Stress‐induced reduction in hippocampal volume and connectivity with the ventromedial prefrontal cortex are related to maladaptive responses to stressful military service

Previous studies have shown that people who develop psychopathology such as posttraumatic stress disorder (PTSD) following stress exposure are characterized by reduced hippocampal (HC) volume and impaired HC functional connectivity with the ventromedial prefrontal cortex (vmPFC). Nevertheless, the exact interrelationship between reduced HC volume and HC‐vmPFC connectivity deficits in the context of stress has yet to be established. Furthermore, it is still not clear whether such neural abnormalities are stress induced or precursors for vulnerability. In this study, we combined measurements of MRI, functional MRI (fMRI), and diffusion tensor imaging (DTI) to prospectively study 33 a priori healthy Israeli soldiers both pre‐ and post‐exposure to stress during their military service. Thus, we were able to assess the contributions of structural and functional features of the HC and its connectivity to the onset and progression of maladaptive response to stress (i.e., increased PTSD symptoms post‐exposure). We found that soldiers with decreased HC volume following military service (i.e., post‐exposure) displayed more PTSD‐related symptoms post‐exposure as well as reduced HC‐vmPFC functional and structural connectivity post‐exposure, compared to soldiers with increased HC volume following military service. In contrast, initial smaller HC volume pre‐exposure did not have an effect on any of these factors. Our results therefore suggest that reduction in HC volume and connectivity with the vmPFC together mark a maladaptive response to stressful military service. As stress‐induced HC volume reductions were previously shown to be reversible, these localized biological markers may carry valuable therapeutic potential. Hum Brain Mapp 34:2808–2816, 2013. © 2012 Wiley Periodicals, Inc.     

Successful unrelated umbilical cord blood transplantation in Lesch-Nyhan syndrome

Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood–brain barrier.     

Association of matrix Gla protein gene allelic polymorphisms (G?7→A,T?138→C and Thr83→Ala) with acute coronary syndrome in the Ukrainian population

BACKGROUND:

Several allelic variants of matrix γ-carboxyglutamic acid protein (MGP) can differentially affect the development of certain forms of ischemic heart disease depending on specific characteristics of each population.

OBJECTIVE:

To study the distribution of allelic variants of MGP promoter T⁻¹³⁸→C (rs1800802) and G⁻⁷→A (rs1800801), and Thr₈₃→Ala exon 4 (rs4236) polymorphisms in a Ukrainian population of patients with acute coronary syndrome (ACS).

METHODS:

Polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis were used to detect the above-mentioned variants of the MGP gene in 115 patients with ACS and in 140 essentially healthy individuals.

RESULTS:

The distribution of homozygous carriers of a major allelic variant, and heterozygous and homozygous minor allele variants of the T⁻¹³⁸→C MGP promoter polymorphism in patients with ACS were 59.8%, 32.7% and 7.5%, respectively. The corresponding distributions of variants in the control group were 54.0%, 41.0% and 5.0%, respectively (P>0.05 [χ² test]). With respect to the G⁻⁷→A polymorphism, the respective distributions were 42.1%, 45.6% and 12.3%, compared with 50.7%, 45.0% and 4.3% in the control group, respectively (P<0.05). Finally, the respective distributions according to the Thr₈₃→Ala exon 4 polymorphism were 42.6%, 43.5% and 13.9%, respectively, compared with 45.3%, 43.0% and 11.7% in the control group. Using logistic regression analysis, it was estimated that the A/A genotype (G⁻⁷→A polymorphism) was significantly (P=0.02) associated with ACS (OR 4.302 [95% CI 1.262 to 14.673]).

CONCLUSION:

The allelic A/A promoter variant of MGP G⁻⁷→A polymorphism can be considered a risk factor for ACS in the Ukrainian population.     

