The current study aims to assess the beliefs of the general public in Pakistan towards conspiracy theories, acceptance, willingness to pay, and preference for the COVID-19 vaccine. A cross-sectional study was conducted through an online self-administered questionnaire during January 2021. The Chi-square test or Fisher exact test was utilized for statistical data analysis. A total of 2158 respondents completed the questionnaire, among them 1192 (55.2%) were male with 23.87 (SD: ±6.23) years as mean age. The conspiracy beliefs circulating regarding the COVID-19 vaccine were believed by 9.3% to 28.4% of the study participants. Among them, 1040 (48.2%) agreed to vaccinate on its availability while 934 (43.3%) reported the Chinese vaccine as their preference. The conspiracy beliefs of the participants were significantly associated with acceptance of the COVID-19 vaccine. The existence of conspiracy beliefs and low vaccine acceptance among the general population is a serious threat to successful COVID-19 vaccination.

The introduction of new office procedures to easily identify all patients receiving oral therapy and improvement in patients' ability to manage symptoms at home with the use of self-care guidelines contributed to an improvement in managing patients who are taking oral oncolytics.

Experimental results concerning the radon exhalation rate from samples of building materials which were collected from the districts of Muzaffarabad and Neelum Valley, Azad Kashmir, Pakistan are presented. The study aims at assessing the contribution of building materials towards the total indoor radon exposure to the inhabitants of the studied area. In this context, samples of building materials, namely, soil, sand, gravel aggregates, and bricks were collected from different parts of the districts of Muzaffarabad and Neelum Valley. After processing, the samples were placed in plastic containers and box type radon detectors were installed in it at heights of 25 cm above the surface of the samples. The containers were then hermetically sealed. After 80 days of exposure to radon, CR-39 detectors were etched in 25% NaOH at 80 °C for 16 h and counted under an optical microscope. The measured track densities were related to radon concentrations. Radon exhalation rate from soil, gravel aggregates, sands, and bricks varied from 171 ± 11 to 344 ± 11, 168 ± 17 to 322 ± 11, 366 ± 8 to 649 ± 8 and 184 ± 14 to 231 ± 14 mBq m–2 h–1, respectively. Present data have been compared with the published data for other parts of the world. © 2011, V.S. Sobolev IGM, Siberian Branch of the RAS. Published by Elsevier B.V. All rights reserved.

Measurements of indoor radon concentrations in 200dwellings of four districts of Azad Kashmir have been carried out using CR-39-based radon dosimeters. Indoor radon levels were calculated for four seasons (i.e. spring, summer, autumn and winter) in Muzaffarabad, Hattian, Neelum and Poonch districts. Maximum value of radon concentration (398 AE 2 BqÁm À3 ) has been found in Muzaffarabad district (in bedrooms) and minimum value (23 AE 9 BqÁm À3 ) is reported for Hattian district (in living rooms). Elevated values of radon levels have been found in winter, whilst lower values are observed in summer season. Seasonal correction factors calculated for spring, summer, autumn and winter seasons were found to be 1.02 AE 0.91, 0.86 AE 0.77, 0.98 AE 0.92 and 1.14 AE 1.04, respectively. Measured values for winter/spring, winter/summer and winter/autumn radon ratios were found as 1.11 AE 1.28, 1.33 AE 1.21 and 1.15 AE 1.17. Radon doses have been calculated and yearly mean effective dose has been found 2.52 AE 1.22 mSv, which is less than the lower limit of the recommended action level 3-10 mSv.

