Comparison of programmed death-ligand 1 expression in adenocarcinoma and squamous cell carcinoma of the cervix in paraffin blocks of patients with cervical cancer.

AIMS: Cervical cancer (CC) is a common malignancy in women, predominantly caused by human papillomavirus. The most subtypes are adenocarcinomas (AC) and squamous cell carcinomas (SCC), which show various features and treatment responses. Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) as Immune checkpoint molecules, play a role in immune evasion. We investigated PD-L1 expression in AC and SCC of the cervix and explored its link to clinical characteristics. METHODS AND RESULTS: The present cross-sectional research was done between 2016 and 2022 on samples in Shahid Beheshti University of Medical Sciences-affiliated hospitals in Iran. Histological tissue samples of CCs (16 AC and 48 SCC) were assessed, and clinical information was obtained by reviewing their medical documents. PD-L1 expression was evaluated by immunohistochemistry and we used the combined positive score. SCC cases showed a higher (not significant) PD-L1 expression. The PD-L1 expression and clinical characteristics were not significantly correlated in both subgroups. CONCLUSION: Although SCC cases exhibited higher PD-L1 expression, this difference was non-significant. More investigations should highlight the role of PD-L1 in CC and the potential benefits of immunotherapy.

Evaluation of the Cutoff Point and Diagnostic Value of the Neutrophil-to-Lymphocyte Ratio in Predicting Ovarian Cancer Compared to Pathological Findings.

PURPOSE: This research aims to establish a neutrophil-to-lymphocyte ratio (NLR) threshold and evaluate its diagnostic accuracy compared to pathological criteria for diagnosing Epithelial Ovarian Cancer (EOC). METHODS: We conducted a cross-sectional study at Imam Hossein Hospital involving 204 women aged 18 and older with confirmed ovarian mass based on pathology. We recorded clinical, pathological, and preoperative blood count data, including neutrophil-to-lymphocyte ratio (NLR). Patients were categorized into malignant and benign ovarian mass groups based on postoperative pathology. The power of NLR to diagnosis of EOC was evaluated using ROC curve. RESULTS: At total, 204 patients (Benign 75.5% vs. Malignant 24.5%) were included in the analysis with mean age of 54.26 ±12.04 yrs in malignant and 46.31±13.21 in benign. In all cases, the proportion of patients with the following tumor markers HE4 (>140 Pm), CA 125 (> 35U/Ml) and CEA (>5 ng/Ml) were 52.45%, 41.67% and 3.43%, respectively, and proportion of abnormal tumor markers was statistically higher in malignant group compared to benign mass (p <0.05).  Odds of having higher NLR levels in the malignancy group was higher than benign group (e.g., OR of 4.45 for NLR in quartile 4 vs. quartile 1).  According to model selection criteria, the full model with including NLR level and age, BMI and tumor markers has best performance for diagnosis of malignancy (AUC =0.87). CONCLUSION: High NLR in combination with tumor markers including CA125, HE4 and CEA were associated with malignancy in patients with ovarian mass. More attention and further examinations should be devoted for patients with ovarian mass having high NLR and abnormal tumor markers levels to detect the probable malignancy as soon as possible.

Validity and Reliability of The Persian Version of Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire: A Psychometric Study.

BACKGROUND: Women with uterine fibroids (UFs) experience many clinical manifestations that affect their quality of life (QOL). The Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) questionnaire is an English instrument specifically designed to assess fibroid-related symptoms and their impact on QOL. This study aims to investigate the reliability and validity of the Persian version of the UFS-QOL questionnaire in Iranian women with UF. MATERIALS AND METHODS: In this psychometric study, women with UFs who presented to Imam Hossein Hospital (Tehran, Iran) between August 2022 and January 2023 were enrolled in this study. A forward-backward approach was applied to translate the UFS-QOL questionnaire into Persian. The reliability of the UFS-QOL questionnaire was assessed by internal consistency and test-retest correlation. Confirmatory factor analysis (CFA) was used to assess convergent validity between items and subscales of the UFS-QOL questionnaire. Pearson's correlation coefficient was used to assess convergence validity between subscales of the UFS-QOL and the World Health Organization Quality of Life Brief Version 26 questionnaire (WHOQOL-BREF-26). RESULTS: Overall, we assessed 226 women with UFs. All subscales of the UFS-QOL questionnaire had acceptable internal consistency (Cronbach's alpha>0.7). Test-retest analysis indicated significant positive correlations between two measurements of all subscales of the UFS-QOL questionnaire: symptom severity (P<0.001), concern (P<0.001), activities (P<0.001), energy/mood (P<0.001), control (P<0.001), self-consciousness (P=0.002), and sexual function (P<0.001). The Kaiser-Meyer-Olkin (KMO) measure value was 0.920, and the result of Bartlett's test of sphericity was significant (P<0.001). CFA identified six factors for the health-related QOL (HRQL) questionnaire, which explained 73.827% of the total variation. Most subscales of the UFS-QOL questionnaire correlated with domains of the WHOQOL-BREF-26 questionnaire (P<0.05). CONCLUSION: The Persian version of the UFS-QOL questionnaire is a valid and reliable instrument to evaluate UFrelated symptoms and QOL among Iranian women.

