Identifying the public health needs of a UK probation cohort: a cross-sectional analysis.

BACKGROUND: The health needs of those under probation are likely high, but they have received very little public health attention. Limited evidence exists on the public health needs and interventions to support this cohort. METHODS: Surveys were completed by 257 people on probation as part of a local health needs assessment. Results were compared with the general population responses from the National Survey for Wales (2021-22). RESULTS: People on probation were 4.2 times more likely to self-report not-good general health (fair, bad or very bad) than the general population (adjusted Odds Ratio [aOR] 4.2, 95% Confidence Intervals [CI] 3.2-5.4). The odds of having a mental health condition were over eight times higher than the general population (aOR 8.8, 95% CI 6.8-11.4). Prevalence of smoking (52%), drug use (60%), attention-deficit hyperactivity disorder (21%), autism (4%) and dyslexia (15%) were all higher than the general population. General Practitioner usage and hospital stays were higher, but dentist or optician usage lower than the general population (P < 0.05). Emergency departments were accessed by 35%, with 9% frequenting them three or more times. CONCLUSIONS: People on probation have poorer self-reported health, higher prevalence of unhealthy behaviours and higher accessing of reactive health services than the general population.

Omission of Axillary Dissection in Node Positive Breast Cancer After Neoadjuvant Systemic Therapy.

INTRODUCTION: Guidelines recommend axillary lymph node dissection (ALND) for ypN + positive patients as patients receiving neoadjuvant systemic therapy (NST) were excluded from trials omitting ALND in pN + patients. We sought to characterize trends in omission of ALND in patients with ypN + disease. METHODS: Adult women with invasive breast carcinoma in the National Cancer Database between 2012 and 2019 who received NST (chemotherapy or endocrine) and had ypN + disease were included. Patients were excluded if they did not have definitive surgery within eight months of diagnosis. The primary study outcome was completion of ALND versus omission. Differences in demographics, tumor characteristics, and treatment were identified using bivariate and multivariate logistic regression models. RESULTS: In total, 103,121 women were included. Most had cT1 (26%) or cT2 (45%) tumors, cN + disease (71%), and ductal histology (83%). 69% of patients received neoadjuvant chemotherapy and 31% neoadjuvant endocrine without chemotherapy (30% both). ALND was performed in 77% of patients. Omission of ALND became more prevalent each year from 2012 (14%) to 2019 (34%). On multivariate modeling, year of diagnosis, black race, cN status, higher grade, estrogen receptor+/HER2-receptor subtype, and mastectomy were associated with increased prevalence of ALND. Age, Charlson/Deyo comorbidity index score, endocrine versus chemotherapy, and adjuvant radiation were not associated with receipt of ALND. CONCLUSIONS: Despite guidelines recommending ALND, omission is common in patients with ypN + breast cancer after NST. Omission of ALND increased significantly over time and is associated with clinical and demographic factors. Future study is needed to determine the oncologic safety of this approach.

Quantifying cardiovascular disease risk and heart age predictions for men in the prison environment.

OBJECTIVES: Cardiovascular disease (CVD) and associated risk factors within the prison population often present at a younger age in this cohort. Given CVD is largely preventable, it warrants investigation to fully quantify this risk. This study explored the relative predicted 10-year CVD risk and examined the calculated heart age in a representative sample of male individuals aged 25-84 years within the prison environment. STUDY DESIGN: This was a cross-sectional study. METHODS: Data were collected on 299 men who underwent a cardiometabolic risk assessment in HMP Parc, Bridgend. The QRISK2 algorithm was used to calculate 10-year CVD risk, relative risk (to general population) and the predicted heart age of an individual. Between-group differences (prison population vs general community) in cardiovascular risk predictions (10-year CVD risk and heart age) were assessed. RESULTS: We observed that at all age groups, the relative risk of predicted 10-year CVD scores in the prison population was double that of the community risk (2.1 ± 0.6), and this was most apparent in the oldest age group (≥50 years: 17.0% compared to 8.8%; P < 0.001). Overall, the heart age of the sample was 7.5 (6.7-8.2) years higher than their own chronological age, and this difference increased to above 9 years in those aged ≥40 years. CONCLUSIONS: This study provides quantifiable evidence to the elevated CVD risk in prison. Heart age predictions were almost a decade higher in those aged ≥40 years. Lowering the screening age for CVD by around 5 years in the prison population should be considered.

Burden of respiratory syncytial virus hospitalisation among infants born at 32-35 weeks' gestational age in the Northern Hemisphere: pooled analysis of seven studies.

