An Alternative Airway Intervention to Preserve the Surgical Field in Oral and Maxillofacial Surgery.

Background/need. Office-based sedation has become increasingly commonplace in dental offices in recent years, allowing for practitioners to provide broader scope of care for their patients. Maintaining high standards of safety is of utmost importance when sedation is utilized in the office-based setting, especially for patients deemed at a higher-risk for intraoperative airway obstruction. This demographic includes but is not limited to individuals with a medical history significant for obstructive sleep apnea, chronic obstructive pulmonary disease, and morbid obesity. Presently, a wide variety of airway devices exist for use in the event of airway obstruction. However, in the context of oral and maxillofacial surgery, placement of these devices can encroach upon the surgical field, extending the perioperative period and putting the patient at greater long-term risk for maintaining adequate oxygenation. Methodology. The authors describe a preliminary technique trialed in our offices which utilizes a size 5.0 endotracheal tube (5OET) as an adjunct supraglottic airway to help mitigate the issue of oxygen saturation maintenance, as well as unimpeded access to the oral cavity. Implementation of the device requires identifying appropriate candidates during preoperative screening and placing the device through the nare and securing it above the glottis. Device Description. The 'tube kit' is comprised of a standard size straight 5.0 cuffed oral ETT, a 5-mL syringe for inflation of the cuff post insertion, lubricant, flex extension tubing, end tidal sampling line for capnography, tape for securement of the 5OET, and an anesthesia breathing circuit. Optional equipment pieces include an elbow connecter and a foam piece for comfort. Results/Current Status. Preliminary results have demonstrated oxygen saturations maintained above 98% when the 5OET is placed preoperatively. Continued use of the trial device will inform the development of a tube by our clinicians, and its efficacy will be studied in our offices. The next steps will be to start developing a pilot cuff that will be submitted for patent approval after its use in IRB-approved clinical studies.

A comparative study to assess thoracic kyphotic index in adults with and without mechanical neck pain.

OBJECTIVE: To assess thoracic kyphotic index in adults, and to find out the correlation between Neck Disability Index and Thoracic Kyphotic Index. METHODS: The analytical cross-sectional study was conducted from October 2020 to January 2021 at the Shifa Tameer-e-Millat University, Islamabad, Pakistan, and comprised adults aged 18-35 years. Those with neck pain formed group A, while those without neck pain formed group B. The Numeric Pain Rating Scale and the Neck Disability Index were used to measure mechanical neck pain, while the Thoracic Kyphotic Index value was measured using a flexicurve ruler. Data was analyzed using SPSS 24. RESULTS: Of the 74 subjects, 37(50%) were in each of the two groups. There were 19 (51.40%) females and 18(48.60%) males in group A, while in group B there were 18(48.60%) females and 19(51.40%) males. The overall mean age of the sample was 23.35±3.31 years. Group A showed higher Thoracic Kyphotic Index value than group B (p=0.0001). The Neck Disability Index showed negative weak (r=-0.18, p=0.28) correlation with Thoracic Kyphotic Index in group B and moderate positive correlation (r=0.33, p=0.04) in group A. CONCLUSIONS: Higher Thoracic Kyphotic Index value was found among adults with mechanical neck pain compared to healthy adults.

Breast Cancer Management Consensus By The Society of Surgeons and Surgical Oncology Society of Pakistan.

The Society of Surgeons of Pakistan and The Society of Surgical Oncology of Pakistan with factions from various major centres comprising of surgical oncology, medical and radiation oncology collaborated to reach consensus on breast cancer management guidelines and a framework of "good practice" minimum standards of care. The aim of the task force was to enhance treatment standards, which have a direct correlation with improving patient mortality and morbidity and long-term survival whilst taking into consideration economic limitations of access to leading centers of excellence as well as minimum expertise required in health care. These multidisciplinary guidelines, whilst not exhaustive, aim to provide an algorithm of care for breast cancer patients at tertiary care centres and district level hospitals to provide most appropriate treatment.

Effect of quitting smoking on health outcomes during treatment for tuberculosis: secondary analysis of the TB & Tobacco Trial.

