The Impact of Mitral Stenosis on Left Atrial Function Assessed by Two‐Dimensional Speckle Tracking Echocardiography

Aims: The aim of this study is to investigate the effect of mitral stenosis (MS) on left atrial (LA) function using two‐dimensional speckle tracking echocardiography (2DSTE). Methods and Results: The study subjects consisted of 52 patients with asymptomatic MS and 52 control subjects. LA function was assessed using prototype speckle tracking software and manual tracking method. Maximal LA volume (LAVmax) and minimal LA volume (LAVmin) and LA volume before atrial contraction (LAVpre‐a) were measured. Using these volumes, LA reservoir, conduit and booster pump fuction parameters were calculated. Indexed LAVmax, LAVmin, and LAVpre‐a measurements via speckle tracking were highly correlated with manual tracing methods in both groups. Expansion index (67.8 ± 36.4 vs. 148.3 ± 44.2), diastolic emptying index (37.7 ± 12.9 vs. 58.0 ± 8.5), passive emptying (37.3 ± 14.1 vs. 70.4 ± 10.4) and passive emptying index (13.3 ± 6.3 vs. 41.3 ± 10.6) were decreased significantly in MS patients (P < 0.001). In contrast active emptying index (62.6 ± 4.1 vs. 29.5 ± 10.1) increased in MS group (P < 0.001) while active emptying (28.1 ± 13.0 vs. 28.3 ± 6.9) remained same among both groups. Conclusions: This is the first study relating LA volumes and function assessed by 2DSTE to MS. 2D speckle tracking analysis of LA volume is relatively easy and provides more detailed information regarding the changes in LA volumes during the cardiac cycle.     

Long-term impacts of vaginal birth with mediolateral episiotomy on sexual and pelvic dysfunction and perineal pain

Objective: To investigate whether spontaneous vaginal birth with mediolateral episiotomy has any long-term impact on urinary and/or fecal incontinence, sexual dysfunction and perineal pain in primiparous women.

Methods: This matched case-control study included 150 women between 25 and 35 years old who had a singleton childbirth at least five years previously. Patients were grouped as; women who had a spontaneous vaginal delivery with mediolateral episiotomy (Group 1), an elective cesarean delivery (Group 2), and who had no delivery (Group 3). Controls were matched for age and delivery time. Urinary/fecal incontinence were questioned and Female Sexual Function Index (FSFI) questionnaire was completed. Total FSFI and domain scores were compared. Statistical evaluation was performed using One-way ANOVA test or χ² test. Statistical significance was defined as p?Results: No women had urinary/fecal incontinence nor sexual dysfunction. Mean total FSFI points in Group 1 were significantly lower than in Groups 2 and 3 (p?=?0.001). There were significant differences in sexual desire between groups 1 and 3 (p?=?0.005), in arousal and in orgasm between both groups 1 and 2 (p?=?0.001 and p?=?0.038, respectively) and groups 1 and 3 (p?=?0.001 and p?=?0.001, respectively). There was no significant difference between groups 2 and 3 in any parameters or total points.

Conclusions: Vaginal delivery with mediolateral episiotomy is not associated with urinary and/or fecal incontinence and sexual dysfunction but associated with a decreased sexual functioning as well as sexual desire, arousal and orgasm within postpartum five years.     

Progesterone modulates m TOR in the hippocampus of mice after traumatic brain injury

the mechanistic target of rapamycin(m tor) is an intracellular protein kinase that functions as an energy and nutrient sensor in the cellular microenvironment of neurons. modulation of m tor is vital when nutrient and energy sources become limited. hypoxia, traumatic brain injury, cellular energy states, and growth factors all regulate the phosphorylation and total levels of m tor in cells. alterations in the microenvironment induce transduction of signals to downstream proteins by m tor allowing for cells to make the necessary adjustments to counteract stressors and survive. progesterone, a hydrophobic steroid hormone, has been shown in studies of non-neural tissue to be a suppressor of m tor and modulator of m tor phosphorylation. our study tested the effects of progesterone on m tor expression following traumatic brain injury. c57 bl/6 mice were treated with progesterone(8 mg/kg) at 1(intraperitoneal), 6(subcutaneous), 24(subcutaneous), and 48(subcutaneous) hours post closed skull traumatic brain injury. the hippocampus was then harvested 72 hours post injury and prepared for western blot analysis. we found that progesterone significantly decreased total m tor levels in all groups compared to sham treated with vehicle. this was further confirmed by immunostaining showing decreased cytoplasmic m tor levels compared to sham. our study shows progesterone is a significant modulator of m tor levels in the hippocampus of mice following traumatic brain injury.     

