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The teacher is an educator who is assigned to provide knowledge. In providing knowledge, an educator must use learning strategies so that teaching and learning activities become fun and not boring so as to improve the quality of student learning. The main purpose of the discussion is to find out how the method of teachers from Madrasah Aliyah Negeri (MAN) Karo in delivering the material. The research was conducted using qualitative methods by collecting detailed data through interviews. Teachers at Madrasah Aliyah Negeri (MAN) Karo have different learning strategies for each subject in delivering the material, such as using understanding strategies by providing understanding through powerpoint or conducting learning activities outside the classroom (outdoor) by observing the development of plants around. Learning strategies are an important key in improving the quality of student learning by raising students' enthusiasm and making the classroom atmosphere more pleasant. Another strategy carried out by Madrasah Aliyah Negeri (MAN) Karo in improving the quality of learning for its students is by applying the principle where an educator becomes a father, mother, friend, brother, sister, and closest relative so that students feel comfortable and are not afraid to express themselves his opinion.

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that is associated with an increased risk of infertility. This study aims to evaluate the neurobehavioral and neurochemical changes along with the associated changes in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) of the dehydroepiandrosterone (DHEA)-induced PCOS model rats. Methods: A total of 12 female juvenile Wistar rats (30 to 50 g) about 22 to 44 days old were divided into 2 groups. The control group received sesame oil while the PCOS group received sesame oil plus DHEA. All treatment was done via daily subcutaneous injection for 21 days. Results: Subcutaneous DHEA-induced PCOS significantly depleted the line crossing and rearing frequency in the open field, along with the percentage of the time in the white box, line crossing, rearing, and peeping frequency in the black and white box, and the percentage of alternation in the Y-maze. PCOS significantly increased the immobility time, freezing period, and the percentage of time in the dark area in the forced swim test, open field test, and black and white box, respectively. The level of luteinizing hormone, follicle-stimulating hormone, malondialdehyde (MDA), reactive oxygen species (ROS), and interleukin-6 (IL-6) increased significantly, while norepinephrine depleted significantly with an obvious decrease in the brain-derived neurotrophic factor level in the PCOS model rats. PCOS rats exhibited cystic follicles in the ovaries and necrotic or degenerative like features in the hippocampal pyramidal cells. Conclusion: DHEA-induced PCOS results in anxiety and depressive behavior with structural alteration in rats, possibly through the elevation of MDA, ROS, and IL-6 levels, which also attributes to impaired emotional and executive functions in the mPFC and ACC.

The author chose the title Academic Supervision To Improve Teacher Performance at Madrasah Tsanawiyah State (MTsN) Karo, the first goal is to find out the planning of the academic supervision program at Madrasah Tsanawiyah State (MTsN) Karo, the second is to know the implementation of the academic supervision program at Madrasah Tsanawiyah State (MTsN) Karo, and the last is to know the evaluation of the academic supervision program at Madrasah Tsanawiyah State (MTsN) Karo. This study uses a qualitative descriptive analytic method in which the results of observations, interviews, document analysis, field notes are obtained and are not made in the form of numbers. This research was conducted at Madrasah Tsanawiyah State (MTsN) Karo directly conducted an interview with the Head of the Madrasah. From the results of the study, it was found that 1) the implementation of supervision carried out by the Head of the Madrasah Tsanawiyah State (MTsN) Karo was carried out once a month and the implementation was carried out in stages, first holding a meeting, second checking the completeness of learning tools, third class visits and finally any follow-up or evaluation after supervision is carried out, 2) the implementation of supervision at Madrasah Tsanawiyah State (MTsN) Karo using class visit techniques, 3) Evaluation carried out by the Head of Madrasah at MTsN Karo to improve teacher performance is through learning assessment by monitoring students' test results and it is hoped that through In this evaluation, teachers further improve their perform.

