The healing power of Aloe vera mucilage: induction of insulin-like growth factor gene expression and regeneration tissue in mouse damaged skin

زمینه و هدف: گیاه آلوئه ورا (Aloe barbadensis Miller) از جمله گیاهان استوایی بوده که به منظور ترمیم بسیاری از سوختگی ها و دیگر زخم ها کاربرد فراوان دارد؛ مطالعه حاضر با هدف بررسی اثرات موسیلاژ آلوئه ورا بر فرآیند ترمیم زخم در پوست آسیب دیده موش انجام شده است. روش بررسی: در این مطالعه تجربی 30 سر موش سوری نر نژادbalb/c در محدوده وزنی 2±22 گرم به پنج گروه بدون زخم (کنترل منفی)، زخم با تیمار سرم فیزیولوژیک به مدت 8 روز، زخم با تیمار سروم فیزیولوژیک به مدت 16 روز، زخم با تیمار موسیلاژ آلوئه ورا به مدت 8 روز و زخم با تیمار آلوئه ورا به مدت 16 روز تقسیم شدند. بر روی پشت هر موش دو زخم مساوی به قطر 2 ±10 میلی متر با برداشت ضخامت کامل پوست (Full-thickness) ایجاد گردید. پس از 8 و 16 روز از هر گروه نمونه برداری های به عمل آمدو از تکنیک RT-PCR جهت بررسی میزان بیان ژن فاکتور رشد شبه انسولینی (IGF) و در مطالعات بافت شناسی تغییرات بافتی مورد بررسی قرار گرفت. جهت بررسی آماری از آزمون آماری آنالیز واریانس یک طرفه (ANOVA) و آزمون تعقیبی توکی (Tukey) استفاده شد. یافته ها: تیمار با موسیلاژ آلوئه ورا سبب افزایش بیان ژن فاکتور رشد شبه انسولینی (IGF) در 8 و 16 روز پس از ایجاد زخم نسبت به گروه شم گردید (05/0

Evaluation of the cytotoxicity and protein expression alteration induced by nanoparticles of silver in the rat sperm and testis

زمینه و هدف: اگرچه امروزه به طور گسترده از نانو ذرات نقره در صنعت و پزشکی استفاده می گردد، اما هنوز اطلاعات اندکی درباره سمیت نقره خصوصاً بر سیستم تولید مثلی نر وجود دارد. مطالعه حاضر با هدف بررسی اثرات سمی و تغییراتی که به واسطه نانو ذرات نقره در پروتئین های داخل سلولی، در دستگاه تولید مثلی نر ایجاد می گردد، انجام شد. روش بررسی: در این مطالعه تجربی 24 سر موش صحرایی نر نژاد ویستار به طور تصادفی به 4 گروه مساوی تقسیم شدند. در گروه های تجربی 1،2 و 3 نانو نقره به صورت خوراکی به مدت 45 روز متوالی به ترتیب با غلظت ppm1، 10 و 20 داده شد. موش های صحرایی گروه 4 (گروه شاهد) نیز اتیلن گلیکول با غلظت ppm20 را به مدت 45 روز از راه دهان (گاواژ) دریافت کردند. نتایج بدست آمده از مطالعات روش سنجش میزان انتشار DNA (DNA Diffusion Assay) با آزمون آماری ANOVAو تست تعقیبی Tukey مورد تجزیه و تحلیل آماری قرار گرفتند؛ نتایج حاصله از انجام الکتروفورز نیز با استفاده از نرم افزار Image J مقایسه شدند. یافته ها: نتایج بررسی رخداد آپوپتوز به روش DNA diffusion assay در گروه های تجربی نشان دهنده افزایش معنی دار در تعداد اسپرم هایی داشت که آپوپتوز در آن ها رخ داده بود (05/0>P). همچنین نتایج بررسی تغییر بیان پروتئین ها در سلول های بیضه، افزایش بیان پروتئین های داخل سلولی با افزایش غلظت نانوذرات را در مقایسه با گروه شاهد نشان داد. نتیجه گیری: بر اساس نتایج این مطالعه نانو ذرات نقره می توانند موجب القای آپوپتوز در اسپرم و تغییر بیان پروتئین های سلولی در بیضه های موش های صحرایی شوند

The Effect of Short-term, Medium, and Long-term Time Horizons on the Prediction of Future Cash Flows: A Comparative Study of the Ability of Operating Earnings and Cash Flows

