Sulforaphane protects against LPS-induced liver injury in mice by antagonizing oxidative stress and apoptosis through AMPK activation.

Objectives: Given the adverse effect of liver injury on a multitude of body functions, it is vital to understand its underlying mechanism and how to overcome it. In this study, lipopolysaccharide (LPS) was used to induce liver injury, while sulforaphane (SFN), a natural phytochemical, was used as the antagonist to overcome the deleterious effect. Methods: Twenty-four mice were divided into three groups: Control group (0.9% saline), LPS induction group (0.75 mg/kg), and SFN treatment (25 mg/kg) followed by LPS induction group (0.75 mg/kg), all with access to food and water ad libitum. Blood samples from retro-orbital sinus were used to measure liver function through two aminotransferases (i.e., alanine transaminase [ALT] and aspartate transaminase [AST]) whereas liver homogenate was used to measure glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) (antioxidant activity markers); caspase-3 (apoptosis marker); malondialdehyde (MDA) (lipid peroxidation marker); and NO. AMP-activated protein kinase (AMPK), a cellular energy homeostasis and lipid metabolism sensor, was also measured. Statistical analysis including normalization, analysis of variance, Kruskal-Wallis test, and significance of P < 0.05 were applied to all collected data. Results: SFN treatment significantly attenuated all tests compared to the induced liver injury by LPS where significant reduction was observed in the levels of hepatic function markers (AST and ALT), lipid peroxidation marker (MDA) as well as apoptosis marker (caspase-3) whereas a marked increase was observed for antioxidant activity markers (SOD, CAT, and GSH) and AMPK. Conclusion: These results indicate the protective effect of SFN as it re-instated the levels of antioxidation while decreasing the level of the biomarkers, which were significantly increased during liver injury induction by LPS.

CT-derived radiomics predict the growth rate of renal tumours in von Hippel-Lindau syndrome.

AIM: To predict renal tumour growth patterns in von Hippel-Lindau syndrome by utilising radiomic features to assist in developing personalised surveillance plans leading to better patient outcomes. MATERIALS AND METHODS: The study evaluated 78 renal tumours in 55 patients with histopathologically-confirmed clear cell renal cell carcinomas (ccRCCs), which were segmented and radiomics were extracted. Volumetric doubling time (VDT) classified the tumours into fast-growing (VDT <365 days) or slow-growing (VDT ≥365 days). Volumetric and diametric growth analyses were compared between the groups. Multiple logistic regression and random forest classifiers were used to select the best features and models based on their correlation and predictability of VDT. RESULTS: Fifty-five patients (mean age 42.2 ± 12.2 years, 27 men) with a mean time difference of 3.8 ± 2 years between the baseline and preoperative scans were studied. Twenty-five tumours were fast-growing (low VDT, i.e., <365 days), and 53 tumours were slow-growing (high VDT, i.e., ≥365 days). The median volumetric and diametric growth rates were 1.71 cm3/year and 0.31 cm/year. The best feature using univariate analysis was wavelet-HLL_glcm_ldmn (area under the receiver operating characteristic [ROC] curve [AUC] of 0.80, p<0.0001), and with the random forest classifier, it was log-sigma-0-5-mm-3D_glszm_ZonePercentage (AUC: 79). The AUC of the ROC curves using multiple logistic regression was 0.74, and with the random forest classifier was 0.73. CONCLUSION: Radiomic features correlated with VDT and were able to predict the growth pattern of renal tumours in patients with VHL syndrome.

The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study.

Background: Spinal muscular atrophy (SMA) is a rare debilitating condition with a significant burden for patients and society. However, little is known about how it affects Saudi Arabia's population. The socioeconomic and medical characteristics of affected SMA patients and their caregivers are lacking. Purpose: This study aimed to describe the socioeconomic and medical characteristics of SMA patients and caregivers in Saudi Arabia. Patients and methods: A cross-sectional questionnaire-based study was conducted using snowball sampling. Assessment tools including EuroQol (EQ-5D-5L) and visual analog scale (EQ-VAS), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Costs for Patients Questionnaire (CoPaQ) were used to assess the quality of life (QoL), anxiety, depression, and out-of-pocket expenditures. Results: Sixty-four caregivers of SMA patients participated. Type I patients had higher sibling concordance, ICU hospitalization, and mechanical support needs. Type III patients had better QoL. Type I patients' caregivers had higher depression scores. Type III patients' caregivers had higher out-of-pocket expenditures. Forty-eight percent received supportive care, while others received SMA approved therapies. Conclusion: SMA imposes a significant socioeconomic burden on patients and caregivers, requiring more attention from the healthcare system. Access to innovative therapies varied across SMA types. Pre-marital screening and early detection are crucial to reduce disease incidence and ensure timely treatment.

