PLGA Nanoparticles for Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Novel Approach towards Reduction of Renal Radiation Dose

BACKGROUND:Peptide receptor radionuclide therapy (PRRT), employed for treatment of neuroendocrine tumors (NETs) is based on over-expression of Somatostatin Receptors (SSTRs) on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, (177)Lu-DOTATATE loaded PLGA nanoparticles (NPs) were formulated in the present study, as a potential therapeutic model for NETs. METHODOLOGY AND FINDINGS:DOTATATE was labeled with Lutetium-177 ((177)Lu) (labeling efficiency 98%; R(f)∼0.8). Polyethylene Glycol (PEG) coated (177)Lu-DOTATATE-PLGA NPs (50:50 and 75:25) formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated) and 303.8±67.2 and 494.3±71.8 nm (coated) for PLGA(50:50) and PLGA(75:25) respectively. Encapsulation efficiency (EE) and In-vitro release kinetics for uncoated and coated NPs of PLGA (50:50 & 75:25) were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated) and 65.385±5.67% & 58.495±5.35% (coated). NPs showed initial burst release between 16.64-21.65% with total 42.83-44.79% over 21 days. The release increased with coating to 20.4-23.95% initially and 60.97-69.12% over 21 days. In-vivo studies were done in rats injected with (177)Lu-DOTATATE and (177)Lu-DOTATATE-NP (uncoated and PEG-coated) by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With (177)Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated (177)Lu-DOTATATE-NP. The high liver uptake with uncoated (177)Lu-DOTATATE-NP (13.68±3.08% ID/g), reduced to 7.20±2.04%ID/g (p = 0.02) with PEG coating. CONCLUSION:PLGA NPs were easily formulated and modified for desired release properties. PLGA 50:50 NPs were a more suitable delivery vehicle for (177)Lu-DOTATATE than PLGA 75:25 because of higher EE and slower release rate. Reduced renal retention of (177)Lu-DOTATATE and reduced opsonisation strongly advocate the potential of (177)Lu-DOTATATE-PLGA-PEG NPs to reduce radiation dose in PRRT

Assessing COVID-19 Booster Hesitancy and Its Correlates: An Early Evidence from India

The emergence of SARS-CoV-2 mutants, waning immunity, and breakthrough infections prompted the use of booster doses of the COVID-19 vaccine to fight against the pandemic. India started booster doses in January 2022 and it is critical to determine the intention of booster dose uptake and its correlates. Therefore, the current cross-sectional study aimed to investigate booster dose acceptability and associated predictors among the Indian population. A convenience sampling technique was utilized to recruit a sample of 687 Indian residents. A 55-item psychometric validated survey tool was used to assess booster dose acceptability, vaccine literacy and vaccine confidence. Univariate, bivariate, and multivariate statistical methods were used to analyze the data. Over 50% of participants reported their willingness to take the booster dose. Among the group not willing to take the booster dose (n = 303, 44.1%), a significantly larger proportion of respondents were unvaccinated with the primary series (12.2% vs. 5.2%, p \u3c 0.001), had an annual income below 2.96 lacs/annum (52.8% vs. 33.1, p \u3c 0.001), were residents of rural areas (38.0% vs. 23.2%, p \u3c 0.001), were not living with vulnerable individuals (78.5% vs. 65.2%, p \u3c 0.001) and did not have family/friends who had tested positive for COVID-19 (54.6% vs. 35.1%, p = 0.001). Demographic, vaccine variables and multi-theory model subscales to predict the initiation of booster dose among hesitant participants were statistically significant, R2 = 0.561, F (26, 244) = 11.978, p \u3c 0.001; adjusted R2 = 0.514. Findings of this study highlight the need to develop evidence-based interventions to promote vaccine uptake, particularly among hard-to-reach communities living in developing countries

Systemic Lycopene as an adjunct to Non-Surgical Periodontal Therapy in Generalized Chronic Periodontitis

Aim: To evaluate the potency of systemic anti-oxidants in the non-surgical treatment of generalised chronic periodontitis. Objective: Purpose of this short term clinical study is to ascertain whether or not daily systemic supplementation of antioxidants adjunctively used after scaling and root planing (SRP) would improve clinical condition in generalised chronic periodontitis using C-reactive protein (CRP) as inflammatory markers and chronic periodontitis treatment index needs (CPTIN Index) to evaluate reduction in periodontal pockets. Results: Each group involved 10 participants with age group 30-65 years. The test group was provided with treatment with 20 mg Lycopene once daily after 24 hours of completion of scaling and root planing. The CRP value at baseline ranged from 3- 6.2 with a mean value of 4.87± 1.09. After one month of treatment, the CRP value ranges between 1.1- 4.8 with a mean value of 3.10 ± 1.05. This clearly indicates a significant decrease in CRP with t value 10.83 and >0.00 p value. The CRP value of control group at baseline ranged from 3-5.9 with a mean value of 4.58± 1.08. After one month of treatment with scaling and root planing, the CRP value ranges to 2.2- 5.4 with a mean value of 3.96 ± 1.08. This clearly indicates a significant decrease in CRP with t value 13.29 and > 0.00 p value. Conclusion: Lycopene as an antioxidant is a promising treatment modality as an adjunct to full mouth scaling. It helps to modulate oxidative stress in periodontium during periodontitis. It also leads to maintenance of periodontal health.&nbsp