To provide comprehensive information on the epidemiology and burden of respiratory syncytial virus hospitalisation (RSVH) in preterm infants, a pooled analysis was undertaken of seven multicentre, prospective, observational studies from across the Northern Hemisphere (2000-2014). Data from all 320-356 weeks' gestational age (wGA) infants without comorbidity were analysed. RSVH occurred in 534/14 504 (3.7%) infants; equating to a rate of 5.65 per 100 patient-seasons, with the rate in individual wGA groups dependent upon exposure time (P = 0.032). Most RSVHs (60.1%) occurred in December-January. Median age at RSVH was 88 days (interquartile range (IQR): 54-159). Respiratory support was required by 82.0% of infants: oxygen in 70.4% (median 4 (IQR: 2-6) days); non-invasive ventilation in 19.3% (median 3 (IQR: 2-5) days); and mechanical ventilation in 10.2% (median 5 (IQR: 3-7) days). Intensive care unit admission was required by 17.9% of infants (median 6 days (IQR: 2-8) days). Median overall hospital length of stay (LOS) was 5 (IQR: 3-8) days. Hospital resource use was similar across wGA groups except for overall LOS, which was shortest in those born 35 wGA (median 3 vs. 4-6 days for 32-34 wGA; P < 0.001). Strategies to reduce the burden of RSVH in otherwise healthy 32-35 wGA infants are indicated.

CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

BACKGROUND: We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. MATERIALS AND METHODS: CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. RESULTS: Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. CONCLUSIONS: Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection.

Cardiorespiratory fitness testing and cardiovascular disease risk in male steelworkers.

BACKGROUND: The workplace has been advocated as a setting to perform cardiovascular disease (CVD) risk assessments. These risk assessments usually focus on traditional risk factors rather than cardiorespiratory fitness (CRF) despite established associations between CRF and CVD. The lack of guidance on interpreting health-related CRF values has been suggested as a barrier to utilizing CRF in practice. AIMS: To assess the merits of CRF testing in the workplace and explore whether a CRF value identified male individuals above the recommended threshold for further clinical investigation. METHODS: Cross-sectional analysis of male steelworkers from Carmarthenshire, South Wales, UK who completed a workplace-based CVD risk assessment with an added CRF protocol based on heart rate responses (Chester Step Test). Receiver operating characteristic (ROC) analysis was undertaken to explore the possibility of a CRF value to identify individuals at an increased 10-year risk of CVD (QRISK2 ≥ 10%). RESULTS: There were 81 participants. ROC analysis revealed that a CRF level of 34.5ml/kg/min identified those individuals above the ≥10% QRISK2 threshold with the best sensitivity (0.800) and specificity (0.687) to discriminate against true- and false-positive rates. Further analysis revealed that individuals with either 'Average' or 'Below Average' CRF would be five times more likely to have a 10-year CVD risk above the ≥10% QRISK2 threshold than individuals with an 'Excellent' or 'Good' level of fitness [OR 5.10 (95% CI 1.60-16.3)]. CONCLUSIONS: This study suggests CRF assessments are a useful addition to a workplace CVD assessment and could identify male individuals at increased predicted risk of the condition.

Algorithm that delivers an individualized rapid-acting insulin dose after morning resistance exercise counters post-exercise hyperglycaemia in people with Type 1 diabetes.

AIMS: To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes. METHODS: Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM). In a randomized and counterbalanced order, the participants were administered an individualized dose of rapid-acting insulin (2 ± 1 units, range 0-4 units) immediately after resistance exercise (insulin session) by means of an algorithm or were not administered this (no-insulin session). Venous blood glucose concentrations were measured for 125 min after resistance exercise. Data (mean ± sem values) were analysed using anova (P ≤ 0.05). RESULTS: Participants had immediate post-resistance exercise hyperglycaemia (insulin session 13.0 ± 1.6 vs. no-insulin session 12.7 ± 1.5 mmol/l; P = 0.834). The decline in blood glucose concentration between peak and 125 min after exercise was greater in the insulin exercise session than in the no-insulin session (3.3 ± 1.0 vs. 1.3 ± 0.4 mmol/l: P = 0.015). There were no episodes of hypoglycaemia (blood glucose <3.9 mmol/l). CONCLUSIONS: Administration of rapid-acting insulin according to an individualized algorithm reduced the hyperglycaemia associated with morning resistance exercise without causing hypoglycaemia in the 2 h post-exercise period in people with Type 1 diabetes.