BACKGROUND: Despite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB outcomes. METHODS: The TB & Tobacco Trial was a double-blind, placebo-controlled randomised trial of cytisine for smoking cessation in 2472 patients with pulmonary TB in Bangladesh and Pakistan. In a secondary analysis, we investigated the hypothesis that smoking cessation improves health outcomes in patients during the TB treatment course. The outcomes included an eight-point TB clinical score, sputum conversion rates, chest X-ray grades, quality of life (EQ-5D-5L), TB cure plus treatment completion rates and relapse rates. These were compared between those who stopped smoking and those who did not, using regression analysis. RESULTS: We analysed the data of 2273 (92%) trial participants. Overall, 25% (577/2273) of participants stopped smoking. Compared with non-quitters, those who quit had better TB cure plus treatment completion rates (91% vs 80%, p<0.001) and lower TB relapse rates (6% vs 14%, p<0.001). Among quitters, a higher sputum conversion rate at week 9 (91% vs 87%, p=0.036), lower mean TB clinical scores (-0.20 points, 95% CI -0.31 to -0.08, p=0.001) and slightly better quality of life (mean EQ-5D-5L 0.86 vs 0.85, p=0.015) at 6 months were also observed. These differences, except quality of life, remained statistically significant after adjusting for baseline values, trial arm and TB treatment adherence rates. CONCLUSION: Patients with TB who stop smoking may have better outcomes than those who don't. Health professionals should support patients in stopping smoking.

Attitudes of smokers towards tobacco control policies: findings from the Studying Tobacco users of Pakistan (STOP) survey.

BACKGROUND: Public attitude is a political driver in successful implementation of tobacco control policies. We assessed support for a range of tobacco control policies among smokers in Pakistan. METHODS: We conducted a household survey among adult smokers in 10 cities of Pakistan, using a two-stage random sampling strategy to select households and Kish grid method to select one smoker per household. Attitudes were measured using a five-point ordinal scale on four policy statements: a complete ban on tobacco sale within 10 years; raising the legal age to buy tobacco from 18 to 21; increasing tobacco taxes to fund healthcare and a ban on smoking in cars with minors. RESULTS: 6014 participants were interviewed between September 2019 and March 2020. Most participants demonstrated strong support for all policy statements: a ban on smoking in cars with minors (86.5%); a complete ban on tobacco sale within 10 years (82.1%); raising the legal age to buy tobacco (77.9%) and increasing tobacco taxes (68.1%). Smokers' support for tobacco control policies increased with age but decreased with higher educational attainment and heaviness of smoking. CONCLUSIONS: There is strong support among smokers in Pakistan to strengthen tobacco control. Given this, policy-makers should strongly consider strengthening existing national policies on tobacco control.

Illicit cigarette trade in the cities of Pakistan: comparing findings between the consumer and waste recycle store surveys.

BACKGROUND: Concerns about the magnitude of illicit cigarette trade have prevented the Government of Pakistan from increasing tobacco taxes. We estimated the proportion of illicit cigarettes sold in Pakistani cities. Moreover, we compared two methods for collecting cigarette packs and investigated if the illicit cigarette trade equates to tax evasion. METHOD: We analysed cigarette packs collected from 10 cities of Pakistan using two methods: consumer survey based on a two-stage random sampling strategy to recruit adult smokers and photograph their cigarette packs and waste recycle store survey to purchase used cigarette packs. Cigarettes were considered illicit if any one of the following was absent from their packs: text and pictorial health warning, underage sale prohibition warning, retail price and manufacturer's name. From the consumer survey, we also estimated the proportion of smokers who purchased loose cigarettes (illegal) and packs below the minimum retail price. Taxation officers (n=4) were consulted to assess their level of confidence in judging tax evasion using the above criteria. RESULTS: Out of 2416 cigarette packs in the consumer survey, 454 (17.8%; 95% CI 15.4% to 20.2%) were illicit. Similarly, out of 6213 packs from waste recycle shops, 1046 (16.8%; 95% CI 15.9% to 17.7%) were illicit; the difference was not statistically significant (p=0.473). Among consumers, 29.5% bought loose cigarettes and 13.8% paid less than the minimum retail price. The taxation officers considered the manufacturer's name and retail price on cigarette packs as the most relevant criteria to detect tax evasion. CONCLUSIONS: One in six cigarette packs consumed in Pakistan could be illicit. These figures are far less than those propagated by the tobacco industry. Collecting packs from waste recycle stores is an efficient and valid method to estimate illicit cigarette trade.

Scaling up tobacco cessation within TB programmes: findings from a multi-country, mixed-methods implementation study.

