Progress and prospects on vaccine development against monkeypox infection.

The monkeypox virus (MPOX) is an uncommon zoonotic illness brought on by an orthopoxvirus (OPXV). MPOX can occur with symptoms similar to smallpox. Since April 25, 2023, 110 nations have reported 87,113 confirmed cases and 111 fatalities. Moreover, the outspread prevalence of MPOX in Africa and a current outbreak of MPOX in the U.S. have made it clear that naturally occurring zoonotic OPXV infections remain a public health concern. Existing vaccines, though they provide cross-protection to MPOX, are not specific for the causative virus, and their effectiveness in the light of the current multi-country outbreak is still to be verified. Furthermore, as a sequel of the eradication and cessation of smallpox vaccination for four decades, MPOX found a possibility to re-emerge, but with distinct characteristics. The World Health Organization (WHO) suggested that nations use affordable MPOX vaccines within a framework of coordinated clinical effectiveness and safety evaluations. Vaccines administered in the smallpox control program and conferred immunity against MPOX. Currently, vaccines approved by WHO for use against MPOX are replicating (ACAM2000), low replicating (LC16m8), and non-replicating (MVA-BN). Although vaccines are accessible, investigations have demonstrated that smallpox vaccination is approximately 85% efficient in inhibiting MPOX. In addition, developing new vaccine methods against MPOX can help prevent this infection. To recognize the most efficient vaccine, it is essential to assess effects, including reactogenicity, safety, cytotoxicity effect, and vaccine-associated side effects, especially for high-risk and vulnerable people. Recently, several orthopoxvirus vaccines have been produced and are being evaluated. Hence, this review aims to provide an overview of the efforts dedicated to several types of vaccine candidates with different strategies for MPOX, including inactivated, live-attenuated, virus-like particles (VLPs), recombinant protein, nucleic acid, and nanoparticle-based vaccines, which are being developed and launched.

NIR laser-conjugated glutathione-coated Mn-doped CuS nanoprisms as photothermal agent for cancer treatment.

The cancer treatment by laser-conjugated nanomaterial has become a new developing trend due of their unique physicochemical performance. The previous few studies reported the preparation of undoped CuS nanoprisms. The current research was concerned with the Mn doping effect on the CuS nanoprisms and its activity in tumor toxicity of M.D. Anderson-Metastatic Breast 231 (MDA-MB-231) cell line with laser treatment. To prepare a novel CuS and Mn-doped CuS nanoprisms with high surface area by two-phase colloidal method, copper nitrate and sulfur powder were used as sources of copper and sulfur respectively. The prepared nanoprisms were investigated as antibacterial and photothermal agents in MDA-MB-231 cancer treatment using near-infrared (NIR) laser. The Mn-CuS nanoprisms were modified with glutathione (GSH) to decrease the cytotoxicity and increase the biocompatibility. The characterization of synthesized nanoprisms involved the structural, compositional, surface charges, optical, and morphological property analyses. X-ray diffraction (XRD) showed the peaks of hexagonal covellite copper sulfide nanoparticles and additional diffraction peaks at Mn-CuS which are assigned to orthorhombic chalcocite CuS. The transmission electron microscopy (TEM) images showed that the CuS and Mn-CuS nanoparticles have nanoprism morphology. The antibacterial activity test revealed that the activity enhances by doping and the prepared Mn-CuS nanostructures were more effective against the Staphylococcus aureus and Escherichia coli bacteria. The results of photothermal treatment indicated that the cancer cells were effectively killed and the GSH@Mn-CuS nanoprisms are able to be used as an efficient theranostic agent for tumor photothermal therapy in the future.

A genetic study of Wilson's disease in the United Kingdom.

