An evaluation of the relationship between 'atopic skin' and skin irritability in metalworker trainees

Skin hyperirritability to irritants as well as atopy are considered to be predisposing factors for contact dermatitis. The aim of the study was to evaluate whether these predictive factors are independent or whether they are so closely related that one could possibly replace the oilier. 205 metalworker trainees underwent skill examination for skin atopy, including standardised questionnaire, clinical examination of the skin and a series of skin irritability tests. These tests included measurements of transepidermal water loss (TEWL) before and after irritation with 3 different irritants: sodium lauryl sulfate (SLS), dimethylsulfoxide (DMSO) and sodium hydroxide (NaOH). The results of the linear regression analysis demonstrate that skin atopy is not associated with increased skin irritability, as assessed by the irritability testing methods presented.     

Multimodal therapy improves survival in patients with CNS metastasis from uterine cancer: a retrospective analysis and literature review

OBJECTIVE: Brain metastasis from uterine cancer is a rare event. Consequently, the optimal management strategy is not defined. We reviewed our institution's experience with brain metastasis from endometrial cancer along with the extant medical literature to develop management recommendations. METHODS: Twenty patients with CNS metastasis were identified. Information regarding symptoms, treatment, and survival was collected. The Kaplan-Meier method was used to compare survival data. RESULTS: The incidence of CNS metastasis was 0.97%. Median patient age at initial diagnosis of endometrial cancer was 62.0 years and 64.0 years at diagnosis of brain metastasis. Most patients initially presented with advanced FIGO stage: 9 stage IVB, 4 stage IIIC, 4 stage IIIA, 2 stage IB, and 1 stage IA. The median interval from diagnosis of endometrial cancer to diagnosis of brain metastasis was 11.5 months (range 0.6-73.6). Median survival after diagnosis of brain metastasis was 2.0 months (range 0.1-39.2). Improved survival was seen in patients treated with multimodal therapy compared to patients who only received whole brain radiotherapy (WBRT) (p=0.0001) or compared to patients who received no treatment (p=0.009). No difference in survival was seen between patients treated with WBRT versus no therapy. The survival advantage associated with multimodal therapy was also supported by case reports and case series in the literature. CONCLUSIONS: Based upon the data presented along with the medical literature, multimodal therapy appears to improve the survival of patients with CNS metastasis from uterine cancer.     

Elements of affective instability associated with suicidal behaviour in patients with borderline personality disorder

OBJECTIVE: To identify elements of affective instability associated with an increased likelihood of impulsivity and then to determine whether these elements characterize patients with borderline personality disorder (BPD) and suicidal behaviour. METHOD: We prospectively followed 82 individuals with BPD and a history of recurrent suicidal behaviour who recorded their current mood states, impulsivity, suicide ideation, and environmental stressors (triggers) 6 times daily over 3 weeks. RESULTS: Our results suggested that mood amplitude was correlated with impulsivity and that 4 subgroups defined by mean scores on mood amplitude and negative mood intensity significantly differed in the number of suicidal behaviours reported in the last year. CONCLUSIONS: A subgroup of BPD patients appears to be at elevated risk for suicidal behaviour based on high mood amplitude and mean negative mood intensity. Clinicians might target this group for monitoring and interventions to reduce the likelihood of suicidal behaviour.     

Differentiation of MSC and annulus fibrosus cells on genetically engineered silk fleece‐membrane‐composites enriched for GDF‐6 or TGF‐β3

Intervertebral disc (IVD) repair is a high‐priority topic in our active and increasingly ageing society. Since a high number of people are affected by low back pain treatment options that are able to restore the biological function of the IVD are highly warranted. Here, we investigated whether the feasibility of genetically engineered (GE)‐silk from Bombyx mori containing specific growth factors to precondition human bone‐marrow derived mesenchymal stem cells (hMSC) or to activate differentiated human annulus fibrosus cells (hAFC) prior transplantation or for direct repair on the IVD. Here, we tested the hypothesis that GE‐silk fleece can thrive human hMSC towards an IVD‐like phenotype. We aimed to demonstrate a possible translational application of good manufacturing practice (GMP)‐compliant GE‐silk scaffolds in IVD repair and regeneration. GE‐silk with growth and differentiation factor 6 (GDF‐6‐silk) or transforming growth factor β3 (TGF‐β3, TGF‐β3‐silk) and untreated silk (cSilk) were investigated by DNA content, cell activity assay and glycosaminoglycan (GAG) content and their differentiation potential by qPCR analysis. We found that all silk types demonstrated a very high biocompatibility for both cell types, that is, hMSC and hAFC, as revealed by cell activity, and DNA proliferation assay. Further, analyzing qPCR of marker genes revealed a trend to differentiation toward an NP‐like phenotype looking at the Aggrecan/Collagen 2 ratio which was around 10:1. Our results support the conclusion that our GE‐silk scaffold treatment approach can thrive hMSC towards a more IVD‐like phenotype or can maintain the phenotype of native hAFC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1324–1333, 2018.

