Conectar
by Nico Tannemann, Raimund Erbel, Markus M. Nöthen, Karl-Heinz Jöckel, Sonali Pechlivanis
Short telomeres are associated with cardiovascular disease (CVD). We aimed to investigate, if genetically determined telomere-length effects CVD-risk in the Heinz-Nixdorf-Recall study (HNRS) population. We selected 14 single-nucleotide polymorphisms (SNPs) associated with telomere-length (p−8) from the literature and after exclusion 9 SNPs were included in the analyses. Additionally, a genetic risk score (GRS) using these 9 SNPs was calculated. Incident CVD was defined as fatal and non-fatal myocardial infarction, stroke, and coronary death. We included 3874 HNRS participants with available genetic data and had no known history of CVD at baseline. Cox proportional-hazards regression was used to test the association between the SNPs/GRS and incident CVD-risk adjusting for common CVD risk-factors. The analyses were further stratified by CVD risk-factors. During follow-up (12.1±4.31 years), 466 participants experienced CVD-events. No association between SNPs/GRS and CVD was observed in the adjusted analyses. However, the GRS, rs10936599, rs2487999 and rs8105767 increase the CVD-risk in current smoker. Few SNPs (rs10936599, rs2487999, and rs7675998) showed an increased CVD-risk, whereas rs10936599, rs677228 and rs4387287 a decreased CVD-risk, in further strata. The results of our study suggest different effects of SNPs/GRS on CVD-risk depending on the CVD risk-factor strata, highlighting the importance of stratified analyses in CVD risk-factors.by Se Min Kim, Namu Park, Hye Bin Park, JuKyung Lee, Changho Chun, Kyung Hoon Kim, Jong Seob Choi, Hyung Jin Kim, Sekyu Choi, Jung Hyun Lee
Triple-negative breast cancer (TNBC) demands urgent attention for the development of effective treatment strategies due to its aggressiveness and limited therapeutic options [1]. This research is primarily focused on identifying new biomarkers vital for immunotherapy, with the aim of developing tailored treatments specifically for TNBC, such as those targeting the PD-1/PD-L1 pathway. To achieve this, the study places a strong emphasis on investigating Ig genes, a characteristic of immune checkpoint inhibitors, particularly genes expressing Ig-like domains with altered expression levels induced by "cancer deformation," a condition associated with cancer malignancy. Human cells can express approximately 800 Ig family genes, yet only a few Ig genes, including PD-1 and PD-L1, have been developed into immunotherapy drugs thus far. Therefore, we investigated the Ig genes that were either upregulated or downregulated by the artificial metastatic environment in TNBC cell line. As a result, we confirmed the upregulation of approximately 13 Ig genes and validated them using qPCR. In summary, our study proposes an approach for identifying new biomarkers applicable to future immunotherapies aimed at addressing challenging cases of TNBC where conventional treatments fall short.by Fatou Ndiaye, Abdoulaye Diop, Joseph Chabi, Katherine Sturm-Ramirez, Massila Senghor, El Hadji Diouf, Badara Samb, Seynabou Mocote Diedhiou, Omar Thiaw, Sarah Zohdy, Ellen Dotson, Doudou Sene, Mame Birame Diouf, Valerie Koscelnik, Lilia Gerberg, Abdoulaye Bangoura, Tiffany Clark, Ousmane Faye, Ibrahima Dia, Lassana Konate, El Hadji Amadou Niang
Urban malaria has become a challenge for most African countries due to urbanization, with increasing population sizes, overcrowding, and movement into cities from rural localities. The rapid expansion of cities with inappropriate water drainage systems, abundance of water storage habitats, coupled with recurrent flooding represents a concern for water-associated vector borne diseases, including malaria. This situation could threaten progress made towards malaria elimination in sub-Saharan countries, including Senegal, where urban malaria has presented as a threat to national elimination gains. To assess drivers of urban malaria in Senegal, a 5-month study was carried out from August to December 2019 in three major urban areas and hotspots for malaria incidence (Diourbel, Touba, and Kaolack) including the rainy season (August-October) and partly dry season (November–December). The aim was to characterize malaria vector larval habitats, vector dynamics