Impact of Repetitive Transcranial Magnetic Stimulation on Cognitive and Psychiatric Dysfunction in Patients with Fibromyalgia: A Double-Blinded, Randomized Clinical Trial.

Few randomized controlled trials have reported that repetitive transcranial magnetic stimulation (rTMS) has controversial results for managing multiple domains of fibromyalgia-related symptoms. This work aimed to evaluate the effect of low-frequency rTMS over the right dorsolateral prefrontal area (DLPFC) on the Fibromyalgia Impact Questionnaire (FIQ) concerning psychiatric and cognitive disorders. Forty-two eligible patients with fibromyalgia (FM) were randomized to have 20 sessions of active or sham rTMS (1 Hz, 120% of resting motor threshold with a total of 1200 pules/session) over the right DLPFC. All participants were evaluated at baseline, post sessions, and 3 months after sessions with the FIQ, Hamilton depression, and anxiety rating scales (HDRS and HARS), Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Tower of London test (TOL), the Trail Making, and Digit Span Tests. Both groups showed improvement in most rating scales at 1 and 3 months follow-up, with greater improvement in the active group, with significant correlation between FIQ cognitive rating scales, including RAVLT and TOL. Twenty sessions of low-frequency rTMS over the right DLPFC can improve FIQ scores regarding the psychiatric and cognitive symptoms of medicated patients with FM to a greater extent than sham. Changes in RAVLT and TOL correlated with changes in FIQ results.

Ezetimibe-Loaded Nanostructured Lipid Carrier for Oral Delivery: Response Surface Methodology; In Vitro Characterization and Assessing the Antihyperlipidemic Effect in Rats.

Among the independent risk factors for the occurrence of cardiovascular diseases like atherosclerosis is hyperlipidemia. To decrease cardiovascular events and patient mortality, antihyperlipidemia therapy is crucial. Our study aimed to enhance the solubility of the poorly soluble lipid-lowering agent ezetimibe (EZ), a member of class II as per the Biopharmaceutics Classification System (BCS). The drug was formulated as a nanostructured lipid carrier (NLC) employing the ultrasonication technique. A response surface D-optimal design was employed to study the effect of changing the liquid lipid type and the percentage of liquid lipid with respect to total lipid amount on the particle size, zeta potential, percentage entrapment efficiency, and percentage of drug released after 24 h. Nine NLC formulations were prepared and pharmaceutically evaluated, and the optimized NLC formulation was selected, further characterized, and evaluated as well. Optimized EZ-NLC was assessed in the high-fat diet model to induce hyperlipidemia in rats in comparison with the EZ suspension. The results of the optimized formulation showed that the prepared NLCs were spherical with no aggregation having a particle size of 204.3 ± 19.17 nm, zeta potential equal to -32 ± 7.59 mV, and entrapment efficiency of 81.5 ± 3.58% and 72.15 ± 4.58% drug released after 24 h. EZ-NLC significantly decreased the elevated serum lipid parameters, including total cholesterol, triglycerides, and LDL-C, but significantly normalized serum HDL-C levels of rats kept on a high-fat diet. The results demonstrated the improved efficacy of EZ-NLC in ameliorating the elevated serum lipid parameters compared to EZ.

Green Synthesis of Highly Fluorescent Carbon Dots from Bovine Serum Albumin for Linezolid Drug Delivery as Potential Wound Healing Biomaterial: Bio-Synergistic Approach, Antibacterial Activity, and In Vitro and Ex Vivo Evaluation.