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), is a poly-chlorinated pyridine cholesteryl carbonate whose MOA is via alkylation of DNA @ N7 - guanine and N6 - cytosine and via oxidative stress. DM-CHOC-PEN underwent a phase I study in patients with advanced cancer +/- CNS involvement and is being evaluated in a phase II trial in patients with primary brain cancer and brain metastases from melanoma, breast, and lung cancers. The aims are to assess clinical responses when DM-CHOC-PEN is administered I.V, at maximum tolerated dose (MTD) and to monitor safety/toxicities, pharmacokinetics, and cardiac functions - IND 68,876. Patients & Methods: In phase I, DM-CHOC-PEN was administered as a 3-hr IV infusion once every 21-days to patients with advanced cancer - melanoma (n = 3), colorectal CA (n = 4), breast (n = 3), lung (n = 8) and glioblastoma multiforme (GBM) (n = 9) - the most common tumor treated. Cohorts were treated with escalating doses from 39 to 111 mg/m2. The phase II dose schedule is 2-tiered: 85.8 mg/m2 for patients with liver involvement and 98.7 mg/m2 for patients with normal livers. Results: Forty (40) patients have been treated to date - 27 in phase I and 13 in phase II. The drug was well tolerated; the most common adverse effects were fatigue (n = 2), liver dysfunction - elevated bilirubin (Gr-3, n = 3; Gr-2, n = 1), ALT/AST (Gr-2, n = 3), alk phos (Gr-2, n = 3), nausea (Gr-1/2, n = 5) and an allergic reaction (Gr-2, n = 1). Three (3) patients with liver metastasis had hyperbilirubinemia (Gr-3 SLT) - two (2) at 98.7 mg/m2 and one (1) at 111 mg/m2 levels. No neuro/psychological, hematological, cardiac or renal toxicities were observed. PK studies revealed the following profile for DM-CHOC-PEN 98.7 mg/m2: AUC o-t = 1850 mg.h/L, CL - 3.0 L/h, T1/2 α - 3.3 h & Tβ - 79.1 h. DM-CHOC PEN and DM-PEN (metabolite) showed a rebound phenomenon at ∼50 hours post-infusion with a T release of 26.7 h for plasma and rbcs. DM-CHOC-PEN and DM-PEN were detected 3 and 15 days bound to RBCs (70 - 111 mg/m2); DM-CHOC-PEN was also detected in the urine (Cmax = 17.5 μg/mL) until day 21. The AUC was linear for all doses. DM-CHOC-PEN was detected in spinal sarcoma and in lung cancer tissues (75 & 190 ng/g, resp.) surgically obtained from patients 21-days post single injection of 39 & 98.7 mg/m2, resp. Patients receiving dexamethasone demonstrated lower blood levels of DM-CHOC-PEN along with induction of steroid esterase activities. After multiple doses, DM-CHOC-PEN also induced steroid esterase levels, which reversed within 4 weeks. Steroid esterase assays may be a valuable companion assay. Conclusion: DM-CHOC-PEN is safe at the presented dose levels and shows a favorable PK profile. To date, 15 patients have had responses with significant PFS/OS, including 10 with CNS involvement. DM-CHOC-PEN is well tolerated with manageable toxicities. Complete patient responses/toxicities will be presented. Supported by NCI/SBIR grant - R43/44CA132257 Citation Format: Roy S. Weiner, P Friedlander, T Mahmood, Adilia Hormigo, C Gordon, Y Saenger, ML Ware, VK Thirukonda, VM Patel, TJ Cosgriff, AH Rodgers, LR Morgan, G Bastian. Results from the early cancer clinical trials for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT218. doi:10.1158/1538-7445.AM2015-CT218

Procarbazine is a chemotherapy methylating agent that has been used in combination with other drugs, perhaps most successfully in the treatment of Hodgkin's disease. There are several side effects that it is commonly associated with; however, it has only rarely been reported to cause lung injury. The resulting pneumonitis may be severe and irreversible. There are eight reported cases in the literature. Here, we report another such case.