     

Obstetric fistula in Niger: 6-month postoperative follow-up of 384 patients from the Danja Fistula Center

Introduction and hypothesis

The impoverished West African country of Niger has high rates of obstetric fistula. We report a 6-month postoperative follow-up of 384 patients from the Danja Fistula Center and assess factors associated with operative success or failure.

Methods

The medical records of 384 women who had completed a 6-month follow-up after fistula surgery were reviewed. Cases were categorized as “easy,” “of intermediate complexity,” or “difficult” based on a preoperative points system. Data were analyzed using simple chi-squared statistics and logistic regression.

Results

The patients were predominantly of Hausa ethnicity (73%), married young (average 15.9 years), had teenage first pregnancies (average first delivery 16.9 years), and experienced prolonged labor (average 2.3 days) with poor outcomes (89% stillbirth rate). The average parity was four. Patients commonly developed their fistula during their first delivery (43.5%), but over half sustained a fistula during a subsequent delivery (56.5%). Prior fistula surgery elsewhere (average 1.75 operations) was common. The overall surgical success (“closed and dry”) was 54%. When the 134 primary operations were analyzed separately, the overall success rate was 80%. Increasing success was seen with decreasing surgical difficulty: 92% success for “easy” cases, 68% for “intermediate” cases, and 57% success for “difficult” cases. Success decreased with increasing numbers of previous attempts at surgical repair.

Conclusions

These data provide further evidence that clinical outcomes are better when primary fistula repair is performed by expert surgeons in specialist centers with the support of trained fistula nurses.

     

A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy

Dystrophic epidermolysis bullosa (DEB) is a severe skin fragility disorder associated with trauma-induced blistering, progressive soft tissue scarring, and increased risk of skin cancer. DEB is caused by mutations in type VII collagen. In this study, we describe the generation of a collagen VII hypomorphic mouse that serves as an immunocompetent animal model for DEB. These mice expressed collagen VII at about 10% of normal levels, and their phenotype closely resembled characteristics of severe human DEB, including mucocutaneous blistering, nail dystrophy, and mitten deformities of the extremities. The oral blistering experienced by these mice resulted in growth retardation, and repeated blistering led to excessive induction of tissue repair, causing TGF-beta1-mediated contractile fibrosis generated by myofibroblasts and pseudosyndactyly in the extremities. Intradermal injection of WT fibroblasts resulted in neodeposition of collagen VII and functional restoration of the dermal-epidermal junction. Treated areas were also resistant to induced frictional stress. In contrast, untreated areas of the same mouse showed dermal-epidermal separation following induced stress. These data demonstrate that fibroblast-based treatment can be used to treat DEB in a mouse model and suggest that this approach may be effective in the development of clinical therapeutic regimens for patients with DEB.     

Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development

Members of the Bcl-2 protein family play crucial roles in the maintenance of tissue homeostasis by regulating apoptosis in response to developmental cues or exogenous stress. Proapoptotic BH3-only members of the Bcl-2 family are essential for initiation of cell death, and they function by activating the proapoptotic Bcl-2 family members Bax and/or Bak, either directly or indirectly through binding to prosurvival Bcl-2 family members. Bax and Bak then elicit the downstream events in apoptosis signaling. Mammals have at least eight BH3-only proteins and they are activated in a stimulus-specific, as well as a cell type-specific, manner. We have generated mice lacking the BH3-only protein Bcl-2-modifying factor (Bmf) to investigate its role in cell death signaling. Our studies reveal that Bmf is dispensable for embryonic development and certain forms of stress-induced apoptosis, including loss of cell attachment (anoikis) or UV irradiation. Remarkably, loss of Bmf protected lymphocytes against apoptosis induced by glucocorticoids or histone deacetylase inhibition. Moreover, bmf(-/-) mice develop a B cell-restricted lymphadenopathy caused by the abnormal resistance of these cells to a range of apoptotic stimuli. Finally, Bmf-deficiency accelerated the development of gamma irradiation-induced thymic lymphomas. Our results demonstrate that Bmf plays a critical role in apoptosis signaling and can function as a tumor suppressor.