D-dimer, Fibrinogen and Tumor Marker Levels in Patients with benign and Malignant Ovarian Tumors.

Limited studies have investigated the differences between the levels of plasma coagulants and tumor markers in ovarian cancer. Therefore, we conducted this study to determine and compare the level of coagulation, fibrinolysis and tumor markers in patients with benign and malignant ovarian tumors. This cross-sectional study was conducted between January 2022 and February 2023 in Imam Hossein Hospital on patients with ovarian mass. Laboratory tests included platelet count, PT, INR, PTT, fibrinogen and D-dimer were sent to the pathology laboratory to be examined by a pathologist. Based on histopathology, patients were divided into benign, borderline and malignant groups. Logistic regression was used for determine predictors of malignancy. Receiver operating characteristics (ROC) curves and their corresponding 95% CI were determined for the predictor value of the full model. From 141 investigated patients, tumor type in 124 (87.94%) patients were benign, in 12 (8.51%) was malignant and in 5 (3.55%) was borderline. D-dimer, Ca-125 and HE4 were significantly higher in the patients with malignant tumor type (P<0.001), whereas AFP was significantly higher in patients with borderline tumor type (P<0.001). With one-unit increase in D-dimer odds of borderline/malignant tumor 0.3% increases (OR=1.003, 95% CI: 1.001, 1.006) and with one-unit increase in Ca-125 odds of borderline/malignant tumor 1% increases (OR=1.01, 95% CI: 1.003, 1.02). We found that plasma fibrinogen, D-dimer and Ca-125 levels are independently associated with malignant ovarian tumors and combined use of these markers has the high discriminant power for distinction of benign and malignant ovarian masses.
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The Effect of Radiofrequency Therapy on Sexual Function in Female Cancer Survivors (Gynecologic and Breast) and Non-cancer Menopausal Women: A Single-Arm Trial.

Introduction: Up to 90% of postmenopausal women and female cancer survivors may be affected by the genitourinary syndrome of menopause (GSM), with a negative impact on sexual function and quality of life. A novel energy-based device among the treatment options for GSM is radiofrequency therapy (RFT). RFT is a treatment option that uses energy from radio waves to heat the tissue. The objective of this study was to assess the impact of RFT on sexual function in female cancer survivors (gynecologic and breast) and non-cancer menopausal women. Methods: In a single-arm prospective trial, the efficacy of RFT in both female cancer survivors (gynecologic and breast) and non-cancer menopausal women with sexual dysfunction at a tertiary and referral center (Imam Hossein Medical Center, Tehran, Iran) was evaluated between April 2022 and December 2022. The study protocol consisted of 3 monthly RFT sessions. Examination was performed at baseline (T0) and 3 months after the last RFT session (T1). The primary outcome was sexual function, which was assessed using the Female Sexual Function Index (FSFI). In addition, adverse events were evaluated during treatment and at T1. Results: A total of 37 female cancer survivors (mean [SD] age: 49.4 [8.9] years) and 37 non-cancer menopausal women (mean [SD] age: 53.8 [5.5] years) were enrolled. Patients exposed to RFT showed a significant improvement in FSFI scores when compared to baseline scores for both female cancer survivors (13.07, 95% CI: 12.27 - 13.86) and non-cancer menopausal women (13.18, 95% CI: 12.34 - 14.03). There was no difference in FSFI total score improvement between the two groups (t(72)=0.06, P=0.951). There were no serious adverse events associated with RFT. Conclusion: The efficacy of RFT as a treatment for sexual dysfunction has been demonstrated in both non-cancer menopausal women and female cancer survivors. In both groups, a significant improvement was confirmed.