BACKGROUND: Brief behavioural support can effectively help tuberculosis (TB) patients quit smoking and improve their outcomes. In collaboration with TB programmes in Bangladesh, Nepal and Pakistan, we evaluated the implementation and scale-up of cessation support using four strategies: (1) brief tobacco cessation intervention, (2) integration of tobacco cessation within routine training, (3) inclusion of tobacco indicators in routine records and (4) embedding research within TB programmes. METHODS: We used mixed methods of observation, interviews, questionnaires and routine data. We aimed to understand the extent and facilitators of vertical scale-up (institutionalization) within 59 health facility learning sites in Pakistan, 18 in Nepal and 15 in Bangladesh, and horizontal scale-up (increased coverage beyond learning sites). We observed training and surveyed all 169 TB health workers who were trained, in order to measure changes in their confidence in delivering cessation support. Routine TB data from the learning sites were analysed to assess intervention delivery and use of TB forms revised to report smoking status and cessation support provided. A purposive sample of TB health workers, managers and policy-makers were interviewed (Bangladesh n = 12; Nepal n = 13; Pakistan n = 19). Costs of scale-up were estimated using activity-based cost analysis. RESULTS: Routine data indicated that health workers in learning sites asked all TB patients about tobacco use and offered them cessation support. Qualitative data showed use of intervention materials, often with adaptation and partial implementation in busy clinics. Short (1-2 hours) training integrated within existing programmes increased mean confidence in delivering cessation support by 17% (95% CI: 14-20%). A focus on health system changes (reporting, training, supervision) facilitated vertical scale-up. Dissemination of materials beyond learning sites and changes to national reporting forms and training indicated a degree of horizontal scale-up. Embedding research within TB health systems was crucial for horizontal scale-up and required the dynamic use of tactics including alliance-building, engagement in the wider policy process, use of insider researchers and a deep understanding of health system actors and processes. CONCLUSIONS: System-level changes within TB programmes may facilitate routine delivery of cessation support to TB patients. These strategies are inexpensive, and with concerted efforts from TB programmes and donors, tobacco cessation can be institutionalized at scale.

The Impact of COVID-19 on Smoking Patterns in Pakistan: Findings From a Longitudinal Survey of Smokers.

INTRODUCTION: We investigated the influence of COVID-19 on smoking patterns in Pakistan. METHODS: In a longitudinal survey, we asked cigarette smokers in Pakistan about their smoking behaviors before and since COVID-19. Smokers were recruited before COVID-19 using two-stage random probability sampling. Since COVID-19, three subsequent waves were conducted over the telephone, asking additional questions on social determinants, mental health, and well-being. Based on the first two waves, we estimated the proportion of smokers who stopped, decreased, maintained, or increased smoking. We also explored any factors associated with the change in smoking patterns. In those who stopped smoking soon after COVID-19, we estimated the proportion relapsed in subsequent waves. We estimated all proportions based on complete-case analysis. RESULTS: We recruited 6014 smokers between September 2019 and February 2020; of these, 2087 (2062 reported smoking outcomes) were followed up in May 2020 after COVID-19. Since COVID-19, 14% (290/2062) smokers reported quitting. Among those who continued smoking: 68% (1210/1772) reduced, 14% (239/1772) maintained, and 18% (323/1772) increased cigarette consumption; 37% (351/938) reported at least one quit attempt; 41% (669/1619) were more motivated; while 21% (333/1619) were less motivated to quit. Changes in smoking patterns varied with nicotine dependence, motivation to quit, and financial stability since COVID-19. Among those reporting quitting soon after COVID-19, 39% (81/206) relapsed in the subsequent months (June-July 2020). CONCLUSIONS: There have been significant bidirectional changes in smoking patterns since COVID-19 in Pakistan. Although many people stopped, reduced, or tried quitting smoking, some increased smoking and some relapsed after quitting. IMPLICATIONS: We observed significant and complex changes in people's smoking patterns, which are likely to be attributable to the COVID-19 pandemic and replicated in similar events in the future. Assessing these changes is essential for most low- and middle-income countries like Pakistan, where the vast majority of tobacco users live, but cessation support is still rudimentary. If provided routinely, smoking cessation interventions can potentially support millions of highly motivated individuals in quitting successfully both in general and in global events like COVID-19, in particular.

Using behaviour change theory to train health workers on tobacco cessation support for tuberculosis patients: a mixed-methods study in Bangladesh, Nepal and Pakistan.

