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Sektörlerin birbirleriyle olan etkileşimleri, diğer bir ifadeyle bağınlaşma ilişkisindeki değişimleri ortaya koyan yapısal değişim analizi; ekonomi politika yapıcıları açısından önem taşımaktadır. Söz konusu yapısal değişimi nicel olarak ortaya konulmasında, girdi-çıktı modelleri sıkça kullanılan bir analiz aracıdır. Bu kapsamda yapısal değişim analizi, genel olarak iki farklı dönem için ilgili ekonomilerin kilit sektörlerindeki değişimleri incelemektedir. Buna ek olarak iki farklı dönem için çarpan üretim matrisinin (multiplier product matrix) hesaplanmasıyla, sektörler arası bağınlaşma ilişkilerindeki farklılıklar tespit edilebilmektedir. Bu çalışmada, Türkiye ekonomisindeki olası yapısal değişimlerin analiz edilmesi amacıyla; 1995 ve 2018 yıllarına ilişkin girdi-çıktı tabloları kullanılmıştır. OECD veri tabanından elde edilen girdi-çıktı tablolarında toplulaştırma işlemine gidilerek, 20 sektöre indirgenen tablolar aracılığıyla bağlantı etkileri hesaplanarak ilgili yıllara ilişkin kilit sektörler tanımlanmıştır. Buna göre her iki dönem için imalat ile elektrik, gaz, buhar ve havalandırma sistemi üretim ve dağıtımı sektörleri kilit sektör niteliğindedir. 1995 yılında kilit sektörler arasında yer alan gayrimenkul faaliyetlerinin, 2018 yılında kilit sektör niteliğini yitirdiği; tarım, ormancılık ve balıkçılık ile ulaştırma ve depolama sektörlerinin ise son dönemde kilit sektör niteliği kazandığı sonucuna ulaşılmıştır. Olası yapısal değişim incelenmesi için kullanılan çarpan üretim matrisinden elde edilen bulgulara göre; Türkiye ekonomisi için tarım, ormancılık ve balıkçılık, elektrik, gaz, buhar ve havalandırma sistemi üretim ve dağıtımı ile toptan ve perakende ticaret; motorlu taşıtların ve motosikletlerin onarımı sektörlerinin ekonomideki ağırlığının arttığı sonucuna ulaşılmıştır. Öte yandan gayrimenkul faaliyetleri, eğitim ile kültür, sanat eğlence, dinlence ve spor sektörlerinin ise bağınlaşma ilişkileri açısından öneminin önceki döneme göre azaldığı tespit edilmiştir.

Neuromas form as a result of disorganized sensory axonal regeneration following nerve injury. Painful neuromas lead to poor quality of life for patients and place a burden on healthcare systems. Modern surgical interventions for neuromas entail guided regeneration of sensory nerve fibers into muscle tissue leading to muscle innervation and neuroma treatment or prevention. However, it is unclear how innervating denervated muscle targets prevents painful neuroma formation, as little is known about the fate of sensory fibers, and more specifically pain fiber, as they regenerate into muscle. Golgi tendon organs and muscle spindles have been proposed as possible receptor targets for the regenerating sensory fibers; however, these receptors are not typically innervated by pain fibers, as these free nerve endings do not synapse on receptors. The mechanisms by which pain fibers are signaled to cease regeneration therefore remain unknown. In this article, we review the physiology underlying nerve regeneration, the guiding molecular signals, and the target receptor specificity of regenerating sensory axons as it pertains to the development and prevention of painful neuroma formation while highlighting gaps in literature. We discuss management options for painful neuromas and the current supporting evidence for the various interventions.

We introduce ASSIST, a software package for ephemeris-quality integrations of test particles. ASSIST is an extension of the REBOUND framework and makes use of its IAS15 integrator to integrate test-particle trajectories in the field of the Sun, Moon, planets, and 16 massive asteroids, with the positions of the masses coming from the Jet Propulsion Laboratory’s DE441 ephemeris and its associated asteroid perturber file. The package incorporates the most significant gravitational harmonics and general-relativistic corrections. ASSIST also accounts for position- and velocity-dependent nongravitational effects. The first-order variational equations are included for all terms to support orbit fitting and covariance mapping. This new framework is meant to provide an open-source package written in a modern language to enable high-precision orbital analysis and science by the small-body community. ASSIST is open source, freely distributed under the GNU General Public license v3.0.