Producer Price Index is an index number that describes the level of price change at the producer level. Data users can take advantage of the development of producer prices as an early indicator of wholesale and retail prices. In addition, it can also be used to assist in the preparation of the economic balance, distribution of goods, trade margins, and so on. Every year the Badan Pusat Statistika (BPS) updates data on the producer price index to facilitate producer price standards, including rice and grain producers. To determine the Price Prediction Index, a prediction algorithm is needed, namely Naive Bayes based on data from Quarters I and II of 2021. The Naïve Bayes Algorithm, can be used to predict the Producer Price Index. This prediction is made to provide an overview of Quarter III, considering that in 1 year BPS updates the Producer Price Index’s data up to Quarter IV in 1 year. The prediction obtained is an increase for Quarter III with a maximum value between 0.961 – 0.980 based on data from Quarters I and II.

Background: Sodium fluoride (NaF) is a highly consumed food additive, that is capable of disrupting the activities of several brain areas. whether this compound affects the autonomic activities of the brain is unclear. Objective: Therefore, the study was designed to investigate the ameliorative potentials of exogenous melatonin on sodium fluoride-induced pontine toxicity in adult male Wistar rats, as melatonin has been implicated to have a high concentration in the cerebrospinal fluid of injured brains. Method: Thirty-two rats were randomly divided into 4 groups (n=8, per group). Groups I, II.III and IV received 0.2 ml of normal saline (NS), 500 ppm of sodium fluoride (NaF) via their drinking water, 10 mg/kg melatonin (MLT), and melatonin with sodium fluoride concurrently (MLT+NaF) respectively for fourteen days. At the end of these treatments, the rats were euthanized and brainstem tissues were excised for histological, histochemical, and biochemical analyses. Results: There were shreds of evidence of DNA fragmentation, vacuolation, dispersion of the Nissl bodies, and axonal disruption in the cells of the basilar pons of the sodium fluoride-treated animals; this was coupled with high concentrations of malondialdehyde and low-level concentrations of glutathione reductase. Melatonin, however, was observed to limit neuronal injury in the cells of the basilar pons in the experimental animals by reducing the extent of cells undergoing process pyknosis, chromatolysis, and demyelination. Also, melatonin was able to reduce the concentration of malondialdehyde and increase glutathione reductase activities in the pons. Conclusion: This study revealed that sodium fluoride injured the pontine histoarchitecture, and induced oxidative damage which were ameliorated by exogenous melatonin treatments.

Sorting algorithm in the computational process makes it easy for users when the data sorting process because the data is sorted by the process quickly and automatically. In addition to speed in sorting data, memory efficiency must also be considered. In this research, a retesting of two sorting methods is conducted, namely the bubble sort method and the insertion sort method based on the comparison of two programming languages, Java with Visual Basic 2010 using the decision tree method. This research aims to find out which algorithm has lower memory consumption in the sorting process using Java or Visual Basic 2010. The results of the comparison show, in Visual Basic 2010. insertion sort algorithm which has the lowest average memory consumption of 4.3243KB for .vb extensions and 2.0145KB for .exe extensions. while the bubble sort method with a consumption amount of 4.4358KB for the .vb extension and 2.0352 for extension.exe. Furthermore, if you use the Java programming language. So the bubble sort method still consumes the highest average memory, which is 546,242KB for the .jar extension and 4,337KB for the .exe extension, whereas from the insertion sort method, which has a low average memory consumption of 543,578 KB for extension .jar, and 4,381KB for extension .exe.

Abstract: This paper presents a discussion of the contribution of muslim scientists to the development of modern science. It is well known that in the golden ages of Islam many scientists are very competent in their respective fields emerging. They succeeded in emerging as philosophers and scientists capable of filling various fields of science, such as medicine, mathematics, chemistry, physics, and so forth others. Their scholarship is valuable especially for the development of science in the future. So precious their scholarship and what they dedicated, so not infrequently the scientists who come later dub them as the father of science in their respective fields. However, not all of them will be discussed in this paper, but only the triumvirate of muslim scientists, namely Ibn Rushd, Ibn al-Haytham, dan Jabir ibn Hayyan. Their contribution is so great to the development of modern science and is recognized by scientists both in the East, and especially in the West. Abstrak: Tulisan ini menyuguhkan pembahasan mengenai kontribusi ilmuwan-ilmuwan muslim bagi perkembangan sains modern. Sudah jamak diketahui bahwa pada zaman keemasan Islam banyak bermunculan ilmuwan yang sangat kompeten di bidangnya masing-masing. Mereka berhasil tampil sebagai filosof dan saintis yang mengisi berbagai bidang keilmuwan, seperti kedokteran, matematika, kimia, fisika dan sebagainya. Keilmuwan mereka sangat berharga terutama bagi perkembangan sains pada masa-masa berikutnya. Begitu berharganya keilmuwan dan apa yang dipersembahkan oleh mereka, sehingga tidak jarang para ilmuwan yang datang belakangan menjuluki mereka sebagai bapak sains di bidangnya masing-masing. Namun, tidak semua dari mereka akan dibahas dalam tulisan ini, melainkan hanya triumvirat ilmuwan muslim, yakni Ibn Rushd, Ibn al-Haytham, dan Jabir ibn Hayyan. Kontribusi ketiganya begitu besar bagi perkembangan sains modern dan diakui kalangan saintis, baik di Timur dan khususnya di Barat.