Previous studies have failed to identify mutations in the Wilson's disease gene ATP7B in a significant number of clinically diagnosed cases. This has led to concerns about genetic heterogeneity for this condition but also suggested the presence of unusual mutational mechanisms. We now present our findings in 181 patients from the United Kingdom with clinically and biochemically confirmed Wilson's disease. A total of 116 different ATP7B mutations were detected, 32 of which are novel. The overall mutation detection frequency was 98%. The likelihood of mutations in genes other than ATP7B causing a Wilson's disease phenotype is therefore very low. We report the first cases with Wilson's disease due to segmental uniparental isodisomy as well as three patients with three ATP7B mutations and three families with Wilson's disease in two consecutive generations. We determined the genetic prevalence of Wilson's disease in the United Kingdom by sequencing the entire coding region and adjacent splice sites of ATP7B in 1000 control subjects. The frequency of all single nucleotide variants with in silico evidence of pathogenicity (Class 1 variant) was 0.056 or 0.040 if only those single nucleotide variants that had previously been reported as mutations in patients with Wilson's disease were included in the analysis (Class 2 variant). The frequency of heterozygote, putative or definite disease-associated ATP7B mutations was therefore considerably higher than the previously reported occurrence of 1:90 (or 0.011) for heterozygote ATP7B mutation carriers in the general population (P < 2.2 × 10(-16) for Class 1 variants or P < 5 × 10(-11) for Class 2 variants only). Subsequent exclusion of four Class 2 variants without additional in silico evidence of pathogenicity led to a further reduction of the mutation frequency to 0.024. Using this most conservative approach, the calculated frequency of individuals predicted to carry two mutant pathogenic ATP7B alleles is 1:7026 and thus still considerably higher than the typically reported prevalence of Wilson's disease of 1:30 000 (P = 0.00093). Our study provides strong evidence for monogenic inheritance of Wilson's disease. It also has major implications for ATP7B analysis in clinical practice, namely the need to consider unusual genetic mechanisms such as uniparental disomy or the possible presence of three ATP7B mutations. The marked discrepancy between the genetic prevalence and the number of clinically diagnosed cases of Wilson's disease may be due to both reduced penetrance of ATP7B mutations and failure to diagnose patients with this eminently treatable disorder.

Upper gastrointestinal bleeding in hospital inpatients: the role of antithrombotic drugs.

BACKGROUND: Critically ill patients are considered to be most at risk from developing non-variceal upper gastrointestinal bleeding (NVGIB) while in hospital. The increasing prescription of low-dose aspirin and other antithrombotic drugs for protection against thromboembolism to many patients admitted to hospital may increase the vulnerability of a wider group to NVGIB. OBJECTIVE: This study compares two groups of patients with NVGIB: group I, inpatients cared for outside the intensive care unit; and group II, patients admitted with this condition, while considering the use of antithrombotic drugs. METHODS: We identified all patients who developed NVGIB in the two calendar years between 2008 and 2009 and compared group I with group II while taking into account their clinical details including Rockall scores and drug usage. RESULTS: Compared with group II (n=274), group I (n=96) were older (median age of 77 years vs 68; p<0.001), had fewer males (45.8% vs 60.6%; p=0.016), higher prevalence of cardiovascular disease (52.1% vs 29.2%; p<0.001), more patients with complete Rockall score ≥ 3 (84.4% vs 66.7%; p=0.001) and more patients treated with aspirin or other antithrombotic drugs (64.6% vs 44.5%; p=0.001). After adjustment for age and sex, group I were still significantly more likely to be taking antithrombotic drugs than group II (OR (95% CIs), 2.15 (1.25 to 3.68); p=0.006). The endoscopic abnormalities in more than 80% of patients included erosive oesophagitis, gastric or duodenal ulcers or erosions. CONCLUSIONS: Subjects who develop NVGIB as inpatients have higher Rockall scores are mainly older females with cardiovascular disease and using antithrombotic drugs. Secondary care clinicians should be mindful of this at-risk group of patients and consider giving them prophylactic antiulcer therapy.

A density functional theory study on the potential application of Ni and Co doped ZnO nanosheets as a carrier for ciclopirox anticancer drug.

The Ni and Co doping effect on the ciclopirox (CPX) drug delivery performance of a ZnO nanosheet (ZnO-NS) was investigated theoretically. Doping Ni and Co metals into the ZnO-NS increased the adsorption energy of CPX from -7.9 to -27.4 and -31.7 kcal/mol, respectively. The CPX adsorption reduced the ZnO-NS gap (Eg) from 3.81 to 3.46 eV, while the CPX adsorption reduced the Eg of the Ni- and Co-doped ZnO-NS from 2.74 and 2.68 eV to 1.87 and 1.71 eV, respectively. The CPX adsorption performance increased after doping process. A drug release mechanism was introduced in cancerous tissues based on the PH. .

