Oral Bioactive Self-Nanoemulsifying Drug Delivery Systems of Remdesivir and Baricitinib: A Paradigmatic Case of Drug Repositioning for Cancer Management.

Oral anticancer therapy mostly faces the challenges of low aqueous solubility, poor and irregular absorption from the gastrointestinal tract, food-influenced absorption, high first-pass metabolism, non-targeted delivery, and severe systemic and local adverse effects. Interest has been growing in bioactive self-nanoemulsifying drug delivery systems (bio-SNEDDSs) using lipid-based excipients within nanomedicine. This study aimed to develop novel bio-SNEDDS to deliver antiviral remdesivir and baricitinib for the treatment of breast and lung cancers. Pure natural oils used in bio-SNEDDS were analyzed using GC-MS to examine bioactive constituents. The initial evaluation of bio-SNEDDSs were performed based on self-emulsification assessment, particle size analysis, zeta potential, viscosity measurement, and transmission electron microscopy (TEM). The single and combined anticancer effects of remdesivir and baricitinib in different bio-SNEDDS formulations were investigated in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines. The results from the GC-MS analysis of bioactive oils BSO and FSO showed pharmacologically active constituents, such as thymoquinone, isoborneol, paeonol and p-cymenene, and squalene, respectively. The representative F5 bio-SNEDDSs showed relatively uniform, nanosized (247 nm) droplet along with acceptable zeta potential values (+29 mV). The viscosity of the F5 bio-SNEDDS was recorded within 0.69 Cp. The TEM suggested uniform spherical droplets upon aqueous dispersions. Drug-free, remdesivir and baricitinib-loaded bio-SNEDDSs (combined) showed superior anticancer effects with IC50 value that ranged from 1.9-4.2 µg/mL (for breast cancer), 2.4-5.8 µg/mL (for lung cancer), and 3.05-5.44 µg/mL (human fibroblasts cell line). In conclusion, the representative F5 bio-SNEDDS could be a promising candidate for improving the anticancer effect of remdesivir and baricitinib along with their existing antiviral performance in combined dosage form.

Effects of various doses of glutathione on the proliferation, viability, migration, and ultrastructure of cultured human melanocytes.

Normal human cultured melanocytes were exposed to various glutathione concentrations (0.1, 0.5, 1.0, 5.0, and 10.0 mg/mL) for 72 hours. At the end of the experiment, proliferation, viability, migration, and ultrastructural changes were monitored. Glutathione at the doses of 0.5 to 10.0 mg/mL reduced the viability of melanocytes significantly as compared to the control (P < .05). Glutathione significantly reduced the proliferation of melanocytes at the doses of 0.5 to 10.0 mg/mL as compared to the control (P < .001). Glutathione at 0.5 to 10.0 mg/mL significantly reduced the migration of melanocytes as compared to the control (P < .001). The percentage of mature melanosomes was 53.43% in control and 50.58%, 41.83%, 33.4%, and 8.95% in 0.1, 0.5, 1.0, and 5.0 mg/mL glutathione exposed cells, respectively. This reduction in the number of mature melanosomes was statistically significant as compared to the control. However, no cytotoxic effects were recognized by electron micrographs. These results encourage the potential implementation of glutathione as a skin-lightening agent. However, this study is limited by cell culture and ultrastructural. It should therefore be expanded in the future to include patients with pigmentary disorders.

Safety and efficacy of parenteral glutathione as a promising skin lightening agent: A controlled assessor blinded pharmacohistologic and ultrastructural study in an animal model.

