Multisystem inflammatory syndrome in children (MIS-C) post-COVID-19 in Iran: clinical profile, cardiac features, and outcomes.

BACKGROUND: In April 2020, an association between multisystem inflammatory syndromes (MIS-C) was observed in children with severe acute respiratory syndrome coronavirus infection (SARS-CoV-2). Most patients had heart involvement alone, and most patients had pericardial effusion. This study aimed to express and emphasize cardiac involvement in pediatric patients with respiratory symptoms who were diagnosed with COVID-19. METHODS: This study was conducted in July 2021 in Kerman province, Southeastern Iran, during a notable surge in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The study included 904 pediatric patients diagnosed with COVID-19. Data collection involved a comprehensive assessment of clinical symptoms and manifestations. Patients with fever lasting more than five days were admitted to the hospital. Echocardiography was utilized for cardiac involvement diagnosis, with 47 patients undergoing this diagnostic procedure. RESULTS: Of the 904 patients, most of them had high fevers (74%). Fifty-five patients had a fever for more than five days and were hospitalized. Of the 47 patients who underwent echocardiography, 45 (81%) had heart involvement. In 75% of patients, pericardial effusion was the only cardiac involvement. Patients with pericardial effusion were treated with dexamethasone up to 3 mg every 8 h for 72 h. CONCLUSIONS: MIS-C has a wide range of clinical symptoms. In cases where the fever is prolonged and there are gastrointestinal symptoms, physicians have clinical suspicion to diagnose this syndrome. Most cases of pericardial effusion are alone and improve with treatment with glucocorticosteroids.

Prognostic risk factors for early outcomes of patients with myelomeningocele: a prospective study.

INTRODUCTION: Myelomeningocele (MMC) is a prevalent form of neural tube defect. Despite advancements in treatment, MMC still poses significant health risks, including complications leading to chronic disability and mortality. Identifying prognostic risk factors for early outcomes is crucial for tailored intervention strategies. METHODS: This prospective study involved newborns and infants diagnosed with MMC who underwent surgery between 2020 and 2023 at Urmia University of Medical Sciences. Demographic data and surgical outcomes were collected, and participants were followed up for six months. Statistical analyses were conducted using descriptive statistics, Chi-Square, and independent t-test. RESULTS: The study included 29 MMC cases, with an incidence rate of 1.4 per 10,000 live births. Lesions were predominantly located in the lumbar spine. Although mortality rates appeared to increase with ascending lesion sites, this trend was not statistically significant. Short-term outcomes revealed high morbidity and mortality rates, with neurological deficits being the most prevalent complication. Multivariable analysis identified head circumference as a significant predictor of adverse outcomes (IRR = 1.37, 95% CI = 1.02 to 1.86, p = 0.04). Furthermore, an increase in birth weight was associated with a reduction in the incidence of requiring a ventriculoperitoneal shunt (IRR = 0.99, 95% CI = 0.998 to 0.999, p = 0.02). CONCLUSION: This prospective study highlights prognostic risk factors for early outcomes in MMC patients, emphasizing the need for personalized intervention strategies. By addressing modifiable risk factors and implementing targeted interventions, healthcare providers can strive to improve outcomes and enhance the quality of life for MMC patients.

Comparison of Viability of the Preserved Autologous Aspirated Fat Tissue Transfer in Refrigerated and Frozen Specimens.

Background: Fat graft surgery is one of the most effective procedures in plastic surgery, and since some patients request multiple surgeries and these cases sometimes take hours, it endangers the viability of the fat graft. In this study, we intend to evaluate the viability of adipose tissue aspirated with a syringe at refrigerator (4°C) and freezer (-20 °C) temperatures. Methods: This was a cross-sectional study. After receiving the ethics committee's approval (IR.MUMS.MEDICAL.REC.1401.423), 17 volunteers entered the study. The harvested fat tissue sample was divided into 3 parts, and each of them was transferred to 3 separate sterile tubes. The first tube was sent to the laboratory for preliminary examination of fresh fat, and the second tube was transferred to a 4°C refrigerator for 72 hours. The sample from the third tube was first passed through a strainer and after drying, it was transferred to a -20°C freezer for 72 hours. After treatment with trypsin, we placed the sample inside the centrifuge using the Coleman method. Finally, 3 layers were formed, and the white middle layer was extracted as a fat cell suspension. Tissue samples were stained with trypan blue, and the percentage of viable cells was calculated using an optical microscope. Results: There was a significant difference between the mean number and percentage of viable cells in all 3 groups. Samples in the 4°C refrigerator had significantly more cellular viability than those in the -20°C freezer (mean difference, 72.842%; P < 0.001). Conclusion: Our findings showed that after 72 hours at 4°C, adipose tissue has significantly higher survival than at -20°C (98.93% vs 75.31%). Since the survival of fat cells is one of the direct determinants of fat retention, it can affect the results after surgery. The present study recommends fresh adipose tissue for immediate transplantation unless there is an urgent need for cold storage.