Similar magnitude of post-exercise hyperglycemia despite manipulating resistance exercise intensity in type 1 diabetes individuals.

The aim of this study was to compare the glycemic and glucoregulatory hormone responses to low- and moderate-intensity morning resistance exercise (RE) sessions in type 1 diabetes (T1DM). Following maximal strength assessments (1RM), eight T1DM (HbA1C :72 ± 12 mmol/mol, age:34 ± 7 years, body mass index:25.7 ± 1.6 kg/m(2) ) participants attended the research facility on two separate occasions, having fasted and taken their usual basal insulin but omitting rapid-acting insulin. Participants performed six exercises for two sets of 20 repetitions at 30%1RM during one session [low-intensity RE session (LOW)] and two sets of 10 repetitions at 60%1RM during another session [moderate-intensity RE session (MOD)], followed by 65-min recovery. Sessions were matched for total mass lifted (kg). Venous blood samples were taken before and after exercise. Data (mean ± SEM) were analyzed using analysis of variance (P ≤ 0.05). There were no hypoglycemic occurrences throughout the study. Blood glucose rose similarly between sessions during exercise (P = 0.382), remaining comparable between sessions throughout recovery (P > 0.05). There was no effect of RE intensity on metabolic acidosis (P > 0.05) or peak growth hormone responses (P = 0.644), but a tendency for greater catecholamine responses under LOW (individualized peak concentrations: adrenaline MOD 0.55 ± 0.13 vs LOW 1.04 ± 0.37 nmol/L, P = 0.155; noradrenaline MOD 4.59 ± 0.86 vs LOW 7.11 ± 1.82 nmol/L, P = 0.082). The magnitude of post-exercise hyperglycemia does not differ between equal volume low and moderate intensity RE sessions performed in the morning.

Simulated games activity vs continuous running exercise: a novel comparison of the glycemic and metabolic responses in T1DM patients.

To compare the glycemic and metabolic responses to simulated intermittent games activity and continuous running exercise in type 1 diabetes. Nine patients (seven male, two female; 35 ± 4 years; HbA1c 8.1 ± 0.2%/65 ± 2 mmol/mol) treated on a basal-bolus regimen completed two main trials, a continuous treadmill run (CON) or an intermittent running protocol (INT). Patients arrived to the laboratory fasted at ∼ 08:00 h, replicating their usual pre-exercise meal and administering a 50% reduced dose of rapid-acting insulin before exercising. Blood glucose (BG), K(+) , Na(++) , pH, triglycerides, serum cortisol and NEFA were measured at baseline and for 60 min post-exercise. Interstitial glucose was measured for a further 23 h under free-living conditions. Following exercise, BG declined under both conditions but was less under INT (INT -1.1 ± 1.4 vs CON -5.3 ± 0.4 mmol/L, P = 0.037), meaning more patients experienced hypoglycemia (BG ≤ 3.5 mmol/L; CON n = 3 vs INT n = 2) but less hyperglycemia (BG ≥ 10.9 mmol/L; CON n = 0 vs INT n = 6) under CON. Blood lactate was significantly greater, and pH lower, with a temporal delay in K(+) under INT (P < 0.05). No conditional differences were observed in other measures during this time, or in interstitial glucose concentrations during the remaining 23 h after exercise. Simulated games activity carries a lower risk of early, but not late-onset hypoglycemia than continuous running exercise in type 1 diabetes.

Impact of single and multiple sets of resistance exercise in type 1 diabetes.

To examine glycemic and glucoregulatory responses to resistance exercise (RE) sessions of different volume in type 1 diabetes (T1DM). Eight T1DM (seven males: one female; age: 38 ± 6 years, HbA1C : 8.7 ± 1.0%/71 ± 11 mmol/mol) attended the research facility fasted and on four separate occasions, having taken their usual basal insulin, but omitted morning rapid-acting insulin. Participants completed a 1SET (14 min), 2SET (28 min), 3SET (42 min) RE session (eight exercises × 10 repetitions) at 67 ± 3% one-repetition-maximum followed by 60-min recovery, or a resting trial (CON). Venous blood samples were taken before and after exercise. Data (mean ± SEM) were analyzed using repeated-measures analysis of variance (P ≤ 0.05). RE did not induce hypoglycemia (BG < 4 mmol/L). During recovery, blood glucose (BG) concentrations remained above pre-exercise after 1SET (15-60 min, P < 0.05) and 2SET (0-60 min, P < 0.05) but comparable (P > 0.05) with pre-exercise after 3SET. BGIAUC(area-under-curve) (mmol/L/60 min) was greater after 1SET and 2SET vs CON (1SET 103.6 ± 36.9 and 2SET 128.7 ± 26.1 vs CON -24.3 ± 15.2, P < 0.05), but similar between 3SET and CON (3SET 40.7 ± 59.3, P > 0.05). Under all trials, plasma creatine kinase levels at 24 h post-exercise were similar (P > 0.05) to pre-exercise. RE does not induce acute hypoglycemia or damage muscle. BG progressively rose after one and two sets of RE. However, inclusion of a third set attenuated exercise-induced hyperglycemia and returned BG to that of a non-exercise trial.

