Sorafenib and Piperine co-loaded PLGA nanoparticles: Development, characterization, and anti-cancer activity against hepatocellular carcinoma cell line.

Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for the treatment of advanced HCC; however, the reported response rate to such a therapeutic is suboptimal (<3%). Piperine (PIP) is an alkaloid demonstrated to exert a direct tumoricidal activity in HCC and improve the pharmacokinetic profiles of anticancer drugs including SORA. In this study, we developed a strategy to improve efficacy outcomes in HCC using PIP as an add-on treatment to support the first-line therapy SORA using biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs). SORA and PIP (both exhibit low aqueous solubility) were co-loaded into PLGA NPs (PNPs) and stabilized with various concentrations of polyvinyl alcohol (PVA). The SORA and PIP-loaded PNPs (SP-PNPs) were characterized using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Powder Diffraction (XRD), Dynamic Light Scattering (DLS), and Scanning Electron Microscopy (SEM), Release of these drugs from SP-PNPs was investigated in vitro at both physiological and acidic pH, and kinetic models were employed to assess the mechanism of drug release. The in vitro efficacy of SP-PNPs against HCC cells (HepG2) was also evaluated. FTIR and XRD analyses revealed that the drugs encapsulated in PNPs were in an amorphous state, with no observed chemical interactions among the drugs or excipients. Assessment of drug release in vitro at pH 5 and 7.4 showed that SORA and PIP loaded in PNPs with 0.5 % PVA were released in a sustained manner, unlike pure drugs, which exhibited relatively fast release. SP-PNPs with 0.5 % PVA were spherical, had an average size of 224 nm, and had a high encapsulation efficiency (SORA âˆ¼ 82 %, PIP âˆ¼ 79 %), as well as superior cytotoxicity compared to SORA monotherapy in vitro. These results suggest that combining PIP with SORA using PNPs may be an effective strategy for the treatment of HCC and may set the stage for a comprehensive in vivo study to evaluate the efficacy and safety of this novel formulation using a murine HCC model.

Exploring the molecular mechanisms of increased intensity of pyrethroid resistance in Central African population of a major malaria vector Anopheles coluzzii.

Molecular mechanisms driving the escalation of pyrethroid resistance in the major malaria mosquitoes of Central Africa remain largely uncharacterized, hindering effective management strategies. Here, resistance intensity and the molecular mechanisms driving it were investigated in a population of Anopheles coluzzii from northern Cameroon. High levels of pyrethroid and organochloride resistance were observed in An. coluzzii population, with no mortality for 1× permethrin; only 11% and 33% mortalities for 5× and 10× permethrin diagnostic concentrations, and <2% mortalities for deltamethrin and DDT, respectively. Moderate bendiocarb resistance (88% mortality) and full susceptibility to malathion were observed. Synergist bioassays with piperonyl butoxide recovered permethrin susceptibility, with mortalities increasing to 53.39%, and 87.30% for 5× and 10× permethrin, respectively, implicating P450 monooxygenases. Synergist bioassays with diethyl maleate (DEM) recovered permethrin and DDT susceptibilities (mortalities increasing to 34.75% and 14.88%, respectively), implicating glutathione S-transferases. RNA-seq-based genome-wide transcriptional analyses supported by quantitative PCR identified glutathione S-transferase, GSTe2 (RNA-seqFC = 2.93 and qRT-PCRFC = 8.4, p < 0.0043) and CYP450, CYP6Z2 (RNA-seqFC = 2.39 and qRT-PCRFC = 11.7, p < 0.0177) as the most overexpressed detoxification genes in the pyrethroid-resistant mosquitoes, compared to mosquitoes of the susceptible Ngousso colony. Other overexpressed genes include P450s, CYP6M2 (FC = 1.68, p < 0.0114), CYP4G16 (FC = 2.02, p < 0.0005), and CYP4G17 (FC = 1.86, p < 0.0276). While high frequency of the 1014F kdr mutation (50%) and low frequencies of 1014S (6.61%) and 1575Y (10.29%) were observed, no ace-1 mutation was detected in bendiocarb-resistant populations, suggesting the preeminent role of metabolic mechanism. Overexpression of metabolic resistance genes (including GSTe2 and CYP6Z2 known to confer resistance to multiple insecticides) in An. coluzzii from the Sudan Savannah of Cameroon highlights the need for alternative management strategies to reduce malaria burden in northern Cameroon.

Nationwide surveillance identifies yellow fever and chikungunya viruses transmitted by various species of Aedes mosquitoes in Nigeria.

