The potential role of Tirzepatide as adjuvant therapy in countering colistin-induced nephro and neurotoxicity in rats via modulation of PI3K/p-Akt/GSK3-ß/NF-kB p65 hub, shielding against oxidative and endoplasmic reticulum stress, and activation of p-CREB/BDNF/TrkB cascade.

Although colistin has a crucial antibacterial activity in treating multidrug-resistant gram-negative bacteria strains; it exhibited renal and neuronal toxicities rendering its use a challenge. Previous studies investigated the incretin hormones either glucose-dependent insulinotropic polypeptide (GIP) or glucagonlike peptide-1 (GLP-1) for their neuroprotective and nephroprotective effectiveness. The present study focused on investigating Tirzepatide (Tirze), a dual GLP-1/GIP agonist, as an adjuvant therapy in the colistin treatment protocol for attenuating its renal and neuronal complications. Rats were divided into; The normal control group, the colistin-treated group received colistin (300,000 IU/kg/day for 7 days; i.p.). The Tirze-treated group received Tirze (1.35 mg/kg on the 1,4,7thdays; s.c.) and daily colistin. Tirze effectively enhanced histopathological alterations, renal function parameters, and locomotor activity in rats. Tirze mechanistically acted via modulating various signaling axes evolved under the insult of phosphatidylinositol 3-kinases (PI3K)/phosphorylated protein kinase-B (p-Akt)/ glycogen synthase kinase (GSK)3-ß hub causing mitigation of nuclear factor (NF)-κB (NF-κB) / tumor necrosis factor-α (TNF-α), increment of nuclear factor erythroid 2-related factor 2 (Nrf2)/ glutathione (GSH), downregulation of ER stress-related biomarkers (activation transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP)), antiapoptotic effects coupling with reduction of glial fibrillary acidic protein (GFAP) immunoreactivity and enhancement of phosphorylated c-AMP response element-binding (p-CREB) / brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) neuroprotective pathway. Briefly, Tirze exerts a promising role as adjuvant therapy in the colistin treatment protocol for protection against colistin's nephro- and neurotoxicity according to its anti-inflammatory, antioxidant, and antiapoptotic impacts besides its ability to suppress ER stress-related biomarkers.

Impact of childbirth on pelvic floor dysfunction in women who have undergone previous pelvic floor reconstructive surgery: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to perform a systematic review and meta-analysis of the impact of pregnancy and childbirth (vaginal delivery [VD]) or cesarean section (CS) on the recurrence of pelvic floor disorders in women who had previously undergone pelvic floor reconstructive surgery for pelvic organ prolapse (POP) or stress urinary incontinence (SUI), to facilitate future evidence-based counseling. METHODS: PubMed, Cochrane, Embase, BJOG, Scopus, etc. were screened, from 1990 to date. Inclusion criteria included cohort studies, case-control studies, case series, and case reports that reported on the primary outcome measure of the review. Exclusion criteria included studies on surgical procedures whose outcomes are unlikely to be impacted by pregnancy and childbirth or are obsolete. Meta-analysis was performed using Review Manager 5.3. RESULTS: Seven papers on midurethral slings (MUS; 181 women in both VD and CS groups respectively) and three papers on different hysteropexy techniques (47 and 29 women in the VD and CS groups respectively), were included in the meta-analysis. No difference was seen between the two groups regarding the recurrence of SUI in women who had previously undergone MUS surgery (OR: 1.18 [0.66, 2.09]; Z = 0.56; p = 0.58) or the recurrence of POP following hysteropexy using various apical suspension procedures (OR: 1.81 [0.04, 80.65]; Z = 0.31; p = 0.76). There are insufficient data to support meta-analyses for individual MUS sub-types or hysteropexy procedures. CONCLUSION: Current literature does not demonstrate a protective effect of CS in preventing recurrent SUI in women who had undergone MUS surgery for SUI. When hysteropexy is considered irrespective of the apical suspension procedure employed, the incidence of recurrent POP appears similar after CS and VD.

