Hidrogeokemična in izotopska karakterizacija ter ocena hidravličnega delovanja kompleksnega kraškega območja Izeh, provinca Khuzestan, jugozahodni Iran

Proper water resources management requires recognizing and evaluating the factors that affect the quantity and quality of water resources. The Ilam-Sarvak (Upper Cretaceous) and Asmari (Oligocene to Miocene) limestone- dolomite formations in the Zagros structural belt have formed a promising karst groundwater horizon. In the present study, the hydraulic relationship between the karst structures of the Izeh territory in the northeast of Khuzestan province was investigated using hydrogeochemical and isotopic information of springs and wells. The results enabled to understand various components influencing the recharge of water resources. In this study, samples were collected from the karst springs and wells of Mongasht, Shavish-Tanosh and Kamarderaz anticlines and Naal-e-Asbi (Horseshoe) syncline and meteoric water to understand the hydrochemical and isotopic characterization, and hydrogeological and hydraulic behavior of the Izeh karst system. The meteoric and groundwater samples were analyzed to determine major and minor ion concentrations and δ18O and δ2H isotope ratios. Isotopic content ranged from -31.6 to -2.9‰ and from -6.32 to -1.87‰ for δ2H and δ18O, respectively, and d-excess values were high and positive. The study of the isotopic content of water samples of springs and wells in the region shows three groups of water sources. The first group, related to the Mongasht anticline springs, has lower isotopic values, indicating that it is recharged by rainfall at high altitudes and snow melting. The isotopic value of the second group is richer than that of the first group, indicating rainfall recharge as well as groundwater mixing (ex­amples of Naal-e-Asbi syncline and Shavish-Tanosh anticline). The highest value in the third group (samples of Kamarderaz anticline) is attributed to evaporation and longer distance from the recharge site to the discharge point, as well as to the diffu­sion system. The trend of decrease in Sr+2 and increase in Ba+2 in the samples of dolomitic limestone formations (Shavish Ta­nosh and Mongasht anticlines) compared to the water samples of Kamarderaz anticline and Naal-e-Asbi syncline indicates the possibility that karst aquifers of the region are recharged from the Mongasht anticline and that there is a hydraulic relation­ship between these structures. D-excess and δ18O show a linear trend, illustrating the effect of altitude difference on isotopic content and recharge sources. The major and minor changes in the concentration of ions, the isotopic content of groundwa­ter and the relationship between TDS and δ18O and d-excess and δ18O indicate the mixing and recharging of karst aquifers (Shavish-Tanosh, Kamarderaz and Naal-e-Asbi aquifers) from the Mongasht karst aquifer and their hydraulic connection.Ustrezno gospodarjenje z vodnimi viri temelji na prepoznavanju in vrednotenju dejavnikov, ki vplivajo na količino in kakovost vodnih virov. Apnenčasto-dolomitni formaciji Ilam-Sarvak (zgornja kreda) in Asmari (oligocen do miocen) v strukturnem pasu Zagros sta oblikovali obetaven kraški vodonosnik. V tej študiji je bil hidravlični odnos med kraškimi strukturami ozemlja Izeh, ki je na severovzhodu province Khuzestan, ocenjen z uporabo hidrogeokemičnih in izotopskih analiz vode v izvirih in vodnjakih. Rezultati so omogočili razumevanje komponent, ki vplivajo na napajanje vodnih virov. Zbrani so bili vzorci iz kraških izvirov in vodnjakov antiklinal Mongašt, Šaviš-Tanoš, Kamarderaz, sinklinale Naal-e-Asbi (podkev) in meteorne vode, da bi razumeli hidrokemično in izotopsko karakterizacijo ter hidrogeološko in hidravlično delovanje kraškega sistema Izeh. Za določitev koncentracij glavnih in drugotnih ionov ter razmerja izotopov δ18O in δ2H so bili analizirani vzorci meteorne in podzemne vode. Vsebnosti izotopov so bile v razponu od ‒31,6 do ‒2,9 ‰ za δ2H in od ‒6,32 do ‒1,87 ‰ za δ18O, vrednosti devterijevega presežka pa so bile visoke in pozitivne. Analize vsebnosti izotopov v vzorcih vode iz izvirov in vodnjakov v regiji kažejo na tri skupine vodnih virov. Prva skupina, ki je povezana z izviri antiklinale Mongašt, ima nižje izotopske vrednosti, kar kaže, da se napaja s padavinami na višjih nadmorskih višinah in s talje­njem snega. Izotopska vrednost druge skupine je bogatejša od prve skupine, kar kaže na napajanje s padavinami in na mešanje podzemnih vod (primera sinklinale Naal-e-Asbi in antiklinale Šaviš-Tanoš). Najvišja vrednost v tretji skupini (vzorci antiklina­le Kamarderaz) je posledica delno izhlapevanja in daljše razdalje med mestoma napajanja in iztekanja ter delno difuzijskega siste­ma. Trend padanja Sr2+ in naraščanja Ba2+ v vzorcih v formacijah dolomitnih apnencev (antiklinali Šaviš-Tanoš in Mongašt) v pri­merjavi z vzorci vode antiklinale Kamarderaz in sinklinale Naal­-e-Asbi kaže na možnost, da se kraški vodonosniki napajajo iz območja antiklinale Mongašt, in na hidravlični odnos med temi strukturami. Devterijev presežek in δ18O kažeta linearni trend, ki ponazarja učinek višinske razlike na vsebnost izotopov in vire napajanja. Večje in manjše spremembe v koncentraciji ionov, vsebnosti izotopov v podzemni vodi in razmerju med TDS in δ18O ter devterijevim presežkom in δ18O kažejo na mešanje in napajanje kraških vodonosnikov (vodonosniki Šaviš-Tanoš, Ka­marderaz in Naal-e-Asbi) s kraškega vodonosnika Mongašt in na njihovo hidravlično povezanost

