Strategizing Spray Drying Process Optimization for the Manufacture of Redispersible Indomethacin Nanoparticles Using Quality-by-Design Principles.

The present study adopted a Quality by Design (QbD) approach to spray dry indomethacin nanosuspension (IMC-NS) consisting of HPC-SL, poloxamer 407, and lactose monohydrate. The Box-Behnken Design was used to systematically evaluate the effects of inlet temperature, aspiration rate, and feed rate on the critical quality attributes (CQAs) [redispersibility index (RDI; minimize), % yield (maximize), and % release at 15 min (maximize)] of the indomethacin spray dried nanosuspension (IMC-SD-NS). To identify significant main and quadratic effects, two-way interactions, and create a predictive model for the spray drying process, regression analysis and ANOVA were utilized. Following optimization, the IMC-SD-NS was analyzed for its physicochemical properties using X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. Statistical analysis revealed significant independent variables, including inlet temperature, feed rate, and aspiration rate, that critically impacted the solidified end product's RDI, % yield, and % release at 15 min. The models developed for critical quality attributes (CQAs) were significant at a p-value of 0.05. The crystalline state of IMC was maintained in the solidified product, as confirmed by XRPD, and no interactions were observed between IMC and the excipients as evaluated by FTIR. In vitro dissolution studies showed improved dissolution rate for the IMC-SD-NS (3.82-fold increase in overall drug release), which may be attributed to the readily redispersible nanosized drug particles. The implementation of a well-designed study, utilizing Design of Experiments (DoE) methodology, played a crucial role in the development of a highly effective spray drying process.

Mechanical Properties of Rubberised Geopolymer Concrete.

The environmental impact of non-biodegradable rubber waste can be severe if they are buried in moist landfill soils or remain unused forever. This study deals with a sustainable approach for reusing discarded tires in construction materials. Replacing ordinary Portland cement (OPC) with an environmentally friendly geopolymer binder and integrating crumb rubber into pre-treated or non-treated geopolymer concrete as a partial replacement of natural aggregate is a great alternative to utilise tire waste and reduce CO2 emissions. Considering this, two sets of geopolymer concrete (GPC) mixes were manufactured, referred to as core mixes. Fine aggregates of the core geopolymer mixes were partially replaced with pre-treated and non-treated rubber crumbs to produce crumb rubber geopolymer concrete (CRGPC). The mechanical properties, such as compressive strength, stress-strain relationship, and elastic modulus of a rubberised geopolymer concrete of the reference GPC mix and the CRGPC were examined thoroughly to determine the performance of the products. Also, the mechanical properties of the CRGPC were compared with the existing material models. The result shows that the compressive strength and modulus of elasticity of CRGPC decrease with the increase of rubber content; for instance, a 33% reduction of the compressive strength is observed when 25% natural fine aggregate is replaced with crumb rubber. However, the strength and elasticity reduction can be minimised using pre-treated rubber particles. Based on the experimental results, stress-strain models for GPC and CRGPC are developed and proposed. The proposed models can accurately predict the properties of GPC and CRGPC.

Navigating Perinatal Challenges: A Comprehensive Review of Cholestasis of Pregnancy and Its Impact on Maternal and Fetal Health.

Cholestasis of pregnancy (CP), or intrahepatic CP (ICP), represents a condition peculiar to pregnancy, marked by impaired bile acid flow and consequent accumulation in the maternal bloodstream. Primarily emerging in the third trimester, CP is linked with considerable risks to both the mother and fetus, including heightened incidences of preterm birth, fetal distress, and stillbirth, alongside maternal complications such as intense pruritus and liver dysfunction. Despite its clinical significance, the etiology of CP, which involves genetic, hormonal, and environmental factors, remains partially understood. This comprehensive review delves into the physiology and pathophysiology of CP, outlines its clinical manifestations and diagnostic criteria, and discusses the associated maternal and fetal complications. Furthermore, it evaluates current management strategies, prognostic implications, and potential long-term effects on maternal and child health. It also explores future research directions, emphasizing the need for advancements in understanding the pathophysiology of CP, developing novel therapeutic interventions, and improving risk stratification models. By offering a thorough overview of CP, this review aims to enhance clinical awareness, guide management practices, and identify areas requiring further investigation, ultimately contributing to better health outcomes for affected women and their babies.

Technical considerations in robotic aberrant right subclavian artery resection for dysphagia lusoria.