AIMS: Hyperglycemia causes generation of free radicals which leads to oxidative stress and apoptosis in various cells. The present study was undertaken to investigate the correlation between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wounds. METHODS: Thirty healthy, thirty uncontrolled type 2 diabetes mellitus (T2DM) and thirty uncontrolled T2DM with chronic, non healing, neuropathic diabetic foot patients were included in this study. Indices of oxidative stress inside the lymphocyte lysate were estimated by measuring content of superoxide dismutase (SOD), Catalase, Glutathione and malonaldialdehyde (MDA). Protein expression studies of pro and anti apoptotic markers were carried out to elucidate their possible involvement in diabetic context. RESULTS: SOD and MDA activity was significantly higher in the lymphocytes of diabetic patients having chronic, non healing diabetic wound as compared with healthy (p<0.001); whereas catalase and GSH activity was significantly reduced (p<0.001) in the same group. Expressions of pro apoptotic markers (Caspase-3, Fas and Bax) were significantly higher whereas reduced expression of anti-apoptotic marker (Bcl-2) were obtained in lymphocytes of diabetic and non diabetic individuals. CONCLUSIONS: Hyperglycemia confers pro apoptotic manifestations which are mostly through altered indices of oxidative stress within lymphocytic milieu. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the evidence surrounding the use of certain complementary supplements in otolaryngology. We specifically focussed on four commonly used supplements: spirulina, Ginkgo biloba, Vertigoheel and nutritional supplements (cod liver oil, multivitamins and pineapple enzyme). MATERIALS AND METHODS: A systematic review of the English and foreign language literature. Inclusion criteria: in vivo human studies. Exclusion criteria: animal trials, in vitro studies and case reports. We also excluded other forms of 'alternative medicine' such as reflexology, acupuncture and other homeopathic remedies. RESULTS: Lack of common outcome measures prevented a formal meta-analysis. Three studies on the effects of spirulina in allergy, rhinitis and immunomodulation were found. One was a double-blind, placebo, randomised, controlled trial (RCT) of patients with allergic rhinitis, demonstrating positive effects in patients fed spirulina for 12 weeks. The other two studies, although non-randomised, also reported a positive role for spirulina in mucosal immunity. Regarding the use of Ginkgo biloba in tinnitus, a Cochrane review published in 2004 showed no evidence for this. The one double-blind, placebo-controlled trial that followed confirmed this finding. Regarding the use of Vertigoheel in vertigo, two double-blind RCTs and a meta-analysis were identified. The first RCT suggested that Vertigoheel was equally effective in reducing the severity, duration and frequency of vertigo compared with betahistine. The second RCT suggested that Vertigoheel was a suitable alternative to G. biloba in the treatment of atherosclerosis-related vertigo. A meta-analysis of only four clinical trials confirms that Vertigoheel was equally effective compared with betahistine, G. biloba and dimenhydrinate. Regarding multivitamins and sinusitis, two small paediatric pilot studies reported a positive response for chronic sinusitis and otitis media following a course of multivitamins and cod liver oil. Regarding bromelain (pineapple enzyme) and sinusitis, one randomised, multicentre trial including 116 children compared bromelain monotherapy to bromelain with standard therapy and standard therapy alone, for the treatment of acute sinusitis. The bromelain monotherapy group showed a faster recovery compared with the other groups. CONCLUSION: The positive effects of spirulina in allergic rhinitis and of Vertigoheel in vertigo are based on good levels of evidence, but larger trials are required. There is overwhelming evidence that G. biloba may play no role in tinnitus. There is limited evidence for the use of multivitamins in sinus symptoms, and larger randomised trials are required. [ABSTRACT FROM AUTHOR]

BackgroundDespite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS).ResultsArchival strains and two "present day" type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the "military" isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of "military" isolates on lactate-containing media, and showed that the "military" strains exhibited a hypersporulating phenotype.ConclusionsOur analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.

BACKGROUND: The anthrax letter attacks of 2001 highlighted the need for rapid identification of biothreat agents not only for epidemiological surveillance of the intentional outbreak but also for implementing appropriate countermeasures, such as antibiotic treatment, in a timely manner to prevent further casualties. It is clear from the 2001 cases that survival may be markedly improved by administration of antimicrobial therapy during the early symptomatic phase of the illness; i.e., within 3 days of appearance of symptoms. Microbiological detection methods are feasible only for organisms that can be cultured in vitro and cannot detect all genetic modifications with the exception of antibiotic resistance. Currently available immuno or nucleic acid-based rapid detection assays utilize known, organism-specific proteins or genomic DNA signatures respectively. Hence, these assays lack the ability to detect novel natural variations or intentional genetic modifications that circumvent the targets of the detection assays or in the case of a biological attack using an antibiotic resistant or virulence enhanced Bacillus anthracis, to advise on therapeutic treatments. METHODOLOGY/PRINCIPAL FINDINGS: We show here that the Roche 454-based pyrosequencing can generate whole genome draft sequences of deep and broad enough coverage of a bacterial genome in less than 24 hours. Furthermore, using the unfinished draft sequences, we demonstrate that unbiased identification of known as well as heretofore-unreported genetic modifications that include indels and single nucleotide polymorphisms conferring antibiotic and phage resistances is feasible within the next 12 hours. CONCLUSIONS/SIGNIFICANCE: Second generation sequencing technologies have paved the way for sequence-based rapid identification of both known and previously undocumented genetic modifications in cultured, conventional and newly emerging biothreat agents. Our findings have significant implications in the context of whole genome sequencing-based routine clinical diagnostics as well as epidemiological surveillance of natural disease outbreaks caused by bacterial and viral agents.

