Hypotensive effect of potent angiotensin-I-converting enzyme inhibitory peptides from corn gluten meal hydrolysate: Gastrointestinal digestion and transepithelial transportation modifications.

The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with -7.83 and - 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.

Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

Milk Exosome-Glow Nanosystem for Cancer Cellular and Tissue Bioimaging.

Milk-derived exosomes are widely used for diagnosis, delivery, imaging, and theranostic applications. Near-Infrared (NIR) based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications. However, almost all NIR imaging agents tend to have poor photostability, short half-life, nonspecific protein binding, and concentration-dependent aggregation(s). Therefore, there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents. Bovine milk exosomes are natural, biocompatible, safe, and efficient nanocarriers that facilitate the delivery of micro- and macromolecules. Herein, we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility and photostability of NIR dye. Following the acetic acid based extracellular vesicle (EV) treatment method, we extracted the bovine milk exosomes from a variety of pasteurized grade milk. The EVs were screened for their physicochemical properties such as particle size and concentration and zeta potential. The stability of these exosomes was also determined under different conditions, including storage temperatures, pH, and salt concentrations. Next, indocyanine green, a model NIR dye was loaded into these exosomes (Exo-Glow) via a sonication method and further assessed for their improved fluorescence intensity and photostability using an IVIS imaging system. Initial screening suggested that size of the selected bovine milk exosomes was ∼100-135 nm with an average particle concentration of 5.8 × 102 particles/mL. Exo-Glow further demonstrated higher fluorescence intensity in cancer cells and tissues when compared to free dye. These results showed that Exo-Glow has the potential to serve as a safer NIR imaging tool for cancer cells/tissues.

Safety and early efficacy of involved-field SBRT for nodal oligo-recurrent prostate cancer.

Purpose: Following treatment for localized prostate cancer, a subset of men will develop recurrent disease in the abdominopelvic nodes. For radiation therapy (RT), the optimal treatment volume, fractionation schedule, and dose remain unanswered questions. We report early outcomes for patients treated with involved-field stereotactic body radiation therapy (SBRT) (IF-SBRT) for nodal oligo-recurrent (NOR) prostate cancer. Methods: Between January 2018 and October 2023, 67 patients with a median age of 75 with NOR prostate cancer treated with 74 courses of IF-SBRT at Georgetown were eligible for this analysis. NOR was defined as any volume of disease that could be safely treated within an IF. All patients were treated with five-fraction IF-SBRT (27.5-35 Gy). The IF treatment volume was defined as the nodal basin containing the gross disease as well as the immediately adjacent basins. Disease progression was defined as a prostate-specific antigen (PSA) rise above the pretreatment baseline or initiation of a second treatment. Local control and progression-free survival were calculated using the Kaplan-Meier method. Results: Detection of pre-SBRT NOR was ascertained by prostate-specific membrane antigen (PSMA) (38%), fluciclovine (50%), or MRI/CT (12%). Median follow-up was 50 months (1-262). The median pre-salvage PSA was 6.5 ng/mL (range, 0.1-335). The median number of involved nodes was 3 (range, 1-16). The local control at 1 and 2 years was 98% and 93%, respectively. The 1- and 2-year progression-free survival was 78% and 50%, respectively. Twenty percent of treatment courses were followed by acute Grade 2 gastrointestinal (GI) toxicity: diarrhea (9%) and/or nausea (14%). Two patients (3%) experienced late Grade 2 nausea. On univariate analysis, measures of disease volume such as hormone sensitivity (p = 0.03), increasing involved node number (p = 0.008), and abdominal treatment (p = 0.03) were significantly associated with GI toxicity. Conclusions: With the widespread adoption of PSMA agents, NORs are likely to increase. The optimal combination of local and systemic therapy in this population is unknown. With a favorable toxicity profile, IF-SBRT represents a safe and convenient local therapy treatment option for an elderly patient population. Patient- and treatment-related factors such as a large number of involved nodes and/or abdominal treatment may be associated with an increased risk of GI toxicity.

Cangrelor versus crushed ticagrelor in patients with acute myocardial infarction and cardiogenic shock: rationale and design of the randomised, double-blind DAPT-SHOCK-AMI trial.

Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety. The DAPT-SHOCK-AMI trial (ClinicalTrials.gov: NCT03551964; EudraCT: 2018-002161-19) will assess the benefits of cangrelor in patients with an initial CS-AMI undergoing primary angioplasty. This randomised, multicentre, placebo-controlled trial of approximately 550 patients (with an allowed 10% increase) in 5 countries using a double-blind design will compare initial P2Y12 inhibitor treatment strategies in patients with CS-AMI of (A) intravenous cangrelor and (B) ticagrelor administered as crushed tablets at a loading dose of 180 mg. The primary clinical endpoint is a composite of all-cause death, myocardial infarction (MI), or stroke within 30 days. The main secondary endpoints are (1) the net clinical endpoint, defined as death, MI, urgent revascularisation of the infarct-related artery, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium criteria; (2) cardiovascular-related death, MI, urgent revascularisation, or heart failure; (3) heart failure; and (4) cardiovascular-related death, all (1-4) within 1 year after study enrolment. A platelet reactivity study that tests the laboratory antiplatelet benefits of cangrelor, when given in addition to standard antiplatelet therapy, will be conducted using vasodilator-stimulated phosphoprotein phosphorylation. The primary laboratory endpoints are the periprocedural rate of onset and the proportion of patients who achieve effective P2Y12 inhibition. The DAPT-SHOCK-AMI study is the first randomised trial to evaluate the benefits of cangrelor in patients with CS-AMI.

Comparative Efficacy and Safety of Low-Dose Versus Standard-Dose Rabbit Antithymocyte Globulin Induction Strategy in Kidney Transplant Recipients: Insights From a Single-Center Experience in North India.

Background Rabbit antithymocyte globulin (rATG) is frequently utilized as an induction therapy in kidney transplant recipients (KTRs). Full-dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity. However, definitive data on the appropriate rATG dosage remains scarce. In this study, we evaluated the efficacy and tolerability of varying rATG doses in KTRs. Methodology A single-center, retrospective, observational study was conducted between 2009 and 2014 in a cohort of 208 KTRs who received rATG induction therapy. Patients included in the study had received two to three consecutive doses of rATG as part of their planned induction protocol. Participants were categorized into the following two groups based on the cumulative dosage of rATG received during induction therapy: group A received 2 or 2.5 mg/kg, while group B received ≥3 mg/kg. The five-year follow-up data were analyzed. Results A cumulative rATG dose of 2 or 2.5 mg/kg and ≥3 mg/kg was given to 122 and 86 patients, respectively. The incidence of delayed graft function (DGF), acute rejection episodes, total graft loss, death, and death-censored graft loss was 6.25%, 3.84%, 7.21%, 4.32%, and 2.88%, respectively. Two malignancies and 141 infectious complications were noted. There was no significant difference between the groups regarding DGF, total graft loss, death, death-censored graft loss, infectious complications, and incidence of acute rejection episodes. Deceased donor kidney transplantation was identified as a significant predictor of acute rejection episodes (odds ratio = 9.19, 95% confidence interval = 1.567-53.907; p = 0.014). Conclusions The dosage for rATG induction therapy for KTRs should be tailored based on immunological and other factors impacting graft survival, along with a comprehensive risk assessment for potential infectious complications. A cumulative dose of 2.0 or 2.5 mg/kg could be optimal, offering effective induction therapy in KTRs with excellent graft survival rates and potentially fewer infectious complications.

The Evaluation of Tumor Budding in Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

Background and objective Oral submucous fibrosis (OSMF) is a common and potentially malignant disorder with a high risk of malignant transformation to oral squamous cell carcinoma (OSCC). Tumor budding is a scattered pattern of invasion and is related to the aggressive behavior of malignant tumors, increased depth of invasion, higher clinical staging, size, and grade of the tumor. The present study aimed to evaluate tumor budding in OSCC arising in the background of OSMF. Materials and methods A total of 120 patients with OSCC (30 each of OSCC arising in the background of OSMF, well-differentiated, moderately differentiated, and poorly differentiated OSCC) were included in the study. Hematoxylin and eosin (H&E)-stained sections were evaluated for the presence of tumor buds at the invasive front of the tumor. Kappa statistics and chi-square tests were employed to statistically compare the results by using IBM SPSS Statistics 23 software (IBM Corp., Armonk, NY). A p-value of less than or equal to 0.05 was considered statistically significant.  Results The mean age of the occurrence of OSCC arising in the background of OSMF was 45.3 ±7.62 years. A progressive increase in the tumor buds was noted in OSCC arising in the background of OSMF, well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (WDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). The chi-square test showed no significant difference between OSCC in the setting of OSMF and WDSCC (p=0.604) groups; however, a significant difference was noted with MDSCC (p=0.001) and PDSCC (p=0.000) groups. Conclusions OSCC arising in the background of OSMF shows lower tumor budding at the invasive front of the tumor. This histopathological parameter can be easily identified in the H&E sections and is fairly reproducible. Hence, reporting the presence of tumor budding will help in predicting the prognosis of these patients.

