Intratumoral injection of schwannoma with attenuated Salmonella typhimurium induces antitumor immunity and controls tumor growth.

Schwannomas are slow-growing benign neoplasms that develop throughout the body causing pain, sensory/motor dysfunction, and death. Because bacterial immunotherapy has been used in the treatment of some malignant neoplasms, we evaluated attenuated Salmonella typhimurium strains as immunotherapies for benign murine schwannomas. Several bacterial strains were tested, including VNP20009, a highly attenuated strain that was previously shown to be safe in human subjects with advanced malignant neoplasms, and a VNP20009 mutant that was altered in motility and other properties that included adherence and invasion of cultured mammalian cells. VNP20009 controlled tumor growth in two murine schwannoma models and induced changes in cytokine and immune effector cell profiles that were consistent with induction of enhanced innate and adaptive host immune responses compared with controls. Intratumoral (i.t.) injection of S. typhimurium led to tumor cell apoptosis, decreased tumor angiogenesis, and lower growth of the injected schwannoma tumors. Invasive VNP20009 was significantly more efficacious than was a noninvasive derivative in controlling the growth of injected tumors. Bacterial treatment apparently induced systemic antitumor immunity in that the growth of rechallenge schwannomas implanted following primary bacterial treatment was also reduced. Checkpoint programmed death-1 (PD-1) blockade induced by systemic administration of anti-PD-1 antibodies controlled tumor growth to the same degree as i.t. injection of S. typhimurium, and together, these two therapies had an additive effect on suppressing schwannoma growth. These experiments represent validation of a bacterial therapy for a benign neoplasm and support development of S. typhimurium VNP20009, potentially in combination with PD-1 inhibition, as a schwannoma immunotherapy.

Prenatal depression among pregnant women attending public health facilities in Babile district, Eastern Ethiopia: a cross-sectional study.

BACKGROUND: Depression during pregnancy is a significant health concern that can lead to a variety of short and long-term complications for mothers. Unfortunately, there is a lack of information available on the prevalence and predictors of prenatal depression in rural eastern Ethiopia. This study assessed prenatal depression and associated factors among pregnant women attending public health facilities in the Babile district, Eastern Ethiopia. METHOD: An institution-based cross-sectional study was conducted among 329 pregnant women attending Babile District Public Health Facilities from November 1 to December 30, 2021. Bivariable and multivariable logistic regression were used to identify factors associated with prenatal depression. The adjusted odds ratio (AOR) with a 95% confidence interval was used to report the association, and the significance was declared at a p-value < 0.05. RESULTS: The prevalence of prenatal depression was 33.1% (95% CI = 28.0%, 38.2%). A lower income (AOR = 3.85, 95% CI = 2.08, 7.13), contraceptive use (AOR = 0.53, 95% CI = 0.28, 0.98), unintended pregnancy (AOR = 2.24, 95% CI = 1.27, 3.98), history of depression (AOR = 5.09, 95% CI = 2.77, 9.35), poor social support (AOR = 5.08, 95% CI = 2.15, 11.99), and dissatisfied marriage (AOR = 2.37, 95% CI = 1.30, 4.33) were the factors associated with increased prenatal depression among pregnant women. CONCLUSIONS: One in every three pregnant women in rural eastern Ethiopia had prenatal depression. Monthly income, contraceptive use, pregnancy intention, history of depression, social support, and marriage satisfaction status were the determinants of prenatal depression. Preventing unintended pregnancies by encouraging women to utilize modern contraceptive methods is essential for mitigating and controlling the risks and burdens of prenatal depression and its negative consequences.

The effect of Pilates exercise during pregnancy on delivery outcomes: a systematic review and meta-analysis.

