Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Cranial prostheses are frequently required for patients with cranial defects secondary to trauma, decompressive craniectomy, or other pathologies. When the resected or craniotomized bone cannot be reused, cranioplasty with artificial materials offers both aesthetic and protective benefits. However, high-end custom-made options, like polyether ether ketone or titanium prostheses, are expensive and not widely available. Heat-cured polymethyl methacrylate (PMMA) prostheses are generally preferred over their cold-cured counterparts. In-house dental laboratories can provide a cost-effective and practical solution by employing a lost-wax technique akin to denture fabrication, utilizing a three-dimensional printed custom open mold. Fabricating large heatcured PMMA cranioplasts presents certain challenges, such as the need for large flasks and potential porosity. These can be overcome by using a large stainless steel container (a tiffin box) and M-Seal epoxy to ensure an airtight curing process. This method can be easily adopted by standard dental laboratories. At our center, four patients have successfully fitted with cranioplasty prostheses produced using this technique. Even though the patients are outside of the scope of this technical note all of them indicated high satisfaction, and no complications were reported. This straightforward approach demonstrates that in-house, heat-cured PMMA cranioplasts can represent a viable, cost-effective option for cranial reconstruction.

Background/Aims: Self-expanding metallic stents (SEMS) are an alternative to emergency surgery (ES) for malignant colorectal obstruction. This study aimed to compare surgical outcomes between SEMS as a bridge to surgery (BTS) and ES in patients with malignant colorectal obstruction. Methods: A comprehensive database search was conducted until October 2023 to compare outcomes between SEMS as a BTS and ES. A subgroup analysis of results by malignancy site was performed. Results: We analyzed 57 studies, including 7,223 patients over a mean duration of 35.4 months. SEMS as a BTS showed clinical and technical success rates of 88.0% (95% confidence interval [CI], 86.1%–90.1%; I2=68%) and 91.6% (95% CI, 89.7%–93.7%; I2=66%), respectively. SEMS as a BTS revealed reduced postoperative adverse events (odds ratio [OR], 0.51; 95% CI, 0.41–0.63; I2=70%; p<0.001) and 30-day mortality (OR, 0.52; 95% CI, 0.37–0.72; I2=10%; p<0.001) compared to ES. Subgroup analysis showed postoperative mortality of 5% and 1.5% for left- and right-sided malignancies, respectively. Adverse events were 15% and 33% for the right and left colon, respectively. Conclusions SEMS as a BTS demonstrated a higher success rate, fewer postoperative adverse events, and a reduced 30-day mortality rate than ES, supporting its use as the preferred initial intervention for right- and left-sided obstructions and indicating broader clinical adoption.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

INTRODUCTION: Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. METHODS: A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. RESULTS: At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS ( P = 0.026) and OS ( P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. CONCLUSION Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; Mouth Neoplasms/mortality* ; Mouth Mucosa/radiation effects* ; Treatment Outcome ; Aged ; Adult ; Radiation Dose Hypofractionation ; Disease-Free Survival ; India ; Kaplan-Meier Estimate ; Dose Fractionation, Radiation ; Aged, 80 and over

Background and Objectives: Monosyllable words are the most common speech recognition stimuli since they test auditory perception and are used to assess speech recognition. However, there is a lack of resources available for the Urdu-speaking Pakistani population. This study aims to develop and psychometrically evaluate a digitally recorded Urdu monosyllabic word list for Word Recognition Score (WRS) testing. Subjects and Methods: A total of 135 monosyllabic words were selected from a previous study. These words were digitally recorded by a native female Urdu speaker in a studio. The recordings were psychometrically assessed by 30 native Urdu speakers with normal hearing. The 100 most familiar words were selected and organized into two lists, each further divided into four halves to ensure that the words were relatively homogeneous in terms of audibility. Results: The average psychometric slope between 20% and 80% for the full list was 4.78%/dB±0.22%/dB, while it was 4.81%/dB±0.35%/dB for the half list. No statistically significant difference in p-values was observed between the full and half lists. The mean psychometric slope for 50% intelligibility was 6.04%/dB for both the full list (SD=0.44) and the half lists (SD=0.40). Conclusions Digitally recorded Urdu monosyllabic word lists are valid for assessing speech recognition in native Urdu speakers with normal hearing.

