Comparison of laparoscopic and hysteroscopic surgical treatments for isthmocele: A prospective cohort.

Objective: To evaluate the clinical outcomes of laparoscopic and hysteroscopic surgical approaches for treating symptomatic isthmocele and identify their associated factors. Materials and Methods: Forty-six patients with symptomatic isthmocele diagnosed using transvaginal saline infusion sonohysterography were enrolled in this prospective cohort study. Patients underwent either laparoscopic or hysteroscopic isthmoplasty based on their residual myometrial thicknesses and fertility desires and were subsequently followed by clinical and ultrasonographic examinations. Results: Twenty-two patients underwent laparoscopy and 24 underwent hysteroscopic surgery. At baseline, there was no significant difference in the mean age and years since the last cesarean section between the two groups. However, the hysteroscopy group had a higher mean parity and previous cesarean sections (p=0.00, 0.03). The most common symptoms were abnormal uterine bleeding, infertility, and dysmenorrhea. The mean baseline residual myometrial thickness was significantly higher in the laparoscopy group (p=0.00), and only laparoscopic surgery led to a significant increase in residual myometrial thickness in patients (p=0.00). Both procedures significantly reduced abnormal uterine bleeding (p=0.00), but only laparoscopy reduced infertility (p=0.00) and hysteroscopy reduced dysmenorrhea (p=0.03). Hysteroscopy showed better symptom resolution in younger patients (p=0.01), whereas age did not affect laparoscopy outcomes. Conclusion: Both approaches showed similar effectiveness in resolving abnormal uterine bleeding, with laparoscopy excelling in infertility resolution and hysteroscopy excelling in dysmenorrhea resolution.

Moving Forward: A Close Look at Healing Process After Traumatic Parental Death.

Recovery from traumatic grief after parental loss is a challenging and gradual process. The current study aimed to capture the rich and nuanced experiences of adolescents' healing process after traumatically losing their parent(s). A phenomenological approach was utilized for data collection and analysis. To reach the research aim, interviews with 15 Iranian adolescents who had lost their parent(s) at least three-year ago were conducted. Two main themes from Colaizzi's analysis including Grief work and Rebuilding new life were extracted from data. Findings highlight an understanding of how adolescents with an experience of traumatic parental death would heal and could provide valuable insights into creating successful interventions and support systems tailored to help them cope with the devastating effects of traumatic loss and grief.

Assessment of the clinical outcomes and complications of hysteroscopic and laparoscopic approaches in the treatment of symptomatic isthmocele: An observational study.

OBJECTIVES: To investigate the outcomes of patients undergoing laparoscopic or hysteroscopic approaches for isthmoplasty. METHODS: A total of 99 isthmocele patients with an average age of 38.45 ± 4.72 years were included in the 2 years of this retrospective cohort study. Forty-five underwent laparoscopic and 54 underwent hysteroscopic isthmocele excision and myometrial repair. RESULTS: Pain scores were significantly higher in the hysteroscopy group before the procedure, but there were no significant pain score differences after the surgery. In 1 year of follow up, dysmenorrhea and dyspareunia were higher among hysteroscopy patients. Furthermore, hysteroscopy significantly improved postmenstrual spotting after surgery better than laparoscopy, but in the follow up, there was no significant difference between the two groups in this regard (mean rank for hysteroscopy vs. laparoscopy: 32.30 vs. 37.48, U = 418, P = 0.29). CONCLUSION: In patients with a history of infertility, ectopic pregnancy, lower gravidity, lower parity, and a lower number of cesarean sections, laparoscopic isthmoplasty is preferred over the hysteroscopic approach. Both methods have similar effects on midcycle vaginal bleeding, duration of postmenstrual spotting, and pain. However, a higher rate of dyspareunia and dysmenorrhea could be associated with hysteroscopy.

Synthetic lethality of drug-induced polyploidy and BCL-2 inhibition in lymphoma.