A systematic review and meta-analysis were conducted to investigate the effectiveness of the Pilates exercise program during pregnancy on different delivery outcomes. Various databases were searched from inception until November 2022. The included studies compared Pilates exercise to routine antenatal care in pregnant women. The primary outcomes assessed were vaginal and cesarean delivery rates, as well as labor duration. Secondary outcomes included episiotomy incidence, Apgar scores, and epidural analgesia. Seven studies met the inclusion criteria, involving a total of 1,003 patients. Results indicated a significant increase in the vaginal delivery rate among the Pilates exercise group compared to the control group (p < .001). Moreover, the Pilates exercise group exhibited significantly reduced rates of cesarean delivery and shorter labor duration. Pilates exercise was associated with a significant decline in the incidence of episiotomy and the number of women requiring epidural analgesia during delivery (p < .001 & p = .008). In addition, Apgar scores at one and five minutes were significantly higher in the Pilates exercise group compared to the control group (p < .001). In conclusion, Pilates exercise during pregnancy has a positive effect on maternal outcomes and Apgar scores. However, more trials are needed to confirm these findings.

A pilot study to compare propranolol and misoprostol versus misoprostol and placebo for induction of labor in primigravidae; a randomized, single-blinded, placebo-controlled trial.

BACKGROUND: The Induction of labor is the most common obstetric procedure in daily practice. Introducing propranolol as a new drug to augment the action of prostaglandins will help in the induction process and decrease CS rates. Several researchers have used propranolol in the augmentation of labor. AIM: This pilot study compares propranolol and misoprostol versus misoprostol alone for labor induction in primigravids. METHODS: This is a Randomized clinical trial, single-blinded, placebo-controlled trial at Ain Shams University Maternity hospital. This study included 128 pregnant full-term primigravid women candidates for labor induction, randomized into two groups. All candidates underwent labor induction with 25 µg of vaginal misoprostol. Group I received 20 mg of oral propranolol tablets, while group II received sugary pills as a placebo. Candidates who responded successfully to induction were assessed for possible augmentation of labor by amniotomy or oxytocin infusion. The Primary outcome was induction to delivery interval, while the secondary outcomes were the duration of the latent phase, mode of delivery, and APGAR score of the neonate. RESULTS: The induction-delivery time was (11.8 ± 8.1 h. vs. 12.6 ± 8.9 h., P value = 0.027) and the duration of the latent phase of labor (7.9 ± 5.6 h. vs. 9.2 ± 6.03 h., P value = 0.017) were significantly shorter in the group of misoprostol and propranolol compared to the group of misoprostol and placebo. There was no statistically significant difference between both groups' mode of delivery, indications for cesarean section, misoprostol, and oxytocin doses, or neonatal outcome. (P value > 0.05). CONCLUSION: Propranolol, when used with misoprostol for induction of labor, results in augmentation of action of misoprostol and a significantly shorter induction-delivery interval. TRIAL REGISTRATION: We retrospectively registered this trial in clinicaltrial.gov on 01/09/2020 (NCT04533841). https://clinicaltrials.gov/ct2/show/NCT04533841.

Schwannoma Gene Therapy via Adeno-Associated Viral Vector Delivery of Apoptosis-Associated Speck-like Protein Containing CARD (ASC): Preclinical Efficacy and Safety.

Schwannomas are tumors derived from Schwann-lineage cells, cells that protect and support myelinated nerves in the peripheral nervous system. They are typically slow-growing, encapsulated and benign. These tumors develop along peripheral, spinal and cranial nerves causing pain, sensory-motor dysfunction and death. Primary treatment for schwannoma is operative resection which can be associated with significant morbidity. Pharmacotherapy is largely restricted to bevacizumab, which has minimal or no efficacy for many patients and can be associated with treatment-limiting adverse effects. Given the suffering and morbidity associated with schwannoma and the paucity of therapeutic options, there is an urgent need for safe and effective therapies for schwannomas. We previously demonstrated that adeno-associated virus serotype 1 (AAV1) vector mediated delivery of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) under the control of the P0 promoter, produced a prolonged reduction in tumor volume and tumor-associated pain in human xenograft and mouse syngeneic schwannoma models. Here, we present data essential for the translation of our AAV1-P0-ASC schwannoma gene therapy to clinical trials. We determine the minimum effective dose of AAV1-P0-hASC required to induce an anti-tumor effect in the xenograft human-schwannoma model. We also show that the presence of preexisting AAV1 immunity does not alter the antitumor efficacy of AAV-P0-mASC in a syngeneic mouse schwannoma model. Furthermore, the maximum deliverable intratumoral dose of AAV1-P0-ASC was not associated with neuronal toxicity in immunocompetent mice. Taken together, these safety and efficacy data support the translation of the AAV1-P0-ASC schwannoma gene therapy strategy to clinical trials.

