Design, Synthesis and Molecular Modeling of Pyrazolo[1,5-]pyrimidine Derivatives as Dual Inhibitors of CDK2 and TRKA Kinases with Antiproliferative Activity.

Background: The increasing prevalence of drug resistance in cancer therapy underscores the urgent need for novel therapeutic approaches. Dual enzyme inhibitors, targeting critical kinases such as CDK2 and TRKA, represent a promising strategy. The goal of this investigation was to design, synthesize, and evaluate a set of pyrazolo[1,5-]pyrimidine derivatives for their dual inhibition potential toward CDK2 and TRKA kinases, along with their potential antiproliferative against cancer cell lines.

Novel isatin conjugates endowed with analgesic and anti-inflammatory properties: design, synthesis and biological evaluation.

Aims: This study aimed to develop novel molecular hybrid conjugates integrating isatin, rhodanine, and phthalimide pharmacophores to create effective analgesic and anti-inflammatory agents with improved safety profiles over existing treatments.

Materials & Methods: A series of hybrid conjugates () were synthesized and evaluated through in vitro and in vivo biological assays. The most promising compound, , underwent extensive pharmacological and toxicological evaluations.

High-risk human papillomavirus infection and cervical cytopathology: relationship with cervical nitric oxide levels.

Background: Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia.

Chronic Caffeine Consumption, Alone or Combined with Agomelatine or Quetiapine, Reduces the Maximum EEG Peak, As Linked to Cortical Neurodegeneration, Ovarian Estrogen Receptor Alpha, and Melatonin Receptor 2.

Rationale: Evidence of the effects of chronic caffeine (CAFF)-containing beverages, alone or in combination with agomelatine (AGO) or quetiapine (QUET), on electroencephalography (EEG), which is relevant to cognition, epileptogenesis, and ovarian function, remains lacking. Estrogenic, adenosinergic, and melatonergic signaling is possibly linked to the dynamics of these substances.

Objectives: The brain and ovarian effects of CAFF were compared with those of AGO + CAFF and QUET + CAFF.

Identification of thienopyrimidine derivatives tethered with sulfonamide and other moieties as carbonic anhydrase inhibitors: Design, synthesis and anti-proliferative activity.

Eighteen novel compounds harboring the privileged thienopyrimidine scaffold (5a-q, and 6a),were designed based on molecular hybridization strategy. These compounds were synthesized and tested for their inhibitory activity against four different carbonic anhydrase isoforms: CA I, II, IX, and XII. Microwave and conventional techniques were applied for their synthesis.

Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives.

Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole and thiazole-based compounds were designed, synthesized, and evaluated as potential Bcl-2 inhibitors with anti-proliferative activity.

Biogenic Zinc oxide nanoparticles from : toward improved antioxidant, antibacterial, and anticancer activities.

Biogenic Zinc oxide (ZnO) nanoparticles (NPs) were synthesized from () plant extract. Structural analysis confirms the successful synthesis of biogenic zinc oxide NPs from . extract.

Feasibility of linking universal child and family healthcare and financial counselling: findings from the Australian Healthier Wealthier Families (HWF) mixed-methods study.

Objectives: 'Healthier Wealthier Families' (HWF) seeks to reduce financial hardship in the early years by embedding a referral pathway between Australia's universal child and family health (CFH) services and financial counselling. This pilot study investigated the feasibility and short-term impacts of HWF, adapted from a successful Scottish initiative.

Methods: Setting: CFH services in five sites across two states, coinciding with the COVID-19 pandemic.

Serum level of MicroRNA 15a and interleukin 6 as biomarkers for sepsis in critically Ill Patients.

This study intended to evaluate the diagnostic efficacy of serum interleukin-6 (IL-6) and serum expression level of microRNA 15a (miRNA 15a) in sepsis patients admitted to the medical intensive care unit (ICU), and to correlate the results with the outcome of patients. This observational case-control study, was done from January 2022 to June 2022, included 75 adult ICU patients ≥18 years old, divided into 2 groups. Group 1: included 38 adults, critically ill sepsis patients and Group 2 (control group), included 37 adults, non-sepsis patients admitted to the ICU.