Endometrial cancer in women with abnormal uterine bleeding: Data mining classification methods.

Background: Over the last decade, artificial intelligence in medicine has been growing. Since endometrial cancer can be treated with early diagnosis, finding a non-invasive method for screening patients, especially high-risk ones, could have a particular value. Regarding the importance of this issue, we aimed to investigate the risk factors related to endometrial cancer and find a tool to predict it using machine learning. Methods: In this cross-sectional study, 972 patients with abnormal uterine bleeding from January 2016 to January 2021 were studied, and the essential characteristics of each patient, along with the findings of curettage pathology, were analyzed using statistical methods and machine learning algorithms, including artificial neural networks, classification and regression trees, support vector machine, and logistic regression. Results: Out of 972 patients with a mean age of 45.77 ± 10.70 years, 920 patients had benign pathology, and 52 patients had endometrial cancer. In terms of endometrial cancer prediction, the logistic regression model had the best performance (sensitivity of 100% and 98%, specificity of 98.83% and 98.7%, for trained and test data sets respectively,) followed by the classification and regression trees model. Conclusion: Based on the results, artificial intelligence-based algorithms can be applied as a non-invasive screening method for predicting endometrial cancer.

Platelet-Rich Plasma in Regenerative Medicine: Possible Applications in Management of Burns and Post-Burn Scars: A Review.

Contribution of platelets in tissue regeneration and their possible application in regenerative medicine, which is primarily mediated via secretion of granular components following platelet activation, has been well established in the recent decades. Therefore, platelet rich plasma (PRP), as a portion of plasma with higher concentrations of platelets than the baseline level, is now an attractive therapeutic option in various medical fields mainly for tissue repair and regeneration following injuries. Burn injuries are devastating trauma with high rate of morbidities affecting several aspects of the patient's life. They require a long-time medical care and high costs. However, even following the best treatment procedures, post-burn scars are inevitable consequence of burn healing process. Therefore, development of new treatment modalities for both burn healing and prevention of post-burn scar establishment seems to be necessary. Regarding the well-known role of PRP in wound healing, here we aimed to provide a comprehensive insight in the possible application of PRP as an adjuvant therapy for the management of burn injuries and subsequent scars. In terms of the following keywords (individually or in combination), original/review articles were searched in PubMed, Scopus, and Google Scholar databases from 2009 to 2021: platelet rich plasma, PRP therapy, platelet biology, platelet function, burn healing, burn scar, scar formation, burn management, wound healing, regenerative medicine. All type of articles or book chapters in English language and relevant data were included in this review. This review initially focused on PRP, its mechanisms of action, preparation methods, and available sources. Then, pathophysiology of burns and subsequent scars were discussed. Finally, their current conventional therapeutic modalities and implication of PRP in their healing process were highlighted.

Synthesis and evaluation of modified lens using plasma treatment containing timolol-maleate loaded lauric acid-decorated chitosan-alginate nanoparticles for glaucoma.

Reducing intraocular pressure (IOP) with eye drops is one of the most common ways to control glaucoma. Low bioavailability and high frequency of administration in eye drops are major challenges in ocular pharmacotherapy. Contact lenses have attracted the attention of scientists in recent decades as an alternative method. In this study, with the aim of long-term drug delivery and better patient compatibility, contact lenses with surface modification and nanoparticles were used. In this study, timolol-maleate was loaded into polymeric nanoparticles made of chitosan conjugate with lauric acid and sodium alginate. Then silicon matrix was mixed with a curing agent (10:1), and the suspension of nanoparticles was added to the precursor and cured. Finally, for surface modification, the lenses were irradiated with oxygen plasma at different exposure times (30, 60, and 150 s) and soaked in different BSA concentrations (1, 3, and 5% w/v). The results showed nanoparticles with a size of 50 nm and a spherical shape were synthesized. The best surface modification of the lenses was for 5 (% w/v) albumin concentration and 150 s exposure time, which had the highest increase in hydrophilicity. Drug release from nanoparticles continued for 3 days and this amount increased to 6 days after dispersion in the modified lens matrix. The drug model and kinetic study show the Higuchi model completely supported the release profile. This study represents the novel drug delivery system to control intra-ocular pressure as a candidate platform for glaucoma treatment. Improved compatibility and drug release from the designed contact lenses would prepare new insight into the mentioned disease treatment.

