Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase 1 multicenter study of BMS-986365 in patients with progressive mCRPC. PATIENTS AND METHODS: Patients who progressed on androgen deprivation therapy, ≥ 1 ARPI, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (Part A) and expansion (Part B) of BMS-986365 up to 900 mg twice daily (BID). Primary objectives were safety, tolerability, and to define maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS). RESULTS: Parts A and B enrolled 27 and 68 patients, respectively. In Part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events (TRAEs) were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A MTD was not reached and RP2D selection is ongoing. Across Part B three highest doses (400-900 mg BID, n = 60), PSA50 was 32% (n = 19), including 50% (n = 10/20) at 900 mg; median rPFS (95% CI) was 6.3 months (5.3-12.6), including 8.3 months (3.8-16.6) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5-not evaluable) versus 5.5 months (2.7-8.3), respectively. Efficacy was observed in patients with AR ligand binding domain (LBD) WT or with AR LBD mutations. CONCLUSIONS: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with potentially higher benefit in chemotherapy-naïve patients. These data show BMS-986365's potential to overcome resistance to current ARPIs, regardless of AR LBD mutation status.

Resumption of ovulation in anovulatory women with PCOS and obesity is associated with reduction of 11ß-hydroxyandrostenedione concentrations.

STUDY QUESTION: Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-Müllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory? SUMMARY ANSWER: Resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11ß-hydroxyandrostenedione (11OHA4) concentrations. WHAT IS KNOWN ALREADY: Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. STUDY DESIGN, SIZE, DURATION: We used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29 kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 95) were included in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: We defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n = 34) and persistently anovulatory women (RO-, n = 61) at 3 and 6 months after intervention. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, the mean ± SD age was 27.5 ± 3.6 years in the RO+ group and 27.9 ± 4.1 years in the RO- group (P = 0.65), and the mean ± SD weights were 101.2 ± 9.5 kg and 105.0 ± 14.6 kg, respectively (P = 0.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction = 0.03). There was a similar trend for SHBG (interaction P-value = 0.07), and DHEA-S (interaction P-value = 0.06), with the most pronounced differences observed in the first 3 months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups. LIMITATIONS, REASONS FOR CAUTION: No high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results. WIDER IMPLICATIONS OF THE FINDINGS: Reduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).

Impact of COVID-19 on Dental Care Utilization and Oral Health Conditions in the United States.

PURPOSE: We aim to understand the impact of the COVID-19 on health care utilization and oral health conditions of patients at federally qualified health centers (FQHCs), where patients are disproportionately low income, publicly insured, or uninsured. METHODS: Using deidentified electronic health records of patients at FQHCs in the United States from January 2019 through December 2020 (n = 431,509), variations in health care utilization since the COVID-19 outbreak were observed by procedure types and patient characteristics. Changes in dental utilization and oral health conditions were characterized using mixed-effect negative binomial and logistic regression models. RESULTS: Dental utilization decreased more drastically than medical utilization during shelter-in-place periods in 2020 and rebounded more slowly after the reopening. Greater demands for oral surgery and teledentistry and less demands for preventive services were observed in 2020. As compared to 2019, patients experienced more psychological stress-related dental conditions with odds ratios of 1.52 (95% confidence interval [CI], 1.31-1.76) for uninsured, 1.48 (95% CI, 1.07-2.02) for Medicaid enrollees, and 2.38 (95% CI, 1.68-3.40) for private insurance beneficiaries. CONCLUSION: As a result of COVID-19, patients received more invasive dental procedures due to delayed treatment and experienced a higher risk of psychological stress-related dental conditions. Continued support for statewide policies to expand access to oral health care and oral health promotion strategies for the vulnerable populations would be encouraged. KNOWLEDGE TRANSFER STATEMENT: Our study describes the impact of COVID-19 on dental care use and oral health conditions at Federally Qualified Health Centers, targeted to provide care for some of the most vulnerable populations in the United States. The results of this retrospective cohort study can be used by clinicians and policymakers on understanding the clinical needs of the vulnerable populations after the pandemic. It highlights the need for continued support to expand access to oral health care and oral health promotion to these populations.

Evaluating Trust in the Patient-Dentist Relationship: A Mixed-Method Study.