Hydroxyurea ( HU) is a drug used for the treatment of haemoglobinopathies. Hydroxyurea functions by upregulating γ-globin transcription and fetal haemoglobin ( Hb F) production in erythroid cells. The K562 erythroleukaemia cell line is widely used as a model system in which to study the mechanism of γ-globin induction by HU. However, the transcription factors required for the upregulation of γ-globin expression by HU in K562 cells have not been identified. Similarities between the HU and sodium butyrate ( SB) pathways suggest cAMP response element-binding protein ( CREB) 1 as a potential candidate. Thus, the aim of the present study was to investigate the possible role of CREB1 in the HU pathway., Experiments were performed using transient and stable RNA interference ( RNAi) to show that CREB1 is necessary for HU-mediated induction of γ-globin expression and haemoglobin production in K562 cells., Furthermore, western blot analyses demonstrated that CREB1 becomes phosphorylated in a dose-dependent manner after HU (100-400 µmol/ L) treatment of K562 cells for 72 h., We also investigated role of a Gγ promoter CREB1 response element ( G- CRE) in this pathway. Quantitative amplification refractory mutation system-polymerase chain reaction experiments were performed to demonstrate that HU induces the expression of both Gγ and Aγ in this cell line. In addition, electrophoretic mobility shift assays were used to show that levels of CREB1 complexes binding to the G- CRE site are increased following HU treatment and are decreased in CREB1-knockdown cells., The results suggest that CREB1 is necessary for γ-globin induction by HU in K562 cells, a role that may be mediated, in part, through the G- CRE element. [ABSTRACT FROM AUTHOR]

Democratic life is a dream for every person, every family, all the people and the state. A democratic life will knit a harmonious and peaceful atmosphere. Touches of humanism instinct will keenly felt when the democratic behavior deeply coloring this life. Touch of affection, love, respect, helpful, gentle, good manners, tolerance and all kinds of noble characters will always be enjoyed by all communities on earth. For a long time, we are always looks for a model of life which is considered to be appropriate and harmonious with human nature. All models of life that had been coloring the world is not spared from the coverage of the series of human lives and almost all the models had been tried to be applied in their life. However, all of them are just trying a model that will certainly not be able to give satisfaction to them. We almost forgot a near-perfect model of life for the prerequisites of democratic life. That's the life model that was exhibited by the Prophet and his companions. Kehidupan demokratis merupakan dambaan bagi setiap insan, setiap keluarga, segenap masyarakat dan negara. Dalam kehidupam yang demokratis akan terajut suatu suasana yang harmonis dan damai. Sentuhan-sentuhan naluri kemanusiaan akan amat terasa bila perilaku demokratis benar-benar mewarnai kehidupan ini. Sentuhan kasih sayang, sentuhan cinta, saling menghormati, saling menghargai, tolong-menolong, sikap lemah lembut, sopan santun, toleransi dan selaksa pernik-pernik dan aksessori akhlak mulia nan agung akan senantiasa bisa dinikmati oleh segenap komonitas yang mendiami planet Bumi ini. Selama ini, kita selalu mencari-cari dan mereka-reka model kehidupan yang dianggap cocok dan selaras dengan watak manusia. Semua model kehidupan yang pernah mewarnai dunia ini tidak luput dari liputan seri kehidupan anak manusia dan hampir keseluruhannya dicoba untuk diterapkan dalam kehidupan. Namun apa hendak dikata, kesemuanya hanyalah model coba-coba yang sudah pasti tidak akan bisa memberikan kepuasan bagi si penikmatnya. Kita hampir saja melupakan suatu model kehidupan yang mendekati sempurna bagi prasyarat kehidupan demokratis. Itulah model kehidupan yang diperagakan oleh Rasulullah dan para sahabat