Nanocarriers significantly augment the absorption of ocular-delivered drugs: A comparative meta-analysis study.

This study presents a meta-analysis that compiles information collected from several studies aiming to prove, by evidence, that nanocarriers out-perform conventional formulations in augmenting the bioavailability of ocular topically administered drugs. Data was further categorized into two subgroups; polymeric-based nanocarriers versus their lipid-based counterparts, as well as, naturally-driven carriers versus synthetically-fabricated ones. After normalization, the pharmacokinetic factor, area under the curve (AUC), was denoted as the "effect" in the conducted study, and the corresponding Forest plots were obtained. Our meta-analysis study confirmed the absorption enhancement effect of loading drugs into nanocarriers as compared to conventional topical ocular dosage forms. Interestingly, no significant differences were recorded between the polymeric and lipidic nanocarriers included in the study, while naturally-driven nanoplatforms were proven superior to the synthetic alternatives.

Quality of maternal and newborn health care at private hospitals in Iraq: a cross-sectional study.

BACKGROUND: Approximately 25% of facility births take place in private health facilities. Recent national studies of maternal and newborn health (MNH) service availability and quality have focused solely on the status of public sector facilities, leaving a striking gap in information on the quality of maternal and newborn care services. METHODS: A rapid cross-sectional assessment was conducted in November 2022 to assess the quality of MNH services at private hospitals in Iraq. Multi-stage sampling was used to select 15% of the country's 164 private hospitals. Assessment tools included a facility assessment checklist, a structured health worker interview tool, and a structured client exit interview tool. Data collection was conducted using KoboToolbox software on Android tablets, and analysis conducted using SPSS v28. RESULTS: All hospitals visited provided MNH services and had skilled personnel present or on-call 24 h/day, 7 days/week. Most births (88%) documented between January and June 2022 were cesarean births. Findings indicate that nearly all hospitals have the human resources, equipment, medicines and supplies necessary for quality antenatal, intrapartum and early essential newborn care, and many are also equipped with special units and resources needed to care for small and sick babies. However, while resources are in place for basic and advanced care, there are gaps in knowledge and practice of high-impact interventions that require few or no resources to perform, including skin-to-skin thermal care and support for early initiation of breastfeeding. Person-centered maternity care scores suggest that private hospitals offer a positive experience of care for all clients, however there is room for improvement in provider-client communication. CONCLUSIONS: This assessment highlights the need for deeper dives into factors that underly decisions about how and where to give birth, and both understanding and practice of early essential newborn care and pre-discharge examinations and counseling at private healthcare facilities in Iraq. Engaging private health facility staff in efforts to monitor and improve the quality of maternal and newborn care, with a focus on early essential newborn care and provider-client communication for all clients, will ensure that women and newborns benefit from the best care possible with available resources.

Biodegradation of COVID19 antibiotic; azithromycin and its impact on soil microbial community in the presence of phenolic waste and with temperature variation.

The increase in using antibiotics, especially Azithromycin have increased steadily since the beginning of COVID19 pandemic. This increase has led to its presence in water systems which consequently led to its presence upon using this water for irrigation. The aim of the present work is to study the impact of irrigation using Azithromycin containing water on soil microbial community and its catabolic activity in the presence of phenolic wastes as compost. Wild berry, red grapes, pomegranate, and spent tea waste were added to soil and the degradation was monitored after 5 and 7 days at ambient and high temperatures. The results obtained show that at 30 °C, soil microbial community collectively was able to degrade Azithromycin, while at 40 °C, addition of spent tea as compost was needed to reach higher degradation. To ensure that the degradation was biotic and depended on degradation by indigenous microflora, a 25 kGy irradiation dose was used to kill the microorganisms in the soil and this was used as negative control. The residual antibiotic was assayed using UV spectroscopy and High Performance Liquid Chromatography (HPLC). Indication of Azithromycin presence was studied using Fourier Transform Infrared Spectroscopy (FTIR) peaks and the same pattern was obtained using the 3 used detection methods, the ability to assign the peaks even in the presence of soil and not to have any overlaps, gives the chance to study this result in depth to prepare IR based sensor for quick sensing of antibiotic in environmental samples.

