Impact of early admission in labor on method of delivery.

OBJECTIVE: The effect of the timing of admission in labor unit on the method of delivery was evaluated in a cohort study. METHOD: Four hundred and sixty six low-risk nulliparous women who were admitted in the labor unit in latent phase (group 1) were compared with 329 parturient women who were admitted in the active phase (group 2) to determine rate of and reasons for cesarean section, cervical dilation at the time of cesarean, and the rate of labor augmentation. RESULT: The number of cesarean deliveries in group 1 was greater than that in the group 2 (301 vs 80, p<0.0001 ). The main reason for cesarean section in group 1 was dystocia, and in 2, fetal distress. The rate of cesarean section in the women who were augmented was greater in group 1 than in group 2 (54% vs 23%, p<0.0001). CONCLUSION: Later admission in labor increases the rate of spontaneous vaginal delivery in low risk nulliparous women.     

Predictive role of PI-RADSv2 and ADC parameters in differentiating Gleason pattern 3 + 4 and 4 + 3 prostate cancer

Purpose

To compare the predictive roles of qualitative (PI-RADSv2) and quantitative assessment (ADC metrics), in differentiating Gleason pattern (GP) 3 + 4 from the more aggressive GP 4 + 3 prostate cancer (PCa) using radical prostatectomy (RP) specimen as the reference standard.

Methods

We retrospectively identified treatment-naïve peripheral (PZ) and transitional zone (TZ) Gleason Score 7 PCa patients who underwent multiparametric 3T prostate MRI (DWI with b value of 0,1400 and where unavailable, 0,500) and subsequent RP from 2011 to 2015. For each lesion identified on MRI, a PI-RADSv2 score was assigned by a radiologist blinded to pathology data. A PI-RADSv2 score ≤ 3 was defined as “low risk,” a PI-RADSv2 score ≥ 4 as “high risk” for clinically significant PCa. Mean tumor ADC (ADC_T), ADC of adjacent normal tissue (ADC_N), and ADC_ratio (ADC_T/ADC_N) were calculated. Stepwise regression analysis using tumor location, ADC_T and ADC_ratio, b value, low vs. high PI-RADSv2 score was performed to differentiate GP 3 + 4 from 4 + 3.

Results

119 out of 645 cases initially identified met eligibility requirements. 76 lesions were GP 3 + 4, 43 were 4 + 3. ADC_ratio was significantly different between the two GP groups (p = 0.001). PI-RADSv2 score (“low” vs. “high”) was not significantly different between the two GP groups (p = 0.17). Regression analysis selected ADC_T (p = 0.03) and ADC_ratio (p = 0.0007) as best predictors to differentiate GP 4 + 3 from 3 + 4. Estimated sensitivity, specificity, and accuracy of the predictive model in differentiating GP 4 + 3 from 3 + 4 were 37, 82, and 66%, respectively.

Conclusions

ADC metrics could differentiate GP 3 + 4 from 4 + 3 PCa with high specificity and moderate accuracy while PI-RADSv2, did not differentiate between these patterns.

     

Functional interaction with filamin A and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca2+-activated K+ (SK2) channel