Pendidikan merupakan suatu pembelajaran untuk meningkatkan pengetahuan, sikap, dan keterampilan seseorang. proses kegiatan belajar siswa yang perlu diperhatikan terutama dalam pengerjaan tugas kelompok kerja siswa, terkadang dalam pembagian kelompok kerja siswa tidak merata sehingga mengakibatkan terjadinya kualitas siswa yang didalam kelompok tersebut tidak merata juga. Hal ini menjadi perhatian dikalangan pendidikan untuk meningkatkan mutu belajar siswa, penelitian ini menawarkan model pengelompokan bussines intelligence, metode yang digunakan adalah Algoritma Clustering K-Means dan Algoritma Greedy. Hasil penelitian ini dari 37 siswa terbagi pada 5 cluster kualitas siswa, sehingga dari cluster tersebut terbentuk kelompok kerja siswa sebanyak 7 kelompok, semua kelompok mempunyai 5 anggota dengan bobot kelompok bernilai 13 kecuali kelompok 3 dan 7 sebanyak 6 orang dengan bobot kelompok bernilai 14. Kata kunci: Algoritma Greedy, bussines intelligence, Clustering, Kelompok Kerja Siswa, Pendidikan

Development of Islam in Indonesia or in the local domain did not show the same performance as in his home land, namely in the Arab lands. This is due to the acculturation the values of Islam and the local culture. Variabilities in Islamic appearance is also showed the variabilities in understanding on Islam. Applying variable approaches on Islam, textual-contextual and functional-structural, will show the varieties of Islam too: normative Islam, factual Islam, ideal Islam or universal Islam, and Local Islam. From this illustrates that in reality, we are often confronted with the face of normative Islam, Islamic factual, ideal or universal Islam and the local Muslim. The study found the patterns of understanding and attitude of inclusive-exclusive, with all the effects that will be caused, either constructive or destructive, supporting or undermined the development of Islam. Based on the finding, it is needed a concept and strategy of da‘wa which is really effective and approved by multy-culture society like Indonesia. *** Perkembangan Islam di Indonesia atau di lokalitas yang lain tidak menampak­kan wajah Islam yang sama seperti di tanah kelahirannya, yaitu di tanah Arab. Hal tersebut disebabkan karena sudah terjadi akulturasi ajaran Islam dengan nilai-nilai budaya lokal. Inilah bentuk interkoneksi antara ajaran Islam dengan kearifan lokal. Dari kajian tersebut, didapati pemahaman Islam yang bermacam-macam. Tampilan rumusan Islam tersebut dihampiri dengan berbagai pendekatan untuk memudahkan pemetaan terhadap pemahaman keislaman. Dari tampilan tersebut menggambarkan bahwa dalam realitas, kita sering diperhadapkan pada wajah Islam normatif, Islam faktual, Islam ideal atau universal dan Islam lokal. Sedangkan pendekatan yang dipakai untuk menelaah hal tersebut adalah pen­dekatan tekstual-kontekstual dan struktural-fungsional. Dari telaah tersebut, didapati pola pemahaman dan pola sikap yang inklusif dan eksklusif, dengan segala dampak yang akan ditimbulkan, baik yang konstruktif maupun yang destruktif, yang mendukung maupun yang menggerogoti perkembangan Islam. Dari realitas tersebut, diperlukan suatu konsep dan strategi dakwah yang betul-betul mengena dan diterima masyarakat multikultural seperti Indonesia ini.