A simple and green approach was developed to produce novel highly fluorescent bovine serum albumin carbon dots (BCDs) via facile one-step hydrothermal treatment, using bovine serum albumin as a precursor carbon source. Inherent blue photoluminescence of the synthesized BCDs provided a maximum photostability of 90.5 ± 1.2% and was characterized via TEM, FT-IR, XPS, XRD, UV-visible, and zeta potential analyses. By virtue of their extremely small size, intrinsic optical and photoluminescence properties, superior photostability, and useful non-covalent interactions with the synthetic oxazolidinone antibiotic linezolid (LNZ), BCDs were investigated as fluorescent nano-biocarriers for LNZ drug delivery. The release profile of LNZ from the drug delivery system (LNZ-BCDs) revealed a distinct biphasic release, which is beneficial for mollifying the lethal incidents associated with wound infection. The effective wound healing performance of the developed LNZ-BCDs were evaluated through various in vitro and ex vivo assays such as MTT, ex vivo hemolysis, in vitro antibacterial activity, in vitro skin-related enzyme inhibition, and scratch wound healing assays. The examination of LNZ-BCDs as an efficient wound healing biomaterial illustrated excellent biocompatibility and low cytotoxicity against normal human skin fibroblast (HSF) cell line, indicating distinct antibacterial activity against the most common wound infectious pathogens including Staphylococcus aureus (ATCC® 25922) and methicillin-resistant Staphylococcus aureus, robust anti-elastase, anti-collagenase, and anti-tyrosinase activities, and enhanced cell proliferation and migration effect. The obtained results confirmed the feasibility of using the newly designed fluorescent LNZ-BCDs nano-bioconjugate as a unique antibacterial biomaterial for effective wound healing and tissue regeneration. Besides, the greenly synthesized BCDs could be considered as a great potential substitute for toxic nanoparticles in biomedical applications due to their biocompatibility and intense fluorescence characteristics and in pharmaceutical industries as promising drug delivery nano-biocarriers for effective wound healing applications.

Characteristics of suicidal poisoned patients admitted to tertiary care center during COVID-19 pandemic.

Background: Suicidal poisoning is a major concern during the COVID-19 pandemic that has several physical and mental hazards. This study aimed to evaluate the characteristics of suicidal poisoned patients admitted to a tertiary poison control center during the pandemic lockdown and assess COVID-related knowledge and attitude among those patients to identify the high-risk group for suicide. This cross-sectional study was conducted on acutely poisoned patients admitted to Tanta University Poison Control Center from June to December 2020. Upon admission, socio-demographic data, causative poisoning agents, COVID-related knowledge and attitude, Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D) were collected from all participants. Results: A total of 254 poisoned patients were categorized into suicidal (85.04%) and accidental (14.96%) poisoning groups. The former was caused mainly by phosphides and was significantly associated with a history of using psychotropic medications and high HAM-A and HAM-D results. Logistic regression analysis showed that a history of psychiatric illness, low attitude scores, and high HAM-D scores were significant risk factors for suicidal poisoning. Conclusions: Considerable number of suicidal poisoned patients had moderate-to-severe depressive symptoms, highlighting the importance of providing specialized psychiatric services in poisoning centers, particularly among vulnerable populations, to prevent the overwhelming repeated suicidal attempts. Supplementary Information: The online version contains supplementary material available at 10.1186/s41983-022-00577-4.

Novel linezolid loaded bio-composite films as dressings for effective wound healing: experimental design, development, optimization, and antimicrobial activity.

Biphasic release bio-composite films of the low water-soluble drug, linezolid (LNZ), were formulated using the solvent casting technique. Different polymers and plasticizers (gelatin, Tween 80, polyethylene glycol 400, and glycerol) were assessed for the preparation of bio-composite films. An I-optimal design was applied for the optimization and to study the impact of polymer concentration (X1), plasticizer concentration (X2), polymer type (X3), and plasticizer type (X4) on different LNZ-loaded bio-composite films. The film thickness, moisture content, mechanical properties, swelling index, and percentage of drug release at fixed times opted as dependent variables. Results demonstrated a significant effect of all independent variables on the drug release from the prepared bio-composite films. The plasticizer concentration significantly increased the thickness, moisture content, elongation at break, swelling index, and in vitro drug release and significantly reduced the tensile strength. The optimized LNZ-loaded bio-composite film comprised of 15% Tween 80 and 30% PEG 400 was highly swellable, elastic, acceptable tensile properties, safe, maintained a moist environment, and indicated great antimicrobial activity against both Staphylococcus aureus (ATCC® 25922) and methicillin-resistant Staphylococcus aureus (MRSA), which are common wound infectious bacteria. The present study concludes that the optimized LNZ-loaded bio-composite film was successfully designed with fast drug release kinetics and it could be regarded as a promising novel antimicrobial wound dressing formulation.