Field observations of stratification in stormwater wet ponds.

Stratification is one of the fundamental physical processes that may have a significant impact on water quality in stormwater wet ponds. However, the role of thermal and chemical stratifications in governing water quality processes is not fully understood. This is in part due to the lack of detailed field measurements of sufficient governing parameters over time periods that span a wide range of environmental conditions. To fill this gap, a comprehensive 2-year field program was undertaken in two stormwater wet ponds in Calgary, Alberta, Canada, during the ice-free season from May to November in 2018 and 2019. At different locations in each pond, thermal and chemical stratifications were observed, thermocline depth and strength were determined, and continuous water velocity profiles were measured. In addition, the effect of local weather conditions on stratification, thermocline, and hydrodynamics was investigated. The results showed that the ponds had vertical water temperature differences >1 °C for 99% of the time, May to August. In addition, salt-laden inflows from road deicing salts led to strong chemical stratification up to five times stronger in the sediment forebays than in the main cells in spring. Wind-induced surface currents were insignificant, scaling at 0.3% of the wind speed with negligible impact on vertical mixing in the ponds. Our results demonstrate that the ponds' strong and prolonged stratification decreased pollutant retention capacity and caused the water at depth to become anoxic, degrading the quality of the water discharged downstream. Hence, additional consideration of stratification is required when designing new stormwater ponds.

Predictors of Limb Outcome Following Arterial Ligation of Infected Femoral Pseudoaneurysms in Drug Abusers.

BACKGROUND: We aimed to study variables affecting limb outcome following ligation of infected femoral pseudoaneurysms in intravenous drug abusers (IVDA)in the emergency setting and to propose an algorithm for management. DESIGN: Prospective study. METHODS: We studied short-term outcomes of 26 IVDA presenting with infected femoral pseudoaneurysms who underwent arterial ligation, hematoma evacuation, and debridement. Long-term results pertaining to limb functionality were unfeasible, as all patients were lost to follow-up. We aimed to study the potential predictors that might impact limb outcome in the emergency setting, namely: 1) mode of presentation (impending versus ruptured), 2) site of arterial ligation (above versus below inguinal ligament), 3) presence or absence of pedal Doppler flow post-ligation, and 4) ankle brachial pressure index (ABI) pre- and post-ligation. RESULTS: Arterial ligation without revascularization was done in 19 (73.1%) of our patients, requiring no further intervention for limb salvage during their hospital stay. Four patients (15.4%) required iliopopliteal bypass, and 3 patients (11.5%) required major amputations (2 hip disarticulations and one above-knee amputation). In total, 23 limbs (88.5%) were salvaged. Proximal arterial ligation was done below the inguinal ligament (common femoral artery) in 21 patients (80.8%), while in the remaining 5 patients (19.2%), higher ligation was done above the inguinal ligament (external iliac artery). All 19 patients who were compensated had pedal Doppler flow post-ligation, and 18 of them had arterial ligation done below the inguinal ligament. The mean preoperative ABI (±SD) was 0.87 ± 0.34, and the mean postoperative ABI (±SD) was 0.37 ± 0.27. The mean change in ABI (±SD) was 0.50 ± 0.32. CONCLUSIONS: Arterial ligation with local debridement alone is a safe procedure and would have salvaged 73.1% of limbs in this study. However, implementing a selective approach for post-ligation revascularization and our proposed algorithm increased limb salvage rate to 88.5%. The detection of pedal Doppler flow after ligation can stratify patients in whom urgent revascularization might not be required for limb salvage. Additionally, all efforts should be made to ligate the femoral artery below the inguinal ligament to preserve important juxta-inguinal collateral branches.