BACKGROUND: Low- and middle-income countries (LMICs) are disproportionately impacted by interacting epidemics of tuberculosis (TB) and tobacco consumption. Research indicates behavioural support delivered by health workers effectively promotes tobacco cessation. There is, however, a paucity of training to support LMIC health workers deliver effective tobacco cessation behavioural support. The TB and Tobacco Consortium undertook research in South Asia to understand factors affecting TB health workers' delivery of tobacco cessation behavioural support, and subsequently developed a training package for LMICs. METHODS: Using the "capability, opportunity, and motivation as determinants of behaviour" (COM-B) framework to understand any issues facing health worker delivery of behaviour support, we analysed 25 semi-structured interviews and one focus group discussion with TB health workers, facility in-charges, and national tuberculosis control programme (NTP) staff members in each country. Results were integrated with findings of an adapted COM-B questionnaire on health worker confidence in tobacco cessation support delivery, administered to 36 TB health workers. Based on findings, we designed a guide and training programme on tobacco cessation support for health workers. RESULTS: Qualitative results highlighted gaps in the majority of health workers' knowledge on tobacco cessation and TB and tobacco interaction, inadequate training on patient communication, insufficient resources and staff support, and NTPs' non-prioritization of tobacco cessation in all three countries. Questionnaire results reiterated the knowledge deficits and low confidence in patient communication. Participants suggested strengthening knowledge, skills, and competence through training and professional incentives. Based on findings, we developed an interactive two-day training and TB health worker guide adaptable for LMICs, focusing on evidence of best practice on TB and tobacco cessation support, communication, and rapport building with patients. CONCLUSIONS: TB health workers are essential in addressing the dual burden of TB and tobacco faced by many LMICs. Factors affecting their delivery of tobacco cessation support can be identified using the COM-B framework, and include issues such as individuals' knowledge and skills, as well as structural barriers like professional support through monitoring and supervision. While structural changes are needed to tackle the latter, we have developed an adaptable and engaging health worker training package to address the former that can be delivered in routine TB care. TRIAL REGISTRATION: ISRCTN43811467 .

High-throughput screening of a GlaxoSmithKline protein kinase inhibitor set identifies an inhibitor of human cytomegalovirus replication that prevents CREB and histone H3 post-translational modification.

To identify new compounds with anti-human cytomegalovirus (HCMV) activity and new anti-HCMV targets, we developed a high-throughput strategy to screen a GlaxoSmithKline Published Kinase Inhibitor Set. This collection contains a range of extensively characterized compounds grouped into chemical families (chemotypes). From our screen, we identified compounds within chemotypes that impede HCMV protein production and identified kinase proteins associated with inhibition of HCMV protein production that are potential novel anti-HCMV targets. We focused our study on a top 'hit' in our screen, SB-734117, which we found inhibits productive replication of several HCMV strains. Kinase selectivity data indicated that SB-734117 exhibited polypharmacology and was an inhibitor of several proteins from the AGC and CMCG kinase groups. Using Western blotting, we found that SB-734711 inhibited accumulation of HCMV immediate-early proteins, phosphorylation of cellular proteins involved in immediate-early protein production (cAMP response element-binding protein and histone H3) and histone H3 lysine 36 trimethylation (H3K36me3). Therefore, we identified SB-734117 as a novel anti-HCMV compound and found that inhibition of AGC and CMCG kinase proteins during productive HCMV replication was associated with inhibition of viral protein production and prevented post-translational modification of cellular factors associated with viral protein production.

Management of undernutrition and failure to thrive in children with congenital heart disease in low- and middle-income countries.

Poor growth with underweight for age, decreased length/height for age, and underweight-for-height are all relatively common in children with CHD. The underlying causes of this failure to thrive may be multifactorial, including innate growth potential, severity of cardiac disease, increased energy requirements, decreased nutritional intake, malabsorption, and poor utilisation of absorbed nutrition. These factors are particularly common and severe in low- and middle-income countries. Although nutrition should be carefully assessed in all patients, failure of growth is not a contraindication to surgical repair, and patients should receive surgical repair where indicated as soon as possible. Close attention should be paid to nutritional support - primarily enteral feeding, with particular use of breast milk in infancy - in the perioperative period and in the paediatric ICU. This nutritional support requires specific attention and allocation of resources, including appropriately skilled personnel. Thereafter, it is essential to monitor growth and development and to identify causes for failure to catch-up or grow appropriately.

Estimated GFR Decline Following Sodium Phosphate Enemas Versus Polyethylene Glycol for Screening Colonoscopy: A Retrospective Cohort Study.

