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Proceedings of the National Academy of... Jul 2024In 1967, in this journal, Evelyn Witkin proposed the existence of a coordinated DNA damage response in , which later came to be called the "SOS response." We revisited...
In 1967, in this journal, Evelyn Witkin proposed the existence of a coordinated DNA damage response in , which later came to be called the "SOS response." We revisited this response using the replication inhibitor azidothymidine (AZT) and RNA-Seq analysis and identified several features. We confirm the induction of classic Save our ship (SOS) loci and identify several genes, including many of the pyrimidine pathway, that have not been previously demonstrated to be DNA damage-inducible. Despite a strong dependence on LexA, these genes lack LexA boxes and their regulation by LexA is likely to be indirect via unknown factors. We show that the transcription factor "stringent starvation protein" SspA is as important as LexA in the regulation of AZT-induced genes and that the genes activated by SspA change dramatically after AZT exposure. Our experiments identify additional LexA-independent DNA damage inducible genes, including 22 small RNA genes, some of which appear to activated by SspA. Motility and chemotaxis genes are strongly down-regulated by AZT, possibly as a result of one of more of the small RNAs or other transcription factors such as AppY and GadE, whose expression is elevated by AZT. Genes controlling the iron siderophore, enterobactin, and iron homeostasis are also strongly induced, independent of LexA. We confirm that IraD antiadaptor protein is induced independent of LexA and that a second antiadaptor, IraM is likewise strongly AZT-inducible, independent of LexA, suggesting that RpoS stabilization via these antiadaptor proteins is an integral part of replication stress tolerance.
Topics: Escherichia coli; DNA Damage; Gene Expression Regulation, Bacterial; Escherichia coli Proteins; DNA Replication; SOS Response, Genetics; Bacterial Proteins; Serine Endopeptidases
PubMed: 38935560
DOI: 10.1073/pnas.2407832121 -
Voprosy Kurortologii, Fizioterapii, I... 2024Climate change and formation of regional weather features increase both direct (immediate effects of extremal temperature and other weather and climatic anomalies) and...
UNLABELLED
Climate change and formation of regional weather features increase both direct (immediate effects of extremal temperature and other weather and climatic anomalies) and indirect (environmental deterioration, etc.) consequences of global climate change. The development of investigations of medical weather assessment, medical and meteorological forecasting system, the use of treatment and preventive measures give the opportunity to prepare for weather biotropic conditions and reduce weather-conditioned exacerbations.
OBJECTIVE
To assess the clinical effectiveness of non-drug comprehensive methods, including balneotherapy and physiotherapy, in patients with somatic diseases, complicated by increased meteosensitivity, depending on the features of weather conditions in the Moscow region.
MATERIAL AND METHODS
The study included 120 patients diagnosed with «osteoarthrosis/osteoarthritis» with predominant hip and knee joint damage. The majority of patients had comorbidities, namely hypertensive disease (67.2%), ischemic heart disease (32.8%), chronic obstructive pulmonary disease and bronchial asthma (10.8%), grade II-III obesity (10%) and compensated diabetes mellitus (9.2%). The severity and main symptoms of the meteopathic reactions' manifestation were assessed by questionnaires consisting of three blocks, HAM, SF-36 tests and psychological stress scale. Medical and meteorological assessment of weather conditions in Moscow included analysis of the main weather-forming factors for 4 main synoptic observations in 10-minute mode for current and predictive 2 days, as well as daily characteristics of solar activity. Treatment methods included alternating magnetic field (AMF) procedures, general sodium chloride baths, massage and rehabilitation exercises (RE) (1st group); AMF, «dry» carbon dioxide baths, applications with brine on the affected joints and RE (2nd group); AMF, «dry» radon baths, applications with brine and RE (3rd group).
RESULTS
The conducted studies have revealed the trigger role of most biotropic combinations of weather-forming factors that provoke exacerbation in patients with joint diseases. Sodium chloride, «dry» carbon dioxide and radon baths combined with AMF, applications with brine on the affected joints and RE are pathogenetically justified and contribute to increase of adaptive potential, functional reserves of the body and provide significantly high (0.05) meteocorrective action.
CONCLUSION
The obtained results can be used for rehabilitation of patients with joint diseases complicated by increased meteosensitivity.