Nosocomial infections and antimicrobial susceptibility patterns among patients admitted to intensive care unit of Imam Khomeini hospital in Ilam, Iran.

INTRODUCTION: Nosocomial infections (NIs) are a major challenge worldwide. Identification of antibiotic resistance pattern extended spectrum beta-lactamases (ESBLs) and carbapenem-resistant Enterobacteriaceae (CRE) were the objectives of this study. METHODS: In this cross-sectional study, the antimicrobial susceptibility pattern of bacterial isolates collected from patients with NIs in ICU was determined. Overall, 42 Escherichia coli and Klebsiella pneumoniae isolates from different infection sites were used to determine phenotypic tests of ESBLs, Metallo-ß-lactamases (MBLs) and CRE. Detection of ESBLs, MBLs and CRE genes were performed by the polymerase chain reaction (PCR) method. RESULTS: From 71 patients with NIs, 103 different bacterial strains were isolated. The most frequently isolated bacteria were E. coli (n = 29; 28.16%), Acinetobacter baumannii (n = 15; 14.56%), and K. pneumoniae (n = 13; 12.26%). Also, the rate of multidrug-resistant (MDR) isolates was 58.25% (60/103). Based on phenotypic confirmation tests, 32 (76.19%) isolates of E. coli and K. pneumoniae produced ESBLs, and 6 (14.28%) isolates were identified as CRE producers. PCR showed the high prevalence of the blaCTX-M (n = 29; 90.62%) in ESBL genes. In addition, blaNDM was detected in 4 (66.66%), blaOXA-23 in 3 (50%), and blaOXA-48 gene in 1 (16.66%) isolates. The blaVIM, blaKPC, and blaIMP genes were not detected in any of the isolates. CONCLUSION: The Gram-negative bacteria E. coli, A. baumannii, and K. pneumoniae with high resistance levels were the most common bacteria causing NIs in the ICU. This study for the first time identified blaOXA-11, blaOXA-23, and blaNDM-1 genes in E. coli and K. pneumoniae in Ilam city of Iran.

The association of the age, period, and birth cohort with 15-year changes in body mass index and waist circumference in adults: Tehran lipid and glucose study (TLGS).

OBJECTIVE: To examine the association of age, period, and birth cohort with body mass index (BMI) and waist circumference (WC) changes among the participants of the Tehran Lipid and Glucose Study from 1999 to 2015. METHODS: This prospective cohort study included 4895 participants aged ≥20 years (41.3% men), who were divided into twelve gender stratified groups, having a ten-year age difference between them. Analyses were conducted to explicitly assess the association of age vs. period on BMI and WC changes. In addition, we evaluated BMI and WC changes among different birth cohorts. RESULTS: Upon 15 years of follow-up, the mean BMI of men and women increased from 26.0 ± 3.9 to 27.5 ± 4.3 kg/m2 and from 27.5 ± 4.8 to 29.9 ± 5.4 kg/m2 (P trend < 0.001), and this trend was accompanied by an increase in WC from 88.8 ± 10.9 to 97.8 ± 10.4 cm and from 87.3 ± 12.4 to 95.8 ± 12.1 cm, respectively (P trend < 0.001). Men and women in all age cohorts tended to have a rise in their BMI and WC with aging throughout the follow-up period. For men, this trend was more prominent in younger birth cohorts at phase III for BMI and at phases III and V for WC (indicating a significant negative association with birth cohort). For women, this trend was more prominent in older birth cohorts at both phases III and V for BMI and WC (indicating a significant positive association with the birth cohort). CONCLUSION: The rise in BMI and WC was strongly associated with age in both sexes. The men born in the recent birth cohorts and the women born in earlier birth cohorts had the most alarming BMI and WC trends. More efforts must be spent on obesity prevention policies, especially for younger men.