Background: Since its reemergence in 2017, yellow fever (YF) has been active in Nigeria. The Nigeria Centre for Disease Control (NCDC) has coordinated responses to the outbreaks with the support of the World Health Organization (WHO). The National Arbovirus and Vectors Research Centre (NAVRC) handles the vector component of these responses. This study sought to identify the vectors driving YF transmission and any of the targeted arboviruses and their distribution across states. Methods: Eggs, larvae and pupae as well as adult mosquitoes were collected in observational, analytical, and cross-sectional surveys conducted in sixteen YF outbreak states between 2017 and 2020. Adult mosquitoes (field-collected or reared from immature stages) were morphologically identified, and arboviruses were detected using RT-qPCR at the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID). Results: Aedes mosquitoes were collected in eleven of the sixteen states surveyed and the mosquitoes in nine states were found infected with arboviruses. A total of seven Aedes species were collected from different parts of the country. Aedes aegypti was the most dominant (51%) species, whereas Aedes africanus was the least (0.2%). Yellow fever virus (YFV) was discovered in 33 (~26%) out of the 127 Aedes mosquito pools. In addition to YFV, the Chikungunya virus (CHIKV) was found in nine pools. Except for Ae. africanus, all the Aedes species tested positive for at least one arbovirus. YFV-positive pools were found in six (6) Aedes species while CHIKV-positive pools were only recorded in two Aedes species. Edo State had the most positive pools (16), while Nasarawa, Imo, and Anambra states had the least (1 positive pool). Breteau and house indices were higher than normal transmission thresholds in all but one state. Conclusion: In Nigeria, there is a substantial risk of arbovirus transmission by Aedes mosquitoes, with YFV posing the largest threat at the moment. This risk is heightened by the fact that YFV and CHIKV have been detected in vectors across outbreak locations. Hence, there is an urgent need to step up arbovirus surveillance and control activities in the country.

Assessment of Female Pelvic Pathologies: A Cross-Sectional Study Among Patients Undergoing Magnetic Resonance Imaging for Pelvic Assessment at the Maternity and Children Hospital, Qassim Region, Saudi Arabia.

Background and objectives Pelvic pathologies affect females in all age groups. They vary in size and location and can be wide in classification, such as masses, ectopic pregnancy, ovarian torsion, and ruptured ovarian follicles. Patients commonly present with gynecological complaints such as menstrual irregularities, abnormal pelvic bleeding, and infertility. Extra-gynecological symptoms such as dysuria and painful defecation can also manifest. To diagnose these pathologies, magnetic resonance imaging (MRI) and other imaging modalities can be useful alongside history and physical examination for early clinical diagnosis. Due to the importance of prevalence rate in predicting pathologies in a certain age and due to the lack of research studies on pelvic MRI studies in Qassim region, Saudi Arabia, this study aimed to demonstrate the wide spectrum of female pelvic pathologies that can be diagnosed using MRI in Qassim region, Saudi Arabia.  Methods and results A cross-sectional study was conducted among patients referred to the MRI Department for evaluation of female pelvic pathologies at the Department of Radiology at Maternity and Children Hospital in Buraydah, Qassim region, Saudi Arabia. A total of 325 patients were included in the study, with the majority being in the age group of 31-40 years. Fibroids were the most common pathology, being present in more than one-fifth of the study sample, followed by neoplastic growths and placental pathologies. Inflammatory pathologies were the least common pathologies, being present in approximately 5% of the participants. Statistically significant associations were found between the age groups, and the presence of anomalies (p = 0.009), existence of neoplastic changes (p < 0.001), presence of placental pathologies (p < 0.001), inflammatory changes (p = 0.025), and adenomyosis (p = 0.028). Conclusion MRI data offer important new information about the prevalence of various disorders among different age groups in the Qassim region of Saudi Arabia. Younger age groups had much higher rates of anomalies, whereas older age groups had much lower rates. Adenomyosis and neoplastic alterations were more prevalent in the later age groups, but endometrioma was more prevalent in younger age groups. Placental pathologies were more prevalent in women in their middle years, while scar pregnancy was more prevalent in women between 31 and 40 years of age. Younger people, especially those between 16 and 20 years of age, were more likely to experience inflammatory alterations. In the younger age group, there was no discernible association between age and the prevalence of normal outcomes. These findings help us understand how different illnesses manifest differently as we get older and emphasize the value of taking aging into account when diagnosing and treating disorders.

Carbohydrate fatty acid monosulphate ester is a potent adjuvant for low-dose seasonal influenza vaccines.

