Symptom-Free Intervals Following Laser Wedge Excision for Recurrent Idiopathic Subglottic Stenosis.

OBJECTIVE: Analyze the duration of symptom-free intervals following laser wedge excision (LWE) for recurrent idiopathic subglottic stenosis (iSGS). Secondary aim includes evaluating the influence of patient-related or disease factors. STUDY DESIGN: Retrospective review. SETTING: Tertiary center. METHODS: Review of iSGS patients who underwent LWE between 2002 and 2021. LWE patients without prior airway surgery were labeled LWE primary (LWEP) and those with prior history of dilation were labeled LWE secondary (LWES). A conditional frailty repeated events model was used to analyze the median time to recurrence (MTR) for each nth recurrence. Secondary analysis included stratification by use of medical therapy and initial preoperative characteristics of scar (Myer-Cotton grade, distance between the glottis and superior-most aspect of scar, DGS; length of scar, DL). RESULTS: Two hundred and ten iSGS patients underwent LWE (131 LWEP, 79 LWES). The proportion of patients experiencing at least 1, 3, 6, and 12 recurrences, respectively, was 68.0% (n = 143), 40.7% (n = 85), 20.0% (n = 42), and 5.2% (n = 11). There was exponential time-shortening from the 1st to 12th recurrence (P < .0001). While MTR was 4.1 years after the first LWE, this fell to 2.8, 1.7, 1.0, and 0.7 years for the 2nd, 3rd, 6th, and 12th recurrences. Furthermore, LWEP patients experienced longer MTR than LWES counterparts within the first 6 recurrences (P < .01). There was no significant relationship between intersurgical interval and medication adherence, DL, DGS, or grade for recurrences beyond the first (P = .207, P = .20, P = .43, P = .16). CONCLUSION: Symptom-free intervals in iSGS shorten with each subsequent recurrence and LWE. The difference in MTR between LWEP and LWES groups was significant within the first 6 recurrences with LWEP having longer MTR.

Discovery and Anticancer Screening of Novel Oxindole-Based Derivative Bearing Pyridyl Group as Potent and Selective Dual FLT3/CDK2 Kinase Inhibitor.

Protein kinases regulate cellular activities and make up over 60% of oncoproteins and proto-oncoproteins. Among these kinases, FLT3 is a member of class III receptor tyrosine kinase family which is abundantly expressed in individuals with acute leukemia. Our previous oxindole-based hit has a particular affinity toward FLT3 (IC50 = 2.49 µM) and has demonstrated selectivity towards FLT3 ITD-mutated MV4-11 AML cells, with an IC50 of 4.3 µM. By utilizing the scaffold of the previous hit, sixteen new compounds were synthesized and screened against NCI-60 human cancer cell lines. This leads to the discovery of a potent antiproliferative compound, namely 5l, with an average GI50 value against leukemia and colon cancer subpanels equalling 3.39 and 5.97 µM, respectively. Screening against a specific set of 10 kinases that are associated with carcinogenesis indicates that compound 5l has a potent FLT3 inhibition (IC50 = 36.21 ± 1.07 nM). Remarkably, compound 5l was three times more effective as a CDK2 inhibitor (IC50 = 8.17 ± 0.32 nM) compared to sunitinib (IC50 = 27.90 ± 1.80 nM). Compound 5l was further analyzed by means of docking and molecular dynamics simulation for CDK2 and FLT3 active sites which provided a rational for the observed strong inhibition of kinases. These results suggest a novel structural scaffold candidate that simultaneously inhibits CDK2 and FLT3 and gives encouragement for further development as a potential therapeutic for leukemia and colon cancer.

Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia.

Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4+ T cell responses in vitro and whether HVEM gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). HVEM gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4+ T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. HVEM expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, p = 0.086) compared with normal embryonic kidney cells (Hek293). CD4+ T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells (p = 0.0033). Significant HVEM differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL (p = 0.0011) and relapsed/refractory (p = 0.0051) B cell ALL (p = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 (p = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.

Effect of tobacco use on Zenker's diverticulotomy outcomes.