Exercise training and muscle-cartilage cross-talk: A potential therapeutic target for osteoarthritis

Dear Editor-in-ChiefOsteoarthritis (OA) is a progressive disease and up to now, no effective cure has been found for these diseases. OA was characterized by destruction of articular cartilage (extracellular matrix). As we age, chondrocytes show less response to growth factors, also, there is an increase abnormal accumulation of advanced glycation products (AGEs), mitochondrial dysfunction, and oxidative stress. As a result, cartilage homeostasis is impaired and ECM becomes more vulnerable to injury, leading to the onset of OA (Abramoff & Caldera, 2020). Chondrocytes are the only cell type present in articular cartilage that are solely responsible for circulating and maintaining the matrix. Exercise training with increased mechanical stress can affect the extracellular matrix in the joints. However, exercise apart from mechanical stress can also indirectly affect cartilage metabolism by increasing muscle contraction and the expansion of some myokines, which is a potential therapeutic target for osteoarthritis.A variety of growth factors and cytokines are actively secreted by muscle tissue. Thus, muscle can act as an endocrine and paracrine organ. Secretoms are secreted not only through muscle tissue but also from other tissues and affect other organs of the body. Adipokines include adiponectin, leptin, resistin, chemerin, IL-6, and TNF-α playing an important role not only during inflammation but also in the metabolic regulation of joint cells including cartilage, osteoblasts, osteoclasts, and mesenchymal stem cells (Xie & Chen, 2019). Muscle tissue also affects cartilage metabolism with its myokines.    FNDC5 is an important exercise myokine for slowing down age-related diseases, such as sarcopenia, osteoporosis, obesity, and neurodegeneration. Loss of FDNC5 has been shown to be associated with chondrocyte aging in the development of OA in humans and mice. Myokine maintains chondrocyte activity by preserving the metabolism and biology of the mitochondrial TCA cycle to protect against inflammation-induced aging. Myokine maintains chondrocyte survival and ECM synthesis by suppressing the cartilaginous inhibitory factor Wnt3a to control autophagy programs and apoptosis (Chen et al., 2020). Recently, it has been discovered that Sox9 was expressed in MTJ, tendon, and bone progenitor cells at E13 and in bone at E16. The expression of Sox9 in muscle precursor cells is also being studied. It is hypothesized that an increase in this factor of muscle tissue after exercise can also affect cartilage metabolism because it is stated that decreased Sox9 expression in connective tissues, tendons and bones is associated with cartilage hypoplasia (Nagakura et al., 2020). These hypotheses elucidated that the role of Sox9 secreted by muscle tissue can also play an important role in the development and healing of joint and cartilage, requiring animal and human studies

The comparison of selected statistical indicators of a hospital before and after the implementation of health reform plan: Isfahan-2015

