Emergence of the novel infectious bursal disease virus variant in vaccinated poultry flocks in Egypt.

RESEARCH HIGHLIGHTS: New variant IBDV which emerged in Egypt clustered with Chinese nVarIBDV.nVarIBDV spread subclinically across a wide geographic area.Mutation at 321 represents capsid's most exposed part, a defining feature.Antigenically modified vvIBDV still circulating in Egypt with typical lesions.

Assessment of the in Vitro Effects of Folate Core-Shell Conjugated Iron Oxide Nanoparticles as a Potential Agent for Acute Leukemia Treatment.

BACKGROUND AND OBJECTIVE: There is a growing need to comprehend the potential outcomes of nanoparticles (NPs) on human well-being, including their potential for detecting and treating leukemia. This study examined the role of iron folate core-shell and iron oxide nanoparticles in inducing apoptosis and altering the expression of the B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and Caspase-3 genes in leukemia cells. METHODS: The obtained iron oxide and iron folate core-shell nanoparticles were analyzed using a variety of analytical techniques, including ultraviolet-visible (UV-Vis) absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM). Additionally, FTIR and UV-Vis were used to characterize doxorubicin. The MTT test was utilized to investigate the cytotoxicity of iron oxide and iron folate core-shell nanoparticles. The expression of the apoptotic signaling proteins Bcl-2, Bax, and Caspase-3 was evaluated using the real-time reverse transcription polymerase chain reaction (RT-qPCR) method. Additionally, flow cytometry was performed to gauge the degrees of necrosis and apoptosis. RESULTS: UV-Visible spectroscopy analysis showed that the generated iron oxide and iron folate core-shell NPs had a distinctive absorption curve in the 250-300 nm wavelength range. The XRD peaks were also discovered to index the spherical form with a size of less than 50 nm, which validated the crystal structure. The FTIR analysis determined the bonds and functional groups at wavenumbers between 400 and 4000 cm-1. A viable leukemia treatment approach is a nanocomposite consisting of iron and an iron folate core-shell necessary for inhibiting and activating cancer cell death. The nearly resistant apoptosis in the CCRF-CEM cells may have resulted from upregulating Bax and Casepase-3 while downregulating Bcl-2 expression. CONCLUSIONS: Our study documents the successful synthetization and characterization of iron oxide, which has excellent anticancer activities. A metal oxide conjugation with the nanoparticles' core-shell enhanced the effect against acute leukemia.

Beetroot extract@chitosan nanocomposite as a promising approach towards cancer therapy.

The exceptional antioxidant properties of beetroot (BR) and the cancer antiproliferative effects of chitosan nanoparticles (CS NP) have led to the synthesis of a BR@CS nanocomposite (NC) in this study. The novel BR@CS NC was applied to human epithelial colorectal adenocarcinoma (Caco-2), human epithelial ductal breast carcinoma (T-47D), and human epithelial lung carcinoma (A549) cells. SEM characterization of CS NP revealed a variety of particle shapes ranging from 20 to 58 nm in diameter. UV-VIS analysis confirmed the formation of the BR@CS NC, while FTIR analysis demonstrated strong hydrogen bonds between CS NP and BR. These bonds reduced the positive surface charge of CS NP, as indicated by zeta potential analysis. When applied to cancer cell lines at a concentration of 250 µg/mL, the BR@CS NC successfully eradicated 89 % of A549, 88 % of T-47D, and 83 % of Caco-2 cell lines. The cell death mode exhibited extensive, apoptotic, and massive necrotic changes in all cell lines treated with BR@CS NC. Caspase 3 (CasP3) and P53 levels were elevated in BR@CS NC-treated cells. This study merges BR's antioxidant and anti-inflammatory properties with the antiangiogenic mechanism and inhibition of tumors by CS NP, resulting in a unique and innovative strategy for cancer treatment.

First Detection and Molecular Characterization of Novel Variant Infectious Bursal Disease Virus (Genotype A2dB1b) in Egypt.