Efficient lung-targeted delivery of risedronate sodium/vitamin D3 conjugated PAMAM-G5 dendrimers for managing osteoporosis: Pharmacodynamics, molecular pathways and metabolomics considerations.

AIMS: This study aims at formulating combined delivery of Risedronate sodium (RIS) and Vitamin D3 (VITD3) for augmented therapeutic outcome against osteoporosis (OP) using deep lung targeted PAMAM-G5-NH2 dendrimers to minimize RIS gastrointestinal side effects and enhance both drugs bioavailability through absorption from the alveoli directly to the blood. METHODS: RIS-PAMAM-G5-NH2, VITD3-PAMAM-G5-NH2, and RIS/VITD3-PAMAM-G5-NH2 were prepared and evaluated in vitro for particle size (PS), zeta potential (ZP), %loading efficiency (%LE), morphology and FTIR. The efficacy of the RIS/VITD3-PAMAM-G5-NH2 compared to oral RIS was evaluated in OP-induced rats by comparing serum calcium, phosphorus, and computed bone mineral density (BMD) pre- and post-treatment. Additionally, a comprehensive metabolomics and molecular pathways approach was applied to find serum potential biomarkers for diagnosis and to evaluate the efficacy of inhaled RIS/VITD3-PAMAM-G5-NH2. KEY FINDINGS: RIS/VITD3-PAMAM-G5-NH2 was successfully prepared with a %LE of 92.4 ± 6.7 % (RIS) and 83.2 ± 4.4 % (VIT-D3) and a PS of 252.8 ± 34.1 adequate deep lung delivery. RIS/VITD3-PAMAM-G5-NH2 inhalation therapy was able to restore serum calcium, phosphorus, and BMD close to normal levels after 21 days of treatment in OP-induced rats. The WNT-signalling pathway and changes in the metabolite levels recovered to approximately normal levels upon treatment. Moreover, histone acetylation of the WNT-1 gene and miR-148a-3p interference proved to play a role in the regulation of the WNT-signalling pathway during OP progression and treatment. SIGNIFICANCE: Pulmonary delivery of RIS/VITD3-PAMAM-G5-NH2 offers superior treatment for OP treatment compared to the oral route. Molecular and Metabolic pathways represents key indicators for OP diagnosis and progression.

Formulation, characterization and cellular toxicity assessment of a novel bee-venom microsphere in prostate cancer treatment.

Bee venom (B.V.) is a toxin produced naturally by honey bees with several toxic and therapeutic efficacies. It is used in the treatment of different cancer kinds like renal, hepatic, and prostate cancer. Due to its protein nature, it is degraded in the upper gastrointestinal tract. Colon-targeted drug delivery systems represent a useful tool to protect B.V. from degradation and can be administered orally instead of I.V. infusion and traditional bee stinging. In the present study, B.V. loaded enteric-coated cross-linked microspheres were prepared by emulsion cross-linking method. Percentage yield, entrapment efficiency %, swelling degree, and in-vitro release are evaluated for prepared microspheres. Free B.V., optimized microspheres formula (F3), and doxorubicin cytotoxic effects were tested by MTT assay. Results concluded that free B.V. was more effective against the growth of human prostate adenocarcinoma (PC3) cells followed by optimized microspheres than doxorubicin. But both free B.V. and doxorubicin have a cytotoxic effect on normal oral epithelial cells (OEC). According to flow cytometric analysis, the optimized microsphere formula induced apoptosis and reduced necrosis percent at IC50 concentration. Furthermore, microspheres did not affect the viability of OEC. These results revealed that microspheres have a degree of specificity for malignant cells. Therefore, it seems that this targeted formulation could be a good candidate for future clinical trials for cancer therapy.

Serum interleukin-23 levels: relation to depression, anxiety, and disease activity in psoriatic arthritis patients.