Comparison of Ki67 index and P16 expression in different grades of cervical squamous intraepithelial lesions.

Background: the assessment of P16 expression and Ki-67 proliferative index is now proposed as an adjunct test for the diagnosis of high-risk precursor lesions for cervical cancer. The aim of the present study was to elucidate the quality expression of P16 and quantification Ki-67 index in different types of cervical intraepithelial neoplasia and also to determine the cutoff for Ki67 index to predict the severity of CIN lesions. Methods: This cross-sectional study was conducted on patients with colposcopic indication. Selected samples with different CIN grades were examined for P16 and Ki-67 index by immunohistochemical (IHC) methods. Results: All LSIL (CIN I) cases were negative for P16, while in 58.7% of HSIL cases (CIN 2/3), P16 was positive. The mean Ki67 index in the present study was 3.13 ± 2.65 in the upper two/third of the squamous epithelium in the LSIL group and 19.04 ±36.40 in the HSIL group, which was statistically significant. Also, the mean Ki67 index in full thickness squamous epithelium in HSIL group was significantly higher than LSIL. The sensitivity of P16 and Ki67 index in our study was 58.73%, 66.67% and the specificity was 100% and 100%, respectively. Conclusion: Assessment of P16 expression and Ki67 index can be used to distinguish low grade (CIN1) intraepithelial lesion from high grade (CIN2/3) intraepithelial or precancerous lesions.

Screening of Lynch syndrome in endometrial cancer in Iranian population with mismatch repair protein by immunohistochemistry.

Background: Lynch syndrome (LS) is one of the commonest genetic cancer syndromes, with an incidence rate of 1 per 250-1000 population. The aim of this study was to evaluate the frequency and characteristics of MMR deficiency in endometrial cancer in Iranian women. Methods: One hundred endometrial carcinoma cases who referred to the gynecological oncology clinic of Imam Hossein Medical Center located in Tehran, Iran, from 2018 to 2020 were included in the study. Immunohistochemistry (IHC) evaluation was performed mainly on the hysterectomy specimens of all endometrial cancer (EC) patients to assess MMR proteins (MLH1, MSH2, MSH6, and PMS2) expression. Results: A total of 23 out of 100 (23%) cases were identified through IHC screening to be MMR-deficient. The most common types were loss of MLH1/PMS2 (17.4%) and solitary MSH2 (17.4%) expressions followed by PMS2/MSH2 loss (13%). MMR deficiency (dMMR) histopathology was significantly overrepresented in patients with family history of cancer or Lynch syndrome (LS) associated cancers (p-values of 0.016 and 0.005, respectively). The rate of myometrial invasion and lower uterine segment involvement were also significantly higher in dMMR EC patients compared to MMR-intact EC (p-value of 0.021 and 0.018, respectively). Conclusion: MMR deficiency, observed in 23% of endometrial cancer cases, was associated with higher rates of poor prognostic factors including myometrial invasion and lower uterine segment involvement. The presence of positive family history of cancer and family history of LS-associated cancer increased the probability of MMR-deficiency in endometrioid endometrial cancer to 47% and 70%, respectively.

A case-control study on the severity postpartum depression among COVID19 positive mother.

BACKGROUND: COVID19 pandemic has caused a variety of psychological problems including panic disorder, anxiety and depression. It is also associated with adverse psychological outcomes in pregnant women. The aim of this study was to compare the severity of postpartum depression in pregnant women with and without COVID-19 during the coronavirus epidemic. METHODS: This case-control study was performed on 102 pregnant women referred to the hospitals of (XXX). Using questionnaire, consisting of demographic and maternal data (age, number of pregnancies, type of delivery, history of any disease, history of drug use, breastfeeding experience, separation of mother from infant due to coronavirus) and score from Edinburgh postnatal depression scale (EPDS) score data from all the participants obtained and analyzed statistically using SPSSv23. RESULTS: The results showed that the mean EPDS score in COVID-positive mothers was 26.64 and in COVID-negative mothers was 24.76, which was statistically significant, p < 0.001. The score did not vary among the two group with respect to age group and type of delivery method. The score was significantly higher among the women with 3-4 pregnancies. CONCLUSION: COVID-positive status is associated with increased postnatal depression among women. Perinatal and postnatal psychological consultancy is required in such patients along with monitoring of maternal and neonate physical and mental health.