Hyperpigmentation was induced in the skin of experimental animals using UVB at 6 J/cm2 three times a week for three consecutive weeks. Subsequently, glutathione was injected intraperitoneally in the experimental animals at doses of 10, 20, and 40 mg/kg body weight three times a week for three consecutive weeks. At the end of the experiment, blood samples and lung, kidney, liver, and skin tissue specimens were collected from animals for hematological, biochemical, histological, and electron microscopy examination. Glutathione at 40 mg/kg body weight/day reduced skin hyperpigmentation significantly, except at low doses. The skin lightening effect assessed by a chromameter was dose-dependent. There were no statistically significant differences among the mean values of AST, ALT, creatinine, BUN, and CBC counts across the four groups. Lung, kidney, and liver tissue specimens did not show any histological toxic changes. The number of melanin granules was significantly lower in the group treated with the highest dose of glutathione compared to that in the control. Electron microscopy proved that glutathione at 20 and 40 mg/kg body weight/day was able to reduce the number of melanized cells significantly compared to that in the control. Parenteral glutathione was effective as a skin lightening agent and did not provoke any toxic effects in the employed animal model. The limitation of the study was conducted in guinea pigs and was of short-term duration.

The welcoming attitude of dermatologists towards complementary and alternative medicine despite their lack of knowledge and training.

Background/aim: Although complementary and alternative medicine (CAM) use is highly prevalent, there is very limited information on dermatologists' attitudes and knowledge about CAM. In this survey, we aimed to study the knowledge and attitude of dermatologists in Saudi Arabia towards CAM. Furthermore, we assessed dermatologists' intention to receive CAM education and training. Methods and design: We collected data through an online cross-sectional survey sent to email addresses of dermatologists in Saudi Arabia. Questions included socio-demographic data, knowledge and attitudes towards CAM practice. Results: A total of 93 questionnaires were returned from dermatologists in various regions of Saudi Arabia. The mean age was 41.7 ± 10.3 (range, 25-63) years. A total of 67% of dermatologists had welcoming attitudes towards CAM. We did not find any significant relationship between age, gender, experience or any other factor and positive attitudes towards CAM. More than 70% of participants reported an interest in learning about CAM. However, only 9 (9.7%) dermatologists had attended CAM courses. Sixty-one participants (65.6%) were eager to receive CAM-specific education, and 66% of dermatologists acknowledged having previously discussed CAM with their patients. The most important reason that dermatologists did not discuss CAM with their patients was a lack of studies supporting CAM (66.7%) and the belief that doctors' knowledge on CAM is insufficient (58.1%). Conclusion: A greater number of dermatologists have an affirmative attitude towards CAM. The willingness to improve knowledge and training indicates that the CAM field could potentially grow in dermatology.

Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia.

BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.

Ultra-structural effects of different low-level lasers on normal cultured human melanocytes: an in vitro comparative study.

The aim of this study was to investigate the effects of the different types of low-level laser therapy (LLLT) on the ultra-structure and number of melanosomes in normal cultured human melanocytes. Specific effects of various types of LLLT on the ultra-structure of melanosomes have not yet been reported. Melanocytes were exposed to LLLT at an energy level of 2.0 J/cm2, using a blue (457 nm), red (635 nm), or ultraviolet (UV) (355 nm) laser. After 72 h of irradiation, the melanocytes were fixed in 2.5 % glutaraldehyde (pH 7.2) phosphate buffer for 8 h and analyzed by transmission electron microscopy. Four developmental stages (I to IV) of melanosomes were observed, and their numbers were counted manually. The percentage of stages I, II, III, and IV melanosomes was 12.8, 14.2, 22.6, and 50.3 %, respectively, in the control (sham light). However, the melanosome percentages were 41.2, 5.4, 8.2, and 24.2 % in stages I, II, III, and IV, respectively, in the blue laser-treated group; 58.4, 6.1, 9.3, and 26.2 % for stages I, II, III, and IV, respectively, in the red laser-treated group; and 31.3, 11.1, 16.5, and 41.1 % for stages I, II, III, and IV, respectively, in the UV laser-treated group. The present data show that the amount of stage I is significantly higher (P < 0.0001) in the LLLT-treated cells compared to the control, which indicates significant stimulation of melanogenesis. The red laser was more effective than the other lasers. Moreover, the effects of LLLT on the ultra-structure of melanosomes need to be studied in a larger number of subject groups.