Ex Utero Intrapartum Treatment for Prenatally Diagnosed Cervicofacial Lymphatic Malformations.

INTRODUCTION: Cervicofacial lymphatic malformations (cf-LM) may be identified on prenatal ultrasound, prompting consideration of ex utero intrapartum treatment (EXIT) to secure the fetal airway. Furthermore, the recent shift in postnatal management of cf-LM from resection alone toward a multimodal approach including sirolimus and sclerotherapy may impact the neonatal outcomes of cf-LM. This study aims to characterize the neonatal outcomes of patients with prenatally diagnosed cf-LM who underwent EXIT-to-airway. METHODS: Retrospective, single-center review of all patients who underwent EXIT-to-airway for cf-LM (2011-2020) was performed. Demographics, prenatal imaging, intraoperative details, and outcomes were analyzed using descriptive statistics (median [interquartile range]). RESULTS: Six patients with prenatally diagnosed cf-LM underwent EXIT-to-airway at a median gestational age of 36 (33.8-36.9) wk. The median volume on fetal magnetic resonance imaging was 187.5 mL (142.3-237.8) and median tracheoesophageal displacement index was 11 mL (9.25-15). All were successfully intubated on placental support with a median duration of 25 (15.25-91) d. There was one fatality at day of life 10 due to necrotizing enterocolitis totalis. Among survivors, 2 of 5 underwent tracheostomy placement, 4 of 5 underwent gastrostomy tubes placement, and all 5 received sirolimus at day of life of 9 [8-10] d. Four patients underwent debulking or excision of their cf-LM during the initial hospitalization. Patients had a median length of stay of 68 (45-129) d. One patient experi enced a pneumothorax with evidence of barotrauma following EXIT-to-airway requiring chest tube placement (duration 8 d). CONCLUSIONS: EXIT-to-airway procedure remains a feasible strategy for mitigating neonatal hypoxia in cases of prenatally diagnosed cervicofacial lymphatic malformations. However, postnatal outcomes are variable with potential long-term aerodigestive sequelae.

Pattern of care and treatment outcomes of metastatic non-clear cell kidney cancer: a single centre experience from India.

Background: Non-clear-cell renal cell carcinoma (nccRCC) refers to a rare diverse heterogeneous group of tumours; usually treated with immune check point inhibitors and or tyrosine kinase inhibitors (TKIs). Prospective large-scale data from Asian countries is limited. Methods: This is a retrospective study of patients with metastatic nccRCC treated at Tata Medical Centre, Kolkata, India, from 2012 to 2022. Demographic profiles, histologic subtypes, treatment details, response to therapy (by response evaluation criteria in solid tumours (RECIST v1.1)) and survival status were captured from electronic medical records (EMRs) of hospitals up till May 2023. Kaplan Meier methods were estimated to assess progression-free survival (PFS) and overall survival (OS). Results: A total of 89 consecutive patients were screened for this study, 24 were excluded due to inadequate data in EMR. 65 patients were included in the final analysis, with a median age at diagnosis of 59 years (range 20-84) of which 81% were male. Histologic subtypes comprised of 43% papillary, 31% clear cell with mixed histology, 3% sarcomatoid and 23% others including chromophobe, mucinous-tubular, spindle cell, oncocytic, medullary, poorly differentiated and rhabdoid). The most common site of metastasis was the lung 62% (n = 40) followed by non-regional nodes 32%, bone 26% and liver 14%. 15% patients presented with haematuria and 62% underwent nephrectomy prior to systemic therapy. The majority received pazopanib 46% (n = 30), chemotherapy 20% (n = 13) including bevacizumab plus erlotinib, sunitinib 15% (n = 10) or cabozantinib 14% (n = 9). Only 3(5%) patients received nivolumab plus cabozantinib combination. Response to treatment showed complete response in 1.5%, partial response in 20%, stable disease in 51% and progressive disease in 23% as per RECIST v1.1. 17 patients required dose reduction and interruption due to adverse effects and 33% (n = 22) received second-line therapy with nivolumab 18% (n = 4), axitinib and everolimus among others. After a median follow up of 44 months, the median PFS was 13 months (95%CI 7.2-18.9) and the median OS was 17 months (95%CI 12.1-22.1) for the entire cohort. Conclusion: The overall response and survival for metastatic nccRCC was relatively better in comparison with published data, despite the limited number of patients treated with ICIs due to cost and access barriers.

