A novel objective evaluation method, shear wave elastography, in the treatment of atrophic vaginitis by nonablative intravaginal Er:YAG laser, a randomized-sham controlled pilot study.

OBJECTIVE: The aim of the study was to investigate the effectiveness of intravaginal Er:YAG laser for treating atrophic vaginitis in postmenopausal women utilizing shear wave elastography. METHODS: In this prospective randomized sham-controlled double-blind pilot study, 20 participants were included (laser group [n = 12] / sham-control group [n = 8]). A nonablative (Smooth mode) Er:YAG laser with a wavelength of 2,940 nm was used. Objective evaluation of laser treatment efficacy was conducted using a special ultrasonic technique: shear wave elastography. Ultrasonic velocity measurements were taken from the anterior and posterior vaginal walls. Mean elasticity (Emean) was expressed in kilopascals (kPa). Additional outcome parameters were vaginal pH, Vaginal Health Index (VHI), Female Sexual Function Index (FSFI), and visual analog scale (VAS) scores for dyspareunia. RESULTS: Baseline clinical characteristics, vaginal pH, VHI, VAS and FSFI scores, and Emean values were comparable between the laser and sham-control groups. Statistically significant differences were observed in the final Emean values of the anterior vaginal wall (13.1 ± 6.3 vs 20.0 ± 3.3 kPA, P = 0.01) and posterior vaginal wall (12.7 ± 10.3 vs 19.4 ± 6.9 kPA, P = 0.04) between the laser and sham-control group. Despite comparable baseline Emean values, significant differences in vaginal wall stiffness posttreatment indicated a notable increase in tissue elasticity following laser treatment. Statistically significant differences were also observed in final vaginal pH values, VHI, VAS scores, and FSFI score improvement in favor of laser treatment. CONCLUSIONS: Shear wave elastography may be considered as a reliable and objective technique for evaluating the efficacy of Er:YAG laser treatment in women with atrophic vaginitis. However, additional studies with larger sample sizes are necessary to establish conclusive evidence.

Recurrent de-novo gain-of-function mutation in SPTLC2 confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specific gain-of-function mutations in SPTLC1 were identified in patients with juvenile form of ALS. SPTLC2 encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex. METHODS: We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants in SPTLC2. The de-novo status was confirmed by Sanger sequencing. Sphingolipidomics was performed using liquid chromatography and high-resolution mass spectrometry. RESULTS: Two unrelated patients presented with early-onset progressive proximal and distal muscle weakness, oral fasciculations, and pyramidal signs. Both patients carried the novel de-novo SPTLC2 mutation, c.203T>G, p.Met68Arg. This variant lies within a single short transmembrane domain of SPTLC2, suggesting that the mutation renders the SPT complex irresponsive to regulation through ORMDL3. Confirming this hypothesis, ceramide and complex sphingolipid levels were significantly increased in patient plasma. Accordingly, excessive sphingolipid production was shown in mutant-expressing human embryonic kindney (HEK) cells. CONCLUSIONS: Specific gain-of-function mutations in both core subunits affect the homoeostatic control of SPT. SPTLC2 represents a new Mendelian ALS gene, highlighting a key role of dysregulated sphingolipid synthesis in the pathogenesis of juvenile ALS. Given the direct interaction of SPTLC1 and SPTLC2, this knowledge might open new therapeutic avenues for motor neuron diseases.

Another de novo mutation in the SOD1 gene: the first Turkish patient with SOD1-His47Arg, a case report.

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease of motor neurons. Most ALS cases are considered sporadic due to the presence of a combination of environmental and complex genetic risk factors, while approximately 10% of cases have a family history. Pathogenic variants in the SOD1 gene are the second most frequent causative factor of genetics-based ALS worldwide, after C9ORF72 hexanucleotide repeat expansion. The De novo occurrence of pathogenic mutations in ALS-associated genes and its effect on disease progression have been studied previously, especially in the FUS gene. Recent studies have shown that a very small portion of SOD1 cases occurred de novo. Here, we present the first de novo case of the SOD1 His47Arg mutation in a young female patient with mild symptoms and, currently, a slow progression for 7 years.

The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database.

The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with ~70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlights DECR1, ATL1, HDAC2, GEMIN4, and HNRNPA3 as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).

Relationship between Sarcopenia and Mortality in Elderly Inpatients.

OBJECTIVE: Sarcopenia, a geriatric syndrome, is an indicator of poor prognosis in elderly inpatients. In this study, we aimed to determine the effect of sarcopenia on mortality in elderly patients. MATERIALS AND METHODS: Mobile/immobile geriatric inpatients, treated in the internal medicine ward between February and November 2018, were included in the study between Days 2 and 7 of hospitalization. The patients' fat-free mass (FFM) was measured by bioimpedance. The FFM index (FFMI) (kg/m2) was determined by dividing fat-free mass by body surface area (FFM/BSA). Sarcopenia was defined as a FFMI value at least two standard deviations below the gender-specific mean of normal young adults. RESULTS: The study included 200 geriatric inpatients; 96 (48.0%) were men, and the mean age was 74.49±6.32 years. Sarcopenia was detected in 28 (14%) of the patients. Diabetes mellitus was associated with a significantly lower sarcopenia prevalence (p=0.006). The risk of sarcopenia was 9.046 times higher in malnourished patients. The sarcopenia group had more deaths (p=0.012). CONCLUSION: Sarcopenia in geriatric inpatients increased the length of hospital stay and mortality. Our findings may guide future studies examining the relationship between sarcopenia and mortality among elderly inpatients in other hospitals.