Malignant neoplasms of the pancreas. A study based on autopsy data from 1953 to 1982 in Bialystok, Poland. II. A survey of 195 cases

Among 195 malignant neoplasms of the pancreas (MNP) diagnosed at autopsy in 1953--1982 the exocrine carcinomas comprised 85.6% and inmular carcinomas 13.8% of cases. MNP were localized most frequently in the head of the pancreas (54.4%), then in the whole pancreas in 14.9%, in the head and the body or in the body and the tail in 20.5%, in the body or in the tail in 10.3% of MNP. There were no infiltrations and no metastases in other organs only in 16 patients (8.2% of MNP). The biliary tracts and duodenum were the most frequent sites of secondary infiltrations. Metastases were most frequent in the liver, then in the liver hilus and mesentery lymph nodes. The concordance of clinical and post mortem diagnosis of MNP was stated in 40.5% cases.     

Evidence for abnormal cholinergic neuromuscular transmission in diabetic rat small intestine

Proximal and distal rat small intestine from control, diabetic, and insulin-treated diabetic rats was cut into strips measuring 6.0 X 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, while those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (0.1-1.0-ms pulse duration, 30-270 mA, 1-26 Hz) in the presence of Krebs' solution and Krebs' solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in all strips. Significant differences among the three groups were found in the amplitudes of atropine-sensitive contractions in strips from distal longitudinal muscle. Controls showed the highest amplitude contractions and diabetics the lowest, whereas the insulin-treated diabetics showed contractions intermediate in amplitude. No significant differences were noted among the atropine-resistant contractions. Field stimulation delivered at pulse durations of 5.0 and 50.0 ms in the presence of neural blockade with tetrodotoxin (5 X 10(-6) M) produced similar contraction amplitudes among the three groups. These results suggest that streptozotocin-induced diabetes mellitus is associated with defective cholinergic neuromuscular transmission in the myenteric plexus of the distal small intestine. Insulin therapy seems to improve the abnormality.     

Pattern of microbial translocation in patients living with HIV-1 from Vietnam,Ethiopia and Sweden

Introduction

The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.

Methods

Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.

Results

All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.

Conclusions

Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.     

Social Network Effects of Nonlifesaving Early-Stage Breast Cancer Detection on Mammography Rates

Objectives. We estimated the effect of anecdotes of early-stage, screen-detected cancer for which screening was not lifesaving on the demand for mammography.Methods. We constructed an agent-based model of mammography decisions, in which 10 000 agents that represent women aged 40 to 100 years were linked together on a social network, which was parameterized with a survey of 716 women conducted through the RAND American Life Panel. Our model represents a population in equilibrium, with demographics reflecting the current US population based on the most recent available census data.Results. The aggregate effect of women learning about 1 category of cancers—those that would be detected but would not be lethal in the absence of screening—was a 13.8 percentage point increase in annual screening rates.Conclusions. Anecdotes of detection of early-stage cancers relayed through social networks may substantially increase demand for a screening test even when the detection through screening was nonlifesaving.Women often overestimate the mortality reduction from mammograms,1–3 and anecdotes of women with early-stage breast cancer being diagnosed through mammography can serve as particularly powerful motivators in encouraging other women to have screening mammograms.4–6 Such diagnoses, which are often shared through discussions between friends, family, coworkers, and other acquaintances, are also often viewed by patients as lifesaving.7 These discussions can be viewed as the transmission of information through a social network. Typically, social networks are defined as sets of individuals with links between pairs of individuals. In this article, we define 2 individuals as linked if they discuss their health history and outcomes (such as breast cancer diagnosis and treatment) with each other.Although women often view the detection of early-stage breast cancer through mammography as lifesaving, a recent study estimated that more than three quarters of women with screen-detected cancer have not actually had their lives saved by early detection.8 Rather, these women have cancers that (1) would never have been detected clinically if not detected through screening (thus, they were overdiagnosed), (2) eventually would have been detected clinically but would not be lethal, or (3) eventually would be lethal despite being detected by screening. Physicians and epidemiologists have long understood that high rates of early-stage diagnosis through screening do not necessarily indicate that the screening reduces mortality. Furthermore, when issuing cancer screening recommendations, professional organizations generally use mortality reduction as a primary measure of the screening’s efficacy.9–12Understanding how nonlifesaving early detection of breast cancer through screening drives patient demand for screening has several important implications. First, professional organizations currently disagree about when and how frequently women should be screened for breast cancer.9,10 Those who believe that some women are screened too early and too often may find demand for mammograms driven by such nonlifesaving diagnoses problematic. Our analysis estimated how much demand for mammograms may be driven by women’s incorrect assumptions about whether breast cancer screening was lifesaving for individuals in their social networks. More generally, the fact that patients often use frequency of early detection as a proxy for the screening efficacy7 means that patients with limited time and resources might prioritize a screening test that is relatively ineffective at reducing mortality over a test that more successfully reduces mortality if the former has higher early detection rates than the latter. We examined the potential patient-driven demand for screening that is motivated by nonlifesaving screen-detected cancers discussed in a social network.It is challenging to quantify this demand through observation or experiment because it is often not possible to determine at the individual level whether early detection through screening affected mortality. If a woman with early-stage, screen-detected breast cancer does not die of breast cancer, it is usually not possible to know with certainty if she would have died from breast cancer had she not been screened. If a woman with early-stage, screen-detected breast cancer ultimately dies of breast cancer, we know that screening was not lifesaving, but there may be many years between her initial diagnosis and death from breast cancer. Therefore, we used an agent-based simulation model to estimate how nonlifesaving early-stage breast cancer detection relayed through a social network might influence mammography rates. A major advantage of using a simulation model to study this problem is that, within the model, we can distinguish between agents (individual women) whose early detection of breast cancer through screening was lifesaving and those whose early detection was not lifesaving.In our analysis, we explored how population-level mammography rates might change if individuals were able to account for the fact that not all early-stage, screen-detected cancers are lifesaving. We used the results of a customized survey conducted through RAND’s American Life Panel to inform and parameterize our behavioral model. Many individuals assume that detection of early-stage breast cancer through mammography is lifesaving,7 and we assumed that if those diagnoses were known to be nonlifesaving, they would not serve as such powerful motivators in encouraging others to screen. Mammography is lifesaving only when a cancer that would have been lethal when detected clinically is not lethal when detected by mammography. We focused our analysis on categories of cancers whose detection by screening was not lifesaving. First, we simulated changing the incidence of cancers that would not have been detected in the absence of mammography (i.e., were overdiagnosed). Second, we simulated hypothetical interventions that allowed individuals in our model to know that mammography was nonlifesaving for (1) cancers that would be detected but would not have been lethal in the absence of mammography (never-lethal cancers) and (2) cancers that were ultimately lethal despite being screen detected (always-lethal cancers).     