BACKGROUND: Associations between sodium phosphate enemas and nephropathy have raised concerns about the safety of use as part of a bowel-cleansing regimen administered prior to colonoscopies. The objectives of this analysis are to evaluate the impact of sodium phosphate enema versus polyethylene glycol powder for oral solution (PEG) use prior to colonoscopy screening on estimated glomerular filtration rate (eGFR) decline in Veterans Affairs (VA) patients and identify other risk factors contributing to eGFR decline. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 70,499 VA patients receiving sodium phosphate enemas (with or without PEG) or PEG alone prior to colonoscopy screenings. PREDICTOR: Use of either sodium phosphate or PEG. OUTCOMES: A 50% increase in serum creatinine level over a 15-month, over a 6-week, and between a 9- and 15-month period was used to define any, acute, or long-term eGFR decline, respectively. MEASUREMENTS: Multivariable logistic regressions estimated the likelihood of eGFR decline conditional on the use of sodium phosphate enemas versus PEG alone, controlling for potential confounders. RESULTS: A greater proportion of patients using sodium phosphate enemas versus PEG had any (P<0.001) or long-term (P=0.003) eGFR declines, whereas similar proportions had acute eGFR declines (P=0.9). In the adjusted analyses, use of sodium phosphate enemas (± PEG was associated with an increased likelihood of having any (OR, 1.3; 95% CI, 1.2-1.5) or long-term (OR, 1.4; 95% CI, 1.1-1.8) eGFR decline, but not acute eGFR decline (OR, 1.0; 95% CI, 0.6-1.7). Other risk factors for eGFR decline included diabetes and non-iron deficient anemia. LIMITATIONS: Unobserved heterogeneity due to volume depletion and potential selection bias due to higher-risk patients preferentially prescribed sodium phosphate enemas. CONCLUSIONS: Use of sodium phosphate enemas versus PEG alone prior to colonoscopy screening increases the risk for VA patients having long-term eGFR decline. Patients with non-iron deficient anemia are at particularly high risk for eGFR decline. These findings motivate the need to re-examine prescribing practices for sodium phosphate enemas as part of a bowel-cleansing regimen.

Smokeless Tobacco Supply Chain in South Asia: A Comparative Analysis Using the WHO Framework Convention on Tobacco Control.

INTRODUCTION: Most South Asian countries are signatories to the WHO Framework Convention for Tobacco Control (FCTC). However, there is little information on the extent to which FCTC standards are effectively implemented for controlling smokeless tobacco (SLT)-used by over 250 million people in the region. We assessed the feasibility of a novel approach based on interviewing the key actors of SLT supply chain and analyzing its findings using standards set by FCTC. METHODS: Using a snowball-sampling technique, we interviewed point-of-sale vendors, wholesale retailers, manufacturers, raw-tobacco retailers, and farmers involved in the supply chain of SLT in Bangladesh, Nepal, and Pakistan. Using a structured-questionnaire, participants were asked about their customer profiles; product types; marketing practices; suppliers; profit margins, awareness and adherence to legislation. RESULTS: We recruited 72% (130/180) of all supply chain actors approached. Findings indicate several loopholes in the existing taxation, regulatory, and inspection systems. A significant proportion of smuggled and counterfeit SLT products are available in the market. Most SLT products are sold without recommended warnings, information on their ingredients, and manufacturers' details. There appear to be no restrictions on sale of SLT products to minors. On the other hand, there are also several incentives built-in the supply chain that makes tobacco farming, SLT manufacturing, and its sale a profitable business. CONCLUSIONS: Our novel approach to study SLT control was successful in identifying and interviewing actors involved in its supply chain. The analysis using FCTC could provide valuable information to policy makers and enable them to effectively regulate SLT products.

Breast cancer treatment in high-risk elderly patients: A challenging situation and difficult decisions.

OBJECTIVE: To assess whether high-risk elderly patients with aggressive tumour biology can be offered standard treatment despite having multiple comorbid conditions. METHODS: This retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of breast cancer patients aged 65 years or above treated between 2006 and 2012,. Data was collected regarding patients' demographics, baseline clinical characteristics, comorbidities, treatment and outcomes. Stata 12 was used for data analysis. RESULTS: Of the 407 patients in the study, 399(98%) were women and 8(2%) were men. The overall mean age at diagnosis was 70±4.9 years (range: 65-90 years). Overall, 59(14.5%) participants had family history of breast cancer. Bilateral disease was seen in 17(4.2%). Invasive ductal carcinoma was seen in 299(73.5%). Besides, 101(24.8%) patients had no comorbid conditions, while 138(34%) had one, 102(25%) had two and 66(16%) had three or more comorbid conditions. There was no statistically significant difference between those receiving standard treatment including surgery or other modalities. CONCLUSIONS: Elderly patients of breast cancer may be offered treatment according to the tumour biology and their overall functional status.