BACKGROUND: The objective of this article was to understand the trust of study participants in dental providers and trust-building practices used by dentists to establish and maintain trust with their patients. METHODS: This study used a concurrent cross-sectional mixed-methods design to measure the participants' trust in their dental providers. An 11-item Dental Trust Scale (DTS) questionnaire was administered to 150 White, Black, and Hispanic study participants. In addition, the research team conducted semistructured interviews with 7 dentists in order to understand their perspectives related to patient trust. The internal consistency of the DTS was tested using Cronbach's α. Univariate and multivariable logistic regression models were run to test the association between the DTS mean score and individual participant factors. Qualitative information from interviews was analyzed using a thematic analysis approach. RESULTS: The overall mean score of dental trust for the entire sample was 3.4. The DTS had good internal consistency (α = 0.93). Overall, dental trust was significantly higher in participants who had a regular dentist (F = 8.74, P = 0.003). The qualitative data were grouped under these key thematic categories: the importance of trust, building trust, and trust in treatment planning. Qualitative analysis also showed that the 2 main trust-building tools used by dentists were communication and understanding the patient's lifestyle or social determinants of health. KNOWLEDGE TRANSFER STATEMENT: This study provides insight into the dentist-patient relationship. It increases our understanding of levels of dental trust among patients and examines methods used by the dentist to build trust. The outcomes of this study can be considered by dentists in their everyday practice as they seek to build trust with their patients.

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Determinants of Tooth Loss in a Medicaid Adult Population.

BACKGROUND: The objective of this retrospective cohort study is to examine the determinants of tooth loss in a Medicaid-enrolled population using claims data from 2016 to 2018. METHODS: Deidentified administrative claims data for Medicaid-enrolled adults between the ages of 50 and 90 y in 2016 to 2018 were examined using the IBM Watson MarketScan Medicaid Database. The sample size was 91,468. The entire sample was divided into 2 cohorts: no tooth loss cohort (n = 54,786) and tooth loss cohort (n = 36,682). The tooth loss cohort was further divided into 2 groups: 1 to 5 teeth lost (n = 29,141) and 6 or more teeth lost (n = 7,541). Tooth loss was described by age, gender, race, number of commodities, and if periodontal treatment was performed. Logistic regression models were conducted to examine factors associated with tooth loss. RESULTS: Within the tooth loss cohort, the patients who had periodontal treatment had higher odds of losing at least 1 tooth (odds ratio [OR], 1.15; confidence interval [CI], 1.10-1.20) and lower odds of losing 6 or more teeth (OR, 0.25; CI, 0.22-0.29). In the regression analysis, the predictive margins of tooth loss for 1 tooth and 6 or more teeth follow a linear path. Compared to no comorbidities, the odds of losing 6 or more teeth increased with 1, 2, or 3+ comorbidities. KNOWLEDGE TRANSFER STATEMENT: This study provides significant information about the quantification of comorbidities and its direct correlation with the increased odds of tooth loss. This study also highlighted the protective effect of periodontal treatment on tooth loss. This knowledge can be useful to dental care providers to understand the risk of tooth loss in their patient population.

Age of First Oral Health Examination and Dental Treatment Needs of Medicaid-Enrolled Children.

INTRODUCTION: Early childhood caries (ECC), despite being preventable, remains the most prevalent disease of childhood, particularly in children between the ages of 2 and 5 y. The association between the type of health care provider completing initial oral health examinations and subsequent dental caries in children under 6 y of age is unclear. OBJECTIVE: The objective of the current study is to longitudinally assess the association between age at first oral health examination and provider type at first oral health examination on dental treatment for children under 6 y of age. METHODS: Deidentified administrative claims data were used from the IBM Marketscan Multi-State Medicaid Database (n = 2.41 million Medicaid-enrolled children younger than 6 y in 13 states from 2012 to 2017). A Kaplan-Meier survival analysis was used to examine the association between age at first oral health examination and provider type with first treatment of dental caries at follow-up. RESULTS: The adjusted hazard ratio (HR) of dental caries for children whose first oral health examination at 4 y of age is 5.425 times higher than for children whose first oral health examination was before 1 y of age (95% confidence interval [CI], 5.371-5.479). The adjusted HR of dental caries for children seen by pediatric dentists (HR = 1.215; 95% CI, 1.207-1.223) and physicians (HR = 2.618; 95% CI, 2.601-2.635) was higher than those seen by a general dentist. CONCLUSIONS: Findings from this study highlight the importance of children having their first oral health examination no later than 12 mo of age in accordance with existing guidelines and referrals from physicians to prevent the need for invasive treatment. KNOWLEDGE OF TRANSFER STATEMENT: Results of this study emphasize the need for a child's first oral health examination to be completed no later than 12 mo of age to prevent dental caries. Reinforcement and referrals by physicians based on this recommendation facilitate early establishment of a dental home in young children.