زمینه و اهداف: مرحله سوم طرح تحول نظام سلامت با ابلاغ کتاب ارزش نسبی خدمات و مراقبت‌های سلامت اجرایی شد. با توجه به تأثیر این کتاب بر عملکرد بیمارستان‌ها و مراکز آموزشی درمانی، مطالعه حاضر با هدف تعیین ومقایسه نشانگرهای آماری منتخب یک مرکز آموزشی درمانی قبل و بعد از اجرای مفاد این کتاب انجام گرفت. مواد و روش‌ها: مطالعه توصیفی- تحلیلی حاضر، به صورت مقطعی در سال 1394 انجام شد. نشانگرهای آماری، با بررسی فرم‌های فعالیت مرکز و مراجعه به مدیریت آمار دانشگاه علوم پزشکی اصفهان، با کسب مجوز و رعایت اصل محرمانگی اطلاعات، جمع‌آوری و با نرم افزار آماري SPSS  (ويرايش 17) تحلیل شد. مقایسه نشانگرها توسط آزمون‌های آماری برای نمونه‌های زوج شده انجام و در سطح معنی‌داری 0/05>P تحلیل شد. یافته‌ها: ابلاغ کتاب ارزش نسبی، موجب افزایش معنادار در نشانگرهای درصد اشغال تخت، تخت روز اشغالی، میانگین مدت اقامت بیمار و تعداد مرگ و میر و کاهش معنادار در نشانگرهای فاصله چرخش تخت و چرخش اشغال تخت شد. در نشانگرهای میانگین تعداد بستری شدگان و ترخیص شدگان افزایش و در نشانگرهای تعداد مراجعین اورژانس و سزارین کاهش معنادار مشاهده شد. نتیجه‌ گیری: اجرای کتاب مذکور، بر برخی از نشانگرها (درصد اشغال تخت، تخت روز اشغالی، تعداد سزارین) تأثیر گذار و بر دیگر نشانگرها (تعداد بستری شدگان، مراجعین سرپایی، مراجعین اورژانس، ترخیص شدگان و تعداد اعمال جراحی) بدون تأثیر بوده است. البته تعمیم نتایج مطالعه به سایر بیمارستان‌ها، نیازمند مطالعه گسترده‌تری می‌باشد.Background and Aim: The third phase of health reform plan in Iran came into force since the announcement of the book named value of the notification. Due to the influence of this book on hospitals performance,this study aimed to determine and compare the selected statistical indicators of a teaching hospital before and after the implementation of the contents of this book.Materials and Methods: The present cross-sectional descriptive-analytical study was conducted in 2015. Data (statistical indicators) were collected, with the permission and considering the confidentiality of information, through reports review and on-site visiting and analyzed using SPSS (version 17) software.The comparison of selected indicators between paired samples were performed. Correlations were considered significant at α=0.05.Results: Announcement of the value of the notification book resulted in a statistically significant increase in bed occupancy ratio, occupied bed day, average length of stay, and number of hospital death and also a significant decrease of bed turnover interval and rate. Furthermore, a significant increase of inpatients andoutpatients visits and significant decrease of emergency visits and caesarean were also observed.Conclusion: Implementation of the aforementioned book significantly affected some statistical indicators (bed occupancy ratio, occupied bed day, and caesarian), but it has no significant effect on other statistical indicators (inpatients and outpatients visits, emergency visits and number of surgeries). However, extendingthe results of this study to other hospitals requires more extensive studies

Assessment of the hydrogeochemical and isotopic characterization and hydraulic behavior of the Izeh complex karstic area, Khuzestan province, southwest Iran

Proper water resources management requires recognizing and evaluating the factors that affect the quantity and quality of water resources. The Ilam-Sarvak (Upper Cretaceous) and Asmari (Oligocene to Miocene) limestone- dolomite formations in the Zagros structural belt have formed a promising karst groundwater horizon. In the present study, the hydraulic relationship between the karst structures of the Izeh territory in the northeast of Khuzestan province was investigated using hydrogeochemical and isotopic information of springs and wells. The results enabled to understand various components influencing the recharge of water resources. In this study, samples were collected from the karst springs and wells of Mongasht, Shavish-Tanosh and Kamarderaz anticlines and Naal-e-Asbi (Horseshoe) syncline and meteoric water to understand the hydrochemical and isotopic characterization, and hydrogeological and hydraulic behavior of the Izeh karst system. The meteoric and groundwater samples were analyzed to determine major and minor ion concentrations and δ18O and δ2H isotope ratios. Isotopic content ranged from -31.6 to -2.9‰ and from -6.32 to -1.87‰ for δ2H and δ18O, respectively, and d-excess values were high and positive. The study of the isotopic content of water samples of springs and wells in the region shows three groups of water sources. The first group, related to the Mongasht anticline springs, has lower isotopic values, indicating that it is recharged by rainfall at high altitudes and snow melting. The isotopic value of the second group is richer than that of the first group, indicating rainfall recharge as well as groundwater mixing (ex­amples of Naal-e-Asbi syncline and Shavish-Tanosh anticline). The highest value in the third group (samples of Kamarderaz anticline) is attributed to evaporation and longer distance from the recharge site to the discharge point, as well as to the diffu­sion system. The trend of decrease in Sr+2 and increase in Ba+2 in the samples of dolomitic limestone formations (Shavish Ta­nosh and Mongasht anticlines) compared to the water samples of Kamarderaz anticline and Naal-e-Asbi syncline indicates the possibility that karst aquifers of the region are recharged from the Mongasht anticline and that there is a hydraulic relation­ship between these structures. D-excess and δ18O show a linear trend, illustrating the effect of altitude difference on isotopic content and recharge sources. The major and minor changes in the concentration of ions, the isotopic content of groundwa­ter and the relationship between TDS and δ18O and d-excess and δ18O indicate the mixing and recharging of karst aquifers (Shavish-Tanosh, Kamarderaz and Naal-e-Asbi aquifers) from the Mongasht karst aquifer and their hydraulic connection