There is still a need for a better and affordable seasonal influenza vaccine and the use of an adjuvant could solve both issues. Therefore, immunogenicity of a combination of low dose of 1/5TH (3 µg of HA) a licensed seasonal flu vaccine with the novel carbohydrate fatty acid monosulfate ester (CMS)-based adjuvant was investigated in ferrets and safety in rabbits. Without CMS, hemagglutination inhibition (HI) antibody titers ranged from ≤5 to 26 three weeks post immunization 1 (PV-1) and from 7 to 134 post-immunization 2 (PV-2) in ferrets. Virus neutralizing (VN) antibody titers ranged from 20 to 37 PV-1 and from 21 to 148 PV-2. CMS caused 10 to 111- fold increase in HI titers and 3 to 58- fold increase in VN titers PV-1 and PV-2, depending on influenza strain and dose of adjuvant. Eight mg of CMS generated significantly higher antibody titers than 1 or 4 mg, while 1 and 4 mg induced similar responses. Three µg of HA plus 4 mg of CMS was considered the highest human dose and safety of two-fold this dose was determined in acute and repeated-dose toxicity studies in rabbits conducted according to OECD GLP guidelines. The test item did not elicit any clinical signs, local reactions, effect on body weight, effect on urine parameters, effect on blood biochemistry, or gross pathological changes. In blood, increased numbers of neutrophils, lymphocytes and/or monocytes were noted and in iliac lymph nodes, increased cellularity of macrophages of minimal to mild degree were observed. In both ferrets and rabbits, body temperature increased with increasing dose of CMS to a maximum of 1 ˚C during the first day post-immunization, which returned to normal values during the second day. In the local tolerance study, histopathology of the site of injection at 7 days PV-1 revealed minimal, mild or moderate inflammation in 5, 8 and 5 animals, respectively. In the repeated-dose study and 21 days PV-3, minimal, mild or moderate inflammation was observed in 15, 18 and 3 animals, respectively. We concluded that the data show CMS is a potent and safe adjuvant ready for further clinical development of a seasonal influenza vaccine and combines high immunogenicity with possible antigen-sparing capacity.

Formulation of multicomponent inclusion complex of cyclodextrin-amino acid with Chrysin: Physicochemical characterization, cell viability and apoptosis assessment in human primary glioblastoma cell line.

Chrysin (CR) is a water-insoluble drug reported for different therapeutic effects. The microwave irradiation method was used in this study to create a multicomponent inclusion complex (CR-MC) containing CR (drug) and carrier hydroxyl propyl beta cyclodextrin (HP ß CD) and L-arginine (LA). The prepared inclusion complex (CR-MC) was evaluated for dissolution study and results were compared with chrysin physical mixture (CR-PM). Further, the samples were assessed for infra-red (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM) and molecular docking. Finally, the cell viability, reactive oxygen species and flow cytometer studies were also assessed to check the potential of the prepared inclusion complex on the human primary glioblastoma cell line (U87-MG cell). The phase solubility findings revealed a stability constant (773 mol L-1) as well as a complexation efficiency of 0.027. The dissolution study displayed a significant increase in CR release from CR-MC (99.03 ± 0.39%) > CR-PM (70.58 ± 1.16%) > pure CR (35.29 ± 1.55%). NMR and IR spectral data revealed no interaction between CR and carriers. SEM and DSC study results revealed the conversion into amorphous form. The molecular docking results illustrated a high docking score, which supports the findings of complex formation. The cell viability, reactive oxygen species, and flow cytometry studies results showed enhanced activity from CR-MC against the tested human primary glioblastoma cell line. From the results it has been observed that chrysin solubility significantly increased after complexation and there in vitro activity also enhanced against cancer cell line.

Eflornithine Hydrochloride-Loaded Electrospun Nanofibers as a Potential Face Mask for Hirsutism Application.

Hirsutism is a distressing condition that can affect women's self-esteem due to the excessive amount of hair growth in different body parts, including the face. A temporary managing option is to develop a self-care routine to remove unwanted hair through shaving or waxing. Laser or electrolysis are alternative methods, but in some cases, the use of medications, such as the topical cream Vaniqa®, can help in reducing the growth of unwanted hair. Electrospun fibers have been used in several drug delivery applications, including skin care products, owing to their biocompatibility, biodegradability, high surface area-to-volume ratio, and dry nature that can release the encapsulated drugs with maximum skin penetration. Therefore, polyvinyl pyrrolidone (PVP) fibers were fabricated in combination with hyaluronic acid to deliver the active compound of Vaniqa®, i.e., Eflornithine hydrochloride (EFH), as a face mask to inhibit excess facial hair growth. The prepared drug-loaded fibers showed a diameter of 490 ± 140 nm, with an encapsulation efficiency of 88 ± 7% and a drug loading capacity of 92 ± 7 µg/mg. The in vitro drug release of EFH-loaded fibers exhibited an initial burst release of 80% in the first 5 min, followed by a complete release after 360 min, owing to the rapid disintegration of the fibrous mat (2 s). The in vitro cytotoxicity indicated a high safety profile of EFH at all tested concentrations (500-15.625 µg/mL) after 24-h exposure to human dermal fibroblast (HFF-1) cells. Therefore, this drug-loaded nanofibrous system can be considered a potentially medicated face mask for the management of hirsutism, along with the moisturizing effect that it possesses. Topical applications of the developed system showed reduced hair growth in mice to a certain extent.

