Novel synergistic interactions between monolaurin, a mono-acyl glycerol and ß lactam antibiotics against Staphylococcus aureus: an in vitro study.

BACKGROUND: A major worldwide health issue is the rising frequency of resistance of bacteria.Drug combinations are a winning strategy in fighting resistant bacteria and might help in protecting the existing drugs.Monolaurin is natural compound extracted from coconut oil and has a promising antimicrobial activity against Staphylococcus.aureus. This study aims to examine the efficacy of monolaurin both individually and in combination with ß-lactam antibiotics against Staphylococcus aureus isolates. METHODS: Agar dilution method was used for determination of minimum inhibitory concentration (MIC) of monolaurin against S.aureus isolates. Scanning electron microscope (SEM) was used to detect morphological changes in S.aureus after treatment with monolaurin. Conventional and Real-time Polymerase chain reaction (RT-PCR) were performed to detect of beta-lactamase (blaZ) gene and its expressional levels after monolaurin treatment. Combination therapy of monolaurin and antibiotics was assessed through fractional inhibitory concentration and time-kill method. RESULTS: The antibacterial activity of monolaurin was assessed on 115 S.aureus isolates, the MIC of monolaurin were 250 to 2000 µg/ml. SEM showed cell elongation and swelling in the outer membrane of S.aureus in the prescence of 1xMIC of monolaurin. blaZ gene was found in 73.9% of S.aureus isolates. RT-PCR shows a significant decrease in of blaZ gene expression at 250 and 500 µg/ml of monolaurin. Synergistic effects were detected through FIC method and time killing curve. Combination therapy established a significant reduction on the MIC value. The collective findings from the antibiotic combinations with monolaurin indicated synergism rates ranging from 83.3% to 100%.In time-kill studies, combination of monolaurin and ß-lactam antibiotics produced a synergistic effect. CONCLUSION: This study showed that monolaurin may be a natural antibacterial agent against S. aureus, and may be an outstanding modulator of ß-lactam drugs. The concurrent application of monolaurin and ß-lactam antibiotics, exhibiting synergistic effects against S. aureus in vitro, holds promise as potential candidates for the development of combination therapies that target particularly, patients with bacterial infections that are nearly incurable.

Ultrasonic synthesis of green lipid nanocarriers loaded with Scutellaria barbata extract: a sustainable approach for enhanced anticancer and antibacterial therapy.

Ultrasonic manufacturing has emerged as a promising eco-friendly approach to synthesize lipid-based nanocarriers for targeted drug delivery. This study presents the novel ultrasonic preparation of lipid nanocarriers loaded with Scutellaria barbata extract, repurposed for anticancer and antibacterial use. High-frequency ultrasonic waves enabled the precise self-assembly of DSPE-PEG, Span 40, and cholesterol to form nanocarriers encapsulating the therapeutic extract without the use of toxic solvents, exemplifying green nanotechnology. Leveraging the inherent anticancer and antibacterial properties of Scutellaria barbata, the study demonstrates that lipid encapsulation enhances the bioavailability and controlled release of the extract, which is vital for its therapeutic efficacy. Dynamic light scattering and transmission electron microscopy analyses confirmed the increase in size and successful encapsulation post-loading, along with an augmented negative zeta potential indicating enhanced stability. A high encapsulation efficiency of 91.93% was achieved, and in vitro assays revealed the loaded nanocarriers' optimized release kinetics and improved antimicrobial potency against Pseudomonas aeruginosa, compared to the free extract. The combination of ultrasonic synthesis and Scutellaria barbata in an eco-friendly manufacturing process not only advances green nanotechnology but also contributes to sustainable practices in pharmaceutical manufacturing. The data suggest that this innovative nanocarrier system could provide a robust platform for the development of nanotechnology-based therapeutics, enhancing drug delivery efficacy while aligning with environmental sustainability.

Synthesis and molecular docking of new N4-piperazinyl ciprofloxacin hybrids as antimicrobial DNA gyrase inhibitors.