Antibacterial and hemocompatibility potentials of nano-gold-cored alginate preparation against anaerobic bacteria from acne vulgaris.

Acne is a prevalent dermatological disease, with high global incidence, and is a health menace. The current study aimed to isolate and characterize the anaerobic bacteria responsible for the condition. Causes of a total of 70 acne-based bacterium isolates obtained from patients of mild, moderate, and severe acne, 24 were Clostridium innocuum, 21 were Lactobacillus plantarum, 13 were Anaerococcus prevotii, and 12 were Peptoniphilus asaccharolyticus. Nearly 69% of males were suffering, while the rest were females at 31%. The 15-30 years old age group was the most affected. The gold/alginate nanoparticles' nanopreparation (GANPs) produced from chloroauric acid and sodium alginate was an effective treatment against the acne conditions under the experimental conditions. The nanopreparation exhibited significant inhibitory activity against anaerobic bacterial isolates, with a minimum inhibitory concentration of 200 µg/ml for A. prevotii and P. asaccharolyticus, and 400 µg/ml for C. innocuum and L. plantarum. The in vitro efficacy of the GANPs on human blood parameters was also assessed. The concurrent results suggested potential antibacterial activity and hemocompatibility of the product, which has promise to be used as a successful antibacterial agent for acne.

Enhanced Mucoadhesion of Thiolated ß-Cyclodextrin by S-Protection with 2-Mercaptoethanesulfonic Acid.

This study aimed at designing an S-protected thiolated ß-cyclodextrin (ß-CD) exhibiting enhanced mucoadhesive properties. The native ß-CD was thiolated with phosphorus pentasulfide resulting in a thiolated ß-CD (ß-CD-SH) and subsequently S-protected with 2-mercaptoethanesulfonate (MESNA) to form ß-CD-SS-MESNA. The structure of the novel excipient was confirmed by 1H NMR and Fourier-transform infrared spectroscopy. The sulfhydryl content of ß-CD-SH, determined by Ellman's test, was 2281.00 ± 147 µmol/g, and it was decreased to 45.93 ± 19.40 µmol/g by S-protection. Due to thiolation and S-protection, the viscosity of the mixture of mucus with ß-CD-SH and ß-CD-SS-MESNA increased 1.8 and 4.1-fold, compared to native ß-CD, respectively. The unprotected ß-CD-SH diffused to a lesser extent into the mucus than native ß-CD, while S-protected ß-CD-SS-MESNA showed the highest mucodiffusion among the applied CDs. A 1.5- and 3.0-fold higher cellular uptake of ß-CD-SH and ß-CD-SS-MESNA, compared to the native one, was established on Caco-2 cell line by flow cytometry, respectively, causing slightly decreased cell viability. On account of the enhanced mucoadhesion, this higher cellular uptake does not affect the application potential of ß-CD-SS-MESNA as an oral drug delivery system since the carrier remains in the mucus and does not reach the underlying epithelial layer. According to these results, the S-protection of ß-CD-SH with MESNA promotes improved mucodiffusion, strong mucoadhesion, and prolonged mucosal residence time.

Comparative study between efficacy of Excimer light with topical Tacrolimus 0.1% versus excimer light with topical Bimatoprost 0.01% in treatment of facial Vitiligo.

Loss and absence of melanocytes due to a number of factors is responsible for vitiligo; known to be the commonest disorder of pigmentation. The aim of the current work was to compare the efficacy and safety of excimer light with topical tacrolimus ointment 0.1% versus excimer light with topical bimatoprost gel 0.01% in treatment of facial vitiligo. The study was carried out on 48 patients presented with facial vitiligo. The patients were divided randomly using sealed envelope method into two groups (24 patients each). Group 1 were treated with excimer light plus topical tacrolimus ointment 0.1% and group 2 treated with excimer light plus topical bimatoprost gel 0.01%. Clinical improvement based on the quartile grading scale at the end of treatment did not show any statistically significant difference between groups. The majority of subjects in both groups experienced good to excellent improvement. Only 20.9% of patients in group 1 and 33.3% of subjects in group 2 achieved less than 50% repigmentation (p = 0.889). Our study demonstrated that 0.01% topical bimatoprost gel in combination with excimer light is considered safe and effective as treatment of nonsegmental facial vitiligo with comparable results to 0.1% tacrolimus.