Effect of resveratrol and environmental enrichment on biomarkers of oxidative stress in young healthy mice.

Resveratrol (RESV) and Environmental Enrichment (EE) have been separately reported to protect organisms against various diseases. This study investigated the potential benefit of the combination of RESV and EE on biomarkers of oxidative stress in young healthy mice. Fifty mice of both sexes were randomly divided into five groups of 10 animals each: group I served as control, group II were maintained on alternate day feeding, group III received RESV 50 mg/kg, suspended in caboxymethylcellulose orally per kg/day. Group IV received CMC and kept in an Enriched Environment, group V received RESV + EE. The treatment lasted for 28 days. The animals were sacrificed 24 h after the last treatment and brain samples were collected for biochemical evaluation. The results obtained showed a significant decrease (P < 0.05) in malondialdehyde concentration in EE group and RESV treated group kept EE when compared to the control. A significant decrease was also observed in glutathione peroxidase activity in all the treatment groups when compared to the control. A significant decrease in GPx activities in RESV, EE and RESV + EE treated groups in male and female mice when compared to the control groups respectively. However, a significant increase in GPx activities was observed in EE group in male mice and EODF, RESV groups in female mice when compared to RESV + EE groups respectively. In conclusion, the result of our study indicates that EE possesses antioxidant properties by decreasing MDA concentration and attenuating lipid peroxidation in the brain of young Swiss albino mice.

Superficial incisional surgical site infection rate after cesarean section in obese women: a randomized controlled trial of subcuticular versus interrupted skin suturing.

PURPOSE: To compare the superficial incisional surgical site infection (SSI) rate after cesarean section (CS) in obese women using subcuticular versus interrupted skin suturing. METHODS: The current randomized controlled clinical trial was conducted at Ain Shams University Maternity Hospital. Obese non-diabetic women who underwent elective CS were randomized into two groups: group I included women who had their skin closed with interrupted mattress suture using non-absorbable polypropylene, and group II included women who had their skin closed with subcuticular suture using the same suture material. Primary outcome measure was superficial incisional SSI and secondary outcome measures were skin closure time, postoperative pain assessed by ten-point visual analog scale (VAS) and short-term cosmetic wound outcome according to the Stony Brook Scar Evaluation Scale (SBSES). RESULTS: A total of 130 obese women were finally analyzed. Group II (n = 67) was associated with higher incidence of superficial incisional SSI. There were nine cases (13.4 %) compared to three cases (4.8 %) in group I (n = 63); however, this difference was statistically not significant (P = 0.088). Skin closure time was significantly prolonged in group I (8.6 ± 2.3 min versus 5.7 ± 2.2 min, respectively, P < 0.001). Postoperative pain was significantly lower in group I and the mean VAS in group I was 4.7 ± 2 versus 5.5 ± 1.8 in group II (P = 0.017). Using SBSES, group II had mean score 4.5 ± 0.7, while group I had mean score 2.7 ± 1.1. This was statistically significant (P < 0.001), which means a better cosmetic outcome in group II. CONCLUSION: Subcuticular skin closure during CS for non-diabetic obese women was significantly associated with better short-term cosmetic outcome, less skin closure time, yet, with slightly higher risk of superficial incisional SSI and significantly more postoperative pain.

Effect of Antibiotic Treatment on Attenuated Salmonella typhimurium VNP20009 Mediated Schwannoma Growth Control.