Randomized, Double-Blind, Placebo-Controlled Phase II Study of Yeast-Brachyury Vaccine (GI-6301) in Combination with Standard-of-Care Radiotherapy in Locally Advanced, Unresectable Chordoma.

BACKGROUND: Brachyury is a transcription factor overexpressed in chordoma and is associated with chemotherapy resistance and epithelial-to-mesenchymal transition. GI-6301 is a recombinant, heat-killed Saccharomyces cerevisiae yeast-based vaccine targeting brachyury. A previous phase I trial of GI-6301 demonstrated a signal of clinical activity in chordomas. This trial evaluated synergistic effects of GI-6301 vaccine plus radiation. MATERIALS AND METHODS: Adults with locally advanced, unresectable chordoma were treated on a randomized, placebo-controlled trial. Patients received three doses of GI-6301 (80 × 107 yeast cells) or placebo followed by radiation, followed by continued vaccine or placebo until progression. Primary endpoint was overall response rate, defined as a complete response (CR) or partial response (PR) in the irradiated tumor site at 24 months. Immune assays were conducted to evaluate immunogenicity. RESULTS: Between May 2015 and September 2019, 24 patients enrolled on the first randomized phase II study in chordoma. There was one PR in each arm; no CRs were observed. Median progressive-free survival for vaccine and placebo arms was 20.6 months (95% confidence interval [CI], 5.7-37.5 months) and 25.9 months (95% CI, 9.2-30.8 months), respectively. Hazard ratio was 1.02 (95% CI, 0.38-2.71). Vaccine was well tolerated with no vaccine-related serious adverse events. Preexisting brachyury-specific T cells were detected in most patients in both arms. Most patients developed T-cell responses during therapy, with no difference between arms in frequency or magnitude of response. CONCLUSION: No difference in overall response rate was observed, leading to early discontinuation of this trial due to low conditional power to detect statistical difference at the planned end of accrual. IMPLICATIONS FOR PRACTICE: Chordoma is a rare neoplasm lacking effective systemic therapies for advanced, unresectable disease. Lack of clinically actionable somatic mutations in chordoma makes development of targeted therapy quite challenging. While the combination of yeast-brachyury vaccine (GI-6301) and standard radiation therapy did not demonstrate synergistic antitumor effects, brachyury still remains a good target for developmental therapeutics in chordoma. Patients and their oncologists should consider early referral to centers with expertise in chordoma (or sarcoma) and encourage participation in clinical trials.

Multifocal calcific periarthritis with distinctive clinical and radiological features in patients with CD73 deficiency.

OBJECTIVES: Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5'-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. METHODS: Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. RESULTS: Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. CONCLUSION: This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms.

Soil cadmium and lead affecting biochemical properties of Matricaria chamomilla L. at different growth stages in the greenhouse and field.

Heavy metals bioremediation by medicinal plants is an important research issue, which has yet to be investigated. Matricaria chamomilla accumulation of soil cadmium (Cd, 0, 10 and 40 mg/kg) and lead (Pb, 0, 60 and 180 mg/kg) affecting plant biochemical properties L. at different growth stages in the greenhouse and field was investigated. The 10-kg experimental pots (located in the greenhouse and field with 80% of field capacity moisture) were filled with the treated soils, and were planted with M. chamomilla L. seeds (three replicates). Plants were sampled to determine their biochemical properties including Cd and Pb contents, pigments, proline (Pro), leaf relative water (LRW), lipid peroxidation (LX), and superoxide dismutase (SOD, EC 1.15. 1.1), and catalase (CAT, EC 1.11.1.6) activities. Soil final concentration of Cd and Pb was also determined. Heavy metal stress significantly decreased plant pigment contents; however, it significantly increased plant PRO, LRW, LX and SOD, and not CAT. Heavy metal, growth stage, growth location, and their interactions significantly affected plant heavy metal concentrations. Interestingly, although significantly higher concentration of Cd was observed in plant aerial part under greenhouse conditions, plant roots had significantly higher concentrations of Cd under field conditions, and it was reverse for Pb. Increased concentration of Cd and Pb significantly enhanced plant Pro content and the highest one was resulted by Pb3 (913.46 mg/g fresh weight) significantly higher than other treatments including Cd3 (595.34 mg/g fresh weight). M. chamomilla is a suitable species for the bioremediation of soils polluted with Cd and Pb.