BACKGROUND: Despite the global threat caused by arthropod-borne viruses, there is not an efficient method for screening vector populations to detect novel viral sequences. Current viral detection and surveillance methods based on culture can be costly and time consuming and are predicated on prior knowledge of the etiologic agent, as they rely on specific oligonucleotide primers or antibodies. Therefore, these techniques may be unsuitable for situations when the causative agent of an outbreak is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explored the use of high-throughput pyrosequencing for surveillance of arthropod-borne RNA viruses. Dengue virus, a member of the positive strand RNA Flavivirus family that is transmitted by several members of the Aedes genus of mosquitoes, was used as a model. Aedes aegypti mosquitoes experimentally infected with dengue virus type 1 (DENV-1) were pooled with noninfected mosquitoes to simulate samples derived from ongoing arbovirus surveillance programs. Using random-primed methods, total RNA was reverse-transcribed and resulting cDNA subjected to 454 pyrosequencing. CONCLUSIONS/SIGNIFICANCE: In two types of samples, one with 5 adult mosquitoes infected with DENV-1- and the other with 1 DENV-1 infected mosquito and 4 noninfected mosquitoes, we identified DENV-1 DNA sequences. DENV-1 sequences were not detected in an uninfected control pool of 5 adult mosquitoes. We calculated the proportion of the Ae. aegypti metagenome contributed by each infecting Dengue virus genome (p(IP)), which ranged from 2.75×10(-8) to 1.08×10(-7). DENV-1 RNA was sufficiently concentrated in the mosquito that its detection was feasible using current high-throughput sequencing instrumentation. We also identified some of the components of the mosquito microflora on the basis of the sequence of expressed RNA. This included members of the bacterial genera Pirellula and Asaia, various fungi, and a potentially uncharacterized mycovirus.

Loss of plasma gelsolin (pGSN), a protein that lyses actin filaments, is implicated in the pathology of inflammatory and neurodegenerative diseases. We hypothesized that because pGSN is depleted in a murine model of decompression sickness (DCS), supplementation by administration of human recombinant (rhu-) pGSN would ameliorate inflammatory events. We observed that pGSN levels were persistently decreased in mice for at least 12 days post-exposure to 790 kPa of air for 2 hours. This decline was associated with elevated levels of inflammatory microparticles (MPs) in the blood and cervical lymph nodes, which previously were shown to cause neuroinflammation. Additionally, these mice exhibited reduced expression of synaptic proteins, impaired neurogenesis as well as impaired cognitive and motor functions. Rhu-pGSN ameliorated the inflammatory changes and resulted in restored synaptic protein expression, neurogenesis and neurological function. These findings demonstrate that neuronal dysfunction in our murine model of DCS is mediated by MPs and that rhu-pGSN can ameliorate injury even when administered in a delayed fashion.

Bipolar plates, a critical component of proton exchange membrane fuel cell (PEMFC), are constructed out of alloys of Ti, Pt, Cr, or graphitic materials that have limitations. Electrical conductivity, cost, and corrosion resistance are among the critical considerations for bi-polar plate material. Graphene, which possesses impressive conductivity and toughness, is an attractive option as coating on metallic substrates of PEMFC bipolar plates. This study investigates corrosion resistance and its durability due to graphene developed by chemical vapor deposition on a pure Ni-Cu alloy and a commercial Ni-Cu alloy in 0.5 m H 2 SO 4 environment, with a view to exploring use of graphene coated Ni-Cu alloys for the construction of PEMFC bipolar plates. The graphene coating on the pure alloy shows remarkably superior corrosion resistance than the commercial alloy that is attributed to the former's ability to develop considerably defect-free graphene., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

Graphene coatings developed by chemical vapor deposition (CVD) that possess extraordinary/unique characteristics as barrier against aggressive environment can improve the corrosion resistance of Ni and Cu by up to two orders of magnitude. However, because of some compelling technical reasons, it has thus far been a nontrivial challenge to develop graphene coatings on the most commonly used engineering alloy, mild steel (MS). To circumvent the challenge simply by first electroplating MS with a Ni layer is attempted, and then developing CVD graphene over the Ni layer. However, this approach proved too simplistic and does not work. This necessitated an innovative surface modification of MS (based on basic metallurgical principles) that enabled successful CVD of graphene coating on MS. The graphene coating thus developed is demonstrated to improve the corrosion resistance of mild steel by two orders of magnitude in an aggressive chloride solution, through electrochemical testing. This improvement was not only sustained for the entire test duration of >1000 h; but there is a clear trend for the resistance to be possibly everlasting. The optimized surface modification that enabled development of CVD graphene coating on mild steel is generic in nature, and it should enable graphene coating on other alloy systems, which would otherwise not be possible., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