Docetaxel-tethered di-Carboxylic Acid Derivatised Fullerenes: A Promising Drug Delivery Approach for Breast Cancer.

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use.

Preclinical Assessment of the PI3Kα Selective Inhibitor Inavolisib and Prediction of Its Pharmacokinetics and Efficacious Dose in Human.

1. Small molecule inhibitors of the PI3K pathway have been extensively investigated as potential anticancer agents. Among the effectors in this pathway, PI3Kα is the kinase most frequently associated with the development of tumors, through mutations and amplifications of the PIK3CA gene encoding the p110α catalytic subunit.2. Inavolisib (GDC-0077) is a potent and PI3Kα-selective inhibitor that also specifically triggers the degradation of the mutant p110α protein.3. We characterized inavolisib ADME properties in preclinical in vitro and in vivo studies, assessed its efficacy in the PIK3CA mutant KPL-4 breast cancer xenograft model, and predicted its pharmacokinetics and efficacious dose in humans.4. Inavolisib had a moderate permeability (1.9•10-6 cm/s) in MDCK cells and was a P-gp and Bcrp1 substrate. It appeared metabolically stable in hepatocytes incubations from human and preclinical species. The systemic clearance was low in mouse, monkey and dog and high in rat. Oral bioavailability ranged from 57.5% to 100%. Inavolisib was efficacious in the KPL-4 sub-cutaneous xenograft model.5. The PK/PD model parameters estimated from the efficacy study, combined with PBPK model-predicted human PK profiles, projected that a dose of 3 mg could lead to clinical response. Inavolisib is currently being tested in phase 3 trials.

Effect of anesthetic technique on antitumor immunity in patients undergoing surgery for gall bladder cancer: A prospective randomized comparative study.

There is a paucity of literature regarding the effect of anesthetic techniques on antitumor immunity, especially in gall bladder malignancies. We designed a study to compare the effect of propofol-based total intravenous anesthesia and sevoflurane-based general anesthesia-on antitumor immunity, including tumor growth factor-ß (TGF-ß), T-helper cell profile, and inflammatory markers. A pilot prospective randomized trial was conducted in 64 patients undergoing surgery for gall bladder malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of ASA physical status I-III fulfilling the inclusion criteria were randomized to either group S (sevoflurane-based general anesthesia) or group T (propofol-based total intravenous anesthesia). Preoperative (morning of surgery) and postoperative (24 h and 1 month after surgery) blood samples were obtained. Demographic profile and preoperative parameters were comparable between both groups. There was a statistically significant difference in the postoperative value of TGF-ß (higher in group T). There was a statistically significant difference in postoperative interleukin-17A value (indicative of TH17 cells), and it was found to be higher in group S. Propofol-based TIVA increases serum TGF-ß levels. At the same time, Sevoflurane modulates T-helper cells-based immunity to increase TH17 cells in patients with gall bladder cancer. Multiple larger studies will be required to validate the results and provide useful recommendations.

The Use of Cangrelor in Cardiogenic Shock: Insights from the CAMEO Registry.