Topics: Humans; Female; Male; Moscow; Weather; Balneology; Middle Aged; Physical Therapy Modalities; Aged
PubMed: 38934952
DOI: 10.17116/kurort20241010315 -
Biofabrication Jun 2024Breast cancer develops in close proximity to mammary adipose tissue and interactions with the local adipose environment have been shown to drive tumor progression. The...
Breast cancer develops in close proximity to mammary adipose tissue and interactions with the local adipose environment have been shown to drive tumor progression. The specific role, however, of this complex tumor microenvironment in cancer cell migration still needs to be elucidated. Therefore, in this study, a 3D bioprinted breast cancer model was developed that allows for a comprehensive analysis of individual tumor cell migration parameters in dependence of adjacent adipose stroma. In this co-culture model, a breast cancer compartment with MDA-MB-231 breast cancer cells embedded in collagen is surrounded by an adipose tissue compartment consisting of adipose-derived stromal cell (ASC) or adipose spheroids in a printable bioink based on thiolated hyaluronic acid. Printing parameters were optimized for adipose spheroids to ensure viability and integrity of the fragile lipid-laden cells. Preservation of the adipogenic phenotype after printing was demonstrated by quantification of lipid content, expression of adipogenic marker genes, the presence of a coherent adipo-specific extracellular matrix, and cytokine secretion. The migration of tumor cells as a function of paracrine signaling of the surrounding adipose compartment was then analyzed using live-cell imaging. The presence of ASC or adipose spheroids substantially increased key migration parameters of MDA-MB-231 cells, namely motile fraction, persistence, invasion distance, and speed. These findings shed new light on the role of adipose tissue in cancer cell migration. They highlight the potential of our 3D printed breast cancer-stroma model to elucidate mechanisms of stroma-induced cancer cell migration and to serve as a screening platform for novel anti-cancer drugs targeting cancer cell dissemination.
Topics: Humans; Breast Neoplasms; Spheroids, Cellular; Cell Movement; Printing, Three-Dimensional; Bioprinting; Adipose Tissue; Female; Cell Line, Tumor; Stromal Cells; Coculture Techniques; Tumor Microenvironment
PubMed: 38934608
DOI: 10.1088/1758-5090/ad57f7 -
European Journal of Psychotraumatology 2024Childhood maltreatment (CM) can be divided into: emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN). CM is...
Types of childhood maltreatment as predictors of posttraumatic stress disorder severity and complex posttraumatic stress disorder in patients with substance use disorders.
Childhood maltreatment (CM) can be divided into: emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN). CM is associated with (Complex)Posttraumatic stress disorder (PTSD/CPTSD) and substance use disorder (SUD). This cross-sectional study examined the relationships between CM-subtypes with PTSD-severity and CPTSD in patients with SUD-PTSD. Participants ( = 209) were treatment-seeking SUD-PTSD patients who completed the Childhood Trauma Questionnaire-short form, the Clinician-Administered PTSD Scale for DSM-5 and the International Trauma Questionnaire. Regression analyses and a model selection procedure to select an optimal model were used to examine CM-subtypes as predictors of (C)PTSD, adjusted for sex and age. Total CM and all CM-types significantly predicted PTSD-severity in the univariate regression analysis, with EA begin the strongest predictor. In the multiple regression only SA predicted PTSD-severity. Subsequently, model selection indicated that the optimal model to predict PTSD-severity included EA and SA. In the univariate analyses total CM, EA, and PN significantly predicted CPTSD-classification, and total CM and all CM-types significantly predicted CPTSD-severity. In the multiple regression for CPTSD-classification only EA and PA were significant predictors and for CPTSD-severity EA, PA and SA were significant predictors. In post-hoc multiple regression analyses, only EA was a significant predictor of CPTSD-classification and CPTSD-severity. Finally, in the model selection the most parsimonious model only included EA for both CPTSD-classification and CPTSD-severity. Sex was not a moderator in the relationship between CM and PTSD, nor in CM and CPTSD. These findings indicate that for SUD-PTSD patients, several CM-types have predictive value for (C)PTSD-severity, however SA and especially EA appear to contribute to these complaints. Since EA does not constitute an A-criterion, it is generally more overlooked in PTSD treatment. Its impact should therefore be underlined, and clinicians should be attentive to EA in their treatment.
