Investigation of CXCR4 Chemokine Receptor Involvement in the Uptake and Penetration of siRNA Nanoparticles in Pancreatic Cancer Cell Lines and 3D Tumor Spheroids

With the urgency of developing novel therapies for pancreatic cancer, the Oupický lab designed a polymer, PAMD-Toc, that incorporates AMD3100, an antagonist of the most widely expressed chemokine receptor in cancer cells, CXCR4. This study seeks to determine if the CXCR4 receptor is involved in the uptake and penetration of siRNA-carrying PAMD-Toc nanoparticles into pancreatic cancer cells and tumors. Findings suggest that the presence of CXCR4 increases the efficacy of PAMD-Toc nanoparticle uptake and tumor penetration, which makes PAMD-Toc nanoparticles a promising siRNA delivery vector for pancreatic cancer gene therapy.https://digitalcommons.unmc.edu/surp2022/1027/thumbnail.jp

The changing epidemiology of dengue in Delhi, India

BACKGROUND: A major DHF outbreak occurred in Delhi in 1996. Following this another outbreak was reported in the year 2003. In the years 2004 and 2005, though no outbreak was reported, a definitely higher number of samples were received in the virology laboratory of A.I.I.M.S. from suspected cases of dengue infection. This study was designed to compare the serological and virological profiles of confirmed dengue cases in the years 2003, 2004 and 2005. RESULTS: Out of 1820 serum samples received from suspected cases in all three years, 811 (44.56%) were confirmed as dengue infection serologically. Out of these confirmed dengue cases maximum cases, in all three years, were seen in the age group 21–30 years. There was an increase in the number of samples received in the post monsoon period (September to November) with a peak in the second and third week of October. More samples were received from DHF cases in the year 2005 than 2004 and 2003. All four dengue serotypes were seen co-circulating in the year 2003, followed by complete predominance of dengue serotype 3 in 2005. CONCLUSION: Epidemiology of dengue is changing rapidly in Delhi. Dengue infections are seen every year thus making it an endemic disease. After co-circulation of all serotypes in 2003, now dengue serotype 3 is emerging as the predominant serotype

CLINICAL EVALUATION OF PANCHKOLAPHANT IN THE MANAGEMENT OF MANDAGNIJANYA STHAULYA WITH SPECIAL REFERENCE TO OBESITY

Obesity is one among the major diseases of modern era, increasing in prevalence. The Word Health report of W.H.O. listed Obesity under 10 top selected risks to the health. Sthaulya (Obesity) is well known from the Samhita period and is considered to be one of the eight undesirable conditions (Ashta Nindita). It can be caused due to Mandagni as Agni is considered to be responsible for metabolism. Thus, Ama formed moves within body, further causing Medovruddhi, which produces excessive stoutness. According to modern science, one of the causes for obesity is sedentary lifestyle, where there is more intake of junk food and less physical activity. This also signifies in increased BMI, further leading to obesity. In order to treat this problem, 30 patients of Sthaulya were registered to evaluate Sthaulya management with Panchakola Phant. Panchakola Phant containing Shunthi, Pippali, Pippalimula, Chavya, Chitrak; being Katu Rasaatmak helps in digestion and removal of Ama from body and further helps in management of Meda Dhatu Dushti. Patients were assessed on the basis of signs and symptoms before starting the treatment and administered Panchakola Phant. Duration for treatment was 3 months and patients were regularly followed up after 1 month to evaluate the clinical effects of the trial drug

Innovation in Renovation: Optimizing interior insulation application workflow

In the times of growing attention towards renovation for energy efficiency in the built environment, the building stock particularly associated with heritage value deemed monumental or protected is currently exempted under the Dutch law to comply with the energy performance guidelines. Limitations with regards to protecting the aesthetics of these heritage buildings make interventions for energy saving restricted to interior application. While it is necessary for these buildings to be more efficient, the process of interior energy renovation is complex in terms of financing, space, thermal performance and managing stakeholders. This thesis researches into ways to simplify and streamline the process of interior renovation with a focus on application of thermal insulation to the envelope to reduce transmission losses. The present challenges are addressed by three interventions in the workflow of the renovation process starting with a shift to super insulation material for better performance and space saving. Digital data capture and processing create opportunity of an integrated process of digital design to production. Lastly prefabrication of insulation ensures reduction of onsite time.The result is a globally adaptable approach towards an optimized renovation workflow that creates an synergy between energy efficiency, performance, production and preservation of the architectural heritage while keeping the occupants central.Architecture, Urbanism and Building Science

