Search

Evidence of autoimmune disease associated with hepatitis C virus (HCV)-infection has important clinical implications. A systematic profile of these autoantibodies in relevant clinical cohorts relative to healthy controls is needed to better inform current standard of care for chronic hepatitis C. Samples from an Australian cohort of chronic HCV-infected subjects (n=127) were tested for the presence of 19 diagnostic autoantibodies and compared with data available from a control cohort representing a general Caucasian population (n=198). Chronic HCV-infected individuals had a greater number of autoantibodies than controls (p

Abacavir hypersensitivity syndrome (ABC HSS) is strongly associated with carriage of human leukocyte antigen (HLA)-B*57:01, which has a 100% negative predictive value for the development of ABC HSS. However, 45% of individuals who carry HLA-B*57:01 can tolerate ABC. We investigated immune and non-immune related genes in ABC HSS (n = 95) and ABC tolerant (n = 43) HLA-B*57:01 + patients to determine other factors required for the development of ABC HSS. Assignment of phenotype showed that ABC HSS subjects were significantly less likely than tolerants to carry only ERAP1 hypoactive trimming allotypes (p = 0.02). An altered self-peptide repertoire model by which abacavir activates T cells is in keeping with observation that endoplasmic reticulum aminopeptidase 1 (ERAP1) allotypes that favour efficient peptide trimming are more common in ABC HSS patients compared to patients who tolerate ABC. Independently, non-specific immune activation via soluble cluster of differentiation antigen 14 (sCD14) may also influence susceptibility to ABC HSS.

250 words Background A breast cancer biobank with retrospectively collected patient data and FFPE tissue samples was established in 2018 at Prashanti Cancer Care Mission, Pune, India. It runs a cancer care clinic with support from a single surgeon's breast cancer practice. The clinical data and tissue sample collection is undertaken with appropriate patient consent following ethical approval and guidelines. Methods The biobank holds clinical history, diagnostic reports, treatment and follow-up information along with FFPE tumor tissue specimens, adjacent normal and, in few cases, contralateral normal breast tissue. Detailed family history and germline mutational profiles of eligible and consenting patients and their relatives are also deposited in the biobank. Results Here, we report the first audit of the biobank. A total number of 994 patients with breast disease have deposited consented clinical records in the biobank. The majority of the records (80%, n = 799) are of patients with infiltrating ductal carcinoma (IDC). Of 799 IDC patients, 434 (55%) have deposited tumor tissue in the biobank with consent. In addition, germline mutation profiles of 84 patients and their family members are deposited. Follow-up information is available for 85% of the 434 IDC patients with an average follow-up of 3 years. Conclusion The biobank has aided the initiation of translational research at our center in collaboration with eminent institutes like IISER Pune and SJRI Bangalore to evaluate profiles of breast cancer in an Indian cohort. The biobank will be a valuable resource to the breast cancer research community, especially to understand South Asian profiles of breast cancer.

Primary angiosarcoma of the breast is a rare (0.04% of all malignant breast tumors) and potentially life-threatening disease. Given its variable and non-specific clinical, radiological and pathological presentation, accurate diagnosis is a challenge. Primary angiosarcoma of the breast predominantly occurs in younger patients and it is often overlooked and misdiagnosed at radiology and pathology. To ensure that this aggressive malignancy is not overlooked, radiologists need to be aware of the fact that such tumors may present with non-specific imaging features. We report a case of a 32-year-old female with primary angiosarcoma of the breast presenting with non-specific imaging features. It was initially interpreted as a capillary cavernous hemangioma at histopathology following an ultrasound-guided biopsy. This eventually turned out to be angiosarcoma after a second histopathology opinion was sought in light of the radiology-pathology discordance.

Summary The aim of this study was to determine the prevalence and type of autoantibodies in a general Australian population cohort. Samples collected from 198 individuals included in a cross sectional Busselton Health Study were tested using autoantibody assays routinely performed at Clinical Immunology, PathWest Laboratory Medicine, Western Australia. At least one autoantibody was detected in 51.5% of individuals (males = 45.1%, females = 58.3%). The most frequently detected serum autoantibodies were anti-beta-2-glycoprotein I (12.1%) followed by anti-smooth muscle (11.6%) and anti-thyroid peroxidase (8.6%). Vasculitis associated anti-neutrophil cytoplasmic antibodies were present in 5.1%, while anti-nuclear antibodies were detected in 8.6% of individuals. Notably, 65% of positive results were detected at low levels with the exception of anti-myeloperoxidase and anti-beta 2 glycoprotein I IgG antibodies. Autoantibodies are commonly detected at low levels in a predominantly Australian or European population cohort. No large Australian study has yet provided these data for contemporary routine tests. This paper gives important information on the background frequency of autoantibodies in the general population. Due to the nature of this study we are unaware of whether these individuals have subsequently developed an autoimmune disease, however this was not clinically diagnosed at the time of sample collection.