Design and evaluation of chrysin-loaded nanoemulsion against lithium/pilocarpine-induced status epilepticus in rats; emphasis on formulation, neuronal excitotoxicity, oxidative stress, microglia polarization, and AMPK/SIRT-1/PGC-1α pathway.

OBJECTIVES: The present study aims to formulate and evaluate the efficacy of chrysin-loaded nanoemulsion (CH NE) against lithium/pilocarpine-induced epilepsy in rats, as well as, elucidate its effect on main epilepsy pathogenesis cornerstones; neuronal hyperactivity, oxidative stress, and neuroinflammation. METHODS: NEs were characterized by droplet size, zeta potential, pH, in vitro release, accelerated and long-term stability studies. Anti-convulsant efficacy of the optimized formula and underlying mechanisms involved were assessed and compared to that from CH suspension given orally at a 30 folds higher dose. RESULTS: Optimized formula displayed a droplet size of 48.09 ± 0.83 nm, PDI 0.25 ± 0.011, sustained release, and good stability. CH treatment reduced seizures scoring, corrected behavioral and histological changes induced by Li/Pilo. Moreover, CH restored neurotransmitters balance and oxidative stress markers levels. Besides, CH induced microglia polarization from M1 to M2 hindering inflammation induced by Li/Pilo. Also, CH restored energy metabolism homeostasis via regulating protein expression of AMPK/SIRT-1/PGC-1α pathway markers. CH NE formulation was found to significantly enhance drug delivery to rats' hippocampus compared to CH suspension. CONCLUSION: Our findings prove the therapeutic efficacy of CH NE at a lower dose which could be a potential brain targeting platform to combat epilepsy.

Bacillus spizizenii DN and microbial consortia biostimulation followed by gamma irradiation for efficient textile wastewater treatment.

Textile wastewater still poses a huge environmental problem due to its high water consumption and high effluent release that is full of toxic chemicals. In the present study, different approaches were studied to layout an operating procedure for textile wastewater treatment in order to obtain treated wastewater that is safe for non-potable uses. Our approach depended on (1) co-substrate to biostimulate indigenous microbial textile wastewater community by adding Tryptone Soy Broth (TSB) and TSB supplemented with 1% glucose, (2) co-culture (bioaugmentation) with Bacillus spizizenii DN cells (previously isolated, identified and characterized as efficient decolorizing bacteria), and (3) co-metabolites using Bacillus spizizenii DN metabolites. The obtained results show that using Bacillus spizizenii DN cells resulted in 97.78% decolorization while adding Bacillus spizizenii DN metabolites resulted in 82.92% decolorization, both after 48 h incubation under microaerophilic conditions. The phyla identified for all treatments were Bacteroidota, Firmicutes, and Proteobacteria. The dynamic changes in the bacteria showed that both Clostridium and Acinetobacter disappeared for co-substrate, co-culture, and co-metabolite cultures. While Alkalibacterium and Stenotrophomonas appeared after adding Bacillus spizizenii DN cells, Flavobacterium increased for co-substrate and co-metabolic cultures while iron reducing bacteria appeared only for co-metabolic cultures. The use of 25 kGy gamma irradiation as a sterilization dose post bioremediation ensured safe use of treated wastewater. This was confirmed by cytotoxicity assay; the obtained IC50 tested on BJ fibroblasts obtained from skin showed that gamma irradiated treated wastewater are about 80.1% less toxic than non-irradiated treated wastewater. We conclude that (1) we can use combined bioaugmentation and biostimulation as initial steps for in situ bioremediation in collection tanks and that (2) the proposed protocol for bioremediation of industrial wastewater should be tailored based on the required application and level of safety needed for re-use.

Taxonomic and functional structure of macrobenthic invertebrate communities and their response to environmental variables along the subbranches of the Nile River (rayahs), Egypt.