TD-DFT calculations, dipole moments, and solvatochromic properties of 2-aminochromone-3-carboxaldehyde and its hydrazone derivatives.

2-Aminochromone-3-carboxaldehyde (ACC) and its hydrazones (ACMHCA and ACMNPHTCA) with semicarbazide hydrochloride and N-phenylthiosemicarbazide were synthesized and characterized by elemental analysis and spectral studies. The solvatochromic behavior of the title compounds in various solvents showed distinct bathochromic shifts on going from nonpolar to polar solvents, suggesting intramolecular-charge-transfer (ICT) solute-solvent interactions. The ground and excited state dipole moments of ACC, ACMHCA, and ACMNPHTCA were determined experimentally by the solvatochromic shift method using the Bilot-Kawski, Lippert-Mataga, Bakhshiev, Kawski-Chamma-Viallet functions, and a microscopic Reichardt's solvent polarity parameter (ENT). All the investigated molecules showed a substantial increase in the dipole moment upon excitation to the emitting state. The experimental results were generally consistent with the values obtained by the TD-DFT, B3LYP/6-311G++(d,p) method. Molecular electrostatic potential (MEP) mapping and natural charge and natural bonding orbital (NBO) analysis were performed and the results were discussed. The 1H NMR chemical shifts of the prepared compounds were simulated by the gage independent atomic orbital (GIAO) method and compared with their experimental chemical shift values. The biological activity data were correlated with the frontier molecular orbitals. The photovoltaic behavior of the title compounds showed there was sufficient electron injection.

Molecular modeling for sensing of cisplatin drug by graphdiyne: electronic study via DFT.

CONTEXT: By utilizing first-principles calculations, we studied the electronic properties of graphdiyne nanosheet (GDY) and its Si-doped counterpart, Si-GDY. Both GDY and Si-GDY sheet surfaces were examined for the drug cisplatin (CP) adsorption using adsorption energy, charge transfer, and changes in electrical conductivity as indicators. Pure GDY has little affinity for CP, according to this study. Only 7.83% of the GDY surface's bandwidth energy changed after CP adsorption. CP on Si-GDY has a gaseous energy value of -18.75 kcal/mol and an aqueous energy value of - 49.39 kcal/mol. METHODS: The prescribed medications' water-phase solubility is determined by their solvation energy value. These charges are transferred between CP and the Si-GDY sheet, which is extremely positively charged, and this gives CP the necessary binding energy. After CP adsorption, electrical conductivity of Si-GDY increased by approximately 19.01%.

Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers.

OBJECTIVES: We performed two 24-week double-blind trials (REDUCE-1 and -2 (Registration Endoscopic Studies to Determine Ulcer Formation of HZT-501 Compared with Ibuprofen: Efficacy and Safety Studies)) to assess whether double-dose famotidine given in a single-tablet combination with ibuprofen (HZT-501) significantly reduces gastric and duodenal ulcers as compared with ibuprofen. METHODS: Patients (40-80 years) requiring daily non-steroidal anti-inflammatory drugs (NSAIDs) for ≥6 months with no prior ulcer complications, negative H. pylori stool test, and baseline endoscopy showing no ulcers and <5 erosions were randomly assigned in a 2:1 ratio to HZT-501 or identical-appearing ibuprofen 800 mg tablets thrice daily. Study endoscopies were done at 8, 16, and 24 weeks. After unblinding and initial analyses, 12 patients were found to be misclassified as having gastric ulcers based on the adjudication of endoscopy reports, and analyses were re-run. RESULTS: In REDUCE-1, the primary end point analysis of gastric ulcers at 24 weeks with HZT-501 vs. ibuprofen was 12.7% vs. 22.9% (P=0.0044) in the post-adjudication analysis. In REDUCE-2, the primary end point analysis of upper gastrointestinal (GI) ulcers was 13.0% vs. 20.5% (P=0.0587) in the post-adjudication analysis. Prespecified pooled analyses showed significantly fewer gastric (12.5% vs. 20.7%) and duodenal ulcers (1.1% vs. 5.1%) with HZT-501 vs. ibuprofen. Proportional hazards analysis of multiple potential risk factors showed the risk ratio of upper GI ulcers with HZT-501 vs. ibuprofen was 0.46, 95% confidence interval was 0.34-0.61. CONCLUSIONS: Combined results of the REDUCE studies indicate that double-dose famotidine plus ibuprofen, given as a combination tablet, decreases endoscopic upper GI ulcers as compared with ibuprofen alone.