Relationship Between Heart Disease and Obesity Indicators Among Adults: A Secondary Data Analysis.

Background Body mass index (BMI), waist circumference (WC), and hip circumference (HC) determine obesity. Several studies have examined the association between obesity and many diseases, including heart disease, and found it to be a substantial risk factor. However, the relationship between heart disease and obesity has not been investigated. This study investigated the relationship between heart disease and obesity indicators among adults encompassing sociodemographic and lifestyle factors. Methodology This cross-sectional study included data from 3,574 individuals who participated in the 2011-2014 National Survey of Midlife Development in the United States refresher. The presence or absence of heart conditions such as irregular heartbeat, heart murmur, heart attack, and heart failure was determined using self-reported questionnaires. The association between heart disease and obesity indicators such as BMI, WC, HC, and waist-to-hip ratio (WHR) was investigated using linear regression. Results After controlling for all factors, the findings demonstrated a significant relationship between heart disease and BMI, WC, and HC high scores of 1.12 kg/m2, 0.63 inches, and 0.81 inches, respectively. A higher score in all obesity indicators was linked to being 65 years or older; male gender (for HC); having a school/college level of education; being unmarried, divorced, or widowed; having a history of smoking; and avoiding alcohol use. Conclusions Heart disease and sociodemographic and lifestyle factors are substantially associated with a high score in all obesity indicators. The findings of this study are important because they can assist healthcare providers in implementing different therapies to prevent high BMI, WC, HC, and WHR.

Molecular drivers of insecticide resistance in the Sahelo-Sudanian populations of a major malaria vector Anopheles coluzzii.

BACKGROUND: Information on common markers of metabolic resistance in malaria vectors from countries sharing similar eco-climatic characteristics can facilitate coordination of malaria control. Here, we characterized populations of the major malaria vector Anopheles coluzzii from Sahel region, spanning four sub-Saharan African countries: Nigeria, Niger, Chad and Cameroon. RESULTS: Genome-wide transcriptional analysis identified major genes previously implicated in pyrethroid and/or cross-resistance to other insecticides, overexpressed across the Sahel, including CYP450s, glutathione S-transferases, carboxylesterases and cuticular proteins. Several, well-known markers of insecticide resistance were found in high frequencies-including in the voltage-gated sodium channel (V402L, I940T, L995F, I1527T and N1570Y), the acetylcholinesterase-1 gene (G280S) and the CYP4J5-L43F (which is fixed). High frequencies of the epidemiologically important chromosomal inversion polymorphisms, 2La, 2Rb and 2Rc, were observed (~80% for 2Rb and 2Rc). The 2La alternative arrangement is fixed across the Sahel. Low frequencies of these inversions (<10%) were observed in the fully insecticide susceptible laboratory colony of An. coluzzii (Ngoussou). Several of the most commonly overexpressed metabolic resistance genes sit in these three inversions. Two commonly overexpressed genes, GSTe2 and CYP6Z2, were functionally validated. Transgenic Drosophila melanogaster flies expressing GSTe2 exhibited extremely high DDT and permethrin resistance (mortalities <10% in 24h). Serial deletion of the 5' intergenic region, to identify putative nucleotide(s) associated with GSTe2 overexpression, revealed that simultaneous insertion of adenine nucleotide and a transition (T->C), between Forkhead box L1 and c-EST putative binding sites, were responsible for the high overexpression of GSTe2 in the resistant mosquitoes. Transgenic flies expressing CYP6Z2 exhibited marginal resistance towards 3-phenoxybenzylalcohol (a primary product of pyrethroid hydrolysis by carboxylesterases) and a type II pyrethroid, α-cypermethrin. However, significantly higher mortalities were observed in CYP6Z2 transgenic flies compared with controls, on exposure to the neonicotinoid, clothianidin. This suggests a possible bioactivation of clothianidin into a toxic intermediate, which may make it an ideal insecticide against populations of An. coluzzii overexpressing this P450. CONCLUSIONS: These findings will facilitate regional collaborations within the Sahel region and refine implementation strategies through re-focusing interventions, improving evidence-based, cross-border policies towards local and regional malaria pre-elimination.

Knowledge and Practice of Burn Management Among Physicians Using Burn Manikin in Ha'il, Kingdom of Saudi Arabia.

