Aggressive Program Research Articles

PERCEPTION OF WOMEN’S INFERTILITY AMONG THE YORUBAS IN IBADAN, OYO STATE, NIGERIA

Cultural beliefs are consequential in explaining the general perspective of any disease(s) and this has led to discrepancies in the description of the etiology of diseases between patients and professional health care providers, thereby affecting the care provided and patients’ compliance with treatment. Infertility is also seen in that light. This study thus examined the perception of women’s infertility and treatment of infertility among married men and women in Ibadan, Oyo State, Nigeria. Structured questionnaire copies were administered on 400 respondents while data were elicited from 12 married men and women that were yet to give birth (3 in each of the 4 selected LGAs) through Key Informant Interview (KII) guides. The study measured the perception of infertility, causes of infertility, solution to infertility and association between some demographic variables and the perception of infertility. The results revealed that infertility was majorly discerned as a spiritual problem (40%) and ancestral curses (24%). Solutions to the challenges were diverse as shown by indulgence in prayer (39%), consumption of herbal concoction (29%) and making sacrifices to appease the gods (15%.. Statistically, the Chi Square test showed significant relationship between religion and perception of women infertility. The study recommends aggressive public advocacy programs and pragmatic reproductive health education programmes targeted at addressing misconceptions/fallacies about infertility coupled with accessible and affordable health care for couples horse-trading with infertility.

An evaluation of pruning programs to manage shoot blight, caused by the bacterium Erwinia amylovora.

Fire blight is an economically devastating disease caused by the bacterium Erwinia amylovora. Infections lead can shoot blight and, when unmanaged, become systemic and can quickly cause tree death and spread through an orchard via active infections sites producing bacterial ooze. With climate change, increasingly popular high-density training systems, and the susceptibility of many consumers desired apple cultivars, shoot blight management has become exceptionally challenging despite the diverse management tactics available. To better understand pruning as a management practice, we evaluated ten pruning programs in two different orchards over the course of two years. The pruning programs in this study encompass extension recommendations and grower preferences and include a variety of supplemental chemical applications and sanitation practices to answer three primary questions: (i) How do the impacts of pruning on the management of shoot blight compare between a vertical-axis orchard with mature trees and a high-density planting with young trees? (ii) Do sanitation and ancillary chemical management have a significant impact on shoot blight control achieved through pruning? (iii) How do a variety of pruning programs, including those preferred by researchers, growers, and extension agents compare in terms of shoot blight management? The impacts of pruning programs were more pronounced in the vertical-axis orchard in terms of reducing infection spread and overall shoot blight incidence. However, in the high-density plantings pruning programs were mostly ineffective and fire blight spread quickly throughout the trees and planting. Overall, the most aggressive pruning programs, which removed tissue of several seasons of growth, had the greatest impact on fire blight in both plantings. In line with the findings of many previous studies, sanitation and chemical management supplementation were not found to be necessarily beneficial.

The MET Oncogene: An Update on Targeting Strategies.

The MET receptor, commonly known as HGF (hepatocyte growth factor) receptor, is a focus of extensive scientific research. MET has been linked to embryonic development, tissue regeneration following injury, tumorigenesis, and cancer metastasis. These functions underscore its involvement in numerous cellular processes, including stemness, proliferation, motility, cell dissociation, and survival. However, the enigmatic nature of MET becomes apparent in the context of cancer. When MET remains persistently activated, since its gene undergoes genetic alterations, it initiates a complex signaling cascade setting in motion an aggressive and metastatic program that is characteristic of malignant cells and is known as "invasive growth". The expanding knowledge of MET signaling has opened up numerous opportunities for therapeutic interventions, particularly in the realm of oncology. Targeting MET presents a promising strategy for developing novel anti-cancer treatments. In this review, we provide an updated overview of drugs designed to modulate MET signaling, highlighting MET kinase inhibitors, degraders, anti-MET/HGF monoclonal antibodies, and MET-targeted antibody-drug conjugates. Through this review, we aim to contribute to the ongoing advancement of therapeutic strategies targeting MET signaling.