OBJECTIVE: To compare clinical outcomes in patients with and without history of tobacco use who underwent Zenker's diverticulotomy (ZD). STUDY DESIGN: Single institution retrospective review. SETTING: Tertiary care academic hospital. METHODS: A retrospective review of patients who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler or harmonic scalpel, and flexible endoscopic technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, diverticular features, and rates of adverse events and symptomatic recurrence. RESULTS: Out of 424 patients, 146 (34.4 %) had a history of tobacco use: 126 (29.7 %) were former smokers, and 20 (4.7 %) were active smokers. In univariable cross-sectional analyses, the likelihood of postoperative bleeding, perforation, emergency department visits, unplanned readmission, or recurrence did not demonstrate an association with tobacco use history even after adjustment for age, sex, and surgical approach. Similarly, in Cox Proportional Hazards regression, tobacco use was not associated with an increased risk of recurrence, even after correcting for age, sex, and type of surgery. The median time to recurrence observed in our cohort was 11.5 years amongst non-smokers, 8.7 years amongst former smokers, and 1.2 years amongst active smokers (p = 0.94). CONCLUSIONS: There were no significant differences in post-operative adverse events or frequency of recurrence of ZD between active, former, and non-smokers. Although underpowered and not statistically significant, median time to recurrence appears to be shorter in smokers when compared with former and non-smokers following surgery.

Nicotinic Receptor Alpha-5 Subunit Gene Polymorphism is Associated with Heavy Smoking Under a Range of Nicotine Dosing Conditions.

INTRODUCTION: This study aimed to assess the role of the rs16969968 variant of nicotinic receptor alpha-5 subunit in regulating smoking behavior and nicotine intake in response to nicotine manipulations among dependent smokers in a naturalistic environment. METHODS: Sixty-nine adults (19 females) smoking 10 or more cigarettes per day were asked to complete four 2-week study phases during which they smoked exclusively one of two types of Spectrum nicotine research cigarettes (FTC nicotine yield 0.8 and 1.6 mg, respectively), their usual brand of cigarettes, or their usual brand of cigarettes while wearing a 21-mg nicotine patch. Measurements included rs16969968 genotype, number of cigarettes per day, smoking topography, and plasma cotinine. RESULTS: Compared to controls (G/G carriers), A allele carriers reported smoking 4 to 5 more cigarettes per day across all conditions (all ps < .05). Mean total smoke volume per day and cotinine were greater in A allele carriers than in controls (ps = 0.05, 0.046, respectively). No significant genotype differences were found in smoking compensation indices for the switch from Medium to High nicotine yield cigarettes. Nicotine patch-induced reductions in cigarettes smoked per day and total smoke volume per day showed significant interactions between genotype and pre-patch levels, heavier smokers showing greater effects of genotype (p = .052 and p =.006, respectively). CONCLUSIONS: Results suggest that the rs16969968 variants regulate heaviness of smoking primarily by their impact on daily numbers of cigarettes smoked, but no genotype differences were found in smoking compensation after switching from Medium to High nicotine cigarettes. IMPLICATIONS: The differences in daily cigarette consumption between rs16969968 risk-allele carriers and controls are shown to be consistent regardless of manipulations of cigarette nicotine content and transdermal nicotine supplementation and markedly greater among dependent smokers than those observed in the general smoker populations. G/G allele carriers, relative to A allele carriers, appeared to be more sensitive to the nicotine patch manipulation, reducing their smoking to a greater extent. These findings support continued efforts in the development of personalized intervention strategies to reduce the rs16969968-conveyed genetic propensity for heavy smoking.

New Theobromine Apoptotic Analogue with Anticancer Potential Targeting the EGFR Protein: Computational and In Vitro Studies.