Background Burn is a skin injury that results in the death of the impacted cells. Burn injuries are frequently unintentional and very avoidable. With proper management, the outcome is improved, and the need for surgical intervention is reduced. This article discusses healthcare providers' knowledge and practice of burn first aid and management to highlight the need for the enhanced practice of burn management and first-aid skills. Objective This study aims to assess the knowledge and practice of burn injuries management among healthcare workers in different specialties in Hail city. Methods  A cross-sectional study was conducted via an interviewer-administrated face-to-face questionnaire and video recording of a simulated case of burn injury collected from our skill lab at Hail University and evaluated by a board-certified plastic surgeon. Result The study analyzed 119 physicians (mean age = 36.3 years, SD = 6.7) managing burn cases. Of these, 59.7% were male, and 40.3% were female. The mean evaluation score was 7.71 (SD = 2.84). None of the factors studied, including gender (p = 0.353), age (p = 0.970), education level (p = 0.127), specialty (p = 0.871), professional experience (p = 0.118), working sector (p = 0.178), nationality (p = 0.742), or participation in burn management course (p = 0.131), had a significant effect on burn management skills of physicians. However, some groups had higher mean evaluation scores than others. Further research is needed to explore potential reasons for the observed differences in mean evaluation scores among different groups of physicians. Conclusion We discovered that most physicians were found to have poor practical knowledge of proper burn management, and most of them had not engaged in a burn first aid training, therefore more courses targeting physicians who may meet burn patients are required.

Topical Application of Linezolid-Loaded Chitosan Nanoparticles for the Treatment of Eye Infections.

Linezolid (LZ) loaded chitosan-nanoparticles (CSNPs) was developed by the ionic-gelation method using Tripolyphosphate-sodium as a crosslinker for topical application for the treatment of bacterial eye infections. Particles were characterized by Zeta-Sizer (Malvern Nano-series). TEM was used for structural morphology. Encapsulation and drug loading were estimated by measuring the unencapsulated drug. In-vitro drug release in STF (pH 7) was performed through a dialysis membrane. Storage stability of LZ-CSNPs was checked at 25 °C and 40 °C for six months. The antimicrobial potency of NPs was evaluated on different Gram-positive strains. Ocular irritation and pharmacokinetic studies were completed in rabbits. Ex-vivo transcorneal permeation of the drug was determined through the rabbit cornea. Ionic interaction among the oppositely charged functional groups of CS and TPP generated the CSNPs. The weight ratio at 3:1, wt/wt (CS/TPP) with 21.7 mg of LZ produced optimal NPs (213.7 nm with 0.387 of PDI and +23.1 mV of ZP) with 71% and 11.2% encapsulation and drug loading, respectively. Around 76.7% of LZ was released from LZ-AqS within 1 h, while 79.8% of LZ was released from CSNPs at 12 h and 90% at 24 h. The sustained drug release property of CSNPS was evaluated by applying kinetic models. The linearity in the release profile suggested that the release of LZ from CSNPs followed the Higuchi-Matrix model. LZ-CSNPs have shown 1.4 to 1.6-times improved antibacterial activity against the used bacterial strains. The LZ-CSNPs were "minimally-irritating" to rabbit eyes and exhibited 4.4-times increased transcorneal permeation of LZ than from LZ-AqS. Around 3-, 1.2- and 3.1-times improved Tmax, Cmax, and AUC0-24 h, respectively were found for LZ-CSNPs during the ocular pharmacokinetic study. AqS has shown 3.1-times faster clearance of LZ. Conclusively, LZ-CSNPs could offer a better alternative for the prolonged delivery of LZ for the treatment of bacterial infections in the eyes.

Association of oral candidiasis with oral lichen planus in patients using corticosteroid therapy - Meta-analysis.

Oral lichen planus (OLP) is a chronic inflammatory disease that commonly affects the skin and mucous membranes. There is a difference of opinion among clinicians about whether OLP has been associated with oral candidiasis. Nonetheless, in OLP patients, the oral candidiasis prevalence rate ranges from 7.7 to 16.6%, as established through biopsy findings, whereas 37-50% of the prevalence rate has been noticed in culture findings. Oral candidiasis has been linked to several local and systemic factors, including salivary gland dysfunction, dental prostheses, topical or inhaled corticosteroids, smoking, and the use of systemic medications. The aim was to highlight the association of Candida in patients diagnosed with OLP, correlate the use of steroid therapy, and enumerate the factors of using steroid therapy as implicated causes for oral candidiasis. A search was made using search engines such as PubMed, Scopus, Cochrane Database of Systematic Reviews, Science Citation Index, NIH Public Access, and Clarivate Analytics (Figure 1). The keywords using the research option for this field were "Oral Candidiasis" AND "Oral Lichen planus" or "Candidiasis" AND "Corticosteroids" or "Topical Corticosteroids" AND Oral Lichen planus or "Inhalation Corticosteroids" AND "Candidiasis" or "Oral Lichen planus" AND "Corticosteroids." The database search was made for the duration of 1991 to -2021 (Table 1). Additional articles were obtained regarding the literature on OLP and oral candidiasis and were considered background material. The incidence of oral candidiasis and associated lichen planus following steroid therapy enlisted by various authors has been addressed. According to the results of this study, there is a positive correlation between the presence of oral candidiasis in the OLP's patients treated with corticosteroids. Finally, this meta-analysis concluded that there is a positive correlation between the presence of Candida species in OLP and steroid medication.