BACKGROUND/AIM: This study evaluated the effect of enrofloxacin antibiotic treatment on the ability of an attenuated Salmonella typhimurium (S. typhimurium) strain VNP20009 to control schwannoma growth in a preclinical mouse schwannoma tumor model. MATERIALS AND METHODS: The antitumor efficacy of VNP20009 intratumoral (i.t.) injection was assessed in a syngeneic mouse-NF2 schwannoma model, with and without subcutaneous (s.c.) injection of enrofloxacin beginning on day-1 or day-8 post-VNP20009 injection. S. typhimurium colonization was assessed in excised tumor samples following antibiotic treatment. RESULTS: I.t. injection of the VNP20009 significantly decreased the growth of schwannoma tumors in mice compared to PBS-treated controls. Treatment of mice with enrofloxacin on day-1 post-VNP20009 injection resulted in abrogation of VNP20009-mediated tumor growth control. In contrast, tumor growth in i.t. VNP20009-injected mice infused with enrofloxacin beginning on day 8 was significantly decreased compared to i.t. PBS-injected controls. Enrofloxacin significantly reduced the number of viable VNP20009 bacteria in excised tumor samples within one day of antibiotic infusion. Viable bacteria were either few or essentially eliminated at the end of the experiment in antibiotic-treated animals compared to VNP20009-only. CONCLUSION: Viable VNP20009 can persist for as long as 2.5 weeks following intratumoral injection of schwannoma, during which time tumor growth is retarded. Antibiotic treatment starting 1-day following i.t. VNP20009 abrogated bacterial tumor growth control, whereas initiation of antibiotics 8-days following i.t. VNP20009 was associated with control of tumor growth, albeit less than seen in animals unexposed to antibiotics.

Culture of attenuated Salmonella Typhimurium VNP20009 in animal-product-free media does not alter schwannoma growth control.

Schwannomas are slow-growing benign peripheral nerve sheath tumors derived from Schwann-lineage cells that develop in association with NF2-related schwannomatosis (NF2) and schwannomatosis (NF3), as well as spontaneously. Individuals affected with NF2 and NF3 have multiple schwannomas with tumors arising throughout life. Surgical resection, the standard management, is limited in scope and efficacy and is itself associated with significant morbidity. We have previously shown that direct intratumoral injection of attenuated Salmonella Typhimurium (S. Typhimurium), strain VNP20009, showed a potent anti-tumor effect in preclinical NF-2 schwannoma models. The United States Federal Drug Administration (FDA) requires that bacterial products utilized in clinical trials be produced without exposure to animal-derived-products. In this context, we developed, characterized, and tested the antitumor efficacy of an attenuated S. Typhimurium serially passaged in animal-product-free media, naming it VNP20009-AF for "VNP20009-animal-product-free." Our in vitro data did not indicate any significant changes in the viability, motility, or morphology of VNP20009-AF, compared to its parental strain. In vivo efficacy data demonstrated that VNP20009-AF and VNP20009 controlled tumor growth to the same degree in both human NF2-schwannoma xenograft and murine-NF2 schwannoma allograft models. Together, these data support the use of VNP20009-AF for the translation of bacterial schwannoma therapy into clinical trials.

Impact of rainfall characteristics on urban stormwater quality using data mining framework.

Understanding the impact of rainfall characteristics on urban stormwater quality is important for stormwater management. Even though significant attempts have been undertaken to study the relationship between rainfall and urban stormwater quality, the knowledge developed may be difficult to apply in commercial stormwater management models. A data mining framework was proposed to study the impacts of rainfall characteristics on stormwater quality. A rainfall type-based calibration approach was developed to improve water quality model performance. Specifically, the relationship between rainfall characteristics and stormwater quality was studied using principal component analysis and correlation analysis. Rainfall events were classified using a K-means clustering method based on the selected rainfall characteristics. A rainfall type-based (RTB) model was independently calibrated for each rainfall type to obtain optimal parameter sets of stormwater quality models. The results revealed that antecedent dry days, average rainfall intensity, and rainfall duration were the most critical rainfall characteristics affecting the event mean concentrations (EMCs) of total suspended solids, total nitrogen, and total phosphorus, while total rainfall was found to be of negligible importance. The K-means method effectively clustered the rainfall events into four types that could represent the rainfall characteristics in the study areas. The rainfall type-based calibration approach can considerably improve water quality model accuracy. Compared to the traditional continuous simulation model, the relative error of the RTB model was reduced by 11.4 % to 16.4 % over the calibration period. The calibrated stormwater quality parameters can be transferred to adjacent catchments with similar characteristics.