This article is not intended to judge or comment on philo­sophical ideas about the creation of the cosmos from the perspective of modern science, but merely to serve as a comparison and reflection materials. Accurate assessment of the thoughts of philosophers would not be optimal if the modern scientific approaches is used here because their methods are completely different. The philosophers usually use philosophical or spiritual approaches, while the scientists uses mod­ern science and material approaches. If it has been understood that the qualities manifested by something (not the thing itself) is more in­teresting, it can be understood that the Islamic cosmology presents a perspective that has no connection with a scientific cosmology because of its constantly changing. Here there is a qualitative correspondence scheme illustrating the relative position between the God, the cosmos, and humans.

This study explores the phenomena of studying local rituals in Islam, which often become a focus of scholarly research. The studies of local Islam often reveal the map and the sketch of the developed various local rituals of Islam such as tarekat, tahlil and slametan. Scholars and experts have attempted to research these phenomena and employed diverse approaches to explain them. Most of them used textual and contextual approaches. Others sought to use structural and functional approach. Their study help explain the pattern and the attitude of Islamic rituals among certain people. One example pertains to the explanation of the most rural people, especially in Madura East Java regarding their practice of local Islam. One of the fundinds of such scholalrly research asserts that the poeple in the region conduct their rituals independently, without a medium of teachers and pupils.Abstrak: Artikel ini akan memaparkan kajian keislaman yang fenomenanya sering muncul dalam bentuk ritual Islam lokal dan tidak jarang dijadikan sebagai model kajian populer dalam pergulatan pemikiran yang sedang bergulir, khususnya di pentas akademik. Dari kajian tersebut didapati sketsa ritual Islam bermacam-macam dan menjelma dalam ritual-ritual yang berkembang. Sketsa ritual Islam tersebut telah mengundang animo dan atensi para pengkaji, baik dari dalam maupun luar (nonmuslim), dengan berbagai pendekatan yang digunakan untuk memudahkan pemahaman terhadap keislaman. Gambaran dari sketsa tersebut menunjukkan bahwa dalam realitas, kita sering diperhadapkan pada sketsa Islam lokal, dalam bentuk ritual-ritual, seperti tarekat-tarekat, tahlilan, selamatan, dan sebagainya. Pendekatan yang dipakai untuk meneropong hal tersebut adalah pendekatan tekstual-kontekstual dan struktural-fungsional. Dari penelaahan didapati bahwa ternyata pola pemahaman dan pola sikap mayoritas masyarakat pedesaan, khususnya Madura, mempraktekkan ajaran Islam dalam bentuk ritual yang mandiri, berjalan sendiri, tanpa mengenal hubungan antara murid dan syekh atau mursyid.

Dual specificity protein kinase threonine/Tyrosine kinase (TTK) is one of the mitotic kinases. High levels of TTK are detected in several types of cancer. Hence, TTK inhibition is considered a promising therapeutic anti-cancer strategy. In this work, we used multiple docked poses of TTK inhibitors to augment training data for machine learning QSAR modeling. Ligand-Receptor Contacts Fingerprints and docking scoring values were used as descriptor variables. Escalating docking-scoring consensus levels were scanned against orthogonal machine learners, and the best learners (Random Forests and XGBoost) were coupled with genetic algorithm and Shapley additive explanations (SHAP) to determine critical descriptors for predicting anti-TTK bioactivity and for pharmacophore generation. Three successful pharmacophores were deduced and subsequently used for in silico screening against the NCI database. A total of 14 hits were evaluated in vitro for their anti-TTK bioactivities. One hit of novel chemotype showed reasonable dose-response curve with experimental IC 50 of 1.0 μM. The presented work indicates the validity of data augmentation using multiple docked poses for building successful machine learning models and pharmacophore hypotheses., (© 2023 Wiley-VCH GmbH.)

The index case of COVID-19 in Nigeria was in February 2020. The pandemic has resulted in severe social, economic, and public health challenge in Nigeria. Nigeria has experienced pandemic fatigue (PF) characterized by its low testing capacity, poor public adherence to COVID-19 preventive measures, and the urge to return to normal. This viewpoint examines Nigeria's obvious PF amongst Nigerians and believed that community engagement would be a master key to reducing Nigeria's PF and preventing another wave of the pandemic in Nigeria. Community engagement (CE) is a viable way for monitoring the spread of the SARS-CoV-2. CE is cost-effective, improves the chances of people voluntarily presenting themselves for COVID-19 testing at the grass-root level, and could halt the spread of COVID-19 in Nigeria especially with the detection of the delta and omicron variants in Nigeria., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