Virtual consultations for patients with obstructive sleep apnoea: a systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 pandemic has accelerated the adoption of virtual care strategies for the management of patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS). RESEARCH QUESTION: What is the effectiveness of virtual consultations compared to in-person consultations for the management of continuous positive airway pressure (CPAP) therapy in adult patients with OSAHS? METHODS: A systematic review and meta-analysis (PROSPERO; CRD42022297532) based on six electronic databases plus manually selected journals was conducted in January 2022. Two researchers independently selected, quality appraised and extracted data. The co-primary outcomes were patient-reported sleepiness, assessed by the Epworth Sleepiness Scale (ESS), and reported cost-effectiveness. RESULTS: 12 studies (n=1823 adults) were included in the review. Seven studies (n=1089) were included in the meta-analysis which showed no difference in the magnitude of improvement in patient-reported sleepiness scores between virtual and in-person consultations (mean difference -0.39, 95% CI -1.38-0.60; p=0.4), although ESS scores improved in both groups. Virtual care strategies modestly increased CPAP therapy adherence and were found to be less costly than in-person care strategies in the three Spanish trials that reported cost-effectiveness. CONCLUSION: The findings of this review suggest that virtual care delivered by telephone or video consultations is as effective as in-person consultations for improving subjective sleepiness in patients with OSAHS treated with CPAP. This clinical management strategy may also improve CPAP adherence without increasing the costs, supporting its potential as a follow-up management strategy, where patients prefer this approach.

Acute Upper Extremity Vein Thrombosis in Recurrent Shoulder Dislocation.

The shoulder joint is a commonly dislocated joint in the human body. Shoulder dislocations are commonly associated with fractures of greater tuberosity and neurovascular injuries and are rarely associated with venous complications like deep vein thrombosis (DVT). Ten percent of all venous thrombosis is related to upper extremity venous thrombosis (UE-VT). Severe UE-VT cases are associated with endovenous catheters. Moreover, UE-VT often occurs in specific medical conditions, including hematological malignancy, solid neoplasia, and progressive infection. UE-VT can lead to serious complications such as pulmonary embolism and postthrombotic syndrome. This article presents a case of acute superficial thrombus in the cephalic vein and DVT in the subclavian vein following recurrent shoulder dislocation, which we believe is a rare presentation.

Impact of the COVID-19 Pandemic on Elderly Medical Admissions and Outcomes in a Tertiary Hospital in Northeastern Nigeria: A Comparative Retrospective Study.

BACKGROUND: The coronavirus infectious disease 2019 (COVID-19) has been shown to be more lethal in the elderly (>65 years), especially those with co-morbidities. This study examined the impact of the pandemic lockdown period on trends in elderly medical admissions and deaths. METHODOLOGY: This is a retrospective study of elderly medical admissions and deaths in the medical wards of a Nigerian hospital. Data for the months of March, April, May, June, and July of 2020 was compared to the same months before (2019) and after (2021). Analysis was done using STATA version 15.0. RESULTS: During the study period, two hundred and seventy-six elderly patients were admitted, with a mean age (±SD) of 73.4 ± 7.4 years. The most common diagnoses at admission were chronic kidney disease (CKD) (26.85%, n=74) and hypertensive heart disease (HHD) (21.7%, n=60). The highest admission was in 2021, with a total of 99 (35.9%). Overall, 60 mortalities were recorded, with a proportional mortality rate of 21.7%, which was highest in 2020 (25.0%) and lowest in 2021 (17.1%). There was no difference between the mortality rates of 2019 versus 2020 (P=0.82) and 2020 versus 2021(P=0.18). Sepsis (35.0%) and CKD (25.0%) were the major contributors in 2019. CONCLUSION: CKD and HHD were the most common diagnoses at admission, whereas sepsis, CKD, and CVD were the commonest causes of death. The Covid-19 pandemic did not significantly alter the elderly admission pattern in our setting.