OBJECTIVES: Assessment of serum levels of IL-23 in PsA patients and its correlation with depression, anxiety, and disease activity. METHODS: Eighty psoriatic arthritis (PsA) patients and eighty healthy volunteers matched for age and gender were included in this observational case-control study. All participants suspected to detailed history, clinical assessment, PsA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI), and ultrasonographic assessments of the entheses were examined according to the Madrid Sonographic Enthesitis Index (MASEI). Depression and anxiety were assessed by Hospital Anxiety and Depression Scale (HADS). Serum IL-23 was measured and correlated with disease activity, depression, and anxiety. RESULTS: There was no significant difference between patients and controls regarding demographic data. Thirty-six PsA patients (45%) had anxiety and 28 patients (35%) had depression, while in the control group, 16 persons (20%) had anxiety and 12 (15%) had depression, with significant differences between the 2 groups (p < 0.0001). There were significant differences in HADS anxiety and depression scores between patients and controls with significant positive correlations between HADS depression, anxiety scores and IL-23, DAPSA, PASI, and MASEI scores (p < 0.05). IL-23 was positively correlated with DAPSA, PASI, and HADS scores; we observed that interleukin 23, higher DAPSA, and PASI were independently associated with depression and anxiety. CONCLUSION: Serum interleukin-23 levels were elevated in PsA patients and were found to be correlated with depression, anxiety, and disease activity. Key Points • Psoriatic arthritis is a multidimensional disorder with psychiatric drawbacks. • Interleukin-23 is a proinflammatory cytokines that was correlated with depression and anxiety in PsA patients. • Interleukin-23 was correlated with disease activity in PsA. • Depression and anxiety were positively correlated with disease activity in PsA.

Prevalence of Anti-nuclear and Anti-phospholipid Antibodies in an Egyptian Cohort with Schizophrenia: A Case-control Study.

BACKGROUND: Psychiatric disorders, including schizophrenia, could herald other manifestation( s) of systemic lupus erythematosus (SLE) potentially hindering timely and optimal management. Moreover, schizophrenia is among the described 'extra-criteria' manifestations of anti-phospholipid syndrome (APS). Hence, screening schizophrenia patients for SLE and APS may pose diagnostic and therapeutic implications. OBJECTIVES: Examine schizophrenia patients with no overt connective tissue disease(s) manifestation( s) for clinical and/or serologic evidence of SLE and/or APS. METHODS: The study included 92 schizophrenia patients (61 (66.3%) males) and 100 age- and gender- matched healthy controls. Both groups were tested for anti-nuclear antibodies (ANAs), antidouble stranded deoxyribonucleic acid (anti-dsDNA) antibodies, complement 3 (C3) and C4, and criteria anti-phospholipid antibodies (aPL) (anticardiolipin Immunoglobulin (Ig) G and IgM, antibeta- 2-glycoprotein I IgG and IgM, and lupus anticoagulant (LAC)). RESULTS: The patients' mean age and disease duration were 28.8 ± 8.1 and 5.7 ± 2.2 years, respectively. The prevalence of ANA positivity, height of titre, and pattern was comparable between patients and controls (p = 0.9, p = 0.8 and p = 0.1, respectively). Anti-dsDNA antibodies and hypocomplementemia were absent in both groups. A significantly higher frequency of positive LAC was observed among patients compared with controls (7.6% vs. 1%, p = 0.02), whereas other aPL were comparable between both groups. None of the patients or controls demonstrated clinically meaningful (medium or high) aPL titres. CONCLUSION: In our study, schizophrenia was solely associated with LAC. Thus, in the absence of findings suggestive of SLE or APS, routine screening for both diseases is questionable.

An international study on psychological coping during COVID-19: Towards a meaning-centered coping style.