across both seasons, and to identify the primary eco- environmental entomological factors contributing to observed urban malaria transmission. A total of 145 Anopheles larval habitats were found, mapped, and monitored monthly. This included 32 in Diourbel, 83 in Touba, and 30 in Kaolack. The number of larval habitats fluctuated seasonally, with a decrease during the dry season. In Diourbel, 22 of the 32 monitored larval habitats (68.75%) were dried out by December and considered temporary, while the remaining 10 (31.25%) were classified as permanent. In the city of Touba 28 (33.73%) were temporary habitats, and of those 57%, 71% and 100% dried up respectively by October, November, and December. However, 55 (66.27%) habitats were permanent water storage basins which persisted throughout the study. In Kaolack, 12 (40%) permanent and 18 (60%) temporary Anopheles larval habitats were found and monitored during the study. Three malaria vectors (An. arabiensis, An. pharoensis and An. funestus s.l.) were found across the surveyed larval habitats, and An. arabiensis was found in all three cities and was the only species found in the city of Diourbel, while An. arabiensis, An. pharoensis, and An. funestus s.l. were detected in the cities of Touba and Kaolack. The spatiotemporal observations of immature malaria vectors in Senegal provide evidence of permanent productive malaria vector larval habitats year-round in three major urban centers in Senegal, which may be driving high urban malaria incidence. This study aimed to assess the presence and type of anopheline larvae habitats in urban areas. The preliminary data will better inform subsequent detailed additional studies and seasonally appropriate, cost-effective, and sustainable larval source management (LSM) strategies by the National Malaria Control Programme (NMCP).by Laia Bertran, Jordi Capellades, Sonia Abelló, Carmen Aguilar, Teresa Auguet, Cristóbal Richart
There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women.by Álvaro Huerta Ojeda, Emilio Jofré-Saldía, Jimena Arriagada Molina, Patricia Rojas Quinchavil, María Paz Parada Toledo, Sergio Galdames Maliqueo, María-Mercedes Yeomans-Cabrera, Carlos Jorquera-Aguilera, Frano Giakoni-Ramirez, Maximiliano Bravo
Functional autonomy (FA) is a critical factor in determining the quality of life of older adults (OA), especially in the case of older women (OW), as they face a decline in FA in their later years of life. FA should be assessed early, using valid, reliable, and low-cost tests. This study evaluated the test-retest reliability of GDLAM and GDLAM autonomy index (GI) in OW. Thirty-nine OW (71.2 ± 6.50 years) participated in the study. A repeated measures design was used to compare the interday test-retest reliability of the five GDLAM tests (seconds) and the GI (points). The five tests represent activities of daily living, such as dressing or wandering around the house, while the GI provides a weighting of the results of the five tests. The analysis consisted of the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and coefficient of variation (CV). A CV ≤ 10% and an ICC ≥ 0.80 were considered acceptable reliability, whereas a CV ≤ 5% and an ICC ≥ 0.90 were considered high reliability. The outcome of the five tests, represented by the GI, showed high interday test-retest reliability (CV = 6.00% and ICC = 0.91). The results of this study demonstrate that the five tests of the GDLAM protocol and the GI have high interday test-retest reliability and good interday reproducibility. From a practical point of view, the GDLAM protocol allows the assessment of FA of community-dwelling OW, providing background for early diagnosis and, with it, the possibility of developing an individualized physical exercise prescription.by Oluwafemi Adeleke Ojo, Akingbolabo Daniel Ogunlakin, Christopher Oloruntoba Akintayo, Olaoluwa Sesan Olukiran, Juliana Bunmi Adetunji, Omolola Adenike Ajayi-Odoko, Theophilus Oghenenyoreme Ogwa, Olorunfemi Raphael Molehin, Omolara Olajumoke Ojo, Ramzi A. Mothana, Abdullah R. Alanzi
Background and objectiveDiabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway.
MethodsTwenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined.
ResultsWe observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine).
ConclusionTherefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.
by Todd M. Hillhouse, Kaitlyn J. Partridge, Patrick I. Garrett, Sarah C. Honeycutt, Joseph H. Porter
Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52- and 56-degree hot plate test and acetic acid writhing) and pain-depressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1–32 mg/kg) failed to produce antinociception in the 52- and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2–32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez
Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.by Anna Kis, Katinka Tóth, Lívia Langner, József Topál
When pre-treated with social stimuli prior to testing, dogs are more susceptible to human influence in a food preference task. This means, after a positive social interaction they are more willing to choose the smaller amount of food indicated by the human, as opposed to their baseline preference for the bigger amount. In the current study we investigate if and how various forms of social interaction modulate choices in the same social susceptibility task, testing dogs with varying early life history (pet dogs, therapy dogs, former shelter dogs). In line with previous studies, dogs in general were found to be susceptible to human influence as reflected in the reduced number of “bigger” choices in the human influence, compared to baseline, trials. This was true not only for pet dogs with a normal life history, but also for dogs adopted from a shelter. Therapy dogs, however, did not uniformly change their preference for the bigger quantity of food in the human influence trials; they only did so if prior to testing they had been pre-treated with social stimuli by their owner (but not by a stranger). Pet dogs were also more influenced after pre-treatment with social stimuli by their owner compared to ignoring and separation; however after pre-treatment by a stranger their behaviour did not differ from ignoring and separation. Former shelter dogs on the other hand were equally influenced regardless of pre-treatment by owner versus stranger. In summary these results show that dogs’ social susceptibility is modulated by both interactions immediately preceding the test as well as by long term social experiences.by Daniela Tamas, Nina Brkic Jovanovic, Stanka Stojkov, Danijela Cvijanović, Bozana Meinhardt–Injac
ObjectiveMost previous studies have examined emotion recognition in autism spectrum condition (ASC) without intellectual disability (ID). However, ASC and ID co-occur to a high degree. The main aims of the study were to examine emotion recognition in individuals with ASC and co-occurring intellectual disability (ASC-ID) as compared to individuals with ID alone, and to investigate the relationship between emotion recognition and social functioning.
MethodsThe sample consisted of 30 adult participants with ASC-ID and a comparison group of 29 participants with ID. Emotion recognition was assessed by the facial emotions test, while. social functioning was assessed by the social responsiveness scale–second edition (SRS-2).
ResultsThe accuracy of emotion recognition was significantly lower in individuals with ASC-ID compared to the control group with ID, especially when it came to identifying angry and fearful emotions. Participants with ASC-ID exhibited more pronounced difficulties in social functioning compared to those with ID, and there was a significant negative correlation between emotion recognition and social functioning. However, emotion recognition accounted for only 8% of the variability observed in social functioning.
ConclusionOur data indicate severe difficulties in the social-perceptual domain and in everyday social functioning in individuals with ASC-ID.
by Mahbubur Rahman, Mahbub-Ul Alam, Sharmin Khan Luies, Sharika Ferdous, Zahidul Mamun, Musarrat Jabeen Rahman, Debashish Biswas, Tazrina Ananya, Asadullah, Abul Kamal, Ritthick Chowdhury, Eheteshamul Russel Khan, Dara Johnston, Martin Worth, Umme Farwa Daisy, Tanvir Ahmed
BackgroundThe influx of Forcibly Displaced Myanmar Nationals (FDMNs) has left the Southwest coastal district of Cox’s Bazar with one of the greatest contemporary humanitarian crises, stressing the existing water, sanitation, and hygiene (WASH) resources and services. This study aimed to assess the existing capacity of local institutions involved in delivering WASH services and identify relevant recommendations for intervention strategies.
MethodsWe used a qualitative approach, including interviews and capacity assessment workshops with institutions engaged in WASH service delivery. We conducted five key informant interviews (KII) with sub-district level officials of the Department of Public Health Engineering (DPHE), Directorate General of Health Services (DGHS), Directorate of Primary Education (DPE) and Bangladesh Rural Advancement Committee (BRAC) to have a general idea of WASH service mechanisms. Seven capacity assessment workshops were organized with the relevant district and sub-district level stakeholders from August 2019 to September 2019. These workshops followed three key areas: i) knowledge of policy, organizational strategy, guidelines, and framework; ii) institutional arrangements for service delivery such as planning, implementation, coordination, monitoring, and reporting; and iii) availability and management of human, financial and infrastructural resources. Data were categorized using thematic content analysis.