Immunity to Amoeba

Amoebic infections in fish are most likely underestimated and sometimes overlooked due to the challenges associated with their diagnosis. Amoebic diseases reported in fish affect either gills or internal organs or may be systemic. Host response ranges from hyperplastic response in gill infections to inflammation (including granuloma formation) in internal organs. This review focuses on the immune response of Atlantic salmon to Neoparamoeba perurans, the causative agent of Amoebic Gill Disease (AGD).     

A single nucleotide polymorphism −35 kb T > C (rs9264942) is strongly associated with psoriasis vulgaris depending on HLA-Cw06

HLA class I molecules play a role both in viral infection control and in autoimmune diseases development. rs9264942T > C polymorphism in HLA-C gene was found to impact on HLA-C surface expression level and to be associated with HIV-1 control. It was found that these HLA alleles which protect against AIDS are associated with autoimmune disease e.g. psoriasis vulgaris (PsV). Whether rs9264942 SNP is associated with PsV was investigated here. rs9264942T > C was genotyped in 292 PsV patients, and 254 controls using TaqMan Genotyping Assay.     

Signaling effects of α-thrombin and SFLLRN in rat glioma C6 cells

Effects of thrombin on brain cells, including change of neurite outgrowth and astrocyte shape, are described, but the molecular mechanisms are unclear. We investigated the effects of human α-thrombin and a six amino acid thrombin receptor activating peptide (TRAP-6, SFLLRN) on [Ca²⁺]₁, phosphoinositide hydrolysis, and protein kinase C in rat glioma C₆ cells. Stimulation of C₆ cells with both α-thrombin and TRAP-6 resulted in [Ca²⁺]₁ mobilization, [³H]Inositol phosphate response, and enhanced immunoreactivity of the protein kinase C (PKC) isoenzymes α, β, γ, δ, and ϵ. Results suggest that α-thrombin and TRAP-6 activate at least partially the same intracellular signaling pathways in rat glioma C₆ cells, which is evidence for involvement of “tethered ligand” receptor in thrombin induced signaling in glioma C₆ cells. © 1996 Wiley-Liss, Inc.     

Synthesis and Potential Applications of Lipid Nanoparticles in Medicine

Currently, carriers of active ingredients in the form of particles of a size measured in nanometers are the focus of interest of research centers worldwide. So far, submicrometer emulsions, liposomes, as well as microspheres, and nanospheres made of biodegradable polymers have been used in medicine. Recent studies show particular interest in nanoparticles based on lipids, and at the present time, are even referred to as the “era of lipid carriers”. With the passage of time, lipid nanoparticles of the so-called first and second generation, SLN (Solid Lipid Nanoparticles) and nanostructured lipid carriers and NLC (Nanostructured Lipid Carriers), respectively, turned out to be an alternative for all imperfections of earlier carriers. These carriers are characterized by a number of beneficial functional properties, including, among others, structure based on lipids well tolerated by the human body, high stability, and ability to carry hydro- and lipophilic compounds. Additionally, these carriers can enhance the distribution of the drug in the target organ and alter the pharmacokinetic properties of the drug carriers to enhance the medical effect and minimize adverse side effects. This work is focused on the current review of the state-of-the-art related to the synthesis and applications of popular nanoparticles in medicine, with a focus on their use, e.g., in COVID-19 vaccines.