Author Correction: Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans.

High fat feeding impairs skeletal muscle metabolic flexibility and induces insulin resistance, whereas exercise training exerts positive effects on substrate handling and improves insulin sensitivity. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation. HFD markedly induced expression of immune and inflammatory genes, which was not attenuated by Ex. Conversely, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed a significant association between DNA methylation and gene expression changes were PYGM, which was epigenetically regulated in both groups, and ANGPTL4, which was regulated only following Ex. In conclusion, while short-term Ex did not prevent a HFD-induced inflammatory response, it provoked a genomic response that may protect skeletal muscle from atrophy. These epigenetic adaptations provide mechanistic insight into the gene-specific regulation of inflammatory and metabolic processes in human skeletal muscle.

Prevalence of Bartonella species infections in cats in Southern Germany.

Bartonella species are zoonotic pathogens, and infections in cats are common. However, prevalence in cats in Southern Germany is still unknown. Therefore, prevalence of Bartonella species DNA in blood of 479 Southern German cats was determined using a previously published conventional PCR targeting a fragment of the 16S-23S rRNA intergenic spacer region. Associations between Bartonella bacteraemia, housing conditions, feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) status, including progressive, regressive and abortive FeLV infection, were evaluated using Fisher's exact test. Prevalence of Bartonella species bacteraemia was 2.5 per cent (12/479; CI 0.01-0.04 per cent). Bartonella henselae DNA was amplified in 11 of the 12 cats. One cat was positive for Bartonella clarridgeiae DNA. Of the infected cats, 2/12 cats were ill; 6/12 cats had thrombocytopenia. There was a significantly higher risk of Bartonella species infection in young and shelter cats, but not in FIV-infected or FeLV-infected cats. Prevalence of Bartonella species bacteraemia is low in Southern German cats, but there is still a risk of zoonotic transmission associated with ownership of young cats. Most of the infected cats did not show clinical signs. Thrombocytopenia was common in Bartonella species-infected cats and further studies are required to define its clinical relevance.

Clinical practice guidelines for oral management of Sjögren disease: Dental caries prevention

"BACKGROUND: Salivary dysfunction in Sjögren disease can lead to serious and costly oral health complications. Clinical practice guidelines for caries prevention in Sjögren disease were developed to improve quality and consistency of care. METHODS: A national panel of experts devised clinical questions in a Population, Intervention, Comparison, Outcomes format and included use of fluoride, salivary stimulants, antimicrobial agents, and nonfluoride remineralizing agents. The panel conducted a systematic search of the literature according to pre-established parameters. At least 2 members extracted the data, and the panel rated the strength of the recommendations by using a variation of grading of recommendations, assessment, development, and evaluation. After a Delphi consensus panel was conducted, the experts finalized the recommendations, with a minimum of 75% agreement required. RESULTS: Final recommendations for patients with Sjögren disease with dry mouth were as follows: topical fluoride should be used in all patients (strong); although no study results link improved salivary flow to caries prevention, the oral health community generally accepts that increasing saliva may contribute to decreased caries incidence, so increasing saliva through gustatory, masticatory, or pharmaceutical stimulation may be considered (weak); chlorhexidine administered as varnish, gel, or rinse may be considered (weak); and nonfluoride remineralizing agents may be considered as an adjunct therapy (moderate). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The incidence of caries in patients with Sjögren disease can be reduced with the use of topical fluoride and other preventive strategies."

BILL E. KUNKLE INTERDISCIPLINARY BEEF SYMPOSIUM: A meta-analysis of research efforts aimed at reducing the impact of fescue toxicosis on cattle weight gain and feed intake.