BACKGROUND/OBJECTIVE: This study examined the role of different psychological coping mechanisms in mental and physical health during the initial phases of the COVID-19 crisis with an emphasis on meaning-centered coping. METHOD: A total of 11,227 people from 30 countries across all continents participated in the study and completed measures of psychological distress (depression, stress, and anxiety), loneliness, well-being, and physical health, together with measures of problem-focused and emotion-focused coping, and a measure called the Meaning-centered Coping Scale (MCCS) that was developed in the present study. Validation analyses of the MCCS were performed in all countries, and data were assessed by multilevel modeling (MLM). RESULTS: The MCCS showed a robust one-factor structure in 30 countries with good test-retest, concurrent and divergent validity results. MLM analyses showed mixed results regarding emotion and problem-focused coping strategies. However, the MCCS was the strongest positive predictor of physical and mental health among all coping strategies, independently of demographic characteristics and country-level variables. CONCLUSIONS: The findings suggest that the MCCS is a valid measure to assess meaning-centered coping. The results also call for policies promoting effective coping to mitigate collective suffering during the pandemic.

ANTECEDENTES/OBJETIVO: Este estudio examinó el papel de diferentes estrategias de afrontamiento psicológico en la salud mental y física durante las fases iniciales de la crisis de COVID-19. MÉTODO: 11,227 personas de 30 países representando todos los continentes participaron en el estudio y completaron medidas de malestar psicológico (depresión, estrés y ansiedad), soledad, bienestar, salud física, medidas de afrontamiento centrado en el problema y en la emoción, y una medida denominada Escala del Afrontamiento Centrado en el Sentido (MCCS) que fue desarrollada en este estudio. El análisis de validación de la MCCS se realizó en todos los países, y los datos se evaluaron mediante un modelo multinivel. RESULTADOS: La MCCS mostró una estructura unifactorial en 30 países con buenos resultados de validez test-retest, concurrente y divergente. Los análisis mostraron resultados mixtos en cuanto a las estrategias de afrontamiento centradas en la emoción y en el problema. La MCCS fue el predictor positivo más fuerte de salud física y mental, independientemente de las características demográficas y las variables a nivel de país. CONCLUSIONES: Los resultados sugieren que la MCCS es un insrumento fiable para medir afrontamiento centrado en el sentido. Estos resultados pueden servir para dirigir políticas que promuevan un afrontamiento eficaz con el fin de mitigar el sufrimiento colectivo durante la pandemia.

Downregulation of MMP1 expression mediates the anti-aging activity of Citrus sinensis peel extract nanoformulation in UV induced photoaging in mice.

Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine metabolites. CSPE was standardized to a hesperidin content of 15.53 ± 0.152 mg% using RP-HPLC. It was suggested that the optimized formulation (F7) had (245 nm) particle size, (91.065%) EE, and (91.385%) occlusive effect with a spherical and smooth surface. The visible appearance of UV-induced photoaging in mice was significantly improved after topical application on CSPE-NLC cream for 5 weeks, levels of collagen and SOD were significantly increased in CSPE- NLC group, while levels of PGE2, COX2, JNK, MDA, and elastin was reduced. Finally, The prepared anti-aging CSPE-NLC cream represents a safe, convenient, and promising skincare cosmetic product.

Pharmaceutical and Pharmacological Evaluation of the Effect of Nano-Formulated Spironolactone and Progesterone on Inflammation and Hormonal Levels for Managing Hirsutism Experimentally Induced in Rats.

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.

Demographic & clinical correlates of admission into a specialized psychiatric inpatient service for children and adolescents in Egypt: An observational retrospective study.

WHAT IS KNOWN ON THE SUBJECT: Admitting children and adolescents in psychiatric inpatient units is a relatively new and still debatable practice in Egyptian society and in the entire Arab world. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Egyptian young people diagnosed with complex behavioural problems, such as in other parts of the world, desperately need and do get benefit from inpatient psychiatric service. The demographic and clinical characteristics of children in need for such service are not clearly different from those reported in other parts of the world. WHAT ARE THE IMPLICATIONS FOR PRACTICE: More should be done to spread awareness, remove obstacles, and develop more specialized inpatient units, with trained child psychiatrists and psychiatric nurses to provide best care for children and adolescents diagnosed with severe emotional and behavioural problems in Egypt, the Arab world and other developing countries in the world. ABSTRACT: Background To our knowledge, this is the first study that aims to investigate the demographic and clinical correlates of admission into a specialized inpatient psychiatric unit for children and adolescents in Egypt and the Arab world. Methods The files of all service users who presented for care in the outpatient service for children and adolescents in Tanta University between July 2017 and December 2019 were reviewed. Of the 1,195 files reviewed, 100 patients were admitted to the inpatient unit for 133 admission episodes with an average duration of 18.5 days per episode. Results The most common diagnosis among admitted children and adolescents was disruptive behaviour disorder. Having a diagnosis of bipolar disorder, eating disorder, or trauma-related disorders powerfully predicted admission. Both physical and sexual abuse also predicted admission, readmission and longer duration of admission. Conclusions The need for admission into specialized psychiatric inpatient units for children and adolescents is comparable to that in other parts of the world. There is an urgent necessity to develop such therapeutic units across the entire Arab world with subsequent need to establish suitable training programs for mental health workers to deal with children and adolescents diagnosed with severe psychiatric disorders in inpatient setting.