A pre-anesthetic bolus of ketamine versus dexmedetomidine for prevention of postoperative delirium in elderly patients undergoing emergency surgery: a randomized, double-blinded, placebo-controlled study.

BACKGROUND: We aimed to evaluate whether a single dose of ketamine or dexmedetomidine before induction of general anesthesia could reduce the incidence of postoperative delirium (primary outcome) or cognitive dysfunction (secondary outcome) in elderly patients undergoing emergency surgery. PATIENTS AND METHODS: This randomized, double-blinded, placebo-controlled trial included 60 elderly patients who were scheduled for emergency surgery. The patients were randomly assigned into one of three groups (n = 20): group I received 0.9% normal saline, group II received 1 µg/kg dexmedetomidine, and group III received 1 mg/kg ketamine right before anesthesia induction. Patients were observed for three days after surgery and tested for postoperative delirium and cognitive dysfunction using the delirium observation screening scale and the mini-mental state examination score, respectively. RESULTS: The dexmedetomidine group had the lowest incidence of delirium (p = 0.001) and cognitive dysfunction (p = 0.006) compared to the ketamine and placebo groups. The multivariate logistic regression model revealed that dexmedetomidine reduced the incidence of postoperative delirium by 32% compared to placebo (reference) (OR = 0.684, 95% CI: 0.240-0.971, p = 0.025), whereas ketamine increased the risk by threefold (OR = 3.012, 95% CI: 1.185-9.681, p = 0.013). Furthermore, dexmedetomidine reduced the incidence of postoperative cognitive dysfunction by 62% (OR = 0.375, 95% CI: 0.091-0.543, p = 0.012), whereas ketamine increased the risk by 4.5 times (OR = 4.501, 95% CI: 1.161-8.817, p = 0.006). CONCLUSION: A single pre-anesthetic bolus of dexmedetomidine is a practical choice for preventing postoperative delirium in elderly patients undergoing emergency surgery. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Aswan University Hospital (approval number: aswu/548/7/2021; registration date: 06/07/2021) and registered on ClinicalTrials.gov (NCT05341154) (22/04/2022).

Treating maternal depression: understanding barriers and facilitators to repetitive transcranial magnetic stimulation treatment in Canada-a protocol.

Background: Peripartum depression (PPD) is a serious public health issue associated with severe and potentially long-term adverse maternal and child developmental outcomes. Suicide and overdose, for example, accounts for up to a third of maternal deaths. A current depression diagnosis with no active treatment is a common risk factor for maternal suicide. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment that has recently shown some promise as an effective treatment with limited side effects for PPD, but more research is required. This study aims to identify current barriers and potential facilitators for women with PPD accessing treatment in general, and rTMS specifically. Methods: This study will consist of two anonymous, self-administered surveys, focus groups, and interviews. A descriptive interpretative approach will be employed, and thematic analysis will be completed for the focus groups and interviews. Participants who are currently, or have previously experienced depressive symptoms, as well as health providers will be recruited. Our study will follow an equity, diversity, and inclusion (EDI) perspective on sex, gender, and ethnicity and the gender-based analysis plus (GBA+) analytic tool will be used. Both a qualitative and quantitative analysis of the data will be conducted. Discussion: We expect to find education and accessibility to be primary treatment barriers for persons with PPD. Identifying and addressing barriers is a critical first step towards the devolvement of initiatives that can work towards improving mental health in this population.

Characterization of human umbilical cord blood-derived mast cells using high-throughput expression profiling and next-generation knowledge discovery platforms.

Mast cells (MCs) are tissue-resident innate immune cells that express the high-affinity receptor for immunoglobulin E and are responsible for host defense and an array of diseases related to immune system. We aimed in this study to characterize the pathways and gene signatures of human cord blood-derived MCs (hCBMCs) in comparison to cells originating from CD34- progenitors using next-generation knowledge discovery methods. CD34+ cells were isolated from human umbilical cord blood using magnetic activated cell sorting and differentiated into MCs with rhIL-6 and rhSCF supplementation for 6-8 weeks. The purity of hCBMCs was analyzed by flow cytometry exhibiting the surface markers CD117+CD34-CD45-CD23-FcεR1αdim. Total RNA from hCBMCs and CD34- cells were isolated and hybridized using microarray. Differentially expressed genes were analyzed using iPathway Guide and Pre-Ranked Gene Set Enrichment Analysis. Next-generation knowledge discovery platforms revealed MC-specific gene signatures and molecular pathways enriched in hCBMCs and pertain the immunological response repertoire.

A new cirrhotic animal protocol combining carbon tetrachloride with methotrexate to address limitations of the currently used chemical-induced models.

Background: Chemically induced cirrhotic animal models are commonly used. However, they have limitations such as high mortalities and low yield of cirrhotic animals that limit their uses. Aims: To overcome limitations of the chemically induced cirrhotic animal model via combined administration of methotrexate (MTX) with CCl4 and decrease their commonly used doses depending on the proposed synergetic cirrhotic effect. Methods: Rats were divided into six groups: normal (4 weeks), normal (8 weeks), MTX, CCl4 (4 weeks), CCl4 (8 weeks), and MTX + CCl4 (4 weeks) groups. Animals' hepatic morphology and histopathological characterization were explored. Hepatic Bcl2 and NF-κB-p65 tissue contents were determined using the immunostaining technique, and hepatic tissue damage, oxidative status, and inflammatory status biochemical parameters were determined. Results: CCl4 + MTX combined administration produced prominent cirrhotic liver changes, further confirmed by a substantial increase in oxidative stress and inflammatory parameters, whereas mortalities were significantly lower than in other treated groups. Conclusion: The present study introduced a new model that can significantly improve the major limitations of chemically induced cirrhotic animal models with new pathological features that mimic human cirrhosis. Compared to other chemically induced methods, the present model can save time, cost, and animal suffering.

Fabrication of CAD-CAM custom-made bar clip for implant-supported overdentures using an intraoral scanner: A dental technique.

This article describes a digital technique for fabricating individually designed overdenture bar clips. The patient was scanned intraorally using a Medit i700 scanner; the custom clip was designed using the Blender software program and milled from polyoxymethylene blocks. This low-cost technique offers more available options compared with traditional clips, improving the management of retention loss.

Pharmacological Studies on the Antidiabetic, Antioxidant, and Antimicrobial Efficacies of Commiphora myrrha Resin in Streptozotocin-Induced Diabetes in Rats: A Preclinical Study.

Results: The aqueous extracts of MAE were phytochemically analyzed, and the results revealed the presence of high concentrations of tannins, sterols, and isoprenoids (terpenoids), while steroids and flavonoids were found in moderate concentrations. The plant extract showed promising inhibition of the growth of gram-positive and gram-negative pathogens. It also showed that MAE has potential antihyperglycemic and antioxidant activities. Microscopic examination of the pancreas showed degenerative changes and atrophy associated with dilatation of the exocrine ducts in the STZ-induced diabetic rats, while the treatment revealed that the Langerhans islets were close to normal without any histopathological alteration. Conclusion: The present results suggested that an aqueous extract of MAE could be considered an efficient antidiabetic, antioxidant, and antimicrobial treatment in the future.

Protective Effect of Vitamin D against Hepatic Molecular Apoptosis Caused by a High-Fat Diet in Rats.

The protective effects of vitamin D (VitD) in different diseases were studied. The liver is of great interest, especially with the presence of VitD receptors. A high-fat diet (HFD) is associated with many diseases, including liver injury. Consumption of saturated fatty acids triggers hepatic apoptosis and is associated with increased inflammation. We aimed in this study to investigate the protective effects of VitD on hepatic molecular apoptotic changes in response to an HFD in rats. Forty male Wistar albino rats were used and divided into four groups: control, HFD, control + VitD, and VitD-supplemented HFD (HFD + VitD) groups. After six months, the rats were sacrificed, and the livers were removed. RNA was extracted from liver tissues and used for the quantitative real-time RT-PCR of different genes: B-cell lymphoma/leukemia-2 (BCL2), BCL-2-associated X protein (Bax), Fas cell surface death receptor (FAS), FAS ligand (FASL), and tumor necrosis factor α (TNF-α). The results showed that an HFD increased the expression of the pro-apoptotic genes Bax, FAS, and FASL, and reduced the expression of the anti-apoptotic gene BCL2. Interestingly, a VitD-supplemented HFD significantly increased the BCL2 expression and decreased the expression of all pro-apoptotic genes and TNFα. In conclusion, VitD has a protective role against hepatic molecular apoptotic changes in response to an HFD.

Comparison of the efficacy of two doses of dexmedetomidine as an adjunct to levobupivacaine in infraclavicular brachial plexus block: prospective double-blinded randomized controlled trial.

BACKGROUND: This prospective, double-blind, randomized, controlled trial compared the efficacy of two dexmedetomidine doses (50 and 100-µg) combined with levobupivacaine on sensory block duration in infraclavicular brachial plexus block. We hypothesized that perineural dexmedetomidine would extend sensory block duration dose-dependently. METHODS: The study included 60 patients aged 20 to 60 years of both sex with an ASA I/II undergoing forearm and hand surgery. The patients were randomly assigned into three equal groups (n = 20) for ultrasound-guided infraclavicular brachial plexus block. The L group received 35-mL 0.5% levobupivacaine plus normal saline, the LD50 group received 35-mL 0.5% levobupivacaine plus 50-µg dexmedetomidine, and the LD100 group received 35-mL 0.5% levobupivacaine plus 100-µg dexmedetomidine. Patients were investigated for onset and duration of sensory blockade, time to first postoperative rescue analgesia, and the total 24-h postoperative morphine requirement. RESULTS: The LD100 group had a longer sensory block duration (15.55 ± 1.1 h; 95% confidence interval (CI), 15.04-16.06) than the LD50 group (12.8 ± 1.2 h; 95% CI, 12.24-13.36 h) (p < 0.001) or the L group (9.95 ± 1.05 h; 95% CI, 9.46-10.44 h) (p < 0.001). The LD100 group took longer to request postoperative rescue analgesia and required fewer postoperative morphine doses than the LD50 and L groups (P < 0.001). CONCLUSIONS: Sensory block duration was longer with perineural 100-µg dexmedetomidine as an adjunct to levobupivacaine than with 50-µg dexmedetomidine. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Aswan University Hospital (approval number: aswu/125/4/17) (date of registration: 04/04/2017). Furthermore, the trial was retrospectively registered at ClinicalTrial.gov (NCT04729868) with a verification date of January 2021.

A High Dose, Not Low Dose, of Vitamin D Ameliorates Insulin Resistance in Saudi Women.

Vitamin D has been traditionally seen to be mainly involved in the regulation of bone homeostasis. However, vitamin D has also been clinically linked to various diseases, including metabolic syndrome. The aim of this study was to examine the effect of low and high doses of a vitamin D supplement on the serum levels of 25(OH)D3 and insulin resistance. A total of 120 females were recruited in this study and supplemented weekly with 25,000 IU vitamin D or 50,000 IU vitamin D for three months. Anthropometric measurements were taken at the beginning of the study. Blood samples were collected at the beginning of the study to determine the baseline of the clinical variables and collected again after three months. Insulin resistance was measured using Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). After vitamin D supplementation, a non-significant increase was observed in the serum levels of 25(OH)D3 in the group treated with a low dose of vitamin D (LDVD) and a highly significant increase was seen in the group treated with a high dose of vitamin D (HDVD). In the group treated with a higher dose (HDVD), a significant improvement in insulin sensitivity was observed. The high dose of vitamin D (50,000 IU) supplementation was more effective in both correcting the blood levels of vitamin D and improving the sensitivity of insulin.

A Single Vitamin D3 Bolus Supplementation Improves Vitamin D Status and Reduces Proinflammatory Cytokines in Healthy Females.

Vitamin D deficiency is a global health problem that not only leads to metabolic bone disease but also to many other illnesses, most of which are associated with chronic inflammation. Thus, our aim was to investigate the safety and effectiveness of a single high dose of vitamin D3 (80,000 IU) on vitamin D status and proinflammatory cytokines such as interleukin (IL)6, IL8 and tumor necrosis factor (TNF) in healthy Saudi females. Fifty healthy females were recruited and orally supplemented with a single vitamin D3 bolus (80,000 IU). All participants donated fasting blood samples at baseline, one day and thirty days after supplementation. Serum 25-hydroxyvitamin D3 (25(OH)D3), IL6, IL8, TNF, calcium, phosphate, parathyroid hormone (PTH) and blood lipid levels were determined. Serum 25(OH)D3 significantly increased one and thirty days after supplementation when compared with baseline without causing elevation in calcium or phosphate or a decrease in PTH to abnormal levels. In contrast, the concentrations of the three representative proinflammatory cytokines decreased gradually until the end of the study period. In conclusion, a single high dose (80,000 IU) is effective in improving serum vitamin D status and reducing the concentration of the proinflammatory cytokines in a rapid and safe way in healthy females.

A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males.

Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4-) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4- or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.

Studying the Anticancer Effects of Thymoquinone on Breast Cancer Cells through Natural Killer Cell Activity.

Cancer immunotherapy is quickly growing and can now be viewed as the "fifth column" of cancer treatment. In addition, cancer immunotherapy has shown promising results with different kinds of cancers and may be used as a complementary therapy with various types of treatments. Thus, "immuno-oncology" is showing astounding advantages. However, one of the main challenges that face this type of therapy is that cancer cells can evade immune system elimination through different mechanisms. Many studies were done to overcome this issue including adding immune stimulants to generate synergistic effects or by genetically modifying NK cells themselves to be stronger and more resistant. Nigella sativa, also known as black cumin, is a well-known example of a widely applicable herbal medicine. It can effectively treat a variety of diseases, such as hypertension, diabetes, bronchitis, gastrointestinal upset, and cancer. The anticancer qualities of Nigella sativa appear to be mediated by an immune-modulatory effect that stimulates human natural killer (NK) cells. These are a type of lymphocyte and first line of defense against pathogens. Objectives. In this study, we investigated the therapeutic effect of thymoquinone, a major component of Nigella sativa, on the cytotoxic pathways of NK cells. Methods. NK cells were cultured with breast cancer cell line Michigan Cancer Foundation-7 (MCF-7); and were treated with Thymoquinone. The cytotoxicity of NK cells on cancer cells was measured. The cultured media were then collected and measured via enzyme-linked immunosorbent assay (ELISA) for concentrations of perforin, granzyme B and interferon-α (IFN-α). Results. The cytotoxic effect of NK cells on tumor cells was increased in the presence of thymoquinone, with an increased release of perforin, granzyme B, and IFN-α. Conclusion. Thymoquinone promotes the cytotoxic activity of NK cells against breast cancer MCF-7 cells.

Evaluation of miRNA 223/125a and COBLL1 Expressions and ROR-1 Levels as Reliable Markers in B- chronic Lymphocytic Leukemia.

BACKGROUND: miRNA 223 /125a and Cordon-bleu Protein Like 1 (COBLL1) are novel biomarkers that can predict prognosis and guide treatment decisions in patients with chronic lymphocytic leukemia (CLL). Also, there is a growing interest in CLL monitoring based on flow cytometry of receptor tyrosine kinase-like orphan receptor-1 (ROR-1).  Objective: This study aimed to evaluate the relationship between miRNA 223 /125a and COBLL1 expressions and ROR-1 expression in patients with CLL. Also, the study evaluated the relationship between the expression of these biomarkers with tumor staging and cancer progression. METHODS: Our study included 40 patients newly diagnosed with B-CLL. In peripheral blood (PB), miRNA 223/125a and COBLL1 expressions were detected by real-time polymerase chain reaction (real-time PCR) and ROR-1 percentage was detected by flow cytometry before and after treatment.  Results: High level of COBLL1 expression was statistically significantly associated with high ROR-1 percentage expression (P= 0.03). However, a high level of miRNA 223/125a expression was statistically significantly associated with low ROR-1 percentage expression (P=0.002). The sensitivity and specificity of ROR-1 as a predictor of high WBCs count after treatment were 96.6 and 81.1%, respectively. There was a statistically significant reduction of ROR-1 percentage after treatment compared to before treatment (P <0.001). CONCLUSION: ROR-1 percentage expression can be considered a possible prognostic predictor in CLL along with miRNA 223/125a and COBLL1 expressions. This can be explained by the significant correlation between ROR-1 and the studied molecular biomarkers; miRNA 223/125a and COBLL1. In addition, there was a significantly higher ROR-1 percentage in patients with higher WBC counts. Moreover, there was a significant reduction in ROR-1 percentage after treatment.

Genetic Association between Different Metabolic Variants in APOA5 and PLIN1 in Type 2 Diabetes Mellitus among the Western Saudi Population: Case-Control Study.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a high global incidence. Hypertriglyceridemia is a major risk factor for both cardiovascular disease and T2DM. In this study, we determined the allele and genotype frequencies of apolipoprotein A5 (APOA5) single nucleotide polymorphism (SNP) rs662799 and perilipin 1 (PLIN1) SNPs rs894160, rs6496589, and rs1052700 and evaluated their association with T2DM risk in western Saudis. Only rs6496589 was found to be significantly associated with T2DM risk. We determined the risk allele for each SNP based on relative risk, and found that the G allele of rs662799, T allele of rs894160, G allele of r6496589, and T allele of rs1052700 correlated with T2DM risk. The effect of each SNP on T2DM risk and five of its clinical phenotypes was explored using multiple logistic regression. We found significant correlations between the C/G and G/G genotypes of rs6496589 and T2DM risk in the unadjusted model, whereas G/G was the only genotype that correlated with the risk of T2DM in the adjusted model. There was no significant correlation between rs662799, rs894160, and rs1052700 genotypes and T2DM risk. In conclusion, we have identified novel risk alleles and genotypes that contribute to genetic risk for T2DM in the western Saudi population.

Peripheral blood CD26 positive leukemic stem cells as a possible diagnostic and prognostic marker in chronic myeloid leukemia.

Background: CD26 is expressed in all chronic myeloid leukemia (CML) patients. This study investigated the role of CD26+ LSCs in diagnosis and follow up of CML patients. Method: Flow cytometry was performed to evaluate CD26+ LSC in peripheral blood (PB) in CML patients. BCR-ABL1 transcript level measurement was performed using standard qRT-PCR technique. Results: CD26+ LSCs were significantly correlated with BCR-ABL1 transcript level at diagnosis and after three months of treatment. CD26+ LSCs also were significantly associated with the risk score after 12 months of treatment. Conclusion: CD26+ LSCs can be a useful marker in diagnosis and follow up of patients with CML.

Clinical significance of cytokeratin 19 and OCT4 as survival markers in non-metastatic and metastatic breast cancer patients.

Introduction: Cytokeratin 19 (CK19) is highly expressed in epithelial tumours such as breast cancer (BC). Octamer-binding transcription factor 4 (OCT4), a transcription factor of the POU (Pit-Oct-UNC) family, plays a criti-cal role in the self-renewal and maintenance of pluripotency of embryonic stem cells; therefore, it has been used as a promising CSC marker. Material and methods: CK19 was assessed in peripheral blood using flow-cytometric analysis while OCT4 was evaluated in breast tissue samples by immunohistochemistry from 70 patients (non-metastatic BC, meta-static BC, and non-malignant breast tumours). Results: CK19 and OCT4 were significantly associated with BC patients compared to control (p < 0.001). CK19 was detected in 38 patients with BC (62.2%); meanwhile, OCT4 was positive in 37 BC patients (60.6%). CK19 was positively associated with grade (p = 0.002), HER2 (p = 0.009), metastasis (p = 0.026), molecular subtypes and LN (p < 0.001), and stage (p = 0.001) while OCT4 expression was positively associated with BMI (p < 0.023), aggressive molecular subtype (p < 0.019), ER expression (p = 0.025), presence of LN metastases (p < 0.017), and distant metastasis (p < 0.018). A non-significant relation was found between the expression of CK19 and OCT (p = 0.291). The positive expression of CK19 and OCT4 was significantly and inversely associated with both 3-year OS and 3-year PFS. Conclusions: CK19 and OCT4 are associated with BC, so they can be considered as prognostic and predictive markers for poor OS and PFS in non-metastatic as well as metastatic BC patients.

A case of sudden mixed hearing loss in SARS-CoV-2.

The current global pandemic caused by coronavirus has uncovered multiple symptoms, including sudden hearing loss in either one or both ears, with different outcomes. We present a 68-year-old female with sudden onset bilateral hearing loss, fever, generalized body weakness, and gastrointestinal disturbances. She tested positive for severe acute respiratory syndrome coronavirus 2, was isolated, and was treated with a variety of medications for 5 days before being discharged home to self-isolate. The audiological assessment revealed both sensorineural and conductive hearing loss with a progressive favorable outcome on follow-up visits, with resolution occurring approximately 2 months after the onset. The majority of cases have reported sensorineural hearing loss. However, this case is one of the few that has reported mixed hearing loss. This report highlights an alternate clinical feature of the coronavirus that requires a comprehensive audiological examination by clinicians to ensure proper identification and treatment.