Exercise stress echocardiography detects patients with paroxysmal/persistent atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most prevalent atrial tachyarrhythmia, affecting an estimated 2-4% of adults worldwide. AF is a well-recognized and treatable risk factor for stroke, but it often remains asymptomatic or subclinical, leading to underdiagnosis. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF). Methods An international prospective cohort comprising 1035 consecutive patients was initially considered from 12 cardiology institutions. These patients were referred for clinically-driven ESE as part of the Stress Echo 2020-2030 study network. All patients underwent comprehensive ESE with the ABCDE protocol, which included assessment of B-lines, left ventricle contractile reserve (LVCR), ECG-based heart rate reserve (HRR), LV ejection fraction (EF), LV end-diastolic volume, E/e’, pulmonary artery systolic pressure estimation, tricuspid annular plane sytolic excursion (TAPSE), left atrium volume index (LAVi) and left atrium reservoir phase strain (LASr) at rest and with exercise. Results After excluding 89 patients who were in AF during the ESE, 946 patients in SR were included as the main study cohort (101 with and 845 without a history of PAF). A scoring system was then constructed using all independent variables that differentiate the two groups (those with and without history of PAF). Presence of systemic hypertension, rest LAVI>31ml/m2, rest |LASr|< 21%, stress LAVI >29 ml/m2, stress |LASr| <24%, stress E/e’ >7, ∆TAPSE <4.5 mm, HRR<1.87, and LVCR<1.6 were identified as the discriminators between patients with and without PAF. The composite score, summing all 9 items (with a total score range from 0 to 9), yielded a score of >4 as the best balance between sensitivity (87%) and specificity (60%) in predicting those with PAF. The receiver operating characteristic curve analysis of the scoring model showed an AUC of 0.79 (p-value <0.0001), Figure. Conclusion ESE evaluation can be a valuable adjunct for identifying patients in SR with history of PAF. This multifaceted approach enhances the potential for more accurate detection and clinical management of individuals in SR at risk for AF, who could be considered for aggressive monitoring programs to prevent the development of new onset AF and subsequent increase in cardiovascular risk.

Outcome of End to Side Nerve Modified Double Oberlin Procedure and End to End Dorsal Approach Spinal Accessory to Suprascapular Nerve in Partial Postganglionic BPI: A Case Report

Introduction: Brachial plexus injury (BPI) is a devastating peripheral nerve injury that mostly affecting young men, often due to motor vehicle accidents. BPIs can be classified into preganglionic and postganglionic lesions, with postganglionic injuries allowing potential nerve regeneration. The Oberlin method, aimed at reinnervating the biceps, and the Mackinnon technique, targeting both biceps and brachialis muscles, have shown promising outcomes in BPI management. Case report: A 45-year-old man presented with right hand weakness and occasional tingling in the upper arm and fingers two months after a motorcycle accident. Motor examination revealed muscle strength of 0/5 in the right trapezius, rhomboids, serratus anterior (positive winging scapula), pectoralis minor and major, latissimus dorsi, deltoid, biceps, and elbow flexion. Wrist and finger functions remained intact. Diagnosed with post-ganglionic BPI, the patient underwent two nerve transfer surgeries: the Mackinnon technique, transferring the spinal accessory nerve to the suprascapular nerve to reinnervate shoulder muscles, and the Double Oberlin procedure, transferring fascicles from the median and ulnar nerves to the musculocutaneous nerve for reinnervation of the biceps and brachialis muscles. Post-surgery, the patient engaged in an aggressive rehabilitation program focusing on strength, range of motion, and sensory re-education. Over nine months, the patient showed significant improvement in elbow flexion (MRC grade 3), wrist extension (MRC grade 5), hand grip strength (MRC grade 3) with improved sensation across the affected limb. He returned to work and daily activities with mild residual weakness and sensory deficits. Discussion: This case illustrates the effectiveness of the Mackinnon and Double Oberlin nerve transfer techniques in restoring function in a patient with total post-ganglionic BPI. The Mackinnon technique enabled shoulder muscle reinnervation, essential for abduction and stabilization, while the Double Oberlin procedure enhanced elbow flexion by reinnervating both the biceps and brachialis muscles. The combined surgical and intensive rehabilitation approach facilitated significant functional recovery. Conclusion: The successful application of the Double Oberlin and Mackinnon techniques in this case demonstrates their potential in managing total post-ganglionic BPI. Early surgical intervention and consistent rehabilitation are crucial for optimizing recovery outcomes. This case highlights the importance of a multidisciplinary approach in treating complex peripheral nerve injuries. Keywords: Double Oberlin, Mackinnon, Brachial Plexus Injury

