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Prostate cancer (PCa) is a malignancy originating from the epithelial cells of the prostate gland, strongly influenced by androgens, and is one of the most common cancers in men. Androgen deprivation therapy (ADT) is the primary treatment for prostate cancer. However, after prolonged ADT treatment, nearly all patients experience an increase in prostate-specific antigen (PSA) levels and tumor regrowth. The regrowth is primarily driven by the reactivation of androgen signaling pathways within the tumor cells, leading to the development of castration-resistant prostate cancer (CRPC). The overall survival for patients with CRPC is typically less than two years. The reactivation of androgen signaling after ADT is a key mechanism leading to the progression of CRPC. In particular, abnormal expression of androgen receptor (AR) family genes, particularly AKR1C3 and AR-V7, are beleived to play central roles in the emergence of CRPC. Beyond hormonal factors, various molecular mechanisms contribute to the development of castration resistance, such as genetic mutations and the role of the tumor microenvironment. Additionally, dysregulation of signaling pathways and interactions between tumor cells and the surrounding matrix furrher promote tumor survival and growth, even in the absence of androgens. Understanding these mechanisms is essential for developing more effective treatment strategies for CRPC.

Abstract Background Atrial fibrillation (AF) is characterized by the absence of p-waves on ECG and irregular rhythm. It often presents with palpitations either palpitations may occur acutely over a short period or intermittently over several years. Other cardinal symptoms of atrial fibrillation include fatigue, dyspnea, and lightheadedness; it is important however to note that most affected individuals are asymptomatic. Concurrently, sleep disorders such as obstructive sleep apnea (OSA), insomnia, narcolepsy, and circadian rhythm disorders which are a group of conditions associated with the body’s internal clock that affect the timing of sleep and alertness, are raising concerns due to their potential associations to arrhythmias. This review explores the bidirectional relationship between AF and sleep disorders, highlighting their implications for risk stratification and management strategies. Main body The narrative approach of this review synthesizes evidence from numerous studies obtained through meticulous literature searches. Specific sleep disorders with a bidirectional relationship with AF are the focus, with scrutiny on the prevalence of this connection. The examination delves into the pathophysiology of sleep-related autonomic dysregulation and inflammation, emphasizing potential management modalities. Various meta-analysis cohorts have highlighted a strong connection between sleep disorders and atrial fibrillation (AF). Patients with sleep disorders, especially OSA, have a higher likelihood of developing AF, and conversely, those with AF are more prone to sleep disorders. This impact is not limited to development, as sleep disorders also contribute to the progression of AF, with AF, in turn, negatively impacting sleep duration and quality. Sleep disorders may play an important role in atrial remodeling as well as electrophysiological abnormalities, rendering the atrial tissue more susceptible to arrhythmogenesis. The narrative review suggests that treating sleep disorders could not only improve sleep quality but also reduce risk factors associated with atrial fibrillation. The effective management of sleep disorders emerges as a potential challenge in preventing and treating atrial fibrillation. Conclusion In conclusion, this narrative study highlights the bidirectional relationship between sleep disorders and atrial fibrillation. There is a positive correlation, affecting the development, progression, and management of atrial fibrillation. The detrimental impact of sleep disorders on atrial remodeling and electrophysiological abnormalities underscores the significance of their diagnosis and treatment. Education about the importance of sleep and the benefits of sleep disorder treatment becomes imperative for patients with AF and sleep disorders.