Spontaneous whole genome duplication and the adaptive mutations that disrupt genome integrity checkpoints are infrequent events in B cell lymphomas. This suggests that lymphomas might be vulnerable to therapeutics that acutely trigger genomic instability and polyploidy. Here, we report a therapeutic combination of inhibitors of the Polo-like kinase 4 and BCL-2 that trigger genomic instability and cell death in aggressive lymphomas. The synthetic lethality is selective for tumor cells and spares vital organs. Mechanistically, inhibitors of Polo-like kinase 4 impair centrosome duplication and cause genomic instability. The elimination of polyploid cells largely depends on the pro-apoptotic BAX protein. Consequently, the combination of drugs that induce polyploidy with the BCL-2 inhibitor Venetoclax is highly synergistic and safe against xenograft and PDX models. We show that B cell lymphomas are ill-equipped for acute, therapy-induced polyploidy and that BCL-2 inhibition further enhances the removal of polyploid lymphoma cells.

The older adults' experiences of living in the nursing home during the COVID-19 pandemic: A qualitative study in Iran.

AIM: This study aimed to describe the experiences of older adults living in a nursing home during the COVID-19 pandemic. DESIGN: A qualitative descriptive study. METHODS: In present study, 20 older adults living in a nursing home in Rasht, northern Iran, participated. Purposeful sampling was applied until data saturation. The qualitative content analysis was done according to the steps proposed by Zhang and Wildemuth. RESULTS: The central theme was "Intensification of life problems in the nursing home", which emerged from the 115 primary codes, 4 main categories and 7 subcategories. The main categories included "feelings about COVID-19," "intensification of isolation and loneliness," "imprisonment and feeling forgotten" and "difficulty in adapting". CONCLUSION: Quarantine and special protocols have aggravated the hardships of life for older adults, and they experienced negative emotions in the nursing home. However, the older adults hoped that the situation would improve, and the pandemic would end.

Assessing The Role and Accuracy of Ultrasonographic Imaging in The Diagnosis of Deep Infiltrating Endometriosis: A Cross-Sectional Study.

BACKGROUND: Deep infiltrating endometriosis (DIE) is described as an endometriotic tissue that penetrates more than 5 mm under the peritoneal surface. It's suggested that trans vaginal sonography (TVS) is 79% sensitive and 94% specific in the assessment of intestinal DIE. Considering the possibility that DIE ultrasonography (rectal and\or vaginal ultrasonography) might be more accurate, we designed this study to assess this study to evaluate the accuracy of DIE ultrasonography. MATERIALS AND METHODS: In this retrospective cross-sectional study, we designed and conducted this study from 2019 to 2020 on patients suspected of severe endometriosis. Our patients underwent ultrasonographic imaging and based on the results became candidates for surgery. We compared histopathological results with sonographic findings using crosstabulation and chi-square tests were used to measure accuracy. P<0.05 were considered statistically significant. RESULTS: Following pathological assessments of 109 cases, 97 cases had ovarian endometrioma, 42 cases had intestinal involvement and 56 cases had uterosacral DIE. The results for accuracy were as the following; uterosacral ligament (USL) involvement SE: 96.4% and SP: 59.1%; intestinal involvement SE: 97.6% and SP: 73.8%; and Cul de sac involvement with SE: 100% and SP: 50.8%. With regards to ovarian endometrioma, ultrasonographic imaging was 99.0% sensitive and 84.6% specific. With regards to intestinal involvement, ultrasonography performed a reliable overall diagnosis (97.6% sensitive and 73.8% specific). However, the results showed lower accuracy regarding the level of intestinal involvement. The accuracy for other sites and cavities was low except for ovarian endometrioma. CONCLUSION: The results of the present study demonstrated that pre-operative TVS and Transrectal ultrasound (TRUS) can be a helpful paraclinical tool in the assessment and diagnosis of DIE and endometriosis in general and particularly with adnexal and bowel lesions, it can have some shortcomings with respect to cul de sac and USLs.

TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma.