Innovative Percutaneous Quadricepsplasty for Knee Extension Contracture in Arthrogryposis: A Case Report.

A 15-year-old male patient diagnosed with arthrogryposis presented with a left knee extension contracture. He underwent an innovative percutaneous quadricepsplasty performed arthroscopically. Subsequent to the procedure, the patient was enrolled in an aggressive physiotherapy program. Over a follow-up period of 12 months, significant improvement was observed, with the patient achieving a 95° range of motion in his left knee. Noninvasive percutaneous quadricepsplasty, combined with methods such as arthroscopy, may enhance therapeutic outcomes and alleviate chronic knee extension contractures in patients with arthrogryposis. This combination of treatment methods has the potential to revolutionize the management of such conditions.

Post-COVID economic crisis, citizen-state relations, and the Electronic Transactions Levy (E-levy) controversy in Ghana

In 2021, the Government of Ghana sparked controversy by introducing the Electronic Transactions Levy (E-Levy) as part of an aggressive programme of revenue mobilisation in response to the debt-induced economic crisis that swept through the Global South in the wake of the COVID-19 pandemic. This paper contributes to the literature on the politics of economic crisis by demonstrating the consequences of prioritising revenue mobilisation over social protection during times of economic shocks. Drawing on in-depth interviews with a range of respondents, we argue that the outrage triggered by the introduction of the E-levy was rooted in longstanding grievances against the lack of reciprocity in citizen-state relations and an apparent breakdown of the fiscal contract. The tax provoked denunciatory narratives of economic mismanagement and government insensitivity, thereby underscoring the crisis of political legtimacy in Ghana. By ‘loosening the safety net’ and ‘tightening the tax net’ at a time when the country was battling an economic crisis and still grappling with the fallouts of the COVID-19 pandemic, the government created the conditions that exacerbated the already fraught citizen-state relations. Given the low tax morale, citizens are actively adopting various strategies to avoid paying the tax, including reverting to the use of cash and reducing the value and frequency of transactions.

New dynamic suture material for tendon transfer surgeries in the upper extremity – a biomechanical comparative analysis

BackgroundEarly mobilization after tendon surgery is crucial to avoid commonly observed postoperative soft tissue adhesions. Recently, a new suture was introduced (DYNACORD; DC) with a salt-infused silicone core designed to minimize laxity and preserve consistent tissue approximation in order to avoid gap formation and allow early mobilization.AimsTo compare the biomechanical competence of DC against a conventional high strength suture (FiberWire; FW) in a human cadaveric tendon transfer model with an early rehabilitation protocol.MethodsSixteen tendon transfers (flexor digitorum superficialis (FDS) IV to flexor pollicis longus (FPL)) were performed in 8 pairs human cadaveric forearms using either DC or FW. Markings were set 0.8 cm proximally and 0.7 cm distally to the level of the interweaving zone of the transfer. All specimens underwent repetitive thumb flexion against resistance in 9 intermittent series of 300 cycles each, simulating an aggressive postoperative rehabilitation protocol. After each series, the distance of the proximal marker to the interweaving zone (proximal), the length of the interweaving zone (intermediate) and the distance of the distal marker to the interweaving zone (distal) were measured.ResultsPooled data over all nine series, normalized to the immediate postoperative status, demonstrated no significant differences between FW and DC (p ≥ 0.355) for the proximal and distal markers. However, at the intermediate zone, DC was associated with significant length shortening (p < 0.001) compared to FW without significant length changes (p = 0.351). Load to catastrophic failure demonstrated significant higher forces in FW (p = 0.011). Nevertheless, due to failure mainly proximal or distal of the transfer zone, these loads are not informative.ConclusionFrom a biomechanical perspective, DC preserved tissue approximation and might be considered as a valid alternative to conventional high-strength sutures in tendon transfer surgery. DC might allow for a shorter interweaving zone and a more aggressive early postoperative rehabilitation program, possibly avoiding commonly observed postoperative soft tissue adhesions and stiffness.