Cash flow prediction is an essential component of economic decision making, particularly in investment and credit evaluation. This paper examines the comparative predictive ability of earnings and operating cash flows variables on future operating cash flows, during short-term, medium, and long-term periods. For this purpose, the data collected from financial statements of 203 companies listed in Tehran Stock Exchange, during a ten-year period (2005-2015) were used. In regression model, the changes of current operating cash flows (as proxy for future operating cash flows) under the influence of past one, three and five years of earnings and operating cash flows (as predictors), are evaluated. The results from the regression analysis reveal earnings and operating cash flows are significant in predicting future operating cash flows but their predictive powers are different, so that comparative predictive ability of operating earnings variable about future operating cash flows is more than that of the operating cash flow itself. The results also show that using both operating earnings and operating cash flow with each other for the prediction, has better outcomes. Moreover, the results indicate that the longer the period of prediction is, the higher the prediction power will be

Cijeljenje tetivnih ozljeda uporabom G-90 na modelu kunića: biokemijska i histopatološka procjena.

Tendon injuries are one of the most common and disabling acute orthopedic disorders. Several techniques are used to restore the mobility of patients, but all have significant limitations. In some studies utilization of biomaterials has been investigated in the healing of tendons, skin and nerves. The present study was designed to investigate the effects of G-90, as a stimulating factor agent, on the healing of the superficial digital flexor tendon (SDFT) of rabbits after 35 days post tenotomy and surgical repair. Twenty male rabbits, 12 months old and weighing 2.0 ± 0.5 kg were used in this study. All rabbits were anesthetized, and the superficial flexor tendons of both hind limbs were cut transversely and then sutured with a Bunnel-Mayer suture pattern. After suturing tendons and skin, 0.5 mL of normal saline was injected in the injured tendon area of the left leg and 0.5 mL earthworm extract (EW) G-90 was injected at a concentration of 10 mg/mL into the injured tendon area of the right leg. Every two weeks 4 rabbits were euthanized, and samples were collected and sent for histopathological and biomechanical evaluation. In the histopathological evaluation less inflammation, more maturity of fibrocytes and more aggregation of collagen fibers were observed in tendons treated with G-90 in comparison with untreated tendons. In the biomechanical evaluation the ultimate strength of tendons treated with G-90 was superior to untreated tendons. The findings of the present experiment clearly show that administration of G-90 could enhance the structural and biomechanical properties of the experimentally tenotomized SDFT in rabbits.Ozljede tetiva predstavljaju jedan od najčešćih akutnih ortopedskih poremećaja što dovode do njihove funkcionalne oslabljenosti. Razvijeno je nekoliko postupaka za ponovnu uspostavu pokretnosti pacijenata, ali svi imaju znatna ograničenja. U nekim istraživanjima opisana je uporaba biomaterijala za cijeljenje ozljeda tetiva, kože i živaca. U ovom su radu istraženi učinci G-90, kao stimulacijskog čimbenika cijeljenja tetive površinskog digitalnog fleksora kunića 35 dana nakon tenotomije i kirurškog liječenja. U pokus je bilo uzeto 20 kunića u dobi od 12 mjeseci, tjelesne mase 2,0 ± 0,5 kg. Svim su kunićima pod anestezijom bile poprečno prerezane tetive površinskog digitalnog fleksora stražnjih nogu te potom spojene Bunnel-Mayer-ovim šavom. Nakon šivanja tetive i kože, 0,5 mL fiziološke otopine bilo je ubrizgano u područje tetivne ozljede lijeve noge, a 0,5 mL iscrpka G-90 kišne gujavice u koncentraciji od 10 mg/mL bilo je ubrizgano u područje tetivne ozljede desne noge. Svaka dva tjedna bila su eutanazirana 4 kunića te su im bili uzeti uzorci za patohistološke i biokemijske pretrage. Patohistološkom pretragom tetiva kunića kojima je bio primijenjen G-90 ustanovljena je slabija upala, veća zrelost fibrocita i veće nakupljanje kolagenih vlakana u usporedbi s tetivama kojima nije bio primijenjen G-90. Kod biokemijske procjene konačna čvrstoća tetiva obrađenih s G-90 bila je veća u odnosu na one neobrađene. Rezultati ovog pokusa jasno su pokazali da primjena G-90 može osnažiti strukturu i biokemijska svojstva tetiva kunića nakon tenotomije i kirurškog liječenja

Effect of Curcuma zedoaria hydro-alcoholic extract on learning, memory deficits and oxidative damage of brain tissue following seizures induced by pentylenetetrazole in rat