Alpha NSW: What would it take to create a state-wide paediatric population-level learning health system?

Background: The health and well-being of children in the first 2000 days has a lasting effect on educational achievement and long-term chronic disease in later life. However, the lack of integration between high-quality data, analytic capacity and timely health improvement initiatives means practitioners, service leaders and policymakers cannot use data effectively to plan and evaluate early intervention services and monitor high-level health outcomes.

Objective: Our exploratory study aimed to develop an in-depth understanding of the system and clinical requirements of a state-wide paediatric learning health system (LHS) that uses routinely collected data to not only identify where the inequities and variation in care are, but also to also inform service development and delivery where it is needed most.

Design, synthesis, and biological evaluation with molecular dynamics study of novel pyrazolo[3,4-]pyrimidine derivatives as anti-cancer agents.

In continuation of our efforts to discover new structural chemotypes with significant chemotherapeutic activities, a novel series of pyrazolo[3,4-]pyrimidine-based compounds linked to a piperazine ring, bearing different aromatic moieties, through different linkages was designed and synthesized as FLT3 inhibitors. All of the newly synthesized compounds were evaluated for their cytotoxicity on 60-NCI cell lines. Compounds with the piperazine acetamide linkage XIIa-f & XVI exhibited a remarkable anticancer activity among all of the tested compounds, especially against non-small cell lung cancer, melanoma, leukemia and renal cancer models.

Protective Potential of (Falc.) Lipsch. Roots against Cyclophosphamide-Induced Pulmonary Injury in Rats and Its In Vitro Antiviral Effect.

Diseases and infections of the respiratory tract are common global causes of morbidity and mortality. Our study attempts to elucidate a novel remedy for respiratory ailments, in addition to identifying and quantifying the metabolites of root extract (SCRE) using HPLC. Then, in vitro antiviral and in vivo lung protective effects were elucidated.

A Fluorescence-Based Assay to Probe Inhibitory Effect of Fructose Mimics on GLUT5 Transport in Breast Cancer Cells.

Rapid cell division and reprogramming of energy metabolism are two crucial hallmarks of cancer cells. In humans, hexose trafficking into cancer cells is mainly mediated through a family of glucose transporters (GLUTs), which are facilitative transmembrane hexose transporter proteins. In several breast cancers, fructose can functionally substitute glucose as an alternative energy supply supporting rapid proliferation.

New NSAID Conjugates as Potent and Selective COX-2 Inhibitors: Synthesis, Molecular Modeling and Biological Investigation.

New sets of ibuprofen and indomethacin conjugates comprising triazolyl heterocycle were synthesized via click chemistry, adopting an optimized protocol through the molecular hybridization approach affording the targeted agents in good yields. The new non-steroidal anti-inflammatory drug (NSAID) conjugates were designed and synthesized and could be considered as potential drug candidates for the treatment of pain and inflammation. The anti-inflammatory properties were investigated for all the synthesized conjugates.

PTEN rs701848 Polymorphism is Associated with Trastuzumab Resistance in HER2-positive Metastatic Breast Cancer and Predicts Progression-free Survival.

Background: Trastuzumab is an effective therapeutic approach for HER2-positive metastatic breast cancer (BC). However, a considerable number of patients develop resistance along the course of the disease. PTEN rs701848 polymorphisms are associated with an increased risk of developing cancer and have a potential role in predicting drug resistance.

Offshore detention: cross-sectional analysis of the health of children and young people seeking asylum in Australia.

Objective: To describe the health and well-being of children and young people (CYP) seeking asylum subjected to Australia's immigration policy of indefinite mandatory detention on Nauru.

Design: Cross-sectional analysis of a cohort of CYP seeking asylum.

Setting: Australian paediatric clinicians from 10 health services completed detailed health assessments around the time of transfer from Nauru, mostly to Australia.

Cardiac autonomic neuropathy linked to left ventricular dysfunction in type 1 diabetic patients.