COVID-19 outcomes in haemopoietic stem cell transplant recipients in Western Australia: the value of vaccination and antiviral therapy.

Coronavirus-19 (COVID-19) mortality rates among haemopoietic stem cell transplant (HSCT) patients are high, ranging between 20% and 40%. We prospectively evaluated the mortality outcomes of COVID-19 in Western Australian HSCT patients. A total of 32/492 (6.5%) HSCT recipients contracted COVID-19 during the study, of whom 30/32 (94%) developed mild or asymptomatic disease. Two allogeneic HSCT patients were hospitalised for severe COVID-19; one patient died. Stringent healthcare, social isolation practices, aggressive vaccination programmes and rapid access to COVID-19 antivirals may have promoted mild COVID-19 illness in Western Australian HSCT patients, resulting in one of the lowest COVID-19 mortality rates in HSCT recipients worldwide.

Programming temporal stiffness cues within extracellular matrix hydrogels for modelling cancer niches

Extracellular matrix (ECM) stiffening is a common occurrence during the progression of many diseases, such as breast cancer. To accurately mimic the pathophysiological context of disease within 3D in vitro models, there is high demand for smart biomaterials which replicate the dynamic and temporal mechanical cues of diseased states. This study describes a preclinical disease model, using breast cancer as an example, which replicates the dynamic plasticity of the tumour microenvironment by incorporating temporal (3-week progression) biomechanical cues within a tissue-specific hydrogel microenvironment. The composite hydrogel formulation, integrating adipose-derived decellularised ECM (AdECM) and silk fibroin, was initially crosslinked using a visible light-mediated system, and then progressively stiffened through spontaneous secondary structure interactions inherent between the polymer chains (∼10–15 kPa increase, with a final stiffness of 25 kPa). When encapsulated and cultured in vitro, MCF-7 breast cancer cells initially formed numerous, large spheroids (>1000 μm2 in area), however, with progressive temporal stiffening, cells demonstrated growth arrest and underwent phenotypic changes resulting in intratumoral heterogeneity. Unlike widely-investigated static mechanical models, this stiffening hydrogel allowed for progressive phenotypic changes to be observed, and fostered the development of mature organoid-like spheroids, which mimicked both the organisation and acinar-structures of mature breast epithelium. The spheroids contained a central population of cells which expressed aggressive cellular programs, evidenced by increased fibronectin expression and reduction of E-cadherin. The phenotypic heterogeneity observed using this model is more reflective of physiological tumours, demonstrating the importance of establishing temporal cues within preclinical models in future work. Overall, the developed model demonstrated a novel strategy to uncouple ECM biomechanical properties from the cellular complexities of the disease microenvironment and offers the potential for wide applicability in other 3D in vitro disease models through addition of tissue-specific dECM materials.

Current status of ECMO for massive pulmonary embolism.