First molecular survey of Anaplasma phagocytophilum in hard ticks (Ixodidae) from Southwestern Iran.

Anaplasma phagocytophilum is a gram-negative obligate intracellular tick-borne rickettsia with veterinary and public health importance worldwide. This organism is an etiologic agent of tick-borne fever (TBF) in domesticated animals and human granulocytic anaplasmosis (HGA) as well. Hard ticks (Ixodida: Ixodidae) are incriminated as the main biologic vectors for Anaplasma spp. Studies represent that Ixodes spp. are the main vectors for A. phago-cytophilum and few reports hinted that other tick species may play this role. So, the goal of the presented work was to investigate the A. phagocytophilum in 2000 hard ticks in Khuzestan province of Iran by specific nested-PCR performing two consecutive amplifications of 16SrRNA gene fragment with highly variable nucleotide region. Each reaction included 10 salivary glands of distinct tick species. Specific nested-PCR on accumulated salivary glands detected specific bands in 15.5% of reactions (31 of 200) in electrophoresis only in Rhipicephalus sanguineous and Hyalomma marginatum ticks. We concluded that the broad distribution of A. phagocytophilum infection is not only is due to the existence of Ixodes spp. but other hard ticks may also play a role in this issue.

Impaired spermatogenesis associated with changes in spatial arrangement of Sertoli and spermatogonial cells following induced diabetes.

The current study was conducted to assess the relationship between testicular cells in spermatogenesis, through which the production of healthy and mature sperm is essential. However, it seems necessary to obtain more information about the three-dimensional pattern of the testis cells arrangement, which is directly related to the function of the testis after induction of diabetes. Twelve adult mice (28-30 g) were assigned into two experimental groups: (1) control and (2) diabetic (40 mg/kg STZ). The epididymal sperm collected from the tail of the epididymis and testes samples were taken for stereology, immunocytochemistry and RNA extraction. Our data showed that diabetes could notably decrease the number of testicular cells, together with a reduction of total sperm count. In addition, the results from the second-order stereology indicated the significant changes in the spatial arrangement of Sertoli cells and spermatogonial cells in the diabetic groups, in comparison with the control (P < .05). Moreover, the immunohistochemistry results showed a significant reduction in Sex-determining Region Y (SRY) box 9 gene (SOX9), vimentin, occludin, and connexin-43 positive cells in the diabetic groups compared with the control (P < .05). Furthermore, our data showed that the expression of steroidogenic acute regulatory protein steroidogenic acute regulatory protein (StAR) and peripheral benzodiazepine receptor peripheral benzodiazepine receptor (PBR) was significantly reduced in the diabetic groups, in comparison with the control (P < .05). These findings suggest that structural and functional changes of testis cells after induction of diabetes cause the alterations in the spatial arrangement of Sertoli and spermatogonial cells, ultimately influencing the normal spermatogenesis in mice.

Talbot effect of azimuthally periodic Bessel-based structures.

In this work, the theory of self-imaging in the polar coordinates for azimuthally periodic Bessel-based structures (APBBSs) is presented. For the first time, to the best of our knowledge, we define single- and multi-frequency APBBSs and show that these structures have self-images under plane-wave illumination. We also define sinusoidal and binary-like single-frequency APBBSs and theoretically and experimentally investigate the near-field diffraction of these structures. The diffraction from these structures provides 2D arrays of optical traps that can be used in multi-trapping.

Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial.

BACKGROUND: Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients. METHODS: In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer's lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed. RESULTS: During 21 months, a total of 414 patients (mean age 55.5 ±â€Š17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % - 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % - 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % - 21.4 %] in group B). There was no significant difference between the two groups in PEP severity (P = 0.59), amylase levels after 2 hours (P = 0.31) or 24 hours (P = 0.08), and length of hospital stay (P = 0.07). CONCLUSIONS: The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.

