Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

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Neurologic abnormalities in children presenting with diskitis

BACKGROUND: Neurologic impairment is not considered a clinical manifestation of diskitis in children and has seldom been associated with it in the medical literature. OBJECTIVE: To describe neurologic findings and their implications in children with diskitis. STUDY DESIGN: Retrospective medical records review of children discharged with a diagnosis of diskitis between January 1992 and December 2000. The study included children in whom the diagnosis was based on the presence of clinical findings, laboratory evidence of an inflammatory process, and findings on imaging studies compatible with diskitis. RESULTS: Neurologic findings of decreased muscle strength or hyporeflexia in the lower extremities were found in 7 (41%) of 17 children who met the diagnostic criteria for diskitis. Five of the 7 underwent magnetic resonance imaging, 2 of whom demonstrated intraspinal inflammatory involvement. CONCLUSIONS: Neurologic impairment does not exclude the diagnosis of diskitis and may be a common manifestation of the disease in children. Nevertheless, when neurologic findings are present, advanced imaging studies are needed to exclude intraspinal involvement.     

Risk factors and maternal outcomes following preterm premature rupture of membrane in the second trimester of gestation

Archives of Gynecology and Obstetrics - To characterize the population of women who underwent mid-trimester preterm premature rupture of membrane (PPROM) in a country where mid-trimester abortions...     

Right ductus arteriosus: facts and theory

ObjectiveTo report fetal right-sided persistent ductus arteriosus (RPDA) in association with right aortic arch (RAA).Study designExtensive sonographic fetal anatomical scans were consecutively performed on 19,874 private, self-referred pregnant women who wanted early sonographic detection of fetal anomalies.ResultsOf 19,874 transvaginal (TVS) sonographic examinations 40 fetuses had right aortic arch (RAA) and four of them (10%) had RPDA. We also diagnosed seven cases of RPDA with involvement of the left aortic arch where a right-curving pattern (“L” shape) parallel to the right pulmonary artery was suggestive of Rt. DA with left aortic arch. Only one (9%) of the RPDA cases was associated with a cardiac anomaly (double outlet right ventricle). None of the other eight RPDA cases had any discernible anomalies, and all of the fetuses with RPDA had normal karyotypes.ConclusionsIn 10% of the fetuses with right aortic arch the ductal arch was also on the right side. An unusual-looking DA may be a RPDA associated with the left aortic arch.In most cases, the RPDA is a normal variant not associated with other anomalies.     

Spondyloenchondrodysplasia Due to Mutations in <Emphasis Type="Italic">ACP5</Emphasis>: A Comprehensive Survey

Purpose

Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.

Methods

We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations.

Results

We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy.

Conclusions

Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.

     

Sildenafil citrate for the sexual dysfunction in antidepressant-treated male patients with posttraumatic stress disorder. A preliminary pilot open-label study

BACKGROUND: Previous studies have suggested that posttraumatic stress disorder (PTSD) may be associated with pervasive sexual dysfunction. Sildenafil citrate was established as a highly effective and well-tolerated oral agent for the treatment of sexual dysfunction of various etiologies. There are no studies that have examined the efficacy of oral sildenafil in PTSD patients with sexual dysfunction. OBJECTIVE: The current study evaluated the impact of sildenafil added to an ongoing antidepressive treatment in male PTSD patients. METHODS: Ten consecutive male PTSD patients who complained of sexual dysfunction were enrolled in an open-label 4-week fixed-dose study of sildenafil citrate 50 mg/day p.r.n. Patients were evaluated at baseline and after treatment with the Clinician-Administered PTSD Scale (CAPS); sexual function assessments were performed using the International Index of Erectile Function. RESULTS: All patients completed the study and statistically significant improvement was observed in all evaluated domains of sexual functioning: erectile function (53.5%), orgasmic function (40.3%), sexual desire (53%), intercourse satisfaction (82%) and overall satisfaction (57.4%). Oral sildenafil treatment appeared to be well tolerated and no single patient stopped the treatment. Improvements in various CAPS subscales were also obtained; however, there was no significant correlation between improvement in sexual functioning and the changes in CAPS subscale scores. CONCLUSION: Sildenafil seems to be an efficacious, safe and well-tolerated treatment of sexual dysfunction in antidepressant-treated male PTSD patients.     

Genetic diagnosis and renal biopsy findings in the setting of a renal genetics clinic

As genetic testing becomes more available, its utilization as an early diagnostic tool in nephrology is more common. The objective of the study is to examine diagnostic agreement between the renal biopsy findings and genetic diagnoses. A retrospective study was conducted in February 2022. A total of 28 patients had both genetic diagnosis and histologic results (n = 1 nephrectomy, n = 27 biopsy). We collected clinical, renal biopsy findings, and genetic information. The relationship between the histologic findings and the genetic diagnoses was classified as: concordant, nonspecific, and discordant. A total of 15 males and 13 females were included (mean age = 9.6 years). Clinical suspicion of Alport syndrome was the most common reason for referral (n = 11, 39.3%), followed by nephrotic syndrome (n = 8, 28.5%), “other” (n = 6, 21.4%), cystic kidney disease (n = 1, 3.6%), isolated hematuria (n = 1, 3.6%), and non-nephrotic proteinuria (n = 1, 3.6%). The overall concordance rate between renal histologic and genetic diagnoses was 71.4% (20/28), nonspecific biopsy results were observed in 17.9% (5/28), and discordant results were observed in 10.7% (3/28). All patients referred for suspected Alport Syndrome had pathogenic/likely pathogenic variants in one of the COL4A genes. Two cases of Lowe syndrome and one of PAX2-associated nephropathy had discordant histology findings. Agreement between renal histologic findings and genetic results varies based on the reason for referral. There was a complete agreement for patients referred for Alport Syndrome; However, there were examples that renal biopsy showed secondary findings that were not specifically associated with the underlying genetic results.     

Sesame food allergy and sensitization in children: the natural history and long-term follow-up

Sesame food allergy (SFA) in children is an increasingly recognized one in many countries. Our objective was to describe the course and natural history of SFA. Seventy-four patients sensitized to sesame were evaluated using clinical records, questionnaires, skin prick tests (SPT), in vitro specific immunoglobulin (sIg) E, and oral challenges (OC) and categorized into three groups: group A: patients who experienced allergic reaction after ingestion of sesame-containing food (n = 45); group B: patients evaluated for atopic dermatitis and found to be sesame SPT-positive (n = 11); group C: patients with sensitization to sesame allergen (n = 18). Group A patients were followed for an average of 6.7 yr. Analysis of our results revealed that 76% of patients in group A developed the allergy by the age of 2. The median age at onset of allergy in these patients was 1 yr. Immediate reaction to a minimal amount of sesame was characteristic. Skin was the most common site of involvement, followed by respiratory and gastrointestinal systems. Tolerance developed in only 20% of the patients. High sIgE (>0.15 IU) was demonstrated only in 75% of those in which it was examined. Sixteen patients performed oral sesame food challenge which was found positive in 88%. No correlation was found between the size of SPT and the level of in vitro sesame IgE antibodies, the outcome of OC results, and the development of tolerance to sesame. In conclusion, SFA tends to appear early in life, but unlike cow's milk and egg allergy, persists in 80% of the cases. Typical reactions combined with positive sesame SPT are reliable for diagnosis.