A series of N-4 piperazinyl ciprofloxacin derivatives as urea-tethered ciprofloxacin-chalcone hybrids 2a-j and thioacetyl-linked ciprofloxacin-pyrimidine hybrids 5a-i were synthesized. The target compounds were investigated for their antibacterial activity against S. aureus, P. aeruginosa, E. coli, and C. albicans strains, respectively. Ciprofloxacin derivatives 2a-j and 5a-i revealed broad antibacterial activity against either Gram positive or Gram negative strains, with MIC range of 0.06-42.23 µg/mL compared to ciprofloxacin with an MIC range of 0.15-3.25 µg/mL. Among the tested compounds, hybrids 2b, 2c, 5a, 5b, 5h, and 5i exhibited remarkable antibacterial activity with MIC range of 0.06-1.53 µg/mL against the tested bacterial strains. On the other hand, compounds 2c, 2e, 5c, and 5e showed comparable antifungal activity to ketoconazole against candida albicans with MIC range of 2.03-3.89 µg/mL and 2.6 µg/mL, respectively. Further investigations showed that some ciprofloxacin hybrids have inhibitory activity against DNA gyrase as potential molecular target compared to ciprofloxacin with IC50 range of 0.231 ± 0.01-7.592 ± 0.40 µM and 0.323 ± 0.02 µM, respectively. Docking studies of compounds 2b, 2c, 5b, 5c, 5e, 5h, and 5i on the active site of DNA gyrase (PDB: 2XCT) confirmed their ability to form stable complex with the target enzyme like that of ciprofloxacin.

Engagement of private health sector in communicable disease and immunization programmes in Pakistan.

Background: In Pakistan, where the burden of communicable diseases remains high, the private sector accounts for 62% of health care provision. Aim: To describe the role of the private sector in communicable disease management in Pakistan and inform a more effective engagement towards achieving Universal Health Coverage. Methods: We searched the literature and available documents on policies, regulations and experiences in private health sector engagement in Pakistan. We interviewed policy level experts regarding the formulation of national health policies and plans and a sample of private providers using a structured questionnaire to assess their awareness of and engagement in communicable disease programmes. Results: Published reports described initiatives to engage the private sector in improving coverage for a package of care and programme-specific initiatives. Pakistan did not have a national policy for structural engagement, and regulations were limited. Policy level experts interviewed perceived the private sector as market-driven and poorly regulated. Thirty-nine percent of private sector providers interviewed were aware or had been trained in procedures or guidelines, and 23% of them had had their performance monitored by government. Conclusion: We recommend that the Ministry of Health provide overall vision for the operations of the public and private health sectors so that both sectors can complement each other towards the achievement of Universal Health Coverage, including for communicable diseases.

Shifting cold to hot tumors by nanoparticle-loaded drugs and products.

Cold tumors lack antitumor immunity and are resistant to therapy, representing a major challenge in cancer medicine. Because of the immunosuppressive spirit of the tumor microenvironment (TME), this form of tumor has a low response to immunotherapy, radiotherapy, and also chemotherapy. Cold tumors have low infiltration of immune cells and a high expression of co-inhibitory molecules, such as immune checkpoints and immunosuppressive molecules. Therefore, targeting TME and remodeling immunity in cold tumors can improve the chance of tumor repression after therapy. However, tumor stroma prevents the infiltration of inflammatory cells and hinders the penetration of diverse molecules and drugs. Nanoparticles are an intriguing tool for the delivery of immune modulatory agents and shifting cold to hot tumors. In this review article, we discuss the mechanisms underlying the ability of nanoparticles loaded with different drugs and products to modulate TME and enhance immune cell infiltration. We also focus on newest progresses in the design and development of nanoparticle-based strategies for changing cold to hot tumors. These include the use of nanoparticles for targeted delivery of immunomodulatory agents, such as cytokines, small molecules, and checkpoint inhibitors, and for co-delivery of chemotherapy drugs and immunomodulatory agents. Furthermore, we discuss the potential of nanoparticles for enhancing the efficacy of cancer vaccines and cell therapy for overcoming resistance to treatment.

Advancing therapeutic efficacy: nanovesicular delivery systems for medicinal plant-based therapeutics.

