental group and in 82.75% recipients of the control group. The average systolic blood pressure in test group was 146 +/- 20 mm Hg, and in the control 129 +/- 16 mm Hg (p < 0.001). Average diastolic blood pressure was 90 +/- 11 mm Hg in experimental group, and 83 +/- 10 mm Hg in the control (p < 0.03). CONCLUSIONS: Age of the donor has significant influence on long-term survival of the kidney graft in the living-related transplantation. Survival of the graft in examinees without hypertension is significantly longer. Treatment of post-transplantation hypertension is one of the most important tasks in the treatment of patients with transplanted kidney.

The possible role of early post-transplant inflammation in later anemia in kidney transplant recipients.

UNLABELLED: Delayed kidney graft function and acute rejection in the early post-transplant period affect both short and long-term allograft survival. Allograft rejection, as an inflammatory state, results in increased erythropoietin resistance, which leads to decreased haemoglobin (Hb) level. We conducted this study to evaluate whether inflammation in the early post-transplant period could predict later anemia.This is a retrospective cohort study based on the analysis of 64 existing clinical records. PREDICTOR: White blood cells (WBC) count obtained by the end of the first week post-transplant (W1). Covariates: Donor's age, recipient's age and sex. OUTCOME: Anemia identified at 12 months (M12) post engraftment. Median WBC count at W1 was 9,5 x103/microL (5th - 95th percentile 5,2 x103/microL -17,8 x103/microL). Mean Hb values at M12 were 129,9 +/- 20,3 g/L, in males 136,2 +/- 20,1 g/L and in females 119,4 +/- 16,2 g/L. The significant correlation was found between WBC at W1 and Hb at M12. Pearson coefficient of correlation r was -0,26, and 95% confidence interval (CI) for r was -0,47 to -0,015 (p=0,03). Univariate logistic regression showed significant association between WBC at W1 and Hb at M12 (OR 1,20; 95% CI 1,04 to 1,39, p=0,01). After the adjustment for donor's and recipient's age by transplantation and recipient's sex, multiple regression showed that WBC count remained predictive of anemia at M12 (OR 1,17; 95% CI 1,01 to 1,36, p=0,03). Early post-transplant inflammatory response predicts later anemia in kidney transplant recipients. An increase in WBC count in the first week post-transplant by 109/L increases the risk for anemia after twelve months by 17%.