We hypothesized that early intra-central nervous system (CNS) responses in a murine model of decompression sickness (DCS) would be reflected by changes in the microparticles (MPs) that exit the brain via the glymphatic system, and due to systemic responses the MPs would cause inflammatory changes lasting for many days leading to functional neurological deficits. Elevations on the order of threefold of blood-borne inflammatory MPs, neutrophil activation, glymphatic flow, and neuroinflammation in cerebral cortex and hippocampus were found in mice at 12 days after exposure to 760 kPa of air for 2 h. Mice also exhibited a significant decline in memory and locomotor activity, as assessed by novel object recognition and rotarod testing. Similar inflammatory changes in blood, neuroinflammation, and functional impairments were initiated in naïve mice by injection of filamentous (F-) actin-positive MPs, but not F-actin-negative MPs, obtained from decompressed mice. We conclude that high pressure/decompression stress establishes a systemic inflammatory process that results in prolonged neuroinflammation and functional impairments in the mouse decompression model. NEW & NOTEWORTHY Elevated glymphatic flow due to astrocyte and microglial activation from high-pressure exposure triggers release of microparticles (MPs) to the circulation where neutrophil activation and production of filamentous (F)-actin expressing MPs result in a persistent feed-forward neuroinflammatory cycle and functional deficits lasting for at least 12 days.

A blood component analysis is an early step for evaluating inflammatory disorders, but it can be unfeasible in some settings. This pilot study assessed whether extracellular vesicle (EV) changes in perspiration are parallel to those occurring in blood as an alternative or complementary option to diagnose an inflammatory response. In parallel studies, EVs were analyzed in perspiration and blood obtained before and after five self-contained underwater breathing apparatus (SCUBA) divers at the National Aquarium in Baltimore performed a dive to 3.98 m of sea water for 40 min, and five non-divers performed an exercise routine at ambient atmospheric pressure. The results demonstrated that microparticles (MPs) are present in perspiration, their numbers increase in the blood in response to SCUBA diving, and the interleukin (IL)-1β content increases. In contrast, while blood-borne MPs became elevated in response to terrestrial exercise, no statistically significant increases occurred in perspiration, and there were no changes in IL-1β. There were no statistically significant elevations in the exosomes in perspiration or blood in response to SCUBA diving and few changes following terrestrial exercise. These findings suggest that an MP perspiration analysis could be a non-invasive method for detecting inflammatory responses that can occur due to the oxidative stress associated with SCUBA diving.

Abstract: Background: The objective of this study was to investigate whether transrectal intracolon (TRIC) cooling can prolong the survival duration in a rat hemorrhagic shock (HS) model. Methods: A lethal HS was induced by bleeding 47% of the total blood volume. A TRIC device was placed into the colon to maintain the intracolon temperature either at 37°C (TRIC37) or at 10°C (TRIC10) post-HS. In the surface cooling (SC) rats, the body temperatures were maintained at the same level as the esophageal temperature of the TRIC10 rats. A separated group of TRIC10 rats were resuscitated (Res) at 90 min post-HS. A total of six groups were as follows: (i) Sham TRIC37 (n = 5), (ii) Sham TRIC10 (n = 5), (iii) HS TRIC37 (n = 5), (iv) HS TRIC10 (n = 6), (v) HS SC (n = 6), and (vi) HS TRIC10 + Res (n = 6). Results: An average post-HS survival time was 18.4 ± 9.4 min in HS TRIC37 and 82 ± 27.82 min in the HS SC group. In striking contrast, the HS TRIC10 group exhibited an average survival time of 150.2 ± 66.43 min. The post-HS blood potassium level rose significantly in the HS TRIC37 and HS SC, whereas it remained unchanged in the TRIC10 groups. Post-HS intestinal damage occurred in HS TRIC37 and HS SC groups but virtually absent in HS TRIC10 groups. After resuscitation at 90 min post-HS, all HS TRIC10 rats were fully recovered from the lethal HS. Conclusions: TRIC10 reversed the high blood potassium level, prevented the intestinal damage, and prolonged the survival duration by sixfold relative to normothermia and by twofold compared with SC post-HS. All TRIC10 rats were successfully resuscitated at 90 min post-HS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by the Shock Society.)

