Evidence on major gene control of cortical index in pedigree data from Middle Dalmatia,Croatia

It was recently reported that the inheritance of the metacarpal cortical index (CI) in the Chuvashian population can be described in terms of a major gene (MG) model. By applying transmission probability tests, the hypothesis was accepted that not only baseline level of CI but also its sex‐specific dependence on age were under control of the same putative large‐effect gene. Using a pedigree sample from the population of the islands of Middle Dalmatia, Croatia (847 observed individuals in 278 pedigrees), data are presented to support the above findings. The following hypotheses were accepted: (i) inheritance of baseline CI in the Croatian population can be attributed to the effect of a MG responsible for about 42% of the variation; (ii) the same MG takes part in the control of the dependence of CI on age, particularly the age at onset of involutive bone changes (inflection point), and of the rate of decrease in CI with age (slope coefficient). Issues related to the assortative mating effect on CI and the determination of the most parsimonious model are discussed. Am. J. Hum. Biol. 13:398–408, 2001. © 2001 Wiley‐Liss, Inc.     

Identification and Characterization of a 29-Kilodalton Protein from Mycobacterium tuberculosis Culture Filtrate Recognized by Mouse Memory Effector Cells

Culture filtrate proteins from Mycobacterium tuberculosis induce protective immunity in various animal models of tuberculosis. Two molecular mass regions (6 to 10 kDa and 24 to 36 kDa) of short-term culture filtrate are preferentially recognized by Th1 cells in animal models as well as by patients with minimal disease. In the present study, the 24- to 36-kDa region has been studied, and the T-cell reactivity has been mapped in detail. Monoclonal antibodies were generated, and one monoclonal antibody, HYB 71-2, with reactivity against a 29-kDa antigen located in the highly reactive region below the antigen 85 complex was selected. The 29-kDa antigen (CFP29) was purified from M. tuberculosis short-term culture filtrate by thiophilic adsorption chromatography, anion-exchange chromatography, and gel filtration. In its native form, CFP29 forms a polymer with a high molecular mass. CFP29 was mapped in two-dimensional electrophoresis gels as three distinct spots just below the antigen 85 complex component MPT59. CFP29 is present in both culture filtrate and the membrane fraction from M. tuberculosis, suggesting that this antigen is released from the envelope to culture filtrate during growth. Determination of the N-terminal amino acid sequence allowed cloning and sequencing of the cfp29 gene. The nucleotide sequence showed 62% identity to the bacteriocin Linocin from Brevibacterium linens. Purified recombinant histidine-tagged CFP29 and native CFP29 had similar T-cell stimulatory properties, and they both elicited the release of high levels of gamma interferon from mouse memory effector cells isolated during the recall of protective immunity to tuberculosis. Interspecies analysis by immunoblotting and PCR demonstrated that CFP29 is widely distributed in mycobacterial species.     

Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for alpha-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant alpha-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.     

Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1beta stimulated rheumatoid synovial fibroblasts

Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.     

Implementing a Stratified Vocational Advice Intervention for People on Sick Leave with Musculoskeletal Disorders: A Multimethod Process Evaluation

Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on...     

Interactional practices in person‐centred care: Conversation analysis of nurse‐patient disagreement during self‐management support

BackgroundPerson‐centred care implies a change in interaction between care professionals and patients where patients are not passive recipients but co‐producers of care. The interactional practices of person‐centred care remain largely unexplored.ObjectiveThis study focuses on the analysis of disagreements, which are described as an important part in the co‐production of knowledge in interaction.DesignA qualitative exploratory study using conversation analysis.Setting and participantsData were collected from a nurse‐led person‐centred intervention in a hospital outpatient setting. Interactions between adult patients with irritable bowel syndrome (n = 17) and a registered nurse were audio‐recorded. COREQ guidelines were applied.ResultsDisagreements were found after demonstration of the nurse''s or patients’ respective professional or personal knowledge. Disagreements were also evident when deciding on strategies for self‐management. Although negotiations between opposing views of the nurse and patient were seen as important, the patient generally claimed final authority both in knowing how IBS is perceived and in the right to choose self‐management strategies. The nurse generally oriented towards patient authority, but instances of demonstration of nurse authority despite patient resistance were also found.Discussion and conclusionsThis study provides information on how co‐production of knowledge and decisions occur in the context of a person‐centred care intervention. Negotiations between nurse and patient views require a flexible approach to communication, adapting interaction to each context while bearing in mind the patients having the final authority. To facilitate co‐production, the patient''s role and responsibilities in interaction should be explicitly stated.     

Obesity in early onset breast cancer in African American patients

Obesity is a modifiable risk factor in breast cancer patients and is predictive of disease outcomes in early-onset breast cancer survivors. The purpose of this review is to summarize the current evidence in the association between early-onset breast cancer and obesity, specifically in African-American women. Reviewing the molecular mechanisms and social determinants of disease in this population can provide a foundation for future interventions in prevention, detection, and treatment aiming at improving outcomes for young breast cancer patients.     

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1–2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6–7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.     

Longitudinal assessment of anti-Müllerian hormone after cesarean section and influence of bilateral salpingectomy on ovarian reserve

ObjectiveThis study aimed to compare longitudinal changes in ovarian reserve markers after cesarean section (CS) with and without bilateral salpingectomy (BS).Study designWe prospectively enrolled women >35 weeks’ gestation scheduled for CS alone or CS + BS and obtained blood samples for anti-Müllerian hormone prior to surgery and at 3 and 6 months after surgery. At the 3-month visit, we similarly performed transvaginal ultrasound for antral follicle count.ResultsWe enrolled 50 women; 30 underwent CS only and 20 underwent CS + BS. Although anti-Müllerian hormone level increased over 6 months of follow-up in both groups, no clinically important differences in the geometric mean (interquartile range) (ng/mL) were observed at any timepoint (baseline [0.69 {0.36?1.21} {CS only} vs 0.49 {0.32?2.10} {CS + BS}, p = 0.64]; 3 months [1.35 {0.58?3.13} vs 1.45 {1.04?2.25}, p = 0.79]; and 6 months [1.74 {0.93?4.45} vs 2.60 {1.41?5.10}, p =0.27]). Similarly, we detected no difference in antral follicle count.ConclusionBS at the time of CS does not have a negative impact on ovarian reserve 6 months after surgery.ImplicationWhile our results provide reassuring data that bilateral salpingectomy for permanent contraception at the time of cesarean section does not impact ovarian reserve, longer adequately powered studies are needed.     

Loneliness in adolescence: a Rasch analysis of the Perth A-loneness scale

Quality of Life Research - The psychometric properties of the Perth A-loneness Scale (PALs) have been extensively validated using classical test theory, but to date no studies have applied a Rasch...