We aimed to assess the antitumor activity of Orobanche crenata methanolic extract and evaluate its cytotoxic effect on different cancer cell lines to develop an effective natural anticancer drug. Components of O. crenata methanolic extract were analyzed using gas chromatography-mass spectrometry. The extract's antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power procedures and cytotoxicity of the extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays. Caspase-3 activity was also estimated. O. crenata methanolic extract shows powerful antioxidant activity. The extract inhibited the propagation of human hepatocellular carcinoma (HepG2), human prostate cancer (PC3), human breast adenocarcinoma (MCF-7), and human colon carcinoma (HCT-116) in a dose-dependent manner. O. crenata- treated cells displayed obvious morphological structures distinctive of apoptosis. MTT assay exposed that the extract presented prevention of cell persistence in a dose-dependent means and revealed extremely cytotoxic activity against HepG2, PC3, MCF-7, and HCT-116 with 50% inhibitory concentration values 30.3, 111, 89.6, and 28.6 µg/mL, respectively, after 24 h of incubation. In addition, treatment of HCT-116 with various concentrations of the extract caused the release of lactate dehydrogenase and induction of caspase-3 activity in a dose-dependent way. In conclusion, our findings suggested that the O. crenata extract possesses potent antioxidant, cytotoxic activity, and anticancer properties which are possibly due to the principal bioactive phytochemical composites existing in this plant. These results can be used to develop new drugs for cancer treatment.

Rheumatoid arthritis (RA) is characterized by chronic inflammation and synovial hyperplasia that eventually leads to the destruction of the joints. CXCL10 has been originally identified as a pro-inflammatory chemokine that mediate leukocyte trafficking and modulate innate and adaptive immune responses. It plays a critical role in the inflammatory response and is involved in several biological processes. The aim of the study was to assess the diagnostic efficacy of serum CXCL10 levels in early RA patients. Patients and methods: The study included 60 RA patients; 30 of them were early diagnosed, and 30 longstanding RA and 30 healthy controls. Clinical examination was done for all patients. Measurement of serum CXCL10 level was done by ELISA, while assessment of disease activity in patients was done using disease activity score (DAS-28). Serum levels of CXCL10 were significantly higher in RA patients than controls (P < 0.001), and was more elevated in early diagnosed than longstanding RA patients, with a a significant positive correlation with DAS-28 ESR (r=0.361, P=0.005), number of tender joint (r=0.319, P=0.013), and number of swollen joint (r=0.280, P=0.030). A cutoff at 470.0 pg/ml was able to recognize longstanding RA with a sensitivity of 88.3% and a specificity of 90% , while a cutoff of 793 pg/ml was able to diagnose early RA with 65% sensitivity and 77% specificity (P=0.009). in conclusion, serum CXCL10 may be a useful biomarker for diagnosis of early RA and determination of disease activity., (Copyright© by the Egyptian Association of Immunologists.)

Diabetes mellitus is a metabolic disease that is characterized by chronic hyperglycemia. Type 2 diabetes is a global health problem and leading to many dangerous complications. Diabetic nephropathy is a significant microvascular complication resulting from diabetes mellitus that is affecting up to 50% of patients with end stage renal disease. Vitamin D deficiency may occur due to many different factors and is associated with many serious diseases as diabetic nephropathy. To investigate the 25-hydroxyvitamin D deficiency and predictive factors in patients with diabetic nephropathy in type 2 diabetes mellitus. One hundred type 2diabetic patients were divided into two groups according to Alb/creat ratio to diabetic patients with and without nephropathy and 50 non-diabetic controls. We measured the serum 25-hydroxyvitamin D levels in all the study populations. The mean serum level of 25 (OH) D was significantly decreased in patients with diabetic nephropathy (13.41±4.99 ng/ml, P=0.002). There was a significant correlation with vitamin D deficiency and the patients residency and also a significant positive correlation with eGFR (r = 0.317, P = 0.025) and a significant negative correlation with Alb/creat Ratio(r = -0.323, P = 0.022). The significant best-fitting predictors of vitamin D deficiency were living in rural area (OR=4.030, P < 0.021) and eGFR < 60 (OR=5.412, P < 0.034). In conclusion, vitamin D deficiency is prevalent in patients with diabetic nephropathy living in rural areas. Low eGFR < 60, Alb/creat ratio more than 30 mg/24h and HbA1c > 9 could be considered as predictive factors of vitamin D deficiency in these patients., (Copyright© by the Egyptian Association of Immunologists.)

