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Background: The natural history and complications of Fontan-associated liver disease (FALD) are not well-characterized. We aim to describe the incidence and prevalence of and risk factors for adverse liver-related complications in FALD. Methods: This is a single-center, retrospective cohort study of adult Fontan patients followed in an adult congenital heart disease center from 2006 to 2019. The primary outcome was clinical complications of liver disease (CCLD) defined as portal hypertension (pHTN)-related ascites, pHTN-related gastrointestinal bleeding, hepatic encephalopathy, or hepatocellular carcinoma. We also explored the composite outcome of CCLD, transplantation, or death. Results: Among 182 adult Fontan patients (46% female), median time from Fontan to first liver evaluation was 25.5 years (interquartile range [IQR] 22.3–30.4) with median subsequent follow-up of 4.1 years (IQR 2.5–7.6). There were 14 CCLD, 6 heart-liver and 1 heart transplant, and 16 deaths. The cumulative incidence of CCLD and the composite outcome were 2.6 per 1000-person years and 6.2 per 1000 person-years, respectively. Median time from Fontan to CCLD was 26.8 years (IQR 23.1–31.2), and to the composite outcome 26.6 years (IQR 23.1–30.5). Prior diuretic use was associated with the development of CCLD (hazard ratio [HR] 10.03, 95% confidence interval [CI] 1.25–80.22, P 0.030). Diuretic use (HR 16.47, 95% CI 3.90–69.57, P

يعد "الغلايفوسات" أكثر مبيدات الأعشاب استخداماً عالمياً نظراً لفعاليته الفريدة ورخص ثمنه. في عام2015 صنفت الوكالة الدولية لأبحاث السرطان التابعة لمنظمة الصحة العالمية الغلايفوسات في المجموعة2A كمادة مسرطنة محتملة اعتماداً على أدلة كافية على السرطنة عند حيوانات التجربة وأدلة محدودة لدى البشر. نتيجةً لما سبق ولكون الغلايفوسات مستخدماً في منطقتنا بشكل غير مضبوط كان لابد من تحديد تراكيزه في البيئة. يهدف هذا البحث إلى تحديد تراكيز الغلايفوسات في بعض مصادر المياه في محافظة اللاذقية عن طريق تطبيق طريقة طيفية لونية باستخدام كاشف Mo(VI)-Mo(V). ضمت الدراسة 48 عينة من آبار قليلة العمق وعميقة ونهر الكبير الشمالي. لوحظ عند مقارنة التراكيز المقاسة في الدراسة مع القيم المرجعية العالمية أن جميعها كانت ضمن الحدود المسموحة من قبل وكالة حماية البيئة الأمريكية (700 مكغ/ل لمياه الشرب و1800 مكغ/ل لحماية الحياة المائية) ووزارة البيئة الكندية (280 مكغ/ل لمياه الشرب و800 مكغ/ل لحماية الحياة المائية)، بينما تجاوزت الحدود المسموحة في الاتحاد الأوروبي (0.1 مكغ/ل لمياه الشرب)، وعند مقارنتها مع الدراسات المرجعية أنها كانت أعلى من أغلب الدراسات. كما لوحظ أن تراكيز الغلايفوسات كانت الأعلى في عينات الآبار قليلة العمق إذ تراوحت القيم بين 72.41-11.58 مكغ/ل، تليها عينات النهر التي تراوحت قيمتها بين 48.25-6.59 مكغ/ل، ثم عينات الآبار العميقة التي تراوحت بين 23.65-2.46 مكغ/ل، وإجمالاً كانت التراكيز في فصل الخريف أعلى منها بقية الفصول.

يعد تلوث المياه واحداً من أكبر المشاكل البيئية التي تواجه الإنسان في هذا العصر نتيجة الاستخدام الواسع للماء للتخلص من المخلفات البشرية والصناعية المختلفة، الأمر الذي أدى إلى تفاقم مشكلة تلوث المياه العذبة في الأنهار والبحيرات والمياه الجوفية، مما جعل المياه أقل صلاحية للشرب بسبب تغير خصائصها الفيزيائية والكيميائية والبيولوجية. يهدف هذا البحث إلى تحديد تراكيز شوراد الأمونيوم في بعض مصادر مياه الشرب من المياه الجوفية في ريف محافظة حماة عن طريق تطبيق طريقة طيفية لونية باستخدام كاشف Nessler ومقارنتها مع التعداد الجرثومي العام وتحري وجود جراثيم الكوليفورم البرازي وجراثيم الإيشريشيا كولي في المياه حيث تم أخذ العينات خلال فصلي الشتاء والصيف. لوحظ أن جميع تراكيز شوارد الأمونيوم المقاسة والتعداد الجرثومي العام كانت ضمن الحدود المسموحة الموافقة للمواصفات القياسية السورية لمياه الشرب ما عدا الآبار المتواجدة بالقرب من مجرى نهر العاصي في آبار العشارنة حيث كانت تراكيز الأمونيوم والتعداد الجرثومي العام أعلى من الحدود المسموحة مع غياب تام لوجود الكوليفورم البرازي والإيشريشيا كولي في جميع الآبار, كما أن تراكيز الأمونيوم والتعداد الجرثومي العام كانت أعلى في فصل الصيف. توافق ارتفاع تراكيز الأمونيوم مع ازدياد التعداد الجرثومي العام ولكن دون وجود جراثيم ممرضة مما يدل أن الأمونيوم مؤشر لزيادة النمو الجرثومي ولكن لا يكفي تحديد تراكيز الأمونيوم فقط للحكم ع صلاحية المياه للشرب.