Minimal residual disease detectable by quantitative assessment of WT1 gene before allogeneic stem cell transplantation in patients in first remission of acute myeloid leukemia has an impact on their future prognosis

Overall 42 patients (pts) transplanted in hematological CR1 were retrospectively analyzed. Median follow‐up was 15 months (range 2–77). The expression of WT1 gene was measured according to the European Leukaemia Net recommendations. At the time of allogeneic stem cell transplantation (allo‐SCT) 29 pts were WT1‐negative and 13 pts were WT1‐positive. In the univariate analysis, significantly better results were observed in the group of WT1 neg in terms of progression‐free survival (in three yr 77% vs. 27%, p = 0.001). In multivariate analysis, the only significant feature in terms of better OS was WT1 negativity (p = 0.029). Our results show that minimal residual disease status measured by quantitative assessment of WT1 gene in acute myeloid leukemia pts in CR1 significantly affects their future prognosis after allo‐SCT.     

Impact of triple pelvic osteotomy on contact stress pressure distribution in the hip joint

Purpose

We studied changes of contact stress distribution in the hip joint after Tonnis triple pelvic osteotomy applied in the treatment of dysplasia and hip joint incongruence in adolescents.

Methods

In a group of 75 patients, 54 (72 %) female, who underwent surgery by triple pelvic osteotomy in adolescence for developmental disorder of the hip and avascular necrosis of the femoral head, a three-dimensional hip joint model was used based on the radiography of the pelvis with hips. The following biomechanical parameters were calculated: resultant hip force normalised to body weight (R/Wb), inclination of the resultant hip force (θ−R), the position of the stress pole (θ), peak contact hip stress (Pmax), and peak contact hip stress normalised to body weight (Pmax/Wb). Gait quality was also assessed.

Results

After surgery the Wiberg CE angle was increased by 17.85° (114 %), resultant hip force normalised to body weight (R/Wb) was decreased by 0.107 (3.3 %), the position of the stress pole was shifted medially by 27.59° (63.5 %), and peak contact hip stress normalised to body weight (Pmax/Wb) was decreased by 2249.74 (55.9 %). Waddling gait was reduced from 17 (23.9 %) to four cases (5.6 %). All changes were statistically highly significant (p<0.01).

Conclusions

The effect of Tonnis triple pelvic osteotomy lies in the improvement of stress distribution across the acetabular cartilage of the hip joint, thus slowing down the degenerative damage of the hip joint.     

Applications of complementary therapies during rehabilitation for individuals with traumatic Spinal Cord Injury: Findings from the SCIRehab Project

Objective: Evaluate the use of complementary therapies during rehabilitation for patients with traumatic spinal cord injury (SCI).

Design: Secondary analyses were conducted to identify the use and associated outcomes of complementary therapies provided by occupational therapists (OTs) and physical therapists (PTs) during rehabilitation from a public dataset.

Setting: Inpatient rehabilitation.

Participants: A public dataset composed of 1376 patients with SCI that were enrolled in a five-year, multi-center investigation, the SCIRehab Project. Secondary analyses focused on a subset of 93 patients (47 who received complementary therapy during treatment and 46 case-matched controls who received no complementary therapy).

Interventions: OTs and PTs recorded use of complementary therapies during sessions, including yoga, Pilates, tai chi, aromatherapy, relaxation techniques, imagery and other.

Outcome Measures: Pain interference, pain severity, mobility, and social integration.

Results: Three percent of participants received any complementary therapies. Patients who received complementary therapies showed greater reductions in pain severity from 6 months to 12 months relative to matched controls. Furthermore, the amount of time that patients received complementary therapies during physical therapy sessions was associated with reduced pain interference at 6 months and with reduced pain severity at the 6-month and 12-month follow-ups. Complementary therapy use was not associated with mobility or social integration.

Conclusion: The current study provides preliminary evidence documenting the limited use of complementary therapies in rehabilitation settings and highlights the opportunity for further research, particularly regarding pain-related outcomes.