IFNG-AS1 and MAF4 long non-coding RNAs are upregulated in acute leukemia patients who underwent bone marrow transplantation.

PURPOSE OF THE STUDY: Acute graft versus host disease (aGVHD) is an immune-mediated reaction that results in impaired immune and body function after allogeneic hematopoietic stem cell transplantation (allo-HSCT). lncRNAs have been discovered as particular T cell regulators, and alloreactive T cells have been known as a critical factor in aGVHD. As a result, we investigated the importance of lnc-MAF4 and IFNG-AS1 expression levels in aGVHD patients versus non-aGVHD patients. MATERIAL AND METHODS: This research included 38 patients with hematological disorders who were undergoing primary allo-HSCT. Human identical siblings or unrelated donors were used to collect stem cell. Samples were taken within days 0, 7, 14, 28, and 52±8 after transplantation. The expression of lncRNA levels was measured using the QRT-PCR technique. And the data were analyzed using GraphPad Prism 6 RESULTS: Our data revealed that LncRNA MAF4 and INFG-AS1 expression levels in aGVHD were not significantly different compared to the non-GVHD group immediately after transplantation, nor at day 7 or 14. However, the aGVHD group showed an overt up-regulation of the two lncRNAs on samples taken at day 28 and 52±8 compared to non-GVHD patients. DISCUSSION: Since the intracellular pathway of these lncRNAs shows a direct relationship with the IFNγ cytokine production resulting in differentiation to TH1 cells and inhibition of differentiation to TH2 cells, they can be, therefore, considered as suitable molecular candidates for the prediction of aGVHD in patients receiving HSCT.

Evaluation of clinical outcomes of neonates born to mothers with coronavirus (COVID-19) in Shahid Beheshti Hospitals.

BACKGROUND: The coronavirus, which is caused by acute respiratory syndrome, appeared in Wuhan, China, in December 2019 and gradually spread around the world until almost all countries became infected with the coronavirus. In Iran, the outbreak of coronavirus began on February 21, 2020, with the report of infection of two people in the city of Qom. The aim of this study is to evaluate the clinical findings of neonates born to pregnant women with corona disease. MATERIALS AND METHODS: During this case study (February 21 to November 30, 2020), out of 88 pregnant mothers who referred to the hospitals of Shahid Beheshti University of Medical Sciences, 44 live neonates were born from 42 pregnant women with COVID-19, who were evaluated for clinical signs by studying their files and reported as a case series, due to limited samples, No statistical analysis of the study was performed. RESULTS: In studies of clinical records of hospitalized mothers and infants, among the polymerase chain reactions (PCRs) provided for all infants, one PCR was reported positive 2 days after birth, whereas this infant 10 min after birth, immediately after routine procedures, due to positive mother's PCR was isolated from the operating room. However, all of the infant's clinical symptoms were normal during the 3-day hospital stay for routine postpartum care. Twenty-eight days after birth, the baby was reevaluated for clinical, laboratory, and chest X-ray symptoms, all of which were normal. The PCR of other neonates was negative, and five intubated neonates, two twin, and two single died, and the other neonates were discharged. In evaluating the clinical records of mothers of these infants, the mean age is 30 years, and the average gestational age is 35 weeks, 32 cases of caesarean section, and 10 cases of normal delivery. CONCLUSION: We describe epidemiological data, demographics, signs and symptoms on admission, laboratory results, comorbidities, infection COVID-19 in the mothers and neonates, chest radiography and computed tomography findings, treatment received for COVID-19, and clinical maternal, fetal, and neonatal outcomes. Due to the fact that the study population is small consist of 42 mothers with COVID-19 infection, among all PCR samples from infants born to COVID-19 positive mothers, the PCR result of one case was positive, and the rest of was negative. Therefore, vertical transmission of COVID-19 through the placenta to the fetus cannot be confirmed or denied, nor can the COVID-19 confirmed or denied the baby's postnatal complication during pregnancy.

