A Comparative Review of Standardized Incidence Ratios of De Novo Malignancies Post Liver Transplantation in Males Versus Females.

After liver transplantation (LTx), the most common cause of death in the long-term is de-novo malignancy (DNM). The aim is to review the gender differences in the standardized incidence ratio (SIR) of DNM within the same geographical locations. METHODS: Four studies were identified comparing post-LTx SIR between males and females. RESULTS: From 6663 males and 2780 females LTx recipients, the mean SIR from each of the four studies for males is 2.8, 2.0, 1.94, and 3.4, and 3.5, 1.3, 1.95, and 2.3 for females. On meta-analysis using a random effect model for each gender group. No significant difference was revealed after logarithmic transformation and subgroup meta-analysis. Overall mean SIR with 95% Confidence Interval (CI) for males is 2.53 (95% CI 1.65-3.88) and 2.3 (1.25-4.24) for females. lung malignancy, 1.97 (1.14-3.41) for males and 2.65 (0.67-10.47) for females. For colorectal malignancy, the combined SIR for males is 1.98 (0.58-6.78) and 1.85 (1.02-3.37) for females. The SIR for female gender-specific malignancies; SIR for breast is 1.1 ± 4.4, cervix 2.9 ± 1.9, uterus 2.8, and ovarian 0.7, and for males, testis 1.6 ± 1.3, prostate 1.2 ± 0.4. However, rare malignancies, male breast cancers (n = 1, SIR, 22.6), and Kaposi's sarcoma, in males (n = 6) and in females (n = 1), had SIR 120. and 212.7, respectively. CONCLUSION: Overall, there are no statistical differences between male and female DNM. Female-specific cervix, uterus, ovarian, and male-specific testis and prostate have similar SIR. Rare malignancies have very high SIR.

Prospective Comparison of Urinary Measured Creatinine Clearance With eGFR and Cystatin C Based Cis-eGFR, Including Kinetic eGFR in the Immediate Post-transplant Period With Prompt Allograft Function.

BACKGROUND: The estimated glomerular filtration rate (eGFR) and kinetic estimated glomerular filtration rate (KeGFR) have not been compared, with urinary measured creatinine clearance (mCrCl) or serum cystatin C (CysC) eGFR, soon after kidney transplantation (KTx) with prompt primary function. This study aims to compare post-KTx, urinary mCrCl, and eGFR CysC with eGFR and KeGFR. METHODS: Post-KTx, urine was collected every 12 hours from 25 of the 34 consenting subjects to calculate mCrCl and compare with Modification of Diet in Renal Disease (MDRD)-4, Jelliffe eGFR, Cockcroft-Gault creatinine clearance (CrCl), and KeGFR by Chen and Brater formulae. Serum CysC levels were also measured in the last 14 subjects to compare with creatinine, mCrCl, and eGFR CysC. RESULTS: At 12 to 96 hours post-KTx (n = 25), mCrCl was 55.8% to 13.6% higher than MDRD-4 eGFR. The mean CysC level (n = 14) was 58% to 14% lower than creatinine for up to 3.0 days post-KTx, with higher MDRD-4 eGFR CysC. Chen and Brater KeGFR were significantly lower than mCrCl and eGFR (Fig 1B, Table 1). Within 3 days post-KTx, a 50% decrease in creatinine provided ≥ 50 mL/min CrCl in 90% of cases (mean mCrCl 61.7 ± 22.8). This difference was greater when the initial creatinine was higher with the rapid decrease in creatinine. CONCLUSIONS: (1) Post-KTx eGFR/KeGFR formulae underestimated mCrCl. (2) Serum CysC levels were lower than creatinine, corresponding with higher eGFR CysC. (3) A 50% decrease from initial serum creatinine; mean mCrCl was 61.7 ± 22.8 mL/min, and 90% of them have mCrCl > 50 mL/min. Post-KTx, until creatinine is stabilized, recipients are often receiving subtherapeutic dosing of renally adjusted medications. More prospective studies are necessary, including radioisotope clearance.

Indications of Helicobacter pylori Eradication Treatment and Its Influence on Prescriptions and Effectiveness (Hp-EuReg).

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.