Background Previous studies have shown that seizures can cause cognitive disorders. On the other hand, theCurcuma zedoaria(CZ) has beneficial effects on the nervous system. However, there is little information on the possible effects of the CZ extract on seizures. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats. Methods Rats were randomly divided into different groups. In all rats (except the sham group), kindling was performed by intraperitoneal injection of pentylenetetrazol (PTZ) at a dose of 35 mg/kg every 48 h for 14 days. Positive group received 2 mg/kg diazepam + PTZ; treatment groups received 100, 200 or 400 mg/kg CZ extract + PTZ; and one group received 0.5 mg/kg flumazenil and CZ extract + PTZ. Shuttle box and Morris Water Maze tests were used to measure memory and learning. On the last day of treatments PTZ injection was at dose of 60 mg/kg, tonic seizure threshold and mortality rate were recorded in each group. After deep anesthesia, blood was drawn from the rats' hearts and the hippocampus of all rats was removed. Results Statistical analysis of the data showed that the CZ extract significantly increased the tonic seizure threshold and reduced the pentylenetetrazol-induced mortality and the extract dose of 400 mg/kg was selected as the most effective dose compared to the other doses. It was also found that flumazenil (a GABA(A)receptor antagonist) reduced the tonic seizure threshold compared to the effective dose of the extract. The results of shuttle box and Morris water maze behavioral tests showed that memory and learning decreased in the negative control group and the CZ extract treatment improved memory and learning in rats. The CZ extract also increased antioxidant capacity, decreased MDA and NO in the brain and serum of pre-treated groups in compared to the negative control group. Conclusion: It is concluded that the CZ extract has beneficial effects on learning and memory impairment in PTZ-induced epilepsy model, which has been associated with antioxidant effects in the brain or possibly exerts its effects through the GABAergic system. Keywords:Curcuma zedoaria; Pentylenetetrazole; Repeated seizures; Oxidative stress; Memor

Toward impact-based monitoring of drought and its cascading hazards

Growth in satellite observations and modelling capabilities has transformed drought monitoring, offering near-real-time information. However, current monitoring efforts focus on hazards rather than impacts, and are further disconnected from drought-related compound or cascading hazards such as heatwaves, wildfires, floods and debris flows. In this Perspective, we advocate for impact-based drought monitoring and integration with broader drought-related hazards. Impact-based monitoring will go beyond top-down hazard information, linking drought to physical or societal impacts such as crop yield, food availability, energy generation or unemployment. This approach, specifically forecasts of drought event impacts, would accordingly benefit multiple stakeholders involved in drought planning, and risk and response management, with clear benefits for food and water security. Yet adoption and implementation is hindered by the absence of consistent drought impact data, limited information on local factors affecting water availability (including water demand, transfer and withdrawal), and impact assessment models being disconnected from drought monitoring tools. Implementation of impact-based drought monitoring thus requires the use of newly available remote sensors, the availability of large volumes of standardized data across drought-related fields, and the adoption of artificial intelligence to extract and synthesize physical and societal drought impacts.</p

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Comparative toxicity of fresh and expired butachlor to earthworms Eisenia fetida in natural soil: Biomarker responses

Butachlor as a selective pre-emergent herbicide, is mainly used to control the growth and productivity of certain annual grass and broad-leaf weeds. As non-target soil creatures, earthworms are affected detrimentally due to direct contact with pesticides. Our purpose was to compare the changes in the oxidative stress biomarkers in earthworms Eisenia fetida under the exposure of fresh and expired butachlor in the natural soil. LC50 of the fresh/unexpired and expired butachlor were determined by probit analysis amounting ≤440 and ≤ 471 mg/kg dry soil, respectively. Earthworms were then exposed to three sublethal concentrations (1/5th, 1/10th, and 1/20th of LC50) of both fresh and expired butachlor for 4 and 8 days. The level of oxidative stress biomarkers namely lipid peroxidation, glutathione S-transferase, and carbonylated proteins were increased. Besides, the catalase activity and value of total antioxidant capacity in earthworm's caulomic fluid were found to be decreased. In addition, it was clearly showed that butachlor can cause tissue damages in earthworms. The fresh and expired butachlor trigger the onset of oxidative damages as illustrated by altered oxidative stress biomarkers and tissue damages, particularly at the end of 8 days and high concentrations. Contrary to expiration, we found evidence that expired BUC is acutely toxic to earthworms. The fresh BUC was more deleterious than expired one to earthworms. Meanwhile, it must be considered that the regulations towards disposal of expired toxicants must be strictly followed without impairing the soil ecosystem