ResultsThe majority of stakeholders lacked awareness of national WASH policies. Furthermore, the top-down planning approaches resulted in activities that were not context-specific, and lack of coordination between multiple institutions compromised the optimal WASH service delivery at the local level. Shortage of human resources in delivering sustainable WASH services, inadequate supervision, and inadequate evaluation of activities also required further improvement, as identified by WASH stakeholders.
ConclusionResearch evidence suggests that decision-makers, donors, and development partners should consider learning from the WASH implementers and stakeholders about their existing capacity, gaps, and opportunities before planning for any WASH intervention in any particular area.
by Kimmo Sorjonen, Bo Melin
A recent meta-analysis, of 38 studies with data from 43 independent samples (total N = 24,668), claimed evidence for positive reciprocal prospective effects, and hence for both top-down and bottom-up processes, between general and domain-specific self-esteem. However, the meta-analytic cross-lagged effects were estimated while adjusting for a prior measurement of the outcome variable and it is known that such adjusted cross-lagged effects may be spurious due to correlations with residuals and regression to the mean. In the present reanalyses, we found all of the prospective effects to be spurious. Consequently, claims about increasing prospective effects and top-down and bottom-up processes between general and domain-specific self-esteem can be questioned. It is important for researchers to be aware of the limitations of cross-lagged panel analyses, and of analyses of correlational data in general, in order not to overinterpret findings.by Abdou Fatawou Modiyinji, Lange Tchamba Amorgathe Tankeu, Chavely Gwladys Monamele, Moise Henri Yifomnjou Moumbeket, Paul Alain Tagnouokam Ngoupo, Huguette Tchetgna Simo, Abanda Njei Ngu, Kazanji Mirdad, Richard Njouom
BackgroundFebrile jaundice is a common indicator of certain infectious diseases, including hepatitis E. In Cameroon, the yellow fever virus is the only pathogen that is monitored in patients who present with this symptom. However, more than 90% of the samples received as part of this surveillance are negative for yellow fever. This study aimed to describe the prevalence and hepatitis E virus (HEV) genotype among yellow fever-negative patients in the Far North and West regions of Cameroon.
MethodsIn a cross-sectional study, yellow fever surveillance-negative samples collected between January 2021 and January 2023 were retrospectively analyzed. Anti-HEV IgM and IgG antibodies were tested using commercially available ELISA kits. Anti-HEV IgM and/or IgG positive samples were tested for HEV RNA by real-time RT-PCR, followed by nested RT-PCR, sequencing and phylogenetic analysis.
ResultsOverall, 121 of the 543 samples (22.3%, 95% CI: 19.0% - 26.0%) were positive for at least one anti-HEV marker. Amongst these, 8.1% (44/543) were positive for anti-HEV IgM, 5.9% (32/543) for anti-HEV IgG, and 8.3% (45/544) for both markers. A total of 15.2% (12/79) samples were positive for HEV RNA real-time RT-PCR and 8 samples were positive for HEV RNA by nested RT-PCR. Phylogenetic analysis showed that the retrieved sequences clustered within HEV genotypes/subtypes 1/1e, 3/3f and 4/4b.
ConclusionOur results showed that HEV is one of the causes of acute febrile jaundice in patients enrolled in the yellow fever surveillance program in two regions of Cameroon. We described the circulation of three HEV genotypes, including two zoonotic genotypes. Further studies will be important to elucidate the transmission routes of these zoonotic HEV genotypes to humans in Cameroon.
by Verena Schöneberger, Volkan Tahmaz, Mario Matthaei, Sigrid Roters, Simona L. Schlereth, Friederike Schaub, Claus Cursiefen, Björn O. Bachmann
PurposeTo describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD).
MethodsClinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease. Parameters analysed included demographics, diagnoses, clinical history, thickness measurements using anterior segment OCT, visual acuity, and epithelial status. Regular follow-up visits were scheduled at 6 weeks as well as 3, 6, 9, and 12 and 18 months postoperatively. Main outcome measures were time to graft epithelialisation and the occurrence of corneal endothelial decompensation.