The objective of this paper is to present a systematic review and meta-analysis of research efforts aimed at recovering cattle production losses attributed to toxic endophyte-infected [ (Morgan-Jones & Gams.) Glenn, Bacon, & Hanlin comb. Nov.] tall fescue [ (Schreb.) Darbysh.]. The strategies presented include those 1) applied with forage systems, 2) based on pharmacological compounds and functional foods, and 3) based on supplemental dietary nutrients. Cattle BW gain and DM intake was the dependent response evaluated. Among the forage systems reviewed, studies with nontoxic, endophyte-infected tall fescue as a total replacement forage system demonstrated the greatest improvement in per-hectare (152 ± 27.5 kg/ha) and per-animal (0.29 ± 0.03 kg/d) BW gain. Studies with interseeded legumes have exhibited a small and highly variable BW gain effect size per hectare (52 ± 24.1 kg/ha) and per animal (0.11 ± 0.03 kg/d). The legume response was seasonal, with summer exhibiting the greatest benefit. Studies with chemicals that suppress plant growth demonstrated BW gain responses (0.17 ± 0.06 kg/d) equal to or greater than the response observed with legume studies. Cattle grazing toxic tall fescue responded well to anthelmentics, antimicrobial feed additives, and steroid implants, and the use of these technologies may additively help recover production losses. As a group, functional foods have not improved BW gain ( = 0.85). Studies with cattle supplemented with highly digestible fiber supplements observed a 0.15 kg greater BW gain compared with studies using starch- and sugar-based supplements ( < 0.05). Weight gain was positively impacted by the level of supplementation (0.06 kg/DM intake as percent BW). Supplement feed conversion was estimated at 6:1 for the highly digestible fiber supplements compared with 11:1 for starch-based supplements. Tall fescue forage DM intake was predicted to maximize at a supplemental feeding rate of 0.24% BW with a breakpoint at 0.5% BW, and total maximum DM intake (forage plus supplement) occurred at 2.7% BW when supplemental feeding approached 0.9% BW. Results from this meta-analysis should be useful for 1) establishing and comparing measured responses to theoretical improvements in BW gain when additive strategies are considered, 2) research planning, and 3) producer education.

Supplemental trace minerals (zinc, copper, and manganese) as sulfates, organic amino acid complexes, or hydroxy trace-mineral sources for shipping-stressed calves.

Crossbred calves (n = 350; average BW 240 ± 1 kg) were obtained from regional livestock auctions. Within each set (block, n = 4), calves were stratified by BW and arrival sex into 1 of 8, 0.42-ha pens (10 to 12 calves per pen). Pens were assigned randomly to 1 of 3 treatments consisting of supplemental Zn (360 mg/d), Mn (200 mg/d), and Cu (125 mg/d) from inorganic (zinc sulfate, manganese sulfate, and copper sulfate; n = 2 pens per block), organic (zinc amino acid complex, manganese amino acid complex, and copper amino acid complex; Availa-4, Zinpro Corp., Eden Prairie, MN; n = 3 pens per block), and hydroxy (IntelliBond Z, IntelliBond C, and IntelliBond M; Micronutrients, Indianapolis, IN; n = 3 pens per block) sources. During the 42- to 45-d backgrounding period calves had ad libitum access to bermudagrass hay and were fed corn and dried distillers grain-based supplements that served as carrier for the treatments. After removal of data for chronic (n = 6) and deceased (n = 1) calves, trace-mineral source had no effect on final or intermediate BW (P = 0.86) or ADG (P ≥ 0.24). With all data included in the analysis, dietary treatments had no effect on the number treated once (P = 0.93), twice (P = 0.71), or 3 times (P = 0.53) for bovine respiratory disease or on the number of calves classified as chronic (P = 0.55). Based on these results, trace-mineral source had no effect on total BW gain, ADG, or morbidity during the receiving phase in shipping-stressed cattle.

Concurrent administration of an intranasal vaccine containing feline herpesvirus-1 (FHV-1) with a parenteral vaccine containing FHV-1 is superior to parenteral vaccination alone in an acute FHV-1 challenge model.

The administration of intranasal (IN) or subcutaneous (SC) vaccines containing modified live feline herpesvirus 1 (FHV-1) offers some level of protection against FHV-1 challenge, but relative efficacy is <100%. In this study, clinical signs and viral shedding in kittens were compared among three groups: (1) kittens vaccinated concurrently with IN and SC vaccines containing FHV-1 (Group 1, n = 8); (2) kittens vaccinated with a SC FHV-1 vaccine alone (Group 2, n = 8), and (3) unvaccinated control kittens (Group 3, n = 8). All kittens were FHV-1 naïve at enrolment, and challenge with a virulent strain of FHV-1 was performed 1 week after vaccination. Daily clinical signs and pharyngeal FHV-1 shedding were recorded over a 21-day infection period. Overall, kittens in Group 1 had significantly less severe clinical illness than those in Group 2 (P < 0.05). Additionally, significantly less FHV-1 DNA was detected on pharyngeal swabs from kittens in Group 1 compared to those in Group 2 (P < 0.001). Concomitant administration of IN and SC FHV-1 vaccines was superior to administration of the SC FHV-1 vaccine alone in this challenge model of FHV-1 naïve kittens.