Unlabelled: Type 1 diabetes is a major cause of cardiovascular death; diabetic cardiomyopathy (DCM) is the most important cause of mortality among diabetic patients. There is an increasing body of evidence that the most important inducer of DCM is microvascular injury. The aim of this study is to establish a potential relationship between low frequency/high frequency (LF/HF) ratio and DCM and to set a possible predictive cutoff of LF:HF ratio for early detection of DCM.

Study protocol for a real-world evaluation of an integrated child and family health hub for migrant and refugee women.

Introduction: Continuity of child and family healthcare is vital for optimal child health and development for developmentally vulnerable children. Migrant and refugee communities are often at-risk of poor health outcomes, facing barriers to health service attendance including cultural, language, limited health literacy, discrimination and unmet psychosocial needs. 'Integrated health-social care hubs' are physical hubs where health and social services are co-located, with shared referral pathways and care navigation.

Connecting Healthcare with Income Maximisation Services: A Systematic Review on the Health, Wellbeing and Financial Impacts for Families with Young Children.

Financial counselling and income-maximisation services have the potential to reduce financial hardship and its associated burdens on health and wellbeing in High Income Countries. However, referrals to financial counselling services are not systematically integrated into existing health service platforms, thus limiting our ability to identify and link families who might be experiencing financial hardship. Review evidence on this is scarce.

'Smiles and laughter and all those really great things': Nurses' perceptions of good experiences of care for inpatient children and young people with intellectual disability.

Aim: To understand what constitutes a good experience of care for inpatient children and young people with intellectual disability as perceived by nursing staff.

Design: Interpretive qualitative study.

Methods: Focus groups with clinical nursing staff from speciality neurological/neurosurgical and adolescent medicine wards across two specialist tertiary children's hospitals in Australia were conducted between March and May 2021.

The Prevalence and Associated Factors of Depressive Symptoms Among Medical Students in Bangladesh During the COVID-19 Pandemic: A Cross-Sectional Pilot Study.

Background: Whilst very limited studies have demonstrated a correlation between the COVID-19 pandemic and depressive symptoms amongst Bangladeshi medical students, the prevalence and associated factors of depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9) remains widely unknown.

Objective: The study aimed to investigate the prevalence and factors associated with depression symptoms among Bangladeshi medical students during the COVID-19 pandemic lockdown period.

Method: In this web-based cross-sectional pilot study, medical students' data was collected using the Google Forms web survey platform after obtaining electronic informed consent.

Design and synthesis of ibuprofen-quinoline conjugates as potential anti-inflammatory and analgesic drug candidates.

A new set of ibuprofen-quinoline conjugates comprising quinolinyl heterocycle and ibuprofen moieties linked by an alkyl chain were synthesized in good yields utilizing an optimized reaction procedure in a molecular hybridization approach to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. The synthesized conjugates were screened for their anti-inflammatory, and ulcerogenic properties. Several conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test without showing any ulcerogenic liability.

Connecting healthcare with income maximisation services, and their financial, health and well-being impacts for families with young children: a systematic review protocol.

Introduction: Poverty has far-reaching and detrimental effects on children's physical and mental health, across all geographies. Financial advice and income-maximisation services can provide a promising opportunity for shifting the physical and mental health burdens that commonly occur with financial hardship, yet awareness of these services is limited, and referrals are not systematically integrated into existing healthcare service platforms. We aim to map and synthesise evidence on the impact of healthcare-income maximisation models of care for families of children aged 0-5 years in high-income countries on family finances, parent/caregiver(s) or children's health and well-being.

Antibiotic Use for Febrile Illness among Under-5 Children in Bangladesh: A Nationally Representative Sample Survey.

Fever in children under five years of age is a common and predominantly self-limiting sign of illness. However, in low- and middle-income countries, antibiotics are frequently used in febrile children, although these children may not benefit from antibiotics. In this study, we explored the prevalence of, and factors associated with, antibiotic use in children under five years old with febrile illness in Bangladesh.