Dysphagia lusoria occurs due to compression of the esophagus as an aberrant right subclavian artery (ARSA) crosses the mediastinum. Surgical management includes open, hybrid, and endovascular techniques, with no consensus gold standard. There are few reports of robotic-assisted ARSA resection. We describe the innovative technique and outcomes for two patients who successfully underwent robotic-assisted transthoracic resection of an ARSA after right carotid-subclavian bypass for dysphagia lusoria. Both patients experienced improvement or resolution of their dysphagia and no major complications. In select patients with a noncalcified origin of the ARSA without aneurysmal degeneration, the robotic-assisted approach represents a viable option.

Moderating effect of work fatigue on the association between resilience and posttraumatic stress symptoms: a cross-sectional multi-country study among pharmacists during the COVID-19 pandemic.

INTRODUCTION: In the context of the COVID-19 pandemic, pharmacists, despite their vital contributions, have faced significant challenges that have impacted their mental well-being, potentially leading to the development of Post-Traumatic Stress symptoms (PTSS). The aim of this study was to investigate the role of work-related fatigue as a potential moderator in the relationship between pharmacists' resilience and their likelihood of experiencing PTSS during the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted online in eight countries from January to December 2021, including Brazil, Lebanon, Nigeria, Pakistan, Poland, Serbia, and Tunisia. The mediation analysis was conducted using PROCESS MACRO (an SPSS add-on) v3.4 model 1, taking work fatigue as a moderator in the association between resilience and PTSS. RESULTS: A total of 442 pharmacists were enrolled in this study (mean age = 33.91 ± 10.36 years) with 59.5% of them being females. The results were adjusted over country, gender, working in contact with COVID-19, working patients, working mandatory hours, working voluntary hours, age, household crowding index and number of months engaged in COVID-19. The interactions resilience by physical (Beta = 0.02; p = .029), mental (Beta = 0.02; p = .040) and emotional (Beta = 0.03; p = .008) work fatigue were significantly associated with PTSS; for pharmacists with low to moderate levels of physical (Beta = - 0.33; p < .001 and Beta = - 0.21; p = .001), mental (Beta = - 0.29; p < .001 and Beta = - 0.18; p = .006) and emotional (Beta = - 0.31; p < .001 and Beta = - 0.17; p = .008) work fatigue, higher resilience was significantly related to lower PTSS levels. However, for pharmacists with high levels of physical/mental/emotional work fatigue, the association between resilience and PTSS became non-significant. CONCLUSION: This study highlights the complex relationship between work-related fatigue, resilience, and PTSS in pharmacists. It emphasizes the need to address work-related fatigue for pharmacists' psychological well-being during crises, offering insights for tailored support and interventions.

Surgical resection of an isolated superficial temporal artery aneurysm.

In the present report, we describes a case of surgical resection of an isolated superficial temporal artery aneurysm without underlying systemic pathology. Although aneurysms of this sort most commonly occur in the setting of recent trauma, this case demonstrates an uncommon presentation. We hope to further contribute to the literature regarding this condition.

Nanoparticles Mediated Target-specific Drug Delivery in Prostate Cancer: An In-depth Review.

Nanotechnology has been extensively exploited for its enormous therapeutic and diagnostic potential in the management of multiple disorders. It employs nanomaterials as drug carriers with enhanced efficacy and limited side effects on normal tissues. A lot of nanomaterials have been studied and produced, imminently reforming the treatment and diagnostics of numerous malignancies, including cancer. The purpose of the present study is to explore the role of nanotechnology-based devices/therapies that have a vital function in the therapeutics and diagnostics of cancer with potential impact at three levels: early detection, tumor imaging, and drug delivery methods. Concentrating on cancer, promising nanotechnology-based approaches have been planned to satisfy the need for targeted specificity of traditional agents of chemotherapeutics, in addition to early recognition of malignant and precancerous lesions. Prostate cancer is the fifth most wellknown cancer worldwide and the second most usually detected cancer in men. Therefore, there is a crucial need to improve therapeutic prospects for the diagnosis and treatment of prostate cancer via the exploitation of the potential of nanomaterials for cell-targeted specificity and improved primary diagnosis of precancerous tumors. The present review, therefore, focuses on summarizing all prospective applications of nanotechnology in the prognosis and diagnosis of prostate cancer, which would further help researchers to elucidate a more potent therapeutic approach for the better management of prostate cancer in the days ahead.

4-Hy-droxy-6-(4-meth-oxy-phen-yl)-4-phenyl-1,3-diazinane-2-thione.