NiII and CoII binary and ternary complexes of 3-formylchromone: spectroscopic characterization, antimicrobial activities, docking and modeling studies.

Reactions of 3-formylchromone (L) with Ni(ii) and Co(ii) ions having different anions (acetate, perchlorate, nitrate, and chloride) yielded a series of binary and ternary octahedral complexes with the general formula [ML n L' m X y (S) a ]Z y ·bS, where M = Ni or Co, n = 1-3, L' = auxiliary ligand = 8-hydroxyquinoline or 1,10-phenanthroline, m = 1 or 2, X = acetate or chloride, y = 0 or 2, S = H2O or MeOH, a = 0-2, Z = nitrate or perchlorate and b = 0-1.5. Elemental and thermal analyses and infra-red, electronic, mass, magnetic susceptibility and molar conductivity measurements were successfully utilized to characterize the structures of the chromone complexes. The chromone ligand acts as a neutral bidentate ligand through its formyl and γ-pyrone oxygen atoms. The obtained complexes were formed with molar ratios 1 : 2 and 1 : 3 M : L for the binary and 1 : 2 : 1 and 1 : 1 : 1 M : L : L' for the ternary complexes. The kinetic parameters of the thermal degradation steps were estimated and explained using the Coats-Redfern equations. The synthesized complexes showed antimicrobial activity with higher activity toward Candida albicans and Bacillus subtilis. Docking studies showed good agreement with the antimicrobial activity. Molecular modeling of the synthesized complexes was performed using Hyperchem at the PM3 level and the calculated structures correlate with the experimental data.

Patient Navigators for CKD and Kidney Failure: A Systematic Review.

Rationale & Objective: To what degree and how patient navigators improve clinical outcomes for patients with chronic kidney disease (CKD) and kidney failure is uncertain. We performed a systematic review to summarize patient navigator program design, evidence, and implementation in kidney disease. Study Design: A search strategy was developed for randomized controlled trials and observational studies that evaluated the impact of navigators on outcomes in the setting of CKD and kidney failure. Articles were identified from various databases. Two reviewers independently screened the articles and identified those meeting the inclusion criteria. Setting & Participants: Patients with CKD or kidney failure (in-center hemodialysis, peritoneal dialysis, home hemodialysis, or kidney transplantation). Selection Criteria for Studies: Studies that compared patient navigators with a control, without limits on size, duration, setting, or language. Studies focusing solely on patient education were excluded. Data Extraction: Data were abstracted from full texts and risk of bias was assessed. Analytical Approach: No meta-analysis was performed. Results: Of 3,371 citations, 17 articles met the inclusion criteria including 14 original studies. Navigators came from various healthcare backgrounds including nursing (n=6), social worker (n=2), medical interpreter (n=1), research (n=1), and also included kidney transplant recipients (n=2) and non-medical individuals (n=2). Navigators focused mostly on education (n=9) and support (n = 6). Navigators were used for patients with CKD (n=5), peritoneal dialysis (n=2), in-center hemodialysis (n=4), kidney transplantation (n=2), but not home hemodialysis. Navigators improved transplant workup and listing, peritoneal dialysis utilization, and patient knowledge. Limitations: Many studies did not show benefits across other outcomes, were at a high risk of bias, and none reported cost-effectiveness or patient-reported experience measures. Conclusions: Navigators improve some health outcomes for CKD but there was heterogeneity in their structure and function. High-quality randomized controlled trials are needed to evaluate navigator program efficacy and cost-effectiveness.

Osteosynthesis and outcomes of traumatic periprosthetic femoral fractures after total hip arthroplasty.