Macrobenthic invertebrate communities serve as markers of anthropogenic stress in freshwater ecosystems. In this study, 17 sampling sites were selected from two Nile river subbranches (El-Rayah El-Behery and El-Rayah El-Nassery) and subjected to different anthropogenic influences to explore the ecological environment and characteristics of macrobenthos communities. Macrobenthos were studied using taxonomic diversity and biological trait analysis to investigate how human activity and variation in water quality affect their structure and function. A total of 37 taxa represented by 43,389 individuals were recognized. The communities are composed chiefly of Oligochaeta and aquatic insects. Multivariate statistical analyses found that the most influential environmental variables in the structural and functional community were sodium, dissolved oxygen, silicate, pH, calcium, and cadmium. At high levels of pollution, notably sewage and industrial pollution in the northern part of El-Rayah El-Behery, characteristics such as larger body size, detritus feeders, burrowers, and high tolerance to pollution predominated, whereas at low levels of pollution, features such as small body sizes, scraper and predator feeders, intolerant and fairly tolerant of pollution, and climber and swimmer mobility are predominant. The results confirm our prediction that the distribution of macroinvertebrate traits varies spatially in response to environmental changes. The diversity-based method distinguished impacted sewage and industrial sites from thermal effluent sites, while the trait-based approach illustrated an apparent variance between the ecological status of contaminated regions. Therefore, the biological features should be employed in addition to structural aspects for assessing the biodiversity of macroinvertebrate communities under environmental stressors.

Nanostructured Lipid Carriers for Oral Delivery of a Corticosteroid: Role of Formulation on Biopharmaceutical Performance.

Corticosteroids are potent anti-inflammatory and immunosuppressive drugs widely used world-wide for treatment of diverse conditions. However, their use is restricted by their poor bioavailability and high risk-benefit ratio. Therefore, the aim of this study was to develop nanostructred lipid carriers (NLC) of prednisolone acetate (PA) to improve the drug's therapeutic outcome by altering its pharmacokinetic profile and/or allow preferential targeting to inflammatory tissues. PA-loaded NLCs were formulated by solvent injection method using Compritol (solid lipid), oleic acid (liquid lipid) and Tween 80 or Pluronic F68 (surfactant). Formulation conditions, such as liquid lipid concentration, total lipids, drug:lipid ratio and surfactant type were optimized based on particle size (PS), polydispersity index (PDI), and encapsulation efficiency (EE%) results. Optimized formulation was further characterized for its surface morphology, thermal properties, storage stability and anti-inflammatory activity in an animal acute inflammation model. Selected NLCs displayed PS of 170.7 nm, EE% of 67.4%, sustained release over 72 h and good stability for 30 days at refrigeration conditions. PA NLCs displayed superior anti-inflammatory activity of 83.9 ± 4.46% compared to PA suspension (40.5 ± 7.03%) and drug-free NLCs (54.7 ± 6.12%). The current work delineates the potential of NLCs for distinctly improved biopharmaceutical performance of PA.

Convergent innervations of mesencephalic trigeminal and vestibular nuclei neurons onto oculomotor and pre-oculomotor neurons-Tract tracing and triple labeling in rats.

In studies of vestibulo-ocular reflex (VOR), the horizontal VOR circuit is much clearer than vertical-torsional VOR. The circuit and mechanism of gravity-related vertical-torsional VOR is probably weak. "Somatosensory vestibular interaction" is a known extra source to facilitate VOR, and cervico-ocular reflex is a representative for torsional VOR compensation. Whereas, how the cervical afferents finally reach the oculomotor system is less documented. Actually, when the head tilts, which generates cervico-ocular reflex, not only the neck muscle is activated, but also the jaw muscle is stretched by gravity dragged mandible and/or tissue-muscle connection between the mandible and clavicle. We have previously identified a projection from the jaw muscle afferent mesencephalic trigeminal nucleus (Vme) neurons to oculomotor nuclei (III/IV) and their premotor neurons in interstitial nucleus of Cajal (INC)-a well-known pre-oculomotor center manipulating vertical-torsional eye movements. We hypothesized that these projections may interact with vestibulo-ocular signals during vertical-torsional VOR, because effects of gravity on jaw muscles and bones has been reported. Thus, we injected different anterograde tracers into the Vme and medial vestibular nucleus (MVN)-the subnuclear area particularly harboring excitatory vestibulo-ocular neurons, and immunostained III/IV motoneurons. Retrograde tracer was injected into the III in the same animals after dual anterograde tracers' injections. Under confocal microscope, we observed the Vme and MVN neuronal endings simultaneously terminated onto the same III/IV motoneurons and the same INC pre-oculomotor neurons. We consider that jaw muscle proprioceptive Vme neurons projecting to the III/IV and INC would sense spindle activity if the jaw muscle is stretched by gravity dragged mandible or connection between mandible and clavicle during head rolling. Therefore, the convergent innervation of the Vme and MVN neurons onto the oculomotor and pre-oculomotor nuclei would be a neuroanatomic substrate for interaction of masticatory proprioception with the vestibulo-ocular signals upon the oculomotor system during vertical-torsional VOR.