AIM: The aim of this study was to design and examine a novel epidermal growth factor receptor (EGFR) inhibitor with apoptotic properties by utilizing the essential structural characteristics of existing EGFR inhibitors as a foundation. METHOD: The study began with the natural alkaloid theobromine and developed a new semisynthetic derivative (T-1-PMPA). Computational ADMET assessments were conducted first to evaluate its anticipated safety and general drug-likeness. Deep density functional theory (DFT) computations were initially performed to validate the three-dimensional (3D) structure and reactivity of T-1-PMPA. Molecular docking against the EGFR proteins was conducted to investigate T-1-PMPA's binding affinity and inhibitory potential. Additional molecular dynamics (MD) simulations over 200 ns along with MM-GPSA, PLIP, and principal component analysis of trajectories (PCAT) experiments were employed to verify the binding and inhibitory properties of T-1-PMPA. Afterward, T-1-PMPA was semisynthesized to validate the proposed design and in silico findings through several in vitro examinations. RESULTS: DFT studies indicated T-1-PMPA's reactivity using electrostatic potential, global reactive indices, and total density of states. Molecular docking, MD simulations, MM-GPSA, PLIP, and ED suggested the binding and inhibitory properties of T-1-PMPA against the EGFR protein. The in silico ADMET predicted T-1-PMPA's safety and general drug-likeness. In vitro experiments demonstrated that T-1-PMPA effectively inhibited EGFRWT and EGFR790m, with IC50 values of 86 and 561 nM, respectively, compared to Erlotinib (31 and 456 nM). T-1-PMPA also showed significant suppression of the proliferation of HepG2 and MCF7 malignant cell lines, with IC50 values of 3.51 and 4.13 µM, respectively. The selectivity indices against the two cancer cell lines indicated the overall safety of T-1-PMPA. Flow cytometry confirmed the apoptotic effects of T-1-PMPA by increasing the total percentage of apoptosis to 42% compared to 31, and 3% in Erlotinib-treated and control cells, respectively. The qRT-PCR analysis further supported the apoptotic effects by revealing significant increases in the levels of Casp3 and Casp9. Additionally, T-1-PMPA controlled the levels of TNFα and IL2 by 74 and 50%, comparing Erlotinib's values (84 and 74%), respectively. CONCLUSION: In conclusion, our study's findings suggest the potential of T-1-PMPA as a promising apoptotic anticancer lead compound targeting the EGFR.

Medical Maintenance Therapy Following Laser Excision in Patients With Granulomatosis With Polyangiitis (GPA)-Associated Subglottic Stenosis.

OBJECTIVE: To report on a series of patients with cANCA/PR3-positive, granulomatosis with polyangiitis (GPA)-associated subglottic stenosis (SGS) and evaluate response to medical maintenance therapy with rituximab versus other immunosuppressants following initial endoscopic laser excision. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic center. METHODS: A retrospective chart review of patients with SGS and cANCA/PR3-positive GPA who received immunosuppressive maintenance therapy following endoscopic laser excision at our institution from June 1989 to March 2020 was performed. Data pertaining to patient demographics, clinical features, medications, and endoscopic laser procedures were collected. RESULTS: A total of 27 patients (15 women) with mean age (range) of 40 (19-59) years and mean (range) follow-up of 12.6 years (1.5-28.6) were identified. Sixteen patients (60%) had limited GPA. Six patients (24%) had previously received local intervention with open surgery (n = 1, 4%) or endoscopic techniques (n = 5, 20%). All patients experienced symptom improvement following initial CO2 laser excision at our institution without any procedural complications or adverse events. Following initial laser excision, 15 patients (60%) were treated with rituximab and 10 patients (40%) were treated with nonrituximab immunosuppressive agents. Patients treated with rituximab were less likely to recur (P = 0.040). Limited GPA was associated with an increased incidence of recurrence (P = 0.031). Median time (years) to recurrence (range) was 3.2 (0.3-19.3) and was not significantly associated with treatment or GPA subtype. CONCLUSION: Endoscopic CO2 laser excision is a safe and effective local intervention for GPA-associated SGS. Medical maintenance therapy with rituximab reduces risk of recurrence following initial laser excision relative to treatment with non-rituximab agents.

New thiazolidine-2,4-diones as potential anticancer agents and apoptotic inducers targeting VEGFR-2 kinase: Design, synthesis, in silico and in vitro studies.