Smokeless tobacco control policies in South Asia: a gap analysis and recommendations.

INTRODUCTION: Almost a fifth of the world's tobacco is consumed in smokeless form. Its consumption is particularly common in South Asia, where an increasing array of smokeless tobacco (SLT) products is widely available. Mindful of the growing public health threat from SLT, a group of international academics and policy makers recently gathered to identify policy and knowledge gaps and proposed strategies to address these. METHODS: We reviewed key policy documents and interviewed policy makers and representatives of civil society organizations in 4 South Asian countries: Bangladesh, India, Nepal, and Pakistan. We explored if SLT features in existing tobacco control policies and, if so, the extent to which these are implemented and enforced. We also investigated barriers to effective policy formulation and implementation. The findings were presented at an international meeting of experts and were refined in the light of the ensuing discussion in order to inform policy and research recommendations. RESULTS: We found that the existing SLT control policies in these 4 South Asian countries were either inadequate or poorly implemented. Taxes were low and easily evaded; regulatory mechanisms, such as licensing and trading standards, either did not exist or were inadequately enforced to regulate the composition and sales of such products; and there was little or no cessation support for those who wanted to quit. CONCLUSIONS: Limited progress has been made so far to address the emerging public health threat posed by SLT consumption in South Asia. International and regional cooperation is required to advocate for effective policy and to address knowledge gaps.

Safe negative margin width in breast conservative therapy: results from a population with a high percentage of negative prognostic factors.

BACKGROUND: There remains a controversy in the literature regarding adequate width of negative surgical margins in breast conservative therapy (BCT). It is now advocated that no tumor on an inked margin is a safe negative margin. Majority of studies on the outcomes of BCT had patients with favorable prognostic factors. Pakistani population has a high expression of unfavorable prognostic factors. The objective of this study was to determine a safe negative margin width in Pakistani population that undergoes BCT. METHODS: A total of 603 patients with identifiable surgical margins underwent BCT from 1997 to 2009 in Shaukat Khanum Cancer Hospital. Patients were divided into close (≤2 mm), free (>2-10 mm), and wide (>10 mm) margin groups. Locoregional recurrence was defined as recurrence within the operated breast, ipsilateral axilla, or supraclavicular or internal mammary lymph nodes. Locoregional recurrence-free survival was calculated from the date of surgery to the date of locoregional recurrence. Five-year locoregional recurrence-free survival was determined for margin groups. Univariate and multivariate Cox proportional hazard analyses were performed to determine independent predictors of locoregional recurrence. RESULTS: A total of 415 (69 %) patients were <50 years of age. There were 82 (15 %) T3/T4, 337 (56 %) poorly differentiated, and 238 (39 %) ER/PR -ve tumors. Nodal positivity was present in 314 (52 %) patients. The actual number of locoregional recurrences was 16 (12 %), 8 (3 %), and 10 (4.6 %), respectively (P = 0.002). Expected 5-year locoregional recurrence-free survival was 90, 97, and 96 %, respectively (P = 0.002). On multivariate analysis, tumor size, nodal involvement, and negative margin width were independent predictors of locoregional recurrence. CONCLUSION: A negative margin width of 2 mm might represent an adequate negative margin width in the Pakistani population undergoing breast conservative therapy.

A randomized, double-blind, placebo-controlled study to evaluate the effects of alendronate on bone mineral density and bone remodelling in perimenopausal women with low bone mineral density.

BACKGROUND: Perimenopausal women can experience rapid bone loss at skeletal sites with both cortical and cancellous bone, increasing the prevalence of osteoporosis following menopause. METHODS: We conducted a 12-month randomized placebo-controlled trial evaluating the effects of alendronate 70 mg with 2800 IU cholecalciferol administered once per week for 12 months in comparison with placebo and cholecalciferol. The primary end-point was the percentage change in the lumbar spine bone mineral density (BMD) from baseline to 12 months. Secondary end-points were the change in BMD at the femoral neck and changes in biochemical markers of bone turnover. RESULTS: Forty-five women were recruited to participate in the study. Five subjects withdrew from the study before randomization for unrelated reasons. Forty subjects were randomly allocated to the alendronate and placebo groups. The mean lumbar spine MD in women treated with alendronate increased by 3.66% (mean paired difference, µd = 0.032; ± 0.008 SE) at 12 months, compared with a reduction of 3.33% (µd = -0.030; ± 0.008 SE) in the control group (P < 0.001). In the femoral neck, the mean BMD in the alendronate group increased by 2.07% (µd = 0.014; ± 0.009 SE) at 12 months, compared with a reduction of 1.87% (µd = -0.014; ± 0.008 SE) in the control group (P = 0.046). There were no differences in BMD between the alendronate and placebo groups at the total hip sites after 12 months. At 12 months, both bone-specific alkaline phosphatase and urinary N-telopeptide were significantly reduced, by 37.79% (µd = -9.90; ± 1.92 SE) and 27.21% (µd = -11.68; ± 4.80 SE) respectively, in the alendronate group; in the control group, these levels increased (P < 0.001). CONCLUSION: Weekly treatment with alendronate 70 mg and cholecalciferol 2800 IU increases BMD and decreases bone turnover in perimenopausal women.