Background: Sore throat is one of the major complications of tracheal intubation after general anesthesia. Pregabalin is an analgesic, the anti neuropathic pain and analgesic effects of which have been demonstrated in various studies. This study examined the effects of single dose pregabalin one hour before tracheal intubation, to prevent sore throat after extubation. Methods: In a double-blind, randomized clinical trial, 60 patients who had undergone general and urologic surgeries at Imam Reza hospital in Tabriz, Iran, since March to July 2015 that required tracheal intubation, were included in the study. The patients were randomly divided into two groups (group A, 30 patients and group B, 30 patients). In the group A, an hour before anesthesia, one pregabalin tablet (300mg) was given to the patients. For the patients of the group B, the placebo was given. After awareness of patients, the severity of sore throat was measured and recorded by VAS scale after 2, 6 and 24 hours of the surgery. Results: Severity and incidence of sore throat after tracheal intubation were not significantly different between two groups. Meanwhile, no side effects of pregabalin were observed in the group A. Conclusion: Administration of pregabalin as a single dose of 300 mg one hour prior to anesthesia and intubation decreased the incidence and severity of sore throat in the case group than the control group, although the amount of this reduction was not statistically significant between the two groups.

The study describes the reality of learning motivation among students of the Faculty of Educational Sciences at Irbid National University in light of Active Learning Strategies. The study used the descriptive-analytical approach. The study sample was chosen using a simple random sampling method. The results showed that the reality of Active Learning Strategies (effective learning) received a high degree with a mean of 4.22. Also, there was no statistically significant difference due to the gender variable in all domains and the total degree except for learning strategies. The differences came in favor of females. In light of the current results, the study recommended using Active Learning Strategies in teaching students due to their importance in increasing students' motivation, as well as directing faculty members to increase and excite students' motivation to learn.

This paper aims to derive an analytical modelling of the downlink exposure in 5G massive Multiple Input Multiple Output (MIMO) antenna networks using stochastic geometry. The Poisson point process (PPP) is assumed for base station (BS) distribution. The power received at the transmitter is modeled as a shot-noise process with a modified power law. The distributions of 5G massive MIMO antenna gain and channel gain were obtained by fitting simulation results from the NYUSIM channel simulator. The fitted distributions, e.g., exponential and gamma distribution for antenna and channel gain respectively, were then implemented into an analytical framework. In this paper, we obtained the closed-form expression of the moment-generating function (MGF) for the total exposure in the network. The framework is then validated by numerical simulations. The sensitivity analysis is carried out to investigate the impact of key parameters, e.g., BS density, path loss exponent, and transmission probability. We then proved and quantified the significant impact the transmission probability on global exposure, which indicates the importance of considering the network usage in 5G exposure estimations.

Background: Post-dural puncture headache is one of the common complications after neuraxial anesthesia. Some researchers have used corticosteroids for treatment of this complication. We decided to study the prophylactic effect of administering intravenous hydrocortisone before spinal anesthesia in reducing the incidence and intensity of headache after surgery. Methods: This randomized, double-blind, placebo-controlled trial was carried out in 80 patients undergoing abdominal and lower limb surgery without other health problem (ASA I). We randomly put 40 participants in the placebo group and 40 in the hydrocortisone group for study. The placebo group received 2 ml placebo and hydrocortisone group received 2 ml (100 mg) intravenous hydrocortisone. The incidence of PDPH on the recovery, 12, 24, 48 hours and 7 days after surgery was studied, and the severity of PDPH was assessed using a visual analog scale (VAS). Results: The mean intensity of headache in hydrocortisone group after recovery in the first 12, 24 and 48 hours and the first week of surgery were 0.0, 1.27, 2.35, 2.28 and 0.97 mm whereas in placebo group they were 0.0, 2.02, 3.02, 2.92 and 1.47 mm. The difference of headache intensity between two groups was not significant (P=1, P=0.231, P=0.344, P=0.351, and P= 0.302). The difference of incidence rate between two groups was not significant (P= 1, P=0,502, P=0.633, P=0,579 and p= 0,576). Conclusion: The results indicated that prophylactic administration of 100 mg hydrocortisone did not have any protective effect against post dural puncture headache.