Background: Parkinsonism (PD) is a common neurodegenerative disorders into which dysphagia occurs mainly in the late stage and to a lesser extent in an early stage. Diagnosis of dysphagia particularly in early idiopathic Parkinson's disease (IPD) is important as dysphagia affects the quality of life of patients and most of the patients are unaware of this important symptom., Method: Fifty-four patients were enrolled in this study presented with early IPD attending to the outpatient clinic of Sohag University Hospital. All PD patients were assessed by using Unified Parkinson's Disease Rating Scale (UPDRS) and modified Hoehn and Yahr scale. IPD patients were classified into tremor dominant (TD) and postural instability/gait disorder (PIGD) phenotypes. Swallowing disturbance questionnaire (SDQ) and fiberoptic endoscopic evaluation of swallowing (FEES) were used to evaluate dysphagia., Results: Thirty-five percent of patients experienced dysphagia when the patients were questioned, and this percent rises to 40% on using FEES. The results of SDQ were significantly correlated to the results of more accurate FEES. The percentage of dysphagia was higher in patients with PIGD than TD phenotype. Dysphagia was significantly associated with the mean of the Mini-Mental State Examination (MMSE), UPDRS, and modified Hoehn and Yahr scale., Conclusions: Dysphagia is a prevalent symptom in early IPD and significantly correlated with Parkinsonism phenotype, UPDRS, and modified Hoehn and Yahr scale., Competing Interests: The study was approved by the local Ethical Committee of Sohag Faculty of Medicine, Sohag University on September 7, 2014, with reference number (75). Informed written (when available) consent was obtained from all patients for participation and publication of this study.This manuscript does not contain any personal data.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function-the storage, expression, and replication of genetic information-is still one of the central issues in biology. Here, we describe the much debated 3D architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture ( T2C ), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence., Results: The genome is compacted into a chromatin quasi-fibre with ~5 ± 1 nucleosomes/11 nm, folded into stable ~30-100 kbp loops forming stable loop aggregates/rosettes connected by similar sized linkers. Minor but significant variations in the architecture are seen between cell types and functional states. The architecture and the DNA sequence show very similar fine-structured multi-scaling behaviour confirming their co-evolution and the above., Conclusions: This architecture, its dynamics, and accessibility, balance stability and flexibility ensuring genome integrity and variation enabling gene expression/regulation by self-organization of (in)active units already in proximity. Our results agree with the heuristics of the field and allow "architectural sequencing" at a genome mechanics level to understand the inseparable systems genomic properties.