The utilization of medicinal plant extracts in therapeutics has been hindered by various challenges, including poor bioavailability and stability issues. Nanovesicular delivery systems have emerged as promising tools to overcome these limitations by enhancing the solubility, bioavailability, and targeted delivery of bioactive compounds from medicinal plants. This review explores the applications of nanovesicular delivery systems in antibacterial and anticancer therapeutics using medicinal plant extracts. We provide an overview of the bioactive compounds present in medicinal plants and their therapeutic properties, emphasizing the challenges associated with their utilization. Various types of nanovesicular delivery systems, including liposomes, niosomes, ethosomes, and solid lipid nanoparticles, among others, are discussed in detail, along with their potential applications in combating bacterial infections and cancer. The review highlights specific examples of antibacterial and anticancer activities demonstrated by these delivery systems against a range of pathogens and cancer types. Furthermore, we address the challenges and limitations associated with the scale-up, stability, toxicity, and regulatory considerations of nanovesicular delivery systems. Finally, future perspectives are outlined, focusing on emerging technologies, integration with personalized medicine, and potential collaborations to drive forward research in this field. Overall, this review underscores the potential of nanovesicular delivery systems for enhancing the therapeutic efficacy of medicinal plant extracts in antibacterial and anticancer applications, while identifying avenues for further research and development.

New Therapeutic Strategies for the Inflammatory Rheumatoid Arthritis Disease: Emphasizing Mesenchymal Stem Cells and Associated exo-miRNA or exo-lncRNA.

The most prevalent inflammatory arthritis and a leading contributor to disability is rheumatoid arthritis (RA). Although it may not have arrived in Europe until the 17th century, it was present in early Native American communities several thousand years ago. Exosomes released by mesenchymal stem cells (MSCs) are highly immunomodulatory due to the origin of the cell. As a cell-free therapy, MSCs-exosomes are less toxic and elicit a weakened immune response than cell-based therapies. Exosomal noncoding RNAs (ncRNAs) are closely associated with a number of biological and functional facets of human health, especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Various exo-miRNAs and lncRNAs such as HAND2-AS1, miR-150-5p, miRNA-124a, and miR-320a lodged with MSC could be appropriate therapeutic ways for RA treatment. These MSC-derived exosomes affect RA disorders via different molecular pathways such as NFK-ß, MAPK, and Wnt. The purpose of this review is to review the research that has been conducted since 2020 so far in the field of RA disease treatment with MSC-loaded exo-miRNAs and exo-lncRNAs.

Translating political commitments into actions to enhance Universal Health Coverage in the Eastern Mediterranean Region.

Background: Many countries in the Eastern Mediterranean Region (EMR) have developed packages of services for achieving Universal Health Coverage (UHC), however, policymakers, especially in resource-constrained countries, still face challenges in delivering equitable, efficient and sustainable health services. Aims: To provide guidance for EMR countries and develop packages of services for UHC. Methods: We used information gathered from narrative reviews, national experiences and expert consultations to develop step-by-step guidance for the development of national packages of services for the achievement of UHC by countries in the EMR. Results: The processes used to develop packages of services varied between EMR countries and these processes may not have involved all relevant stakeholders. We highlight in this paper the iterative processes, including several phases and steps, to be used by EMR countries for developing packages of services for UHC. These processes also make provision for continuous monitoring and revision to make necessary improvements as morbidity patterns evolve. Conclusion: Developing a package of services for the achievement of UHC is a significant milestone for EMR countries and it is central to shaping the healthcare system for effective delivery of services.

Government purchasing initiatives involving private providers in the Eastern Mediterranean Region: a systematic review of impact on health service utilisation.