An improvement in acute wound healing in mice by the combined application of photobiomodulation and curcumin-loaded iron particles.

Here, we examined the combined effect of pulse wave photobiomodulation (PBM) with curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles (curcumin), in an experimental mouse model of acute skin wound. Thirty male adult mice were randomly allocated into 5 groups. Group 1 was served as the control group. Group 2 was a placebo and received distilled water, as a carrier of curcumin. Group 3 received laser (890 nm, 80 Hz, 0.2 J/cm2). Group 4 received curcumin by taking four injections around the wound. Group 5 received laser + curcumin. One full-thickness excisional round wound was made on the back of all the mice. On days 0, 4, 7, and 14, bacterial flora, wound surface area, and tensile strength were examined and microbiological examinations were performed. In case of wound closure, the two-way ANOVA shows that wound surface area of entire groups decreased progressively. However, the decrease in laser + curcumin and laser groups, and especially data from laser + curcumin group were statistically more significant, in comparison with the other groups (F statistics = 2.28, sig = 0.019). In terms of microbiology, the two-way ANOVA showed that laser, and laser + curcumin groups have statistically a lower bacterial count than the curcumin, control, and carrier groups (F statistics = 35, sig = 0 = 000). Finally, the one-way ANOVA showed that laser + curcumin, curcumin, and curcumin significantly increased wound strength, compared to the control and carrier groups. Furthermore, laser + curcumin significantly increased wound strength, compared to the control, laser, and curcumin groups (LSD test, p = 0.003, p = 0.002, and p = 0.005, respectively). In conclusion, curcumin nanoparticles, pulse wave laser, and pulse wave laser + curcumin nanoparticles accelerate wound healing, through a significant increase in wound closure rate, as well as wound strength, and a significant decrease in Staphylococcus aureus counts. Furthermore, the statistical analysis of our data suggests that the combined treatment of pulse wave laser + curcumin nanoparticles enhances the wound closure rate, and wound strength, compared to the laser and curcumin nanoparticles alone.

Lipid profile change after bariatric surgeries: laparoscopic gastric plication versus mini gastric bypass.

INTRODUCTION: Bariatric surgeries are known to have profound effects on lipid profile. Laparoscopic gastric plication (LGP) has been shown to have a comparable effect on weight loss rather than Roux-en-Y gastric bypass (RYGB) and mini gastric bypass (MGB). But the post-operative effect on lipid profile is not well-compared. We aimed to compare post-operative lipid profile change after LGP and MGB. METHODS: In a retrospective analysis, we reviewed 91 patients for at least 12 months. Patients were assigned to undergo either LGP (71 patients) or MGB (20 patients). Preoperative and postoperative visits were accomplished and weight, BMI, fasting blood glucose (FBG) and lipid profile including triglyceride (TG), and total cholesterol (TC) levels were repeatedly measured. Follow up rate for the first year was 100%. RESULTS: LGP significantly decreased both TG and TC levels in each follow up (all p values < .05). The same trends were observed in BMI reduction, total body weight loss percentage, and FBG. When comparing either TC or TG level between LGP and MGB, there was just one statistically significant result in TG reduction at 6 months (p value = .042) while MGB showed more reduction. All other variables in different follow up visits were not significantly different between two techniques. CONCLUSIONS: LGP would result in lipid profile improvement lasting at least for one year. Lipid-lowering effect seems to be similar between LGP and MGB. This lipid-lowering property and weight reduction might be indicative that LGP is an alternative for RYGB and MGB in selective patients.

Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study.