Infectious bursal disease (IBD) is an immunosuppressive disease causing significant damage to the poultry industry worldwide. Its etiological agent is infectious bursal disease virus (IBDV), a highly resistant RNA virus whose genetic variability considerably affects disease manifestation, diagnosis and control, primarily pursued by vaccination. In Egypt, very virulent strains (genotype A3B2), responsible for typical IBD signs and lesions and high mortality, have historically prevailed. The present molecular survey, however, suggests that a major epidemiological shift might be occurring in the country. Out of twenty-four samples collected in twelve governorates in 2022-2023, seven tested positive for IBDV. Two of them were A3B2 strains related to other very virulent Egyptian isolates, whereas the remaining five were novel variant IBDVs (A2dB1b), reported for the first time outside of Eastern and Southern Asia. This emerging genotype spawned a large-scale epidemic in China during the 2010s, characterized by subclinical IBD with severe bursal atrophy and immunosuppression. Its spread to Egypt is even more alarming considering that, contrary to circulating IBDVs, the protection conferred by available commercial vaccines appears suboptimal. These findings are therefore crucial for guiding monitoring and control efforts and helping to track the spread of novel variant IBDVs, possibly limiting their impact.

Epidemiological characterization of viral etiological agents of the central nervous system infections among hospitalized patients in Egypt between 2016 and 2019.

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.

Curcumin nanocapsules effect in apoptotic processes, gene expression, and cell cycle on Hep-G2 cell lines.

OBJECTIVES: Curcumin has antioxidant and antiproliferative properties, and its therapeutic effect must be considered. Nanocurcumin capsules showed a potential increase against in vitro biological cancer. This study sought to determine how curcumin nanoparticles and nanocapsules affected the expression of p53, Bcl-2, Bax, and Bax in a liver cancer cell line (Hep-G2). Mechanisms of apoptosis were also examined in this cell line. METHODS: This study used quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the p53, Bcl-2, Bax, and Caspase-3 gene pathways and to evaluate the molecular mechanisms responsible for the efficacy of curcumin nanoparticles (CNPs) and curcumin nanocapsules (CNCs) against liver cell lines. Flow cytometry was used to check for signs of apoptosis and the cell cycle. RESULTS: Curcumin nanocapsules produced by the ball milling process at 90 min significantly boosted the populations of apoptotic cells in a dose- and time-dependent manner. The mRNA expression analysis revealed that the proapoptotic Bax, Caspase-3, and the tumor suppressor gene p53 were upregulated throughout the process started by curcumin nanocapsules and decreased in the Bcl-2/Bax ratio. CONCLUSION: This research provides a fresh understanding of the molecular mechanisms behind the liver cancer-fighting abilities of curcumin nanoparticles. Curcumin nanocapsules produced through a unique mechanical technique can be used as an anticancer agent.

The Hepatoprotective Effect of Two Date Palm Fruit Cultivars' Extracts: Green Optimization of the Extraction Process.

Date palm fruit (Phoenix dactylifera: Arecaceae) is rich in essential nutrients and possesses several pharmacological and medicinal activities. The current study aimed to optimize a water bath-assisted extraction method for two cultivars of date palm fruits, Anbara (An) and Reziz (Rz), and investigated the protective effect of the optimized date palm fruit extract against CCl4-induced liver toxicity in relation to oxidative stress, inflammation, apoptosis, and DNA integrity. The optimization process of two date palm fruit cultivars was applied, using response surface methodology through adjusting three "factors"; time, temperature, and rotation, to allow maximum contents of total phenolic (TPC), total flavonoid (TFC), reducing power (FRAP) and scavenging activity (ABTS) of the extract "responses". Extraction factors' application significantly enhanced TPC, TFC, FRAP, and ABTS responses by 1.30, 1.23, 3.03, and 2.06-fold, respectively in An and 2.18, 1.71, 1.11, and 2.62-fold, respectively in Rz, in relation to the convectional water extraction. Furthermore, co-administered CCl4 with An or Rz optimized extracts enhanced body weight gain, amended hepatic architecture, and diminished collagen fiber accumulation. Furthermore, An or Rz extracts reduced liver enzymes, hydroxyproline, alpha-fetoprotein (AFP), MDA, inflammatory cytokine (TNF-α, NF-κB) levels, and DNA fragmentation, while increasing deteriorated adiponectin (ADP) and antioxidant enzyme (GSH, GPX, NO, and IFN-γ) levels, relative to CCl4-administered animals. The protective effects of An or Rz-optimized extracts were also evidenced by suppressing hepatic fibrosis and improving liver function and structure via modulating oxidative stress, inflammation, and apoptosis, in CCl4-induced hepatic damage. Hence, the optimized extraction process for the two date palm fruits resulted in extracts which are rich in phenolic and flavonoid contents and with an elevated antioxidant power. The presence of these rich extracts could help to explain their proven hepatoprotective activity against CCl4-induced liver toxicity.