Background: Using erupted components of a dental arch to estimate the width of the unerupted dental components are the basis of mixed dentition analysis. Non-radiographic mixed dentition analysis employs a regression equation to assess the width of the unerupted canines and premolars. In this study, we assessed the applicability of two non-radiographic methods of mixed dentition analysis in orthodontic patients. Methods: This cross-sectional research was carried out from the records of Ziauddin College of Dentistry, Department of Orthodontics, from November 2019 to March 2020. Pre-treatment dental casts of 120 subjects (60 males and 60 females) aged between 12-30 years undergoing orthodontic treatment were selected. The mesiodistal widths from the left first molar to the right first molar were measured using a digital Vernier caliper on pretreatment dental casts of both arches. Bachman’s and Tanaka-Johnston methods were applied to estimate the widths of canine and premolars. Gender dimorphism for actual and estimated values was assessed using an independent sample t-test, which compared the actual and estimated mesiodistal widths of canine and premolar. Results: The actual and estimated widths of canine and premolars reported 14.3±1.4 years for males and 13.4±1.2 years for females. In addition, the Bachman’s and Tanaka-Johnston method overestimated the actual widths of unerupted canine and premolar but the difference was statistically insignificant (p≥ 0.05) in both the genders. Conclusion: The two non-radiographic methods were reliable for mixed dentition analysis with minor overestimation between actual and estimated widths (ICC=0.79). This makes both the methods applicable interchangeably in regular clinical practice. Keywords: Mixed Dentition; Unerupted Teeth; Dental Models; Radiography.

In this study, we employed aqueous ginger extract as an eco-friendly approach for the synthesis of chitosan nanoparticles (CsNPs), silver nanoparticles (AgNPs), and chitosan/silver nanocomposites (Cs/AgNCs). Using spectroscopic and microscopic techniques, we thoroughly characterized the physicochemical properties of these nanomaterials, confirming their desirable attributes. The AgNPs displayed a spherical morphology with an average diameter of 19 nm, while the Cs/AgNCs exhibited a size of approximately 28 nm. To assess their antibacterial efficacy, we investigated the activity of both AgNPs and Cs/AgNCs against Gram-negative pathogenic bacteria. Remarkably, these nanomaterials demonstrated significant antibacterial properties. To further enhance their antibacterial capabilities, we conjugated the nanocomposite with tobramycin using Sulfo NHS and EDC, resulting in a four-fold increase in antibacterial activity compared to tobramycin alone. Moreover, we explored the ability of AgNPs, CsNPs, Cs/AgNCs, and Cs/AgNCs/tobramycin (Cs/AgNCs/tbn) to degrade DNA and generate reactive oxygen species (ROS) in the presence of Pseudomonas aeruginosa. Encouraging results were obtained, highlighting their potential applications in antimicrobial strategies. Furthermore, we conducted a comprehensive toxicity assessment of AgNPs, CsNPs, Cs/AgNCs, and Cs/AgNCs/tob using zebrafish embryos. The findings revealed low to moderate levels of toxicity for these nanomaterials, with Cs/AgNCs/tbn demonstrating no observable toxic effects. Our study demonstrates the immense potential of utilizing aqueous ginger extract as a green synthesis method to produce AgNPs and Cs/AgNCs with robust antibacterial properties and minimal toxicity. These findings pave the way for the development of innovative nanomaterials for various biomedical applications.

Abstract This study reports light energy harvesting characteristics of bismuth ferrite (BiFeO3) and BiFO3 doped with rare-earth metals such as neodymium (Nd), praseodymium (Pr), and gadolinium (Gd) dye solutions that were prepared by using the co-precipitation method. The structural, morphological, and optical properties of synthesized materials were studied, confirming that 5–50 nm sized synthesized particles have a well-developed and non-uniform grain size due to their amorphous nature. Moreover, the peaks of photoelectron emission for bare and doped BiFeO3 were observed in the visible region at around 490 nm, while the emission intensity of bare BiFeO3 was noticed to be lower than that of doped materials. Photoanodes were prepared with the paste of the synthesized sample and then assembled to make a solar cell. The natural and synthetic dye solutions of Mentha, Actinidia deliciosa, and green malachite, respectively, were prepared in which the photoanodes were immersed to analyze the photoconversion efficiency of the assembled dye-synthesized solar cells. The power conversion efficiency of fabricated DSSCs, which was confirmed from the I–V curve, is in the range from 0.84 to 2.15%. This study confirms that mint (Mentha) dye and Nd-doped BiFeO3 materials were found to be the most efficient sensitizer and photoanode materials among all the sensitizers and photoanodes tested.