Two weeks of reduced-volume sprint interval or traditional exercise training does not improve metabolic functioning in sedentary obese men.

AIMS: To investigate the effects of short-term, reduced-volume sprint interval training (SIT) compared to traditional exercise recommendations (TER) in sedentary obese men. METHODS: Sixteen subjects [37.8 ± 5.8 years; body mass index (BMI) 32.8 ± 4.7 kg/m(2)] were randomly allocated to 2 weeks of either SIT (6 sessions of 8-12 × 10 s sprints) or TER [10 sessions of 30 min at 65% peak oxygen consumption (VO(2peak))] cycle exercise. Fasting plasma glucose, insulin, non-esterified fatty acids (NEFA), homeostasis model assessment of insulin sensitivity (HOMA-IR), body composition and VO(2peak) were assessed at baseline and approximately 72 h after the final training bout. Skeletal muscle biopsy samples were also obtained before and 72 h after training and analysed for AS160 phosphorylation and COX II, COX IV, GLUT-4, Nur77 and SIRT1 protein expression. RESULTS: No changes in BMI, body composition, VO(2peak), glucose, insulin, NEFA and HOMA-IR were observed after training, either within or between groups. Skeletal muscle markers of glucose metabolism and mitochondrial function also remained unaltered after 2 weeks of exercise training. CONCLUSIONS: Our findings show that 2 weeks of reduced-volume SIT or TER did not elicit any measurable metabolic adaptations in sedentary obese men. Further work is needed to determine the minimal amount of exercise required for short-term adaptations in this population.

Prevalence of Bartonella species, hemoplasmas, and Rickettsia felis DNA in blood and fleas of cats in Bangkok, Thailand.

Flea infestations are common in Thailand, but little is known about the flea-borne infections. Fifty flea pools and 153 blood samples were collected from client-owned cats between June and August 2009 from veterinary hospitals in Bangkok, Thailand. Total DNA was extracted from all samples, and then assessed by conventional PCR assays. The prevalence rates of Bartonella spp. in blood and flea samples were 17% and 32%, respectively, with DNA of Bartonella henselae and Bartonella clarridgeiae being amplified most commonly. Bartonella koehlerae DNA was amplified for the first time in Thailand. Hemoplasma DNA was amplified from 23% and 34% of blood samples and flea pools, respectively, with 'Candidatus Mycoplasma haemominutum' and Mycoplasma haemofelis being detected most frequently. All samples were negative for Rickettsia felis. Prevalence rate of B. henselae DNA was increased 6.9 times in cats with flea infestation. Cats administered flea control products were 4.2 times less likely to be Bartonella-infected.

Bartonella species antibodies and hyperglobulinemia in privately owned cats.

BACKGROUND: Bartonella species are zoonotic agents and primary pathogens in cats. Hyperglobulinemia has been associated with bartonellosis in humans and cats. HYPOTHESIS/OBJECTIVES: To evaluate for associations between Bartonella species immunoglobulin G (IgG) antibodies and serum biochemistry panel results in privately owned cats. ANIMALS: 1,477 privately owned cats. METHODS: Residual sera were collected after biochemical evaluation for this prospective, cross-sectional serosurvey. Bartonella species IgG ELISA was performed with a cutoff value of ≥ 1 : 64. Stepwise logistic regression analysis was performed with the endpoint titer as the outcome variable. The final statistical model included age, albumin, ALP activity, ALT activity, bilirubin, creatinine, glucose, and globulin as covariates. Serum protein electrophoresis was performed with serum from 50 cats with and without antibodies to Bartonella species and hyperglobulinemia. Sera from cats seropositive to Bartonella species and with hyperglobulinemia were assessed for evidence of exposure to other infectious agents associated with hyperglobulinemia. RESULTS: Risk of seropositivity to Bartonella species was positively associated with the natural log of globulin concentration (OR = 11.90, 95% CI 6.15-23.02, P < .0001), and inversely associated with the natural log of glucose concentration (OR = 0.66, 95% CI 0.50-0.87, P = .004). Another explanation for hyperglobulinemia was not identified for most cats with Bartonella species antibodies. Hyperglobulinemia was primarily caused by polyclonal gammopathy in cats that were seronegative and seropositive for Bartonella species. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperglobulinemia was significantly associated with seropositivity to Bartonella species. Testing for bartonellosis is warranted in cats with unexplained hyperglobulinemia and clinical or laboratory findings suggestive of bartonellosis.

What's new since Hippocrates? Preventing type 2 diabetes by physical exercise and diet.