INTRODUCTION: Little is known about the use of cangrelor in patients with myocardial infarction (MI) presenting with cardiogenic shock (CS). METHODS: CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a multicenter observational registry evaluating platelet inhibition in patients with MI. We examined the duration of cangrelor infusion and the amount of time to transition from cangrelor to an oral P2Y12 inhibitor in patients with CS. We also assessed major adverse cardiovascular events (MACEs) and bleeding risks, stratified by dosage duration, time to transition and oral P2Y12 inhibitor potency. RESULTS: Among 2352 cangrelor-treated patients with MI, 249 patients were in CS. Among the patients with CS, 16 (6.4%) received the "bridge" infusion dose, 202 (81.1%) the PCI cangrelor infusion dose, and 30 (12.0%) had a combination of both infusion doses. Patients with CS had a median age of 66 years; 32% were women; 21% were Black patients; 35% had diabetes; 19% received thrombectomy; and 59% received mechanical circulatory support (MCS) (35% intra-aortic balloon pump, 27% Impella). The median duration of infusion was 3.9 (2-21.5 hours) in patients with CS and was 2 (1.6-3.1 hours) for all cangrelor-treated patients. The median duration of transition from cangrelor to oral P2Y12 inhibitor administration was 0.1 (-0.5-21.0 hours) for patients with CS. In multivariable modeling, chronic lung disease and the use of MCS and was associated with longer cangrelor infusions (defined as > 3.9 hours). Among cangrelor-treated patients with CS, 24.1% of these patients had a bleeding event, and 41.8% had a MACE event. After adjustment, a longer cangrelor infusion duration was associated with increased risk of bleeding (P < 0.05). CONCLUSIONS: The median duration of cangrelor infusion was longer for patients presenting with CS. Use of MCS was associated with longer cangrelor infusion durations in patients with CS. Further work is needed to understand the pharmacodynamics of antiplatelet agents in patients with CS.

Does sheath size matter: benchtop comparison of flow and pressure across variety of continuous flow endoscopes.

INTRODUCTION: Laser enucleation utilizes purpose-built endoscopes for laser stabilization and continuous flow. No evaluation has been done with respect to flow or intravesical pressure with these scopes. We sought to evaluate the effect different endoscopes and sheath sizes on irrigation outflow and intravesical pressure. METHODS: Using a benchtop model using a silicone bladder model, five outer/inner sheath combinations were assessed: Storz 28/26Fr, Storz 26/26Fr, Wolf 26/24Fr, Wolf 26/22Fr, and Wolf 24/22Fr. A urodynamics pressure transducer was inserted alongside the scope for bladder pressure measurement and outflow from scope to drain was measured using uroflowmetry device. Four 1-minute trials were recorded for each sheath and the steady state flow and pressure was recorded. RESULTS: The Storz 28 F outer sheath and 26 F inner sheath had the highest outflow (12.4 ± 0.5 mL/s, p < 0.01). The Wolf 24 F outer and 22 F inner had the lowest outflow (7.0 ± 0.0 mL/s, p < 0.01). The steady state bladder pressure was the lowest in the Storz 28/26 (1.5 ± 1.7 cm H2O, p < 0.01)) and the greatest in the Storz 26/26 (24.2 ± 1.9 cm H2O, p < 0.01). CONCLUSION: The Storz 28/26 combination had best outflow rate and lowest intravesical pressures in our benchtop study. Flow rates generally decreased with smaller sheath sizes and steady state bladder pressures increased as the difference between the outflow and inflow sheath size narrowed. These findings provide initial parameters that could guide sheath selection in future to optimize visualization and success of voiding trials.

Current Diagnosis of Bleeding Disorders in Lower Income Countries.

There have been considerable advances in diagnosing and treating bleeding disorders. But the scenario remains dismal in resource-constrained settings in low and lower-middle-income countries (LMICs). Seventy-five percent of the patients with inherited bleeding disorders do not get diagnosed in LMICs. In resource-constrained settings, infectious disease and malignancies take the major focus. Bleeding disorders do not get prioritised in LMICs, and this leads to underdiagnoses and suboptimal treatment. There are various challenges like financial status, inadequacy of health care infrastructure, lack of patient registry and lack of awareness across medical staff, general population and government stakeholders. The lack of skilled laboratory personnel and laboratory infrastructure for optimal bleeding disorder diagnosis adds on to the problem. World Federation of Hemophilia (WFH) has been at the forefront in developing strategies to overcome some of these inadequacies; however, more active participation of the stakeholders including patients, medical professionals and policy makers is the need of the hour. This review highlights the different challenges in LMICs in diagnosing bleeding disorders, the gap between high-income countries and LMICs and the possible strategies in closing the gap.