Comparison of Ho:YAG laser and pneumatic lithotripsy in the treatment of impacted ureteral stones: An analysis of risk factors

The aim was to compare pneumatic and holmium:yttrium-aluminum-garnet laser in the treatment of impacted ureteral stones with different locations and to identify the risk factors for complications. Between March 2005 and November 2012, a total of 230 patients underwent ureteroscopic lithotripsy for impacted stones. Of the patients, 117 had pneumatic and 113 had laser lithotripsy for the fragmentation of the stones. Treatment outcomes based on evidence of being stone free were evaluated. Preoperative, operative, and postoperative follow-up findings were analyzed and compared. There was a difference between the two groups according to overall stone clearance rate (93.8% vs. 80.3%, p = 0.002). There was no statistically significant difference for distal location between the laser and pneumatic groups (96.8% vs. 91.7%, p = 0.288). For 10 patients with intrarenally migrated stones who were managed with flexible ureterorenoscopy in the same session, laser lithotripsy was more successful than pneumatic for proximal ureteral stone (94.4% vs. 67.9%, p = 0.007). The overall complication rate was 26.1%. There was no statistically significant difference between the two groups (29% vs. 23%, p = 0.296). Multivariate logistic regression analysis revealed that the proximal location was a statistically significant parameter for the occurrence of complications in both groups (p = 0.001 for PL, p = 0.004 for laser). The pneumatic and holmium:yttrium-aluminum-garnet laser lithotripsy are effective in the treatment of distal impacted stones. Both treatments with semirigid ureteroscopy are acceptable for proximal impacted ureteral stones, but holmium laser lithotripsy has an advantage of use with flexible ureteroscope for intrarenally migrated stone.     

Inhibition of dentin matrix‐bound cysteine cathepsins by potassium fluoride

Matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs) can break down unprotected type I collagen fibrils in dentin matrix. This study investigated the use of potassium fluoride (KF) as a potential inhibitor of MMPs and CCs in dentin. Demineralized dentin beams were divided into groups (n = 10 in each group) and incubated in artificial saliva (AS, control), either alone or with one of seven concentrations of KF (6–238 mM fluoride) for 1, 7, and 21 d. After 21 d, all groups were further aged in AS for 6 months. Total MMP activity was screened using the colorimetric MMP assay. The activities of MMP‐2 and MMP‐9 were investigated using gelatin zymography. At the end of each incubation, changes in loss of dry mass and CC‐mediated or total dissolution of collagen peptides were measured via precision weighing, C‐terminal crosslinked telopeptide of type I collagen (CTX), and hydroxyproline (HYP) assays. The beams were examined using scanning electron microscopy. After 21 d, total MMP activities, dry mass loss, and CTX release for the groups exposed to 179 and 238 mM fluoride were significantly lower compared with the control group. After 6 months, all groups showed similar total MMP activity, dry mass loss, and HYP release, and CTX levels were significantly lower when the fluoride concentration was ≥24 mM. Calcium fluoride (CaF₂)‐like precipitates were observed over the beams. In summary, KF significantly inhibited the catalytic activity of dentin matrix‐bound CCs but did not seem to be effective for MMP‐mediated activity.     

IL-17 inhibition in axial spondyloarthritis: current and future perspectives

Introduction: Interleukin (IL)-17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) as well as of other spondyloarthritides. There is a number of substances targeting IL-17, which are at different stages of development in the axSpA indication.

Areas covered: This review summarizes the current evidence on the role of IL-17 in the pathophysiology of axSpA and provided a comprehensive review of clinical and radiographic outcomes as well as of safety data from studies with IL-17A inhibitors secukinumab and ixekizumab. Ongoing studies on other IL-17 inhibitors (bimekizumab, brodalumab and BCD-085) that are being developed are also summarized.

Expert opinion: The development of the IL-17 inhibitors has expanded AS treatment with effective options and confirmed the pathophysiological role of IL-17 in axSpA. IL-17 inhibition showed sufficient efficacy against signs and symptoms of the disease even after the failure of tumor necrosis factor inhibitors, being at the same time reasonably safe.