BACKGROUND: High-grade serous ovarian carcinoma is characterised by TP53 mutations, DNA repair defects, and genomic instability. We hypothesised that prexasertib (LY2606368), a cell cycle checkpoint kinase 1 and 2 inhibitor, would be active in BRCA wild-type disease. METHODS: In an open-label, single-centre, two-stage, proof-of-concept phase 2 study, we enrolled women aged 18 years or older with measurable, recurrent high-grade serous or high-grade endometrioid ovarian carcinoma. All patients had a negative family history of hereditary breast and ovarian cancer or known BRCA wild-type status, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status score 0-2, and adequate haematological, renal, hepatic, and bone-marrow function. Patients received intravenous prexasertib 105 mg/m2 administered over 1 h every 14 days in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint of investigator-assessed tumour response, based on RECIST version 1.1, was assessed per protocol (assessable patients who had undergone CT imaging at baseline and attended at least one protocol-specified follow-up) and by intention to treat. The final analysis of this cohort of patients with BRCA wild-type high-grade serous ovarian carcinoma is reported here. This ongoing trial is registered with ClinicalTrials.gov, number NCT02203513, and continues to enrol patients for the BRCA-mutated ovarian cancer cohort. FINDINGS: Between Jan 20, 2015, and Nov 2, 2016, we enrolled 28 women with a median age of 64 years (IQR 58·0-69·5) who had previously received a median of 5·0 (IQR 2·5-5·0) systemic therapies. Most patients (22 [79%]) had platinum-resistant or platinum-refractory disease. All women received at least one dose of prexasertib, but four (14%) of 28 patients were not assessable for RECIST response. Eight (33%, 95% CI 16-55) of 24 patients assessable per protocol had partial responses. In the intention-to-treat population, eight (29%, 95% CI 13-49) of 28 had a partial responses. The most common (in >10% patients) grade 3 or 4 treatment-emergent adverse events were neutropenia in 26 (93%) of 28 patients, reduced white blood cell count in 23 (82%), thrombocytopenia in seven (25%), and anaemia in three (11%). Grade 4 neutropenia was reported in 22 (79%) patients after the first dose of prexasertib and was transient (median duration 6 days [IQR 4-8]) and recovered without growth-factor support in all cases. The treatment-related serious adverse event of grade 3 febrile neutropenia was reported in two (7%) patients. One patient died during the study due to tumour progression. INTERPRETATION: Prexasertib showed clinical activity and was tolerable in patients with BRCA wild-type high-grade serous ovarian carcinoma. This drug warrants further development in this setting, especially for patients with platinum-resistant or platinum-refractory disease. FUNDING: Intramural Research Program of the National Institutes of Health and National Cancer Institute.

Human Bone Marrow Mesenchymal Stem Cell Conditioned Medium Promotes Wound Healing in Deep Second-Degree Burns in Male Rats.

Burn wound treatment is difficult and one of the most challenging problems in the clinic. Researchers have examined the applications of mesenchymal stem cells as a cell-based therapy for skin regeneration. But the role of human bone marrow mesenchymal stem cell conditioned medium (hBM-MSC-CM) in the treatment of burn injury remains unclear. This research aims at detecting whether hBM-MSC-CM can increase the wound healing of deep second-degree burns in male rats. In this study, 32 adult male rats per each time point were randomly divided into four groups: (1) control group, (2) sham group (DMEM), (3) common treatment group (CT), and (4) conditioned media group (CM). A 3 × 3 cm circular burn was created on the back of the rats. On postsurgical days 7, 15, and 28, the wound closure area of each wound was measured and then the skin samples were removed and analyzed using stereological methods. Wound closure area was significantly increased in the CM and CT groups on the 15th and the 28th day after burn injury compared to the control and DMEM groups. The stereological parameters and immunohistochemistry analysis of the wounds revealed significantly improved healing in the CM group compared to the control and other groups. It is concluded that these findings indicate that hBM-MSC-CM promotes skin wound healing by increasing cell proliferation, regulating collagen synthesis and collagen composition, and inducing angiogenesis at the injury site.

Vitamin B12 in Association with Antipsychotic Drugs Can Modulate the Expression of Pro-/Anti-Inflammatory Cytokines in Alzheimer Disease Patients.

INTRODUCTION: Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, and endothelin (ET)-1). MATERIAL AND METHODS: Serum levels of IL-6, IL-8, TGF-ß, TNF-α, and ET-1 were evaluated in the following groups: healthy controls, nonpsychotic AD patients, psychotic AD patients, psychotic AD patients under treatment with risperidone, psychotic AD patients under treatment with risperidone plus vitamin B12, psychotic AD patients under treatment with quetiapine, and psychotic AD patients under treatment with quetiapine plus vitamin B12. RESULTS: Treatment with antipsychotic drugs plus vitamin B12 led to a decreased expression of IL-8 and TNF-α and an increased expression of TGF-ß. Vitamin B12 in association with quetiapine reduced the pain in psychotic AD patients. DISCUSSION: Proinflammatory cytokines play important roles in the pathogenesis of psychosis in AD patients. Antipsychotic drugs plus vitamin B12 can reduce and induce the expression of proinflammatory and anti-inflammatory cytokines to improve psychotic symptoms in AD patients.