Red blood cell alloimmunization in Iran: A Comprehensive review of the literature.

BACKGROUND: Alloimmunization is an immune response against foreign antigens which introduced into the body through transfusion, pregnancy, or transplantation. This phenomenon is a big challenge in patients, which require regular transfusions. In the current study, we tried to have a comprehensive review on the status of alloimmunization in Iran. For this purpose, we searched for papers investigating alloimmunization in transfusion-dependent patients and also in patients with no regular transfusions who are candidate for surgery or who need blood. METHODS: We searched PubMed, Google Scholar, SID, and MAGIRAN databases using the following keywords: "blood transfusion," "alloimmunization," "alloantibodies," "irregular antibodies," "red cell antibodies," and "Iran." No limitation for the date of publication and language of the papers was defined. All the identified records were then screened for the relevance and duplication. RESULTS: A total of 22 papers were included in this study. All of the studies were conducted from 1999 to 2016 and providing alloimmunization data from different cities all over of Iran. In general, the results showed that the most prevalent alloantibodies are anti-Kell (anti-K antigen) and anti-Rh system, mainly anti-E, anti-D, anti-C, and anti-c. CONCLUSION: Anti-Kell and anti-Rh antibodies are the most prevalent antibodies responsible for alloimmunization in Iranian population.

Diagnostic Role of Papanicolaou Smear, Hemoglobin, Blood Group, and Other Clinical Symptoms in Detecting Endometrial Carcinoma: A Clinicopathological Study of 175 Iranian Women with Endometrial Carcinoma.

OBJECTIVES: Endometrial carcinoma (EC) is a common gynecologic malignancy in the female genital tract, especially in postmenopausal women. The current study aimed to analyze Papanicolaou (Pap) smear in patients with EC to assess the relationship between EC and abnormal cells in Pap smear, ABO blood group, and hemoglobin anemia. MATERIALS AND METHODS: A retrospective study was conducted on 175 patients with EC in Imam Hossein Hospital, Tehran, Iran, during the period from 2013 to 2019. The histology information of cases was extracted from the hospital database, and Pap smear slides were taken from pathological archives. The acquired information and slides were then reviewed by an expert pathologist in the hospital. The data were analyzed in SPSS (version 18) by the Chi-square test, Fisher's exact test, and independent-samples t-test. P < 0.05 was assigned as significant. RESULTS: The mean age of patients was 54.47 ± 11.34, ranging from 32 to 85 years, and 31.4% of the patients were premenopausal women. Grade III, invasion ≥ 50% of myometrial, and advanced stage (III and IV) were diagnosed in 30%, 7.4%, and 22.86% of the patients, respectively. The most common histological types of EC were endometrioid (66.9%), papillary (10.3%), and malignant mixed Mullerian tumor (5.7%). The abnormal Pap smear was achieved only in 37 EC patients (21.1%). Endometrial cells, atypical squamous cells of undetermined significance, and atypical glandular cells were observed in 56.8%, 29.7%, and 13.5% of the patients > 40 years of age with abnormal Pap smears, respectively. In patients with normal Pap smears, the most common results were inflammation in 75.1% and atrophy in 14.6% of the patients. Abnormal uterine bleeding was the most important problem observed in patients with EC. CONCLUSION: The efficacy of Pap smear in detecting EC is limited. Therefore, women with EC, >40 years of age, with heavy bleeding, anemia, O blood group, inflammation, and atrophy in Pap smear in the past 3 years need to be precisely checked up for EC. These items can be added as new criteria for EC screening procedures.

Toughening mechanisms of the elytra of the diabolical ironclad beetle.