In the title compound, C(17)H(18)N(2)O(2)S, the 1,3-diazinane-2-thione ring system is not coplanar with the benzene ring and meth-oxy-phenyl ring system, the dihedral angle between the planes being 65.58 (13) and 89.18 (10)°, respectively. The crystal structure is characterized by inter-molecular O-H⋯S, N-H⋯S, N-H⋯O and C-H⋯S hydrogen bonding.

Hypertriglyceridemia treated with Fucus vesiculosus - A case series.

Hypertriglyceridemia is an independent risk factor of coronary heart disease (as established through various previously conducted studies) and it's rising incidence is creating a need for the immediate attention of it's management. Instead of focusing on the controversies involving the toxicity caused due to the long-term use of statin therapy in conventional mode of treatment, opting for a safer alternative system of treatment seems important. Five cases of diagnosed HTG, with triglyceride levels above 200 were treated with homoeopathic medicine - Fucus vesiculosus, in mother tincture form. The primary outcome measure was to evaluate the reduction in the blood triglyceride levels. All the five cases showed a reduction in triglyceride levels to normal range within 4 months of starting the treatment with the Fucus vesiculosus mother tincture. Also, it was observed that the borderline cholesterol levels and high LDL levels in 2 cases were found to reduce to normal. Treatment involving Fucus vesiculosus in cases diagnosed with HTG showed significant reduction in triglyceride levels along with other parameters of lipid profile. Further authentication of results with significant sample sizes may be taken up.

Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture.

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.

Byssinosis: as seen in cotton spinning mill workers of Karachi.

OBJECTIVE: To identify Byssinosis in cotton spinning mill workers, probable associations of disease with factors such as different work areas, safety gadget usage and overtime and to ascertain proportions of byssinosis to accidental injuries. METHODS: This study was conducted in a spinning mill of Karachi in June 2006. Mill workers who had worked for a period of minimum 5 years were selected. A sample size of 83 conveniently selected workers participated in the research study. Data collection was done via questionnaire, and pulmonary function tests. RESULTS: The mean age of the sample was 30 +/- 6.9 years. Of all the workers 72% used safety gadgets (masks) while working and 50% availed overtime. Smokers amounted to 31% of the total subjects. Around 35% workers complained of having respiratory ailments of which 19% (16 workers) closely matched byssinotic symptoms. Pulmonary Function Tests (PFTs) confirmed 13 of 16 workers to be byssinotics, with the remaining being labeled as Probables. The overall proportion of Byssinotics in the mill was 19.28% (95% C.I. 11-27) and that of accidental injuries was 22.9%. The association of byssinosis with respect to work areas was significantly high in Ring area (O.R. = 2.04) followed by carding (O.R. = 1.3). The association of byssinosis was also high in workers who did not use safety gadgets, e.g. dust masks (O.R = 4.89) and in people who worked overtime (O.R. = 1.82). Associations with respect to duration of employment and smoking could not yield significant results. CONCLUSION: Results indicate a very high probability of association of disease to non-usage of safety gadgets and overtime working. Studies comprising of a greater sample size would show precisely the overall prevalence of the disease.

Comparison of Nd:YAG Laser and Surgical Stripping for Treatment of Gingival Hyperpigmentation: A Clinical Trial.

OBJECTIVE: The objective of this study is to evaluate and compare surgical stripping and neodymium-doped: yttrium, aluminum garnet (Nd:YAG) laser techniques for gingival depigmentation and to evaluate their effect on repigmentation. BACKGROUND DATA: Gingival depigmentation is often associated with repigmentation. Recurrence of pigmentation differs according to different treatment modalities. MATERIALS AND METHODS: In this study, 40 maxillary sites from 20 patients presenting bilateral melanin gingival hyperpigmentation were selected. Contralateral quadrants in the maxilla were randomly assigned to receive Nd:YAG laser at 3 W, 30 mJ per pulse, with contact mode, and with a handpiece with a 300 µm diameter optic fiber and surgical stripping. Plaque index, Dummett Oral Pigmentation Index (DOPI), Hedin melanin index, size of pigmented area, time interval and extent of repigmentation, time taken for each of the procedures, assessment of pain, intraoperative bleeding index, and patient preference were compared from baseline to 6 months. RESULTS: Comparison between Nd:YAG laser and surgical stripping group for plaque index, DOPI, Hedin index, size of pigmented area, time interval, and extent of repigmentation, at 6 months was statistically nonsignificant. Intergroup comparison for time taken, pain, and patient preference was statistically significant. Intragroup comparison for Nd:YAG laser and surgical stripping at 6 months for DOPI, Hedin index, and size of pigmented area was statistically significant. CONCLUSIONS: From the present study it can be concluded that Nd:YAG laser can be used as an alternative technique for gingival depigmentation. However, surgical stripping continues to remain as a cost-effective procedure.

