On leveraging self-supervised learning for accurate HCV genotyping.

Hepatitis C virus (HCV) is a major global health concern, affecting millions of individuals worldwide. While existing literature predominantly focuses on disease classification using clinical data, there exists a critical research gap concerning HCV genotyping based on genomic sequences. Accurate HCV genotyping is essential for patient management and treatment decisions. While the neural models excel at capturing complex patterns, they still face challenges, such as data scarcity, that exist a lot in computational genomics. To overcome this challenges, this paper introduces an advanced deep learning approach for HCV genotyping based on the graphical representation of nucleotide sequences that outperforms classical approaches. Notably, it is effective for both partial and complete HCV genomes and addresses challenges associated with imbalanced datasets. In this work, ten HCV genotypes: 1a, 1b, 2a, 2b, 2c, 3a, 3b, 4, 5, and 6 were used in the analysis. This study utilizes Chaos Game Representation for 2D mapping of genomic sequences, employing self-supervised learning using convolutional autoencoder for deep feature extraction, resulting in an outstanding performance for HCV genotyping compared to various machine learning and deep learning models. This baseline provides a benchmark against which the performance of the proposed approach and other models can be evaluated. The experimental results showcase a remarkable classification accuracy of over 99%, outperforming traditional deep learning models. This performance demonstrates the capability of the proposed model to accurately identify HCV genotypes in both partial and complete sequences and in dealing with data scarcity for certain genotypes. The results of the proposed model are compared to NCBI genotyping tool.

Lateral Spinal CSF Leaks in Patients with Spontaneous Intracranial Hypotension: Radiologic-Anatomic Study of Different Variants.

BACKGROUND AND PURPOSE: Spinal CSF leaks cause spontaneous intracranial hypotension. Several types of leaks have been identified, and one of these types is the lateral dural tear. Performing myelography with the patient in the decubitus position allows precise characterization of these leaks. The purpose of the current study was to describe the different variants of spontaneous lateral CSF leaks. MATERIALS AND METHODS: This retrospective cohort study included a consecutive group of patients with spontaneous intracranial hypotension and lateral CSF leaks who underwent digital subtraction myelography in the decubitus position and underwent surgery to repair the CSF leak between July 2018 and June 2023. RESULTS: The mean age of the 53 patients (37 women and 16 men) was 35.5 years. Three different variants of lateral CSF leak could be identified. Forty-nine patients (92.5%) had a lateral dural tear associated with the nerve root sleeve. The dural tear was at the axilla of the nerve root sleeve in 36 patients (67.9%) and at the shoulder in 13 patients (24.5%). Four patients (7.5%) had a lateral dural tear at the level of the pedicle that was not associated with the nerve root sleeve. Findings on digital subtraction myelography were concordant with intraoperative findings in all patients. An extradural CSF collection was seen in all patients with a lateral dural tear associated with the nerve root sleeve but in only 2 of the 4 patients with the pedicular variant of a lateral dural tear. CONCLUSIONS: We identified 3 variants of spontaneous lateral dural tears. Most lateral dural tears are associated with extradural CSF collections and arise from either the axilla (67.9%) or the shoulder (24.5%) of the nerve root sleeve. Lateral dural tears at the level of the pedicle (7.5%) not associated with the nerve root sleeve are uncommon and may require specialized imaging for their detection.

The Role of Phthalocyanine-Gold Nanoconjugates (Pc-Au NCs) in Ameliorating the Hepatic and Renal Toxicity-Induced by Silver Nanoparticles (Ag NPs) in Male Rats.