Knowledge, attitudes and practices of the general public toward sun exposure and protection: A national survey in Saudi Arabia.

Background: Many international studies have been conducted to assess the knowledge, attitudes and practices (KAP) of the public toward sun exposure and sun-protection measures. However, there are scarce data on these factors from the Middle East. Objectives: This study aimed to explore the KAP of the public toward sun exposure and sun-protection measures among Saudis. Methods: A cross-sectional survey using a specially designed questionnaire was conducted on a stratified random sample of the general population in the five geographical regions of Saudi Arabia (central, eastern, northern, southern, and western). Data were collected between October 2010 and March 2011. Multiple logistic regressions were applied to relate the use of sunscreen and skin cancer awareness with various socio-demographic variables. Results: The questionnaire was distributed to 2900 Saudis. A total of 2622 questionnaires were completed, returned, and included in the data analysis, corresponding to a response rate of 90.4%. The mean (SD) age of respondents was 27.8 ± 9.7 years. Fifty percent (1301/1601) of the respondents were males. Fifty-five percent (1406/2544) were aware of the association between sun exposure and skin cancer. Female, young and student respondents were more likely to be aware of the connection between sun exposure and skin cancer (p < 0.001). Likewise, respondents from the middle social class and those with higher education levels were more likely to be informed (p < 0.02). The prevalence of regular sunscreen use among study participants was only 23.7%, and female and employed respondents were more likely to use sunscreen (p < 0.001). Protective clothes were the most commonly used sun protection measure as reported by more than 90% of our participants. Conclusion: This study has shown that sun awareness and protection are generally inadequate in the Saudi population and suggests the need for health education programs.

A comparative study of the effects of different low-level lasers on the proliferation, viability, and migration of human melanocytes in vitro.

The aim of this study was to investigate the effects of different low-level laser therapies (LLLTs) of various wavelengths and energies on normal cultured human melanocytes. Various studies have shown the effects of LLLs on various types of cultured cells. Presently, little is known about the biological effects of LLLTs on melanocytes. Melanocytes were exposed to LLLT at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, or 5.0 J/cm(2) using a blue (457 nm), red (635 nm), or ultraviolet (UV) (355 nm) laser. Melanocyte viability, proliferation, and migration were monitored at 72 h after irradiation. The blue (P < 0.001) and red (P < 0.001 and P < 0.01) lasers significantly enhanced viability at 0.5 to 2.0 J/cm(2), whereas the UV laser (P < 0.001) could significantly enhance viability only at 0.5 and 1.0 J/cm(2) compared with controls. The blue and red lasers also significantly enhanced the proliferation of the melanocytes at 0.5 to 2.0 J/cm(2) (P < 0.001), and the UV laser significantly enhanced proliferation at 0.5 to 1.5 J/cm(2) (P < 0.001 and P < 0.01) compared with controls. The blue laser significantly enhanced melanocyte migration at 0.5 to 4.0 J/cm(2) (P < 0.001 to P < 0.05), but the red (P < 0.001 and P < 0.01) and UV (P < 0.001 to P < 0.05) lasers could significantly enhance such migration at 0.5 to 1.0 J/cm(2) and 0.5 to 2.0 J/cm(2), respectively, compared with controls. LLLT at low energy densities is able to significantly increase melanocyte viability, proliferation, and migration in vitro, and at higher energy densities, it gives non-stimulatory results. Additionally, the blue laser was the best among the three lasers. These findings might have potential application in vitiligo treatment in future.

Nail tube splinting method versus lateral nail avulsion with phenol matricectomy: a prospective randomized comparative clinical trial for ingrown toenail treatment.