Helicobacter pylori: High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort.

BACKGROUND: Helicobacter pylori (H. pylori) eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and metronidazole resistance such as ours, Maastricht VI guidelines suggest high dose amoxicillin dual therapy (HDADT) can be considered, subject to evidence for local efficacy. In this study we assess efficacy of HDADT therapy for H. pylori eradication in an Irish cohort. AIM: To assess the efficacy of HDADT therapy for H. pylori eradication in an Irish cohort as both first line, and subsequent therapy for patients diagnosed with H. pylori. METHODS: All patients testing positive for H. pylori in a tertiary centre were treated prospectively with HDADT (amoxicillin 1 g tid and esomeprazole 40 mg bid × 14 d) over a period of 8 months. Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy. A delta-over-baseline > 4% was considered positive. Patient demographics and treatment outcomes were recorded, analysed and controlled for basic demographics and prior H. pylori treatment. RESULTS: One hundred and ninety-eight patients were identified with H. pylori infection, 10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing. In all 139 were included in the analysis, 55% (n = 76) were female, mean age was 46.6 years. Overall, 93 (67%) of patients were treatment-naïve and 46 (33%) had received at least one previous course of treatment. The groups were statistically similar. Self-reported compliance with HDADT was 97%, mild side-effects occurred in 7%. There were no serious adverse drug reactions. Overall the eradication rate for our cohort was 56% (78/139). Eradication rates were worse for those with previous treatment [43% (20/46) vs 62% (58/93), P = 0.0458, odds ratio = 2.15]. Age and Gender had no effect on eradication status. CONCLUSION: Overall eradication rates with HDADT were disappointing. Despite being a simple and possibly better tolerated regime, these results do not support its routine use in a high dual resistance country. Further investigation of other regimens to achieve the > 90% eradication target is needed.

Physiological and psychological determinants of long-term diet-induced type 2 diabetes (T2DM) remission: A narrative review.

Type 2 diabetes mellitus (T2DM) is a highly prevalent metabolic disease, causing a heavy burden on healthcare systems worldwide, with related complications and anti-diabetes drug prescriptions. Recently, it was demonstrated that T2DM can be put into remission via significant weight loss using low-carbohydrate diets (LCDs) and very low-energy diets (VLEDs) in individuals with overweight and obesity. Clinical trials demonstrated remission rates of 25-77%, and metabolic improvements such as improved blood lipid profile and blood pressure were observed. In contrast, clinical trials showed that remission rate declines with time, concurrent with weight gain, or diminished weight loss. This review aims to discuss existing literature regarding underlying determinants of long-term remission of T2DM including metabolic adaptations to weight loss (e.g., role of gastrointestinal hormones), type of dietary intervention (i.e., LCDs or VLEDs), maintaining beta (ß)-cell function, early glycemic control, and psychosocial factors. This narrative review is significant because determining the factors that are associated with challenges in maintaining long-term remission may help in designing sustainable interventions for type 2 diabetes remission.

Plague Gives Surprises in the Second Decade of the Twenty-First Century.

From 2010 through 2019, the six leading countries by numbers of human plague cases reported to the WHO were, in order from highest to lowest, Madagascar, Congo, Uganda, Peru, Tanzania, and the United States. From these countries, there was a total of 4,547 cases, of whom 786 (17%) died. Top plague events were four outbreaks of primary pneumonic plague in Madagascar that affected 1,936 persons, including index cases, of whom 137 died. One of the outbreaks was caused by a streptomycin-resistant strain of Yersinia pestis. Person-to-person transmission occurred in a taxi, in households with family caregivers, at burial ceremonies and wakes for victims, and at a hospital where cases were treated. Unique clinical presentations in the United States included a dog owner who acquired pneumonic plague from his sick dog, a boy with septicemic plague who developed complications of osteomyelitis and arthritis that required surgery for bone removal and bone grafting, and a prairie dog handler who acquired bubonic plague from a bite by a sick prairie dog. Efficacy of antibiotics in a model of pneumonic plague in African green monkeys for use in bioterrorism revealed the most effective drugs to be gentamicin, ciprofloxacin, and levofloxacin. A recombinant vaccine containing Fraction 1 antigen and V antigen of Y. pestis designed for first responders during a bioterrorism attack and military personnel was tested for safety and immunogenicity but was not licensed for use by the end of the decade.