BACKGROUND: Shoulder arthroplasty is becoming increasingly common. With evolving implant designs, multiple humeral stem options exist for the surgeon to choose from. New stemless and short-stem systems are modular, remove less native bone stock, and better adapt to patient anatomy. It has been suggested that shorter stem implants may be protective against periprosthetic fracture; however, this has not been mechanistically evaluated. Therefore, this study aimed to biomechanically test synthetic humeri with long-stem, short-stem, and stemless arthroplasty components in a torsional manner to evaluate their response to loading and characterize failure. METHODS: Twenty-four synthetic humeri were implanted with long stem, short stem, or stemless uncemented prosthesis, 8 in each group. Humeri were mounted in a custom testing jig with a morse taper interfacing with a mechanical testing system. After a 20N axial force, specimens were torsionally loaded to failure at 15 degrees/sec, with 50 Hz collection. Torque vs. rotation curves were generated for each specimen, and stiffness, yield, ultimate strength, and failure load were measured. ANOVA and post hoc pairwise comparisons were used to assess effect of stem type on mechanical test variable. The association of the stem type with fracture type was analyzed by a Fishers Exact test. Statistical significance was set at P

Alcohol consumption and chronic hepatitis B virus (HBV) infection are two well-established risk factors for Hepatocellular carcinoma (HCC); however, there remains a limited understanding of the molecular pathway behind the pathogenesis and progression behind HCC, and how alcohol promotes carcinogenesis in the context of HBV+ HCC. Using next-generation sequencing data from 130 HCC patients and 50 normal liver tissues, we identified a panel of microRNAs that are significantly dysregulated by alcohol consumption in HBV+ patients. In particular, two microRNAs, miR-944 and miR-223-3p, showed remarkable correlation with clinical indication and genomic alterations. We confirmed the dysregulation of these two microRNAs in liver cell lines treated by alcohol and acetaldehyde, and showed that manipulation of miR-223-3p and miR-944 expression induces significant changes in cellular proliferation, sensitivity to doxorubicin, and the expression of both direct-binding and downstream mRNA targets. Together, the results of this study suggest that alcohol consumption in HBV+ HCCs regulates microRNAs that likely play previously uncharacterized roles in the alcohol-associated carcinogenesis of HCC, and future studies of these microRNAs may be valuable for furthering the understanding and treatment of alcohol and HBV-associated HCC.

Background and Aims: Pediatric upper gastrointestinal (GI) endoscopy is commonly performed under deep sedation, which is frequently associated with respiratory complications. The study compared the respiratory benefits of applying bilateral modified nasopharyngeal airways (NPAs) to conventional low-flow nasal cannula (LFNC). Material and Methods: Fifty patients scheduled for an upper GI endoscopy under deep sedation, with an American Society of Anesthesiologists physical status I/II, were enrolled in the study. The patients were randomly divided into bilateral NPA group and the LFNC group. Fentanyl and propofol were administered to both groups to maintain deep sedation. After the application of NPA or LFNC, the hypoxic incidents (oxygen saturation [SpO2]

Background: Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Methods: Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Results: Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC)

تم في هذه الدراسة تطوير طريقة تحليلية حساسة ودقيقة في هذه الدراسة لتحديد وكشف مركب الكركمين باستخدام الكروماتوغرافيا السائلة عالية الأداء HPLC، وتم التعرف تجريبياً على الشروط المثلى من عمود الفصل، والطور المتحرك، ودرجة الحرارة، وسرعة التدفق وطول الموجة الأعظمي، استخدم محلول عياري للكركمين بتركيز (40ppm) لدراسة الشروط المثلى، وكان عمود الفصل المستخدم الثابت هو العمود (C18) بمواصفات (250×4.6m.m.5µm)، تم الحصول على الشروط المثلى من الطور المتحرك ممثلاً بالمزيج (اسيتونتريل: حمض الفوسفور ذو التركيز 0.1%) بنسبة (40:60 v/v، و كانت درجة الحرارة لعمود الفصل هي (40˚C) ، وسرعة تدفق الطور المتحرك هي (0.8ml/min)، أما طول الموجة الأعظمي للتحليل فكان (425nm). أظهر الكركمين ثلاث قمم بمتوسط مساحة (X1=87279,X2=881260, X3=7641952)، عند متوسط زمن احتفاظ (T1=6.31, T2=6.87, T3=7.50)min بانحراف معياري نسبي مئوي RSD% (0.83, 0.08, 0.01) على الترتيب ومجموع متوسط مساحات القمم (Xt=8610491). تميز منحني المعايرة لمركب الكركمين بمركباته الثلاثة بخطية جيدة ضمن مجال من التراكيز تراوح بين (0.001- 40)ppm ،وتم حساب الاسترجاعية R% وكانت (99.66%)، أما حد الكشف الكمي فكان LOQ (0.056ppb)، وحد الكشف النوعي LOD ( 0.009 ppb). تؤكد نتائج البحث على إمكانية اعتماد هذه الطريقة لتحديد الكركمين بمركباته المختلفة.