To identify drivers of sensitivity and resistance to Protein Arginine Methyltransferase 5 (PRMT5) inhibition, we perform a genome-wide CRISPR/Cas9 screen. We identify TP53 and RNA-binding protein MUSASHI2 (MSI2) as the top-ranked sensitizer and driver of resistance to specific PRMT5i, GSK-591, respectively. TP53 deletion and TP53R248W mutation are biomarkers of resistance to GSK-591. PRMT5 expression correlates with MSI2 expression in lymphoma patients. MSI2 depletion and pharmacological inhibition using Ro 08-2750 (Ro) both synergize with GSK-591 to reduce cell growth. Ro reduces MSI2 binding to its global targets and dual treatment of Ro and PRMT5 inhibitors result in synergistic gene expression changes including cell cycle, P53 and MYC signatures. Dual MSI2 and PRMT5 inhibition further blocks c-MYC and BCL-2 translation. BCL-2 depletion or inhibition with venetoclax synergizes with a PRMT5 inhibitor by inducing reduced cell growth and apoptosis. Thus, we propose a therapeutic strategy in lymphoma that combines PRMT5 with MSI2 or BCL-2 inhibition.

Death and Dying in a Digitalized World.

The impact of digitalization on the topic of death and dying seems to be accelerated in recent years. This study aimed to explore the online ways people used to overcome grief and used the COVID-19 restrictions as an example. Thirty-two bereaved participants were interviewed and the data were analyzed using the constructive grounded theory method. Three main themes were extracted from the data: 1) an online way to remember; 2) digitalization of social support, and 3) continuing the bonds. Findings highlighted the important and inevitable role of the digital world in the grief process when there is a restriction in holding usual ceremonies.

Accuracy of transvaginal and transrectal ultrasounds in the diagnosis of endometriosis: A retrospective cohort study.

Background: Early diagnosis and appropriate treatment of endometriosis are vital and may prevent subsequent complications. Objective: To investigate the diagnostic accuracy of transvaginal ultrasound sonography (TVUS) and transrectal ultrasound sonography for detecting endometriosis considering the age and body mass index (BMI). Materials and Methods: This was a retrospective cohort study of 119 women scheduled for surgery in a tertiary health care center for clinically suspected endometriosis. Married and virgin women underwent TVUS and transrectal ultrasound sonography, respectively, before laparoscopic excision of endometriotic lesions. Results: The accuracy of TVUS in the diagnosis of right endometrioma in women with a normal BMI was superior to that in women with a BMI ≥ 30 (95.6% vs. 75.3%; p < 0.001). For the detection of left endometrioma in women with a normal BMI, TVUS demonstrated a sensitivity of 96.9% and a negative predictive value of 92.9%, which was significantly superior to TVUS in women with obesity (sensitivity: 77.4%, negative predictive value: 58.6%). The accuracy of TVUS in the diagnosis of left endometrioma in women under 35 yr was superior to that in women older than 35 yr (93.2% vs. 77.9%; p = 0.04). Similarly, the accuracy of TVUS in the diagnosis of right endometrioma in women under 35 yr was superior to TVUS in women older than 35 yr (86.5% vs. 73.3%; p = 0.04). Conclusion: Ultrasound can be a useful technique for detecting endometriosis when used adjunctively with the patient's history and physical findings, especially age and BMI.

Personality and Post-Traumatic Growth: the Mediating Role of Career Adaptability Among Traumatized Adolescents.

Trauma needs special attention during the sensitive period of adolescence, which already involves its own psychological challenges and vocational tasks. Coping with trauma requires adaptation. From the perspective of the career construction model of adaptation, career adaptability provides psycho-social resources that promote adaptation. Using this model, the aim of the present study was to investigate the relationship between personality and post-traumatic growth via career adaptability. A total of 266 Iranian adolescents who had experienced the sudden death of a parent recruited. They then completed the Big Five Questionnaire, Post-traumatic Growth Inventory, and Career Adapt-abilities Scale. The results showed career adaptability partially mediated the relationship between neuroticism and openness and post-traumatic growth. In addition, the findings confirmed the full mediator role of career adaptability in the relationship between conscientiousness and post-traumatic growth. The results also indicated a direct relationship between extraversion and post-traumatic growth, but no relationship between agreeableness and post-traumatic growth. These results emphasized the essential role of career adaptability in empowering traumatized adolescents.

Risk Factors for Anti Mullerian Hormone Decline after Laparoscopic Excision of Endometrioma: A Prospective Study.