ENABLE (Exportable Notation and Bookmark List Engine): an Interface to Manage Tumor Measurement Data from PACS to Cancer Databases.

Oncologists evaluate therapeutic response in cancer trials based on tumor quantification following selected "target" lesions over time. At our cancer center, a majority of oncologists use Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 quantifying tumor progression based on lesion measurements on imaging. Currently, our oncologists handwrite tumor measurements, followed by multiple manual data transfers; however, our Picture Archiving Communication System (PACS) (Carestream Health, Rochester, NY) has the ability to export tumor measurements, making it possible to manage tumor metadata digitally. We developed an interface, "Exportable Notation and Bookmark List Engine" (ENABLE), which produces prepopulated RECIST v1.1 worksheets and compiles cohort data and data models from PACS measurement data, thus eliminating handwriting and manual data transcription. We compared RECIST v1.1 data from eight patients (16 computed tomography exams) enrolled in an IRB-approved therapeutic trial with ENABLE outputs: 10 data fields with a total of 194 data points. All data in ENABLE's output matched with the existing data. Seven staff were taught how to use the interface with a 5-min explanatory instructional video. All were able to use ENABLE successfully without additional guidance. We additionally assessed 42 metastatic genitourinary cancer patients with available RECIST data within PACS to produce a best response waterfall plot. ENABLE manages tumor measurements and associated metadata exported from PACS, producing forms and data models compatible with cancer databases, obviating handwriting and the manual re-entry of data. Automation should reduce transcription errors and improve efficiency and the auditing process.

Impact of body size and physical activity during adolescence and adult life on overall and cause-specific mortality in a large cohort study from Iran.

We conducted this study to examine life-course body size and physical activity in relation to total and cause-specific mortality, which has not previously been studied in the low and middle-income countries in Asia. The Golestan Cohort Study is a population-based cohort in northeastern Iran in which 50,045 people above the age of 40 have been followed since 2004. Participants were shown a validated pictogram to assess body size at ages 15, 30, and the time of recruitment. Information on occupational physical activity at these ages was also collected. Subjects were followed up annually, and cause of death was determined. Cox regression models were adjusted for age at cohort start, smoking, socioeconomic status, ethnicity, place of residence, education, and opium use. Models for body size were also adjusted for physical activity at the same age, and vice versa. During a total of 252,740 person-years of follow-up (mean follow-up duration 5.1 ± 1.3 years) through December 2011, 2,529 of the cohort participants died. Larger body sizes at ages 15 or 30 in both sexes were associated with increased overall mortality. Cancer mortality was more strongly associated with adolescent obesity, and cardiovascular mortality with early adulthood body size. Weight gain between these ages was associated with cardiovascular mortality. Obese adolescents who lost weight still had increased mortality from all medical causes in both sexes. Physical activity during adolescence and early adulthood had no association with mortality, but at cohort baseline higher levels of activity were associated with reduced mortality. Mortality in this Middle-Eastern population was associated with obesity both during adolescence and early adult life.

Management of epilepsy in resource-limited areas: establishing an epilepsy surgery program in Iran.

Background Of about 40 million people with epilepsy, who live in developing countries, the majority do not receive appropriate treatment. Nonetheless, there are striking disparities among the so-called developing countries, however generally speaking, access to and availability of epilepsy management programs in developing countries are very limited and therefore, the issue of developing epilepsy centers in resource-limited settings in a large scale is very essential. The surgery for epilepsy, including temporal lobotomy, lesionectomy and corpus colostomy, for patients with medically-refractory seizures, defined as failure of adequate trials of two tolerated, appropriately chosen and using antiepileptic drug to achieve sustained freedom, from seizure has been proved to be feasible and cost-effective in developing countries. However, the success of epilepsy surgery depends upon the accurate identification of good surgical candidates based on the available resources and technologies without jeopardizing safety. In the current paper, we will share our experiences of establishing an epilepsy surgery program in Iran, despite all short-comings and limitations and try to provide some answers to those challenges, which helped us establish our program.