BACKGROUND: Ingrown toenail (IGTN) is a common problem that can affect walking and can preclude daily activities. OBJECTIVE: To compare the safety and efficacy of lateral nail avulsion with phenolization (LNAP) versus sleeve (nail tube splinting) surgical techniques in the treatment of IGTN. METHODS: Patients older than 15 years with IGTN were included. Patients were evaluated for the duration and severity of pain, drainage, complete healing periods, recurrence rate, and overall success rate. Assessment was performed at baseline and at 1, 3, and 6 months. Complications were noted. RESULTS: A total of 53 patients, including 46 males (87.8%), were treated. The mean age was 27.7 ± 1.3 years. Thirty patients underwent LNAP, and 23 underwent sleeve methods. The surgical success rate, defined as >90% improvement, was found to be 80% to 82% for both groups. Recurrence was observed in only 1 patient of each group. None of the observed differences in healing, discharge, and recovery were statistically significant except in reporting shoe-wear discomfort, which was shorter in the sleeve group (p < .05). Postoperative pain experience was also noted to be less in the sleeve group (p = .057). CONCLUSION: Both methods, LNAP and sleeve, seem to be equally effective for the treatment of IGTNs. Postoperative shoe-wearing discomfort and pain are shorter when the sleeve method was used.

Skin care: Historical and contemporary views.

Primary prevention, specifically skin care, is an important principle in Islamic theology just as it is emphasized in contemporary medicine. Many skin diseases can be prevented by a proactive approach to skin care, such as proper hygiene and routine inspections, principles that are constantly highlighted in the Islamic literature. Islam promotes primary prevention of disease, including recommendations for skin care practices. The recommendations for skin care practices in Islamic teachings are analogous to current medical guidelines. Sun avoidance, which is recommended by Islam, is mandatory for diseases such as systemic lupus erythematosus, melasma and skin cancers. Skin care and hygiene practices are recommended in Islam and it is considered an important mechanism for reducing the transmission of infections in modern medicine. The body creases and hair are ideal sites for malicious infestations to grow. The practice of "Wudu" includes washing the hands, feet, and hair with clean water. It is an indispensible part of daily prayers which is mandatory for every Muslim. Oral hygiene is also an integral part of both preventive medicine and Islamic teachings. Genital hygiene, particularly after urination and defecation, is recommended in Islamic teachings and is known to prevent urinary and vaginal infections in contemporary medicine. Male circumcision is an Islamic practice. Recently, it was proven that circumcised men are less likely to have sexually transmitted diseases, including HIV. This paper reviews skin care from an Islamic perspective and its relevance to contemporary medicine by translating the simple self care principles into practical guidelines in everyday use.

Phenol as a novel sclerosing agent: A safety and efficacy study on experimental animals.

BACKGROUND: Varicose and ectatic cutaneous vessels are common chronic conditions that might need surgical treatment. There are several treatment modalities, but all can cause complications and have significant recurrence rates. A new effective and safe treatment with low or no recurrence is needed. Phenol seems to be a potential therapeutic agent. OBJECTIVE: To assess the efficacy and safety of phenol as a sclerosing agent in the treatment of varicose veins and other vascular ectatic conditions. METHODS: The dorsal ear veins of white New Zealand rabbits were injected with 0.1 ml of a sclerosing agent. Four experimental groups were used to test the sclerosant efficacy of different concentrations of phenol (1%, 5%, 20% and 50%). Sodium tetradecyl sulphate (STS), a commonly used sclerosing agent, was used as a positive control, while normal saline was used as a negative control. The blood vessels of the treated ears were photographed before and 1 h, 2 days, 8 days and 45 days after treatment. Biopsies from the treated areas were obtained for histologic examinations. RESULTS: A concentration of 1% phenol was too low to cause significant vascular changes, whereas a concentration of 5% phenol caused 90% lumen narrowing. Interestingly, 1% STS only caused 25% lumen narrowing. Concentrations of 20 and 50% phenol caused 100% lumen narrowing but caused haemorrhage and necrosis. Toxicity monitoring showed no apparent haematologic, cardiac, pulmonary, hepatic or renal toxicity associated with the concentrations of phenol used in this study. CONCLUSION: A concentration of 5% phenol appears to be a potent and safe sclerosing agent for ectatic small vessels. This provides a significant new therapeutic option, which may eventually advance to the clinic and have an impact on the treatment of patients suffering from varicose veins and other vascular ectatic conditions.