Recently, gold nanoparticles (Au Nps) have gained tremendous attention for its unique properties as a safe nanocarrier for delivering drugs that are used in different disease diagnoses. Although silver nanoparticles (Ag NPs) have been generally applied due to their strong antibacterial, antiviral, antifungal, and antimicrobial properties, their toxicity is a subject of sustained debate, thus requiring further studies. The present study aims to evaluate the potential protective effect of gold nanoparticles and phthalocyanine-gold nanoconjugates (Pc-Au NCs) against the hepatorenal toxicity of silver nanoparticles in male rats. Herein, 60 adult male Rattus norvegicus rats were divided into six equal groups (n = 10/group); the first group was kept as control, the second received gold nanoparticles (Au NPs) intraperitoneally (10 µg/kg) daily for 3 weeks, the third group is gold-phthalocyanine (Pc-Au) group where rats were injected intraperitoneally with gold-phthalocyanine for 3 weeks (10 µg/kg), the fourth group received silver nanoparticles (Ag NPs) (4 mg/kg) daily intraperitoneally for 3 weeks, the fifth group is silver + gold nanoparticles group (Ag + Au), and the sixth is silver + gold-phthalocyanine nanoconjugates (Ag + Pc-Au) group in which rats were intraperitoneally injected firstly with Ag NPs (4 mg/kg) for 3 weeks then with gold or gold-phthalocyanine for another 3 weeks (10 µg/kg). Our results revealed that Ag NPs could increase the serum AST, ALT, ALP, urea, creatinine, and lipid profile and significantly decreased the total protein and albumin. Moreover, histopathological alterations detected in the kidney and the liver of the Ag NPs group included vascular congestion, inflammatory cell infiltration, and tissue distortion. Alongside, exposure to Ag NPs induces hepatic and renal oxidative stress by suppressing the antioxidant-related genes including glutathione peroxidase 1 (gpx1), superoxide dismutase (sod), and catalase (cat). Ag NPs also upregulated the hepatic and renal genes involved in inflammation such as the interleukin-6 (il-6) and tumor necrosis factor-α (tnf-α), nuclear factor kappa B (nf-κß), apoptosis such as the BCL2 associated X (bax), casp3, and other related to metabolism including asparagine synthetase (asns), suppressor of cytokine signaling 3 (socs3), MYC proto-oncogene (myc), and C-C motif chemokine ligand 2 (ccl2). On the other hand, treatment with Au NPs and Pc-Au NCs could effectively ameliorate the hepatorenal damages induced by Ag NPs and improve liver and kidney architecture and function, especially in the Pc-Au NCs group. Briefly, our study revealed the underlined mechanism of Ag NPs hepatotoxic and nephrotoxic effects and that Pc-Au NCs could alleviate these adverse impacts via their anti-oxidative, anti-apoptotic, and anti-inflammatory activities.

Long noncoding RNAs (CTC-471J1.2, NeST) as epigenetic risk factors of active juvenile lupus nephritis: a case-control study.

BACKGROUND: Measurement of the circulating levels of long-non-coding RNAs (lncRNAs) in lupus nephritis (LN) patients could dramatically explore more insights about the disease pathogenesis. Hence, we aimed to quantify the level of expression of CTC-471J1.2 and NeST in LN patients and to correlate it with the disease activity. METHOD: This case-control study was conducted on a group of children with juvenile LN attending to Mansoura University Children's Hospital (MUCH). Demographics, clinical, and laboratory findings were collected besides the measurement of lncRNAs by quantitative real-time PCR. RESULTS: The expression level of lncRNAs-CTC-471J1.2 was significantly down-regulated in children with active LN versus inactive cases or controls. In contrast, the NeST was significantly up-regulated in active LN cases. A significant correlation was found between CTC-471J1.2 expression and LN activity parameters. Additionally, both lncRNAs showed a reasonable sensitivity and specificity in differentiation of active LN. A regression analysis model revealed that CTC-471J1.2 and NeST were independent predictors of active nephritis. CONCLUSION: The expression level of circulatory lncRNAs-CTC-471J1.2 and NeST can be used as sensitive and specific biomarkers for active LN. Furthermore, both could serve as predictors for nephritis activity.

The Stigma of Burnout Impeding Formal Help: A Qualitative Study Exploring Residents' Experiences During Training.