BACKGROUND: Laparoscopic excision of ovarian endometrioma is believed to decrease the ovarian reserve, but the risk factors of declining ovarian reserve are not well studied. This study aimed to determine the risk factors of anti mullerian hormone (AMH) decline after laparoscopic surgery of endometrioma.
Materials and Methods: This prospective study was recruited in Yas and Arash Hospitals affiliated to Tehran University of Medical Sciences from 2020 to 2021. Women between 18-45 years with ovarian endometriomas with a diameter greater than 3 centimeters who were candidates for laparoscopy were included. AMH, luteinizing hormone (LH),
and follicular stimulating hormone (FSH) as well as cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) were obtained and compared pre and postoperatively. Indeed, the relation of AMH decline rate and the demographic, symptoms and endometrioma characteristics were investigated either.
Results: In this study, 100 women were recruited. The mean ± SD age of the participants was 29.08 ± 4.6. AMH (P<0.000) and LH (P=0.013) declined significantly postoperatively. Whereas, no significant difference was observed between pre and postoperative FSH (P=0.520). AMH decline rate was 30.07 ± 2.30% and didn't have significant relation with the demographic characteristics, preoperative AMH, and the amount of CA125. Otherwise in the multivariate analysys, CA125 (P=0.160) and the grade of endometriosis (P=0.05) had significant correlation with AMH decline rate.
Conclusion: Ovarian reserve decline after laparoscopic excision of endometrioma. Otherwise, there may no specific risk factor to predict the degree of ovarian reserve decline. Therefore, the selection of patients for laparoscopic excision of endometrioma should be taken more cautiously as the ovarian reserve diminishes even in the patients with the lowest risks.

Comparing the effect of adjunctive N-acetylcysteine plus low dose contraceptive with low dose contraceptive alone on recurrence of ovarian endometrioma and chronic pelvic pain after conservative laparoscopic surgery: a randomised clinical trial study.

This study aimed to compare the effectiveness of NAC plus low dose contraceptive with low dose contraceptives alone. This was a randomised trial on a sample of women who underwent conservative laparoscopic surgery for ovarian endometrioma. Patients were randomly assigned either to the NAC plus low dose contraceptive group (n = 48) or low dose contraceptive alone (n = 52). To evaluate the recurrence rate transvaginal ultrasound was performed. Pelvic pain was assessed using a visual analogue scale (VAS). All assessments were performed at two points in time: 3 and 6 months post-surgery and compared between the two regimens. The findings indicated that reduction in the recurrence rate of endometrioma and pelvic pain were similar between both groups. The findings showed that adding N-acetylcysteine to low dose contraceptive treatment has a similar effect in reducing the recurrence rate of endometrioma and pelvic pain when compared to low dose contraceptives alone.Impact statementWhat is already known on this subject? Endometriosis is a frequent benign disease-producing inflammatory response with mild to severe symptoms. Although surgical removal of ectopic lesions is the first-line intervention, the recurrence rate of the disease is high. Thus this study aimed to compare the effectiveness of N-acetylcysteine plus low dose contraceptive with low dose contraceptive alone.What do the results of this study add? The findings showed that adding N-acetylcysteine to low dose contraceptive treatment has a similar effect in reducing the recurrence rate of endometrioma and pelvic pain when compared to low dose contraceptives alone.What are the implications of these findings for clinical practice and/or further research? It is recommended to increase the duration of drug administration in future studies.

Beyond a traumatic loss: The experiences of mourning alone after parental death during COVID-19 pandemic.

Millions of adolescents around the world lost their loved ones due to the COVID-19 pandemic; at the same time, health protocols in many countries do not allow mourners to practice their familiar rituals around death and dying. This study explored the experience of 15 Iranian adolescents who had lost their parent(s) during the pandemic through a phenomenological approach. Two main themes including distress in a shattered life and crisis in crisis were extracted from the interviews. Findings highlight the importance of immediate and alternative ways of support for adolescents who lost their parents during the pandemic.

Fertility outcomes subsequent to medical and surgical treatment for ectopic pregnancy: A retrospective cohort study in Iran.