Joining dissimilar materials such as plastics and metals in engineered structures remains a challenge1. Mechanical fastening, conventional welding and adhesive bonding are examples of techniques currently used for this purpose, but each of these methods presents its own set of problems2 such as formation of stress concentrators or degradation under environmental exposure, reducing strength and causing premature failure. In the biological tissues of numerous animal and plant species, efficient strategies have evolved to synthesize, construct and integrate composites that have exceptional mechanical properties3. One impressive example is found in the exoskeletal forewings (elytra) of the diabolical ironclad beetle, Phloeodes diabolicus. Lacking the ability to fly away from predators, this desert insect has extremely impact-resistant and crush-resistant elytra, produced by complex and graded interfaces. Here, using advanced microscopy, spectroscopy and in situ mechanical testing, we identify multiscale architectural designs within the exoskeleton of this beetle, and examine the resulting mechanical response and toughening mechanisms. We highlight a series of interdigitated sutures, the ellipsoidal geometry and laminated microstructure of which provide mechanical interlocking and toughening at critical strains, while avoiding catastrophic failure. These observations could be applied in developing tough, impact- and crush-resistant materials for joining dissimilar materials. We demonstrate this by creating interlocking sutures from biomimetic composites that show a considerable increase in toughness compared with a frequently used engineering joint.

Pharmacological management of rare coagulation factor deficiencies besides hemophilia.

INTRODUCTION: Rare coagulation factor deficiencies are less-known disorders with variable effects on the patient's life. Management of such patients is a challenge due to the paucity of evidence-based data, more so when patients with these rare disorders encounter a more rare, related condition, like inhibitor development or thrombosis. AREA COVERED: A comprehensive literature search related to RCFDs and management was performed in PubMed in order to discuss therapeutic options and challenges, prophylaxis, management of minor and major surgeries, obstetric and gynecological complications, inhibitor development, and thrombosis. EXPERT OPINION: Although significant changes have occurred in the management of RCFDs in recent years, more evidence-based studies besides expert opinion are needed for optimal management.

Maternal death due to COVID-19.

BACKGROUND: Despite 2.5 million infections and 169,000 deaths worldwide (as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity have been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and fatal respiratory disease previously documented among pregnant women following other coronavirus-related outbreaks (SARS-CoV in 2003 and MERS-CoV in 2012) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. OBJECTIVE: To describe maternal and perinatal outcomes and death in a case series of pregnant women with COVID-19 disease. STUDY DESIGN: We describe here a multiinstitution adjudicated case series from Iran that includes 9 pregnant women diagnosed with severe COVID-19 disease in their second or third trimester. All 9 pregnant women received a diagnosis of SARS-CoV-2 infection by reverse transcription polymerase chain reaction nucleic acid testing. Outcomes of these women were compared with their familial/household members with contact to the affected patient on or after their symptom onset. All data were reported at death or after a minimum of 14 days from date of admission with COVID-19 disease. RESULTS: Among 9 pregnant women with severe COVID-19 disease, at the time of reporting, 7 of 9 died, 1 of 9 remains critically ill and ventilator dependent, and 1 of 9 recovered after prolonged hospitalization. We obtained self-verified familial/household cohort data in all 9 cases, and in each and every instance, maternal outcomes were more severe compared with outcomes of other high- and low-risk familial/household members (n=33 members for comparison). CONCLUSION: We report herein maternal deaths owing to COVID-19 disease. Until rigorously collected surveillance data emerge, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed as having COVID-19 disease in their second or third trimester.

The effects of autologous platelet-rich plasma in repeated implantation failure: a randomized controlled trial.

Repeated implantation failure is a major challenge in reproductive medicine and despite several methods that have been described for management, there is little consensus on which is the most effective. This study was conducted to evaluate the effectiveness of autologous platelet-rich plasma in improving the pregnancy rate in repeated implantation failure. Between 2016 and 2017, a total of 138 patients who failed to conceive after 3 or more embryo transfers with high quality embryos and candidate for frozen-thawed embryo transfer were assessed for eligibility to enter the study. Intrauterine infusion of 0.5 ml platelet-rich plasma (PRP) that contained platelets at 4-5 times higher concentration than peripheral blood was performed 48 h before blastocyst transfer. A control group received standard treatment. Ninety-seven patients completed the study procedure. There were no significant differences between the two groups in terms of age, body mass index and number of previous embryo transfers. The chemical pregnancy rate was higher in the PRP group than control group (53.06% versus 27.08%, respectively; p value: 0.009). Clinical pregnancy rate was higher in PRP group than control group (44.89% versus 16.66%, respectively; p value: 0.003). In conclusion, intrauterine platelet-rich plasma may be effective in the improvement of pregnancy outcome in repeated implantation failure.