Strategies for the Purification of Membrane Proteins.

Membrane proteins account for approximately 30% of the coding regions of all sequenced genomes, and they play crucial roles in many fundamental cell processes. However, there are relatively few membrane proteins with known three-dimensional structures. This is likely due to technical challenges associated with membrane protein extraction, solubilization, and purification. Membrane proteins are classified based on the level of interaction with membrane lipid bilayers, with peripheral membrane proteins associating non-covalently with the membrane, and integral membrane proteins associating more strongly by means of hydrophobic interactions. Generally speaking, peripheral membrane proteins can be purified by milder techniques than integral membrane proteins, with the latter's extraction requiring phospholipid bilayer disruption using detergents or organic solvents. In this chapter, important considerations for membrane protein purification are addressed, with a focus on the initial stages of membrane protein solubilization, where problems are most frequently encountered. Protocols are outlined for the extraction of peripheral membrane proteins, solubilization of integral membrane proteins, and sample clean-up and concentration.

The Associations of Chronotype and Shift Work With Rheumatoid Arthritis.

The circadian clock regulates multiple aspects of human physiology including immunity. People have a circadian preference termed chronotype. Those with an evening preference may be better suited to shift work, but also carry higher risk of adverse health. Shift work leads to misalignment of circadian rhythms and is associated with increased risk of inflammatory disease such as asthma and cancer. Here, we investigate the association between chronotype, shift work, and rheumatoid arthritis (RA). The associations between exposures of shift work and chronotype on risk of RA were studied in up to 444,210 U.K. Biobank participants. Multivariable logistic regression models were adjusted for covariates: age, sex, ethnicity, alcohol intake, smoking history, Townsend Deprivation Index (TDI), sleep duration, length of working week, and body mass index (BMI). After adjusting for covariates, individuals with a morning chronotype had lower odds of having rheumatoid arthritis (RA; odds ratio [OR]: 0.93, 95% confidence interval [CI]: 0.88-0.99) when compared to intermediate chronotypes. The association between morning chronotype and RA persisted with a more stringent RA case definition (covariate-adjusted OR: 0.89, 95% CI: 0.81-0.97). When adjusted for age, sex, ethnicity, and TDI, shift workers had higher odds of RA (OR: 1.22, 95% CI: 1.1-1.36) compared to day workers that attenuated to the null after further covariate adjustment (OR: 1.1, 95% CI: 0.98-1.22). Morning chronotypes working permanent night shifts had significantly higher odds of RA compared to day workers (OR: 1.89, 95% CI: 1.19-2.99). These data point to a role for circadian rhythms in RA pathogenesis. Further studies are required to determine the mechanisms underlying this association and understand the potential impact of shift work on chronic inflammatory disease and its mediating factors.

Chat Generative Pre-trained Transformer: why we should embrace this technology.

With the advent of artificial intelligence that not only can learn from us but also can communicate with us in plain language, humans are embarking on a brave new future. The interaction between humans and artificial intelligence has never been so widespread. Chat Generative Pre-trained Transformer is an artificial intelligence resource that has potential uses in the practice of medicine. As clinicians, we have the opportunity to help guide and develop new ways to use this powerful tool. Optimal use of any tool requires a certain level of comfort. This is best achieved by appreciating its power and limitations. Being part of the process is crucial in maximizing its use in our field. This clinical opinion demonstrates the potential uses of Chat Generative Pre-trained Transformer for obstetrician-gynecologists and encourages readers to serve as the driving force behind this resource.

'It's like being pushed into sea on a boat with no oars': Breast cancer survivorship and rehabilitation support in Ireland and the UK.