CONTEXTE: Il a été démontré que la maladie infectieuse à coronavirus 2019 (COVID-19) est plus mortelle chez les personnes âgées (>65 ans), en particulier celles qui présentent des comorbidités. Cette étude a examiné l'impact de la période de verrouillage pandémique sur les tendances des admissions médicales et des décès de personnes âgées. MÉTHODOLOGIE: Il s'agit d'une étude rétrospective des admissions et des décès de personnes âgées dans les services médicaux d'un hôpital nigérian. Les données relatives aux personnes âgées pour les mois de mars, avril, mai, juin et juillet 2020 ont été comparées aux mêmes mois avant (2019) et après (2021). L'analyse a été réalisée à l'aide de STATA version 15.0. RÉSULTATS: Au cours de la période, deux cent soixante-seize patients âgés ont été admis, avec un âge moyen et un écart-type (ET) de 73,4 7,4 ans. Les diagnostics les plus fréquents à l'admission étaient l'insuffisance rénale chronique (IRC) (26,85 %, n=74) et la cardiopathie hypertensive (HHD) (21,7 %, n=60). Le nombre d'admissions le plus élevé a été enregistré en 2021, avec un total de 99 (35,9 %). Au total, 60 décès ont été enregistrés, avec un taux de mortalité proportionnel de 21,7 %, qui était le plus élevé en 2020 (25,0 %) et le plus faible en 2021 (17,1 %). Les preuves étaient insuffisantes pour montrer une différence entre les taux de mortalité de 2019 par rapport à 2020 (P=0,82) et de 2020 par rapport à 2021 (P=0,18). Le sepsis (35,0 %) et l'IRC (25,0 %) étaient les principaux facteurs de mortalité en 2019. CONCLUSION: L'IRC et l'HHD étaient les diagnostics les plus courants à l'admission, tandis que la septicémie, l'IRC et les MCV étaient les causes les plus fréquentes de décès. La pandémie de Covid-19 n'a pas modifié de manière significative le schéma d'admission des personnes âgées dans notre contexte. Mots clés: COVID-19, Personnes âgées, Mode d'admission, Mortalité.

Nanocrystallization Improves the Solubilization and Cytotoxic Effect of a Poly (ADP-Ribose)-Polymerase-I Inhibitor.

Olaparib (OLA) is an anticancer agent that acts by inhibiting the poly (ADP-ribose)-polymerase-I (PARP-I). Due to its low solubility and low permeability, it has been placed as a BCS Class-IV drug and hence its clinical use is limited. In this study, we develop the nanocrystals of OLA as a way to improve its solubility and other performances. The OLA-NCs were prepared by antisolvent precipitation method through homogenization and probe sonication technique using a novel amphiphilic polymeric stabilizer (Soluplus®). Particle characterization resulted approximately 103.13 nm, polydispersity-index was 0.104 with positive zeta-potential of +8.67 mV. The crystal morphology by SEM of OLA-NCs (with and without mannitol) exhibited nano-crystalline prism-like structures as compared to the elongated OLA-pure. The DSC, XRD and FTIR were performed to check the interaction of Soluplus, mannitol and OLA did not exhibit any physical interaction among the OLA, Soluplus® and mannitol that is indicated by the presence of parent wave number peak. Two-fold increased solubility of OLA was found in PBS with Soluplus® from the NCs (69.3 ± 6.2 µgmL−1) as compared to pure drug (35.6 ± 7.2 µgmL−1). In vitro release of drug from OLA-NCs was higher (78.2%) at 12 h at pH 6.8 and relatively lower (53.1%) at pH 1.2. In vitro cellular cytotoxicity and anticancer effects were examined on MCF-7 cells. OLA-NCs were found effectively potent to MCF-7 cells compared with OLA-pure with approximately less than half IC50 value during MTT assay. Estimation of p53, Caspase-3 and Caspase-9 in MCF-7 cells indicated that OLA-NCs have significantly (p < 0.05) increased their expressions. After single oral dose in rats, 12 h plasma drug concentration-time profile indicated approximately 2.06-, 2.29-, 2−25- and 2.62-folds increased Cmax, AUC0-12 h, AUC0-∞ and AUMC0-∞, respectively, from the NCs as compared to OLA-pure. Storage stability indicated that the OLA-NCs was physically and chemically stable at 4 °C, 25 °C and 40 °C up to 6-months. Overall, OLA-NCs were deliberated; its potential feasibility to overwhelm the formulation challenges related to poorly soluble drugs and its future clinical applications.

Recent Developments in Cassava (Manihot esculenta) Based Biocomposites and Their Potential Industrial Applications: A Comprehensive Review.

The rapid use of petroleum resources coupled with increased awareness of global environmental problems associated with the use of petroleum-based plastics is a major driving force in the acceptance of natural fibers and biopolymers as green materials. Because of their environmentally friendly and sustainable nature, natural fibers and biopolymers have gained significant attention from scientists and industries. Cassava (Manihot esculenta) is a plant that has various purposes for use. It is the primary source of food in many countries and is also used in the production of biocomposites, biopolymers, and biofibers. Starch from cassava can be plasticized, reinforced with fibers, or blended with other polymers to strengthen their properties. Besides that, it is currently used as a raw material for bioethanol and renewable energy production. This comprehensive review paper explains the latest developments in bioethanol compounds from cassava and gives a detailed report on macro and nano-sized cassava fibers and starch, and their fabrication as blend polymers, biocomposites, and hybrid composites. The review also highlights the potential utilization of cassava fibers and biopolymers for industrial applications such as food, bioenergy, packaging, automotive, and others.

The Prevalence and Level of Awareness of Medication Overuse Headache in Qassim Province, Saudi Arabia: A Cross-Sectional Study.