Perceptions, attitudes and practices toward research among senior medical students.

We aimed to explore perceptions, attitudes and practices toward research among medical students. A self-administered questionnaire was distributed among senior medical students at the King Saud University, Riyadh, Saudi Arabia. Hundred and seventy two students participated in the study, with 97 males (65.5%). The majority of the students agreed that research is important in the medical field (97.1%, 167/172). A total of 67.4% (116/172) believed that conducting research should be mandatory for all medical students. During medical school, 55.3% (88/159) participated in research. The obstacles that prevented the students from conducting research included lack of professional supervisors (84.7%, 143/169), lack of training courses (88.8%, 151/170), lack of time (72.3%, 123/172) and lack of funding (54.1%, 92/170). Although the majority of students believe that research is important in the medical field, only around half of the students participated in research during medical school.

Perceptions and Attitudes of Primary Care Physicians Toward Dermatologic Surgery.

Purpose: Dermatologic surgery is a well-established subspecialty in dermatology that involves various therapeutic and esthetic procedures. To date, perceptions of primary care physicians (PCPs) regarding dermatologic surgery are poorly understood. This study aimed to assess the perception and attitude of PCPs toward dermatologic surgery and explore the factors that might affect their perception and attitude toward it. Patients and Methods: This cross-sectional study used an online survey. The survey was distributed among PCPs working in various regions of Saudi Arabia and contained questions about demographics, medical training information, participants' awareness of dermatologic surgery, and a list of 10 cutaneous procedures to select the most qualified physician performing these procedures. Univariate and multivariate analyses were performed. P≤0.05 was considered statistically significant. Results: In total, 440 PCPs participated in this study. Overall, 70% of the PCPs had heard about dermatologic surgery, whereas 30% had never heard about it. PCPs reported that dermatologic surgeons were the most qualified physicians to perform laser procedures (60.5%), hair transplantation (60.5%), excision of small benign and malignant skin tumors (46.1%), excision of small melanocytic nevi (55.7%), filler injection (44.8%), and injection of botulinum toxin (48.9%); 64.5% considered plastic surgeons to be the most qualified for liposuction. Both physicians were equally selected for performing cyst excision, procedures involving the fingernails and toenails, and scar correction. Multivariate analysis showed that female physicians had heard significantly more about dermatologic surgery (P=0.047, OR: 1.57, 95% CI: 1.006-2.45) and reported that dermatologic surgeons were the most qualified physicians (P=0.042, OR: 1.51, 95% CI: 1.016-2.25) than male physicians. PCPs working at secondary and tertiary health care hospitals heard more about dermatologic surgery (P=0.015, OR: 2.36, 95% CI: 1.18-4.71) than those working at primary health care centers. Conclusion: Most PCPs were aware of dermatologic surgery and recognized dermatologic surgeons as the most qualified physicians to perform most cutaneous procedures.

Development of Polymeric Micelles for Combined Delivery of Luteolin and Doxorubicin for Cancer Therapy.