BACKGROUND: Cancer survivorship is associated with co-morbidities including anxiety, depression and cardiovascular disease (CVD). Rehabilitative care post-treatment is vital for survivors' psychological and physical well-being. The present study aimed to investigate breast cancer survivors' attitudes towards their health post-treatment; their awareness of co-morbidities associated with treatment; and their awareness of support systems available. METHODS: A qualitative research approach was employed, using semi-structured interviews with breast cancer survivors from the UK and Ireland. Data were analysed using thematic analysis. Eight breast cancer survivors were recruited through purposive sampling. RESULTS: Two themes emerged from the data: (1) health and rehabilitation post-treatment, which included mental and physical health and a desire to control one's own health in survivorship as well as a discussion around co-morbidities, and (2) access to support services in survivorship, which highlighted both positive and negative experiences of accessing support, as well as reasons for not accessing support in survivorship. CONCLUSIONS: Access to rehabilitation support, including diet, exercise and stress management, is key to survivorship. Rehabilitation and support services need to be more readily available for survivors to aid them in this journey and to educate them on the increased risk of conditions such as CVD with cancer treatment. Utilising current cardiac rehabilitation models could be a solution to provide a holistic cancer rehabilitation, thus providing the lifelong support that cancer survivors both want and need.

Palliative Therapies in Metastatic Pancreatic Cancer: Does Medicaid Expansion Make a Difference?

BACKGROUND: The aim of this study was to evaluate the impact of medicaid expansion (ME) on receipt of palliative therapies in metastatic pancreatic cancer patients. PATIENTS AND METHODS: A difference-in-differences (DID) approach was used to analyze patients with metastatic pancreatic cancer identified from the National Cancer Database diagnosed during two time periods: pre-expansion (2010-2012) and post-expansion (2014-2016). Patients diagnosed while residing in ME states were compared with those in non-ME states. Multivariable logistic regression was used to identify predictors of receipt of palliative therapies. RESULTS: Of 87,738 patients overall, 7483(18.1%) received palliative therapies in the pre-expansion, while 10,211(21.5%) received palliative therapies in the post-expansion period. In the pre-expansion period, treatment at a high-volume facility (HVF) (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.18) and non-west geographic location were predictive of increased palliative therapies. In the post-expansion period, treatment at an HVF (OR 1.09, 95% CI 1.02-1.16), geographic location, and living in an ME state at the time of diagnosis (OR 1.14, 95% CI 1.06-1.22) were predictive of increased palliative therapies. Older age, highest quartile median income (zip-code based), and treatment at a nonacademic facility were independently associated with decreased palliative therapies in both periods. DID analysis demonstrated that patients with metastatic pancreatic cancer living in ME states had increased receipt of palliative therapies relative to those in non-ME states (DID = 2.68, p < 0.001). CONCLUSIONS: The overall utilization of palliative therapies in metastatic pancreatic cancer is low. Multiple sociodemographic disparities exist in the receipt of palliative therapies. ME is associated with increased receipt of palliative therapies in patients with metastatic pancreatic cancer.

Chronotype in Patients With Immune-Mediated Inflammatory Disease: A Systematic Review.

Immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel disease, and asthma share common pathophysiological pathways characterized by chronic inflammation and subsequent tissue damage involving multiple body sites. Circadian rhythms are 24-h body cycles that regulate immune activity and control the magnitude of immune response based on time of day. Chronotype is a person's individual circadian phase preference, ranging from morningness to eveningness, which is known to influence the risk of cardiometabolic and mental health disease. We systematically reviewed the literature to assess the association of questionnaire-based chronotype and patients with IMID. A comprehensive search of MEDLINE and Embase identified 12 studies meeting the inclusion criteria, conducted in 7 countries and covering 4 IMIDs to include 15,625 IMID patients and 410,783 healthy controls. Results showed that later chronotype may be a risk factor for worse quality of life and increased symptom burden in patients with IMIDs. In addition, chronotype may be a risk factor for IMID incidence, but the direction and magnitude of this effect were not consistent across individual IMIDs. Chronotype assessment could contribute to risk stratification in patients with IMIDs. Cross-disciplinary collaboration to understand the role of circadian rhythms and chronotype in driving common inflammatory pathways could help to improve outcomes for patients with IMIDs.

Personality traits are consistently associated with blood mitochondrial DNA copy number estimated from genome sequences in two genetic cohort studies.

Background: Mitochondrial DNA copy number (mtDNAcn) in tissues and blood can be altered in conditions like diabetes and major depression and may play a role in aging and longevity. However, little is known about the association between mtDNAcn and personality traits linked to emotional states, metabolic health, and longevity. This study tests the hypothesis that blood mtDNAcn is related to personality traits and mediates the association between personality and mortality. Methods: We assessed the big five personality domains and facets using the Revised NEO Personality Inventory (NEO-PI-R), assessed depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), estimated mtDNAcn levels from whole-genome sequencing, and tracked mortality in participants from the Baltimore Longitudinal Study of Aging. Results were replicated in the SardiNIA Project. Results: We found that mtDNAcn was negatively associated with the Neuroticism domain and its facets and positively associated with facets from the other four domains. The direction and size of the effects were replicated in the SardiNIA cohort and were robust to adjustment for potential confounders in both samples. Consistent with the Neuroticism finding, higher depressive symptoms were associated with lower mtDNAcn. Finally, mtDNAcn mediated the association between personality and mortality risk. Conclusions: To our knowledge, this is the first study to show a replicable association between mtDNAcn and personality. Furthermore, the results support our hypothesis that mtDNAcn is a biomarker of the biological process that explains part of the association between personality and mortality. Funding: Support for this work was provided by the Intramural Research Program of the National Institute on Aging (Z01-AG000693, Z01-AG000970, and Z01-AG000949) and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. AT was also supported by the National Institute on Aging of the National Institutes of Health Grant R01AG068093.

Cells are powered by internal structures called mitochondria which have their own DNA molecules. How many copies of mitochondrial DNA blood cells contain is one aspect of mitochondrial health and is considered to provide a good indication of an individual's ability to convert glucose into energy. Consequently, changes in the amount of mitochondrial DNA in the blood are linked to conditions like diabetes and cancer, and have also been associated with aging and mortality. A set of well-classified personality traits known as 'the Big Five' have also been shown to affect energy levels and the longevity of individuals. However, it remained unclear if there is a relationship between these characteristics and the number of copies of mitochondrial DNA in the blood. To investigate, Oppong et al. used a specialized test to assess the personality traits of participants from two separate cohorts: Baltimore Longitudinal Study of Ageing and the SardiNIA Project. The genomic sequence of each person was then analyzed to calculate the amount of mitochondrial DNA in their blood, and their mortality was recorded based on whether they were alive or dead multiple years later. Oppong et al. found that low levels of mitochondrial DNA were linked with high scores in neuroticism (a trait typically associated with anxiety, depression, and self-doubt). Further statistical tests revealed that mitochondrial DNA levels mediate the relationship between a person's personality and their risk of death. These findings suggest that personality traits impact the number of mitochondrial DNA molecules in a person's blood, which, in turn, influences how long they are likely to live. However, further work is needed to find out what causes this effect.

Putting nutrition education on the table: development of a curriculum to meet future doctors' needs.

COVID-19 has further exacerbated trends of widening health inequalities in the UK. Shockingly, the number of years of life lived in general good health differs by over 18 years between the most and least deprived areas of England. Poor diets and obesity are established major risk factors for chronic cardiometabolic diseases and cancer, as well as severe COVID-19. For doctors to provide the best care to their patients, there is an urgent need to improve nutrition education in undergraduate medical school training.With this imperative, the Association for Nutrition established an Interprofessional Working Group on Medical Education (AfN IPG) to develop a new, modern undergraduate nutrition curriculum for medical doctors. The AfN IPG brought together expertise from nutrition, dietetic and medical professionals, representing the National Health Service (NHS), royal colleges, medical schools and universities, government public health departments, learned societies, medical students, and nutrition educators. The curriculum was developed with the key objective of being implementable through integration with the current undergraduate training of medical doctors.Through an iterative and transparent consultative process, thirteen key nutritional competencies, to be achieved through mastery of eleven graduation fundamentals, were established. The curriculum to facilitate the achievement of these key competencies is divided into eight topic areas, each underpinned by a learning objective statement and teaching points detailing the knowledge and skills development required. The teaching points can be achieved through clinical teaching and a combination of facilitated learning activities and practical skill acquisition. Therefore, the nutrition curriculum enables mastery of these nutritional competencies in a way that will complement and strengthen medical students' achievement of the General Medical Council (GMC) Outcome for Graduates.As nutrition is an integrative science, the AfN IPG recommends that the curriculum is incorporated into initial undergraduate medical studies before specialist training. This will enable our future doctors to recognise how nutrition is related to multiple aspects of their training, from physiological systems to patient-centred care, and acquire a broad, inclusive understanding of health and disease. In addition, it will facilitate medical schools to embed nutrition learning opportunities within the core medical training, without the need to add in a large number of new components to an already crowded programme or with additional burden for teaching staff.The undergraduate nutrition curriculum for medical doctors is designed to support medical schools to create future doctors who will understand and recognise the role of nutrition in health. Moreover, it will equip frontline staff to feel empowered to raise nutrition-related issues with their patients as a fundamental part of enhanced care and to appropriately refer on for nutrition support with a registered associate nutritionist/registered nutritionist (ANutr/RNutr) or registered dietitian (RD) where this is likely to be beneficial.