BACKGROUND: Ectopic pregnancy (EP) and its treatment methods may affect subsequent fertility outcomes. OBJECTIVE: To compare methotrexate (MTX), laparoscopic salpingostomy, and salpingectomy methods of EP treatment and their effects on fertility outcomes. MATERIALS AND METHODS: This retrospective cohort study was performed on women receiving a definitive diagnosis of tubular EP from 2014 to 2017 at Arash Medical Center, Tehran, Iran. In total, 194 women were studied, of which 64 were treated with MTX, 52 underwent salpingostomy, and 78 underwent salpingectomy, depending on their clinical status. Basic information, obstetrics history, and major outcomes of the treatment after an 18-month follow-up, including recurrence of EP, miscarriage, and successful intrauterine pregnancy (IUP), were recorded and variables were compared among the three groups. RESULTS: There was no significant difference in fertility outcomes among the three groups. Among the studied variables, predictors of successful IUP after EP treatment were multiparity (Hazard Ratio (HR): 1.37; 95%CI: 1.06-1.77), no history of miscarriage (HR: 2.37; 95%CI: 1.01-5.56), and a higher number of live births (HR: 1.54; 95%CI: 1.01-2.37). On the other hand, predictors of EP recurrence included nulliparity (HR: 1.61; 95%CI: 1.02-2.53) and a lower number of live births (HR: 3.84; 95%CI: 1.43-10.98). The effect of other factors, including the utilized therapeutic modalities, was not statistically significant. CONCLUSION: The current study results demonstrated that after an 18-month follow-up, fertility outcomes, including recurrence of EP and successful IUP, were not significantly different among the subjects with EP treated with MTX, salpingostomy, or salpingectomy. Further studies with long-term follow-ups are recommended.

Validation of the Persian version of the Positive Mental Health Scale.

BACKGROUND: Positive mental health (PMH) is a factor of far-reaching salutogenetic importance. The present study aimed at validating the Persian version of the Positive Mental Health Scale (PMH-Scale). METHODS: Reliability and validity of the Persian version of the PMH-Scale were established in an Iranian student sample (N = 573). Internal consistency, convergent and discriminant validity were investigated, and exploratory factor analysis was conducted. Furthermore, it was assessed how PMH scores moderate the association between depressive symptoms and suicide ideation/behavior. RESULTS: The Persian version of the PMH-Scale  was shown to have a unidimensional structure with excellent internal consistency, as well as good convergent and divergent validity. PMH differentiated between participants with higher vs. lower suicide risk. Furthermore, PMH proved to moderate the association between depressive symptoms and suicide ideation/behavior. CONCLUSIONS: The results suggest that the PMH-Scale is a brief, reliable, and valid measure of subjective and psychological well-being that can be used in Iranian student samples and research settings.

ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors.

Inhibition of the extracellular signal-regulated kinases ERK1 and ERK2 (ERK1/2) offers a promising therapeutic strategy in cancers harboring activated RAS/RAF/MEK/ERK signaling pathways. Here, we describe an orally bioavailable and selective ERK1/2 inhibitor, ASN007, currently in clinical development for the treatment of cancer. In preclinical studies, ASN007 shows strong antiproliferative activity in tumors harboring mutations in BRAF and RAS (KRAS, NRAS, and HRAS). ASN007 demonstrates activity in a BRAFV600E mutant melanoma tumor model that is resistant to BRAF and MEK inhibitors. The PI3K inhibitor copanlisib enhances the antiproliferative activity of ASN007 both in vitro and in vivo due to dual inhibition of RAS/MAPK and PI3K survival pathways. Our data provide a rationale for evaluating ASN007 in RAS/RAF-driven tumors as well as a mechanistic basis for combining ASN007 with PI3K inhibitors.

Predictive factors of the need to morcellate in total laparoscopic hysterectomy.