Assessment of age specific serum Prostate Specific Antigen (PSA) levels for Indian population: A retrospective analysis at a tertiary healthcare facility.

INTRODUCTION: Prostate-specific antigen (PSA) is a key marker for prostate cancer screening, but its utility is debated, prompting exploration of PSA derivatives for improved accuracy. While racial variations in serum PSA levels are documented, limited data exists for the Indian population. Given increasing life expectancy and heightened awareness of prostate cancer, this study aims to establish age-specific PSA ranges in an Indian cohort, contributing vital insights for population-specific screening and diagnosis. METHODS: A cross-sectional study was conducted on 4860 men with lower urinary tract symptoms (LUTS). Data, collected from April 2016 to March 2023, included age, PSA levels, digital rectal examination (DRE), and biopsy results. Statistical analysis involved Spearman's correlation, descriptive statistics, and confidence intervals. RESULTS: Of the studied participants, 809 underwent prostatic biopsy, revealing malignancy in 500 cases. Age-specific PSA values were studied in 4170 subjects and showed positive correlation with increasing age and prostate size. Most cancers were metastatic (66%), emphasizing the need for early detection. Age-specific PSA ranges were lower in the Indian population compared to the West. This study's Indian cohort exhibited higher PSA values than some previous Indian studies but lower than Western populations, aligning with global trends. The rising incidence of prostate cancer in India underscores the importance of understanding the disease burden. CONCLUSION: PSA levels exhibit race-specific variations, cautioning against direct extrapolation of Western data to the Indian population. This study contributes age-specific PSA ranges for an Indian cohort, facilitating nuanced prostate cancer screening strategies.

The role of extracellular vesicles in the pathogenesis of gynecological cancer.

Gynecological cancer, the most common form of cancers in women worldwide, initiates in the reproductive organs of females. More often, the common treatment measures, i.e. surgery, radiation, and medical oncology are found to be unsuccessful in the treatment of gynecological tumors. Emerging evidence indicates that extracellular vesicles (EVs) play a significant role in the pathogenesis of gynecological cancers by distinct mechanisms. The present review highlights how EVs contribute to the progression of different types of gynecological cancers such as cervical cancer, endometrial cancer, ovarian cancer, vaginal cancer, uterine sarcoma, gestational trophoblastic disease (GTD), and vulvar cancer. The primary focus is to understand how EVs' cargo alters the phenotypic response of the recipient cells, thereby contributing to the progression of the disease, thus can be considered as a prognostic and diagnostic biomarker. A brief discussion on the role of EVs in the diagnosis and prognosis of different gynecological cancer types is also highlighted. Targeting the biogenesis of the EVs, their inside cargo, and EVs uptake by the recipient cells could be a potential therapeutic approach in the treatment of gynecological cancer beside conventional therapeutic means.

Plasmonic semi shells derived from simultaneous in situ gold growth and anisotropic acid etching of ZIF-8 for photothermal ablation of metastatic breast tumor.

Open nanoshells such as nanobowls or nanocups collectively described as 'semi shells' have unique plasmonic properties due to their lack of symmetry. So far, their fabrication was based on multistep and laborious methods such as solid state sputter coating or selective deposition/etching using sacrificial templates. In this work, we report a rapid one step colloidal synthetic protocol for PEGylated semi-shell (SS) fabrication by simultaneous facet specific anisotropic chemical etching of rhombic dodecahedral ZIF-8 and heterogenous nucleation & growth of gold. The SS possesses a strong localized surface plasmon resonance in the near-infrared region, which is retained after surface passivation with polyethylene glycol and subsequent cryopreservation for extended shelf-life. Freshly reconstituted PEGylated SS was found to be safe & non-toxic in healthy C57BL/6 mice post intravenous administration. The PEGylated SS displayed significant photothermal efficiency of ~37% with 808 nm laser irradiation. Preclinical assessment of intra-tumoral photothermal efficacy indicated complete remission of primary breast tumor mass with insignificant metastasis to vital organs in 4T1 FL2 tumor bearing CD1 nude mice. Further, PEGylated SS mediated photothermal therapy also yielded morbidity free survivael of 75% for up to 90 days, indicating their potential to significantly improve outcomes in advanced breast tumors.