Background: Luteolin (LUT) is a bioactive compound with several pharmacological activities including anticancer effect. Doxorubicin (DOX) is an anthracycline chemotherapeutic drug that have proven to be effective in treating various types of cancers. Polymeric micelles (PMs) containing biologically active materials have emerged as prospective dosage forms with high drug-loading, which can add therapeutic benefit to the poorly water-soluble compounds and novel chemical entities. PMs are effective in delivering several drugs, such as anticancer drugs, antifungal drugs, flavonoids and drugs targeting the brain. The aim of the current study is to develop PMs for LUT and DOX as a combined delivery system for cancer therapy. Methods: PMs were prepared using 2.5% of each of LUT and DOX with varying compositions of Poloxamer 188, Poloxamer 407, Vitamin E (TPGS), Poloxamer 123 and Gellucire 44/14 at room temperature. Particle size, polydispersity index, zeta potential, were achieved using Zetasizer Nano particle size analyzer and the sizes were further confirmed with transmission electron microscopy (TEM). Prepared PMs were further characterized using powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FTIR). An MTT assay was performed on breast cancer (MCF-7) cells and liver cancer (HepG2) cells to determine the cytotoxic effect of the different PMs formulations. Results: PMs were successfully developed and optimized using 74.3% Poloxamer 407 with 20.7% Vitamin E (TPGS), and 70% Poloxamer 407 with 25% Gellucire 44/14, respectively. The droplet size and polydispersity index were found to be 62.03 ± 3.99 nm, 91.96 ± 5.80 nm and 0.33 ± 0.05, 0.59± 0.03, respectively for PMs containing TPGS and Gellucire 44/14. Zeta potentials of the PMs containing TPGS and Gellucire 44/14 were recorded as -2.27 ±0.11mV and -7.78 ± 0.10 mV, respectively. The PMs showed a spherical structure with approximately 50-90 nm range evident by TEM analysis. The PXRD spectra of PMs powder presented the amorphization of LUT and DOX. The FTIR spectra of LUT-loaded and DOX-loaded PMs were identical, suggesting consistent PMs composition. The MTT assay showed that the representative combined drug loaded PMs treatment led to a reduction in the viability of MCF-7 and HepG2 cells compared to drug free PMs and pure LUT, DOX alone. Conclusions: PMs with LUT and DOX exhibited significant cytotoxic effects against breast and liver cancer cells and could thus be an important new pharmaceutical formulation to treat cancer.

Biochemical exploration of family GH119 reveals a single α-amylase specificity and confirms shared catalytic machinery with GH57 enzymes.

While hundreds of starch- and glycogen-degrading enzymes have been characterized experimentally in historical families such as GH13, GH14, GH15, GH57 and GH126 of the CAZy database (www.cazy.org), the α-amylase from Bacillus circulans is the only enzyme that has been characterized in family GH119. Since glycosidase families have been shown to often group enzymes with different substrates or products, a single characterized enzyme in a family is insufficient to extrapolate enzyme function based solely on sequence similarity. Here we report the rational exploration of family GH119 through the biochemical characterization of five GH119 members. All enzymes shared single α-amylase specificity but display distinct product profile. We also report the first kinetic constants in family GH119 and the first experimental validation of previously predicted catalytic residues in family GH119, confirming that families GH119 and GH57 can be grouped in the novel clan GH-T of the CAZy database.

Analysis of antibiotic regimens and outcomes in spinal brucellosis: insights from a retrospective cohort study in Makkah, Saudi Arabia.

Background: Brucellosis is a zoonotic disease that is widely spread across the globe, with the number of cases increasing annually. Spinal brucellosis is known to affect about half of patients with brucellosis. Nevertheless, data on the optimal antibiotic regimens for spinal brucellosis are limited. Therefore, this study aims to compare antibiotic treatment regimens for spinal brucellosis at our center in Makkah, Saudi Arabia. Methods: This is a retrospective cohort study of an 11-year period from 2010 to 2021 conducted at a single center in Makkah, Saudi Arabia. All patients with spinal brucellosis were included. Patients were excluded if the duration of the received antibiotic regimen or follow-up was poorly documented. Data analysis was conducted using RStudio (R version 4.1.1). Categorical variables of each regimen used by the patients were presented as frequencies and percentages, while numerical variables were summarized using the median and interquartile range (IQR). Results: A total of 35 patients were included; the median (IQR) age of the patients was 58.0 (48.0 to 63.0) years. The most frequently reported symptoms upon admission included low back pain (83.3%). The most frequently administered regimen was the combination of streptomycin + doxycycline + rifampicin (SDR) (20 patients, 55.6%), followed by the combination of streptomycin + rifampicin + trimethoprim/sulfamethoxazole (SRT) (eight patients, 22.2%). Overall, out of the total 35 patients who received first-line treatment, only six patients experienced therapy failure. Out of the total six patients who experienced first-line treatment failure with SDR (five patients, 83%) and SDT (one patient, 17%), surgery was indicated for three patients. Surgical intervention was deemed necessary in 12 patients (34%). Three patients chose not to undergo surgical intervention but still showed complete improvement upon completing the treatment duration. One patient experienced a postoperative complication, resulting in paraplegia. Conclusions: In this study, we found that among 35 patients, treatment failure was observed only in six patients who received triple therapy. In addition, surgical intervention was indicated in 12 patients; however, three patients refused surgery and improved ultimately after changing or extending the duration of the antibiotic regimen.