Evaluation of pollutant removal efficiency of urban stormwater wet ponds and the application of machine learning algorithms.

Wet ponds have been extensively used for controlling stormwater pollutants, such as sediment and nutrients, in urban watersheds. The removal of pollutants relies on a combination of physical, chemical, and biological processes. It is crucial to assess the performance of wet ponds in terms of removal efficiency and develop an effective modeling scheme for removal efficiency prediction to optimize water quality management. To achieve this, a two-year field program was conducted at two wet ponds in Calgary, Alberta, Canada to evaluate the wet ponds' performance. Additionally, machine learning (ML) algorithms have been shown to provide promising predictions in datasets with intricate interactions between variables. In this study, the generalized linear model (GLM), partial least squares (PLS) regression, support vector machine (SVM), random forest (RF), and K-nearest neighbors (KNN) were applied to predict the outflow concentrations of three key pollutants: total suspended solids (TSS), total nitrogen (TN), and total phosphorus (TP). Generally, the concentrations of inflow pollutants in the two study ponds are highly variable, and a wide range of removal efficiencies are observed. The results indicate that the concentrations of TSS, TN, and TP decrease significantly from the inlet to outlet of the ponds. Meanwhile, inflow concentration, rainfall characteristics, and wind are important indicators of pond removal efficiency. In addition, ML algorithms can be an effective approach for predicting outflow water quality: PLS, GLM, and SVM have shown strong potential to capture the dynamic interactions in wet ponds and predict the outflow concentration. This study highlights the complexity of pollutant removal dynamics in wet ponds and demonstrates the potential of data-driven outflow water quality prediction.

Stratification and its consequences in two constructed urban stormwater wetlands.

Stratification in constructed urban stormwater wetlands is one of the fundamental physical processes that affect hydrodynamics, transport and fate of stormwater pollutants. Adverse effects of stratification include decreasing pollutant retention capacity, causing the water at lower depths to become anoxic, degrading water quality and increasing stress on the downstream aquatic communities. The current study reports on a comprehensive field monitoring program of stratification and hydrodynamics in two ice-free seasons (May - October) in two constructed urban stormwater wetlands in Calgary, Canada, with different inlet, outlet, morphometric and vegetation designs. Despite their small sizes of 0.5 and 1.2 ha and shallow water depths of 0.8 m, stratification was strong and persistent in the wetlands. The response of stratification and mixing to atmospheric forcings (e.g., air temperature, atmospheric instability, rainfall depth, wind speed) and the impact of design characteristics (inlet/outlet design, water depth, surface area and aquatic vegetation) were examined and discussed. Thermal stratification, defined as a vertical temperature gradient >1 °C/m, was found to be significantly higher (up to ten times) near the inlets and last longer (up to twice) than in the main cells and the outlet basins due to the relatively cold summer inflows. The wetland with twice the permanent water volume and surface area and half the length-to-width ratio had denser submerged aquatic vegetation, higher (by up to 2 °C) water temperature and more severe (up to eight times) thermal stratification. Strong densimetric stratification and low wind stress on the water surface caused hypoxic conditions near the bed, potentially adversely affecting water quality and downstream aquatic communities.