Contexte : Les femmes périménopausées peuvent connaître une perte osseuse rapide aux points du squelette qui comptent des os tant corticaux que spongieux, ce qui accroît la prévalence de l'ostéoporose à la suite de la ménopause. Méthodes : Nous avons mené un essai comparatif randomisé avec placebo (d'une durée de 12 mois) qui cherchait à évaluer les effets de l'administration de 70 mg d'alendronate et de 2 800 UI de cholécalciférol (une fois par semaine, pendant 12 mois), par comparaison avec l'administration d'un placebo et de cholécalciférol. Le critère d'évaluation principal était la modification (en pourcentage, entre la valeur de départ et la valeur à 12 mois) de la densité minérale osseuse (DMO) de la colonne lombaire. Parmi les critères d'évaluation secondaires, on trouvait la modification de la DMO du col fémoral et les modifications des marqueurs biochimiques du renouvellement des cellules osseuses. Résultats : Nous avons sollicité la participation de 45 femmes à l'étude. Cinq participantes se sont désistées avant la randomisation pour des raisons n'ayant rien à voir avec l'étude. Quarante femmes ont été affectées au hasard à un groupe devant recevoir de l'alendronate ou à un groupe devant recevoir un placebo. Chez les femmes traitées à l'alendronate, la DMO moyenne de la colonne lombaire a connu une hausse de l'ordre de 3,66 % (différence moyenne appariée, µd = 0,032; ± 0,008 ET) à 12 mois, par comparaison avec une baisse de l'ordre de 3,33 % (µd = −0,030; ± 0,008 ET) au sein du groupe témoin (P < 0,001). Au niveau du col fémoral au sein du groupe « alendronate ¼, la DMO moyenne a connu une hausse de l'ordre de 2,07 % (µd = 0,014; ± 0,009 ET) à 12 mois, par comparaison avec une baisse de l'ordre de 1,87 % (µd = −0,014; ± 0,008 ET) au sein du groupe témoin (P = 0,046). Aucune différence en matière de DMO n'a été constatée entre les groupes « alendronate ¼ et « placebo ¼ pour ce qui est de l'ensemble des sites de la hanche après 12 mois. À 12 mois, tant la phosphatase alcaline propre aux os que le N-télopeptide urinaire ont connu une baisse significative, de l'ordre de 37,79 % (µd = −9,90; ± 1,92 ET) et de 27,21 % (µd = −11.68; ± 4,80 ET) respectivement, au sein du groupe « alendronate ¼; au sein du groupe témoin, les taux de ces marqueurs ont connu une hausse (P < 0,001). Conclusion : L'administration hebdomadaire d'un traitement faisant appel à 70 mg d'alendronate et à 2 800 UI de cholécalciférol entraîne une hausse de la DMO et une baisse du renouvellement des cellules osseuses chez les femmes périménopausées.

Differential roles of cyclooxygenase enzymes in the regulation of murine juvenile undifferentiated spermatogonia.