Background: Sore throat is one of the major complications of tracheal intubation after general anesthesia. Harpagophytum is an herbal medicine, the anti-inflammatory and analgesic effects of which have been demonstrated in various studies. We studied the effects of single dose Harpagophytum one hour before tracheal intubation, to prevent the sore throat after extubation. Methods: In a randomized clinical trial, 60 patients who had undergone general and urologic surgeries at Imam Reza hospital in Tabriz, Iran, since March to July 2015 that required tracheal intubation, were included in the study. The patients were randomly divided into two groups (case group 30 patients and control group 30 patients). In the case group, one hour before anesthesia, one Teltonal capsule (480 mg) was given to the patients. For the control group of patients, the empty capsule of Teltonal was given. After patients regained consciousness, the severity of sore throat was scaled and recorded by VAS scale after 2, 6 and 24 hours of the surgery. Results: Severity and incidence of sore throat after tracheal intubation were not significantly different between case and control groups. Also, no side effects of Harpagophytum were observed in the case group. Conclusion: Administration of Harpagophytum with the single dose of 480 mg one hour before the anesthesia and intubation did not decrease the sore throat severity and incidence.

Syria has been struggling with a prolonged and brutal war for over a decade, leaving much of the country in devastation and its forests severely degraded. While many studies have identified logging for firewood as a significant driver of deforestation during the war, there is a notable absence of research specifically addressing logging behavior within the context of war. This research seeks to address this gap by examining the changes in logging behavior among local communities, the effects of violence and socioeconomic variables on wood harvesting, the contribution of wood income to people's survival during the war. To do that, we conducted survey questionnaires in two coastal villages in Syria—Blouta and Nehel al Annaze—which experienced high and low levels of violence, respectively. Our findings reveal that logging activities increased once the war began, with more people involved in forest harvesting and average days spent logging per week significantly increasing from 1.5 to 4. Additionally, the war appeared to reduce the gender disparity in logging activities: before the conflict, women engaged in logging significantly more frequently than men, but this difference became insignificant during the war. The level of violence alone did not significantly affect the amount of wood logged per month. Furthermore, income generated from wood harvesting played a substantial role in bridging the gap between the monthly income needed to cover their basic necessities and the actual income of families in both villages by 46.94 % and 84.83 % of the gap in Nehel al Annaze and Blouta, respectively. These results highlight the crucial role of forest resources in supporting rural livelihoods during times of war. Post-war effective forest management will be vital to ensure the sustainable use and recovery of forest resources, supporting both ecological restoration and economic stability for the rural communities.

The extreme learning machine is a fast neural network with outstanding performance. However, the selection of an appropriate number of hidden nodes is time-consuming, because training must be run for several values, and this is undesirable for a real-time response. We propose to use moving average, exponential moving average, and divide-and-conquer strategies to reduce the number of training’s required to select this size. Compared with the original, constrained, mixed, sum, and random sum extreme learning machines, the proposed methods achieve a percentage of time reduction up to 98\% with equal or better generalization ability.

The aim of this study was to evaluate the degree of the evaluation of the educational management program in light of the academic accreditation standards in the universities of Jordan in Irbid from the point of view of the faculty members. The researchers used the descriptive analytical approach and the study sample consisted of (17) faculty members specialized in educational administration. The results showed that the degree of evaluation educational administration program in the light of academic accreditation standards from the viewpoint of faculty members was average (3.47), and a mean of (0.46) and the results showed that there were no significant in estimates of faculty members to the degree of evaluation of the educational administration program due to variables (gender, academic rank, and experience), the recommendations include working on improving the educational administration program in light of the academic accreditation standards in terms of the content and goals, study plan.

Nowadays, we face improvements in the field of the Internet of Things (IoT). The primary focus of the Internet of Medical Things (IoMT) is to gather health data from patients and provide healthcare services accordingly. Hence, researchers have been focusing on this wide-ranging system that causes the patient’s private data disclosure. This paper suggests an authentication scheme for IoMT devices to improve the performance and security level of current authentication schemes. The proposed authentication scheme involves the creation of a model for authentication that operates offline and directly verifies identities which effectively authenticates users and IoMT devices within the network established in the local area. Additionally, authentication of all parts of the system is carried out through an online authentication server used by the system. This proposed authentication scheme relies on the utilization of the Elliptic Curve Cryptography (ECC), one-way hash function, and XOR operation. It’s well-suited for the resource-constrained IoMT architecture. Further, this scheme provides stronger security protection, achieves several security goals, and ensures efficiency. To establish its security, this work undergoes a comprehensive analysis. It is evaluated using the extensively utilized ’Real-Or-Random (ROR)’ model, ensuring its robustness. Furthermore, its correctness is proved through BAN-logic, and a formal security verification is conducted using the widely accepted ‘Automated Validation of Internet Security Protocols and Applications (AVISPA)’ tool. Additionally, an informal security analysis is carried out. Finally, the system successfully accomplishes mutual authentication with lower computation and communication costs than other schemes. Additionally, it offers a range of desired attributes. The experimentation results demonstrate that the suggested scheme ensures that the computation overhead remains minimal (30.1978 m) and the communication overhead minimized to the greatest extent possible (544 bits). These results establish the suitability of the proposed work for the IoMT.

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive therapeutic approach that targets particular brain regions that had been used and displayed significant impact in various neurological disorders. This study aimed to explore if high-frequency (HF) rTMS over the parietal cortex could influence sleep quality in Parkinson's disease (PD). Methods This was a prospective sham-controlled study conducted on 40 individuals with PD. The enrolled patients were examined with Unified Parkinson's Disease Rating Scale (UPDRS-III) and Modified Hoehn and Yahr Staging Scale (H&Y staging) for motor disability evaluation and staging. Pittsburgh Sleep Quality Index (PSQI) was used for sleep quality and Epworth Sleepiness Scale (ESS) for excessive daytime sleepiness and Beck Depression Inventory-II (BDI-II) for depression. Patients were classified into 2 groups: patients who underwent real-rTMS positioned over their bilateral parietal cortex. 100% of the motor threshold. Patients had a total of 12 sessions, one every other day. Another group received sham rTMS. Results The patients receiving active rTMS showed significant improvement in UPDRS-III, PSQI, ESS, and BDI-II immediately after the sessions and 1 month later. The follow-up PSQI had a significant positive correlation with the baseline BDI-II (r = 0.88, P = 0.001), H&Y staging (r = 0.78, P = 0.001), and UPDRS-III (r = 0.78, p = 0.001). Multivariate linear regression analysis exhibited that the age of the patients was a significant predictor of sleep quality. Conclusion HF rTMS over the parietal cortex had shown a significant impact on sleep quality by the modulation of affected brain areas and by improving concomitant motor and mood manifestations.

Context and Background: Changes in the way powers are structured in Morocco have had an impact on the dynamics linking territorial stakeholders and on territorial development. Indeed, following the innovations of the 2011 Constitution and the process of advanced regionalization, territorial stakeholders have been given new prerogatives and responsibilities, with the aim of reframing the scope of public policy, which is now intended to be more territorialized and therefore more democratic. Goal and Objectives: Analyze developments in territorial public action in the light of interactions between territorial stakeholders with a view of identifying the dynamics and challenges of the territorial construction process. Methodology: This is an attempt to qualitative analysis of political-institutional developments based on a cross-study combining analysis of doctrinal foundations and appreciation of official documents Results: Many stakeholders are involved in this regional reconstruction, which is bound to change the way public policies are conceived. Whether it's a simple change of scale or a shift in an entire political paradigm, this adjustment could have effects on both the design of public policy and the functions of the stakeholder.

Background: In Egypt, salted fish is considered a typical processed fish, including salted sardine, salted mullet (feseikh), keeled mullet (sahlia), and herrings. High-quality protein, polyunsaturated fatty acids, vital amino acids, and trace minerals like magnesium and calcium are all abundant in fish. However, eating salted fish can expose people to toxins found in the environment, like heavy metals. Aim: In Zagazig, Egypt, four types of locally produced salted fish—salted sardine, feseikh, sahlia, and herrings—were tested for heavy metals, specifically lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg). Second, the assessed heavy metals linked to the Egyptian population's consumption of salted fish were used to calculate estimated daily intakes (EDI) and potential health hazards, such as hazard quotient (HQ) and hazard index (HI). Methods: Samples of salted herrings, feseikh, sahlia, and sardines were gathered from the markets in Zagazig. Samples of salted fish were subjected to acid digestion and then heavy metal extraction. Atomic absorption spectrometers (AAS) were used to measure heavy metals. HI, HQ, and EDI were computed computationally. Results: With the exception of mercury, which was not found in the salted herrings, the recorded results showed that all of the tested metals were present in the samples that were evaluated. The Herrings contained residual Pb and Cd contents that were highest, followed by sardine, feseikh, and sahlia, in that order. After sardine, herrings, and sahlia, Feseikh has the greatest As concentration. Sardine, feseikh, and sahlia had the highest quantities of mercury, in that order. A number of samples were found to be above the maximum allowable levels. There were no apparent hazards associated with consuming such conventional fish products, according to the computed HQ and HI values for the heavy metals under investigation based on the daily intakes. Conclusion: Samples of salted fish sold in Zagazig, Egypt, had high quantities of the hazardous elements Pb, Cd, As, and Hg. Due to the bioaccumulation and biomagnification characteristics of these studied metals, such data should be taken carefully even though the computed health hazards revealed no potential problems. [Open Vet J 2023; 13(12.000): 1738-1743]