OBJECTIVE: This paper provides a systematic review of evidence of government purchase of health services from private providers through stand-alone contracting-out (CO) initiatives and CO insurance schemes (CO-I) on health service utilisation in Eastern Mediterranean Region (EMR) to inform universal health coverage 2030 strategies. DESIGN: Systematic review. DATA SOURCES: Electronic search of published and grey literature on Cochrane Central Register of Controlled Trials, PubMed, CINHAL, Google Scholar and web, including websites of ministries of health from January 2010 to November 2021. ELIGIBILITY CRITERIA: Randomised controlled trials, quasi-experimental studies, time series, before-after and endline with comparison group reporting quantitative utilisation of data across 16 low-income and middle-income states of EMR. Search was limited to publications in English or English translation. DATA EXTRACTION AND SYNTHESIS: We planned for meta-analysis, but due to limited data and heterogeneous outcomes, descriptive analysis was performed. RESULTS: Several initiatives were identified but only 128 studies were eligible for full-text screening and 17 met the inclusion criteria. These included CO (n=9), CO-I (n=3) and a combination of both (n=5) across seven countries. Eight studies assessed interventions at national level and nine at subnational level. Seven studies reported on purchasing arrangements with non-governmental organisations, 10 on private hospitals and clinics. Impact on outpatient curative care utilisation was seen in both CO and CO-I, positive evidence of improved maternity care service volumes was seen mainly from CO interventions and less reported from CO-I, whereas data on child health service volume was only available for CO and indicated negative impact on service volumes. The studies also suggest pro-poor effect for CO initiatives, whereas there was scarce data for CO-I. CONCLUSION: Purchasing involving stand-alone CO and CO-I interventions in EMR positively impact general curative care utilisation, but lacks conclusive evidence for other services. Policy attention is needed for embedded evaluations within programmes, standardised outcome metrics and disaggregated utilisation data.

Evaluation occupationally radiation exposure during diagnostic imaging examinations.

Occupational radiation exposure can occur due to various human activities, including the use of radiation in medicine. Occupationally exposed personnel surpassing 7.4 millions, and respresent the biggest single group of employees who are exposed to artificial radiation sources at work. This study compares the occupational radiation dose levels for 145 workers in four different hospitals located in the Aseer region in Saudi Arabia. The occupational exposure was quantified using thermoluminescence dosimeters (TLD-100). The levels of annual occupational exposures in targeted hospitals were calculated and compared with the levels of the international atomic energy agency (IAEA) Safety Standards. An average yearly cumulative dose for the two consecutive years. The average, highest and lowest resulted occupational doses under examination in this work is 1.42, 3.9 mSv and 0.72 for workers in various diagnostic radiology procedures. The resulted annual effective dose were within the IAEA approved yearly dose limit for occupational exposure of workers over 18, which is 20 mSv. Staff should be monitored on a regular basis, according to current practice, because their annual exposure may surpass 15% of the annual effective doses.

Assessing capacities and resilience of health services during the COVID-19 pandemic: Lessons learned from use of rapid key informant surveys.

This article is part of the Research Topic: 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict.' Problem: Many countries lacked rapid and nimble data systems to track health service capacities to respond to COVID-19. They struggled to assess and monitor rapidly evolving service disruptions, health workforce capacities, health products availability, community needs and perspectives, and mitigation responses to maintain essential health services. Method: Building on established methodologies, the World Health Organization developed a suite of methods and tools to support countries to rapidly fill data gaps and guide decision-making during COVID-19. The tools included: (1) a national "pulse" survey on service disruptions and bottlenecks; (2) a phone-based facility survey on frontline service capacities; and (3) a phone-based community survey on demand-side challenges and health needs. Use: Three national pulse surveys revealed persisting service disruptions throughout 2020-2021 (97 countries responded to all three rounds). Results guided mitigation strategies and operational plans at country level, and informed investments and delivery of essential supplies at global level. Facility and community surveys in 22 countries found similar disruptions and limited frontline service capacities at a more granular level. Findings informed key actions to improve service delivery and responsiveness from local to national levels. Lessons learned: The rapid key informant surveys provided a low-resource way to collect action-oriented health services data to inform response and recovery from local to global levels. The approach fostered country ownership, stronger data capacities, and integration into operational planning. The surveys are being evaluated to inform integration into country data systems to bolster routine health services monitoring and serve as health services alert functions for the future.

Assessment of breast dose and cancer risk for young females during CT chest and abdomen examinations.