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate whose MOA is via alkylation of DNA @ N7 - guanine and induces oxidative stress. The main aims of this first-in human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs) and pharmacokinetics (PK) of DM-CHOC-PEN - IND 68,876. Patients & Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once every 21-days in 21 patients with melanoma (n=3), colorectal CA (CRC, n=3), and glioblastoma multiforme (GBM) (n= 6); the most frequent diagnoses. The trial allowed enrollment of patients with advanced cancer +/- CNS involvement. The starting dose was 39 mg/m2 with escalations to date up to 98.7 mg/m2. Results: Twenty-one (21) patients have been treated to date. MTD was 2-tiered and defined as 85.8 mg/m2 for patients with liver involvement and, for patients without liver abnormality it is not yet defined but is at least 98.7 mg/m2, for the latter population. The drug was well tolerated with the most common adverse effects being fatigue (n=2), liver dysfunction - elevated bilirubin (Gr-3, n=2; Gr-2, n=1), ALT/AST (Gr-2, n=3), alk phos (Gr-2, n=3) and an allergic reaction (Gr-2, n=1). No neuro/psychological, hematological or renal toxicity observed. Two (2) patients with liver metastasis demonstrated hyperbilirubinemia (Gr-3 SLT) at the 98.7 mg/m2 dose level. Five (5) additional patients with liver disease have been treated at 85.8 mg/m2 level without toxicity - the MTD for that stage of cancer. Dose cohorts @ 98.7 mg/m2 are in progress for non-liver staged patients. PK studies in humans revealed the following profile for DM-CHOC-PEN 70 mg/kg: AUC o-t = 980 mg.h/L, CL - 0.141L/h, T1/2 α - 0.63 h & Tβ - 24.1 h. DM-CHOC PEN and DM-PEN showed a rebound phenomenon @ ∼ 50 hours post-infusion with a T release of 26.7h. Same phenomenon is observed in RBCs (estimation using Monolix 3.2). DM-CHOC-PEN and DM-PEN were detected 3 and 15 days bound to RBCs (after 70 mg/m2); DM-CHOC-PEN was also detected in the urine (Cmax=17.5 μg/mL) until day 15. The AUC was linear for all doses. Similar to the rats, the total lipid profiles in the patients were erratic (2o to the lipid emulsion vehicle) during the 3-h infusion period, and then returned to pre-treatment values after 24 h. The triglycerides were the most significantly affected. DM-CHOC-PEN could be identified in spinal sarcoma tissue (in 190 ng/g quantities) obtained surgically from a patient 21- days post single injection of 39 mg/m2. Conclusion: DM-CHOC-PEN is safe at the presented dose levels and shows a favorable PK profile. Seven (7) patients have observed responses or significant PFS, including 5 with CNS involvement. DM-CHOC-PEN is well tolerated with manageable toxicities. Complete patient responses/toxicities will be presented. Supported by NCI/SBIR grant -1R43CA132257. Citation Format: Roy S. Weiner, Philip Friedlander, Craig Gordon, Yvonne Saenger, Marcus Ware, Tallat Mahmood, AH Rodgers, Gerard Bastian, S Urien, Lee Roy Morgan. A first-in-humans phase I cancer clinical trial for 4-Demthyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1185. doi:10.1158/1538-7445.AM2013-1185

4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine carbonate with a MOA via bis-alkylation of DNA @ N 7-guanine and N 4-cytosine that has completed adult clinical Phase I and II trials in individuals with malignancies involving the CNS. We report here objective clinical observations seen in a clinical Phase I DM-CHOC-PEN trial with AYA subjects that have cancer (some of which had CNS involvement). Subjects & Methods: DM-CHOC-PEN was administered as a single 3-hr IV infusion once every 21 days in escalating doses from 50-98.7 mg/m 2 to individuals (aged 15-39 years of age) with advanced malignancies. Results: Twelve (12) AYA individuals have been treated to date (with or without CNS involvement). The drug was well tolerated with fatigue (17%) being the most common adverse effect. No neuro/cognitive, liver dysfunction, hematological, cardiac, renal or GI toxicities were observed. Pharmacokinetic profiling revealed higher AUCs for all dose levels (50-98.7 mg/m 2) than had been seen previously in adults. Three (3) AYA individuals treated (1 each with NSCLC, ALL, and astrocytoma involving the CNS) have responded with CR/PR (RECIST 1.1), improved QOL/PFS (Kaplan-Meier) and OS from 8 to 35+ mos. Conclusion: DM-CHOC-PEN is safe in doses of 50-98.7 mg/m 2 and produced objective responses with improved OS and manageable toxicities in AYA individuals with malignancies involving the CNS. Complete data on subject responses and observed toxicities will be presented. The data support a 3-stage mechanism for tumor cytotoxicity: entry into the CNS and into the tumor via reversible binding to RBC membranes; then transported into cancer cells with L-glutamine; and bis-alkylation as described above.