Muscle-muscle crosstalk and potential therapies for muscle wasting diseases: does exercise matter?

Dear Editor-in-ChiefDifferent types of exercise training with increasing muscle contraction can stimulate muscle secretome called myokines. Myokines are the main mediators of maintaining muscle structure and function in manner of autocrine and paracrine. These myokines can both affect distant tissues and have positive effects on muscle tissue itself (Chen, Wang, You, & Shan, 2021). In various diseases leading to muscle wasting, it seems that exercise and increased contraction can reduce the rate of muscle wasting and muscle atrophy by regulating myokines. Myostatin is a myokine that negatively regulates skeletal muscle development. In animal models, myostatin degradation has been shown to increase muscle mass and inhibit myostatin signals which can control the loss of muscle mass due to cancer cachexia (X. Zhou et al., 2010). Zhou et al. (2021) showed that exercise training (strength or balance in combination with endurance training) seems to be effective in preventing sarcopenia and maintaining muscle mass in non-dialysis-dependent patients with chronic kidney disease (CKD) with inhibition of myostatin signaling (Y. Zhou, Hellberg, Hellmark, Höglund, & Clyne, 2021).Apelin is another myokine that decreases in age-dependent manner (Vinel et al., 2018). Apelin signaling in aging helps to increase muscle function by stimulating mitochondrial biogenesis and anti-inflammatory pathways in myofibers and improving regenerative capacity by targeting muscle stem cells (Vinel et al., 2018). It has been shown that exercise can positively regulate the Apelin and improve muscle growth. Apelin, an exerkine, is elevated due to maternal exercise, and maternal apelin administration mirrors the effect of maternal exercise on mitochondrial biogenesis in fetal muscle (Son et al., 2020). In other words, Apelin inhibits skeletal muscle dysfunction.Leukemia inhibitory factor (LIF) is primarily expressed at low levels in type 1 muscle fibers. LIF has been shown to affect the growth and regeneration of skeletal muscle. For example, the expression of LIF protein in rat plantaris muscle is increased by mechanical load (Sakuma et al., 1998). Furthermore, LIF stimulates the hypertrophic response to increased load in the animal model, and in this respect LIF has been shown to be an important factor in skeletal muscle hypertrophy. In addition, LIF mRNA increases in human skeletal muscle following muscle damage leading to better repair. Therefore, this factor secreted by skeletal muscle can increase in various injuries and diseases with exercise and controls muscle wasting. Irisin is one of the most important muscle myokines that is secreted from muscle tissue through exercise and has auto and paracrine effects. It was shown that the injection of irisin induced muscle hypertrophy, improved muscle strength and reduced necrosis and development of connective tissue in a murine model (Reza et al., 2017). Therefore, increasing this factor with exercise can counteract cachexia and atrophy.Musclin is an exercise-responsive myokine associated with plasma atrial NP (ANP) and cyclic guanosine monophosphate (cGMP) and the expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α) expression in skeletal muscle after exercise training (Subbotina et al., 2015). Musclin helps increase exercise capacity by increasing mitochondrial biogenesis in mice (Subbotina et al., 2015). In addition to its role in exercise, Musclin reduces muscle tissue damage during the development of cachexia-induced tumors and has beneficial effects on cancer patients at risk for cachexia (Re Cecconi et al., 2019). C - X - C motif chemokine ligand 12 (CXCL12) is another type of myokine that is involved in the growth of skeletal muscle. CXCL12 helps proliferate myogenic and angiogenic somite progenitor cells and controls myotoma formation (Abduelmula et al., 2016). Moreover, it has been shown that the concentration of plasma CXCL12 is enhanced in response to training on a bicycle ergometer (Wang, Lee, Lien, & Weng, 2014). Overall, muscle - muscle crosstalk with several myokines mediates the beneficial effects of exercise training, including regulating muscle growth, preventing muscle loss, and increasing muscle function and regeneration, and these factors can decrease muscle wasting diseases