Multi-drug resistant bacteria sometimes known as "superbugs" developed through overuse and misuse of antibiotics are determined to be sensitive to small concentrations of silver nanoparticles. Various methods and sources are under investigation for the safe and efficient synthesis of silver nanoparticles having effective antibacterial activity even at low concentrations. We used a medicinal plant named Salvia moorcroftiana to extract phytochemicals with antibacterial, antioxidant, and reducing properties. Three types of solvents; from polar to nonpolar, i.e., water, dimethyl sulfoxide (DMSO), and hexane, were used to extract the plant as a whole and as well as in fractions. The biosynthesized silver nanoparticles in all extracts (except hexane-based extract) were spherical, smaller than 20 nm, polydispersed (PDI ranging between 0.2 and 0.5), and stable with repulsive force of action (average zeta value = -18.55±1.17). The tested bacterial strains i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis were found to be sensitive to even small concentrations of Ag-NPs, especially P. aeruginosa. The antibacterial effect of these Ag-NPs was associated with their ability to generate reactive oxygen species. DMSO (in fraction) could efficiently extract antibacterial phytochemicals and showed activity against MDR bacteria (inhibition zone = 11-12 mm). Thus, the antibacterial activity of fractionated DMSO extract was comparable to that of Ag-NPs because it contained phytochemicals having solid antibacterial potential. Furthermore, Ag-NPs synthesized from this extract owned superior antibacterial activity. However, whole aqueous extract-based Ag-NPs MIC was least (7-32 μg/mL) as compared to others.

Researchers are now looking to nanomaterials to fight serious infectious diseases that cause outbreaks and even pandemics. SARS-CoV-2 brought chaos to almost every walk of life in the past 2 years and has challenged every available treatment method. Although vaccines were developed in no time against it, the most pressing issue was the emergence of variants of concern arising because of the rapidly evolving viral strains. The higher pathogenicity and, in turn, the higher mortality rate of infections caused by these variants renders the existing vaccines less effective and the effort to produce further vaccines a costly endeavor. While several techniques, such as immunotherapy and repurposed pharmaceutical research, are being studied to minimize viral infection, the fundamentals of nanotechnology must also be considered to enhance the anti-SARS-CoV-2 efforts. For instance, silver nanoparticles (AgNPs) have been applied against SARS-CoV-2 effectively. Similarly, nanomaterials have been tested in masks, gloves, and disinfectants to aid in controlling SARS-CoV-2. Nanotechnology has also contributed to diagnoses such as rapid and accurate detection and treatment such as the delivery of mRNA vaccines and other antiviral agents into the body. The development of polymeric nanoparticles has been dubbed a strategy of choice over traditional drugs because of their tunable release kinetics, specificity, and multimodal drug composition. Our article explores the potential of nanomaterials in managing the variants of concern. This will be achieved by highlighting the inherent ability of nanomaterials to act against the virus on fronts such as inhibition of SARS-CoV-2 entry, inhibition of RNA replication in SARS-CoV-2, and finally, inhibition of their release. In this review, a detailed discussion on the potential of nanomaterials in these areas will be tallied with their potential against the current and emerging future variants of concern.

In this study, Fe2O3 powder was synthesized using the co-precipitation method from scrap iron, which was then treated with varying concentrations of copper. Afterwards, the modified Fe2O3 was reinforced in the PVC matrix by using the solution-casting method to synthesize PVC composite films, which were subjected to a UV-visible spectrophotometer, a Fourier transform infrared spectrophotometer, an X-ray diffractometer, and a thermal gravimetric analyzer to evaluate the optical, chemical, structural, and thermal properties. FTIR analysis reveals the formation of the composite through vibrational bands pertaining to both components present, whereas no significant changes in the XRD patterns of PVC were observed after the doping of modified iron oxide, which reveals the compatibility of fillers with the PVC matrix. The optical properties of the copper-doped iron oxide-PVC composites, including absorbance, refractive index, urbach energy, and optical as well as electrical conductivity are measured, and show an increase in optical activity when compared to the pure PVC compound. Moreover, the increased thermal stability of the synthesized composite was also observed and compared with conventional compounds, which, in accordance with all the other mentioned properties, makes the copper-dopped iron oxide-PVC composite an effective material for electronic, photonic, and optical device applications.

Objectives: To find out the breakfast practices and factors associated with skipping breakfast in medical students of Karachi. Material and Methods: This is is a Descriptive cross-sectional study, conducted in public sector medical institutes of Karachi from 1st January to 31st March 2019. 382 medical students were enrolled after taking informed consent. Data were collected from included students of this study, who had an age of 18 to 24 years, and all other students having a history of lactose intolerance, anorexia nervosa, and food allergies were excluded from the study. Breakfast outcome (practices and skip or omit of breakfast) data were collected by self-made structured questionnaire and anthropometric data (height, weight) were recorded. Body mass index was calculated as weight (Kg)/height (m)2. Collected data were analyzed by using the Statistical Package for social sciences version 22. Results: The mean age and mean Body mass index of students were 20.83±1.54 and 15.53±3.5 respectively. The study outcomes on breakfast practices, among participants, showed 81.4% were taken breakfast, breakfast skippers were 18.6%, gender-based comparison between breakfast-skippers males (14.1%): females (85.9%) were respectively and shortage of time is the main factor (56.3%) associated with breakfast skipping in students. There is no significant (p>0.05) association between Gender-based comparison between factors associated with breakfast skipping. Conclusion: The breakfast skippers were 18.6%, and among the main factors associated with skipping of breakfast was a shortage of time (56.3%).

Background: Aspirin (acetylsalicylic acid) is commonly prescribed to patients with a history of myocardial infarction (MI) or occlusive vascular events (e.g., stroke). Due to the complications associated with failure to follow aspirin usage guidelines, determining predictors of aspirin noncompliance in these patient populations is of clinical value and may help prevent poor outcomes. Methods: This cross-sectional study of all patients with a previously diagnosed MI was conducted over a period of 3 months from May 2015 to July 2015 at a government-based hospital in Karachi, Pakistan. Patients were administered a questionnaire that comprised two parts. Part A was designed to measure sociodemographic data including age, gender, and marital status. Part B determined whether the patient was counseled on aspirin significance, and dosage recommendation, and was participating in cardiac rehabilitation therapy. Results: A total of 456 patients included in the study. Of them, 298 (66.7%) were males. The average age was 59 (standard deviation 11) years. The outcome from univariate logistic regression revealed that with 1 year increase of age, the usage of low dose of aspirin was significantly decreased by 2%. Patients with higher education attributed a significantly different effect on the usage of aspirin. Marital status divulged no significant association with the use of different doses of aspirin. The role of rehabilitation had no effect when adjusted for age and level of education. Conclusion: Post-MI patients with higher education level and undergoing rehabilitative therapy are more likely to take low-dose aspirin as compared to those who failed to have these attributes. There is a need for carrying out further work to confirm these findings and expand our recommendations, particularly the sensitive issue regarding adequate doctor counseling among these high-risk patients.

Pulmonary capillary hemangiomatosis (PCH) is a rare and controversial entity that is known to be a cause of pulmonary hypertension and is microscopically characterized by proliferation of dilated capillary-sized channels along and in the alveolar walls. Clinically, it is mostly seen in adults. Clinical features are characterized by nonspecific findings such as shortness of breath, cough, chest pain, and fatigue. It can be clinically indistinguishable from pre-capillary pulmonary arterial hypertension disorders such as primary pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. However, the diagnostic distinction, which usually requires a multidisciplinary approach, is crucial in order to avoid inappropriate treatment with vasodilator medications usually used for PAH treatment. Prognosis of PCH remains poor with lung transplant being the only definitive treatment. We report an autopsy case of pulmonary capillary hemangiomatosis unmasked at autopsy that was treated with a prostacyclin analog, usually contraindicated in such patients. We emphasize that this entity should always be on the differential diagnosis in a patient with pulmonary hypertension and requires great vigilance on the part of the clinician, radiologist and pathologist to make the diagnosis and guide appropriate management.

Aim of the Study: Coronary artery bypass graft surgery is the gold standard for the treatment of multivessel and left main coronary artery disease. However, there is considerable debate that whether left internal mammary artery (IMA) should be taken as pedicled or skeletonized. This study was conducted to assess the difference in blood flow after the application of topical vasodilator in skeletonized and pedicled IMA. Materials and Methods: In this study, each patient underwent either skeletonized (n = 25) or pedicled IMA harvesting (n = 25). The type of graft on each individual patient was decided randomly. Intraoperative variables such as conduit length and blood flow were measured by the surgeon himself. The length of the grafted IMA was carefully determined in vivo, with the proximal and distal ends attached, from the first rib to IMA divergence. The IMA flow was measured on two separate occasions, before and after application of topical vasodilator. Known cases of subclavian artery stenosis and previous sternal radiation were excluded from the study. Results: The blood flow before the application of topical vasodilator was similar in both the groups (P = 0.227). However, the flow was significantly less in pedicled than skeletonized IMA after application of vasodilator (P < 0.0001). Similarly, the length of skeletonized graft was significantly higher than the length of pedicled graft (P < 0.0001). Conclusion: Our study signifies that skeletonization of IMA results in increased graft length and blood flow after the application of topical vasodilator. However, we recommend that long-term clinical trials should be conducted to fully determine long-term patency rates of skeletonized IMA.

Interleukin-21 (IL-21), a T- cell-derived cytokine, is a signaling molecule secreted by a subpopulation of T cells called follicular T helper (Tfh) cells. Studies have proved that IL-21 co-stimulates T cell proliferation by mediating enhanced T cell viability. This is done when IL-21 binds to its receptor, activating the phosphatidylinositol-3 kinase (PI-3K) signaling pathway and inducing B-cell Lymphoma-2 (Bcl-2) expression. Besides the B and T cells, IL-21 also regulates several Natural Killer (NK) cell functions. Due to its multi-faceted effects on different receptors, IL-21 has been used in multiple diseases. However, it was recently found that IL-21 had potent effect on various viruses including Lymphocytic Choriomeningitis Virus (LCMV), influenza virus and Vesicular Stomatitis Virus (VSV). The study proved that both B and CD4+ T cells need IL-21 signaling for generating long-term humoural immunity by generating long-lived plasma cells, thus, highlighting the importance of IL-21 in humoural immunity to viruses. These findings highlight how IL-21 could be important in the development of antiviral vaccines and vaccines for other potential life-threatening diseases leading scientists to design future vaccines to incorporate IL-21 directly or to use the ability to stimulate IL-21 as a gauge of vaccine activity. It is the need of the hour to go for larger studies which will be needed to better elucidate the cause and effect relationship and to demonstrate the effect size. It may possibly yield appreciable results in the future for untreatable diseases like HIV/AIDS.

Introduction: Depression is a global issue prevalent among developing countries like Pakistan as compared to developed countries. We conducted a study to assess the prevalence and identify the significant predictors of depression in an elite urban settlement in Karachi, Pakistan. Materials and Methods: This cross-sectional study was done in the elitist residential area of Karachi; Defence Housing Authority (DHA). Four hundred and twenty three participants were included by going to their residences. Self-administered questionnaires were handed out after taking informed consent. Level of depression was assessed by Patient Health Questionnaire (PHQ-9). Data were entered and analysed in Predictive Analytical Software v. 18.0. Results: The mean and median total score of the scale were 5.9 ± 5.4 and 4 (7) respectively with minimum score 0 and maximum 27. In this sequence, 139 (32.86%) respondents were identified to be depressed. It was found that females were slight more depressed than males (p = 0.063). Regression Model identified only gender and marital status as significant predictors of depression. Having a female gender increased 0.658 times chance of being depressed (p = 0.047). Unmarried person had 0.296 times more likely to be depressed (p = 0.019). Boredom was considered as significant factor of depression by the participants (p< 0.0001). Odds ratio signified depression occurred 0.310 times more if one was bored. Discussion: Depression should be considered as a major public health issue for the city. Public awareness should be done in all parts of the city in an attempt to reduce depression especially among the female gender.