Taurine and Camel Milk Modulate Neurobehavioral and Biochemical Changes in Aluminum Chloride-Induced Alzheimer's Disease in Rats.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease associated with deficiency in motor coordination, cognitive impairment, and excessive reactive oxygen species production in the brain. OBJECTIVE: The study evaluated effects of taurine and camel milk (CM) on neurobehavior, amyloid-beta peptide 1-42 (Aß) expression, acetylcholinesterase, and superoxide dismutase activities in aluminum chloride (AlCl3) model of Alzheimer's disease in rats. METHODS: Thirty-five female Wistar rats were divided into seven groups (n = 5): Normal saline (0.2 mL/kg body weight); AlCl3 (100 mg/kg) (AD); CM (33 mL/kg); Taurine (50 mg/kg); AlCl3 (100 mg/kg) + CM (33 mL/kg); AlCl3 (100 mg/kg) + Taurine (50 mg/kg); and AlCl3 (100 mg/kg) + CM (33 mL/kg) + Taurine (50 mg/kg). The administration lasted for eight weeks via oral gavage. After the eighth week, neurobehavior assessments were performed. Rats were sacrificed, and brain and blood samples collected for analysis. RESULTS: There was a significant (p < 0.0001) increase in the duration of motor endurance in AD + CM rats, compared to AD rats. Duration of forced swimming time was lowest (p < 0.0001) in AlCl3 + Taurine rats, compared to that of AD rats. Concentration of Aß peptide decreased (p < 0.05) in AD rats, treated with CM and/or combination. In taurine-treated rats, superoxide dismutase activity was significantly (p < 0.05) higher than in AD rats. Treatment with taurine + CM increased (p < 0.05) acetylcholinesterase activity compared to controls. CONCLUSION: Taurine and CM enhanced cognition and sensorimotor activity by decreasing Aß peptide concentration and increasing superoxide dismutase and acetylcholinesterase activities in AD rats.

Transcriptomic signature of painful human neurofibromatosis type 2 schwannomas.

Schwannomas are benign neoplasms that can cause gain- and loss-of-function neurological phenotypes, including severe, intractable pain. To investigate the molecular mechanisms underlying schwannoma-associated pain we compared the RNA sequencing profile of painful and non-painful schwannomas from NF2 patients. Distinct segregation of painful and non-painful tumors by gene expression patterns was observed. Differential expression analysis showed the upregulation of fibroblast growth factor 7 (FGF7) in painful schwannomas. Behavioral support for this finding was observed using a xenograft human NF2-schwannoma model in nude mice. In this model, over-expression of FGF7 in intra-sciatically implanted NF2 tumor cells generated pain behavior compared with controls.

Implementation and impact of mobile health (mHealth) in the management of diabetes mellitus in Africa: a systematic review protocol.

INTRODUCTION: The WHO has proposed the concept of mobile health (mHealth) to support healthcare systems delivery worldwide. mHealth basically involves the use of Information and Communication Technology for healthcare provision or delivery services. Africa has seen a remarkable increase in mobile phone availability and usage in the last decade. The incidence and prevalence of diabetes mellitus (DM) in Africa have also been on the increase in the last decade, in sharp contrast to an ailing healthcare system. We aim to review the extent of implementation of mHealth in the management of DM in Africa, and estimate its impact in helping patients achieve desired glycaemic target, sustain control and prevent complications in the past decade. METHODS AND ANALYSIS: Studies assessing the utilisation of mhealth in the management of patients with DM in Africa will be considered based on the PICO method: Population, Intervention, Comparator, and Outcomes. Medline, PubMed, SCOPUS and the Pan African Clinical Trials Registry, among others will be searched. Two authors independent of each other shall screen titles and abstracts retrieved using the search strategy, retrieve the full text articles and assess them for eligibility and extract data. A third reviewing author will be brought in to resolve any disagreement between the two authors by discussion. The 'Cochrane Collaboration Risk of Bias Tool' will be used to assess the quality of included studies. A narrative synthesis of extracted data and, where the characteristics of the eligible studies permit, a meta-analysis (which will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) will be done. ETHICS AND DISSEMINATION: No ethical approval will be required since only published data will be used. Dissemination of results will be through peer reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42021218674.

Anticoagulation for cerebral venous thrombosis with subarachnoid hemorrhage: a case report.