Prothrombotic markers in Thalassemia major patients: A

Background: It is being increasingly recognised thatthalassemia major patients, like intermedia, have increasedpropensity for thromboembolism. Deficiency of naturalanticoagulants is more recently defined finding contributingto the hypercoagulable state. The aim this study is todetermine natural anticoagulants levels and their correlationwith maternal characteristics, haematological andbiochemical markers.

A survey of attitude and opinions of endodontic residents towards regenerative endodontics.

AIM: The objective of this survey was to study the level of awareness, current state of knowledge and opinions towards regenerative endodontic treatments amongst the endodontic residents of India. SETTINGS AND DESIGN: Questionnaire based survey was designed. MATERIALS AND METHODS: After approval from the organizing committee of 26(th) Federation of Operative Dentistry of India and 19(th) Indian Endodontic Society National conference 2011, 200 copies of the questionnaire were circulated amongst the endodontic residents in conservative dentistry and endodontics at various colleges across the country about regenerative endodontic procedures. The survey included profile of the respondents and consisted of 23 questions about their knowledge, attitude and opinions regarding use of these procedures as part of future dental treatment. RESULTS: The survey showed that half the participants (50.6%) had received continued education in stem cells and/or regenerative dental treatments. The majority of participants were of the opinion (86.6%) that regenerative therapy should be incorporated into dentistry, and most of them (88%) were willing to acquire training in learning this new treatment strategy. The results indicated that half of the participants (52.6%) were already using some type of regenerative therapy in their clinical practice; however, with a majority of these limited to use of membranes, scaffolds or bioactive materials. CONCLUSIONS: These results reflect that endodontic residents are optimistic about the use of regenerative endodontic procedures; however, a need for more research and training was felt.

Multiplex real-time RT-PCR assay for transfusion transmitted viruses in sero-negative allogeneic blood donors: an experience from Southern Pakistan

Background: Blood transfusion safety commences with healthy donor recruitment. The threat of transfusion transmitted infections is greatly minimized by serological tools but not entirely eliminated. Recently, nucleic-acid testing for blood donor screening has virtually eliminated this jeopardy. Methods: This prospective study was conducted from February 2015 to February 2016. Samples from seronegative donors were run on multiplex assay (Cobas, S-201 system platform, Roche) in a batch of six [MP-NAT]. In case of reactive pool, tests were run on every individual sample [IDNAT]. Results: Of 16957 donors, 16836 (99.2%) were replacement donors and the remaining 121 (0.7%) were voluntary donors, with a mean age of 29.09 ± 7.04 years. After serologic screening of all 16957 donors, 955 (5.6%) were found to be reactive; 291(1.71%) were reactive for hepatitis-B surface antigen, 361 (2.12%) for antibody to hepatitis C virus (anti-HCV), 14 (0.08%) for antibody to human immunodeficiency virus, 287 (1.69%) for syphilis and 2 (0.01%) for malaria. 14 (0.08%) NAT reactive donors were identified after testing the 16002 seronegative donors, with an overall NAT yield of one reactivity out of 1143 blood donations; 10 donors for HBV-DNA (HBV NAT yield-1:1600) and remaining 4 for HCV-RNA (HCV-NAT yield-1:4000). None were HIV positive. Conclusion: NAT has improved the safety attributes in blood products. Although the positivity rate for NAT testing is low but in view of the high prevalence of transfusion transmitted infections in our country, we recommend the parallel use of both serology and NAT screening of all donated blood.

Increasing peripheral insulin sensitivity by protein tyrosine phosphatase 1B deletion improves control of blood pressure in obesity.