BACKGROUND: VEGFR-2 has emerged as a prominent positive regulator of cancer progression. AIM: Discovery of new anticancer agents and apoptotic inducers targeting VEGFR-2. METHODS: Design and synthesis of new thiazolidine-2,4-diones followed by extensive in vitro studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay. In silico investigations including docking, MD simulations, ADMET, toxicity, and DFT studies were performed. RESULTS: Compound 15 showed the strongest VEGFR-2 inhibitory activity with an IC50 value of 0.066 µM. Additionally, most of the synthesized compounds showed anti-proliferative activity against HepG2 and MCF-7 cancer cell lines at the micromolar range with IC50 values ranging from 0.04 to 4.71 µM, relative to sorafenib (IC50 = 2.24 ± 0.06 and 3.17 ± 0.01 µM against HepG2 and MCF-7, respectively). Also, compound 15 showed selectivity indices of 1.36 and 2.08 against HepG2 and MCF-7, respectively. Furthermore, compound 15 showed a significant apoptotic effect and arrested the cell cycle of MCF-7 cells at the S phase. Moreover, compound 15 had a significant inhibitory effect on the ability of MCF-7 cells to heal from. Docking studies revealed that the synthesized thiazolidine-2,4-diones have a binding pattern approaching sorafenib. MD simulations indicated the stability of compound 15 in the active pocket of VEGFR-2 for 200 ns. ADMET and toxicity studies indicated an acceptable pharmacokinetic profile. DFT studies confirmed the ability of compound 15 to interact with VEGFR-2. CONCLUSION: Compound 15 has promising anticancer activity targeting VEGFR-2 with significant activity as an apoptosis inducer.

The Digital Era Heralds a Paradigm Shift in Dentistry: A Cross-Sectional Study.

Background The transformation of dental practice from conventional methods to digital technology has been widely discussed. This study aimed to examine the awareness, understanding, and attitudes towards the use of digital technology in dentistry, with a particular focus on computer-aided design/computer-aided manufacturing (CAD/CAM) technology. Methods A cross-sectional study was conducted, involving a questionnaire distributed to a diverse group of participants from the dental field. The questionnaire covered aspects of digital technology in dentistry, including awareness, perceived usefulness, understanding of CAD/CAM technology, perceived benefits and shortcomings, system awareness, and the impact on clinical decision-making. Results Almost all participants (99.3%) reported being aware of digital technology in dentistry. The perceived utility of digital technology varied widely, but it was considered particularly useful for specific dental procedures. Most of the respondents (948 out of 953) were aware of CAD/CAM technology, and many acknowledged its benefits, including fewer appointments, less chairside time, and greater precision. However, high cost, lack of knowledge, and preference for traditional methods were identified as barriers to adoption. Most participants believed that CAD/CAM would influence clinical decision-making and expressed interest in integrating it into their regular workflow. A majority had attended CAD/CAM training programs and believed there was a need to increase education on CAD/CAM during undergraduate and postgraduate courses. While a significant majority agreed that digital technology was the future of dentistry, a substantial number also expressed reservations. Conclusion The study concluded that there is a high level of awareness and readiness to adopt digital technology in dentistry. However, its perceived utility varied among participants, and several barriers to adoption were identified, indicating the need for expanded education and training. Despite some resistance, there is a growing recognition of the potential benefits of CAD/CAM technology and a trend towards integrating it into regular practice.

Phytosynthesis via wasted onion peel extract of samarium oxide/silver core/shell nanoparticles for excellent inhibition of microbes.

The aqueous onion peel extract (OPE) was used to synthesize silver nanoparticles (Ag-onion), samarium oxide nanoparticles (Sm2O3-onion), and silver/samarium oxide core/shell nanoparticles (Ag@Sm2O3-onion). The produced nanoparticles were characterized by thermal gravimetric analysis (TGA), infrared spectra (FT-IR), absorption spectra (UV-Vis), energy band gap, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), zeta potential, and transmission electron microscopy (TEM). OPE and NPs were tested for the disinfection of some water microbes. XRD analysis exhibited an amorphous structure of samarium oxide in both Sm2O3-onion and Ag@ Sm2O3-onion. The isolated bacteria from the water sample were Bacillus subtilis (OQ073500) and Escherichia coli (MW534699), while the isolated fungi were Alternaria brassicae (MZ266540), Aspergillus flavus (MT550030), Aspergillus penicillioides (MW957971), Pythium ultimum (MW830915), Verticillium dahlia (MW830379), Fusarium acuminatum (MZ266538), Candida albicans (MW534712), and Candida parapsilosis (MW960416). High levels of antimicrobial activity were seen in both the nanoparticles and the aqueous onion peel extract. Based on experimental results, Ag@Sm2O3 demonstrated the highest activity as an effective disinfectant, indicating the effectiveness of the modification process.