Background: It has been a matter of debate for long time about the existence of two distinct phenotypes of primary hyperparathyroidism (PHPT) predisposed to either renal or skeletal manifestation., Objective: To differentiate characteristics of symptomatic PHPT patients based on the presence of skeletal or renal involvement., Design: Retrospective analysis of data from the Indian PHPT registry., Patients: PHPT patients were divided into four discrete groups: asymptomatic, presenting with renal manifestations alone, skeletal manifestations alone, and both skeletal and renal manifestations., Measurements: Clinical, biochemical, and tumour weight and histopathological characteristics of these groups were compared., Results: Of the 229 eligible patients, 45 were asymptomatic, 62 had renal manifestations, 55 had skeletal manifestations, and 67 had both skeletal and renal manifestations. Patients with both skeletal and renal manifestations had higher serum calcium levels than those with isolated skeletal involvement [12.5 (11.1-13.7) mg/dL, 11.2 (10.6-12.3) mg/dL, respectively; p < .05]. Serum alkaline phosphatase (AP), plasma parathyroid hormone (PTH) levels, and parathyroid tumour weight were significantly higher in patients with isolated skeletal, and both skeletal and renal manifestations, compared to the other two groups. A preoperative PTH and AP level of 300 pg/mL and 152 U/L, predicted the risk of developing skeletal involvement with sensitivity and specificity of 71%, 70%, and 69%, 67%, respectively., Conclusions: We observed distinct skeletal and renal phenotypic subgroups among PHPT patients with characteristic biochemical and hormonal patterns with higher parathyroid disease burden in patients with skeletal complications compared to those with isolated renal manifestation., (© 2023 John Wiley & Sons Ltd.)

Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 continues to spread globally. Reverse transcriptase polymerase chain reaction (RT-PCR), which is considered the gold standard for diagnosis, does not always indicate contagiousness. This study was planned to evaluate the performance of the rapid antigen test (RAT) with the duration of symptoms and the usefulness of these tests in determining the infectivity of patients by performing sub-genomic RT-PCR. Methodology This prospective, observational study was designed to compare the diagnostic value of the COVID-19 RAT (SD Biosensor, Korea) with COVID-19 RT-PCR (Thermo Fisher, USA) by serial testing of patients. To evaluate the infectivity of the virus, sub-genomic RT-PCR was performed on previous RAT and RT-PCR-positive samples. Results Of 200 patients, 102 were positive on both RT-PCR and RAT, with 87 patients serially followed and tested. The sensitivity and specificity of RAT were 92.73% and 93.33%, respectively, in symptomatic patients. The mean duration of RAT positivity was 9.1 days, and the mean duration of RT-PCR positivity was 12.6 days. Sub-genomic RT-PCR test was performed on samples that were reported to be positive by RAT, and 73/87 (83.9%) patients were found to be positive. RAT was positive in symptomatic patients whose duration of illness was less than 10 days or those with a cycle threshold value below 32. Conclusions Thus, RAT can be used as the marker of infectivity of SARS-CoV-2 in symptomatic patients, especially in healthcare workers., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Arya et al.)

Blood-borne extracellular vesicles and inflammatory mediators were evaluated in divers using a closed circuit rebreathing apparatus and custom-mixed gases to diminish some diving risks. "Deep" divers ( n = 8) dove once to mean (±SD) 102.5 ± 1.2 m of sea water (msw) for 167.3 ± 11.5 min. "Shallow" divers ( n = 6) dove 3 times on day 1, and then repetitively over 7 days to 16.4 ± 3.7 msw, for 49.9 ± 11.9 min. There were statistically significant elevations of microparticles (MPs) in deep divers (day 1) and shallow divers at day 7 that expressed proteins specific to microglia, neutrophils, platelets, and endothelial cells, as well as thrombospondin (TSP)-1 and filamentous (F-) actin. Intra-MP IL-1β increased by 7.5-fold ( p < 0.001) after day 1 and 41-fold ( p = 0.003) at day 7. Intra-MP nitric oxide synthase-2 (NOS2) increased 17-fold ( p < 0.001) after day 1 and 19-fold ( p = 0.002) at day 7. Plasma gelsolin (pGSN) levels decreased by 73% ( p < 0.001) in deep divers (day 1) and 37% in shallow divers by day 7. Plasma samples containing exosomes and other lipophilic particles increased from 186% to 490% among the divers but contained no IL-1β or NOS2. We conclude that diving triggers inflammatory events, even when controlling for hyperoxia, and many are not proportional to the depth of diving.

This project investigated glial-based lymphatic (glymphatic) function and its role in a murine model of decompression sickness (DCS). DCS pathophysiology is traditionally viewed as being related to gas bubble formation from insoluble gas on decompression. However, a body of work implicates a role for a subset of inflammatory extracellular vesicles, 0.1 to 1 µm microparticles (MPs) that are elevated in human and rodent models in response to high gas pressure and rise further after decompression. Herein, we describe immunohistochemical and Western blot evidence showing that following high air pressure exposure, there are elevations of astrocyte NF-κB and microglial-ionized calcium-binding adaptor protein-1 (IBA-1) along with fluorescence contrast and MRI findings of an increase in glymphatic flow. Concomitant elevations of central nervous system-derived MPs coexpressing thrombospondin-1 (TSP) drain to deep cervical nodes and then to blood where they cause neutrophil activation. A new set of blood-borne MPs are generated that express filamentous actin at the surface that exacerbate neutrophil activation. Blood-brain barrier integrity is disrupted due to activated neutrophil sequestration that causes further astrocyte and microglial perturbation. When postdecompression node or blood MPs are injected into naïve mice, the same spectrum of abnormalities occur and they are blocked with coadministration of antibody to TSP. We conclude that high pressure/decompression causes neuroinflammation with an increased glymphatic flow. The resulting systemic liberation of TSP-expressing MPs sustains the neuroinflammatory cycle lasting for days. NEW & NOTEWORTHY A murine model of central nervous system (CNS) decompression sickness demonstrates that high gas pressure activates astrocytes and microglia triggering inflammatory microparticle (MP) production. Thrombospondin-expressing MPs are released from the CNS via enhanced glymphatic flow to the systemic circulation where they activate neutrophils. Secondary production of neutrophil-derived MPs causes further cell activation and neutrophil adherence to the brain microvasculature establishing a feed-forward neuroinflammatory cycle.