Investigation and drug design for novel molecules from natural products as inhibitors for controlling multiple myeloma disease using in-silico tools.

Multiple myeloma (MM) is a disease that causes plasma cell growth in the bone marrow and immune globulin buildup in blood and urine. Despite recent advances in MM therapy, many still die due to its high mortality rate. A study using computational simulations analyzed 100 natural ingredients from the SANC database to determine if they inhibited the IgH domain, a known cause of multiple myeloma. Natural component Diospyrin inhibited the IgH enzyme with the best binding energy of -10.3 kcal/mol and three carbon-hydrogen bonds, followed by Parviflorone F complex with a binding energy of -10.1 kcal/mol and two conventional-hydrogen bonds. As a result, the Molecular Dynamic simulation was used to test the stability of the two complexes. During the simulation, the Diospyrin molecule dissociated from the protein at roughly 67.5 ns, whereas the Parviflorone F molecule stayed attached to the protein throughout. The latter was the subject of the investigation. The analysis of the production run data revealed that the Parviflorone F molecule exhibits a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The analysis of the production run data revealed that the Parviflorone F molecule exhibited a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The root mean square deviation (RMSD) plots for both the protein and complex showed a stable and steady average value of 4.4 Å for the first 82 nanoseconds of manufacture. As a result, the average value increased to 8.3 Å. Furthermore, the components of the binding free energy, as computed by MM-GBSA, revealed that the mean binding energy of the Parviflorone F molecule was -23.88 kcal/mol. Finally, after analyzing all of the examination data, Parviflorone F was identified as a powerful inhibitor of the IgH domain and hence of the MM disease, which requires further in-vivo conformation.Communicated by Ramaswamy H. Sarma.

Exogenous zinc mitigates salinity stress by stimulating proline metabolism in proso millet (Panicum miliaceum L.).

Salinity is one of the most concerning ecological restrictions influencing plant growth, which poses a devastating threat to global agriculture. Surplus quantities of ROS generated under stress conditions have negative effects on plants' growth and survival by damaging cellular components, including nucleic acids, lipids, proteins and carbohydrates. However, low levels of ROS are also necessary because of their role as signalling molecules in various development-related pathways. Plants possess sophisticated antioxidant systems for scavenging as well as regulating ROS levels to protect cells from damage. Proline is one such crucial non-enzymatic osmolyte of antioxidant machinery that functions in the reduction of stress. There has been extensive research on improving the tolerance, effectiveness, and protection of plants against stress, and to date, various substances have been used to mitigate the adverse effects of salt. In the present study Zinc (Zn) was applied to elucidate its effect on proline metabolism and stress-responsive mechanisms in proso millet. The results of our study indicate the negative impact on growth and development with increasing treatments of NaCl. However, the low doses of exogenous Zn proved beneficial in mitigating the effects of NaCl by improving morphological and biochemical features. In salt-treated plants, the low doses of Zn (1 mg/L, 2 mg/L) rescued the negative impact of salt (150mM) as evidenced by increase in shoot length (SL) by 7.26% and 25.5%, root length (RL) by 21.84% and 39.07% and membrane stability index (MSI) by 132.57% and 151.58% respectively.The proline content improved at all concentrations with maximum increase of 66.65% at 2 mg/L Zn. Similarly, the low doses of Zn also rescued the salt induced stress at 200mM NaCl. The enzymes related to proline biosynthesis were also improved at lower doses of Zn. In salt treated plants (150mM), Zn (1 mg/L, 2 mg/L) increased the activity of P5CS by 19.344% and 21%. The P5CR and OAT activities were also improved with maximum increase of 21.66% and 21.84% at 2 mg/L Zn respectively. Similarly, the low doses of Zn also increased the activities of P5CS, P5CR and OAT at 200mM NaCl. Whereas P5CDH enzyme activity showed a decrease of 82.5% at 2mg/L Zn+150mM NaCl and 56.7% at 2mg/L Zn+200 mM NaCl. These results strongly imply the modulatory role of Zn in maintaining of proline pool during NaCl stress.