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug-drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncology drugs are extensively used, more attention should be given to monitoring potential DDIs to minimize risks. Recognition of DDIs is of utmost importance in an era of rapid developments in cancer treatments and introduction of novel treatments and protocols. When managing cancer-associated thrombosis (CAT), the concomitant use of a DOAC and a moderate or strong modulator (inhibitor or inducer) of CYP3A4 or a P-glycoprotein (P-gp) is most likely to be associated with significant DDIs. Therefore, LMWHs remain the first-line option for the long-term management of CAT under these circumstances and physicians must consider utilizing LMWHs as first line. This review describes the risk of DDIs and their potential impact and outcomes in patients with cancer associated thrombosis (CAT) receiving anticoagulation.

A multicenter retrospective study assessing progression of biliary sludge in dogs using ultrasonography.

BACKGROUND: Biliary sludge (BS) frequently is identified on ultrasonographic examination and is described as incidental. It is hypothesized that biliary stasis and hypersecretion play a role in both BS and gallbladder mucocele (GBM) formation. Recent studies have documented similarities in composition of BS and GBM, and there are several examples of progression from BS to GBM in the veterinary literature. OBJECTIVES: To assess the relationship between the presence of BS and later development of GBM in dogs, over time periods >12 months. ANIMALS: A total of 154 dogs with BS and ultrasonographic follow-up >12 months. METHODS: Medical records were retrospectively collected from 9 UK-based referral centers for all available time points. A semiobjective scoring system was used to track volume of BS within the gall bladder (GB) over time. RESULTS: Twenty dogs developed GBM during the study period. Shetland Sheepdogs (odds ratio [OR], 40.99; 95% confidence interval [CI], 3.61-465.95; P = .003) and Border Terriers (OR, 11.66; 95% CI, 3.28-46.63; P < .001) were independent risk factors for the development of GBM. Non-gravity-dependent BS (NDBS) was noted to form before GBM development in 9/20 dogs, and breeds at-risk for GBM were more likely to have NDBS. Odds for the development of GBM increased with BS score. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with NDBS may be at risk for the development of GBM and a stratified BS scoring system could allow for semiobjective monitoring over time, particularly in at-risk breeds.

Circadian rhythms in immunity and host-parasite interactions.

The mammalian immune system adheres to a 24 h circadian schedule, exhibiting daily rhythmic patterns in homeostatic immune processes, such as immune cell trafficking, as well as the inflammatory response to infection. These diurnal rhythms are driven by endogenous molecular clocks within immune cells which are hierarchically coordinated by a light-entrained central clock in the suprachiasmatic nucleus of the hypothalamus and responsive to local rhythmic cues including temperature, hormones and feeding time. Circadian control of immunity may enable animals to anticipate daily pathogenic threat from parasites and gate the magnitude of the immune response, potentially enhancing fitness. However, parasites also strive for optimum fitness and some may have co-evolved to benefit from host circadian timing mechanisms, possibly via the parasites' own intrinsic molecular clocks. In this review, we summarize the current knowledge surrounding the influence of the circadian clock on the mammalian immune system and the host-parasitic interaction. We also discuss the potential for chronotherapeutic strategies in the treatment of parasitic diseases.