PURPOSE: The aim of this retrospective study was to investigate the treatment of traumatic periprosthetic femoral fractures with open reduction and internal fixation. The outcomes with the use of the surgical techniques were also reported. METHODS: Between September 2017 and September 2019, 25 patients with traumatic periprosthetic femoral fractures were managed by open reduction and internal fixation in Ain Shams University Hospital, Egypt. The fixation methods were selected based on the surgeon's preference. Outcomes were assessed using the Harris Hip Score, visual analogue score (VAS) for pain, and EuroQol 5 Dimensions - 5 Level (EQ5D-5L) prior to and after surgery. Patients were regularly followed up for one year. A P value < 0.05 was considered to be statistically significant. RESULTS: The mean age at surgery was 77 years (range, 51 to 95 years), 64% (n = 16) were females. According to the Vancouver classification, there were 1 type AG, 15 type B1, and 9 type C fractures. Postoperative complications included wound site infection (n = 2) and non-union (n = 1). The mean pre-trauma Harris Hip Score was 77.44 ± 8.63 (range, 65 to 90), and the mean Harris Hip Score collected at the final follow-up was 72.47 ± 8.85 (range, 60 to 86) (P < 0.05). The mean pre-trauma VAS was 2.20 ± 1.21 (range, 0 to 4), and the mean VAS recorded at the final follow-up was 3.00 ± 1.41 (range, 0 to 5) (P < 0.05). According to the EQ5D-DL assessed at the final follow-up, no patient felt that their daily life and activities became more problematic. CONCLUSION: This study provided added validation of the current management of periprosthetic femoral fractures after total hip arthroplasty. Using the proper fixation and implant can achieve a reliable fixation and good functional recovery. LEVEL OF EVIDENCE: IVa.

Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial.

BACKGROUND: There are few therapeutic options for the prevention of gastrointestinal mucosal damage caused by low-dose aspirin. We therefore investigated the efficacy of famotidine, a well-tolerated histamine H(2)-receptor antagonist, in the prevention of peptic ulcers and erosive oesophagitis in patients receiving low-dose aspirin for vascular protection. METHODS: Adult patients (aged >/=18 years) from the cardiovascular, cerebrovascular, and diabetes clinics at Crosshouse Hospital, Kilmarnock, UK, were eligible for enrolment in this phase III, randomised, double-blind, placebo-controlled trial if they were taking aspirin 75-325 mg per day with or without other cardioprotective drugs. Patients without ulcers or erosive oesophagitis on endoscopy at baseline were randomly assigned by computer-generated randomisation sequence to receive famotidine 20 mg twice daily (n=204) or placebo twice daily (n=200). Patients had a final endoscopic examination at 12 weeks. The primary endpoint was the development of new ulcers in the stomach or duodenum or erosive oesophagitis at 12 weeks after randomisation. Analysis was by intention to treat, including all randomised patients who received at least one dose of study drug (famotidine or placebo). This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN96975557. FINDINGS: All randomised patients received at least one dose and were included in the ITT population. 82 patients (famotidine, n=33; placebo, n=49) did not have the final endoscopic examination and were assumed to have had normal findings; the main reason for participant withdrawal was refusal to continue. At 12 weeks, comparing patients assigned to famotidine with patients assigned to placebo, gastric ulcers had developed in seven (3.4%) of 204 patients compared with 30 (15.0%) of 200 patients (odds ratio [OR] 0.20, 95% CI 0.09-0.47; p=0.0002); duodenal ulcers had developed in one (0.5%) patient compared with 17 (8.5%; OR 0.05, 0.01-0.40; p=0.0045); and erosive oesophagitis in nine (4.4%) compared with 38 (19.0%; OR 0.20, 0.09-0.42; p<0.0001), respectively. There were fewer adverse events in the famotidine group than in the placebo group (nine vs 15); four patients in the placebo group were admitted to hospital with upper gastrointestinal haemorrhage. The other most common adverse event was angina (famotidine, n=2; placebo, n=4). INTERPRETATION: Famotidine is effective in the prevention of gastric and duodenal ulcers, and erosive oesophagitis in patients taking low-dose aspirin. These findings widen the therapeutic options for the prevention of gastrointestinal damage in patients needing vascular protection. FUNDING: Merck Laboratories and Astellas Pharma.

Antibacterial and cytotoxic activities of cerium oxide nanoparticles prepared by laser ablation in liquid.