BACKGROUND: Acetaminophen and ibuprofen are widely administered to babies due to their presumed safety as over-the-counter drugs. However, no reports exist on the effects of cyclooxygenase inhibitors on undifferentiated spermatogonia and spermatogonial stem cells. Infancy represents a critical period for spermatogonial stem cell formation and disrupting spermatogonial stem cells or their precursors may be associated with infertility and testicular cancer formation. OBJECTIVES: The goal of this study was to examine the molecular and functional impact of cyclooxygenase inhibition and silencing on early steps of undifferentiated spermatogonia (u spg) and spermatogonial stem cell development, to assess the potential reproductive risk of pharmaceutical cyclooxygenase inhibitors. METHODS: The effects of cyclooxygenase inhibition were assessed using the mouse C18-4 undifferentiated juvenile spermatogonial cell line model, previously shown to include cells with spermatogonial stem cell features, by measuring prostaglandins, cell proliferation, and differentiation, using cyclooxygenase 1- and cyclooxygenase 2-selective inhibitors NS398, celecoxib, and FR122047, acetaminophen, and ibuprofen. Cyclooxygenase 1 gene silencing was achieved using a stable short-hairpin RNA approach and clone selection, then assessing gene and protein expression in RNA sequencing, quantitative real-time polymerase chain reaction, and immunofluorescence studies. RESULTS: Cyclooxygenase 2 inhibitors NS398 and celecoxib, as well as acetaminophen, but not ibuprofen, dose-dependently decreased retinoic acid-induced expression of the spg differentiation gene Stra8, while NS398 decreased the spg differentiation marker Kit, suggesting that cyclooxygenase 2 is positively associated with spg differentiation. In contrast, short-hairpin RNA-based cyclooxygenase 1 silencing in C18-4 cells altered cellular morphology and upregulated Stra8 and Kit, implying that cyclooxygenase 1 prevented spg differentiation. Furthermore, RNA sequencing analysis of cyclooxygenase 1 knockdown cells indicated the activation of several signaling pathways including the TGFb, Wnt, and Notch pathways, compared to control C18-4 cells. Notch pathway genes were upregulated by selective cyclooxygenase inhibitors, acetaminophen and ibuprofen. CONCLUSION: We report that cyclooxygenase 1 and 2 differentially regulate undifferentiated spermatogonia/spermatogonial stem cell differentiation. Cyclooxygenases regulate Notch3 expression, with the Notch pathway targeted by PGD2. These data suggest an interaction between the eicosanoid and Notch signaling pathways that may be critical for the development of spermatogonial stem cells and subsequent spermatogenesis, cautioning about using cyclooxygenase inhibitors in infants.

Synthesis of aminolyzed gelatin-mediated chitosan as pH-responsive drug-carrying porous scaffolds.

Bio-based drug delivery devices have gained enormous interest in the biomedical field due to their biocompatible attributes. Extensive research is being conducted on chitosan-based devices for drug delivery applications. Chitosan being hydrophobic under neutral conditions makes it difficult to interact with a polar drug of curcumin. We tended to make it polar through sol-gel synthesis and modification via PEGylation, alkaline hydrolysis, and aminolysis. Such alterations could make the chitosan-based scaffolds porous, hydrophilic, amino-functionalized, and pH-responsive. The ninhydrin assay confirmed that a successful aminolysis occurred, and the chemical interaction among the precursors was explained under infrared spectroscopy. The scanning morphology of the optimum aminolyzed membrane appeared to be porous with an average pore size of 320 ± 20 nm. The aminolyzed chitosan membrane was found thermally stable up to 310 °C, hydrophilic with a water contact angle of 23.4°, moderate flowablity, and porous (97 ± 5 %, w/w) against ethanol. The curcumin-loaded chitosan membrane expressed the UV-protection behavior of 99 %. The curcumin-loading and release phenomena were found pH-responsive. The curcumin release results were evaluated through specific kinetic models. This study could be the first report on the amphiphilic, porous, and swellable drug-loaded gelatin/chitosan membrane with pH-responsive loading and release of curcumin for potential drug delivery applications.

Citrate silver nanoparticles impregnated cellulose as a photocatalytic filter in the degradation of organic dye in the aqueous media.

Photocatalysis is a clean and efficient process pursued under light irradiation with a suitable photocatalyst to degrade a contaminant. We report citrate functionalization of silver nanoparticles (SNPs) for effective immobilization on cellulosic fabric. The porous cellulosic matrix could be explored as microfiltration membranes for the photocatalytic degradation of organic dyes in the aqueous media. Where valid, the citrate functionalized SNPs and the treated cellulose fabrics were considered for optical, structural, surface chemical, thermal, textile, flowability, photocatalytic, and antibacterial attributes. The SNPs expressed the bandgap energy of 2.56 and 2.43 eV and Urbach energy of 3.38 and 5.21 eV before and after functionalization with the citrate moieties, respectively. The liquid chromatographic and FTIR analyses indicated that the crystal violet (CV) organic dye has been successfully photodegraded to environmentally safer and nontoxic species on passing the contaminated water through the SNPs-treated cellulosic filter. The spectroscopic data also supported the said outcomes. The results demonstrated that the citrate-SNPs-treated cellulose could be efficiently employed as antibacterial photocatalytic membranes for degrading organic dyes in the aqueous media for multiple cycles.