Purpose: Burnout is an occupational stress syndrome that gives rise to emotional exhaustion (EE) depersonalization (DP) and reduced personal accomplishment (PA). Increasing rates of burnout among health care professionals has been reported globally. Saudi Arabia appears to be among the highest in prevalence with reports of higher than 70%. Medical residents in training are the highest group at risk. The literature has repeatedly linked burnout among residents with poor academic performance on training exams, impaired quality of life, career choice regret and intentions to abandon medicine. In this study, we explore the factors that contribute to resident burnout, their experiences with burnout and how they choose to mitigate it. Methods: A qualitative design was used to conduct this study in the city of Riyadh, Saudi Arabia. A total of 14 residents from surgical and non-surgical programs were interviewed through in-depth interviews. Interpretive thematic analysis was used in coding and generated coding templates. Categories were repetitively reviewed and revised, expanding to include new data as it emerged and collapsing to remove redundant codes. Categories were organized into the final themes and sub-themes. Results: All participants demonstrated a shared thread of shame in reaching the level of burnout. Three main interlinked themes were identified: Burnout stigma cycle, amalgamated causes of burnout and self-coping with burnout. One of the concerning findings in our study is the participants' pursuit of self-coping strategies and the avoidance of formal help, creating a cycle of suffering in silence. Conclusion: The literature has repeatedly reported high levels of burnout among residents in training. This study has added another dimension to those findings through the exploration of residents actual accounts and appears to link burnout with suboptimal training and working conditions. We have highlighted the pivotal role stigma and shame play in completely preventing residents from seeking professional help.

A comprehensive tool in recycling plant-waste of Gossypium barbadense L agricultural and industrial waste extracts containing gossypin and gossypol: hepatoprotective, anti-inflammatory and antioxidant effects.

Improper management of agricultural and industrial cotton wastes causes environmental pollution and worsens the climate change challenge. Green recycling of cotton could contribute to a circular economy. One of the economic values of cotton wastes lies in their bioactive components. Two types of cotton wastes-agricultural and industrial-of the species Gossypium barbadense L. Giza 95 were targeted in the current study, aiming to maximize their medicinal value and investigate the anti-inflammatory, hepatoprotective, and antioxidant activities of their phytochemical extracts. Phytochemical extraction was performed using different solvents extraction. An anti-inflammatory effect was tested in carrageenan-induced acute edema in a rat paw model. A carbon tetrachloride chronic model of liver injury was used for the assessment of hepatoprotective potential. Liver enzymes (AST and ALT), oxidative stress markers (MDA and GSH), inflammatory biomarkers (C-reactive protein), and histopathological features were investigated. As a result, ethyl acetate proved to be the solvent of best choice to extract the gossypin polyphenolics, where the extracted amount reached 14,826.2 µg/g, followed by butanol (8751.4 µg/g extract). The chloroform (CHCL3) fraction showed the highest amounts of gossypol (190.7 µg/g extract), followed by petroleum ether. Cotton waste's composition analysis showed a wide range of components, including 33 metabolites such as gossypetin, polyphenolics, and other metabolites that possess therapeutic effects. Both chloroform extract and industrial waste extracts showed superior anti-inflammatory and hepatoprotective effects in comparison to other extracts. All tested extracts (ethyl acetate, chloroform, and industrial waste) showed proper antioxidant activities.

Comparative Study of Azithromycin Versus Doxycycline Effect on the Resistin Level in Periodontitis Patients With Type 2 Diabetes: A Randomized Controlled Clinical Trial.