For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca²⁺-activated K⁺ channels (K_Ca2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile. Here, we demonstrate that filamin A, a cytoskeletal protein, augments the trafficking of SK2 channels in cardiac myocytes. The trafficking of SK2 channel is Ca²⁺-dependent. Further, the Ca²⁺ dependence relies on another channel-interacting protein, α-actinin2, revealing a tight, yet intriguing, assembly of cytoskeletal proteins that orchestrate membrane expression of SK2 channels in cardiac myocytes. We assert that changes in SK channel trafficking would significantly alter atrial action potential and consequently atrial excitability. Identification of therapeutic targets to manipulate the subcellular localization of SK channels is likely to be clinically efficacious. The findings here may transcend the area of SK2 channel studies and may have implications not only in cardiac myocytes but in other types of excitable cells.Small-conductance Ca²⁺-activated K⁺ (SK or K_Ca2) channels are highly unique in that they are gated solely by changes in intracellular Ca²⁺ (Ca²⁺_i) concentration. Hence, the channels function to integrate changes in Ca²⁺ concentration with changes in membrane potentials. SK channels have been shown to be expressed in a wide variety of cells (1–3) and mediate afterhyperpolarizations following action potentials in neurons (1, 4, 5). We have previously documented the expression of several isoforms of SK channels in human and mouse atrial myocytes that mediate the repolarization phase of the atrial action potentials (6, 7). We further demonstrated that SK2 (K_Ca2.2) channel knockout mice are prone to the development of atrial arrhythmias and atrial fibrillation (AF) (8). Conversely, a recent study by Diness et al. suggests that inhibition of SK channels may prevent AF (9). Together, these studies underpin the importance of the precise control for the expression of these ion channels in atria and their potential to serve as a future therapeutic target for AF.Current antiarrhythmic agents target the permeation and gating properties of ion channel proteins; however, increasing evidence suggests that membrane localization of ion channels may also be pharmacologically altered (10). Furthermore, a number of disorders have been associated with mistrafficking of ion channel proteins (11, 12). We have previously demonstrated the critical role of α-actinin2, a cytoskeletal protein, in the surface membrane localization of cardiac SK2 channels (13, 14). Specifically, we demonstrated that cardiac SK2 channel interacts with α-actinin2 cytoskeletal protein via the EF hand motifs in α-actinin2 protein and the helical core region of the calmodulin (CaM) binding domain (CaMBD) in the C terminus of SK2 channel. Moreover, direct interactions between SK2 channel and α-actinin2 are required for the increase in cell surface localization of SK2 channel.Here, to further define the functional interactome of SK2 channel in the heart, we demonstrate the role of filamin A (FLNA), another cytoskeletal protein, in SK2 channel surface membrane localization. In contrast to α-actinin2 protein, FLNA interacts not with the C terminus, but with the N terminus of the cardiac SK2 channel. FLNA is a scaffolding cytoskeletal protein with two calponin homology domains that has been shown to be critical for the trafficking of a number of membrane proteins (15–19). Our data demonstrate that FLNA functions to enhance membrane localization of SK2 channels. Moreover, using live-cell imaging, we demonstrate the critical roles of Ca²⁺_i on the membrane localization of SK2 channel when the channels are coexpressed with α-actinin2, but not FLNA. A decrease in Ca²⁺_i results in a significant decrease in SK2 channel membrane localization. Our findings may have important clinical implications. A rise in Ca²⁺_i—for example, during rapid pacing or atrial tachyarrhythmias—is predicted to increase the membrane localization of SK2 channel and result in the abbreviation of the atrial action potentials and maintenance of the arrhythmias.     

Screening colonoscopy in the initial workup of bariatric surgery patients: guidelines are needed

Background

Cancer is one of the most common causes of death among morbidly obese individuals. Obese individuals have a well-documented increased risk of colon cancer. No guidelines are available for the workup of bariatric surgery patients in relation to colon cancer.

Methods

The indications for screening colonoscopy at the Bariatric and Metabolic Institute Abu Dhabi (BMI Abu Dhabi) include all patients older than 50 years [40 years if patients are United Arab Emirates (UAE) nationals] with unexplained abdominal symptoms, anemia of unknown cause, or a family or personal history of colonic pathology. This study retrospectively reviewed the charts of all the patients who had colonoscopy during the period January 2009 to January 2013. The patients were divided into two groups: group A [patients with a body mass index (BMI) > 30 kg/m²] and group B (patients with a BMI < 30 kg/m²). The demographics and the prevalence of polyps and cancer in the two groups were compared.