In-vivo wound healing activity of a novel composite sponge loaded with mucilage and lipoidal matter of Hibiscus species.

Many researches have been undergone to hasten the natural wound healing process. In this study, several Hibiscus species (leaves) were extracted with petroleum ether, methanol, and their mucilage was separated. All the tested species extracts were assessed for their viability percentage using the water-soluble tetrazolium. H.syriacus was the plant of choice to be incorporated in a new drug delivery system and evaluated for its wound healing activity. H.syriacus petroleum ether extract (PEE) showed a high percentage of palmitic and oleic acids while its mucilage demonstrated high glucosamine and galacturonic acid. It was selected to be formulated and pharmaceutically evaluated into three different composite sponges using chitosan in various ratios. Fourier-transformed infrared spectroscopy investigated the chemical interaction between the utilized sponges' ingredients. Morphological characteristics were evaluated using scanning electron microscopy. H.syriacus composite sponge of mucilage: chitosan (1:5) was loaded with three different concentrations of PEE. Medicated formulations were assessed in rat model of excision wound model. The wound healing ability was clearly proved by the clinical acceleration, histopathological examination, and modulation of correlated inflammatory parameters as tumor necrosis factor in addition to vascular endothelial growth factor suggesting a promising valuable candidate that supports the management of excision wounds using single-dose preparation.

Characterization and Pharmacological Evaluation of Anti-Cellulite Herbal Product(s) Encapsulated in 3D-Fabricated Polymeric Microneedles.

Skin health is vital for a healthy body. Herbal remedies have long been used for skin care, and their global use has tremendously increased over the past three decades. Although cellulite is seen as a normal condition by the medical community, it is considered a serious cosmetic concern for most affected women. Many topical anti-cellulite creams are available on the market, but unfortunately, their efficacy has not been proven scientifically. Microneedles (MNs) represent a new approach to enhance the permeation of loaded medication through the skin. In this study, the anti-cellulite effects of Vitex agnus-castus and Tamarindus indica extracts were compared using safe and effective polymeric MNs. This delivery system offers a painless alternative to the combined treatment strategy of microneedling devices and anti-cellulite products. The selected standardized extracts were evaluated for their mineral, phenolic and flavonoid contents, which are correlated to a promising antioxidant effect, as demonstrated by an in vitro radical scavenging activity assay. 3D-printing techniques were chosen for fabrication of a micromold, which is inexpensive for mass production. To ensure that MNs were sufficiently strong to perforate the skin without breaking, axial failure force was measured using a micro-mechanical test machine. The anticellulite effects of MNs were assessed using an in vivo diet-induced obesity guinea pig model. Skin properties, histopathology and inflammatory markers were examined. MNs loaded with plant extracts were statistically comparable in normalizing the oxidative state and reducing inflammation, while myeloperoxidase levels were more significantly reduced by T. indica than by V. agnus-castus. This novel delivery system opens the door for new transdermal strategies for cellulite management.

Design and optimization of topical terbinafine hydrochloride nanosponges: Application of full factorial design, in vitro and in vivo evaluation.

Terbinafine hydrochloride (THCl) has a broad-spectrum antifungal activity. THCl has oral bioavailability 40%, which increases dosing frequency of the drug, thus leads to some systemic side effects. Sustained release THCl nanosponges hydrogel was fabricated to deliver the drug topically. Pure THCl (drug), polyvinyl alcohol (emulsifier), and ethyl cellulose (EC, polymer to produce nanosponges) were used. THCl nanosponges were produced successfully by the emulsion solvent evaporation method. Based on a 32 full factorial design, different THCl: EC ratios and stirring rates were used as independent variables. The optimized formula selected based on the particle size and entrapment efficiency % (EE) was formulated as topical hydrogel. All formulations were found in the nanosize range except F7and F9. EE was ranged from 33.05% to 90.10%. THCl nanosponges hydrogel released more than 90% of drug after 8 h and showed the highest in vivo skin deposition and antifungal activity. The increase in drug: EC ratio was observed to increase EE and the particle size while higher stirring rate resulted in finer emulsion globules and significant reduction in EE. The drug release profile was slow from dosage form when it was incorporated in entrapped form as nanosponges rather than unentrapped one. The nanosponges hydrogel succeeded to sustain THCl release over 8 h. It showed the highest antifungal activity and skin deposition. THCl nanosponges hydrogel represents an enhanced therapeutic approach for the topical treatment of fungal infection.

Micro RNA 146a gene variant / TNF-α / IL-6 / IL-1 ß; A cross-link axis inbetween oxidative stress, endothelial dysfunction and neuro-inflammation in acute ischemic stroke and chronic schizophrenic patients.

This work was purposed to speculate the possible association of rs2910164hsa-miR-146a C>G gene single nucleotide polymorphism in the pathogenesis of schizophrenia and subsequently their relevance to neuro-inflammatory, vascular and oxidative stress pathways as acute ischemic stroke (AIS) risk factors in chronic schizophrenic patients. 450 subjects, 150 healthy controls (group I), 150 chronic schizophrenic patients without any evidences of stroke (group II) and 150 chronic schizophrenic patients with AIS (group III) were included. Genotypes (CC, CG&GG) for hsa-mir-146a gene polymorphism were identified using polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP technique. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1 ß), plasminogen activator-inhibitor 1 (PAI-1), thrombomodulin (TM) and 8-Hydroxy-2-deoxyguanosine (8-OHdG) serum levels were immunoassayed. Complete lipid profile was estimated. The CG and GG hsa-miR-146a genotypes were associated with increased risk of both schizophrenia and AIS in schizophrenic patients with thrombomodulin levels decrement in group II& III. On the other side, the risk genotypes were associated significantly with positive and negative syndrome scale PANSS scores, TNF-α, IL-6, IL-1 ß, PAI-1, and 8-OHdG increment levels in both groups II & III. By contrast, the CG and GG hsa-miR-146a genotypes did not affect the neuro-inflammatory and oxidative stress markers in healthy controls. These findings illustrate a new mechanism strengthening the occurrence of oxidative stress and DNA damage as a result of the neuro-inflammatory and endothelial dysfunction status originated from the hsa-miR-146a C>G gene single nucleotide polymorphism, thus, confirming their role in the pathogenesis of schizophrenia and its AIS risk.

Demographic and clinical characteristics of children seeking psychiatric services in the Nile Delta region: an observational retrospective study.

BACKGROUND: Epidemiological studies, describing both community and clinical samples of youth in need for psychiatric help, are rare in the middle east. To our knowledge, this is the first study that aims to investigate the demographic and clinical characteristics of a sample of children suffering from emotional and behavioral problems seeking psychiatric services in the Nile Delta region and the largest clinical sample to date in Egypt. METHODS: The files of all new cases who presented for care in the outpatient service for children and adolescents between August 2016 and July 2018 were reviewed. Ninety-six files were excluded due to missing data while another 18 files were found to be for adults (ages > 18 years old), so the sample included 886 cases. RESULTS: The ages of our sample (n = 886) ranged from 18 months to 18 years with an average of 7.5 (± 3.8) years. Most of our cases were male, school aged children, living within low-income households and predominantly coming from rural areas. The most common diagnoses were attention deficit hyperactivity disorder (ADHD) (22.6%), intellectual disability (ID) (13.7%), depressive disorders (13.3%), and disruptive behavior disorders (DBD) (12.3%). Strong protective effects were found for family integrity and stability. Corporal punishment and physical and sexual abuse were noted to be significant risk factors for internalizing and externalizing disorders in children and adolescents. CONCLUSIONS: Except for males being a majority in our sample of children seeking psychiatric consultation, demographic patterns and prevalence of psychiatric disorders are comparable to other tertiary clinical samples in other parts of the world.