 ﺧﻠﻔﻴﺔ ﺍﻟﺪﺭﺍﺳﺔ: ﺇﻥ ﺇﺛﺒﺎﺕ ﻭﺟﻮﺩ ﺍﺭﺗﻔﺎﻉ ﻫﺎﻡ ﻓﻲ ﻗﻴﻢ ﻧﺤﺎﺱ ﺍﻟﻤﺼﻞ ﻋﻨﺪ ﻣﺮﺿﻰ ﺍﻻﺣﺘﺸﺎﺀ ﺍﻟﻘﻠﺒﻲ ﺍﻟﺤﺎﺩ ﻭﺇﻳﺠﺎﺩ ﻋﻼﻗﺔ ﺑﻴﻦ ﺍﺭﺗﻔﺎﻉ ﺍﻟﻨﺤﺎﺱ ﻭﺍﺭﺗﻔﺎﻉ ﺍﻟﻮﺍﺳﻢ ﺍﻟﻘﻠﺒﻲ CKmb ﻳﻤﻜﻨﻨﺎ ﻣﻦ ﺗﻤﻴﻴﺰ ﻣﺮﺿﻰ ﺍﻻﺣﺘﺸﺎﺀ ﺍﻟﺤﺎﺩ ﻋﺎﻟﻴﻲ ﺍﻟﺨﻄﻮﺭﺓ ﻭﺍﻟﺬﻳﻦ ﻳﺤﺘﺎﺟﻮﻥ ﻟﻤﺰﻳﺪ ﻣﻦ ﺍﻟﺘﺸﺪﺩ ﻓﻲ ﺿﺒﻂ ﻋﻮﺍﻣﻞ ﺍﻟﺨﻄﻮﺭﺓ ﺍﻟﻘﻠﺒﻴﺔ ﻭﺍﻟﻌﻼﺝ ﺍﻟﻤﻜﺜﻒ ﻭﺍﻟﻤﺘﺎﺑﻌﺔ ﺍﻟﻄﺒﻴﺔ ﺍﻟﻠﺼﻴﻘﺔ.  ﻭﺇﻥ ﺗﺤﺪﻳﺪ ﻣﺠﻤﻮﻋﻪ ﺍﻟﻤﺮﺿﻰ ﺫﻭﻱ ﺍﻟﺨﻄﻮﺭﺓ ﺍﻟﻌﺎﻟﻴﺔ ﺗﻤﻜﻨﻨﺎ ﻣﻦ ﺍﺗﺨﺎﺫ ﺍﻟﻘﺮﺍﺭ ﺑﺈﺟﺮﺍﺀ ﺍﻟﺘﺪﺍﺧﻼﺕ ﺍﻟﻐﺎﺯﻳﺔ ﺑﺸﻜﻞ ﺃﺳﺮﻉ ﺍﻷﻫﺪﺍﻑ: ﺍﻟﻬﺪﻑ ﺍﻟﺮﺋﻴﺴﻲ: ﻗﻴﺎﺱ ﻣﺴﺘﻮﻯ ﻧﺤﺎﺱ ﺍﻟﻤﺼﻞ ﻭﺍﻝ CKmb ﻋﻨﺪ ﻣﺮﺿﻰ ﺍﻻﺣﺘﺸﺎﺀ ﺍﻟﺤﺎﺩ ﺑﺎﻟﻤﻘﺎﺭﻧﺔ ﻣﻊ ﺍﻷﺷﺨﺎﺹ ﺍﻟﻄﺒﻴﻌﻴﻴﻦ CKmb ﻋﻨﺪ ﻣﺮﺿﻰ ﺍﻻﺣﺘﺸﺎﺀ. ﺍﻟﻬﺪﻑ ﺍﻟﺜﺎﻧﻮﻱ: ﺩﺭﺍﺳﺔ ﺍﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻣﺴﺘﻮﻯ ﺍﻟﻨﺤﺎﺱ ﻓﻲ ﺍﻟﻤﺼﻞ ﻭﻣﺴﺘﻮﻯ ﺍﻝ ﺍﻟﺤﺎﺩ. ﺍﻟﻤﻮﺍﺩ ﻭﺍﻟﻄﺮﻕ: ﺩﺭﺍﺳﺔ ﺇﺣﺼﺎﺋﻴﺔ )ﺣﺎﻟﺔ – ﺷﺎﻫﺪ( ﺷﻤﻠﺖ ﻋﻴﻨﺔ ﺍﻟﺒﺤﺚ 50 ﻣﺮﻳﻀﺎ ﻣﻦ ﺍﻟﻤﺮﺿﻰ ﺍﻟﺬﻳﻦ ﺗﻢ ﺇﺩﺧﺎﻟﻬﻢ ﺇﻟﻰ ﻗﺴﻢ ﺍﻟﻄﻮﺍﺭﺉ ﻓﻲ ﻣﺴﺘﺸﻔﻰ ﺗﺸﺮﻳﻦ ﺍﻟﺠﺎﻣﻌﻲ ﻓﻲ ﺍﻟﻼﺫﻗﻴﺔ ﻓﻲ ﻏﻀﻮﻥ 12 ﺳﺎﻋﻪ ﻣﻦ ﻇﻬﻮﺭ ﺍﻷﻋﺮﺍﺽ ﺍﻟﺴﺮﻳﺮﻳﺔ ﻭﺍﻟﺘﻲ ﺗﺸﻴﺮ ﺇﻟﻰ ﻧﻘﺺ ﺗﺮﻭﻳﺔ ﻋﻀﻠﺔ ﺍﻟﻘﻠﺐ ﺧﻼﻝ ﺍﻟﻔﺘﺮﺓ ﺍﻟﺰﻣﻨﻴﺔ ﺑﻴﻦ ﻧﻴﺴﺎﻥ 2022 – 2023 ﻭﺍﻟﻤﺤﻘﻘﻴﻦ ﻣﻌﺎﻳﻴﺮ ﺍﻻ ﺷﺘﻤﺎﻝ ﺑﺎﻟﺒﺤﺚ . ﺗﻢ ﺍﻋﺘﻤﺎﺩ ﻋﻴﻨﺔ 25 ﻣﺮﻳﺾ ﻣﻦ ﺍﻟﻤﺮﺿﻰ ﺍﻟﻤﺮﺍﺟﻌﻴﻦ ﻟﻠﻤﺴﺘﺸﻔﻰ ﻷﺳﺒﺎﺏ ﺃﺧﺮﻯ ﺧﻼﻝ ﺍﻟﻔﺘﺮﺓ ﺍﻟﺰﻣﻨﻴﺔ ﺫﺍﺗﻬﺎ ﺑﻬﺪﻑ ﻣﻘﺎﺭﻧﺔ ﻣﺴﺘﻮﻯ ﺍﻟﻨﺤﺎﺱ ﺍﻟﻤﺼﻠﻲ ﻣﻌﻬﻢ ﻭﺩﺭﺍﺳﺔ ﺍﻻﺭﺗﺒﺎﻁ ﻣﺎ ﺑﻴﻦ ﻣﺴﺘﻮﻯ ﺍﻟﻨﺤﺎﺱ ﺍﻟﻤﺼﻠﻲ ﻭﺍﻟﻮﺍﺳﻢ ﺍﻟﻘﻠﺒﻲ CKmb . ﺗﻢ ﻭﺿﻊ ﺗﺸﺨﻴﺺ ﺍﺣﺘﺸﺎﺀ ﺍﻟﻌﻀﻠﺔ ﺍﻟﻘﻠﺒﻴﺔ ﻣﻦ ﻗﺒﻞ ﺃﻃﺒﺎﺀ ﻗﺴﻢ ﺍﻟﻘﻠﺒﻴﺔ ﻓﻲ ﻣﺴﺘﺸﻔﻰ ﺗﺸﺮﻳﻦ ﺍﻟﺠﺎﻣﻌﻲ ﺑﻨﺎﺀ ﻋﻠﻰ ﺍﻟﻔﺤﺺ ﺍﻟﺴﺮﻳﺮﻱ ﻭﺍﻷﻋﺮﺍﺽ ﺇﺿﺎﻓﺔ ﺇﻟﻰ ﻧﺘﺎﺋﺞ ﺗﺨﻄﻴﻂ ﺍﻟﻘﻠﺐ ﺍﻟﻜﻬﺮﺑﺎﺋﻲ ﻭﻗﻴﻢ ﺍﻟﺘﺤﺎﻟﻴﻞ ﺍﻟﻤﺨﺒﺮﻳﺔ , ﻛﻤﺎ ﺗﻢ ﻣﻌﺎﻳﺮﺓ ﻧﺤﺎﺱ ﺍﻟﻤﺼﻞ ﻓﻲ ﺍﻟﻤﺨﺒﺮ ﺍﻟﻤﺮﻛﺰﻱ ﻓﻲ ﻣﺴﺘﺸﻔﻰ ﺗﺸﺮﻳﻦ ﺍﻟﺠﺎﻣﻌﻲ ﺑﺎﺳﺘﺨﺪﺍﻡ ﺟﻬﺎﺯ HUMAN ﻧﺼﻒ ﺍﻵﻟﻲ، ﺑﻄﺮﻳﻘﺔ CKmb ﻓﻘﺪ ﺗﻤﺖ ﺍﻟﻤﻌﺎﻳﺮﺓ ﻋﻠﻰ ﺍﻷﺟﻬﺰﺓ ﺍﻵﻟﻴﺔ ﻓﻲ ﺍﻟﻤﺴﺘﺸﻔﻰ ﻭﺫﻟﻚ ﺑﺎﻟﻄﺮﻳﻘﺔ ﺍﻻﺧﺘﺒﺎﺭ ﺍﻟﻠﻮﻧﻲ ﺃﻣﺎ ﺍﻟﻮﺍﺳﻢ ﺍﻟﻘﻠﺒﻲ ﺍﻟﺤﺮﻛﻴﺔ . ﺍﻟﻨﺘﺎﺋﺞ: ﺗﺮﺗﻔﻊ ﻗﻴﻤﺔ ﻧﺤﺎﺱ ﺍﻟﻤﺼﻞ ﻋﻨﺪ ﻣﺮﺿﻰ ﺍﻻﺣﺘﺸﺎﺀ ﺍﻟﻘﻠﺒﻲ ﺍﻟﺤﺎﺩ ﻣﻘﺎﺭﻧﺔ ﻣﻊ ﺍﻷﺷﺨﺎﺹ ﺍﻟﻄﺒﻴﻌﻴﻴﻦ . ﺗﺮﺗﻔﻊ ﻗﻴﻤﺔ ﻧﺤﺎﺱ ﺍﻟﻤﺼﻞ ﻋﻨﺪ ﻣﺮﺿﻰ ﺍﻻﺣﺘﺸﺎﺀ ﺍﻟﺤﺎﺩ ﻛﻠﻤﺎ ﺍﺭﺗﻔﻌﺖ ﻗﻴﻤﺔ ﺍﻟﻮﺍﺳﻢ ﺍﻟﻘﻠﺒﻲ CKmb . ﺍﻟﺨﻼﺻﺔ: ﻗﻴﺎﺱ ﻣﺴﺘﻮﻯ ﻧﺤﺎﺱ ﺍﻟﻤﺼﻞ ﻋﻨﺪ ﻣﺮﺿﻰ ﺍﻻﺣﺘﺸﺎﺀ ﺍﻟﻘﻠﺒﻲ ﺍﻟﺤﺎﺩ ﻟﻠﻤﺴﺎﻋﺪﺓ ﻓﻲ ﺗﻘﻴﻴﻢ ﻣﺪﻯ ﺧﻄﻮﺭﺓ ﺍﻹﺻﺎﺑﺔ ﻭﺑﺎﻟﺘﺎﻟﻲ ﺍﻟﻤﺴﺎﻋﺪﺓ ﻓﻲ ﺗﺴﺮﻳﻊ ﺍﻹﺟﺮﺍﺀﺍﺕ ﺍﻟﻤﻨﺎﺳﺒﺔ ﻟﻠﻤﻌﺎﻟﺠﺔ ﻭﻣﻨﻊ ﺣﺪﻭﺙ ﺍﻻﺧﺘﻼﻃﺎﺕ ﺍﻟﺨﻄﻴﺮﺓ . ﺇﺟﺮﺍﺀ ﺍﻟﻤﺰﻳﺪ ﻣﻦ ﺍﻟﺪﺭﺍﺳﺎﺕ ﺣﻮﻝ ﺇﻣﻜﺎﻧﻴﺔ ﺍﺳﺘﺨﺪﺍﻡ ﺧﺎﻟﺒﺎﺕ ﺍﻟﻨﺤﺎﺱ ﻹﻧﻘﺎﺹ ﻋﻼﻣﺎﺕ ﺃﻭ ﺇﺑﻄﺎﺀ ﺗﻄﻮﺭ ﺍﻋﺘﻼﻝ ﺍﻟﻘﻠﺐ ﺍﻹﻗﻔﺎﺭﻱ .