"Spanlastic nanovesicles for enhanced ocular delivery of vanillic acid: design, in vitro characterization, and in vivo anti-inflammatory evaluation".

Spanlastics are novel surfactant-based, elastic vesicular nanocarriers composed of spans and edge activators. The present work aims to exploit their special penetration enhancing properties to enhance the ophthalmic delivery of the versatile nutraceutical vanillic acid (VA), for treatment of ocular inflammation. VA-loaded spanlastics were formulated by ethanol injection method using Tween 80, sodium deoxy cholate or Tween 60 as edge activators (EA) at various Span 60: EA mass ratios. Vesicles were characterized for their particle size (PS), polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), surface morphology, in vitro release profile, thermal properties and long-term stability, in addition to in vivo anti-inflammatory efficacy of the selected formula in an endotoxin-induced uveitis model. Selected formulation composed of Span 60: Tween 80 at a mass ratio of 70:30 displayed smallest PS of 299.8 ± 9.97 nm, PDI of 0.386 ± 0.047, an acceptable EE%, as well as good physical stability for 3 months. According to clinical scoring, inflammatory mediators levels and histopathological examination, VA-loaded spanlastic formulation resulted in significant alleviation of inflammation compared to drug suspension (p < 0.05). Formulation of VA into spanlastic nanoformulation is a promising approach to improve its ocular permeability, absorption and anti-inflammatory activity providing a safer alternative to current regimens.

Are sexual and reproductive health and rights taught in medical school? Results from a global survey.

Our aim was to investigate the inclusion of sexual and reproductive health and rights (SRHR) topics in medical curricula and the perceived need for, feasibility of, and barriers to teaching SRHR. We distributed a survey with questions on SRHR content, and factors regulating SRHR content, to medical universities worldwide using chain referral. Associations between high SRHR content and independent variables were analyzed using unconditional linear regression or χ2 test. Text data were analyzed by thematic analysis. We collected data from 219 respondents, 143 universities and 54 countries. Clinical SRHR topics such as safe pregnancy and childbirth (95.7%) and contraceptive methods (97.2%) were more frequently reported as taught compared with complex SRHR topics such as sexual violence (63.8%), unsafe abortion (65.7%), and the vulnerability of LGBTQIA persons (23.2%). High SRHR content was associated with high-income level (P = 0.003) and low abortion restriction (P = 0.042) but varied within settings. Most respondents described teaching SRHR as essential to the health of society. Complexity was cited as a barrier, as were cultural taboos, lack of stakeholder recognition, and dependency on fees and ranking.

Two-year anatomical and functional outcomes of laparoscopic sacrocolpopexy using light-weight Y shaped mesh for post hysterectomy vaginal prolapse.

OBJECTIVE: The aim of this study is to evaluate the efficacy, safety, anatomical and functional outcomes of patients undergoing laparoscopic sacrocolpopexy (LSC) using light-weight Y mesh for post hysterectomy vaginal prolapse. STUDY DESIGN: A retrospective observational study of women who underwent LSC for post hysterectomy vaginal vault prolapse between January 2010 and January 2019. Y shaped mesh was used for the LSC after dissection of the rectum and the bladder. Pre-operative evaluation included symptoms' assessment using the Prolpase Quality of Life Questionnaire (P-QOL) and objective assessment using the POP-Q scores. Post operatively, patient symptoms, anatomical outcomes, mesh complications and patient global impression of improvement scores were evaluated. Patients were followed up at 12 months and yearly thereafter. RESULTS: 247 consecutive patients were included in this study. Patients' age ranged from 35 to 86 years old with an average BMI of 28.8. The most common presenting symptoms were vaginal bulge (95%), vaginal heaviness (73%) and urinary urgency (46%). The time interval between hysterectomy and LSC was 10.5 years (5 months - 42 years). Complications reported were bladder injury (1.6%), small bowel injury (0.8%), major haemorrhage (0.4%), vaginal mesh extrusion (1.2 %). 85.8% of women reported cure of prolapse symptoms. 14.2% of patients developed further/unresolved prolapse symptoms and 6.5% went on to have further surgery for prolapse. 10% of women developed new onset dyspareunia. Anatomically, postoperative point C (apex) was at -7.6 cm (range -9 - +3 cm) CONCLUSION: LSC using Y mesh for post hysterectomy vaginal prolapse is safe. LSC is effective in 85% of women who develop vaginal prolapse post hysterectomy. Further surgery for bothersome prolapse symptoms were needed in 6.5% with a 1.2% mesh extrusion rate and 10% new onset dyspareunia. This will help in counselling women undergoing this surgery.

Integrated experimental and theoretical insights for Malachite Green Dye adsorption from wastewater using low cost adsorbent.

Water pollution is one of the problems that threaten humanity, and to confront it with only experimental procedures is not enough. It is necessary to integrate both practical methods and theoretical calculations to achieve decontamination with the most accurate interpretation. Hence, discussing the experimental mechanism study of Malachite Green (MG) dye adsorption with the help of the application of density functional theory (DFT) calculations is the main goal of this article. The experimental results affirmed that the preparation of γ-Al2O3 by precipitation method using (NH4)2CO3 improved the porosity, the surface capability, and the adsorbent capacities (qmax = 210 mg/g) at optimum condition compared with the previous studies. Kinetic and equilibrium studies showed that the adsorption follows the pseudo-second-order model and Freundlich isotherm model, respectively. Also, the calculated and observed thermodynamic parameters exerted positive values of ΔH° and ΔS°, which translates into an endothermic process with increasing disorder of the system. Theoretical calculations at DFT- B3LYP/6-31G (d,P) level of theory were calculated to show the selectivity of using the cationic form of MG in the experimental measurements to find the interaction mechanism. The electronic structure and intramolecular charge transfer of MG, its cationic form and the complex of MG-Al were investigated theoretically at the B3LYP/6-31 G (d,p) level of theory. The equilibrium geometries of MG, its cationic form and the complex of MG-Al were determined, and it was found that these geometries are non-planar. The EHOMO and ELUMO energies can be used to calculate the global properties; chemical hardness (η), softness (S) and electronegativity (χ). The calculated non-linear optical parameters (NLO) of the studied compounds, the electronic dipole moment (µ), first-order hyperpolarizability (ß), the hyper-Rayleigh scattering (ßHRS) and the depolarization ratio (DR), showed promising optical properties. Finally, the computational and the experimental results indicated that the adsorption efficiency of MG from wastewater was directly associated with the dye electrophilicity power.

Resilience of health systems in conflict affected governorates of Iraq, 2014-2018.