Background/Aims: The irregular Z-line, defined as a segment of columnar mucosa less than 1 cm in the distal esophagus, is often biopsied despite guidelines advising against it due to a low risk of progression to esophageal adenocarcinoma (EAC). However, the clinical significance of an irregular Z-line remains unclear. This meta-analysis examines the prevalence of Barrett’s esophagus, dysplasia, and EAC in patients with an irregular Z-line. Methods: We searched Medline, Embase, and Scopus databases up to October 2023 for studies on the prevalence of Barrett’s esophagus, dysplasia, and EAC in these patients. A random-effects model was used for meta-analysis, and heterogeneity was assessed using I2 statistics. Results: Nine studies involving 17,637 patients were analyzed. Among those with an irregular Z-line, the prevalence of intestinal metaplasia was 29.4%. In patients with intestinal metaplasia, dysplasia was found in 6.2%, low-grade dysplasia in 5.9%, high-grade dysplasia in 1.6%, and EAC in 1.5%. These rates were higher compared to those without intestinal metaplasia. Conclusions Patients with an irregular Z-line and intestinal metaplasia may be at higher risk and could benefit from endoscopic surveillance. Further studies are needed to determine the necessity of biopsying irregular Z-lines.

Background and Objectives: Monosyllable words are the most common speech recognition stimuli since they test auditory perception and are used to assess speech recognition. However, there is a lack of resources available for the Urdu-speaking Pakistani population. This study aims to develop and psychometrically evaluate a digitally recorded Urdu monosyllabic word list for Word Recognition Score (WRS) testing. Subjects and Methods: A total of 135 monosyllabic words were selected from a previous study. These words were digitally recorded by a native female Urdu speaker in a studio. The recordings were psychometrically assessed by 30 native Urdu speakers with normal hearing. The 100 most familiar words were selected and organized into two lists, each further divided into four halves to ensure that the words were relatively homogeneous in terms of audibility. Results: The average psychometric slope between 20% and 80% for the full list was 4.78%/dB±0.22%/dB, while it was 4.81%/dB±0.35%/dB for the half list. No statistically significant difference in p-values was observed between the full and half lists. The mean psychometric slope for 50% intelligibility was 6.04%/dB for both the full list (SD=0.44) and the half lists (SD=0.40). Conclusions Digitally recorded Urdu monosyllabic word lists are valid for assessing speech recognition in native Urdu speakers with normal hearing.

Background and Objectives: Monosyllable words are the most common speech recognition stimuli since they test auditory perception and are used to assess speech recognition. However, there is a lack of resources available for the Urdu-speaking Pakistani population. This study aims to develop and psychometrically evaluate a digitally recorded Urdu monosyllabic word list for Word Recognition Score (WRS) testing. Subjects and Methods: A total of 135 monosyllabic words were selected from a previous study. These words were digitally recorded by a native female Urdu speaker in a studio. The recordings were psychometrically assessed by 30 native Urdu speakers with normal hearing. The 100 most familiar words were selected and organized into two lists, each further divided into four halves to ensure that the words were relatively homogeneous in terms of audibility. Results: The average psychometric slope between 20% and 80% for the full list was 4.78%/dB±0.22%/dB, while it was 4.81%/dB±0.35%/dB for the half list. No statistically significant difference in p-values was observed between the full and half lists. The mean psychometric slope for 50% intelligibility was 6.04%/dB for both the full list (SD=0.44) and the half lists (SD=0.40). Conclusions Digitally recorded Urdu monosyllabic word lists are valid for assessing speech recognition in native Urdu speakers with normal hearing.