CT scanning deliver much higher radiation doses than planar radiological procedures, which puts patients to high risks. This study measures and evaluates patient doses during chest and abdomen computed tomography procedures. Particular attention is given to measuring the dose to the equivalent breast (mSv) and to estimate the associated risks of breast cancer to young female patients (15-35 years). Data was obtained from standard examinations from three hospitals. The measured values of CT dose indexes, CTDI (mGy) as well as exposure-related parameters were used for assessment. Breast and effective doses were extrapolated using a software. The results showed remarkable variations of the mean organ equivalent doses for similar CT examinations in the studied hospitals. This could be attributed to the variation in CT scanning imaging technique, and clinical indications. The average effective dose to the chest was 7.9 mSv (2.3-47.0 mSv) and for the abdomen the mean dose was 6.6 mSv, ranging from (3.3-27 mSv). The breast received equivalent doses from chest and abdomen procedures as follows: 10.2 (1.6-33 mSv) and 10.1(2.3-19 mS) Sv respectively. Each procedure yielded high risks of breast cancer for young females. Implementation of accurate referral criteria is recommended to avoid unnecessary breast radiation exposure.

Evaluation of the annual occupational effective doses in a SPECT/CT department.

Staff occupational radiation exposure is limited to 20 mSv annually to preclude tissue reaction and lower risk of cancer effect. Staff occupational exposure arises during the preparation, injection, and scanning of the patients. Recent studies reported that nuclear medicine personnel might exceed the annual dose limit in high workload and poor radiation protection circumstances. Therefore, an accurate estimation of the annual dose limit is recommended. The goal of this research is to calculate the cumulative external effective dose (mSv) per year for nuclear medicine physicians, technologists, and nurses at SPECT/CT department. A total of 15 staff worked in the nuclear medicine department at King Saud Medical City (KSMC), Riyadh, Saudi Arabia were evaluated for the last six years. 99mTc is used more frequently for most of the patients. The procedures include renal, cardiac scintigraphy procedures. Staff dose was quantified using calibrated thermoluminecnt dosimeters (TLD-100) with an automatic TLD reader (Harshaw 6600). Exposure to ionizing radiation was evaluated in terms of deep doses (Hp(10) were evaluated. The overall average and standard deviation of the external doses for nuclear medicine physicians, technologists' and nurses were 1.8 ± 0.7, 1.9 ± 0.6, 2.0 ± 0.9, 2.2 ± 0.8, 6.0 ± 2.8, and 3.6 ± 1.3 for the years 2015,2016,2017,2018,2019, and 2020, respectively. Technologists and nurses received higher doses of compared to the nuclear medicine physicians. Technologists and nurses involved in radionuclide preparation, patients' injection, and image acquisition. Staff annual exposure is below the annual dose limits; however, this external dose is considered high compared to the current workload.

Occupational exposure and radiobiological risk from thyroid radioiodine therapy in Saudi Arabia.

Worldwide, thyroid cancer accounts for some 10% of total cancer incidence, most markedly for females. Thyroid cancer radiotherapy, typically using 131I (T1/2 8.02 days; ß- max energy 606 keV, branching ratio 89.9%), is widely adopted as an adjunct to surgery or to treat inoperable cancer and hyperthyroidism. With staff potentially receiving significant doses during source preparation and administration, radiation protection and safety assessment are required in ensuring practice complies with international guidelines. The present study, concerning a total of 206 patient radioiodine therapies carried out at King Faisal Specialist Hospital and Research Center over a 6-month period, seeks to evaluate patient and occupational exposures during hospitalization, measuring ambient doses and estimating radiation risk. Using calibrated survey meters, patient exposure dose-rate estimates were obtained at a distance of 30-, 100- and 300 cm from the neck region of each patient. Occupational and ambient doses were measured using calibrated thermoluminescent dosimeters. The mean and range of administered activity (AA, in MBq) for the thyroid cancer and hyperthyroidism treatment groups were 4244 ± 2021 (1669-8066), 1507.9 ± 324.1 (977.9-1836.9), respectively. The mean annual occupational doses were 1.2 mSv, that for ambient doses outside of the isolation room corridors were found to be 0.2 mSv, while ambient doses at the nursing station were below the lower limit of detection. Exposures to staff from patients being treated for thyroid cancer were less compared to hyperthyroidism patients. With a well-defined protocol, also complying with international safety requirements, occupational exposures were found to be relatively high, greater than most reported in previous studies.