The proinflammatory state associated with diabetes mellitus (DM) remains poorly understood. We found patients with DM have 3- to 14-fold elevations of blood-borne microparticles (MPs) that bind phalloidin (Ph; Ph positive [+] MPs), indicating the presence of F-actin on their surface. We hypothesized that F-actin-coated MPs were an unrecognized cause for DM-associated proinflammatory status. Ph+MPs, but not Ph-negative MPs, activate human and murine (Mus musculus) neutrophils through biophysical attributes of F-actin and membrane expression of phosphatidylserine (PS). Neutrophils respond to Ph+MPs via a linked membrane array, including the receptor for advanced glycation end products and CD36, PS-binding membrane receptors. These proteins in conjunction with TLR4 are coupled to NO synthase 1 adaptor protein (NOS1AP). Neutrophil activation occurs because of Ph+MPs causing elevations of NF-κB and Src kinase (SrcK) via a concurrent increased association of NO synthase 2 and SrcK with NOS1AP, resulting in SrcK S-nitrosylation. We conclude that NOS1AP links PS-binding receptors with intracellular regulatory proteins. Ph+MPs are alarmins present in normal human plasma and are increased in those with DM and especially those with DM and a lower-extremity ulcer., (Copyright © 2023 The Authors.)

The ZAP70 protein tyrosine kinase (PTK) couples stimulated T cell antigen receptors (TCRs) to their downstream signal transduction pathways and is sine qua non for T cell activation and differentiation. TCR engagement leads to activation-induced post-translational modifications of ZAP70, predominantly by kinases, which modulate its conformation, leading to activation of its catalytic domain. Here, we demonstrate that ZAP70 in TCR/CD3-activated mouse spleen and thymus cells, as well as human Jurkat T cells, is regulated by the peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin A (CypA) and that this regulation is abrogated by cyclosporin A (CsA), a CypA inhibitor. We found that TCR crosslinking promoted a rapid and transient, Lck-dependent association of CypA with the interdomain B region, at the ZAP70 regulatory domain. CsA inhibited CypA binding to ZAP70 and prevented the colocalization of CypA and ZAP70 at the cell membrane. In addition, imaging analyses of antigen-specific T cells stimulated by MHC-restricted antigen-fed antigen-presenting cells revealed the recruitment of ZAP70-bound CypA to the immunological synapse. Enzymatically active CypA downregulated the catalytic activity of ZAP70 in vitro, an effect that was reversed by CsA in TCR/CD3-activated normal T cells but not in CypA-deficient T cells, and further confirmed in vivo by FRET-based studies. We suggest that CypA plays a role in determining the activity of ZAP70 in TCR-engaged T cells and impact on T cell activation by intervening with the activity of multiple downstream effector molecules., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The novel coronavirus, SARS-CoV-2, which has caused millions of death globally is recognized to be unstable and recalcitrant in the environment, especially in the way it has been evolving to form new and highly transmissible variants. Of particular concerns are human-environment interactions and the handling and reusing the environmental materials, such as effluents, sludge, or biosolids laden with the SARS-CoV-2 without adequate treatments, thereby suggesting potential transmission and health risks. This study assesses the prevalence of SARS-CoV-2 RNA in effluents, sludge, and biosolids. Further, we evaluate the environmental, ecological, and health risks of reusing these environmental materials by wastewater/sludge workers and farmers. A systematic review of literature from the Scopus database resulted in a total of 21 articles (11 for effluents, 8 for sludge, and 2 for biosolids) that met the criteria for meta-analysis, which are then subdivided into 30 meta-analyzed studies. The prevalence of SAR-CoV-2 RNA in effluent and sludge based on random-effect models are 27.51 and 10 12.25 , respectively, with a 95% CI between 6.14 and 48.89 for the effluent, and 10 4.78 and 10 19.71 for the sludge. However, the prevalence of SARS-CoV-2 RNA in the biosolids based on the fixed-effect model is 30.59, with a 95% CI between 10.10 and 51.08. The prevalence of SARS-CoV-2 RNA in environmental materials indicates the inefficiency in some of the treatment systems currently deployed to inactivate and remove the novel virus, which could be a potential health risk concern to vulnerable wastewater workers in particular, and the environmental and ecological issues for the population at large. This timely review portends the associated risks in handling and reusing environmental materials without proper and adequate treatments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 China University of Geosciences (Beijing) and Peking University. Production and hosting by Elsevier B.V.)