ResultsTwo grafts showed complete epithelial closure at 2 days, two at 14 days. In one eye, complete epithelial closure was not achieved after the first Limbo-DALK, but was achieved one month after the second Limbo-DALK. No endothelial decompensation occurred except in one patient with silicone oil associated keratopathy. Endothelial graft rejection was not observed in any of the grafts.
ConclusionBased on the data from this pilot series, limbo-DALK appears to be a viable surgical approach for eyes with severe LSCD and corneal stromal pathology, suitable for emergency situations (e.g. corneal ulceration with impending corneal perforation), while minimising the risk of corneal endothelial decompensation.
by Urszula Wnorowska, Dawid Łysik, Ewelina Piktel, Magdalena Zakrzewska, Sławomir Okła, Agata Lesiak, Jakub Spałek, Joanna Mystkowska, Paul B. Savage, Paul Janmey, Krzysztof Fiedoruk, Robert Bucki
BackgroundMicrobial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents–DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans.
MethodsThe in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms’ viscoelastic properties characterized by shear storage (G’) and loss moduli (G”), were analyzed with a rotational rheometer.
ResultsOur results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters.
ConclusionDue to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.
by Gerik W. Tushoski-Alemán, Kelly M. Herremans, Patrick W. Underwood, Ashwin Akki, Andrea N. Riner, Jose G. Trevino, Song Han, Steven J. Hughes
BackgroundPancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.
MethodsTissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.
ResultsOur findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.
ConclusionIn this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.
by Gorantla V. Raghuram, Kavita Pal, Gaurav Sriram, Afzal Khan, Ruchi Joshi, Vishalkumar Jadhav, Sushma Shinde, Alfina Shaikh, Bhagyeshri Rane, Harshada Kangne, Indraneel Mittra
Metastatic dissemination following successful treatment of the primary tumour remains a common cause of death. There is mounting evidence that therapeutic interventions themselves may promote development of metastatic disease. We earlier reported that cell-free chromatin particles (cfChPs) released from dying cancer cells are potentially oncogenic. Based on this observation we hypothesized that therapeutic interventions may lead to the release of cfChPs from therapy induced dying cancer cells which could be carried via the blood stream to distant organs to transform healthy cells into new cancers that would masquerade as metastasis. To test this hypothesis, we generated xenografts of MDA-MB-231 human breast cancer cells in severe combined immune-deficient mice, and using immuno-fluorescence and FISH analysis looked for cfChPs in their brain cells. We detected multiple human DNA signals representing cfChPs in nuclei of brain cells of mice which co-localized with eight human onco-proteins. No intact MDA-MB-231 cells were detected. The number of co-localizing human DNA and human c-Myc signals increased dramatically following treatment with chemotherapy, localized radiotherapy or surgery, which could be prevented by concurrent treatment with three different cfChPs deactivating agents. These results suggest that therapeutic interventions lead to the release cfChPs from therapy induced dying cancer cells carrying oncogenes and are transported via the blood stream to brain cells to potentially transform them to generate new cancers that would appear as metastases. cfChPs induced metastatic spread of cancer is preventable by concurrent treatment with agents that deactivate cfChPs.by Richard Okyere Boadu, Godwin Adzakpah, Nathan Kumasenu Mensah, Kwame Adu Okyere Boadu, Jonathan Kissi, Christiana Dziyaba, Rosemary Bermaa Abrefa
BackgroundInformation and communication technology (ICT) has significantly advanced global healthcare, with electronic health (e-Health) applications improving health records and delivery. These innovations, including electronic health records, strengthen healthcare systems. The study investigates healthcare professionals’ perceptions of health information applications and their associated factors in the Cape Coast Metropolis of Ghana’s health facilities.
MethodsWe used a descriptive cross-sectional study design to collect data from 632 healthcare professionals (HCPs), in the three purposively selected health facilities in the Cape Coast municipality of Ghana, in July 2022. Shapiro-Wilk test was used to check the normality of dependent variables. Descriptive statistics were used to report means with corresponding standard deviations for continuous variables. Proportions were also reported for categorical variables. Bivariate regression analysis was conducted to determine the factors influencing the Benefits of Information Technology (BoIT); Barriers to Information Technology Use (BITU); and Motives of Information Technology Use (MoITU) in healthcare delivery. Stata SE version 15 was used for the analysis. A p-value of less than 0.05 served as the basis for considering a statistically significant accepting hypothesis.