Massive pulmonary embolism (MPE) carries significant 30-day mortality and is characterized by acute right ventricular failure, hypotension, and hypoxia, leading to cardiovascular collapse and cardiac arrest. Given the continued high mortality associated with MPE, there has been ongoing interest in utilizing extracorporeal membrane oxygenation (ECMO) to provide oxygenation support to improve hypoxia and offload the right ventricular (RV) pressure in the belief that rapid reduction of hypoxia and RV pressure will improve outcomes. Two modalities can be employed: Veno-arterial-ECMO is a reliable process to decrease RV overload and improve RV function, thus allowing for hemodynamic stability and restoration of tissue oxygenation. Veno-venous ECMO can support oxygenation but is not designed to help circulation. Several societal guidelines now suggest using ECMO in MPE with interventional therapy. There are three strategies for ECMO utilization in MPE: bridge to definitive interventional therapy, sole therapy, and recovery after interventional treatment. The use of ECMO in MPE has been associated with lower mortality in registry reviews, but there has been no significant difference in outcomes between patients treated with and without ECMO in meta-analyses. Considerable heterogeneity in studies is a significant weakness of the available literature. Applying ECMO is also associated with substantial multisystem morbidity due to a systemic inflammatory response, hemorrhagic stroke, renal dysfunction, and bleeding, which must be factored into the outcomes. The application of ECMO in MPE should be combined with an aggressive pulmonary interventional program and should strictly adhere to the current selection criteria.

One size does not fit all: rollback orthodoxy and Anglo-American covert action in Albania and Ukraine in the early Cold War

ABSTRACT Orthodox scholarship claims the CIA-MI6 covert actions in Albania and Ukraine in the early Cold War exemplified a singular effort to rollback Soviet power in Europe. Using recently declassified files, this article presents a case study of Operation BGFiend/Valuable and Aerodynamic to challenge the existence of an aggressive rollback programme. These were limited, diverse and strategically dynamic projects that did not seek regime change in either territory. The west subverted Hoxha’s Albanian regime, focusing on intelligence collection and propaganda. In Ukraine, emphasis was on gathering intelligence, particularly to provide early warning of an anticipated Soviet invasion of Western Europe.

Household Waste Reduction Practices in Ibadan, Nigeria

With an average of 42 million tons of waste produced annually and no effective structure for managing solid waste in Nigeria, indiscriminate disposal of waste poses a serious danger to the constituents of the environment. Waste reduction at source is one of the potent strategies for reducing disposable waste, thereby, making non-reused waste at the household level manageable by municipal authority. Therefore, this study examines household waste reduction practices in Ibadan. A random selection of 281 respondents was conducted using a sampling ratio of 3% among three places within the Ibadan North East Local Government Area. Buying packaging-less products, targeting reusable and not items that are disposable in nature, using reusable bags made of recyclable materials for shopping, reducing food remnants and waste, and maintaining and repairing household items are the five household waste reduction practices that have been identified. Results showed that plastic accounted for more than half (54.4%) of the garbage produced, 14.6% was kitchen waste, 19.2% was glass and bottle, and 11.7% was paper waste. The study suggests an aggressive sensitisation programme by Oyo State Waste Management Authority to raise awareness of the benefits of reducing waste before disposal in Ibadan, to curb indiscriminate disposal of waste.

An assessment of factors associated with early postoperative stiffness in arthroscopic rotator cuff repair.

Postoperative stiffness affects up to 20% of patients following arthroscopic rotator cuff repair. Recent evidence indicates that early postoperative stiffness may associated with lower retear rates. This study aimed to identify the independent predictors of early postoperative stiffness. A retrospective cohort study of 1526 rotator cuff repairs was performed. Range of motion at 6-week postop was used to identify stiff patients. Stiffness was defined as external rotation <27.5o or forward flexion <145o . Multiple logistic regression analysis was used to identify the independent predictors of 6-week stiffness. The independent predictors for external rotation stiffness at 6-week postop were more recent cases (Wald = 60), restricted preoperative external rotation (Wald = 36), younger age (Wald = 21) and poorer surgeon-ranked tissue quality (Wald = 15). The independent predictors for forward flexion stiffness were more recent cases (Wald = 101), restricted preoperative forward flexion (Wald = 16) and external rotation (Wald = 13) and female patients (Wald = 12). All patients that developed early postoperative stiffness had recovered range of motion by 6 months to preoperative levels (P < 0.0001). A significantly greater proportion of younger patients (40-49) developed postoperative stiffness when compared to older patients aged 50-59 (P < 0.0062), 70-79 (P < 0.0126) and 80-89 (P < 0.004). Patients that retore had significantly greater average 6-week postoperative range of motion. Patients earlier in the study were found to have greater postoperative range of motion, which coincided with a more aggressive rehabilitation program with less immobilization. Thus, the data supports the hypothesis that a temporary period of shoulder stiffness facilitates tendon repair and ultimately a better outcome post rotator cuff repair.

Carbapenem-Resistant Klebsiella pneumoniae in Large Public Acute-Care Healthcare System, New York, New York, USA, 2016-2022.

Controlling the spread of carbapenem-resistant Enterobacterales is a global priority. Using National Healthcare Safety Network data, we characterized the changing epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) in a large public health system in New York, New York, USA. During 2016-2020, CRKP cases declined; however, during 2021-June 2022, a notable increase occurred. Of 509 cases, 262 (51%) were considered community-onset, including 149 in patients who were living at home. Of 182 isolates with proven or presumptive (ceftazidime/avibactam susceptible) enzymes, 143 were serine carbapenemases; most confirmed cases were K. pneumoniae carbapenemase. The remaining 39 cases were proven or presumptive metallo-β-lactamases; all confirmed cases were New Delhi metallo-β-lactamases. After 2020, a marked increase occurred in the percentage of isolates possessing metallo-β-lactamases. Most patients with metallo-β-lactamases originated from long-term care facilities. An aggressive and universal program involving surveillance and isolation will be needed to control the spread of CRKP in the city of New York.

"I Can Never Feel Safe": Latinx Youth Voices on Psychosocial Impacts of 287(g) in Georgia.

Increasingly, immigration policies are understood as structural determinants, rooted in racism, nativism, and ethnocentrism, which raise serious public health concerns for Latinx adolescents' mental health. Our objective was to examine how immigration policy enforcement affects mental health of Latinx youth raised in a county with an aggressive interior immigration enforcement program. From 2009 to 2021, Gwinnett County, GA, led the nation in deportations under the 287(g) program as a "universal enforcement model," where local law enforcement were deputized to detain undocumented immigrants, primarily through traffic violations. From June to July 2022, we followed a participatory action research approach with two groups of Latinx youth who grew up in Gwinnett County. In total, 10 youth took photos related to the research question, and engaged in facilitated dialogue using photovoice guide SHOWED/VENCER for four, 2-hour sessions that were audio-recorded and transcribed. Transcripts were analyzed following grounded theory principles to arrive at a conceptual model codeveloped and validated by youth. Youth described how 287(g) led to policing and deportation in their communities, fueling stereotypes, and discrimination that criminalized Latinx immigrants. Youth linked immigration enforcement policies like 287(g) to exclusionary systems that contributed to fear, marginalization, and loss in their communities, bringing experiences of sadness, grief, isolation, hopelessness, and low self-worth. From youth-driven research, we identified mental health implications of the 287(g) program among Latinx youth. The cascading harms of immigration enforcement policies highlight the need to address these policies and identify immediate strategies to promote Latinx youth mental health.

Changing Genotypic Distribution, Antimicrobial Susceptibilities, and Risk Factors of Urinary Tract Infection Caused by Carbapenemase-Producing Pseudomonas aeruginosa.