Introduction Medication overuse headache (MOH) is a secondary headache caused by regular overuse of medication(s) intended to relieve (notably, not prevent) the symptoms of a pre-existing primary headache (most commonly, migraine and tension headaches). MOH places a considerable burden on both patients and society. Understandably, the disorder is the subject of many cross-sectional studies worldwide. Research on MOH in Qassim province, Saudi Arabia, however, has not been conducted; therefore, the present study aims to identify the prevalence and level of awareness of MOH in Qassim province. Methods An observational cross-sectional study was conducted in Qassim province from July 1, 2021, to June 13, 2022. A modified electronic questionnaire was distributed through social media platforms. The questionnaire covers demographics, prevalence of MOH, and awareness of MOH. Prevalence was measured using a scoring system based on the criteria of the International Classification of Headache Disorders, third edition (ICHD-3) for diagnosing MOH. Results A total of 499 people completed the questionnaire, 286 (57.3%) of whom were female and 213 (42.7%) of whom were male. The majority of the participants were Saudi nationals (95.4%). The mean age of the participants was 35 years old (± 12.7 years). Out of the 499 participants, 451 (90.4%) reported that they had experienced headaches in their life. The prevalence of MOH among those who had reported headaches was 4%, compared with a level of awareness of MOH among all the participants of 18%. Conclusion According to our study, there is a high prevalence of MOH in Qassim province. This is also coupled with a high awareness of MOH.

Perspectives of Positively Charged Nanocrystals of Tedizolid Phosphate as a Topical Ocular Application in Rabbits.

The aim of this study was the successful utilization of the positively charged nanocrystals (NCs) of Tedizolid Phosphate (TZP) (0.1% w/v) for topical ocular applications. TZP belongs to the 1, 3-oxazolidine-2-one class of antibiotics and has therapeutic potential for the treatment of many drug-resistant bacterial infections, including eye infections caused by MRSA, penicillin-resistant Streptococcus pneumonia and vancomycin-resistant Enterococcus faecium. However, its therapeutic usage is restricted due to its poor aqueous solubility and limited ocular availability. It is a prodrug and gets converted to Tedizolid (TDZ) by phosphatases in vivo. The sterilized NC1 was subjected to antimicrobial testing on Gram-positive bacteria. Ocular irritation and pharmacokinetics were performed in rabbits. Around a 1.29 to 1.53-fold increase in antibacterial activity was noted for NC1 against the B. subtilis, S. pneumonia, S. aureus and MRSA (SA-6538) as compared to the TZP-pure. The NC1-AqS was "practically non-irritating" to rabbit eyes. There was around a 1.67- and 1.43 fold increase in t1/2 (h) and Cmax (ngmL-1) while there were 1.96-, 1.91-, 2.69- and 1.41-times increases in AUC0-24h,AUC0-∞,AUMC0-∞ and MRT0-∞, respectively, which were found by NC1 as compared to TZP-AqS in the ocular pharmacokinetic study. The clearance of TDZ was faster (11.43 mLh-1) from TZP-AqS as compared to NC1 (5.88 mLh-1). Relatively, an extended half-life (t1/2; 4.45 h) of TDZ and the prolonged ocular retention (MRT0-∞; 7.13 h) of NC1 was found, while a shorter half-life (t1/2; 2.66 h) of TDZ and MRT0-∞(t1/2; 5.05 h)was noted for TZP-AqS, respectively. Cationic TZP-NC1 could offer increased transcorneal permeation, which could mimic the improved ocular bioavailability of the drug in vivo. Conclusively, NC1 of TZP was identified as a promising substitute for the ocular delivery of TZP, with better performance as compared to its conventional AqS.

Population scale latent space cohort matching for the improved use and exploration of observational trial data.

A significant amount of clinical research is observational by nature and derived from medical records, clinical trials, and large-scale registries. While there is no substitute for randomized, controlled experimentation, such experiments or trials are often costly, time consuming, and even ethically or practically impossible to execute. Combining classical regression and structural equation modeling with matching techniques can leverage the value of observational data. Nevertheless, identifying variables of greatest interest in high-dimensional data is frequently challenging, even with application of classical dimensionality reduction and/or propensity scoring techniques. Here, we demonstrate that projecting high-dimensional medical data onto a lower-dimensional manifold using deep autoencoders and post-hoc generation of treatment/control cohorts based on proximity in the lower-dimensional space results in better matching of confounding variables compared to classical propensity score matching (PSM) in the original high-dimensional space (P<0.0001) and performs similarly to PSM models constructed by experts with prior knowledge of the underlying pathology when evaluated on predicting risk ratios from real-world clinical data. Thus, in cases when the underlying problem is poorly understood and the data is high-dimensional in nature, matching in the autoencoder latent space might be of particular benefit.