OBJECTIVES: The objective of this study was to assess the resilience of health systems in four governorates affected by conflict from 2014 to 2018, and to convey recommendations. METHODS: Health managers from Al Anbar, Ninawa, Salah al-Din, and Kirkuk governorates discussed resilience factors of Primary Health Care services affected by the 2014-2017 ISIS insurgency in focus groups, and general discussions. Additional information was gathered from key informants and a UNICEF health facility survey. Three specific aspects were examined: (1) meeting health needs in the immediate crisis response, (2) adaptation of services, (3) restructuring and recovery measures. Data from a MoH/UNICEF national health facility survey in 2017 were analyzed for functionality. RESULTS: There were many common themes across the four governorates, with local variations. (1) Absorption The shock to the public sector health services by the ISIS invasion caught health services in the four governorates unprepared, with limited abilities to continue to provide services. Private pharmacies and private clinics in some places withstood the initial shock better than the public sector. (2) Adaptation After the initial shock, many health facilities adapted by focusing on urgent needs for injury and communicable disease care. In most locations, maternal, neonatal, and child health (MNCH) preventive and promotive PHC services stopped. Ill persons would sometimes consult health workers in their houses at night for security reasons. (3) Restructuring or transformative activities In most areas, health services recovery was continuing in 2020. Some heavily damaged facilities are still functioning, but below pre-crisis level. Rebuilding lost community trust in the public sector is proving difficult. CONCLUSION: Health services generally had little preparation for and limited resilience to the ISIS influx. Governorates are still restructuring services after the liberation from ISIS in 2017. Disaster planning was identified by all participants as a missing component, as everyone anticipated future similar emergencies.

Nose-to-brain delivery of chrysin transfersomal and composite vesicles in doxorubicin-induced cognitive impairment in rats: Insights on formulation, oxidative stress and TLR4/NF-kB/NLRP3 pathways.

Many cancer survivors suffer from chemotherapy-induced cognitive impairment known as 'Chemobrain'. Doxorubicin -topoisomerase II inhibitor- is widely used in breast cancer, hematological cancers and other neoplasms. However, it is reported to precipitate cognitive impairment in cancer patients via inducing oxidative stress and inflammatory response. Chrysin -5,7 dihydroxyflavone- has promising antioxidant, anti-inflammatory and anticancer properties, but suffers low bioavailability owing to its poor solubility and extensive metabolism. In the present study, chrysin was successfully formulated as transfersomal lipid vesicles and chitosan composite vesicles (CCV) exhibiting a nanometric size range, high drug entrapment efficiency, and controlled release over a 72h period. Intranasal administration of optimized chrysin formulations at a reduced dose of 0.5 mg/kg improved doxorubicin-induced memory impairment in rats evidenced by behavioral testing, inhibition of acetylcholinesterase activity and oxidative stress markers; catalase, reduced glutathione, lipid peroxidation and hydrogen peroxide. This could reduce caspase-3 expression inhibiting apoptosis. Moreover, chrysin formulations were able to inhibit doxorubicin-induced Tol-like receptor 4 (TLR4) and p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) protein expression which in turn, reduced procaspase-1, Cysteinyl Aspartate Protease-1 (caspase-1) and Interleukin-1ß (IL-1ß) protein expression via inhibiting Nod-like receptor pyrin containing 3 (NLRP3) inflammasome. Collectively, our findings suggest the enhanced therapeutic potential of chrysin when formulated as transfersomes and CCV against chemotherapy-induced chemobrain via hindering acetylcholinesterase, oxidative stress and TLR4-NF-kB(p65)-NLRP3 pathways.

How the coronavirus disease 2019 pandemic is impacting sexual and reproductive health and rights and response: Results from a global survey of providers, researchers, and policy-makers.

