Pharmacological Evaluation of an Advanced Formulation of Curcumin to Prevent Breast Cancer Bone Metastases

Curcumin has low plasma concentration due to low water solubility and instability. We have formulated alendronate-conjugated curcumin nanoparticles (Aln-Cur-NPs) for the targeted delivery of the drug to the bone. This project aims to investigate the in vitro biological effects of Aln-Cur-NPs that are developed to prevent breast cancer bone metastasis. The loading capacity was found to be 4% and 5.7% for Aln-Cur-NP and Cur-NP, respectively. A significantly higher antitumor activity was observed for Aln-Cur-NP compared to Cur-NP with IC50 values of 13.9, 22.2 and 7.7 µg/mL for MCF-7, MDA-MB-231 and SK-BR-3, respectively. This study showed the enhanced anticancer activity of curcumin nanoparticles conjugated with alendronate compared to Cur-NPs, which strongly supports the synergistic effect of curcumin/bisphosphonates combination considering the similar amount of uptaken curcumin by the cancer cells for both nanoparticle formulations. The impact of nanoparticles on the viability of MDA-MB-231 cells was also investigated using recording time lapse image technology by IncuCyte® over two days. It was demonstrated that the uptake of raw curcumin was much less, and it precipitated outside the cells while, curcumin encapsulated in nanoparticles was effectively uptaken by the cancer cells. The qualitative analysis of confocal images showed higher uptake for Aln-Cur-NPs compared to raw curcumin (p ˂0.0001) and no uptake for the untreated (PBS) control. The effect of our Nanoparticles on the release of PTHrP was determined by PTHrP ELISA assay for quantitative measurement of human PTHrP concentration released by MDA-MB-231 cells. The results suggested the possibility of reducing osteolytic activity of the cancer cells in bone metastasis. These preliminary data suggest Aln-Cur-NPs can offer promises in preventing and treating breast cancer bone metastases

Evaluation of hepatoprotective effect of chloroform and methanol extracts of <i>Opuntia monacantha</i> in paracetamol-induced hepatotoxicity in rabbits

The chloroform and methanol extracts of Opuntia monacantha were studied for its hepatoprotective effect against paracetamol induced liver damage in rabbits. Results proved that both extracts at 200, 400 and 600 mg/kg body weight in one week protocol showed significant (p<0.001) hepatoprotective activity by reducing the magnitude of liver markers including alanine aminotransferase, aspartate aminotransferase, alkaline phasphatase and total bilirubin levels. The results were supported by histopathological studies of liver tissue. Chemical analysis of O. monacantha indicated the presence of alkaloids, tannins, saponins, flavonoids and  polysaccharides and its hepato-protective potential may be due to the presence of flavonoids. Its is concluded that 600 mg/kg is the potent dose of both extracts of O. monacantha as hepatoprotective plant

A Sociological Study about the Adoption of Contraception Methods and Their Effects on the Married Females’ Health in Rural Areas of Tehsil Dera Ghazi Khan-Pakistan

Population is growing rapidly &amp; adoption of FP has been neglected by Govt. of Pakistan due to lack of services, awareness and education, traditional believes, employment &amp; misconception. Mostly people think that the use of contraception methods is against the nature and Islam and is also harmful for health. So present study was designed in rural areas of Tehsil Dera Ghazi Khan in 2013 to investigate the knowledge level, adoption of contraception as well as to perceived positive and negative effects of contraception methods on the health of married females in rural community. 160 rural married females were interviewed to find out their demographic features; utilization of contraception and its side effects on their health in tehsil Dera Ghazi Khan. The data was analyzed by using Uni-variate (frequency distribution and percentage) and Bi-variate analysis (Chi square and Gamma Statistics) was carried out. Predominating age categories were &lt;15 and 16-20 years, 45.6% were illiterate, and 55.6% had good mutual understandings. More than one fifth (26.2%) had 1-2 pregnancies, 59.4% had sometimes heard about contraceptive methods while 84.4% had favorable attitude towards adoption of contraception methods. Whereas 58.1% had sometimes used contraceptive methods, 31.9% got information about contraceptive methods from relatives. In adoption of different contraception methods during the life span, respondents reported both types i.e. modern injections (60.6%), spermicides (50.6%), and in traditional methods i.e. withdrawal (6.2%); adoption of herbs (5.7%) and 44.4% had faced positive effects while 19.4% faced negative effects whereas 36.2% of the respondents had both type of effects (positive/ negative) on their health after the adoption of FP methods during reproductive span. Bi-variate analysis showed positive relationship between desired of family size and utilization of contraception, Freedom of decision making vs utilization of contraception methods and mutual understanding of spouse vs adoption of contraception method. There was a need to bring positive change in societal attitude for the utilization of family planning. Keywords: FP Methods, Contraception adoption, effects, Religious opinion, Decision making, Rural Females, Socio-economic statu

Comprehensive human health risk assessment of heavy metal contamination in urban soils: insights from selected metropolitan zones