Photocatalytic Degradation of Rhodamine-B and Water Densification via Eco-Friendly Synthesized Cr2O3 and Ag@Cr2O3 Using Garlic Peel Aqueous Extract.

The purification and densification of wastewater play an important role in water recycling, especially if the materials used in water recycling are other types of recycled waste. Therefore, considering this view in this study, the biosynthesis of silver-decorated chromium oxide nanoparticles utilizing a wasted Allium sativum (garlic) peel extract is investigated. The aqueous extract of garlic peel (GPE) was treated with silver nitrate, chromium nitrate, and a mixture of silver nitrate and chromium nitrate to synthesize silver nanoparticles (Ag-garlic), chromium oxide nanoparticles (Cr2O3-garlic), and silver-decorated chromium oxide nanoparticles (Ag@Cr2O3-garlic), respectively. The synthesized nanoparticles were elucidated via thermal gravimetric analysis (TGA), infrared spectra (FT-IR), absorption spectra (UV-Vis), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Antimicrobial activity studies were conducted against waterborne germs, bacterial strains (Bacillus subtilis, Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa), and fungal strains (Alternaria porri, Aspergillus flavus, Aspergillus niger, Fuserium oxysporum, and Trichoderma longibrachiatum) and showed significant levels of antimicrobial activity. The results revealed that Ag@Cr2O3 significantly improved antimicrobial activity due to their synergistic effect. The photocatalytic activity of nanoparticles was assessed using Rhodamine B dye (5 ppm) under solar irradiation. Cr2O3-garlic exhibited the best activity as a photocatalyst among the studied nanoparticles, with 97.5% degradation efficiency under optimal conditions.

The relative validity of a semiquantitative food frequency questionnaire among pregnant women in the United Arab Emirates: The Mutaba'ah study.

Background: Food frequency questionnaire (FFQ) is the most frequently used dietary assessment method in estimating dietary intakes in epidemiological studies. Aim: This study aimed to assess the relative validity of a semiquantitative FFQ in evaluating dietary intake among pregnant women in the United Arab Emirates. Methods: Within the Mutaba'ah study, a subsample of 111 pregnant women completed a semiquantitative FFQ and a single 24-hour dietary recall (24-HDR) regarded as the reference method. Absolute and energy-adjusted nutrient and food intakes between the FFQ and 24-HDR were compared using the Wilcoxon signed ranks test, correlations, Bland-Altman analysis, cross-classification, and weighted kappa analysis. Results: There were no significant differences in reported absolute intakes between the FFQ and 24-HDR for carbohydrates, whole grains, white meat, beta-carotene, vitamin K, sodium, and selenium. Spearman's correlation coefficients between the FFQ and 24-HDR ranged from 0.09 (trans fatty acids) to 0.5 (potassium) for absolute intakes. Correlation decreased after energy adjustment. Bland-Altman analysis showed that the FFQ overestimated intakes compared with 24-HDR and that the limits of agreement were wide. The average percentage of pregnant women classified into the same or adjacent quartile of intake by both methods was 73%. Weighted kappa values ranged from -0.02 (white meat) to 0.33 (magnesium). Conclusion: Our findings showed that the semi-quantitative FFQ is a useful tool in ranking pregnant women from the Emirati population according to their dietary intake. However, the validity of some estimated intakes was poor; hence, certain intakes should be interpreted with caution.

Association Between Social Determinants of Health, Distance from Treatment Center, and Treatment Type with Outcomes in Human Papillomavirus Associated Oropharyngeal cancer.