Since the work of Eriksson and Lindgärde, published over two decades ago (Diabetologia 1991;34:891-898), we have known that type 2 diabetes can be prevented or delayed by supervised lifestyle interventions (physical exercise and diet modification) in persons at risk of the disease. Here we discuss a novel, time-efficient approach to physical exercise prescription, low-volume, high-intensity interval training (LVHIT), and its efficacy for inducing a range of health benefits in a variety of populations at risk of inactivity-related diseases. We look to the future and suggest that current guidelines for exercise may need to be revised to include different training techniques to deliver the optimum exercise prescription. Indeed, we predict that subsequent exercise guidelines will include LVHIT as part of a comprehensive 'fitness menu' that allows individuals to select the exercise regimen that best fulfils their medical needs, is suited to their lifestyle and daily time restraints, and meets their personal goals.

Prevalence of Bartonella species, Rickettsia felis, haemoplasmas and the Ehrlichia group in the blood of cats and fleas in eastern Australia.

OBJECTIVES: To define the prevalence of Bartonella spp., Rickettsia felis, Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum' (Mhm) and 'Candidatus Mycoplasma turicensis' (Mtc) in cats and their fleas in eastern Australia. DESIGN AND PROCEDURE: Conventional PCR assays that detect Bartonella spp., M. haemofelis, Mhm, Mtc, Rickettsia spp., Ehrlichia spp., Anaplasma spp. and Neorickettsia spp. were performed on DNA extracted from blood and fleas collected from 111 cats. Cat sera were assayed by ELISA for IgG of Bartonella spp. RESULTS: DNA of M. haemofelis, Mtc and Mhm was amplified from 1 (0.9%), 1 (0.9%) and 17 cats (15.3%), respectively. Only DNA of Mhm was amplified from the 62 of 111 pooled flea samples (flea sets; 55.9%). Overall, the prevalence rates for Bartonella spp. DNA in the cats and the flea sets was 16.2% (18 cats) and 28.8% (32 flea sets), respectively. Bartonella spp. IgG was detected in 42 cats (37.8%), of which 11 (26.2%) were positive for Bartonella spp. DNA in their blood. R. felis DNA was amplified from 22 flea sets (19.8%), but not from cats. Overall, DNA of one or more of the organisms was amplified from 27% (30) of cats and 67.6% (75) of the flea sets. CONCLUSIONS: This is the first Australian study to determine the prevalence of R. felis and B. clarridgeiae in both fleas and the cats from which they were collected. Flea-associated infectious agents are common in cats and fleas in eastern Australia and support the recommendation that stringent flea control be maintained on cats.

Antibodies against Crandell Rees feline kidney (CRFK) cell line antigens, alpha-enolase, and annexin A2 in vaccinated and CRFK hyperinoculated cats.

BACKGROUND: Cats inoculated with feline herpesvirus 1, calicivirus, and panleukopenia (FVRCP) vaccines grown on the Crandell Rees feline kidney (CRFK) cell line have been shown to develop anti-CRFK antibodies. The identities of common CRFK antigens are unknown. HYPOTHESIS: Cats inoculated with CRFK lysates and FVRCP vaccines will develop autoantibodies measurable by Western blot immunoassay. Antigens associated with these antibodies can be isolated for further study. ANIMALS: One CRFK hyperinoculated rabbit, 44 age-matched unvaccinated kittens purchased from a commercial vendor. METHODS: Commonly recognized CRFK antigens were identified by comparison of Western blot immunoassays using sera from a hyperinoculated rabbit and kittens inoculated with CRFK lysate or 1 of 4 commercially available FVRCP vaccines. Antigens were purified from CRFK lysates and sequenced. Antigen recognition was confirmed by Western blot immunoassay and indirect ELISA for 2 proteins using sera from CRFK and FVRCP inoculated kittens. RESULTS: CRFK antigens 47, 40, and 38 kD in size were identified. Protein isolation and sequencing identified 3 CRFK proteins as alpha-enolase, annexin A2, and macrophage capping protein (MCP). Sera from FVRCP and CRFK inoculated cats were confirmed to recognize annexin A2 and alpha-enolase by Western blot immunoassay and indirect ELISA. CONCLUSIONS AND CLINICAL RELEVANCE: This study validated the use of Western blot immunoassay for detection of antibodies against CRFK proteins and identified 3 CRFK antigens. In humans, alpha-enolase antibodies are nephritogenic; alpha-enolase and annexin A2 antibodies have been associated with autoimmune diseases. Further research will be necessary to determine the clinical relevance of these findings.