Obesity is a major risk factor for hypertension. The copresentation of hypertension and insulin resistance (IR) suggests a role for IR in blood pressure (BP) dysregulation. To test this hypothesis, peripheral IR has been genetically subtracted in a model of obesity by crossing leptin receptor mutant mice (K(db)H(PTP)) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, H(db)K(PTP)) to generate obese insulin-sensitive mice (K(db)K(PTP)). BP was recorded in lean (H(db)H(PTP), H(db)K(PTP)) and obese (K(db)H(PTP), K(db)K(PTP)) mice via telemetry, and a frequency analysis of the recording was performed to determine BP variability. Correction of IR in obese mice normalized BP values to baseline levels (H(db)H(PTP): 116 ± 2 mm Hg; K(db)H(PTP): 129 ± 4 mm Hg; K(db)K(PTP): 114 ± 5 mm Hg) and restored BP variability by decreasing its standard deviation and the frequency of BP values over the upper autoregulatory limit of the kidneys. However, although IR-induced increases in proteinuria (versus 53 ± 13 µg/d, H(db)H(PTP)) were corrected in K(db)K(PTP) (112 ± 39 versus 422 ± 159 µg/d, K(db)H(PTP)), glomerular hypertrophy was not. IR reduced plasma aldosterone levels ruling out a role for mineralocorticoids in the development of hypertension. Taken together, these data indicate that correction of IR prevents hypertension, BP variability, and microalbuminuria in obese mice. Although the mechanism remains to be fully determined, increases in aldosterone or sympathoactivation of the cardiovascular system seem to be less likely contributors.

Efficacy of helicobacter pylori eradication as an upfront treatment of secondary immune thrombocytopenia: an experience from Pakistan

Background: The effect of Helicobacter-pylori eradication therapy on the platelet counts in patients with immune thrombocytopenia is still debatable. The aim of this study was to assess the response rates of standard triple eradication therapy in secondary immune thrombocytopenia with Helicobacter pylori infection. Methods: From January 2012 to December 2013, 197 patients were diagnosed to have immune thrombocytopenia, out of which 22(11.1%) patients infected with HelicobacterPylorus were enrolled in this study. Helicobacter-Pylori infection was documented by Helicobacter-pylori stool antigen enzyme immunoassay method. All positive patients were put on triple eradication therapy. The responses rates to treatment were defined as per International Working Group on ITP. Results: Mean age of patients was 43.18±12.5 years. There were 10(45.5%) males and 12 (54.5%) females. Of the 22 patients, 7(31.8%) exhibited a complete response (CR) to Hpylori eradication therapy; 10(45.4%) attained a response; and 5(22.7%) had no response. Mean base line platelet counts were 53.36±24.5x109 /l, while platelet counts at 4 week following eradication was 80.86±51.0x109 /l (P=0.003). The predictive factor of response following eradication therapy was baseline platelet counts. Virtually all responders had baseline platelet counts >30x109 /l and all non-responders had <30x109 /l of platelet counts. Conclusions: Though the prevalence of H-pylori is low, this study confirmed the efficacy of eradication in increasing the platelet counts in H-pylori positive patients with ITP. It is an important measure in short time, safe and very cost effective to achieve platelets increment. We endorse the routine detection and eradication treatment of H-pylori infective ITP patients.

Primary versus secondary immune thrombocytopenia in adults; a comparative analysis of clinical and laboratory attributes in newly diagnosed patients in Southern Pakistan

Back ground: Immune thrombocytopenic purpura (ITP) is a hemorrhagic diathesis, characterized by platelets destruction alongside impaired production. Patients from Asian regions often exhibit distinctive characteristics in comparison to the western patients. We accomplished this study to evaluate the prevalence of primary versus secondary ITP along with the comparative analysis between them. The secondary objective was to determine the etiological spectrum of secondary ITP. Methods: We illustrate the results of a large cohort of newly diagnosed adults ITP from southern Pakistan. The study extended from January 2009-December 2013. Complete blood counts, HbsAg, Anti-HCV, ANA, stool for Helicobacterpylori were done on all. HIV, TSH, anti-dsDNA, RA factor, APLA and direct coombs test were evaluated in cases where indicated. Results: A total of 417 patients were included with a mean age of 40.95±14.82 years. Primarily disease was observed in the 3rd decade of life. Male to female ratio was 1:1.5. Mean platelets count was 46.21±27.45x109 /l. At diagnosis 43.16% (n=180) patients had hemorrhagic manifestations whilst 56.8% (n=237) were asymptomatic. None of the patient presented with visceral, retropharyngeal or intracranial bleed. The prevalence of secondary ITP was substantially higher (64.8%) as compared to primary ITP (35.2%). Secondary ITP was predominantly seen in HCV reactive patients (24.4%) followed by helicobacter-pylori infection (11%). Nevertheless 16.4% patients had underlying autoimmune disorders. Providentially no study subject was found to be HIV reactive. Conclusions: Our study revealed predominance of secondary ITP. However bleeding manifestations and degree of thrombocytopenia were high in primary-ITP. Infectious etiology followed by autoimmune disorders is mainly implicated for secondary ITP in our setting.