Computational and experimental analysis of foxtail millet under salt stress and selenium supplementation.

Salinity stress is a major threat to crop growth and productivity. Millets are stress-tolerant crops that can withstand the environmental constraints. Foxtail millet is widely recognized as a drought and salinity-tolerant crop owing to its efficient ROS scavenging mechanism. Ascorbate peroxidase (APX) is one of the reactive oxygen species (ROS) scavenging enzymes that leads to hydrogen peroxide (H2O2) detoxification and stabilization of the internal biochemical state of the cell under stress. This inherent capacity of the APX enzyme can further be enhanced by the application of an external mitigant. This study focuses on the impact of salt (NaCl) and selenium (Se) application on the APX enzyme activity of foxtail millet using in silico and in-vitro techniques and mRNA expression studies. The NaCl was applied in the concentrations, i.e., 150 mM and 200 mM, while the Se was applied in 1 µM, 5 µM, and 10 µM concentrations. The in silico studies involved three-dimensional structure modeling and molecular docking. The in vitro studies comprised the morphological and biochemical parameters, alongside mRNA expression studies in foxtail millet under NaCl stress and Se applications. The in silico studies revealed that the APX enzyme showed better interaction with Se as compared to NaCl, thus suggesting the enzyme-modulating role of Se. The morphological and biochemical analysis indicated that Se alleviated the NaCl (150 mM and 200 mM) and induced symptoms at 1 µM as compared to 5 and 10 µM by enhancing the morphological parameters, upregulating the gene expression and enzyme activity of APX, and ultimately reducing the H2O2 content significantly. The transcriptomic studies confirmed the upregulation of chloroplastic APX in response to salt stress and selenium supplementation. Hence, it can be concluded that Se as a mitigant at lower concentrations can alleviate NaCl stress in foxtail millet.

A myxoid neurothekeoma of the nose.

Neurothekeoma is a rare neoplasm assigned to the broad category of benign peripheral nerve sheath tumors. Its cell of origin is still unknown, but most ultrastructural and immunohistochemical studies have favoured the Schwann cell perineurium or fibroblast. Neurothekeoma most commonly presents in females, especially in the second and third decades of life. Typically it presents as an asymptomatic solitary, firm, flesh-coloured or hyperpigmented slow-growing papule or nodule that involves the skin and superficial subcutis. It usually involves the face, neck, arm or shoulder but can also involve extracutaneous sites. Neurothekeoma occurs in myxoid (classic), cellular and intermediate (mixed) variants. Here, we report a 45-year-old male patient presenting with a nodule on the nose that was found to be a myxoid variant of neurothekeoma. It was treated with a simple shave excision followed by removal of the lobulated deeper part by forceps. He had no recurrence after three years of follow-up. To the best of our knowledge, this is the first case of a myxoid neurothekeoma of the nose to be reported in the Middle East.