OBJECTIVES: Social determinants of health (SDOH) can influence access to cancer care, clinical trials, and oncologic outcomes. We investigated the association between SDOH, distance from treatment center, and treatment type with outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] patients treated at a tertiary care center. STUDY DESIGN: Retrospective review. METHODS: HPV(+)OPSCC patients treated surgically from 2006 to 2021 were selected from our departmental Oropharyngeal Cancer RedCap database. Demographic data, treatment, and oncologic outcomes were extracted. Distance was calculated in miles between the centroid of each patient zip code and our hospital zip code (zipdistance). RESULTS: 874 patients (89 % male; mean age: 58 years) were identified. Most patients (96 %) reported Non-Hispanic White as their primary race. 204 patients (23 %) had a high-school degree or less, 217 patients (25 %) reported some college education or a 2-year degree, 153 patients (18 %) completed a four-year college degree, and 155 patients (18 %) had post-graduate degrees. Relative to those with a high-school degree, patients with higher levels of education were more likely to live further away from our institution (p < 0.0001). Patients who received adjuvant radiation therapy elsewhere lived, on average, 104 miles further away than patients receiving radiation at our institution (Estimate 104.3, 95 % CI 14.2-194.4, p-value = 0.02). In univariable Cox PH models, oncologic outcomes did not significantly differ by zipdistance. CONCLUSIONS: Education level-and access to resources-varied proportionally to a patient's distance from our center. Patients travelling further distances for surgical management of OPSCC were more likely to pursue adjuvant radiation therapy at an outside institution. Distance traveled was not associated with oncologic outcomes. Breaking down barriers to currently excluded populations may improve access to clinical trials and improve oncologic outcomes for diverse patient populations.

Retraction: Eagle Syndrome: A Rare Cause of Stroke in a Young Patient.

[This retracts the article DOI: 10.7759/cureus.21102.].

The Hausa Northwick Park Neck Pain Questionnaire: translation, cross-cultural adaptation and psychometric assessment in patients with non-specific neck pain.

PURPOSE: To translate and cross-culturally adapt the Northwick Park Neck Pain Questionnaire (NPQ) into Hausa and assess its psychometric properties. MATERIALS AND METHODS: The NPQ was translated and cross-culturally adapted into Hausa using recommended guidelines. A consecutive sample of 92 Hausa-speaking patients with non-specific neck pain recruited from three tertiary hospitals in north-western Nigeria, completed the questionnaire to assess factorial validity (using confirmatory factor analysis), convergent validity (by correlating the Hausa-NPQ with the Numerical Pain Rating Scale [NPRS]), and internal consistency (using Cronbach's α). A subsample of 50 patients completed the questionnaire again 3 days after the first administration to assess relative reliability using intraclass correlation coefficients (ICC) and absolute reliability using standard error of measurement (SEM), smallest detectable change (SDC), and 95% limits of agreement (LOA). RESULTS: The factor analysis confirmed a single-factor structure with excellent internal consistency (α = 0.94). The questionnaire showed a strong positive correlation with the NPRS (rho = 0.68). The ICC was 0.86, with SEM and SDC of 6.32 and 17.5, respectively. The LOA was - 29.3 to + 37.1 with no evidence of proportional bias. CONCLUSIONS: The Hausa-NPQ is a valid and reliable measure of disability due to neck pain.

This study describes the translation, cross-cultural adaptation, and psychometric assessment of the Hausa-NPQ in Hausa-speaking patients with non-specific neck pain.The questionnaire demonstrated adequate psychometric properties in terms of factorial and convergent validity, internal consistency, and test-retest reliability.The questionnaire will be useful in clinical and research settings to assess disability due to neck pain for screening purposes, evaluation of treatment effectiveness, as well as cross-cultural comparisons involving Hausa-speaking individuals with neck pain.

Computer aided drug discovery (CADD) of a thieno[2,3-d]pyrimidine derivative as a new EGFR inhibitor targeting the ribose pocket.