OBJECTIVES: To report the success of anticoagulation (AC) treatment in a case of cerebral venous thrombosis (CVT) with subarachnoid hemorrhage (SAH) in view of the limited evidence seen in the literature supporting such a treatment option. CLINICAL PRESENTATION AND INTERVENTION: A 38-year-old lady with CVT and SAH presented 12 h after the onset of symptoms. AC with low-molecular-weight heparin was started 4 days later, when the repeated brain CT showed regression of the SAH. Heparin was changed to warfarin, and she was asymptomatic over a 12-month follow-up period. DISCUSSION: In a limited number of small studies, AC has been found to be beneficial for cases of CVT with hemorrhagic complications. The proper time to start AC in such cases was not clearly defined, and a delay of 4-33 days was observed after the onset of symptoms. In cases of spontaneous intracranial hemorrhage (ICH) in general, active bleeding is usually confined to the first 6 h, and chances of hematoma enlargement are higher in the first 24 h. On the other hand, it has been advised to rule out a coincidental vascular malformation and to radiologically confirm regression (or at least non-progression) of the ICH before starting AC. CONCLUSION: AC for cases of CVT may remain beneficial in the presence of SAH. The time to start AC for CVT with hemorrhagic complications is unclear; however, AC was successful when given 4 days after the onset of symptoms in our case. It may be wise to repeat CT after at least 24 h from the onset of symptoms (to confirm regression or at least non-progression of the ICH) before starting AC. It may also be prudent to perform magnetic resonance angiography, or digital subtraction angiography to rule out a coincidental intracranial aneurysm before AC.

Correction to: Schwannoma gene therapy by adeno-associated virus delivery of the pore-forming protein Gasdermin-D.

The original version of this Article contained an error in the spelling of the author Ahmed Abdelanabi, which was incorrectly given as Abdelanabi Ahmed. This has now been corrected in both the PDF and HTML versions of the Article.

In-depth hepatoprotective mechanistic study of Phyllanthus niruri: In vitro and in vivo studies and its chemical characterization.

Phyllanthus niruri L. is a widespread tropical plant which is used in Ayurvedic system for liver and kidney ailments. The present study aims at specifying the most active hepatoprotective extract of P. niruri and applying a bio-guided protocol to identify the active compounds responsible for this effect. P. niruri aerial parts were extracted separately with water, 50%, 70% and 80% ethanol. The cytoprotective activity of the extracts was evaluated against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cells. Bioassay-guided fractionation of the aqueous extract (AE) was accomplished for the isolation of the active compounds. Antioxidant activity was assessed using DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and ferric reducing antioxidant power (FRAP). The in vivo hepatoprotective activity of AE was evaluated in CCl4-induced hepatotoxicity in rats at different doses after determination of its LD50. Pretreatment of clone-9 and Hepg2 with different concentrations of AE (1, 0.1, 0.01 mg/ml) had significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) against CCl4 injures, and restored the activity of the natural antioxidants; glutathione (GSH) and superoxide dismutase (SOD) towards normalization. Fractionation of AE gave four fractions (I-IV). Fractions I, II, and IV showed a significant in vitro hepatoprotective activity. Purification of I, II and IV yielded seven compounds; corilagin C1, isocorilagin C2, brevifolin C3, quercetin C4, kaempferol rhamnoside C5, gallic acid C6, and brevifolin carboxylic acid C7. Compounds C1, C2, C5, and C7 showed the highest (p< 0.001) hepatoprotective potency, while C3, C4, and C6 exhibited a moderate (p< 0.001) activity. The AE exhibited strong antioxidant DPPH (IC50 11.6 ± 2 µg/ml) and FRAP (79.352 ± 2.88 mM Ferrous equivalents) activity. In vivo administration of AE in rats (25, 50, 100 and 200 mg/kg) caused normalization of AST, ALT, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total cholesterol (TC), triglycyrides (TG), total bilirubin (TB), glucose, total proteins (TP), urea and creatinine levels which were elevated by CCl4. AE also decreased TNF-α, NF-KB, IL-6, IL-8, IL10 and COX-2 expression, and significantly antagonizes the effect of CCl4 on the antioxidant enzymes SOD, catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GSP). The histopathological study also supported the hepatoprotective effect of AE. P. niruri isolates exhibited a potent hepatoprotective activity against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cell lines through reduction of lipid peroxidation and maintaining glutathione in its reduced form. This is attributable to their phenolic nature and hence antioxidative potential.