During the recent times, environmental antibiotic resistance genes (ARGs) and their potential transfer to other bacterial hosts of pathogenic importance are of serious concern. However, the dissemination strategies of such ARGs are largely unknown. We tested that saprotrophic soil fungi differentially enriched antibiotic resistant bacteria (ARBs) and subsequently contributed in spatial distribution of selective ARGs. Wafergen qPCR analysis of 295 different ARGs was conducted for manure treated pre-sterilized soil incubated or not with selected bacterial-fungal consortia. The qPCR assay detected unique ARGs specifically found in the mycosphere of ascomycetous and basidiomycetous fungi. Both fungi exerted potentially different selection pressures on ARBs, resulting in different patterns of ARGs dissemination (to distant places) along their respective growing fungal highways. The relative abundance of mobile genetic elements (MGEs) was significantly decreased along fungal highways compared to the respective inoculation points. Moreover, the decrease in MGEs and ARGs (along fungal highways) was more prominent over time which depicts the continuous selection pressure of growing fungi on ARBs for enrichment of particular ARGs in mycosphere. Such data also indicate the potential role of saprotrophic soil fungi to facilitate horizontal gene transfer within mycospheric environmental settings. Our study, therefore, advocates to emphasize the future investigations for such (bacteria-fungal) interactive microbial consortia for potential (spatial) dissemination of resistance determinants which may ultimately increase the exposure risks of ARGs.

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BACKGROUND: Angiotensin receptor blockers (ARBs) are commonly prescribed antihypertensive agents that have well-known antifibrotic properties. The purpose of this study was to examine the association between ARB use and the rates of new-onset adhesive capsulitis as well as adhesive capsulitis requiring operative treatment.
METHODS: Using a large national insurance database, a randomly generated cohort of patients with at least 3 continuous months of ARB use between January 2010 and December 2019 (n = 1,000,000) was compared to a separate randomly generated cohort without ARB use (n = 3,000,000). Rates of newly diagnosed adhesive capsulitis and associated manipulation under anesthesia (MUA) and/or arthroscopic capsulotomy were calculated over a 1- and 2-year period following the completion of at least 3 continuous months of ARB therapy. Rates were compared using multivariable logistic regression to control for demographics and comorbidities. Both unadjusted and adjusted odds ratios and 95% confidence intervals were calculated and reported for each comparison. Statistical significance was set at P <.05.
RESULTS: The mean age in the ARB cohort was 61.8 years (standard deviation [SD] = 10.0), whereas in the control cohort, it was 54.8 years (SD = 12.3) (P < .001). The ARB cohort had significantly lower rates of newly diagnosed adhesive capsulitis compared with the control cohort at both 1 year (0.15% vs. 0.55%, P < .001) and 2 years (0.3% vs. 0.78%, P < .001). Similar findings were observed for the arthroscopic capsular release/MUA cohort associated with adhesive capsulitis. After adjusting for confounding factors, the lower rates of adhesive capsulitis and arthroscopic capsular release/MUA associated with adhesive capsulitis in the ARB cohort remained statistically significant (P < .001).
CONCLUSIONS: Patients prescribed ARBs experienced a decreased rate of newly diagnosed adhesive capsulitis, as well as adhesive capsulitis requiring surgical intervention when compared to a control cohort. These findings suggest a potential protective effect of ARBs against the development of adhesive capsulitis. Further investigations are warranted to elucidate the underlying mechanisms and establish a causal relationship.

UNASSIGNED: Ischemic stroke is one of the prevalent neurodegenerative disorders; it is generally characterized by sudden abruption of blood flow due to thromboembolism and vascular abnormalities, eventually impairing the supply of oxygen and nutrients to the brain for its metabolic needs. Oxygen-glucose deprived conditions provoke the release of excessive glutamate, which causes excitotoxicity.
UNASSIGNED: Recent studies suggest that circulatory angiotensin-II (Ang-II) has an imperative role in initiating detrimental events through binding central angiotensin 1 (AT1) receptors. Insufficient energy metabolites and essential ions often lead to oxidative stress during ischemic reperfusion, which leads to the release of proinflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and cytokines like interleukin-18 (IL-18) and interleukin- 1beta (IL-1β). The transmembrane glutamate transporters, excitatory amino acid transporter-2 (EAAT-2), which express in astroglial cells, have a crucial role in the clearance of glutamate from its releasing site and convert glutamate into glutamine in normal circumstances of brain physiology.
UNASSIGNED: During cerebral ischemia, an impairment or dysfunction of EAAT-2 attributes the risk of delayed neuronal cell death. Earlier studies evidencing that angiotensin receptor blockers (ARB) attenuate neuroinflammation by inhibiting the Ang-II/AT1 receptor-mediated inflammatory pathway and that ceftriaxone ameliorates the excitotoxicity-induced neuronal deterioration by enhancing the transcription and expression of EAAT-2 via the nuclear transcriptional factor kappa-B (NF-kB) signaling pathway. The present review will briefly discuss the mechanisms involved in Ang-II/AT1-mediated neuroinflammation, ceftriaxone-induced EAAT-2 expression, and the repurposing hypothesis of the novel combination of ARBs and ceftriaxone for the treatment of cerebral ischemia.

Shem Creek is a Charleston waterway well-known for numerous recreational activities such as paddle boarding, fishing, and kayaking. However, Charleston WaterKeepers, a local organization, has consistently found high levels of coliform bacteria within Shem Creek. With antibiotic prescription rates surging and coastal flooding becoming an increasing concern, antibiotic resistant bacteria (ARBs) have become both a public health and environmental risk. ARBs can lead to the spread of antibiotic-resistant infections (ARIs) within populations. Precipitation influences bacterial concentrations in a body of water. Immediately after rainfall, the levels of bacteria rise tremendously. Runoff from livestock, sewage, and hospitals are known to contribute to the development of ARBs in bodies of water. Consistent water testing is essential to preventing the risk and spread of ARIs and determining what additional factors contribute to the development of ARBs in an aquatic environment. This pilot study found that precipitation was directly associated with the levels of bacteria found within Shem Creek and validated that ARBs are present within local waterways in Charleston, South Carolina.

The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.

The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer\'s dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and β-amyloid (Aβ) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation\'s favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aβ metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.

OBJECTIVE: To evaluate the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections among patients receiving in-center hemodialysis (ICHD), the relationship between the IgG antibody levels against the virus and SARS-CoV-2-associated symptoms, hemodialysis adequacy, and the antihypertensives used in order to control blood pressure.
METHODS: A prospective observational study was carried out at a tertiary care center, King Fahad Kidney Center, Riyadh, Kingdom of Saudi Arabia, between November 2020 and January 2021. A total of 214 ICHD patients with end-stage renal disease (ESRD) were included, and the levels of their anti-SARS-CoV-2 IgG antibodies were assessed after obtaining their informed consent.
RESULTS: Our tests indicated that 15% of the patients in the study\'s population had detectable SARS-CoV-2 IgG antibodies, with more than half of them (53%) being asymptomatic. We also found that ESRD patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) had higher levels of SARS-CoV-2 IgG antibodies than patients not receiving this group of medications.
CONCLUSIONS: More studies are required to assess whether patients with a SARS-CoV-2 infection that do not have an indication for being prescribed ACEIs/ARBs would benefit from receiving these medications.