Replicated evolutionary divergence in the cuticular hydrocarbon profile of male crickets associated with the loss of song in the Hawaiian archipelago.

Female choice based on male secondary sexual traits is well documented, although the extent to which this selection can drive an evolutionary divergence in male traits among populations is less clear. Male field crickets Teleogryllus oceanicus attract females using a calling song and once contacted switch to courtship song to persuade them to mate. These crickets also secrete onto their cuticle a cocktail of long-chained fatty acids or cuticular hydrocarbons (CHCs). Females choose among potential mates based on the structure of male acoustic signals and on the composition of male CHC profiles. Here, we utilize two naturally occurring mutations that have arisen independently on two Hawaiian islands and render the male silent to ask whether the evolutionary loss of acoustic signalling can drive an evolutionary divergence in the alternative signalling modality, male CHC profiles. QST -FST comparisons revealed strong patterns of CHC divergence among three populations of crickets on the islands of Hawaii, Oahu and Kauai. Contrasts between wild-type and flatwing males on the islands of Oahu and Kauai indicated that variation in male CHC profiles within populations is associated with the loss of acoustic signalling; flatwing males had a relatively low abundance of long-chained CHCs relative to the short-chained CHCs that females find attractive. Given their dual functions in desiccation resistance and sexual signalling, insect CHCs may be particularly important traits for reproductive isolation and ultimately speciation.

Reductions in resistance exercise-induced hyperglycaemic episodes are associated with circulating interleukin-6 in type 1 diabetes.

AIMS: To determine the influence of different volumes of resistance exercise on circulating interleukin-6 (IL-6) and to explore the relationships between IL-6 and glycaemia. METHODS: Eight participants with complication-free type 1 diabetes, whose mean ± SEM age was 38 (6) years, mean ± SEM HbA(1c) concentration was 71 ±11 mmol/mol (8.7 ±1.0%) and mean ± SEM type 1 diabetes duration was 15 ±13 years, attended the research facility after an overnight fast on four separate occasions, having administered their basal insulin the night before (glargine 27.5±3.1U, n=8), but omitted morning rapid-acting insulin. Participants completed either a one-set (14-min), two-set (28-min), or three-set (42-min) resistance exercise trial (eight exercises × 10 repetitions) at 67±3% one-repetition maximum followed by a 60-min recovery, or a resting control trial. Venous blood samples were taken before and after exercise. Data were analysed using repeated-measures ANOVA (P≤0.05). RESULTS: Whereas IL-6 levels remained similar to baseline levels after one set of resistance exercises (30 min, P=0.287; 60 min, P=0.318), IL-6 levels were > baseline levels at 60 min post-exercise after a two-set exercise trial (2.94 ± 0.94 pg/ml, P=0.002) and doubled at both 30 min (4.01 ± 1.00 pg/ml, P=0.048) and 60 min (4.28 ± 1.25 pg/ml, P=0.084) post-exercise after the three-set resistance exercise trial. Post-exercise blood glucose area under the curve (mmol/l/60 min) was greater after both the one-set (P=0.025) and two-set trials (P=0.008), than after the control trial, but similar between the three-set trial and the control trial (P=0.240). The rise in IL-6 from baseline to peak concentration significantly correlated inversely with blood glucose area under the curve (r=-0.65, P=0.041). CONCLUSIONS: Circulating IL-6 is increased by resistance exercise in a volume-dependent manner, and resistance exercise-induced increases in IL-6 correlated with reductions in post-exercise hyperglycaemia in type 1 diabetes, suggesting a role for IL-6 in improving post-resistance exercise glycaemic disturbances in type 1 diabetes.

Streptococcus pneumoniae serogroup 6 clones over two decades.