Results

During the study period, 341 colonoscopies were performed: 137 for patients with a BMI higher than 30 kg/m² (mean age, 44 years) and 204 for patients with a BMI lower than 30 kg/m² (mean age, 46 years) (P > 0.05). The overall prevalence of adenomatous polyps was 6.74 % and that of cancer was 1.75 %. Further analysis showed that the prevalences of adenomatous polyps and cancer were respectively 12.4 and 2.1 % for the patients with a BMI higher than 30 kg/m², whereas the prevalences were respectively 2.9 and 0.9 % for the patients with BMI lower than 30 kg/m² (P < 0.001).

Conclusion

The risk for the development of colonic adenomatous polyps and cancer is high among young obese individuals in the Middle East. Guidelines are needed to establish criteria for screening in this group of individuals.     

The effect of nettle (Urtica dioica) supplementation on the glycemic control of patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

Type 2 diabetes mellitus (T2DM) is a major health problem, worldwide, that is associated with increased morbidity and mortality. Several randomized controlled clinical trials (RCTs) have investigated the effect of nettle (Urtica dioica) supplementation on markers of glycemic status in patients with T2DM, with conflicting results. Therefore, the present study assessed the effect of nettle on some glycemic parameters in patients with T2DM. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science, from database inception up to June 2019, to identify RCTs investigating the effect of nettle supplementation on glycemic markers, including fasting blood sugar (FBS) concentrations, insulin levels, homeostasis model assessment‐estimated insulin resistance index, and glycosylated hemoglobin percentage in adults with T2DM. The Cochrane Collaboration tool was used to assess the methodological quality of the included studies. Results of this meta‐analysis were reported based on the random effects model. Eight RCTs, comprising 401 participants, were included in the present systematic review and meta‐analysis. Based on the Cochrane Collaboration risk of bias tool, five studies were considered as good quality, one was fair, and two studies were poor, respectively. The results of the meta‐analysis revealed a significant reduction in FBS concentrations (weighted mean difference [WMD]: ?18.01 mg/dl, 95% confidence interval [CI]: ?30.04 to ?5.97, p < .001, I² = 94.6%) following nettle supplementation. However, no significant reduction was observed in insulin levels (WMD: 0.83 Hedges' g, 95% CI: ?0.26 to 1.92, p = .13, I² = 89.4%), homeostasis model assessment‐estimated insulin resistance index (WMD: ?0.22, 95% CI: ?0.83 to 0.40, p = .49, I² = 69.2%), or glycosylated hemoglobin percentage (WMD: ?0.77%, 95% CI: ?1.77 to 0.22, p = .12, I² = 83.0%). The findings of the present study suggest that nettle supplementation may be effective in controlling FBS for T2DM patients. However, further studies are needed to confirm the veracity of these results.     

Urinary tract infection in the users of depot-medroxyprogesterone acetate

BACKGROUND: The effects of progesterone on muscle tone, peristalsis of the ureter and also urinary vasculature may cause urinary tract infection (UTI) in women who use depot-medroxyprogesterone acetate (DMPA) for contraception. METHODS: In a cohort study, 200 women who chose DMPA for contraception were compared with 200 women who used the withdrawal method for urinary infection and urological symptoms after 3 months of consumption. RESULTS: The rate of urinary infection and urological symptoms in the study group were higher than in the control group (p = 0.018, p < 0.0001, respectively). The most common microorganism that caused urinary infection was Escherichia coli. Among the 10 cases who suffered UTI in the case group, there were six women who had UTI in the previous pregnancy as well. CONCLUSION: We do not recommended administering depot-medroxyprogesterone acetate for contraception in women with a history of urinary tract infection in a previous pregnancy.     

