In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years
. ...Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions
. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank
cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.
Objective
Supporting Early Childhood Development (ECD) is an Australian national priority. Aboriginal children in Western Australia's Kimberley region have much higher rates of developmental concerns ...at school entry than non‐Aboriginal children. We aimed to describe ECD practices in the participating service; document follow‐up of identified developmental concerns; and identify barriers and enablers to incorporating ECD practices into clinic activity.
Design
Mixed‐method design incorporating clinical audit and staff interviews.
Setting
An Aboriginal Community Controlled Health Service (ACCHS) in the Kimberley region.
Participants
A total of 176 children receiving primary health care through the participating ACCHS; interviews with five ACCHS staff members.
Main outcome measures
Frequency of developmental enquiry by age and domain; follow‐up of identified developmental concerns; and barriers and enablers to ECD practices.
Results
Developmental enquiry was documented for 114 of 176 eligible children (65%), including in 80% of ACCHS child health assessments. Standardised ECD assessments were less common. Staff were aware of the importance of developmental enquiry, however, barriers to increasing ECD practices included a lack of resources and structured staff education, time pressures and a lack of role clarity between the ACCHS and government community health clinic.
Conclusions
This study provides insight into ECD practices in an ACCHS setting, highlighting the potential of primary health care to have an enhanced role in ECD if appropriate systems, training and tools are provided. A lack of role clarity across services, combined with poor communication between services, creates a potential risk for missed opportunities to support ECD.
To investigate if early electronic identification and bedside management of inpatients with diabetes improves glycemic control in noncritical care.
We investigated a proactive or early intervention ...model of care (whereby an inpatient diabetes team electronically identified individuals with diabetes and aimed to provide bedside management within 24 h of admission) compared with usual care (a referral-based consultation service). We conducted a cluster randomized trial on eight wards, consisting of a 10-week baseline period (all clusters received usual care) followed by a 12-week active period (clusters randomized to early intervention or usual care). Outcomes were adverse glycemic days (AGDs) (patient-days with glucose <4 or >15 mmol/L <72 or >270 mg/dL) and adverse patient outcomes.
We included 1,002 consecutive adult inpatients with diabetes or new hyperglycemia. More patients received specialist diabetes management (92% vs. 15%,
< 0.001) and new insulin treatment (57% vs. 34%,
= 0.001) with early intervention. At the cluster level, incidence of AGDs decreased by 24% from 243 to 186 per 1,000 patient-days in the intervention arm (
< 0.001), with no change in the control arm. At the individual level, adjusted number of AGDs per person decreased from a mean 1.4 (SD 1.6) to 1.0 (0.9) days (-28% change 95% CI -45 to -11,
= 0.001) in the intervention arm but did not change in the control arm (1.8 2.0 to 1.5 1.8, -9% change -25 to 6,
= 0.23). Early intervention reduced overt hyperglycemia (55% decrease in patient-days with mean glucose >15 mmol/L,
< 0.001) and hospital-acquired infections (odds ratio 0.20 95% CI 0.07-0.58,
= 0.003).
Early identification and management of inpatients with diabetes decreased hyperglycemia and hospital-acquired infections.
For people living with type 1 diabetes (T1D) the challenge of increasing daily physical activity (PA) is compounded by the increased risks of hypoglycemia and glucose variability. Little information ...exists on the lived experience of overcoming these barriers and adopting and maintaining an active lifestyle while living with T1D.
We conducted a patient-led qualitative study consisting of semi-structured interviews or focus groups with 22 individuals at least 16 years old living with T1D. We used existing patient co-researcher networks and snowball sampling to obtain a sample of individuals who reported being regularly physically active and had been diagnosed with T1D for at least one year. We used an interpretive description analysis to generate themes and strategies associated with maintaining an active lifestyle while living with T1D. We involved patient co-researchers in study design, data collection, and interpretation.
14 self-identified women and 8 self-identified men (ages 19-62, median age 32 years) completed the study, led by either a researcher, or a patient co-researcher and research assistant regarding their strategies for maintaining an active lifestyle. We identified five themes that facilitate regular sustained PA: (1) Structure and organization are important to adopt safe PA in daily life "I can't do spontaneous exercise. I actually need a couple hours of warning minimum"; (2) Trial and error to learn how their body responds to PA and food "Once you put the time and effort into learning, you will have greater success"; (3) Psychosocial aspects of PA "…because it's not just your body, it's your soul, it's your mind that exercise is for"; (4) Diabetes technology and (5) Education and peer support. Strategies to overcome barriers included (1) Technology; (2) Integrating psychosocial facilitators; (3) Insulin and carbohydrate adjustments; and (4) Planning for exercise.
Living an active lifestyle with T1D is facilitated by dedicated structure and organization of routines, accepting the need for trial and error to understand the personalized glycemic responses to PA and careful use of food to prevent hypoglycemia. These themes could inform clinical practice guidelines or future trials that include PA interventions.
Recent advances in regenerative medicine, including hematopoietic stem cell (HSC) transplantation, have brought hope for patients with severe alcoholic liver cirrhosis (ALC). The aim of this study ...was to assess the safety and efficacy of administering autologous expanded mobilized adult progenitor CD34+ cells into the hepatic artery of ALC patients and the potential improvement in the liver function.