Rare case presentation of leiomyoma of bladder neck with tuberculous pelvic lymphadenitis in a young female patient.

Bladder neck leiomyoma presenting with gross haematuria and clot retention is a rare clinical scenario. A thirty-three-year-old female presented to the emergency department with a history of lower abdominal pain and gross haematuria for a few days. Abdominal and pelvic ultrasonography examination was complimented with CT and MRI scans showing a 7.6 × 7 × 6.5 cm well-defined mass at the bladder base. There was also pelvic and retroperitoneal lymphadenopathy. Laparotomy with enucleation of the mass along with lymph node biopsy was performed with satisfactory control of the bleeding. Histopathology confirmed the diagnosis of leiomyoma of the bladder neck associated with tuberculous lymphadenopathy.

Hydroxyapatite nanocomposite as a potential agent in osteosarcoma PDT.

Using Nanoplatforms as a hauler for photosensitizers is a bespoke paradigm to improve its bioavailability and to boost the PDT efficacy. Herein, the photodynamic cytotoxicity of methylene blue (MB) loaded on hydroxyapatite nanoparticles (HA-NPs) was tested against human osteosarcoma-derived cells (Saos-2 cell line). HA-NPs and HA-NPs loaded with MB (HA-NPs-MB) were prepared by a chemical precipitation method and characterized by TEM, Zeta potential, FTIR, and XRD. TEM images revealed that HA-NPs have a rod shape with a diameter of 14-17 nm and length around 46-64 nm. FTIR and Zeta potential confirmed the adsorption of cationic MB on HA-NPs. XRD pattern was identical to the standard XRD pattern of HA-NPs. Incubation of Saos-2 cells (24 h) with HA-NPs-MB then irradiation of cells (5 min) with a diode laser (808 nm), causes a higher decrement of cell viability (determined by MTT assay) than that caused by free MB. The LC50 was 57.53 µg/mL and 86.99 µg/mL for HA-NPs-MB and free MB, respectively. Thus, the nanoformulation of MB greatly reduced the dose of MB required for effective PDT. This study also investigated the mode of cell death after incubation of cells with free MB or HA-NPs-MB composite then exposure to laser radiation. The results revealed that the majority of cells died by apoptosis while a minor fraction of cells died by necrosis, especially in the case of HA-NPs-MB. Levels of caspase-3 and death receptor-4 (DR-4) were more elevated in the case of HA-NPs-MB than free MB. The effect of the prepared nanocomposite and free MB on Raw murine macrophage (RAW 264.7) viability was also examined using the MTT assay. The results indicated that HA-NPs-MB in the presence of laser has a great cytotoxic effect on macrophage cells compared to other treatments. This may present an advantage through decreasing macrophage that promotes tumor growth. In conclusion, HA-NPs-MB nanocomposite surmounts free MB and HA-NPs in destroying macrophage cells and Saos-2 cells through apoptosis in the presence of laser irradiation. This study introduces a thorough and new insight on osteosarcoma (cancer cell line Saos-2) PDT using HA-NPs-MB exploiting the biosafety of HA-NPs.

Extrinsic compression neuropathy of the tibial nerve secondary to accessory soleus muscle in a young teenager.