The major evolutionary stresses on Streptococcus pneumoniae are thought to be the widespread use of antibiotics and the deployment of effective vaccines against the capsular polysaccharides. Our current knowledge of genetic lineages among pneumococcal isolates comes largely from investigations just before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) introduced in 2000. We examined 66 serogroup 6 isolates from the 1970s, long before the introduction of PCV7 and before widespread penicillin resistance was common in Birmingham, Alabama, to look for ancestors of the clones that came into play around the introduction of the PCV7 vaccine. The hypothesis was that some clonal complexes, if not individual clones, would be stable enough to persist over this period of time. We compared the 1970s isolates with 122 isolates from the 1990s in US and worldwide collections. Genotyping with pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) revealed that while some clones were probably localized to our area, others have persisted within groups that have expanded or diminished over the years.

'Prosiect Sir Gâr': workplace-based cardiovascular disease and diabetes risk assessments.

BACKGROUND: Cardiovascular disease (CVD) and diabetes remain two of the greatest health challenges in the UK. Government guidelines recommend screening for both of these conditions to identify individuals at high risk. Assessing individuals in the work environment for these two conditions as part of routine annual medicals could have benefits for both the employee and employer. AIMS: To introduce the Prosiect Sir Gâr workplace-based initiative for CVD and diabetes prevention and report some of the baseline measurements in regards to CVD and diabetes risk. METHODS: Individuals from two workplaces (local health board and steelworks) attended a medical health check with an added CVD and diabetes risk assessment component. Demographic and anthropometric data, systolic and diastolic blood pressure, smoking status and family and medical histories were recorded. Blood samples were analysed for total and high-density lipoprotein cholesterol and HbA1c. Ten year risk of CVD and diabetes were predicted using the QRISK2 and QDiabetes algorithms. Individuals at high risk of either condition were referred to a lifestyle intervention programme. RESULTS: Among over 800 individuals screened a high prevalence of central obesity (75%), systolic hypertension (20%) and diastolic hypertension (23%) were observed in both workforces. In addition, a substantial proportion of the workers were either 'overweight' (42%) or 'obese' (28%). CONCLUSIONS: Introducing CVD and diabetes risk assessments to routine annual medicals in the workplace uncovered significant isolated risk factors for both CVD and diabetes that may otherwise have remained undiagnosed. This approach also gave employers a more detailed awareness of the current health of their employees.

Dying whilst on probation: a scoping review of mortality amongst those under community justice supervision.

AIM: Data suggest mortality rates of those under community justice services such as probation or parole have been increasing year on year. Little is known about why and how these individuals are dying. This scoping review explores the causes and contributing factors of mortality in those under community justice supervision. METHODS: Studies published between 2011 and 2021 were identified across CINAHL, Embase, Global Health, Ovid Medline and PsycINFO. Articles were included if they presented original data on either mortality rates among those under community justice supervision or risk factors associated with the mortality of those under community justice supervision. RESULTS: Searches identified 101 unique articles of which 13 were included in the review. Articles were representative of five countries. All articles were either retrospective reviews or retrospective cohort studies. The studies fell into the categories of all-cause mortality, self-inflicted deaths or drug-related deaths. CONCLUSION: Mortality rates of those under community justice supervision were found to be consistently higher than mortality rates for the general population regardless of cause of death. Factors identified as affecting mortality included history of drug use, history of self-harm and previous imprisonment including length of time in custody and experience of hospitalisation or solitary confinement while in custody.

Metal-insulator transition and orbital reconstruction in Mott-type quantum wells made of NdNiO3.

The metal-insulator transition and the underlying electronic and orbital structure in e(g)(1) quantum wells based on NdNiO3 were investigated by dc transport and resonant soft x-ray absorption spectroscopy. By comparing quantum wells of the same dimension but with two different confinement structures, we explicitly demonstrate that the quantum well boundary condition of correlated electrons is critical to selecting the many-body ground state. In particular, the long-range orderings and the metal-insulator transition are found to be strongly enhanced under quantum confinement by sandwiching NdNiO(3) with the wide-gap dielectric LaAlO(3), while they are suppressed when one of the interfaces is replaced by a surface (interface with vacuum). Resonant spectroscopy reveals that the reduced charge fluctuations in the sandwich structure are supported by the enhanced propensity to charge ordering due to the suppressed e(g) orbital splitting when interfaced with the confining LaAlO3 layer.

Asymmetric orbital-lattice interactions in ultrathin correlated oxide films.