Bisphosphonate-related osteonecrosis of the jaw: An insight

Bisphosphonates are potent inhibitors of osteoclast activity that reduce bone turnover and re-establish the balance between bone resorption and formation. They are effective in multiple clinical settings including postmenopausal osteoporosis, low bone mass in men, and drug-induced bone loss. Bisphosphonate-associated osteonecrosis of jaws (BRONJ) may result in serious oral complications, such as osteomyelitis and chronic exposure of necrotic bone. Dentists must be familiar with this disorder and pay special attention to all patients on bisphosphonate therapy due to their defective osteoclast function and reduced osseous tissue vascularity, leading to impaired wound healing and progressive necrosis of jaw bones. The purpose of this article is to review the history and pathogenesis of BRONJ, provide guidance to dentists on possible measures to prevent and manage patients with BRONJ

Diminution of free radical induced DNA damage by extracts/fractions from bark ofSchleichera oleosa(Lour.) Oken

The present study was undertaken to investigate the effect of extracts of Schleichera oleosa (Sapindaceae) for its cytotoxic and hydroxyl radical-scavenging activities. The bark of the tree was used to prepare extracts with different solvents (i.e., hexane, chloroform, ethyl acetate, methanol, and water). The extracts were initially assessed for their in vitro cytotoxicity potential in the sulforhodamine B dye assay against cell lines,such as 502713 (colon), SW-620 (colon), HCT-15 (colon), A-549 (lung), HEP-2 (liver), SK-NS-H (central nervous system), and IMR-32 (neuroblastoma). It was observed that the water extract was effective against all the three colon cancer cell lines, while only methanol and water extracts were effective against A-549 (lung) and HEP-2 (liver), respectively. As DNA damage is one of the hallmarks of cell death, so the extracts were assessed for their ability to scavenge hydroxyl radicals, in the deoxyribose degradation assay (site- and nonsite specific) as well as their protective effect against the hydroxyl radical–induced DNA damage in the plasmid nicking assay, using pBR322. It was observed that all the extracts, except chloroform and hexane, exhibited relatively greater antioxidant activity in the nonsite-specific than in the site-specific assay. Similarly, the extracts were also found to be effective in inhibiting the hydroxyl radical–induced unwinding of supercoiled DNA, which further confirmed the hydroxyl radical–scavenging ability of the extracts in the deoxyribose degradation method

Effects of preoperative walking ability and patient's surgical education on quality of life and functional outcomes after total knee arthroplasty

ABSTRACT OBJECTIVE: Prospectively analyze the effect of preoperative walking status and the patient's surgical education on functional outcomes and the three dimensions of quality of life (QoL) (pain, physical function, and mental health) after elective total knee arthroplasty (TKA). METHODS: A comparative analysis on the QoL and functional outcomes in patients who underwent total knee arthroplasty between January 2014 and June 2015. To compare effects of the patient's walking status and knowledge of the surgical procedure on QoL and functional outcomes following TKA by means of SF-36 questionnaire, CES D10, VAS, KSS, KSFS, WOMAC, as well as Friedmann and Wyman scores, 10MWT, and 30-second timed chair test, assessed before the operation and one, three, and six months after the operation. RESULTS: There were 168 knees in 154 patients: 46.75% men and 53.24% women. 52.38% of knees had grade-III OA and 40.47% of knees had grade-IV OA. Preoperatively, SF-36 PCS was 33.2 and MCS was 35.4. Mean KSS and KSFS in females was 37.3 (16.2) and 31.5 (13.8); in males it was 49.2 (18.4) and 42.5 (15.7), respectively. Mean WOMAC scores were 64.2 in females and 56.5 in males. Mean VAS and CES D10 scores were 8.8 and 8.2 in females, and 6.9 and 6.4 in males, respectively. Post operatively at the first, third, and sixth month, significant improvements in QoL and mean SF-36, CES D10, VAS, KSS, KSFS, WOMAC, and Friedmann and Wyman scores were observed, as well as in the 10MWT and 30 s timed chair test scores. Patients with better preoperative functional activity and satisfactory understanding of TKA presented a better functional performance and achieved a good quality life (p< 0.01). DISCUSSION: Surgeons educate TKA candidates regarding the surgical procedure, the nature of implants, and how the procedure would affect their lifestyle and what their expectations from TKA should be. These crucial considerations should boost their confidence, enhancing their involvement and cooperation in post-surgical rehabilitation, thereby improving their QoL, functional results, and post TKA experience. CONCLUSION: TKA candidates with good preoperative walking ability and understanding of knee arthroplasty have better QoL in early and late post-surgery periods. Patient's lifestyle and understanding significantly enhances the postoperative functional ability

Polyvinyl Alcohol Composite Films Reinforced with Taro (Colocasia esculenta) Stem Fiber: Thermal, Mechanical and Biodegradation Studies

290-297Polyvinyl alcohol/Glycerol/Citric acid based composite samples have been synthesized by the method of solvent casting. The composites have been explored in terms of thermal, tensile, biodegradability, water absorption analysis and SEM study with the addition of Colocasia esculenta stem fiber (2.5-20.0 %). The equilibrium water absorption percentage with the addition of fiber and upon the increasing content of fiber has been found to be increased with an abrupt change above 12.5 % fiber content. The high value of degradation percentage has been however observed with 20 % loading of fiber (29.13±1.28). Thermal stability of the composite films has also been found to show positive results with the addition of fiber with maximum value of onset degradation temperature obtained with 7.5 % reinforcement. The incorporation of fiber has resulted in enhancement of tensile strength due to modified interfacial adhesion between fiber and matrix with maximum value of 36.06±0.25 MPa obtained for composite with 7.5 % loading of fiber. SEM micrographs have shown the smooth and homogeneous surface of composite film without any loading of fiber (CE-0). High loading of fiber (20 %) however has introduced some voids, holes and cracks in the samples making it easy for water molecules to permeate in the composites responsible for its water absorption percentage