Compression neuropathy of the tibial nerve or one of its terminal branches (tarsal tunnel syndrome) is relatively uncommon. Accessory musculature on the posteromedial aspect of the ankle is a rare extrinsic cause of compression. Therefore, it should be considered in patients with prolonged manifestations of tibial nerve compression. A detailed history and physical examination, together with proper radiological evaluation, allow for accurate diagnosis. In this case report, a 13-year old female teenager on history, physical examination, and imaging studies was diagnosed as compression neuropathy of the tibial nerve secondary to accessory soleus muscle. After surgical excision of the accessory soleus muscle with no tarsal tunnel release, the patient presented with complete resolution of her manifestations continued free of symptoms for one and half year postoperatively. The accessory soleus muscle is a potential extrinsic cause for tibial nerve compression neuropathy. LEVEL OF CLINICAL EVIDENCE: 5.

Evaluation of the usefulness of a D dimer test in combination with clinical pretest probability score in the prediction and exclusion of Venous Thromboembolism by medical residents.

INTRODUCTION: Venous thromboembolism (VTE) requires urgent diagnosis and treatment to avoid related complications. Clinical presentations of VTE are nonspecific and require definitive confirmation by imaging techniques. A clinical pretest probability (PTP) score system helps predict VTE and reduces the need for costly imaging studies. d-dimer (DD) assay has been used to screen patients for VTE and has shown to be specific for VTE. The combined use of PTP and DD assay may improve exclusion of VTE and safely avoid imaging studies. MATERIALS AND METHODS: We prospectively used the Wells PTP score and a DD test to evaluate 230 consecutive patients who presented with VTE symptoms. The receiver operating characteristic curve was used to identify a new DD cutoff value, which was applied to VTE diagnosis and compared with the upper limit of locally established reference range for prediction of thrombosis alone and in combination with the clinical PTP score. RESULTS: We evaluated 118 patients with VTE symptoms fulfilling the inclusion criteria, 64 (54.2%) with clinically suspected deep vein thrombosis (DVT) and 54 (45.8%) with symptoms of pulmonary embolism (PE). The PTP was low in 28 (43.8%) and moderate/high in 36 (56.25%) of the suspected DVT patients, and low in 29 (53.7%) and moderate/high in 25 (46.3%) of the suspected PE patients. Eighteen cases were confirmed by imaging studies: 9 DVT and 9 PE. The agreement between confirmed cases and PTP was significant with PE but not DVT. The negative predictive value for both DVT and PE with current DD cutoff value of <250 µg/L DDU was 100%, whereas with the calculated cutoff the NPV was 88%. CONCLUSIONS: We confirm that PTP score is valuable tool for medical residents to improve the detection accuracy of VTE, especially for PE. The DD cutoff value of 250 µg/L FEU is ideal for excluding most cases of low PTP; however, the calculated cutoff was less specific for the exclusion of VTE.

Updated recommendations for the diagnosis and management of osteoporosis: a local perspective.

Postmenopausal osteoporosis and osteoporosis in elderly men are major health problems, with a significant medical and economic burden. Although osteopenia and osteoporosis are more common locally than in the West, fracture rates are generally less than in Western countries. Vitamin D deficiency is common in the region and contributes adversely to bone health. Vitamin D deficiency should be suspected and treated in all subjects with ostopenia or osteoporosis. The use of risk factors to determine fracture risk has been adopted by the World Health Organization and many international societies. Absolute fracture risk methodology improves the use of resources by targeting subjects at higher risk of fractures for screening and management. The King Faisal Specialist Hospital Osteoporosis Working Group recommends screening for women 65 years and older and for men 70 years and older. Younger subjects with clinical risk factors and persons with clinical evidence of osteoporosis or diseases leading to osteoporosis should also be screened. These guidelines provide recommendations for treatment for postmenopausal women and men older than 50 years presenting with osteoporotic fractures for persons having osteoporosis-after excluding secondary causes-or for persons having low bone mass and a high risk for fracture. The Working Group has suggested an algorithm to use at King Faisal Specialist Hospital that is based on the availability, cost, and level of evidence of various therapeutic modalities. Adequate calcium and vitamin D supplement are recommended for all. Weekly alendronate (in the absence of contraindications) is recommended as first-line therapy. Alternatives to alendronate are raloxifene or strontium ranelate. Second-line therapies are zoledronic acid intravenously once yearly, when oral therapy is not feasible or complicated by side effects, or teriparatide in established osteoporosis with fractures.