A Completely Polyherbal Conditioning and Antioxidant Shampoo: A Phytochemical Study and Pharmaceutical Evaluation.

AIM: A recent approach in shampoo research has been to find a natural alternative for synthetic detergents that have deteriorative effects on hair follicles. This study aimed at the formulation of a completely herbal shampoo containing a natural foaming agent, in addition to having conditioning, antioxidant, and antimicrobial effects. MATERIAL AND METHODS: The leaves of Salix babylonica L., Ziziphus spina-christi L. (Willd), and Glycyrrhiza glabra rhizomes were extracted with 70% methanol then quantified for their phenolic and flavonoid contents using colorimetric assays that were qualitatively identified by Ultra-performance liquid chromatography (UPLC) with tandem mass spectrometry (MS-MS). The mineral content was also estimated. The radical scavenging activity was estimated using 1,1-diphenyl-2-Picrylhydrazyl (DPPH) and the half maximal inhibitory concentration (IC50) was determined. Additionally, the antimicrobial activity was tested using agar diffusion assay and compared to vancomycin and ketoconazole. Four formulations, consisting of the different plant extracts and a combination of the extracts, were prepared and evaluated for several physicochemical properties. The best formula was evaluated for its conditioning effects using scanning electron microscope and blind touch tests by asking volunteers for grading the formulations. RESULTS AND DISCUSSION: UPLC-MS-MS analysis of S. babylonica and Z. spina-christi allowed tentative identification of 12 phytoconstituents in each. Z. spina-christi showed the highest phenolic content and a high copper, zinc, and manganese content beside the best antioxidant activity, whereas G. glabra had a high potency against Bacillus cereus and Candida albicans. The polyherbal shampoo formulation (F4) was selected as an optimized formulation because of a high foam stability after 4 min, low wetting time (2 s), surface tension reduction, and comparable results for percent solid content. F4 showed good conditioning effect and consumer contentment. CONCLUSION: The formulated polyherbal shampoo is chemical free, extra-nourishing shampoo with excellent conditioning, cleansing, and antimicrobial effects.

Sleep and psychiatric abnormalities in Gullian Barré Syndrome.

BACKGROUND: The sensori-motor manifestations of Guillain Barré Syndrome (GBS) are usually severe enough to mask the psychiatric and sleep problems which are in need for more attention for better functional outcome. METHODS: This study was performed on 20 GBS patients and 10 healthy controls. Patients were evaluated initially before immunotherapy using the Overall Disability Sum Score (ODSS), Neuropathy Pain Scale (NPS), Hamilton Anxiety Scale (HAS), Montgomery-Åsberg Depression Rating Scale (MADRS) and one-night polysomnography (PSG) followed by the multiple sleep latency test (MSLT) to evaluate the mean sleep latencies. Reevaluation was done using the same parameters 1 month after completing immunotherapy. RESULTS: The study showed significant increase in HAS in GBS patients which were positively correlated with the degree of motor disability. The mean sleep latencies of MSLT were significantly shortened and PSG showed shortening of the total sleep time, sleep efficiency, lowest O2 saturation and pulse transit time with increased wake after sleep onset, sleep stage transition index, apnea hypopnea index, desaturation index, arousal index, snore index and periodic limb movement index. One month after immunotherapy, the anxiety symptoms and sleep abnormalities showed non-significant improvements which were not correlated with the improvements in the sensori-motor manifestations. CONCLUSIONS: GBS patients usually have sleep and psychiatric abnormalities which may take longer time to improve than the sensori-motor manifestations. So, they need more attention in the management protocol for early patients' independence and return to usual daily activities.