Objective: Rapamycin, a powerful geroprotective drug, can have detrimental effects when administered chronically. We determined whether intermittent treatment of mice can reduce negative effects while maintaining benefits of chronic treatment. Methods: From 6 months of age, male and female C3B6F1 hybrid mice were either continuously fed with 42 mg/kg rapamycin, or intermittently fed by alternating weekly feeding of 42 mg/kg rapamycin food with weekly control feeding. Survival of these mice compared to control animals was measured. Furthermore, longitudinal phenotyping including metabolic (body composition, GTT, ITT, indirect calorimetry) and fitness phenotypes (treadmil, rotarod, electrocardiography and open field) was performed. Organ specific pathology was assessed at 24 months of age. Results: Chronic rapamycin treatment induced glucose intolerance, which was partially ameliorated by intermittent treatment. Chronic and intermittent rapamycin treatments increased lifespan equally in males, while in females chronic treatment resulted in slightly higher survival. The two treatments had equivalent effects on testicular degeneration, heart fibrosis and liver lipidosis. In males, the two treatment regimes led to a similar increase in motor coordination, heart rate and Q-T interval, and reduction in spleen weight, while in females, they equally reduced BAT inflammation and spleen weight and maintained heart rate and Q-T interval. However, other health parameters, including age related pathologies, were better prevented by continuous treatment. Conclusions: Intermittent rapamycin treatment is effective in prolonging lifespan and reduces some side-effects of chronic treatment, but chronic treatment is more beneficial to healthspan.