Carbapenem-resistant Pseudomonas aeruginosa (CrPA) is a leading cause of healthcare-associated urinary tract infections (UTIs). Carbapenemase production is an important mechanism that significantly alters the efficacy of frequently used anti-pseudomonal agents. Reporting the current genotypic distribution of carbapenemase-producing P. aeruginosa (CPPA) isolates in relation to antimicrobial susceptibility, UTI risk factors, and mortality is necessary to increase the awareness and control of these strains. In total, 1,652 non-duplicated P. aeruginosa strains were isolated from hospitalized patients between 2015 and 2020. Antimicrobial susceptibility, carbapenemase genotypes, risk factors for UTI, and associated mortality were analyzed. The prevalence of carbapenem-non-susceptible P. aeruginosa isolates showed a decreasing trend from 2015 to 2018 and then increased in the background of the emergence of New Delhi metallo-β-lactamase (NDM)-type isolates since 2019. The CPPA strains showed 100.0% non-susceptibility to all tested antibiotics, except aztreonam (94.5%) and colistin (5.9%). Carbapenems were identified as a risk and common predisposing factor for UTI (odds ratio [OR]=1.943) and mortality (OR=2.766). Intensive care unit (ICU) stay (OR=2.677) and white blood cell (WBC) count (OR=1.070) were independently associated with mortality. The changing trend and genetic distribution of CPPA isolates emphasize the need for relentless monitoring to control further dissemination. The use of carbapenems, ICU stay, and WBC count should be considered risk factors, and aggressive antibiotic stewardship programs and monitoring may serve to prevent worse outcomes.

Collagen VI sustains cell stemness and chemotherapy resistance in glioblastoma

Microenvironmental factors are known fundamental regulators of the phenotype and aggressiveness of glioblastoma (GBM), the most lethal brain tumor, characterized by fast progression and marked resistance to treatments. In this context, the extracellular matrix (ECM) is known to heavily influence the behavior of cancer cells from several origins, contributing to stem cell niches, influencing tumor invasiveness and response to chemotherapy, mediating survival signaling cascades, and modulating inflammatory cell recruitment. Here, we show that collagen VI (COL6), an ECM protein widely expressed in both normal and pathological tissues, has a distinctive distribution within the GBM mass, strongly correlated with the most aggressive and phenotypically immature cells. Our data demonstrate that COL6 sustains the stem-like properties of GBM cells and supports the maintenance of an aggressive transcriptional program promoting cancer cell proliferation and survival. In particular, we identified a specific subset of COL6-transcriptionally co-regulated genes, required for the response of cells to replicative stress and DNA damage, supporting the concept that COL6 is an essential stimulus for the activation of GBM cell response and resistance to chemotherapy, through the ATM/ATR axis. Altogether, these findings indicate that COL6 plays a pivotal role in GBM tumor biology, exerting a pleiotropic action across different GBM hallmarks, including phenotypic identity and gene transcription, as well as response to treatments, thus providing valuable information for the understanding of the complex microenvironmental cues underlying GBM malignancy.

Rethinking an effective AV fistula-graft screening program. An "A B C".

The goal of a vascular access screening program is to detect and preemptively correct hemodynamically significant stenosis, however, a practice pattern allowing toimplementsuch a program still remains to be defined. Achieving balance between the increase in access-related procedures by adopting an aggressive screening program, and the risks associated with the absence of any screening program, i.e., failure or abandonment of the arterio-venousaccess with needforcentral venous catheter placement, can be extremely challenging. All major guidelines agree about the role of arterio-venous access monitoring, but the waysurveillance should be managedis still a controversial issue. Preserving long-term vascular access functionshould be a goal for all hemodialysis teams, yet it ideally requires a multidisciplinary effort with a monitoring program, calling fora great deal of involvement by hemodialysis health professionals. In this context, the engagement of skilled nurses and the role of patient empowerment with collaborative decision-making may be the key to a successfulvascular access screening program. Screening programs should be personalized, shared with thepatients, and tailored according to vascular access type and site. In the near future, new devices and the use of artificial intelligence mayallow to support interpretation of complex data and lead to the development of prediction modelsfor vascular access failure.

When sterilizations lower immunizations: The Emergency experience in India (1975–77)

In the 1970s in India, an aggressive family planning program resulted in more than eight million sterilizations in only a few months. Under the assumption that this extremely unpopular sterilization campaign may have shaped demand for health services, we study the effect of this event on children’s immunization and hospital births. To account for possible non-randomness in coercion intensity, we use a difference-in-difference empirical strategy, which relies on the unexpected timing of the program and mother and village fixed effects. We show that an increase in district-wise sterilizations, compared to the previous period, led to a substantial decrease in the use of these services, especially vaccination. Further evidence supports a decline in trust rather than a change in health supply or valuation of children.