Topics: Humans; Stress Disorders, Post-Traumatic; Male; Female; Substance-Related Disorders; Cross-Sectional Studies; Adult; Surveys and Questionnaires; Child Abuse; Adult Survivors of Child Abuse; Middle Aged; Severity of Illness Index; Child
PubMed: 38934350
DOI: 10.1080/20008066.2024.2367179 -
Tidsskrift For Den Norske Laegeforening... Jun 2024Acute intoxication is a common chief complaint in emergency medicine, but there is a lack of up-to-date studies from the emergency departments in Norway on the incidence...
BACKGROUND
Acute intoxication is a common chief complaint in emergency medicine, but there is a lack of up-to-date studies from the emergency departments in Norway on the incidence and prevalence of various toxic substances. The aim of this study was to survey acute intoxications at the emergency department of St Olav's Hospital, Trondheim.
MATERIAL AND METHOD
In this review of patient records, we used data from the emergency department at St Olav's Hospital in Trondheim in the period 1 January 2019-31 December 2020. All cases with 'acute intoxication' as the reason for the emergency department visit were included.
RESULTS
In a patient population of 836 unique patients, there were a total of 1423 intoxications, of which 168/836 patients (20.0 %) had more than one intoxication episode in the period. The median age was 31 years (interquartile range 22-47), and 395/836 (47.2 %) of the patients were women. Combined drug intoxication constituted 666/1423 (46.8 %) of the cases, and the most frequent intoxications were from ethanol: 802/1423 (56.4 %); benzodiazepines 314/1423 (24.0 %); and opioids 243/1423 (17.1 %). Altogether, 1146/1423 (80.5 %) incidents resulted in hospital admission. There were no deaths during their hospital stay.
INTERPRETATION
Emergency departments must be prepared to manage patients who have taken various poisoning agents. The antidotes must be available, and it must be possible to perform interventions.
Topics: Humans; Norway; Emergency Service, Hospital; Adult; Female; Male; Hospitals, University; Middle Aged; Young Adult; Poisoning; Benzodiazepines; Alcoholic Intoxication; Retrospective Studies; Incidence; Adolescent; Drug Overdose
PubMed: 38934322
DOI: 10.4045/tidsskr.23.0417 -
Frontiers in Public Health 2024Injecting methamphetamine poses significant health risks, but little is known about how methamphetamine injectors filter their injection preparations and experience...
INTRODUCTION
Injecting methamphetamine poses significant health risks, but little is known about how methamphetamine injectors filter their injection preparations and experience related health concerns.
METHODS
A chain-referral sample of Indigenous people who inject methamphetamine ( = 30) was recruited and semistructured interviews were conducted to collect information on filtration practices and health concerns.
RESULTS
Filtration of the injection preparation was described by 53% of injectors. Elevated levels of concern for kidney disease, cancer and heart disease were observed among those who filtered their preparations (ranging from 50 to 56.3%). Concern about liver disease was the most frequent concern among those who filtered their preparations (62.5%) and was elevated in comparison to those who did not use filters (7.1%). Grouped logistic regression revealed a positive association between filtration of the injection preparation and overall health concerns expressed by injectors, after adjusting for gender and age. The marginal posterior distribution of the adjusted odds ratio for filtration of the injection preparation had a posterior median = 35.7, and 95% HPD interval = (5.1, 512.4).
DISCUSSION
Results illustrate a positive relationship between filtration of the injection preparation and health concerns among Indigenous people who inject methamphetamine. This likely reflects the use of filtration to reduce harms, and further research is needed to understand the full scope of prevention that may be associated with filtration of methamphetamine injection preparations.
Topics: Humans; Methamphetamine; Male; Female; Adult; Substance Abuse, Intravenous; Filtration; Middle Aged; Indigenous Peoples; Young Adult; Interviews as Topic
PubMed: 38932776
DOI: 10.3389/fpubh.2024.1390210 -
Soft Matter Jun 2024Several medical applications, like drug delivery and biosensing, are critically preceded by the insertion of needles and microneedles into biological tissue. However,...