AIM: The present study aimed to determine if azithromycin (AZM) and doxycycline therapy, as an adjunct to scaling and root planning (SRP), modulate host response and improve clinical outcomes in periodontitis patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: Forty-five periodontal sites in 15 periodontitis patients with T2DM received nonsurgical periodontal therapy (NSPT). In Group I, patients were placebo (not receiving any medication), Group II patients received systemic AZM therapy (AZM 250 mg/day for five days), and Group III patients received doxycycline (20 mg twice per day for three months. The resistin level was collected and measured by enzyme-linked immunosorbent assay (ELISA). Gingival index (GI), probing depth (PD), and clinical attachment level (CAL) were recorded at baseline, one-month, and three-month intervals. RESULTS: All groups showed improvement in clinical parameters and resistin levels throughout the study. The mean resistin level at three months was the highest in Group I and the lowest in Group III. Patients in Group II showed a larger decrease in mean PD than those in Group I and III. Group III had the highest gain in mean CAL, with an increase of 1.78 mm in attachment. CONCLUSION: Resistin might be a useful indicator of current disease status. In addition, benefits from adjunctive systemic use of AZM and doxycycline have been administered with non-surgical periodontal therapy.

Optic Nerve Sheath MR Imaging Measurements in Patients with Orthostatic Headaches and Normal Findings on Conventional Imaging Predict the Presence of an Underlying CSF-Venous Fistula.

BACKGROUND AND PURPOSE: Spontaneous spinal CSF leaks typically cause orthostatic headache, but their detection may require specialized and invasive spinal imaging. We undertook a study to determine the value of simple optic nerve sheath MR imaging measurements in predicting the likelihood of finding a CSF-venous fistula, a type of leak that cannot be detected with routine spine MR imaging or CT myelography, among patients with orthostatic headache and normal conventional brain and spine imaging findings. MATERIALS AND METHODS: This cohort study included a consecutive group of patients with orthostatic headache and normal conventional brain and spine imaging findings who underwent digital subtraction myelography under general anesthesia to look for spinal CSF-venous fistulas. RESULTS: The study group consisted of 93 patients (71 women and 22 men; mean age, 47.5 years; range, 17-84 years). Digital subtraction myelography demonstrated a CSF-venous fistula in 15 patients. The mean age of these 8 women and 7 men was 56 years (range, 23-83 years). The mean optic nerve sheath diameter was 4.0 mm, and the mean perioptic subarachnoid space was 0.5 mm in patients with a CSF-venous fistula compared with 4.9 and 1.2 mm, respectively, in patients without a fistula (P < .001). Optimal cutoff values were found at 4.4 mm for optic nerve sheath diameter and 1.0 mm for the perioptic subarachnoid space. Fistulas were detected in about 50% of patients with optic nerve sheath diameter or perioptic subarachnoid space measurements below these cutoff values compared with <2% of patients with optic nerve sheath diameter or perioptic subarachnoid space measurements above these cutoff values. Following surgical ligation of the fistula, optic nerve sheath diameter increased from 4.0 to 5.3 mm and the perioptic subarachnoid space increased from 0.5 to 1.2 mm (P < .001). CONCLUSIONS: Concerns about a spinal CSF leak should not be dismissed in patients with orthostatic headache when conventional imaging findings are normal, and simple optic nerve sheath MR imaging measurements can help decide if more imaging needs to be performed in this patient population.

Synthesis and biological evaluation of titanium dioxide/thiopolyurethane composite: anticancer and antibacterial effects.

Nanocomposites incorporating titanium dioxide (TiO2) have a significant potential for various industrial and medical applications. These nanocomposites exhibit selectivity as antimicrobial and anticancer agents. Antimicrobial activity is crucial for medical uses, including applications in food processing, packaging, and surgical instruments. Additionally, these nanocomposites exhibit selectivity as anticancer agents. A stable nanocomposite as a new anticancer and antibacterial chemical was prepared by coupling titanium dioxide nanoparticles with a polyurethane foam matrix through the thiourea group. The titanium dioxide/thiopolyurethane nanocomposite (TPU/TiO2) was synthesized from low-cost Ilmenite ore and commercial polyurethane foam. EDX analysis was used to determine the elemental composition of the titanium dioxide (TiO2) matrix. TiO2NPs were synthesized and were characterized using TEM, XRD, IR, and UV-Vis spectra. TiO2NPs and TPU foam formed a novel composite. The MTT assay assessed Cisplatin and HepG-2 and MCF-7 cytotoxicity in vitro. Its IC50 values for HepG-2 and MCF-7 were 122.99 ± 4.07 and 201.86 ± 6.82 µg/mL, respectively. The TPU/TiO2 exhibits concentration-dependent cytotoxicity against MCF-7 and HepG-2 cells in vitro. The selective index was measured against both cell lines; it showed its safety against healthy cells. Agar well-diffusion exhibited good inhibition zones against Escherichia coli (12 mm), Bacillus cereus (10 mm), and Aspergillus niger (19 mm). TEM of TPU/TiO2-treated bacteria showed ultrastructure changes, including plasma membrane detachment from the cell wall, which caused lysis and bacterial death. TPU/TiO2 can treat cancer and inhibit microbes in dentures and other items. Also, TPU/TiO2 inhibits E. coli, B. cereus, and A. niger microbial strains.