Fever of unknown origin: 98 cases from Saudi Arabia.

BACKGROUND AND OBJECTIVES: Fever of unknown origin (FUO) is mainly secondary to infectious, neoplastic or inflammatory diseases. To increase the body of knowledge on this diagnosis in the region, we collected information on all patients admitted to our institution with FUO in a 13-year period. METHODS: We conducted a retrospective chart review of all immunocompetent males and females aged 13 years and older admitted between January 1995 and June 2008 who fulfilled the criteria for FUO. Data collection included demographics, laboratory investigations, imaging studies, procedures and discharge diagnoses. For true FUO, we recorded the duration of follow-up and the outcome. RESULTS: The 98 patients who met the criteria included 44 males and 54 females with a mean (SD) age of 41.3 (18.5) years and range of 14 to 85 years. The most frequent diagnostic etiology was infectious in 32 (32.7%). Seventeen (17.3%) patients were undiagnosed or had true FUO. Of 9 patients followed up, 8 recovered and 1 expired. The mean duration of follow-up was 20.6 months (range, 0-168 months). CONCLUSION: Infectious diseases, especially TB, continue to be the leading etiology of FUO in our area. Our data did not identify any predictor of certain FUO diagnoses except for older age and neoplastic etiology. True FUO patients generally did well. Reporting local experience is important in guiding clinicians about the epidemiologic patterns of FUO in their regions.

Late-onset rosiglitazone-associated acute liver failure in a patient with Hodgkin's lymphoma.

OBJECTIVE: To report a case of rosiglitazone-associated hepatotoxicity in a patient with Hodgkin's lymphoma. CASE SUMMARY: A 52-year-old man presented with low-grade fever and fatigue that had been present for 4 months. He had been receiving insulin for 5 years and rosiglitazone 4 mg/day for 11 months for control of type 2 diabetes; he was receiving no other drug therapy. During hospitalization, hepatotoxicity was shown, with abnormal liver function test results including alanine aminotransferase 488 U/L, aspartate aminotransferase 344 U/L, alkaline phosphatase 832 U/L, total bilirubin 4.61 mg/dL, and direct bilirubin 3.63 mg/dL. Rosiglitazone was discontinued after further elevation of bilirubin (total 14.67 mg/dL, direct 12.10 mg/dL) occurred. Other causes for hepatotoxicity were ruled out. Hodgkin's lymphoma was diagnosed during the workup; however, liver imaging and biopsy also excluded this as the direct cause of acute liver failure. Despite discontinuation of rosiglitazone, the bilirubin level continued to increase to 49.29 mg/dL (direct > 20 mg/dL). The patient died 3 months after admission. DISCUSSION: Rosiglitazone maleate is a thiazolidinedione approved for treatment of type 2 diabetes mellitus. The first member of this drug class, troglitazone, was withdrawn from the market due to reports of acute liver failure. Rosiglitazone has been shown to be much safer than troglitazone, despite some reported cases of early-onset nonfatal hepatotoxicity. Use of the Naranjo probability scale indicated that rosiglitazone was the probable cause of acute liver failure in our patient. CONCLUSIONS: We conclude that rosiglitazone may be associated with late-onset acute liver failure. Clinicians should be aware of such a complication and monitor liver function in patients receiving the drug.

Update in hypertension: the Seventh Joint National Committee report and beyond.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation on and Treatment of High Blood Pressure (JNC-VII) had new key messages that need to be highlighted for practicing physicians. More than two years has elapsed since its publication and several important trials and meta-analyses were published during this period. Most of these publications supported and reinforced the JNC-VII recommendations, but others did not fully agree. Thus, some questions have arisen that need to be addressed in future research. This review will discuss what is new in JNC-VII and post-JNC-VII evidence that supports or disputes the recommendations. In addition, the results of other significant trials will be addressed. Finally, we outline the clinical "bottom line" and emphasize the practical application of this evidence.