Several medical applications, like drug delivery and biosensing, are critically preceded by the insertion of needles and microneedles into biological tissue. However, the mechanical process of needle insertions, especially at high velocities, is currently not fully understood. Here, we explore the insertion of hollow needles into transparent silicone samples with an insertion velocity ranging from 0.1 mm s to 2.3 m s (with needle radius = 101.5 μm, thus strain rates ∼/ ranging from 1 s to 2.3 × 10 s). We use a double-insertion method, where the needle is inserted and re-inserted at the same location, to estimate the fracture properties of the material. The deflection of the specimen's free surface is found to be different between insertion and re-insertion experiments for identical needle positions, which is associated with different force magnitudes between insertion/reinsertion. This aspect was previously neglected in the original double-insertion method, thus here we develop a method based on imaging, image analyses and force measurements to decompose the measured force into individual force components, including deflection force , frictional and spreading force + , and cutting force . We estimate that the toughness of our silicone samples, calculated using the cutting force and the crack dimensions, increases with needle velocity, and ranges within observed values in previous literature for the same material and for some soft biological materials. In addition to toughness , other parameters, such as critical force and mechanical work , also show strain-rate dependence, suggesting tissue stiffening, due to accumulated strain energy, at high speeds.
PubMed: 38932556
DOI: 10.1039/d4sm00211c -
Viruses Jun 2024Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in...
Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in Victoria, Australia, who inject drugs or are living with hepatitis C, to identify missed opportunities for hepatitis C care. Adult hospital inpatients and emergency department (ED) attendees from 2018 to 2021 with indications for intravenous drug use (IDU) or hepatitis C on their discharge or ED summary were included. Data sources: hospital admissions, pathology, hospital pharmacy, and outpatients. We assessed progression through the testing cascade and performed logistic regression analysis for predictors of hepatitis C care, including testing and treatment. Of 79,923 adults admitted, 1345 (1.7%) had IDU-coded separations and 628 (0.8%) had hepatitis C-coded separations (N = 1892). Hepatitis C virus (HCV) status at the end of the study was unknown for 1569 (82.9%). ED admissions were associated with increased odds of not providing hepatitis C care (odds ratio 3.29, 95% confidence interval 2.42-4.48). More than 2% of inpatients at our hospital have an indication for testing, however, most are not being tested despite their hospital contact. As we work toward HCV elimination in our region, we need to incorporate testing and linkage strategies within hospital departments with a higher prevalence of people at risk of infection.
Topics: Humans; Retrospective Studies; Male; Hepatitis C; Female; Middle Aged; Adult; Inpatients; Hepacivirus; Substance Abuse, Intravenous; Hospitalization; Victoria; Aged; Emergency Service, Hospital; Mass Screening; Young Adult
PubMed: 38932269
DOI: 10.3390/v16060979 -
Viruses Jun 2024Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function... (Review)
Review
Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review.
Topics: Humans; Substance-Related Disorders; South Africa; Hepatitis C; Hepatitis B; HIV Infections; Virus Replication; Illicit Drugs; Hepatitis B virus; Virus Diseases; Blood-Borne Infections; Hepacivirus; Substance Abuse, Intravenous
PubMed: 38932263
DOI: 10.3390/v16060971 -
Viruses Jun 2024Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID)...
Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort of people most at risk of reinfection in a real-world community setting. We conducted a secondary analysis of routinely collected HCV testing and treatment data from treatment episodes initiated with direct-acting antiviral (DAA) therapy between October 2015 and June 2021. The overall proportion of clients (N = 413) reinfected was 9% (N = 37), and the overall incidence rate of HCV reinfection was 9.5/100PY (95% CI: 6.3-14.3). Reinfection incidence rates varied by sub-group and were highest for Aboriginal and/or Torres Strait Islander people (20.4/100PY; 95% CI: 12.1-34.4). Among PWID (N= 321), only Aboriginality was significantly associated with reinfection (AOR: 2.73, 95% CI: 1.33-5.60, = 0.006). High rates of HCV reinfection in populations with multiple vulnerabilities and continued drug use, especially among Aboriginal and Torres Strait Islander people, highlight the need for ongoing regular HCV testing and retreatment in order to achieve HCV elimination. A priority is resourcing testing and treatment for Aboriginal and/or Torres Strait Islander people. Our findings support the need for novel and holistic healthcare strategies for PWID and the upscaling of Indigenous cultural approaches and interventions.
Topics: Humans; Male; Female; Risk Factors; Adult; Substance Abuse, Intravenous; Hepatitis C; Australia; Reinfection; Primary Health Care; Middle Aged; Incidence; Antiviral Agents; Hepacivirus; Native Hawaiian or Other Pacific Islander; Young Adult
PubMed: 38932249
DOI: 10.3390/v16060957