In this work, we have prepared cerium oxide (CeO2) nanoparticles (NPs) by laser ablation in water at different laser energies. The structural and optical properties of synthesized nanoparticles were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Raman spectroscopy, energy dispersive X-ray (EDX), and UV-Vis absorption. XRD results confirmed that the synthesized cerium oxide NPs were crystalline in nature with cubic structure. SEM investigations show that the nanoparticles having a spherical shape with diameter ranged from 26 to 37 nm depending on the laser energy. The antibacterial activity and minimal inhibition concentration of synthesized CeO2 NPs against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa were examined. Bacterial adhesion test of cerium oxide NPs was also determined under different incubation temperatures. Cytotoxicity of CeO2 NP effect against the human throat cancer was studied. The cytotoxicity effect of CeO2 NPs synthesized at 160 mJ on the cancer cells caused a free radical releasing which causing oxidative stress. The cytotoxicity effects of ceria NPs against human throat cancer (RD rhabdomyosarcoma cell line) and mouse fibroblast L cell (L20B cell line) growth were 33% and 13%, respectively.

Spinal-Pelvic Dissociation in Pregnancy: Surgical Fixation of Culture-Negative Extrapulmonary Tuberculosis.

A 33-year-old gravid female from Pakistan presented to the Emergency Department with persistent, intractable low back pain and neuropathic left L5 leg pain, associated with a left foot drop. There was a notable history of weight loss for 1 year. Investigations revealed a large collection in the right posterior paraspinal muscles tracking from a large bony defect in the right half of her sacrum extending into the pelvis. The collection was suggestive of an abscess and underwent US-guided aspiration. Culture, PCR examination, and bone biopsy were culture-negative for tuberculosis (TB). Samples taken from the placenta showed two small granulomata in the chorionic villi only. A multidisciplinary approach commenced with initiation of empirical TB treatment and attempted normal vaginal delivery. An urgent caesarean section for the delivery of the baby was required for failure to proceed. Spinal-pelvic stabilization in two stages was performed for the unstable fracture pattern, followed by pharmacotherapy and physiotherapy rehabilitation. At 12-month follow-up, the patient showed resolving TB and eradication of the paraspinal abscess. There was bony union and stability of the spinal-pelvic reconstruction. Back pain and sciatica can be common in pregnancy. However, this case highlights a rare occurrence of culture-negative extrapulmonary TB leading to an unstable spinal-pelvic fracture requiring a multidisciplinary approach for careful obstetric and orthopaedic treatment with empirical treatment by the infectious disease team and microbiology.

Linalool-Loaded Glutathione-Modified Gold Nanoparticles Conjugated with CALNN Peptide as Apoptosis Inducer and NF-κB Translocation Inhibitor in SKOV-3 Cell Line.

BACKGROUND: Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability. METHODS: We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool-GNP (LG) and linalool-GNP-CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis. RESULTS: Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone. CONCLUSION: We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways.

Implementing integrated community case management during conflict in Yemen.

BACKGROUND: The conflict in Yemen has devastated the health system, with only 51% of health facilities classified as fully functional and 19.7 million people lacking access to health care. To address the urgent need for primary health care services in rural communities, Save the Children launched an iCCM program in Lahj and Taiz Governorates. A qualitative study was conducted to document the challenges to iCCM service delivery and to aid in developing strategies for overcoming service delivery bottlenecks in conflict-affected rural areas. METHODS: Qualitative data were collected in Aden City, Lahj Governorate, and Taiz Governorate. Twenty-three IDIs and six FGDs were conducted with iCCM stakeholders at all levels. RESULTS: Key findings included: 1) Policy, coordination, and funding were challenged by the fact that iCCM was not integrated into the national health system and was implemented as a short-term emergency program. 2) Villages that received services from a CHW who was based in a different community experienced reduced access to services, especially during times of heightened conflict and insecurity, when CHWs could not travel. 3) Supervision, supply chain, and monitoring were all challenges that were exacerbated by difficulties in travel due to the conflict. Potential solutions to these included the use of mobile technology for supervision and data collection and pre-positioning of buffer stocks in locations closer to CHWs. 4) Travel was seen as the primary threat to the safety of CHWs and supervisors. Measures taken to reduce the risk included limiting travel during periods of heightened insecurity, safety training for CHWs, and use of mobile technology for communication. CONCLUSIONS: CHWs were able to provide iCCM services in a challenging and insecure context. The challenges in delivery of services were related to both a weak health system and the conflict. Several adaptations to service delivery to overcome the bottlenecks have been identified and should be considered for future community health programs. The closure of the program in Taiz after only 14 months of implementation is a stark illustration of the failure of the current model of short-term humanitarian funding to address long-term needs in protracted emergencies.