In the present study, a total of 64 road dust samples were collected from five different functional areas (residential, commercial, parks, high-traffic, and industrial) in urban Lucknow to assess the accumulation, distribution, and health risk of heavy metals (HMs) (i.e., Fe, Mn, Zn, Cu, Pb, Cd, As, Cr and Ni). Acid digestion methods were used to analyze HMs, followed by inductively coupled plasma-mass spectrometry (ICPMS). The ascending frequency of HMs was Cd < As < Ni < Cr < Pb < Cu < Zn < Mn < Fe for all different functional areas. Almost all HMs exceed the limits of Indian natural soil background values (INSB) across all functional areas. The pollution assessment results reveal that the urban road dust of Lucknow is highly enriched with Zn and Pb, causing deterioration of dust quality. The spatial distribution of HMs shows that road dust found in the central and southwestern zones of the Lucknow urban area are more contaminated than in other areas. The ecological risk assessment demonstrates that Cd was the highest risk contributor, followed by Pb, Zn and Cu. The result of the health risk assessment i.e., the cumulative hazard index (HI) and the cumulative lifetime cancer risk (LCR), reveal that children (mean HI children = 1.26, LCR children = 0.000187) are more vulnerable to HM exposure than adults (HI adults = 0.14, LCR adults = 0.0000804). For carcinogenic and non-carcinogenic risk, ingestion appears to be the major pathway of HM exposure in both age groups. It is alarming that all studied four carcinogenic HMs were found in concentrations higher than 1 × 10 -6 (the permissible limit for humans). This indicates slight chances of developing cancer for both age groups in all functional areas.

Medicinal plants have been treating various ailments and diseases since ancient times. Aquatic and semiaquatic medicinal plants play an essential role in human welfare to fulfill their daily needs. They have shown biological, pharmacological, nutraceutical, and commercial applications. This review aims to collect and update all recent information on ethnomedicinal, phytochemistry, pharmacological activities, and nanoparticle synthesis and their uses in aquatic and semiaquatic medicinal plants. Original research papers, review papers, short communications, and book chapters on aquatic and semiaquatic plants have been retrieved from PubMed, Web of Science, Scopus, and Google Scholar. Keywords, ethnomedicinal studies, phytochemistry, pharmacological activities, and nanoparticle synthesis from aquatic and semiaquatic medicinal plants are used for the search. Different aquatic and semiaquatic medicinal plants belonging to the families Acanthaceae, Alismataceae, Amaranthaceae, Apiaceae, Araceae, Asteraceae, Boraginaceae, Ceratophyllaceae, Cyperaceae, Fabaceae, Hydrocharitaceae, Lythraceae, Marsileaceae, Menyanthaceae, Nelumbonaceae, Nymphaeaceae, Onagraceae, Plantaginaceae, Poaceae, Polygonaceae, Pontederiaceae, Primulaceae, Scrophulariaceae, and Zingiberaceae have been studied. They are rich in alkaloids, flavonoids, terpenoids, phenolics, saponins, tannins, dietary fiber, glycosidic derivatives, carbohydrates, and proteins. These phytochemicals have been used for their antimicrobial, antioxidant, hepatoprotective, sedative, anticonvulsant, cytotoxic, antiparasitic, and antidiabetic activities. Besides this, various parts of the plants are used as dietary supplements and green nanoparticle synthesis. These plants are also known for their commercial value and are used as an ingredient in some pharmaceutical industries., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this review article., (Copyright © 2022 Ashish Kumar Arya et al.)

Oxygen is a powerful trigger for cellular reactions, but there are few comparative investigations assessing the effects over a large range of partial pressures. We investigated a metabolic response to single exposures to either normobaric (10%, 15%, 30%, 100%) or hyperbaric (1.4 ATA, 2.5 ATA) oxygen. Forty-eight healthy subjects (32 males/16 females; age: 43.7 ± 13.4 years, height: 172.7 ± 10.07 cm; weight 68.4 ± 15.7 kg) were randomly assigned, and blood samples were taken before and 2 h after each exposure. Microparticles (MPs) expressing proteins specific to different cells were analyzed, including platelets (CD41), neutrophils (CD66b), endothelial cells (CD146), and microglia (TMEM). Phalloidin binding and thrombospondin-1 (TSP), which are related to neutrophil and platelet activation, respectively, were also analyzed. The responses were found to be different and sometimes opposite. Significant elevations were identified for MPs expressing CD41, CD66b, TMEM, and phalloidin binding in all conditions but for 1.4 ATA, which elicited significant decreases. Few changes were found for CD146 and TSP. Regarding OPB, further investigation is needed to fully understand the future applications of such findings.

