Influence of spirituality on moral distress and resilience in critical care staff: A scoping review.

OBJECTIVE: The Covid 19 pandemic has created a situation in which critical care staff experience moral distress. For reducing moral distress, resources such as spirituality can be used. The aim of this scoping review is to explore whether spirituality mitigates the moral distress of critical care staff and strengthens their resilience. The spiritual resources will be identified and the ability of the staff to use spiritual resources will be explored. METHODOLOGY: A scoping review of studies reporting on the association between spirituality, moral distress, and resilience. Qualitative and quantitative studies from 2020 that examined critical care staff are included. This scoping review used the five-step framework proposed by Arksey and O'Malley and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework for scoping reviews. The literature searches were conducted in 12 databases. RESULTS: 13 studies met inclusion criteria. Critical care staff declaring themselves as spiritual have a higher risk of moral distress and are often not able to use spiritual resources on their own. For effective use of spiritual resources to reduce moral distress, staff need to be skilled in the practice of spirituality with the aim to find inner peace, focus on the positive, and regain a sense of purpose in the work. CONCLUSION: Spirituality does not automatically help the critical care staff to cope with moral distress and strengthen resilience. Institutions need to create conditions in which the critical care staff are supported to use their spiritual resources. IMPLICATION FOR CLINICAL PRACTICE: Institutions need to involve staff more in the design, implementation, and delivery of spiritual interventions to minimise moral distress. Further research is necessary to examine the impact of critical care staff's demographic characteristics on their spirituality, moral distress, and resilience.

Low maternal folate concentrations and maternal MTHFR C677T polymorphism are associated with an increased risk for neural tube defects in offspring: a case-control study among Pakistani case and control mothers.

BACKGROUND AND OBJECTIVES: There is considerable evidence that periconceptional maternal folate deficiency and coding variants in maternal genes coding for critical enzymes in the folate pathway are associated with neural tube defects (NTDs) in offspring. In a case-control study we investigated C677T polymorphism in the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene in case and control mothers of Pakistani origin, and compared these with the respective maternal folate concentrations measured at the time of delivery. METHODS AND STUDY DESIGN: A case-control study was conducted among 109 case and 100 control mothers identified through the Holy Family Hospital Rawalpindi, Quaid-i-Azam University, Islamabad, Pakistan. Red blood cell (RBC) and serum folate concentrations and MTHFRC677T polymorphism were compared between case and control mothers. RESULTS: Mean RBC folate and serum folate concentrations were significantly lower in cases compared with control mothers (p<0.0001). Maternal MTHFR 677CT and 677TT genotypes were more common among cases compared with control mothers (CC vs TT p<0.0393 and CC/CT vs TT p<0.021). T-allele frequency was higher in cases compared with control mothers (C vs T p<0.017). Case mothers with 677CT or 677TT genotypes had significantly lower serum (p<0.0001) and RBC folate concentrations (p<0.0001) compared with control mothers. CONCLUSIONS: The present study provides further evidence that maternal folate deficiency and MTHFRC677T polymorphism might be associated with an increased risk for NTDs in offspring. Our results are limited by the fact that maternal folate concentrations were not obtained during the periconceptional period, but at delivery. Further analyses, including maternal folate levels during the periconceptional period, are warranted.

Targeted Resequencing of Putative Growth-Related Genes Using Whole Exome Sequencing in Patients with Severe Primary IGF-I Deficiency.

BACKGROUND/AIMS: To elucidate the genetic causes of severe primary insulin-like growth factor-I deficiency (SPIGFD) by systematic, targeted, next-generation sequencing (NGS)-based resequencing of growth-related genes. METHODS: Clinical phenotyping followed by NGS in 17 families including 6 affected sib pairs. RESULTS: We identified disease-causing, heterozygous, de novo variants in HRAS (p.Gly13Cys) and FAM111A (p.Arg569His) in 2 male patients with syndromic SPIGFD. A previously described homozygous GHR nonsense variant was detected in 2 siblings of a consanguineous family (p.Glu198*). Furthermore, we identified an inherited novel variant in the IGF2 gene (p.Arg156Cys) of a maternally imprinted gene in a less severely affected father and his affected daughter. We detected 2 other novel missense variants in SH2B1 and SOCS2, both were inherited from an unaffected parent. CONCLUSIONS: Screening of growth-related genes using NGS-based, large-scale, targeted resequencing identified disease-causing variants in HRAS, FAM111A, and GHR. Considering the increased risk of subjects with HRAS mutations for neoplasms, close clinical monitoring and a thorough discussion of the risk/benefit ratio of the treatment with recombinant IGF-I is mandatory. Segregation analysis proved to be critical in the interpretation of potential SPIGFD-associated gene variations.

Mutations in PTF1A are not a common cause for human VATER/VACTERL association or neural tube defects mirroring Danforth's short tail mouse.

Danforth's short tail (Sd) mutant mice exhibit defects of the neural tube and other abnormalities, which are similar to the human vertebral anomalies, anal atresia, cardiac defects, tracheosophageal fistula and/or esophageal atresia, renal and radial abnormalities, and limb defects (VATER/VACTERL) association, including defects of the hindgut. Sd has been shown to underlie ectopic gene expression of murine Ptf1a, which encodes pancreas-specific transcription factor 1A, due to the insertion of a retrotansposon in its 5' regulatory domain. In order to investigate the possible involvement of this gene in human VATER/VACTERL association and human neural tube defects (NTDs), a sequence analysis was performed. DNA samples from 103 patients with VATER/VACTERL and VATER/VACTERL­like association, all presenting with anorectal malformations, and 72 fetuses with NTDs, where termination of pregnancy had been performed, were included in the current study. The complete PTF1A coding region, splice sites and 1.5 kb of the 5' flanking promotor region was sequenced. However, no pathogenic alterations were detected. The results of the present study do not support the hypothesis that high penetrant mutations in these regions of PTF1A are involved in the development of human VATER/VACTERL association or NTDs, although rare mutations may be detectable in larger patient samples.

Heterozygous FGF8 mutations in patients presenting cryptorchidism and multiple VATER/VACTERL features without limb anomalies.

BACKGROUND: The acronym VATER/VACTERL association describes the combination of at least three of the following cardinal features: vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. Although fibroblast growth factor-8 (FGF8) mutations have mainly found in patients with Kallmann syndrome, mice with a hypomorphic Fgf8 allele or complete gene invalidation display, aside from gonadotropin-releasing hormone deficiency, parts or even the entire spectrum of human VATER/VACTERL association. METHODS: We performed FGF8 gene analysis in 49 patients with VATER/VACTERL association and 27 patients presenting with a VATER/VACTERL-like phenotype (two cardinal features). RESULTS: We identified two heterozygous FGF8 mutations in patients displaying either VATER/VACTERL association (p.Gly29_Arg34dup) or a VATER/VACTERL-like phenotype (p.Pro26Leu) without limb anomalies. Whereas the duplication mutation has not been reported before, p.Pro26Leu was once observed in a Kallmann syndrome patient. Both our patients had additional bilateral cryptorchidism, a key phenotypic feature in males with FGF8 associated Kallmann syndrome. Each mutation was paternally inherited. Besides delayed puberty in both and additional unilateral cryptorchidism in one of the fathers, they were otherwise healthy. Serum hormone levels downstream the gonadotropin-releasing hormone in both patients and their fathers were within normal range. CONCLUSION: Our results suggest FGF8 mutations to contribute to the formation of the VATER/VACTERL association. Further studies are needed to support this observation.