Introduction: This study aims to assess the extent of heavy metal contamination in urban soils in sixteen selected cities of Pakistan, encompassing the elements cadmium (Cd), lead (Pb), cobalt (Co), zinc (Zn), chromium (Cr), nickel (Ni), manganese (Mn), iron (Fe), and copper (Cu).Methods: The data utilized for this study was collected from online literature during the period 2005 to 2019. This study investigated potential threats to human health through a comprehensive analysis, considering standards such as Enrichment Factors (EF), Geo-accumulation Indices (Igeo), and Human Health Risk Assessment (HHRA).Results: Geo-accumulation Index results indicated varied risk intensities, with Cu, Pb, Co, Mn, and Fe exhibiting “no pollution” levels, while other elements show “moderate to extremely contaminated” values. EF analysis provided evidence of heavy metal presence, revealing a spectrum from “no pollution” to “moderate to extremely high pollution” for Cd, Zn, Cr, Ni, and Cu. The health risk assessment identified both carcinogenic and non-carcinogenic dangers for adults and children.Discussion: These findings highlighted the substantial contribution of identified sources such as industrial processes, vehicular emissions, sewage sludge, urban flooding, and the production and use of metallic materials that have elevated heavy metal levels in the urban soils. This established the link between urban industrial zones, human health, and long-term economic sustainability. This study provides essential guidance for decision makers to develop effective strategies for soil remediation, enhanced industrial practices, and regulatory measures to address heavy metal contamination in urban areas, ensuring the wellbeing and sustainable environmental quality management in cities

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The Salient Stylistic Features of Majeed Amjad

&nbsp;Stylistics is defined as the study of style, Phonetics, Morphology, Syntax and Semantics as tools of criticism, relatively modern sources of discovering hidden meaning and layers of expression. According Nills Erik Enkvist the style of a poet is analyzed through Language he used. He suggests this analysis upon the basis of two aspects of style. (1) Choice between alternative expressions. (2) Derivation from the norm. Majeed Amjad having unique style and poetics must be analyzed on modern parameters of stylistics. Majeed Amjad has his own distinguish style among the urdu poets. He carved out a new style other. He experimented with metrical forms and rhythms. Stylistic analysis of Amjad&rsquo;s poetry Lenlighteen the individual traits of his style. Stylistics choice of lexical items, phonetics, Morphological choices and grammatical sources shows distinctive features of his poetics and literary style

The Salient Stylistic Features of Majeed Amjad

&nbsp;Stylistics is defined as the study of style, Phonetics, Morphology, Syntax and Semantics as tools of criticism, relatively modern sources of discovering hidden meaning and layers of expression. According Nills Erik Enkvist the style of a poet is analyzed through Language he used. He suggests this analysis upon the basis of two aspects of style. (1) Choice between alternative expressions. (2) Derivation from the norm. Majeed Amjad having unique style and poetics must be analyzed on modern parameters of stylistics. Majeed Amjad has his own distinguish style among the urdu poets. He carved out a new style other. He experimented with metrical forms and rhythms. Stylistic analysis of Amjad&rsquo;s poetry Lenlighteen the individual traits of his style. Stylistics choice of lexical items, phonetics, Morphological choices and grammatical sources shows distinctive features of his poetics and literary style

The Salient Stylistic Features of Majeed Amjad

&nbsp;Stylistics is defined as the study of style, Phonetics, Morphology, Syntax and Semantics as tools of criticism, relatively modern sources of discovering hidden meaning and layers of expression. According Nills Erik Enkvist the style of a poet is analyzed through Language he used. He suggests this analysis upon the basis of two aspects of style. (1) Choice between alternative expressions. (2) Derivation from the norm. Majeed Amjad having unique style and poetics must be analyzed on modern parameters of stylistics. Majeed Amjad has his own distinguish style among the urdu poets. He carved out a new style other. He experimented with metrical forms and rhythms. Stylistic analysis of Amjad&rsquo;s poetry Lenlighteen the individual traits of his style. Stylistics choice of lexical items, phonetics, Morphological choices and grammatical sources shows distinctive features of his poetics and literary style.</p

Childbearing and parenthood during residency and fellowship

Objective: To evaluate the common concerns and factors affecting planning a family during residency and fellowship and to create required support services particular to those needs. Background: With the rise in burnout amongst physicians, family stress and parenthood during training may be an important factor in early career burnout. Studies have shown that childbearing and parenthood during residency and fellowship affects training and career satisfaction. With women in medicine comprising half the workforce and long training periods, it is a not uncommon for residents to start families during residency. Pregnancy, lactation, maternity/paternity leaves, post partum support affects resident education, training and often program completion time. Design/Methods: We conducted a detailed online survey of all residents and fellows at Henry Ford Hospital utilizing survey monkey. Questions were asked regarding knowledge of parental leave, policies pertaining to training and board examination, breast feeding policies, feasible childcare options and other parental resources. After the survey, parent support group was created which carried out meetings to address trainee\u27s needs. Results: Out of the total house officers surveyed, 78 responded to the survey. Among them 50% responded that due to their career plan, they put off planning a family while still in training. About 80% of them were not aware of the institution\u27s resources for new parents and 60% were unaware of lactation policies. Conclusions: Parent support group was created with the intent to address these issues and mitigate stress associated with childbirth during training. Monthly meetings with focus on specific issues such as lactation, work life integration and parenting as well as faculty panels and mentorship for interested residents are arranged as a part of this project. A more widespread initiative should be taken to provide parenthood support to residents and fellows