Infection is the leading cause of death in rheumatoid arthritis (RA). Corticosteroid (CS) use is a known and important risk factor for serious infections (SIs). Mannose binding lectin (MBL) is a genetically determined component of the innate immune system implicated in neonatal infections.Our aim was to determine whether MBL deficiency is a risk factor for SIs in RA and to compare it with CS use and also synthetic and biologic disease-modifying antirheumatic drug (DMARD) therapy.Data on 228 patients with RA were collected for up to 7 years (median = 5.9 years). Serum MBL concentrations were determined in all patients receiving synthetic (n = 96) or biologic (n = 132) DMARD therapy.High rates of SIs were observed in RA irrespective of treatment (17%). Similar rates of SIs were observed in synthetic and biologic DMARD users. The rates of single and multiple SIs were similar, irrespective of the use of a biologic agent. Undetectable MBL (56 ng/mL) concentrations and maintenance prednisolone at 10 mg per day or higher were associated with an increased risk for an SI, with incident risk ratio of 4.67 (P = .001) and 4.70 (P.001), respectively.Undetectable MBL and prednisolone confer a high risk for an SI. The use of biologic DMARDs did not confer substantial SI risk in this observational study. MBL deficiency is hitherto an unrecognized risk factor for an SI in RA.

Balance is sensed through peripheral and central receptors and mediated by central control through the brain and spinal cord. Although some evidence exists as to the areas of the brain involved and how processing of data occurs in young individuals, nothing has been published on people with diabetes. The purpose of this study was to examine the electroencephalogram (EEG) during common sensorimotor and balance training tasks and to relate these to task difficulty.Postural sway and EEG change of alpha, beta, and sigma wave bands were measured in 17 young subjects, 10 older subjects, and 10 subjects with diabetes during eight progressively more difficult balance tasks with eyes open and closed, feet in tandem or apart, and on foam or a firm surface.EEG power of beta and sigma wave bands showed significant increases on the cortical and parietal areas of the brain relative to the control tasks when eyes were open (P0.05). The cortical involvement decreased as the task became more difficult with vision and somatosensory information reduced, whereas that of the parietal area increased with task difficulty. The greatest increase was in subjects with diabetes, and the least was in younger people. Individuals with diabetes had increased sigma and beta EEG power in all regions of the brain examined with increased complexity of the balance task.This study demonstrated cortical and parietal involvement in static balance tasks commonly used in sensorimotor training. The results support the proposal that there was increased subcortical control with increase in task difficulty in the young subjects, but in subjects with diabetes, there was a major increase in activity across the brain.

With aging, the detrimental effects of stress can impair a person's ability to learn and sustain memory. Humor and its associated mirthful laughter can reduce stress by decreasing the hormone cortisol. Chronic release of cortisol can damage hippocampal neurons, leading to impairment of learning and memory. Objectives • The study intended to examine the effect of watching a humor video on short-term memory in older adults. Design • The research team designed a randomized, controlled trial.The study took place at Loma Linda University in Loma Linda, CA, USA.The study included 30 participants: 20 normal, healthy, older adults-11 males and 9 females-and 10 older adults with type 2 diabetes mellitus (T2DM)-6 males and 4 females.The study included 2 intervention groups of older adults who viewed humorous videos, a healthy group (humor group), aged 69.9 ± 3.7 y, and the diabetic group, aged 67.1 ± 3.8 y. Each participant selected 1 of 2 humorous videos that were 20 min in length, either a Red Skeleton comedy or a montage of America's Funniest Home Videos. The control group, aged 68.7 ± 5.5 y, did not watch a humor video and sat in quiescence.A standardized, neuropsychological, memory-assessment tool, the Rey Auditory Verbal Learning Test (RAVLT), was used to assess the following abilities: (1) learning, (2) recall, and (3) visual recognition. The testing occurred twice, once before (RAVLT1) and once after (RAVLT2) the humorous video for the humor and diabetic groups, and once before (RAVLT1) and once after (RAVLT2) the period of quiescence for the control group. At 5 time points, measurements of salivary cortisol were also obtained. The Kruskal-Wallis test was used to measure significance of the data based on the 3 groups.In the humor, diabetic, and control groups, (1) learning ability improved by 38.5%, 33.4%, and 24.0%, respectively (P = .025); (2) delayed recall improved by 43.6%, 48.1%, and 20.3%, respectively (P = .064); and (3) visual recognition increased by 12.6%, 16.7%, and 8.3%, respectively (P = .321). For levels of salivary cortisol, the research team found significant and borderline decreases for the humor group between baseline and (1) post-RAVLT1 (P = .047), (2) postvideo (P = .046), and (3) post-RAVLT2 (P = .062). The diabetic group showed significant decreases between baseline and (1) post-RAVLT1 (P = .047), (2) postvideo (P = .025), and (3) post-RAVLT2 (P = .034). The study found no significant changes for the control group.The research findings supported potential clinical and rehabilitative benefits for humor that can be applied to whole-person wellness programs for older adults. The cognitive components-learning ability and delayed recall-become more challenging as individuals age and are essential to older adults for providing a high quality of life: mind, body, and spirit. Because older adults can experience age-related memory deficits, complementary, enjoyable, and beneficial humor therapies should be implemented for them.