A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea

OBJECTIVE: To study the effect of vitamin E in the treatment of primary dysmenorrhoea. DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: A secondary school in Tehran, Iran. POPULATION: Two hundred and seventy-eight girls aged 15-17 years who suffered from primary dysmenorrhoea. METHODS: Participants were given 200 units of vitamin E or placebo twice a day, beginning two days before the expected start of menstruation and continued through the first three days of bleeding. Treatment was continued over four consecutive menstrual periods. MAIN OUTCOME MEASURES: The severity and duration of pain, and the amount of menstrual blood loss, at two and four months. A visual analogue scale (VAS) was used to record pain, and a validated Pictorial Blood Loss Assessment Chart (PBLAC) to measure menstrual loss. RESULTS: In the vitamin E group, pain severity was lower with vitamin E at two months (median VAS score 3 vs 5, P > 0.001) and four months (0.5 vs 6, P > 0.001), pain duration was shorter at two months (mean 4.2 [7.1] hours vs 15 [17], P > 0.001) and at four months (1.6 [4.0] hours vs 17 [18] hours, P > 0.0001), and blood loss assessed by PBLAC score was lower at two months (54 [31] vs 70 [40], P > 0.0001) and at four months (46 [28] vs 70 [37], P > 0.0001). CONCLUSION: Vitamin E relieves the pain of primary dysmenorrhoea and reduces blood loss.     

Comparative assessment of the sealing ability of Nd:YAG laser versus a new desensitizing agent in human dentinal tubules: a pilot study

Dentinal hypersensitivity is a painful condition that occurs following periodontal treatment. Many treatment alternatives have been considered for this problem, including treatments with laser and dentinal adhesives. This study compared the sealing ability of Nd:YAG laser versus a new resin in scanning electron microscopy (SEM) micrographs. Ten human premolars were sectioned yielding 30 specimens of each premolar, which were randomly divided into three groups. The laser group was irradiated by Nd:YAG laser (1 W, 10 Hz, 60 s), the resin group was treated with the new Seal & Protect resin according to the manufacturer’s instructions, and the third group served as the control group and did not receive any interventions. After preparation and gold coating of the samples, they were photographed by SEM at two magnifications (1500× and 4000×). The number and diameter (μm) of the dentinal tubules were recorded in selected fields, and analysis of variance (ANOVA) and Tukey tests were used to determine significant differences between groups. The ANOVA results revealed significant differences in both the mean number (P < 0.001) and diameter (P < 0.05) among the three groups. Further statistical analysis showed a significant difference between the laser group and the resin group in both outcome measures (P < 0.05). Thus, both Nd:YAG laser and the new resin reduced the number and diameter of open dentinal tubules, a result that also explains the desensitization mechanism of these interventions. We further conclude that application of the new resin is more effective than Nd:YAG laser in minimizing the number and diameter of exposed dentinal tubules.     

Electrolytic lesion of the nucleus raphe magnus reduced the antinociceptive effects of bilateral morphine microinjected into the nucleus cuneiformis in rats

Several lines of investigation show that the rostral ventromedial medulla is a critical relay for midbrain regions, including the nucleus cuneiformis (CnF), which control nociception at the spinal cord. There is some evidence that local stimulation or morphine administration into the CnF produces the effective analgesia through the nucleus raphe magnus (NRM). The present study tries to determine the effect of morphine-induced analgesia following microinjection into the CnF in the absence of NRM. Seven days after the cannulae implantation, morphine was microinjected bilaterally into the CnF at the doses of 0.25, 1, 2.5, 5, 7.5 and 10 microg/0.3 microl saline per side. The morphine-induced antinociceptive effect measured by tail-flick test at 30, 60, 90 and 120 min after microinjection. The results showed that bilateral microinjection of morphine into the CnF dose-dependently causes increase in tail-flick latency (TFL). The 50% effective dose of morphine was determined and microinjected into the CnF (2.5 microg/0.3 microl saline per side) in rats after NRM electrolytic lesion (1 mA, 30 s). Lesion of the NRM significantly decreased TFLs, 30 (P<0.01) and 60 (P<0.05) but not 90-120 min after morphine microinjection into the CnF, compared with sham-lesion group. We concluded that morphine induces the analgesic effects through the opioid receptors in the CnF. It is also appeared that morphine-induced antinociception decreases following the NRM lesion but it seems that there are some other descending pain modulatory pathways that activate in the absence of NRM.