Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Nurse students’ competences in interprofessional pharmaceutical care in Europe: Cross-sectional evaluation

BackgroundSafe pharmaceutical care requires competent nurses with specific knowledge, skills and attitudes. It is unclear whether nursing students are adequately prepared to perform pharmaceutical care in practice. Mapping their pharmaceutical care competences can lead to a better understanding of the extent to which curricula fit expectations of the labour market.ObjectivesTo assess pharmaceutical care competences of final-year nursing students of different educational levels.DesignA cross-sectional survey design.SettingsIn 14 European countries, nursing schools who offer curricula for level 4 to 7 students were approached.ParticipantsThrough convenience sampling 1741 final-year student nurses of level 4 to 7 were included. Sampling strategies were country-specific.MethodsA web-platform was developed with an assessment of the level in which students mastered pharmaceutical care competences. Knowledge questions, case studies (basic/advanced level), self-reported practical skills and attitudes were evaluated.ResultsMean scores for knowledge questions differed significantly (p < 0.001) between level 5 (56/100), level 6 (68/100) and level 7 students (72/100). For basic cases level 5 students reached lower scores (64/100) compared with level 6 (71/100) and level 7 (72/100) students (p = 0.002 and p = 0.005). For more advanced cases no difference between levels was observed (overall mean 61/100). Most students (63–90 %) considered themselves skilled to perform pharmaceutical care and had positive attitudes towards their participation in pharmaceutical care (65–97 %).ConclusionsRelatively low knowledge scores were calculated for final-year student nurses. In some domains, lower levels of students might be insufficiently prepared to take up responsibilities in pharmaceutical care. Our assessment can be used as a tool for educators to evaluate how prepared nursing students are for pharmaceutical care. Its further implementation for students of different educational levels will allow benchmarking between the levels, both within and between countries.     

Gait and plantar sensation changes following massage and textured insole application in patients after anterior cruciate ligament reconstruction

BackgroundGait impairments following anterior cruciate ligament reconstruction (ACLR) may contribute to reinjury or future osteoarthritis development. Recently, plantar cutaneous sensation deficits have been reported post-ACLR. These sensory deficits may influence gait and represent a mechanism through which to improve gait.Research questionCan established sensory interventions change sensation and gait in patients after ACLR and compared to healthy adults?MethodsTwenty-two adults (n = 11 post-ACLR, age:20.5 ± 1.9years, body mass index[BMI]:24.5 ± 3.6 kg/m²; n = 11 healthy, age:20.7 ± 1.4years, BMI:23.3 ± 2.7 kg/m²) completed two sessions separated by 48 h. Gait and plantar cutaneous sensation were assessed pre- and post-intervention (massage or textured insoles). Gait analysis was completed using 3D motion capture at 1.4 m/s ± 5% and standard inverse dynamics analysis. Plantar cutaneous sensation was assessed using Semmes Weinstein Monofilaments with a 4−2-1 stepping algorithm at the plantar aspect of the first metatarsal head, base of the fifth metatarsal, and lateral and medial malleoli. Plantar massage was a 5-minute massage to both feet. Textured insoles (coarse grit sandpaper) were worn while walking. Biomechanical data were assessed via mixed-models, repeated measures ANOVAs and 90 % confidence intervals. Wilcoxon Signed Rank tests and Mann-Whitney U tests evaluated plantar cutaneous sensation within and between groups, respectively.ResultsKnee adduction moment was lower in the ACLR versus the contralateral limb pre-massage. The vGRF was lower during the first half of stance but greater during the second half of stance in the ACLR versus the control group post-massage. Massage improved ACLR limb sensation over the first metatarsal head (P = 0.042) and medial malleolus (P = 0.027). Textured insole application improved ACLR limb sensation over the first (P = 0.043) and fifth (P = 0.027) metatarsals and medial malleolus (P = 0.028).SignificancePlantar massage and textured insoles improved plantar cutaneous sensation in the ACLR limb. Neither intervention influenced gait. Improving plantar sensation may be beneficial for patients after ACLR; however, sensory interventions to improve gait are necessary.     

Fusion protein His-Hsp65-6IA2P2 prevents type 1 diabetes through nasal immunization in NOD Mice

Human heat shock protein 60 (Hsp60), is an endogenous β-cells autoantigen, it could postpone the onset of insulitis and sooner type 1 diabetes mellitus. P277 is one of Hsp65 determinants at position 437–469 of amino acids cascaded. Meanwhile, it's already well-known that there were several better anti-diabetic B epitopes, such as insulinoma antigen-2 (IA-2). Currently, fusion protein IA2P2 has constructed in order to enhance its pharmacological efficacy. In addition, added homologous bacterial-derived Hsp65 and His tag were beneficial to protein immunogenicity and purification separately. So, finally we examined a fusion protein His-Hsp65-6IA2P2 could regulate Th2 immune response and reduce natural diabetic incidence in NOD mice. We constructed two express vector pET28a–His-Hsp65-6P277 and pET28a–His-Hsp65-6IA2P2. After purification, we observed that triple intranasal administration of these two fusion protein in 4-week-old NOD mice maintained normal blood glucose and weight, with a lower diabetic or insulitis incidence. Consistent with induced splenic T cells proliferation and tolerance, His-Hsp65-6IA2P2-treated mice performed reduced IFN-γ and increased IL-10 level. In conclusion, we suggested that fusion protein His-Hsp65-6IA2P2 could be reconstructed and purified successively. Furthermore, nasal administration of this fusion protein could rebalance T cells population and prevent T1DM.