Nine patients with biopsy-proven ALC, who had abstained from alcohol for at least 6 months, were recruited into the study. Following granulocyte colony-stimulating factor (G-CSF) mobilization and leukapheresis, the autologous CD34+ cells were expanded in vitro and injected into the hepatic artery. All patients were monitored for side effects, toxicities, and changes in the clinical, hematological, and biochemical parameters.
On average, a five-fold expansion in cell number was achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 x 10(8) pre infusion. All patients tolerated the procedure well, and there were no treatment-related side effects or toxicities observed. There were significant decreases in serum bilirubin (P < 0.05) 4, 8, and 12 wk post infusion. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement through the study period and were significant (P < 0.05) 1 wk post infusion. The Child-Pugh score improved in 7 out of 9 patients, while 5 patients had improvement in ascites on imaging.
It is safe to mobilize, expand, and reinfuse autologous CD34+ cells in patients with ALC. The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials.
Key points
In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established.
We conducted ...the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise given their synergistic capacity to promote free radical formation.
Systemic free radical formation was shown to increase during hypoxia and was further compounded by exercise, responses that were attenuated by antioxidant prophylaxis.
In contrast, antioxidant prophylaxis increased thrombin generation at rest in normoxia, and this was normalised only in the face of prevailing oxidation.
Collectively, these findings suggest that human free radical formation is an adaptive phenomenon that serves to maintain vascular haemostasis.
In vitro evidence suggests that blood coagulation is activated by increased oxidative stress although the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise. Healthy males were randomly assigned double‐blind to either an antioxidant (n = 20) or placebo group (n = 16). The antioxidant group ingested two capsules/day that each contained 500 mg of l‐ascorbic acid and 450 international units (IU) of dl‐α‐tocopherol acetate for 8 weeks. The placebo group ingested capsules of identical external appearance, taste and smell (cellulose). Both groups were subsequently exposed to acute hypoxia and maximal physical exercise with venous blood sampled pre‐supplementation (normoxia), post‐supplementation at rest (normoxia and hypoxia) and following maximal exercise (hypoxia). Systemic free radical formation (electron paramagnetic resonance spectroscopic detection of the ascorbate radical (A•−)) increased during hypoxia (15,152 ± 1193 AU vs. 14,076 ± 810 AU at rest, P < 0.05) and was further compounded by exercise (16,569 ± 1616 AU vs. rest, P < 0.05), responses that were attenuated by antioxidant prophylaxis. In contrast, antioxidant prophylaxis increased thrombin generation as measured by thrombin–antithrombin complex, at rest in normoxia (28.7 ± 6.4 vs. 4.3 ± 0.2 μg mL−1 pre‐intervention, P < 0.05) and was restored but only in the face of prevailing oxidation. Collectively, these findings are the first to suggest that human free radical formation likely reflects an adaptive response that serves to maintain vascular haemostasis.
Key points
In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established.
We conducted the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise given their synergistic capacity to promote free radical formation.
Systemic free radical formation was shown to increase during hypoxia and was further compounded by exercise, responses that were attenuated by antioxidant prophylaxis.
In contrast, antioxidant prophylaxis increased thrombin generation at rest in normoxia, and this was normalised only in the face of prevailing oxidation.
Collectively, these findings suggest that human free radical formation is an adaptive phenomenon that serves to maintain vascular haemostasis.
A phase I study was performed to determine the safety and tolerability of injecting autologous CD34(+) cells into five patients with liver insufficiency. The study was based on the hypothesis that ...the CD34(+) cell population in granulocyte colony-stimulating factor (G-CSF)-mobilized blood contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated a candidate CD34(+) stem cell population from the majority of the CD34(+) cells (99%) by adherence to tissue culture plastic. The adherent and nonadherent CD34(+) cells were distinct in morphology, immunophenotype, and gene expression profile. Reverse transcription-polymerase chain reaction-based gene expression analysis indicated that the adherent CD34(+) cells had the potential to express determinants consistent with liver, pancreas, heart, muscle, and nerve cell differentiation as well as hematopoiesis. Overall, the characteristics of the adherent CD34(+) cells identify them as a separate putative stem/progenitor cell population. In culture, they produced a population of cells exhibiting diverse morphologies and expressing genes corresponding to multiple tissue types. Encouraged by this evidence that the CD34(+) cell population contains cells with the potential to form hepatocyte-like cells, we gave G-CSF to five patients with liver insufficiency to mobilize their stem cells for collection by leukapheresis. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were injected into the portal vein (three patients) or hepatic artery (two patients). No complications or specific side effects related to the procedure were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. These observations warrant further clinical trials.
Culture and rural health Farmer, Jane; Bourke, Lisa; Taylor, Judy ...
The Australian journal of rural health,
October 2012, Letnik:
20, Številka:
5
Journal Article
Recenzirano
This paper considers the role of culture in rural health, suggesting that the concept and its impacts are insufficiently understood and studied. It reviews some of the ways that culture has been ...considered in (rural) health, and states that culture is either used ambiguously and broadly – for example, suggesting that there is a rural culture, or narrowly – indeed perhaps interchangeably with ethnicity, for example Aboriginal culture as a unity. The paper notes that, although culture is a dynamic social concept, it has been adopted into a biomedical research paradigm as though it is fixed. Culture is often treated as though it is something that can be addressed simplistically, for example, through cultural sensitivity education. Authors suggest that culture is an unaddressed ‘elephant in the room’ in rural health, and that exploring cultural differences and beliefs and facing up to cultural differences are vital in understanding and addressing rural health and health system challenges.
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