The molecular basis of the neutralization breadth of the RBD-specific antibody CoV11

SARS-CoV-2, the virus behind the COVID-19 pandemic, has changed over time to the extent that the current virus is substantially different from what originally led to the pandemic in 2019–2020. Viral variants have modified the severity and transmissibility of the disease and continue do so. How much of this change is due to viral fitness versus a response to immune pressure is hard to define. One class of antibodies that continues to afford some level of protection from emerging variants are those that closely overlap the binding site for angiotensin-converting enzyme 2 (ACE2) on the receptor binding domain (RBD). Some members of this class that were identified early in the course of the pandemic arose from the VH 3-53 germline gene (IGHV3-53*01) and had short heavy chain complementarity-determining region 3s (CDR H3s). Here, we describe the molecular basis of the SARS-CoV-2 RBD recognition by the anti-RBD monoclonal antibody CoV11 isolated early in the COVID-19 pandemic and show how its unique mode of binding the RBD determines its neutralization breadth. CoV11 utilizes a heavy chain VH 3-53 and a light chain VK 3-20 germline sequence to bind to the RBD. Two of CoV11’s four heavy chain changes from the VH 3-53 germline sequence, ThrFWR H128 to Ile and SerCDR H131 to Arg, and some unique features in its CDR H3 increase its affinity to the RBD, while the four light chain changes from the VK 3-20 germline sequence sit outside of the RBD binding site. Antibodies of this type can retain significant affinity and neutralization potency against variants of concern (VOCs) that have diverged significantly from original virus lineage such as the prevalent omicron variant. We also discuss the mechanism by which VH 3-53 encoded antibodies recognize spike antigen and show how minimal changes to their sequence, their choice of light chain, and their mode of binding influence their affinity and impact their neutralization breadth

Targeting enteroviral 2A protease by a 16-mer synthetic peptide: Inhibition of 2Apro-induced apoptosis in a stable Tet-on HeLa cell line

AbstractEnteroviridae such as coxsackievirus are important infectious agents causing viral heart diseases. Viral protease 2A (2Apro) initiates the virus life cycle, and is an excellent target for developing antiviral drugs. Here, to evaluate the validity of the 2Apro as a proper therapeutic target, and based on the existing information and molecular dynamics, a 16-mer peptide was designed to specifically target the active site of protease 2Apro in order to block the activity of CVB3 2Apro. We showed that the peptide could compete with endogenous substrate in a concentration-dependent manner. Further, we established a HeLa cell line that expressed 2Apro. Expression of 2Apro resulted in significant morphological alteration and eventual cell death. Western blot and viability assay showed that the 16-mer peptide (200 μg/ml) could significantly block 2Apro activity and its cytotoxic effect. Future modification of the 16-mer peptide can improve its affinity for 2Apro and therefore develop effective antiviral drug

Volume Changes After Traumatic Spinal Cord Injury in Animal Studies - A Systematic Review

There are limited data on the lesion volume changes following spinal cord injury (SCI). In this study, a meta-analysis was performed to evaluate the volume size changes of the injured spinal cord over time among animal studies in traumatic SCI. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive electronic search of English literature of PubMed and EMBASE databases from 1946 to 2015 concerning the time-dependent changes in the volume of the spinal cord following mechanical traumatic SCI. A hand-search was also performed for non-interventional, non-molecular, and non-review studies. Quality appraisal, data extraction, qualitative and quantitative analyses were performed afterward. Of 11,561 articles yielded from electronic search, 49 articles were assessed for eligibility after reviewing of titles, abstracts, and references. Ultimately, 11 articles were eligible for quantitative synthesis. The ratio of lesion volume to spinal cord total volume increased over time. Avascularity appeared in spinal cord 4 hours after injury. During the first week, the spinal subarachnoid space decreased. The hemorrhagic lesion size peaked in 1 week and decreased thereafter. Significant loss of gray and white matter occurred from day 3 with a slower progression of white matter damage. Changes of lesion extent over time is critical in pathophysiologic processes after SCI. Early avascularity, rapid loss of gray matter, slow progression of white matter damage, and late cavitation are the pathophysiologic key points of SCI, which could be helpful in choosing the proper intervention on a timely basis

Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe