A familial paracentric inversion: A short review of the current status

Summary We present here a familial case of a paracentric inversion in man with a short review of the literature. A paracentric inversion of chromosome 10(q11q26) was found in the amniocytes drawn for advanced maternal age. The presence of the inversion was investigated in 35 family members in three generations. No recombinants were recognized. The significance of these data for appropriate genetic counselling and possible reproductive risks is discussed.Genetic Nurses, Department of Health and Welfare     

Hypoxia impairs visual acuity in snapper (Pagrus auratus)

We investigated the effect of environmental hypoxia on vision in snapper (Pagrus auratus). Juvenile snapper inhabit estuarine environments where oxygen conditions fluctuate on a seasonal basis. Optomotor experiments demonstrated that visual acuity is impaired by environmental hypoxia, but not until levels approach the critical oxygen tension (P _crit) of this species (around 25 % air-saturated seawater). In 100, 80, and 60 % air-saturated seawater, a positive optomotor response was present at a minimum separable angle (M _SA) of 1°. In 40 % air-saturated seawater, vision was partially impaired with positive responses at M _SAs of 2° and above. However, in 25 % air-saturated seawater, visual acuity was seriously impaired, with positive responses only present at M _SAs of 6° and above. Snapper were found to possess a choroid rete, facilitating the maintenance of high ocular oxygen partial pressures (PO₂) during normoxia and moderate hypoxia (PO₂, between 269 and 290 mmHg). However, at 40 and 25 % water oxygen saturation, ocular PO₂ was reduced to below 175 mmHg, which is perhaps linked to impairment of visual acuity in these conditions. The ability to preserve visual function during moderate hypoxia is beneficial for the maintenance of a visual lifestyle in the fluctuating oxygen environments of estuaries.     

Warm-induced bradycardia and cold-induced tachycardia: mechanisms of cardiac and ventilatory control in a warm-acclimated Antarctic fish

While many Antarctic organisms possess only limited ability to respond to environmental temperature change, there is now substantial evidence to confirm that the notothenioid fish, Pagothenia borchgrevinki, has retained some thermal flexibility and can successfully acclimate to a 5°C increase in temperature. Previous research demonstrated that after acclimation to 4°C, resting cardiac output in this species was thermally independent, while cold-adapted fish demonstrated thermal dependence of cardiac output. Here, we extend this research into cardiovascular plasticity and report the following: (1) The mechanisms responsible for the thermal independence of cardiac output in warm-acclimated (4°C, for 4 weeks) fish include a combination of warm-induced bradycardia and cold-induced tachycardia bouts. (2) These acute responses are under cholinergic control. (3) Changes to the thermal sensitivity of heart rate and ventilation rate result in concomitant changes to cardio-respiratory coupling in warm-acclimated fish.     

The Association between Race and Crohn's Disease Phenotype in the Western Cape Population of South Africa,Defined by the Montreal Classification System

Background

Inter-racial differences in disease characteristics and in the management of Crohn''s disease (CD) have been described in African American and Asian subjects, however for the racial groups in South Africa, no such recent literature exists.

Methods

A cross sectional study of all consecutive CD patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the Western Cape, South Africa between September 2011 and January 2013 was performed. Numerous demographic and clinical variables at diagnosis and date of study enrolment were identified using an investigator administered questionnaire as well as clinical examination and patient case notes. Using predefined definitions, disease behavior was stratified as ‘complicated’ or ‘uncomplicated’.

Results

One hundred and ninety four CD subjects were identified; 35 (18%) were white, 152 (78%) were Cape Coloured and 7(4%) were black. On multiple logistic regression analysis Cape Coloureds were significantly more likely to develop ‘complicated’ CD (60% vs. 9%, p = 0.023) during the disease course when compared to white subjects. In addition, significantly more white subjects had successfully discontinued cigarette smoking at study enrolment (31% vs. 7% reduction, p = 0.02). No additional inter-racial differences were found. A low proportion of IBD family history was observed among the non-white subjects.

Conclusions

Cape Coloured patients were significantly more likely to develop ‘complicated’ CD over time when compared to whites.     

The Association between Childhood Environmental Exposures and the Subsequent Development of Crohn's Disease in the Western Cape,South Africa

Background

Environmental factors during childhood are thought to play a role in the aetiolgy of Crohn''s Disease (CD). However the association between age at time of exposure and the subsequent development of CD in South Africa is unknown.

Methods

A case control study of all consecutive CD patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the Western Cape, South Africa between September 2011 and January 2013 was performed. Numerous environmental exposures during 3 age intervals; 0–5, 6–10 and 11–18 years were extracted using an investigator administered questionnaire. An agreement analysis was performed to determine the reliability of questionnaire data for all the relevant variables.

Results

This study included 194 CD patients and 213 controls. On multiple logistic regression analysis, a number of childhood environmental exposures during the 3 age interval were significantly associated with the risk of developing CD. During the age interval 6–10 years, never having had consumed unpasteurized milk (OR = 5.84; 95% CI, 2.73–13.53) and never having a donkey, horse, sheep or cow on the property (OR = 2.48; 95% CI, 1.09–5.98) significantly increased the risk of developing future CD. During the age interval 11–18 years, an independent risk-association was identified for; never having consumed unpasteurized milk (OR = 2.60; 95% CI, 1.17–6.10) and second-hand cigarette smoke exposure (OR = 1.93; 95% CI, 1.13–3.35).

Conclusion

This study demonstrates that both limited microbial exposures and exposure to second-hand cigarette smoke during childhood is associated with future development of CD.     

REMCARE: Pragmatic Multi-Centre Randomised Trial of Reminiscence Groups for People with Dementia and their Family Carers: Effectiveness and Economic Analysis

BackgroundJoint reminiscence groups, involving people with dementia and family carers together, are popular, but the evidence-base is limited. This study aimed to assess the effectiveness and cost-effectiveness of joint reminiscence groups as compared to usual care.MethodsThis multi-centre, pragmatic randomised controlled trial had two parallel arms: intervention group and usual-care control group. A restricted dynamic method of randomisation was used, with an overall allocation ratio of 1:1, restricted to ensure viable sized intervention groups. Assessments, blind to treatment allocation, were carried out at baseline, three months and ten months (primary end-point), usually in the person''s home. Participants were recruited in eight centres, mainly through NHS Memory Clinics and NHS community mental health teams. Included participants were community resident people with mild to moderate dementia (DSM-IV), who had a relative or other care-giver in regular contact, to act as informant and willing and able to participate in intervention. 71% carers were spouses. 488 people with dementia (mean age 77.5)were randomised: 268 intervention, 220 control; 350 dyads completed the study (206 intervention, 144 control). The intervention evaluated was joint reminiscence groups (with up to 12 dyads) weekly for twelve weeks; monthly maintenance sessions for further seven months. Sessions followed a published treatment manual and were held in a variety of community settings. Two trained facilitators in each centre were supported by volunteers. Primary outcome measures were self-reported quality of life for the person with dementia (QoL-AD), psychological distress for the carer (General Health Questionnaire, GHQ-28). Secondary outcome measures included: autobiographical memory and activities of daily living for the person with dementia; carer stress for the carer; mood, relationship quality and service use and costs for both.ResultsThe intention to treat analysis (ANCOVA) identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes (self-reported QoL-AD mean difference 0.07 (-1.21 to 1.35), F = 0.48, p = 0.53). Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a General Health Questionnaire-28 sub-scale at the ten month end-point (mean difference 1.25 (0.25 to 2.26), F = 8.28, p = 0.04). Compliance analyses suggested improved autobiographical memory, quality of life and relationship quality for people with dementia attending more reminiscence sessions, however carers attending more groups showed increased care-giving stress. Economic analyses from a public sector perspective indicated that joint reminiscence groups are unlikely to be cost-effective. There were no significant adverse effects attributed to the intervention. Potential limitations of the study include less than optimal attendance at the group sessions—only 57% of participants attended at least half of the intervention sessions over the 10 month period, and a higher rate of study withdrawal in the control group.ConclusionsThis trial does not support the clinical effectiveness or cost-effectiveness of joint reminiscence groups. Possible beneficial effects for people with dementia who attend sessions as planned are offset by raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions.

Trial Registration

ISRCTN Registry ISRCTN42430123     

Thermoluminescence characteristics of calcite with a Gaussian process regression model of machine learning

Thermoluminescence (TL) is defined as a luminescence phenomenon that can be detected when an insulator or semiconductor is thermally stimulated. Defective crystals store radiation until they are stimulated. Thermoluminescence is a method of monitoring the absorbed dose of dosimeters. The irradiation crystal is heated to 500°C to display the absorbed dose as a luminescent light. The TL dosimetric properties of calcite obtained from nature were investigated in this study. Machine learning was also examined using Gaussian process regression (GPR) for stimulated TL characteristics. According to the experimental output, the TL glow curve had two main peaks located at 90°C and 240°C with good dosimetric properties. In the four regression models of GPR, the data for the heating rate of 3°C s⁻¹ have the lowest residual.     

Cryopreservation timing is a critical process parameter in a thymic regulatory T-cell therapy manufacturing protocol

Regulatory T cells (Tregs) are a promising therapy for several immune-mediated conditions but manufacturing a homogeneous and consistent product, especially one that includes cryopreservation, has been challenging. Discarded pediatric thymuses are an excellent source of therapeutic Tregs with advantages including cell quantity, homogeneity and stability. Here we report systematic testing of activation reagents, cell culture media, restimulation timing and cryopreservation to develop a Good Manufacturing Practice (GMP)–compatible method to expand and cryopreserve Tregs. By comparing activation reagents, including soluble antibody tetramers, antibody-conjugated beads and artificial antigen-presenting cells (aAPCs) and different media, we found that the combination of Dynabeads Treg Xpander and ImmunoCult-XF medium preserved FOXP3 expression and suppressive function and resulted in expansion that was comparable with a single stimulation with aAPCs. Cryopreservation tests revealed a critical timing effect: only cells cryopreserved 1–3 days, but not >3 days, after restimulation maintained high viability and FOXP3 expression upon thawing. Restimulation timing was a less critical process parameter than the time between restimulation and cryopreservation. This systematic testing of key variables provides increased certainty regarding methods for in vitro expansion and cryopreservation of Tregs. The ability to cryopreserve expanded Tregs will have broad-ranging applications including enabling centralized manufacturing and long-term storage of cell products.