Using resonant x-ray spectroscopies combined with density functional calculations, we find an asymmetric biaxial strain-induced d-orbital response in ultrathin films of the correlated metal LaNiO3 which are not accessible in the bulk. The sign of the misfit strain governs the stability of an octahedral "breathing" distortion, which, in turn, produces an emergent charge-ordered ground state with an altered ligand-hole density and bond covalency. Control of this new mechanism opens a pathway to rational orbital engineering, providing a platform for artificially designed Mott materials.

Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation.

Transplantation of xenogeneic hepatocytes would provide a novel therapy for liver disease and would help to solve the problem of an insufficient supply of donor organs. We have tested whether xenogeneic cells infused into the liver could correct the metabolic defect in the Watanable heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous familial hypercholesterolemia, and we have investigated whether the infused cells traverse the lining of the portal vasculature. We find that porcine hepatocytes are localized in the hepatic sinusoids after surgery and subsequently migrate out of the vessels and integrate into the hepatic parenchyma. The integrated porcine hepatocytes provide functional LDL receptors that lower serum cholesterol in the WHHL rabbit by 30-60% for at least 100 days.

Ulcerative typhlocolitis associated with Helicobacter mastomyrinus in telomerase-deficient mice.

Telomerase deficiency induces early senescence and defects in proliferating cell populations, but in mice it has not been associated with inflammatory bowel disease. Genetically engineered mice lacking either telomerase reverse transcriptase (TERT) or telomerase RNA were examined for chronic diarrhea and wasting. Affected mice had pasty stools, thickened nondistensible colon walls, and contracted ceca. Histologically, the cecal mucosa was largely replaced by inflammatory infiltrate consisting of plasma cells, neutrophils, lymphocytes, and macrophages with marked widespread fibrosis and ulceration. Remaining epithelium was disorganized and hyperplastic, with multifocal dysplasia. Colonic mucosa was markedly hyperplastic with similar inflammation and epithelial dysplasia. Multifocal adenomatous hyperplasia, but no inflammation, was present in the small intestine. Microaerophilic spiral bacteria with 16S rRNA gene sequences identical to Helicobacter mastomyrinus were isolated from the colon and cecum. Severe granulomatous typhlocolitis without epithelial dysplasia developed in germ-free recombination-activating gene (RAG) knockout (KO) recipients of CD4+ T cells and inoculated with cecal contents from affected TERT KO mice and in specific pathogen-free recipient RAG KO mice and interleukin-10 KO mice inoculated with H mastomyrinus. Typhlocolitis in mice given H mastomyrinus was more severe than in mice given Helicobacter hepaticus. Telomerase-deficient mice are susceptible to helicobacter-associated typhlocolitis. H mastomyrinus causes severe disease in susceptible mouse strains.

Assessment of immune function after short-term administration of recombinant human growth hormone in healthy young males.

Growth hormone (GH) is a commonly used drug aimed at improving sport performance. The aim of this study is to evaluate the immunomodulatory effects of short-term administration of recombinant GH (rhGH) in healthy young males. NK cell number, activity and phenotype, T cell number, CD4(+) (Th1/Th2) cytokine production of IL2, IL4, IL6, IL10, TNF-α and IFN-γ and CD4(+)/CD8(+) ratio with particular attention to the possible correlation to IGF-I production were investigated. 30 males (27 ± 9 years) were randomly assigned to placebo (n = 15) or drug (rhGH) 1 mg/day groups (n = 15) with daily injection for 7 days. IGF-I plasma concentration and flow cytometry data were generated at baseline and days 8, 15, 22 and 29 post injection. Data analysis used General Linear Model with repeated measures, Bonferroni correction factor and significance at p ≤ 0.05. Serum IGF-I levels (ng/mL) increased significantly (p ≤ 0.01) on day 8 (0.48 ± 0.78) after injections compared to baseline (0.31 ± 0.07) and days 15 (0.33 ± 0.06), 22 (0.29 ± 0.05) and 29 (0.29 ± 0.06). A significant time effect was noted in IL10 secretion (pg/mL) from day 15 (P = 35.14 ± 19.93, rhGH = 26.63 ± 16.39) to days 22 (P = 61.32 ± 20.41, rhGH = 74.99 ± 46.91) and 29 (P = 101.98 ± 67.25, rhGH = 107.74; ± 122.58). There was no correlation between IGF-I and NK activity, phenotype or number along with T lymphocyte number, CD4(+)/CD8(+) ratio or Th1 and Th2 cytokine production. In conclusion, cytokine secretion spectrum was not affected by short-term rhGH administration in young males.