BACKGROUND: Specimen extraction is a major challenge in total laparoscopic hysterectomy (TLH) and tissue morcellation may be needed to extract a large uterus. AIMS: The study aims to determine preoperative factors that could predict the need for uterine morcellation in TLH, and also find the best cut-off values of each measured parameter leading to optimum sensitivity and specificity. MATERIALS AND METHODS: This was a cross-sectional study of women from August 2019 to May 2020 who underwent TLH, with or without salpingo-oophorectomy in our department. We performed bimanual exams preoperatively to estimate the uterine size and recorded the uterine ultrasonographic dimensions and myoma size in myomatous uteri. Receiver operating characteristic (ROC) were used to establish cut-offs that maximised the sensitivity and specificity of each factor in predicting the need for morcellation. Poisson regression was used to calculate the relative risks (RR) of each cut-off. RESULTS: One hundred and sixty-two women were recruited in the study. ROC curves demonstrated maximum sensitivities and specificities with a cross-sectional area of 36.5 cm2 , the largest leiomyoma dimension of 40 mm, uterine length of 10 cm, and bimanual uterine size of 13 weeks. Multiple modified Poisson regression revealed that the strongest predictors of morcellation were the largest leiomyoma diameter of >40 mm (RR: 3.58), the uterine cross-sectional area of >36.5 cm2 (RR: 6.38), and uterine size in the bimanual exam of >13 weeks pregnancy (RR: 3.57). CONCLUSION: The largest leiomyoma diameter, uterine cross-sectional area, and size on a bimanual exam can all be used to predict needing morcellation preoperatively in TLH.

The Effectiveness of Health Belief Model Initiative in Breast Cancer Screening Behaviors among Women Health Volunteers.

Knowledge of screening methods and regular diagnostic tests play an important role in reducing the incidence of cancers and their mortality. We investigated the effectiveness of health belief model initiative in breast cancer screening behaviors among women health volunteers. A quasi-experimental design and non-probability sampling technique was conducted during 2019 in Abhar, Iran. Two out of six health centers were approached and each was recruited in either experimental or control group. Based on the Iranian and standardized version of the Champion's Health Belief Model Scale, the different domains of the scale and breast cancer screening behaviors of eligible women health volunteers (n = 72) were evaluated. Then, seven training sessions were designed and implemented for the intervention group using local language and different educational approaches. The participants were reevaluated according to the same questionnaire three months after the intervention. There was a meaningful difference regarding breast self-exam, knowledge, perceived susceptibility, perceived severity, perceived benefits, and perceived barriers among both the control and intervention groups before and after the intervention. Training programs using health belief model are crucial in developing breast cancer screening behaviors for women health volunteers. Thus, it is recommended that training programs should be conducted using individual behavioral models.

Comparison of the Number of Spindle Cells in Peritoneal Washings between Laparoscopic Myomectomy with Morcellation and Open Myomectomy without Morcellation.

STUDY OBJECTIVE: This study evaluated peritoneal washings for the detection of spindle cells (SCs) in laparoscopic and open myomectomies. DESIGN: Prospective, nonrandomized clinical trial. SETTING: An academic tertiary referral center. PATIENTS: Women suspected of having benign uterine myoma undergoing laparoscopic or open myomectomy from October 2016 to April 2018. INTERVENTIONS: Washing of the peritoneal cavity to detect SCs was performed twice during the laparoscopic myomectomy. The first washing was after the closure of the myometrial incision and before morcellation. The second one was performed after morcellation. The procedure was also performed once during the open myomectomy, after the completion of the myomectomy and the closure of the incision. After a peritoneal washing with 200 mL normal saline, 30 mL liquid was collected and sent to the laboratory for SC detection. Surgical parameters such as operating time, mean change in serum hemoglobin level, complications, length of hospital stay, and readmission were compared between the 2 groups. MEASUREMENTS AND MAIN RESULTS: A total of 150 participants were included in the analysis: 78 in the laparoscopic group and 72 in the open myomectomy group. After morcellation, the incidence of SCs was 2.6% (n = 2) and 6.9% (n = 5) in the laparoscopic and open myomectomy groups, respectively (p = .204). CONCLUSION: SCs were observed in both the laparoscopic and open myomectomy groups. Thus, morcellation alone could not be the cause for SC dissemination, which might also be triggered by the manipulation of myoma(s).