Characterisation of Hepatitis C virus (HCV)-specific CD8+ T-cell responses in the context of multiple HCV exposures is critical to identify broadly protective immune responses necessary for an effective HCV vaccine against the different HCV genotypes. However, host and viral genetic diversity complicates vaccine development. To compensate for the observed variation in circulating autologous viruses and host molecules that restrict antigen presentation (human leucocyte antigens; HLA), this study used a reverse genomics approach that identified sites of viral adaptation to HLA-restricted T-cell immune pressure to predict genotype-specific HCV CD8+ T-cell targets. Peptides representing these putative HCV CD8+ T-cell targets, and their adapted form, were used in individualised IFN-γ ELISpot assays to screen for HCV-specific T-cell responses in 133 HCV-seropositive subjects with high-risk of multiple HCV exposures. The data obtained from this study i) confirmed that genetic studies of viral evolution is an effective approach to detect novel in vivo HCV T-cell targets, ii) showed that HCV-specific T-cell epitopes can be recognised in their adapted form and would not have been detected using wild-type peptides and iii) showed that HCV-specific T-cell (but not antibody) responses against alternate genotypes in chronic HCV-infected subjects are readily found, implying clearance of previous alternate genotype infection. In summary, HCV adaptation to HLA Class I-restricted T-cell responses plays a central role in anti-HCV immunity and multiple HCV genotype exposure is highly prevalent in at-risk exposure populations, which are important considerations for future vaccine design.

For older adults, the damaging effects of aging and stress can impair the ability to learn and sustain memory. Humor, with its associated mirthful laughter, can reduce stress and cortisol, a stress hormone. Chronic release of cortisol can damage hippocampus neurons, leading to impairment of learning and memory.The primary goal of this study was to determine whether watching a humorous video had an effect on short-term memory in an older population.The research team designed a randomized, controlled trial.The study took place at Loma Linda University in Loma Linda, California.The research team recruited 20 normal, healthy, older adults, 11 males and 9 females.The humor group (n = 10, mean = 69.3 ± 3.7 y) self-selected 1 of 2 humorous videos--a Red Skelton comedy or a montage of America's Funniest Home Videos--and watched it for 20 min. A control group (n = 10, mean = 68.7 ± 5.5 y) sat calmly for 20 min and were not allowed to read, sleep, or talk on a cell phone.The Rey Auditory Verbal Learning Test was used to assess short-term memory--learning ability, delayed recall, and visual recognition. Salivary cortisol levels were measured at predetermined times.Learning ability improved by 38.5% and 24.0% in the humor and control groups, respectively (P = .014). Delayed recall improved by 43.6% and 20.3% in the humor and control groups, respectively (P =.029). Within the humor group, delayed recall (43.6%) was significant compared with learning ability (38.5%) (P = .002). At 3 predetermined time points, significant decreases in salivary cortisol were observed in the humor group (P = .047, P = .046, and P = .062, respectively).The study's findings suggest that humor can have clinical benefits and rehabilitative implications and can be implemented in programs that support whole-person wellness for older adults. Learning ability and delayed recall are important to these individuals for a better quality of life--considering mind, body, spirit, social, and economic aspects. Older adults may have age-associated memory deficiencies. However, medical practitioners now can offer positive, enjoyable, and beneficial humor therapies to improve these deficiencies.

Background It is well established that there is a reduction in the skin blood flow (SBF) in response to heat with age and diabetes. While it is known that high BMI creates a stress on the cardiovascular system and increases the risk of all cause of morbidity and mortality, little is known of the effect of high BMI on SBF response to heat. Since diabetes is associated with age and a higher BMI, the interrelationship between age, BMI and SBF needs to be investigated to better understand the contribution diabetes alone has to endothelial impairment. Material/Methods This study examined the SBF to heat in young and old people with low and high BMI and people with diabetes with high BMI to determine the contribution these variables have on SBF. Subjects were ten young and older people with BMI 20 and ten subjects with diabetes with BMI >20. The SBF response, above the quadriceps, was determined during a 6 minutes exposure to heat at 44°C. Results Even in young people, SBF after the stress of heat exposure was reduced in subjects with a high BMI. The effect of BMI was greatest in young people and lowest in older people and people with diabetes; in people with diabetes, BMI was a more significant variable than diabetes in causing impairment of blood flow to heat. BMI, for example, was responsible for 49% of the reduction in blood flow after stress heat exposure (R=−0.7) while ageing only accounted for 16% of the blood flow reduction (R=−0.397). Conclusions These results would suggest the importance of keeping BMI low not only in people with diabetes to minimize further circulatory vascular damage, but also in young people to diminish long term circulatory vascular compromise.