Solid-State Synthesis of Liquorice-Stabilized Copper-Based Nanoparticles: Structural and Catalytic Studies.

A large-scale quantity of copper oxalate nanoparticles were successfully obtained via a facile and green solid-state chemical reaction. Copper oxalate nanoparticles were obtained by ball-milling between copper chloride, Liquorice (Glycyrrhiza glabra), and ascorbic acid at ambient conditions. The size and morphology of copper oxalate nanoparticles powder were studied by transmission and scanning electron microscopy. The prepared nanoparticles were semi-spherical in shape and ranged from 5 to 15 nm in size. UV/Vis spectroscopy, Fourier transforms infrared spectroscopy, and X-ray photoelectron spectroscopy measurements were carried out to characterize the prepared samples. Copper oxalate nanoparticles were evaluated as a catalyst in the catalytic degradation of 4-nitrophenol, bromophenol blue, reactive yellow, and a mixture of the three pollutants. The present study combined solid-state reaction and green requirements for the mass production of nanomaterials. The proposed reaction is performed in simple steps, inexpensive, low energy consuming, solvent-free, and minimizes the emission of secondary wastes.

Synergistic Effect of Silver Nanoparticles with Antibiotics for Eradication of Pathogenic Biofilms.

BACKGROUND: The increase in nosocomial multidrug resistance and biofilm-forming bacterial infections led to the search for new alternative antimicrobial strategies other than traditional antibiotics. Silver nanoparticles [AgNP] could be a viable treatment due to their wide range of functions, rapid lethality, and minimal resistance potential. The primary aim of this study is to prepare silver nanoparticles and explore their antibacterial activity against biofilms. METHODS: AgNPs with specific physicochemical properties such as size, shape, and surface chemistry were prepared using a chemical reduction technique, and then characterized by DLS, SEM, and FTIR. The activity of AgNPs was tested alone and in combination with some antibiotics against MDR Gram-negative and Gram-positive planktonic bacterial cells and their biofilms. Finally, mammalian cell cytotoxicity and hemolytic activity were tested using VERO and human erythrocytes. RESULTS: The findings of this study illustrate the success of the chemical reduction method in preparing AgNPs. Results showed that AgNPs have MIC values against planktonic organisms ranging from 0.0625 to 0.125 mg/mL, with the greatest potency against gram-negative bacteria. It also effectively destroyed biofilm-forming cells, with minimal biofilm eradication concentrations [MBEC] ranging from 0.125 to 0.25 mg/ml. AgNPs also had lower toxicity profiles for the MTT test when compared to hemolysis to erythrocytes. Synergistic effect was found between AgNPs and certain antibiotics, where the MIC was dramatically reduced, down to less than 0.00195 mg/ml in some cases. CONCLUSION: The present findings encourage the development of alternative therapies with high efficacy and low toxicity.

Synergistic Antibacterial Effect of ZnO Nanoparticles and Antibiotics against Multidrug-Resistant Biofilm Bacteria.

BACKGROUND: The misuse of antibiotics leads to a global increase in antibiotic resistance. Therefore, it is imperative to search for alternative compounds to conventional antibiotics. ZnO nanoparticles (Zn NP) are one of these alternatives because they are an effective option to overcome biofilm bacterial cells and a novel way to overcome multidrug resistance in bacteria. The current research study aims to characterize the efficacy of ZnO nanoparticles alone and in combination with other antibacterial drugs against bacterial biofilms. METHODS: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated. RESULTS: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 µg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 µg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 µg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity. CONCLUSION: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.

Effect of spermidine on long non-coding RNAs MALAT1 in a rotenone induced-rat model of Parkinson's disease.

BACKGROUND: Spermidine is a natural biologically active substance that has widespread influences on the body. OBJECTIVE: This study aims to enhance our understanding of the potential effect of spermidine on long non-coding RNA MALAT1 and explore the underlying mechanism in the rotenone-induced rat model of Parkinson's disease. METHODS: Rats were sacrificed after locomotor behavioral testing. Striatal tissues were used to assess the expression of MALAT1, oxidative stress markers, and autophagy markers. RESULTS: Our study found that treatment with spermidine for 2 weeks during the induction of the model significantly improved behavioral assessment, dopamine levels, and attenuated the histopathological changes that occurred in PD in comparison to the non-treated group. CONCLUSION: Our preliminary study supports the protective effect of spermidine on the activation of autophagy and its antioxidant properties. Part of the antioxidant activity is due to the inhibition of MALAT1. However, MALAT1 does not correlate with the spermidine-induced autophagy pathway.

Effect of different timings of umbilical cord clamping on the level of CD34+ cells in full-term neonates.

Despite the fact that delayed cord clamping (DCC) is recommended by many international organizations, early cord clamping is still widely practiced worldwide. The overarching goal of the DCC practice is to maximize neonatal benefits as achieving higher hemoglobin levels and decreasing the incidence of anemia as well as avoiding the adverse consequences. The current study was conducted to identify the effect of of DCC on the number of CD34+ stem cells in cord blood of full term neonates after two different timings (30 and 60 s after birth). One hundred and three full-term (FT) newborn babies (gestational age 37-40 weeks) delivered by elective cesarean section were randomly assigned into 2 groups: Group 1: babies were subjected to DCC 30 s after birth (50 newborns). Group 2: babies were subjected to DCC 60 s after birth (53 newborns). Neonates in group 2 had significantly higher levels of hemoglobin, hematocrit, total nucleated cells and CD34+ cells compared to those in group 1. The practice of DCC 60 s after birth achieved better CD34+ stem cells transfer in FT neonates than clamping the cord after 30 s.

YKL-40 in serum: a promising biomarker of juvenile SLE and strongly correlated with disease duration.

BACKGROUND: The biological function of YKL-40 is not well determined in different inflammatory and autoimmune diseases; however, some data highlighted its possible connection with disease activity. AIM: We investigated the diagnostic utility of serum YKL-40 in patients with SLE and examined its correlation with disease activity. Additionally, we examined any differences in serum YKL-40 levels between juvenile and adult SLE patients. METHODS: We included 78 female patients with SLE and 42 controls. The level of YKL-40 in serum was measured by ELISA. RESULTS: The serum YKL-40 level in SLE patients was significantly higher compared to the control group (9 (3) ng/mL vs. 5.5 (0.1) ng/mL; p < 0.001). YKL-40 showed excellent diagnostic utility with an AUC of 1 (p < 0.001) and a cutoff point of 5.6, providing sensitivity and specificity of 100%. YKL-40 was higher in adolescents and those with a positive family history of SLE (p = 0.01 for both) and positively correlated with disease duration (r = 0.45, p < 0.001). YKL-40 level was significantly higher in patients with photosensitivity, fever, vasculitis, blood disorders, positive anti-dsDNA, and APL ab (p < 0.05 for all). Conversely, patients with skin manifestations had a significantly lower YKL-40 (p = 0.004). In juvenile SLE, the AUC was 0.65 and a p-value of 0.01, and at a cutoff value of (8.7) ng/mL, the sensitivity and specificity were 72% and 60%, respectively. CONCLUSION: YKL-40 in serum could be a promising biomarker in patients with SLE, especially in adolescent-onset cases. It is independently influenced by disease duration, anemia, thrombocytopenia, positive anti-dsDNA, and APL ab features.

In vitro evaluation of the potential immunosuppressive effect of panobinostat on cultured lymphocytes retrieved from childhood systemic lupus erythematosus patients.

Although many drugs are available for childhood systemic lupus erythematosus (SLE) treatment, the adverse effects and poor response in some cases make it crucial to find new drugs targeting various pathways in disease pathogenesis to improve overall outcomes. This study aimed to (i) investigate the effect of Panobinostat on cultured lymphocytes obtained from children with active SLE and (ii) to compare that effect with standard drugs used in SLE, such as Prednisone and hydroxychloroquine. The study included 24 SLE active patients, divided into four equal groups. Lymphocytes were isolated from blood samples of the study patients. According to the study group, cells were treated with either Panobinostat, Prednisolone, hydroxychloroquine, or not treated (control group). After cell culture, the response of lymphocytes upon drug treatment was analyzed in terms of the production of anti-dsDNA antibodies and levels of apoptosis as detected by flow cytometry using annexin V and propidium iodide (PI) staining. The Panobinostat group showed a significant decrease in the viable cell count (p < 0.001). Both Prednisone and hydroxychloroquine decreased anti-dsDNA expression more than the Panobinostat and control groups (p < 0.001 for both). PI was higher in the Prednisone group, and Annexin V was higher in the Panobinostat group compared to other groups; however, their increase did not reach statistically significant levels (p= 0.12 and 0.85, respectively). This is the first study of the Panobinostat effect on cultured lymphocytes of SLE. In conclusion, Panobinostat could be a prospective treatment for B-cell-driven autoimmune diseases such as SLE. However, its effect on autoantibodies levels and different clinical features of SLE still need a thorough evaluation.

Herpes simplex virus infection and the risk of dementia: a systematic review and meta-analysis.

Aim: The authors aimed to perform a meta-analysis to evaluate the association between herpes simplex virus (HSV) infection and the risk of developing dementia. Methods: The authors searched the following databases: PubMed, Scopus, Cochrane Library, and Web of Science. The authors included any randomized control trials and controlled observational studies that investigated the prevalence of dementia in HSV-infected patients and HSV-free control group. Also, if the studies measured the levels of HSV antibodies and incidence of these antibodies in patients with dementia compared with a healthy control group. Results: After a comprehensive literature search, 19 studies were included in the meta-analysis with 342 535 patients included in the analysis. The pooled analysis showed a statistically significant association between Alzheimer's disease (AD), mild cognitive impairment (MCI), and increased levels of IgG titer group [mean difference (MD) = 0.99, 95% confidence interval (CI) = 0.36-1.63, P-value = 0.002], (MD = 0.80, 95% CI = 0.26-1.35, P-value = 0.004), respectively. Additionally, the generic inverse variance showed a statistically significant association between the HSV group and increased incidence of dementia compared with the no HSV control group [risk ratio (RR) = 2.23, 95% CI = 1.18-2.29, P-value <0.00001]. Moreover, this analysis showed no statistically significant difference between the AD group and the control group in anti-HSV IgM titer n (%) outcome (RR = 1.35, 95% CI = 0.91-2.01, P-value = 0.14), respectively. Conclusion: This study revealed that AD and MCI patients have increased levels of IgG antibodies titer against HSV infection. The study showed a significant association between HSV infection and increased incidence of dementia. Thus, regular follow-up of HSV patients' IgG titer levels could be useful in the prevention of dementia in these patients.

Synthesis, Characterization, and Anticancer Activity of New N,N'-Diarylthiourea Derivative against Breast Cancer Cells.

The goal of the current study was to prepare two new homologous series of N,N'-diarylurea and N,N'-diarylthiourea derivatives to investigate the therapeutic effects of these derivatives on the methodologies of inhibition directed on human MCF-7 cancer cells. The molecular structures of the prepared derivatives were successfully revealed through elemental analyses, 1H-NMR, 13C-NMR and FT-IR spectroscopy. The cytotoxic results showed that Diarylthiourea (compound 4) was the most effective in suppressing MCF-7 cell growth when compared to all other prepared derivatives, with the most effective IC50 value (338.33 ± 1.52 µM) after an incubation period of 24 h and no cytotoxic effects on normal human lung cells (wi38 cells). Using the annexin V/PI and comet tests, respectively, treated MCF-7 cells with this IC50 value of the Diarylthiourea 4 compound displayed a considerable increase in early and late apoptotic cells, as well as an intense comet nucleus in comparison to control cells. An arrest of the cell cycle in the S phase was observed via flow cytometry in MCF-7 cells treated with the Diarylthiourea 4 compound, suggesting the onset of apoptosis. Additionally, ELISA research showed that caspase-3 was upregulated in MCF-7 cells treated with compound 4 compared to control cells, suggesting that DNA damage induced by compound 4 may initiate an intrinsic apoptotic pathway and activate caspase-3. These results contributed to recognizing that the successfully prepared Diarylthiourea 4 compound inhibited the proliferation of MCF-7 cancer cells by arresting the S cell cycle and caspase-3 activation via an intrinsic apoptotic route. These results, however, need to be verified through in vivo studies utilizing an animal model.

Histopathological Patterns and Outcomes of Triple-Positive Versus Triple-Negative Breast Cancer: A Retrospective Study at a Tertiary Cancer Center.

Background One of the leading causes of cancer-related deaths in females under 45 years old is breast cancer (BC). The definition of triple-negative breast cancer (TNBC) is the lack of expression of estrogen receptors (ERs) as well as progesterone receptors (PRs) and Erb-B2 receptor tyrosine kinase 2 (HER2) gene amplification. Triple-positive breast cancer (TPBC), on the other hand, is defined as tumors expressing a high level of ER, PR, and HER2 receptors. This study aims to assess the phenotypes of TNBC and TPBC by comparing their individual clinical behavior patterns and prognosis throughout the course of the disease in a tertiary cancer center in the Kingdom of Saudi Arabia (KSA). Methods Our study is a retrospective study using electronic medical records (EMRs) to identify all female patients diagnosed with BC using the International Classification of Diseases-10 (ICD-10) codes (between C50 and C50.9). About 1209 cases with primary BC female patients were recognized based on histopathology reports. Further subclassification into TPBC and TNBC was performed. Statistical analysis was performed using Rv3.6.2 (R Studio, version 3.5.2, Boston, MA, USA). The descriptive data were presented as means and standard deviations (SD). Survival curves were approximated using the Kaplan-Meier method. The comparison between survival curves between both groups was achieved using the log-rank test. The multivariate model was constructed based on the identified predictors using univariate analysis. Results Univariate analysis of overall survival (OS) showed that mortality was higher in TNBC compared to TPBC (HR = 2.82, P-value <0.05). However, in a multivariate analysis, molecular subtypes did not show a significant effect on OS with a P-value of 0.94. We found that age at diagnosis has been associated with a 4% increase in mortality risk with a yearly rise in age. Conclusion In this limited retrospective cohort study, we found that TNBC may not be associated with a higher risk of death than TPBC. However, other factors, including age at diagnosis, surgical intervention, and lymphovascular invasion (LVI), have been observed to increase the risk of mortality. On the other hand, patients with TNBC were found to have a worse prognosis in terms of local recurrence. This information cannot be generalized to all patients with BC given the limitations of this study. Further, larger cohorts are needed to explore biological and treatment-related outcomes in patients with TNBC and TPBC.