ResultsHealthcare professionals (HCPs) generally perceived moderate benefits (Mean score (M) = 5.67) from information technology (IT) in healthcare. However, they slightly agreed that barriers like insufficient computers (M = 5.11), frequent system downtime (M = 5.09), low system performance (M = 5.04), and inadequate staff training (M = 4.88) hindered IT utilization. Respondents slightly agreed that training (M = 5.56), technical support (M = 5.46), and changes in work procedures (M = 5.10) motivated their IT use. Bivariate regression analysis revealed significant influences of education, working experience, healthcare profession, and IT training on attitudes towards IT utilization in healthcare delivery (BoIT, BITU, and MoITU). Additionally, the age of healthcare providers, education, and working experience significantly influenced BITU. Ultimately, age, education, working experience, healthcare profession, and IT training significantly influenced MoITU in healthcare delivery.
ConclusionsHealthcare professionals acknowledge moderate benefits of IT in healthcare but encounter barriers like inadequate resources and training. Motives for IT use include staff training and support. Bivariate regression analysis shows education, working experience, profession, and IT training significantly influence attitudes towards IT adoption. Targeted interventions and policies can enhance IT utilization in the Cape Coast Metropolis, Ghana.
by Einar Rystedt, Jakob Morén, Johan Lindbäck, Vitor Tedim Cruz, Martin Ingelsson, Lena Kilander, Nuno Lunet, Joana Pais, Luis Ruano, Gabriel Westman
Computerized cognitive tests have the potential to cost-effectively detect and monitor cognitive impairments and thereby facilitate treatment for these conditions. However, relatively few of these tests have been validated in a variety of populations. Brain on Track, a self-administered web-based test, has previously been shown to have a good ability to differentiate between healthy individuals and patients with cognitive impairment in Portuguese populations. The objective of this study was to validate the differential ability and evaluate the usability of Brain on Track in a Swedish memory clinic setting. Brain on Track was administered to 30 patients with mild cognitive impairment/mild dementia and 30 healthy controls, all scheduled to perform the test from home after one week and after three months. To evaluate the usability, the patient group was interviewed after completion of the testing phase. Patients scored lower than healthy controls at both the first (median score 42.4 vs 54.1, pby Manuel Ribeiro, Leonardo Azevedo, André Peralta Santos, Pedro Pinto Leite, Maria João Pereira
During the SARS-CoV-2 pandemic, governments and public health authorities collected massive amounts of data on daily confirmed positive cases and incidence rates. These data sets provide relevant information to develop a scientific understanding of the pandemic’s spatiotemporal dynamics. At the same time, there is a lack of comprehensive approaches to describe and classify patterns underlying the dynamics of COVID-19 incidence across regions over time. This seriously constrains the potential benefits for public health authorities to understand spatiotemporal patterns of disease incidence that would allow for better risk communication strategies and improved assessment of mitigation policies efficacy. Within this context, we propose an exploratory statistical tool that combines functional data analysis with unsupervised learning algorithms to extract meaningful information about the main spatiotemporal patterns underlying COVID-19 incidence on mainland Portugal. We focus on the timeframe spanning from August 2020 to March 2022, considering data at the municipality level. First, we describe the temporal evolution of confirmed daily COVID-19 cases by municipality as a function of time, and outline the main temporal patterns of variability using a functional principal component analysis. Then, municipalities are classified according to their spatiotemporal similarities through hierarchical clustering adapted to spatially correlated functional data. Our findings reveal disparities in disease dynamics between northern and coastal municipalities versus those in the southern and hinterland. We also distinguish effects occurring during the 2020–2021 period from those in the 2021–2022 autumn-winter seasons. The results provide proof-of-concept that the proposed approach can be used to detect the main spatiotemporal patterns of disease incidence. The novel approach expands and enhances existing exploratory tools for spatiotemporal analysis of public health data.
FreshRSS