Synthesis and antibacterial/antitubercular activity evaluation of symmetrical <i style="mso-bidi-font-style:normal">trans</i>-cyclohexane-1,4-diamine derivatives

1441-1450<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-gb;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-GB">A library of symmetrical trans-cyclohexane-1,4-diamine derivatives have been synthesized and evaluated for their activity against the M. tb H37Rv strain. Most of the synthesized compounds show moderate to weak activity against M. tb H37Rv strain. Out of twenty-seven compounds tested, four compounds having substitution at p-position on the aromatic ring exhibit activity with MIC99 value ranging from 12.5 - 25 µM. Compound 9u having i-propyl group substitution at p-position is found to be the most potent among all the tested compounds with MIC99 value of 12.5 µM against M. tb H37Rv strain. All these compounds have also been tested against <i style="mso-bidi-font-style: normal">Methicilin resistant Staphylococcus aureus (MRSA), and four of the compounds <b style="mso-bidi-font-weight: normal">9c, 9i, 9p and 9s possess good antibacterial activity with IC50 ranging from 128 mg/L – 256 mg/L.</span

Polymeric Chloroquine as an Effective Antimigration Agent in the Treatment of Pancreatic Cancer

Hydroxychloroquine (HCQ) has been the subject of multiple recent preclinical and clinical studies for its beneficial use in the combination treatments of different types of cancers. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has been shown to be effective in various cancer models both in vitro and in vivo as an inhibitor of cancer cell migration and experimental lung metastasis. Here, we present detailed in vitro studies that show that low concentrations of PCQ can efficiently inhibit cancer cell migration and colony formation orders of magnitude more effectively compared to HCQ. After intraperitoneal administration of PCQ in vivo, high levels of tumor accumulation and penetration are observed, combined with strong antimetastatic activity in an orthotopic pancreatic cancer model. These studies support the idea that PCQ may be effectively used at low doses as an adjuvant in the therapy of pancreatic cancer. In conjunction with previously published literature, these studies further undergird the potential of PCQ as an anticancer agent

Association Between Alcohol Use and Female Sexual Dysfunction From the Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS)

Introduction: Sexual dysfunction is a common problem in women and the nature of its association with alcohol use remains unclear. Aim: To explore the association between alcohol use and female sexual dysfunction (FSD). Methods: Associations between self-reported drinking and sexual function were evaluated in 2,253 women presenting for consultation to a women’s health specialty clinic. A short version of the Alcohol Use Disorders Identification Test (AUDIT-C) was used to evaluate alcohol use. Women with an AUDIT-C ≥3 were considered at risk for hazardous drinking. Multivariable regression, controlling for depression, anxiety, and abuse (childhood and recent), was used to assess the association between alcohol consumption and FSD (defined as a Female Sexual Function Index [FSFI] ≤26.55 and Female Sexual Distress Scale [FSDS] ≥11) in sexually active women. Main Outcome Measure: The main study outcome measure was the presence of FSD as defined by a score ≤26.55 on the FSFI and ≥11 on the FSDS. Results: 57% of the 1,649 sexually active women were classified as having FSD; 80% reported any alcohol use and 38% reported drinking patterns with the potential to be hazardous. The women at risk for hazardous drinking had significantly higher FSFI domain scores indicating better sexual function (P ≤ .001). However, in multivariable analyses, there was no significant difference in the rates of FSD across alcohol use categories in women. Conclusion: In women presenting for consultation to a women’s health specialty clinic, an association between alcohol use and FSFI scores was seen, in which greater risk of hazardous drinking was associated with better sexual function scores. However, when sexual distress was included to define sexual dysfunction, those with FSD were not at higher risk of hazardous drinking. Given the complex nature of FSD, additional study is needed to further clarify these relationships.Kling JM, Sidhu K, Rullo J, et al. Association Between Alcohol Use and Female Sexual Dysfunction From the Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS). Sex Med 2019;7:162–168. Key Words: Alcohol, Female Sexual Dysfunction, Sexual Distress, Hazardous Alcohol Us