Promoting family practice-based model of care: the role of WHO's professional diploma in family medicine in the Eastern Mediterranean Region.

Strengthening Primary Health Care (PHC) through family practice-based model of care is an essential bedrock in achieving Universal Health Coverage (UHC), as called for in Sustainable Development Goal (SDG) 3, target 3.8. However, the shortage of family practitioners worldwide and in most countries of the Eastern Mediterranean Region (EMR) is a daunting challenge. The current production rate of family physicians in the EMR is around 700 annually, against the needed estimate of 21 000 physicians per year based on one family physician/1300 population and the current EMR population growth rate, which reflects the huge shortage of family physicians in the Region.

Occupational and ambient radiation exposures from Lu-177 DOTATATE during targeted therapy.

Lutetium-177 (DOTATATE) (177Lu; T1/2 6.7 days), a labelled ß- and Auger-electron emitter, is widely used in treatment of neuroendocrine tumours. During performance of the procedure, staff and other patients can potentially receive significant doses in interception of the gamma emissions [113 keV (6.4%) and 208 keV (11%)] that are associated with the particle decays. While radiation protection and safety assessment are required in seeking to ensure practices comply with international guidelines, only limited published studies are available. The objectives of present study are to evaluate patient and occupational exposures, measuring ambient doses and estimating the radiation risk. The results, obtained from studies carried out in Riyadh over an 11 month period, at King Faisal Specialist Hospital and Research Center, concerned a total of 33 177Lu therapy patients. Patient exposures were estimated using a calibrated Victoreen 451P survey meter (Fluke Biomedical), for separations of 30 cm, 100 cm and 300 cm, also behind a bed shield that was used during hospitalization of the therapy patients. Occupational and ambient doses were also measured through use of calibrated thermoluminescent dosimeters and an automatic TLD reader (Harshaw 6600). The mean and range of administered activity (in MBq)) was 7115.2 ± 917.2 (4329-7955). The ambient dose at corridors outside of therapy isolation rooms was 1.2 mSv over the 11 month period, that at the nursing station was below the limit of detection and annual occupational doses were below the annual dose limit of 20 mSv. Special concern needs to be paid to comforters (carers) and family members during the early stage of radioisotope administration.

Risk Assessment and Management of Venous Thromboembolism in Women during Pregnancy and Puerperium (SAVE): An International, Cross-sectional Study.

The clinical burden of obstetric venous thromboembolism (VTE) risk is inadequately established. This study assessed the prevalence and management of VTE risk during pregnancy and postpartum outside the Western world. This international, noninterventional study enrolled adult women with objectively confirmed pregnancy attending prenatal care/obstetric centers across 18 countries in Africa, Eurasia, Middle-East, and South Asia. Evaluations included proportions of at-risk women, prophylaxis as per international guidelines, prophylaxis type, factors determining prophylaxis, and physicians' awareness about VTE risk management guidelines and its impact on treatment decision. Data were analyzed globally and regionally. Physicians ( N = 181) screened 4,978 women, and 4,010 were eligible. Of these, 51.4% were at risk (Eurasia, 90%; South Asia, 19.9%), mostly mild in intensity; >90% received prophylaxis as per the guidelines (except South Asia, 77%). Women in Eurasia and South Asia received both pharmacological and mechanical prophylaxes (>55%), while pharmacological prophylaxis (>50%) predominated in Africa and the Middle-East. Low-molecular-weight heparin was the pharmacological agent of choice. Prophylaxis decision was influenced by ethnicity, assisted reproductive techniques, caesarean section, and persistent moderate/high titer of anticardiolipin antibodies, though variable across regions. Prophylaxis decision in at-risk women was similar, irrespective of physicians' awareness of guidelines (except South Asia). A majority (>80%) of the physicians claimed to follow the guidelines. More than 50% of women during pregnancy and postpartum were at risk of VTE, and >90% received prophylaxis as per the guidelines. Physicians are generally aware of VTE risk and comply with guidelines while prescribing prophylaxis, although regional variations necessitate efforts to improve implementation of the guidelines.