This study presents a spatial assessment of eight potentially toxic elements (PTE: Cd, Cr, Cu, Fe, Pb, Ni, Mn, and Zn) in white button (Agaricus bisporus J.E. Lange) mushroom samples collected from the local vegetable markets of Uttarakhand State, India. Fresh A. bisporus samples were collected from thirteen districts and fifteen sampling locations (M1-M15) and analyzed for the concentration of these PTE using atomic absorption spectroscopy (AAS). The results revealed that A. bisporus contained all eight selected PTE in all sampling locations. Based on the inverse distance weighted (IDW) interpolation, principal component (PC), and hierarchical cluster (HC) analyses, the areas with a plane geographical distribution showed the highest PTE concentrations in the A. bisporus samples as compared to those in hilly areas. Overall, the decreasing order of PTE concentration in A. bisporus was recognized as Fe > Zn > Mn > Cr > Cu > Ni > Cd > Pb. The Kruskal−Wallis ANOVA tests displayed a highly significant (p < 0.05) difference among the sampling locations. However, the concentration of PTE was below permissible limits, indicating no potential hazard in consuming the A. bisporus. Similarly, the health risk assessment studies using the target hazard quotient (THQ) also showed no significant health risk associated with the consumption of A. bisporus being sold in the local mushroom markets of Uttarakhand, India. This study is the first report on state-level monitoring of PTE in A. bisporus mushrooms, which provides crucial information regarding the monitoring and occurrence of potentially toxic metallic elements.

Lysosomes are cellular organelles that regulate essential biological processes such as cellular homeostasis, development, and aging. They are primarily connected to the degradation/recycling of cellular macromolecules and participate in cellular trafficking, nutritional signaling, energy metabolism, and immune regulation. Therefore, lysosomes connect cellular metabolism and signaling pathways. Lysosome's involvement in the critical biological processes has rekindled clinical interest towards this organelle for treating various diseases, including cancer. Recent research advancements have demonstrated that lysosomes also regulate the maintenance and hemostasis of hematopoietic stem cells (HSCs), which play a critical role in the progression of acute myeloid leukemia (AML) and other types of cancer. Lysosomes regulate both HSCs' metabolic networks and identity transition. AML is a lethal type of blood cancer with a poor prognosis that is particularly associated with aging. Although the genetic landscape of AML has been extensively described, only a few targeted therapies have been produced, warranting the need for further research. This review summarizes the functions and importance of targeting lysosomes in AML, while highlighting the significance of lysosomes in HSCs maintenance.

The present study focused on the use of sewage sludge (SS) as a casing material amendment and the potential uptake of metal elements by the cultivated white button ( Agaricus bisporus : MS-39) mushroom. Laboratory experiments were performed under controlled environmental conditions to grow A. bisporus on the composted wheat straw substrate for 50 days. Different treatments (0, 50, 100, 150, and 200 g/kg) of casing material were prepared by mixing garden and dried SS and applied on the mushroom substrate after proper sterilization. The results revealed that SS application was significant ( p < 0.05) in accelerating mushroom yield with a biological efficiency of 65.02% for the mixing rate of 200 g/kg. Moreover, the maximum bioaccumulation of selected metal elements (Cu, Cr, Cd, Fe, Mn, and Zn) was observed using the same treatment. Additionally, the multiple regression models constructed for the uptake prediction of metal elements showed an acceptable coefficient of determination ( R 2 > 0.9900), high model efficiency (ME > 0.98), and low root mean square error (RMSE < 0.410) values, respectively. The findings of this study represent sustainable use of SS for the formulation of mushroom casing material contributing toward synergistic agro-economy generation and waste management.

Context: Primary hyperparathyroidism (PHPT) results from the hypersecretion of parathyroid hormone from parathyroid tumors. A transcription factor, namely Paired box1 (PAX1), is active in parathyroid gland development., Objective: We aimed to study potential epigenetic-mediated mechanism of PAX1 gene in sporadic parathyroid adenomas., Methods: In parathyroid adenomas tissues, we analyzed the DNA methylation via bisulfite-specific polymerase chain reaction (BSP) and histone modifications via chromatin immunoprecipitation in regulating the differential expression of PAX1., Results: The results showed that mRNA and protein expression of PAX1 was significantly reduced in parathyroid adenomas. Bisulfite sequencing demonstrated hypermethylation in the promoter region of PAX1 (35%; 14/40) and lower levels of histone 3 lysine 9 acetylation (H3K9ac) were observed on the promoter region of PAX1 (6-fold; P < .004) in parathyroid adenomas. Furthermore, upon treatment with a pharmacologic inhibitor, namely 5'aza-2 deoxycytidine, in rat parathyroid continuous cells, we found re-expression of PAX1 gene., Conclusion: Our study not only reveals expression of PAX1 is epigenetically deregulated but also paves a way for clinical and therapeutic implications in patients with PHPT., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM)., Methods: We conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index-matched patients with PHPT without T2DM (in 1:2 ratio)., Results: Of the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06)., Conclusion: The prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening., (Copyright © 2021. Published by Elsevier Inc.)