INTRODUCTION: We aimed to give a global overview of trends in access to sexual and reproductive health and rights (SRHR) during the coronavirus disease 2019 (COVID-19) pandemic and what is being done to mitigate its impact. MATERIAL AND METHODS: We performed a descriptive analysis and content analysis based on an online survey among clinicians, researchers, and organizations. Our data were extracted from multiple-choice questions on access to SRHR services and risk of SRHR violations, and written responses to open-ended questions on threats to access and required response. RESULTS: The survey was answered by 51 people representing 29 countries. Eighty-six percent reported that access to contraceptive services was less or much less because of COVID-19, corresponding figures for surgical and medical abortion were 62% and 46%. The increased risk of gender-based and sexual violence was assessed as moderate or severe by 79%. Among countries with mildly restrictive abortion policies, 69% had implemented changes to facilitate access to abortion during the pandemic, compared with none among countries with severe restrictions (P < .001), 87.5% compared with 46% had implemented changes to facilitate access to contraception (P = .023). The content analysis showed that (a) prioritizations in health service delivery at the expense of SRHR, (b) lack of political will, (c) the detrimental effect of lockdown, and (d) the suspension of sexual education, were threats to SRHR access (theme 1). Requirements to mitigate these threats (theme 2) were (a) political will and support of universal access to SRH services, (b) the sensitization of providers, (c) free public transport, and (d) physical protective equipment. A contrasting third theme was the state of exception of the COVID-19 pandemic as a window of opportunity to push forward women's health and rights. CONCLUSIONS: Many countries have seen decreased access to and increased violations of SRHR during the COVID-19 pandemic. Countries with severe restrictions on abortion seem less likely to have implemented changes to SRHR delivery to mitigate this impact. Political will to support the advancement of SRHR is often lacking, which is fundamental to ensuring both continued access and, in a minority of cases, the solidification of gains made to SRHR during the pandemic.

Synthesis, and characterization of chitosan bearing pyranoquinolinone moiety for textile dye adsorption from wastewater.

A novel compound was synthesized by the reaction of the amino group of the chitosan with the formyl group of pyrano[3,2-c]quinoline-3-carboxaldehyde moiety, which produced chitosan modified with a Schiff base (chitosan Schiff base). The structure of the newly prepared composite was elucidated. Chitosan Schiff base was used to remove the textile anionic remazol red (RR) dye from wastewater. The kinetic data and adsorption isotherm were best fitted by the pseudo-second-order kinetic model and the Freundlich isotherm, respectively. Thermodynamic parameters were calculated. Chitosan Schiff base resulted in 100% removal of carcinogenic dye at 2 min only with qm 344.8 mg/g, and may do the same for other anionic reactive dyes, thus avoiding secondary pollution.

Differential Regulation of the Glucocorticoid Receptor in a Rat Model of Inflammatory Pain.

BACKGROUND: Anti-inflammatory corticosteroids are a common treatment for different conditions involving chronic pain and inflammation. Clinically used steroids target the glucocorticoid receptor (GR) for its anti-inflammatory effects. We previously reported that GR in sensory neurons may play central roles in some pain models and that GR immunoreactivity signal in dorsal root ganglia (DRG) decreased after local inflammation of the DRG (a model of low back pain). In the current study, we aimed to determine if similar changes in GR signal also exist in a skin inflammation model, the complete Freund's adjuvant (CFA) model (a model of peripheral inflammatory pain), in which the terminals of the sensory neurons rather than the somata are inflamed. METHODS: A low dose of CFA was injected into the hind paw to establish the peripheral inflammation model in Sprague-Dawley rats of both sexes, as confirmed by measurements of behavior and paw swelling. Immunohistochemical and western blotting techniques were used to determine the expression pattern of the GR in the inflamed hind paw and the DRGs. Plasma corticosterone levels were measured with radioimmunoassay. RESULTS: The immunohistochemical staining revealed that GR is widely expressed in the normal DRG and skin tissues. Paw injection with CFA caused upregulation of the GR in the skin tissue on postinjection day 1, mostly detected in the dermis area. However, paw inflammation significantly reduced the GR signal in the L5 DRG 1 day after the injection. The GR downregulation was still evident 14 days after CFA inflammation. On day 1, western blotting confirmed this downregulation and showed that it could also be observed in the contralateral L5 DRG, as well as in the L2 DRG (a level which does not innervate the paw). Plasma corticosterone levels were elevated in both sexes on day 14 after CFA compared to day 1, suggesting autologous downregulation of the GR by corticosterone may have contributed to the downregulation observed on day 14 but not day 1. CONCLUSIONS: There are distinctive patterns of GR activation under different pain conditions, depending on the anatomical location. The observed downregulation of the GR in sensory neurons may have a significant impact on the use of steroids as treatment in these conditions and on the regulatory effects of endogenous glucocorticoids.