Depending on the pharmacophoric characteristics of EGFR inhibitors, a new thieno[2,3-d]pyrimidine derivative has been developed. Firstly, the potential inhibitory effect of the designed compound against EGFR has been proven by docking experiments that showed correct binding modes and excellent binding energies of -98.44 and -88.00 kcal/mol, against EGFR wild-type and mutant type, respectively. Furthermore, MD simulations studies confirmed the precise energetic, conformational, and dynamic alterations that occurred after binding to EGFR. The correct binding was also confirmed by essential dynamics studies. To further investigate the general drug-like properties of the developed candidate, in silico ADME and toxicity studies have also been carried out. The thieno[2,3-d]pyrimidine derivative was synthesized following the earlier promising findings. Fascinatingly, the synthesized compound (4) showed promising inhibitory effects against EGFRWT and EGFRT790M with IC50 values of 25.8 and 182.3 nM, respectively. Also, it exhibited anticancer potentialities against A549 and MCF-7cell lines with IC50 values of 13.06 and 20.13 µM, respectively. Interestingly, these strong activities were combined with selectivity indices of 2.8 and 1.8 against the two cancer cell lines, respectively. Further investigations indicated the ability of compound 4 to arrest the cancer cells' growth at the G2/M phase and to increase early and late apoptosis percentages from 2.52% and 2.80 to 17.99% and 16.72%, respectively. Additionally, it was observed that compound 4 markedly increased the levels of caspase-3 and caspase-9 by 4 and 3-fold compared to the control cells. Moreover, it up-regulated the level of BAX by 3-fold and down-regulated the level of Bcl-2 by 3-fold affording a BAX/Bcl-2 ratio of 9.Communicated by Ramaswamy H. Sarma.

Microfluidic-based nanoemulsion of Ocimum basilicum extract: Constituents, stability, characterization, and potential biomedical applications for improved antimicrobial and anticancer properties.

This paper reports on the findings from a study that aimed to identify and characterize the constituents of Ocimum basilicum extract using gas chromatography-mass spectrometry (GC-MS) analysis, as well as assess the physicochemical properties and stability of nanoemulsions formulated with O. basilicum extract. The GC-MS analysis revealed that the O. basilicum extract contained 22 components, with Caryophyllene and Naringenin identified as the primary active constituents. The nanoemulsion formulation demonstrated excellent potential for use in the biomedical field, with a small and uniform particle size distribution, a negative zeta potential, and high encapsulation efficiency for the O. basilicum extract. The nanoemulsions exhibited spherical morphology and remained physically stable for up to 6 months. In vitro release studies indicated sustained release of the extract from the nanoemulsion formulation compared to the free extract solution. Furthermore, the developed nanoformulation exhibited enhanced anticancer properties against K562 cells while demonstrating low toxicity in normal cells (HEK293). The O. basilicum extract demonstrated antimicrobial activity against Pseudomonas aeruginosa, Candida albicans, and Staphylococcus epidermidis, with a potential synergistic effect observed when combined with the nanoemulsion. These findings contribute to the understanding of the constituents and potential applications of O. basilicum extract and its nanoemulsion formulation in various fields, including healthcare and pharmaceutical industries. Further optimization and research are necessary to maximize the efficacy and antimicrobial activity of the extract and its nanoformulation. RESEARCH HIGHLIGHTS: This study characterized the constituents of O. basilicum extract and assessed the physicochemical properties and stability of its nanoemulsion formulation. The O. basilicum extract contained 22 components, with Caryophyllene and Naringenin identified as the primary active constituents. The nanoemulsion formulation demonstrated excellent potential for biomedical applications, with sustained release of the extract, low toxicity, and enhanced anticancer and antimicrobial properties. The findings contribute to the understanding of the potential applications of O. basilicum extract and its nanoemulsion formulation in healthcare and pharmaceutical industries, highlighting the need for further optimization and research.

Computer-Assisted Drug Discovery of a Novel Theobromine Derivative as an EGFR Protein-Targeted Apoptosis Inducer.

The overexpression of the Epidermal Growth Factor Receptor (EGFR) marks it as a pivotal target in cancer treatment, with the aim of reducing its proliferation and inducing apoptosis. This study aimed at the CADD of a new apoptotic EGFR inhibitor. The natural alkaloid, theobromine, was used as a starting point to obtain a new semisynthetic (di-ortho-chloro acetamide) derivative (T-1-DOCA). Firstly, T-1-DOCA's total electron density, energy gap, reactivity indices, and electrostatic surface potential were determined by DFT calculations, Then, molecular docking studies were carried out to predict the potential of T-1-DOCA against wild and mutant EGFR proteins. T-1-DOCA's correct binding was further confirmed by molecular dynamics (MD) over 100 ns, MM-GPSA, and PLIP experiments. In vitro, T-1-DOCA showed noticeable efficacy compared to erlotinib by suppressing EGFRWT and EGFRT790M with IC50 values of 56.94 and 269.01 nM, respectively. T-1-DOCA inhibited also the proliferation of H1975 and HCT-116 malignant cell lines, exhibiting IC50 values of 14.12 and 23.39 µM, with selectivity indices of 6.8 and 4.1, respectively, indicating its anticancer potential and general safety. The apoptotic effects of T-1-DOCA were indicated by flow cytometric analysis and were further confirmed through its potential to increase the levels of BAX, Casp3, and Casp9, and decrease Bcl-2 levels. In conclusion, T-1-DOCA, a new apoptotic EGFR inhibitor, was designed and evaluated both computationally and experimentally. The results suggest that T-1-DOCA is a promising candidate for further development as an anti-cancer drug.

Impact of COVID-19 on the Volume of Pediatric Surgery Cases in a Referral Hospital in the Al-Madina Region of Saudi Arabia.

Background The COVID-19 pandemic has affected healthcare systems worldwide, leading to prioritizing resources for the diagnosis and management of COVID-19 cases. As a result, providing medical care to patients with health conditions, including pediatric surgeries, has been significantly affected. Objectives The objective of this research is to evaluate the impact of the COVID-19 pandemic on the prevalence of pediatric surgeries in a referral hospital in Al-Madina, KSA. Method An observational retrospective cross-sectional study was conducted in a referral hospital in the Al-Madina region of Saudi Arabia. We retrospectively reviewed all pediatric surgical records that met the inclusion criteria from March 2018 to March 2022. Results Out of the patients who underwent surgeries (5704), it was indicated that the number of patients who underwent surgeries during the COVID-19 pandemic (42.7%) was less than those who underwent surgeries before the COVID-19 outbreak (57.6%). The number of patients presented to the OPD significantly increased during the COVID-19 period compared to before COVID-19. The number of emergency cases before and during COVID-19 was similar. The period between diagnosis and surgical intervention for emergency cases was significantly shortened during the COVID-19 pandemic. The hospital stay period significantly decreased during the pandemic. Conclusion The study found that the pandemic has caused a considerable decline in the number of pediatric surgery cases compared to the previous years. The longer observation period of this study likely allowed for a better understanding of the pandemic situation, which contributes to strengthening our understanding of the pandemic's impact on healthcare services.

Rationale design and synthesis of new apoptotic thiadiazole derivatives targeting VEGFR-2: computational and in vitro studies.

This work presents the synthesis and in vitro, and in silico analyses of new thiadiazole derivatives that are designed to mimic the pharmacophoric characteristics of vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. A comprehensive evaluation of the inhibitory properties of the synthesized thiadiazole derivatives against the cancer cell lines MCF-7 and HepG2 identified several auspicious candidates. Among them, compound 14 showed remarkably low IC50 values of 0.04 µM and 0.18 µM against MCF-7 and HepG2, respectively. VEGFR-2 inhibitory evaluation of compound 14 revealed a promising IC50 value in the nanomolar range (103 nM). Further examination of the cell cycle revealed that compound 14 has the ability to stop the progression of the cell cycle in MCF-7 cells via G0-G1 phase arrest. Interestingly, compound 14 also demonstrated a noteworthy pro-apoptotic effect in MCF-7 cells, with notable increases in early apoptosis (16.53%) and late apoptosis (29.57%), along with a slight increase in the population of necrotic cells (5.95%). Furthermore, compound 14 showed a significant drop in MCF-7 cells' ability to migrate and heal wounds. Additionally, compound 14 promoted apoptosis by boosting BAX (6-fold) while lowering Bcl-2 (6.2-fold). The binding affinities of the synthesized candidates to their target (VEGFR-2) were confirmed by computational investigations, including molecular docking, principal component analysis of trajectories (PCAT), and molecular dynamics (MD) simulations. Additionally, compound 14's stability and reactivity were investigated using density functional theory (DFT). These thorough results highlight compound 14's potential as a lead contender for additional research in the creation of anticancer drugs that target VEGFR-2. This work establishes a foundation for promising thiadiazole derivatives for future therapeutic developments in anticancer- and angiogenesis-related scientific fields.