Introduction: Heart rate complexity, commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice is not yet widely adopted. We previously demonstrated the ability of this noninvasive technology to predict lifesaving interventions (LSIs) in trauma patients. This study was conducted to prospectively evaluate the utility of real-time, automated, noninvasive, instantaneous sample entropy (SampEn) analysis to predict the need for an LSI in a trauma alert population presenting with normal vital signs., Methods: Prospective enrollment of patients who met criteria for trauma team activation and presented with normal vital signs was conducted at a level I trauma center. High-fidelity electrocardiogram recording was used to calculate SampEn and SD of the normal-to-normal R-R interval (SDNN) continuously in real time for 2 hours with a portable, handheld device. Patients who received an LSI were compared to patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. Treating clinicians were blinded to results., Results: Of 129 patients enrolled, 38 (29%) received 136 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. Lifesaving intervention patients had a lower Glasgow Coma Scale. The mean SampEn on presentation was 0.7 (0.4-1.2) in the LSI group compared to 1.5 (1.1-2.0) in the non-LSI group (P < .0001). The area under the curve with initial SampEn alone was 0.73 (95% confidence interval [CI], 0.64-0.81) and increased to 0.93 (95% CI, 0.89-0.98) after adding sedation to the model. Sample entropy of less than 0.8 yields sensitivity, specificity, negative predictive value, and positive predictive value of 58%, 86%, 82%, and 65%, respectively, with an overall accuracy of 76% for predicting an LSI. SD of the normal-to-normal R-R interval had no predictive value., Conclusions: In trauma patients with normal presenting vital signs, decreased SampEn is an independent predictor of the need for LSI. Real-time SampEn analysis may be a useful adjunct to standard vital signs monitoring. Adoption of real-time, instantaneous SampEn monitoring for trauma patients, especially in resource-constrained environments, should be considered., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: As providing health education, optimizing nutrition, and managing risk factors can be effective for ensuring a healthy outcome for women and her yet un-conceived baby, external influences play a significant role as well. Alcohol, smoking, caffeine use and other similar lifestyle factors, have now become an integral part of the daily life of most men and women, who use/misuse one or more of these harmful substances regularly despite knowledge of their detrimental effects. The adverse health outcomes of these voluntary and involuntary exposures are of even greater concern in women of child bearing age where the exposure has the potential of inflicting harm to two generations. This paper is examining the available literature for the possible effects of caffeine consumption, smoking, alcohol or exposure to chemicals may have on the maternal, newborn and child health (MNCH)., Methods: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception usage of caffeine, tobacco, alcohol and other illicit drugs; and exposure to environmental chemicals and radiant on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture., Results: Heavy maternal preconception caffeine intake of >300 mg/d significantly increase the risk of a subsequent fetal loss by 31% (95% CI: 8-58%). On the other hand, preconception alcohol consumption leads to non-significant 30% increase in spontaneous abortion (RR 1.30; 95% CI: 0.85-1.97). Preconception counselling can lead to a significant decrease in the consumption of alcohol during the first trimester (OR 1.79; 95% CI: 1.08-2.97). Periconception smoking, on the other hand, was found to be associated with an almost 3 times increased risk of congenital heart defects (OR 2.80; 95% CI 1.76-4.47). While the review found limited evidence of preconception environmental exposure on maternal, newborn and child health outcomes, occupational exposure in female radiation workers before conception showed an increased impact in risk of early miscarriages., Conclusion: Identification of substance abuse and environmental history during preconception period provides an opportunity to assist women in reducing major health risks and identify key determinants of healthy pregnancy. Studies have shown that the aversion and prevention of exposure feasibility can play an important role in improving the health of women and their families, however, the results should be interpreted with great caution as there were few studies in each section. Therefore, there is a need for more rigorous studies to test the hypotheses.

Introduction: A large proportion of women around the world suffer from chronic diseases including mental health diseases. In the United States alone, over 12% of women of reproductive age suffer from a chronic medical condition, especially diabetes and hypertension. Chronic diseases significantly increase the odds for poor maternal and newborn outcomes in pregnant women., Methods: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for preventing and managing chronic diseases and promoting psychological health on maternal, newborn and child health outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture., Results: Maternal prepregnancy diabetic care is a significant intervention that reduces the occurrence of congenital malformations by 70% (95% Confidence Interval (CI): 59-78%) and perinatal mortality by 69% (95% CI: 47-81%). Furthermore, preconception management of epilepsy and phenylketonuria are essential and can optimize maternal, fetal and neonatal outcomes if given before conception. Ideally changes in antiepileptic drug therapy should be made at least 6 months before planned conception. Interventions specifically targeting women of reproductive age suffering from a psychiatric condition show that group-counseling and interventions leading to empowerment of women have reported non-significant reduction in depression (economic skill building: Mean Difference (MD) -7.53; 95% CI: -17.24, 2.18; counseling: MD-2.92; 95% CI: -13.17, 7.33)., Conclusion: While prevention and management of the chronic diseases like diabetes and hypertension, through counseling, and other dietary and pharmacological intervention, is important, delivering solutions to prevent and respond to women's psychological health problems are urgently needed to combat this leading cause of morbidity.

Introduction: Infections can impact the reproductive health of women and hence may influence pregnancy related outcomes for both the mother and the child. These infections range from sexually transmitted infections (STIs) to TORCHS infections to periodontal disease to systemic infections and may be transmitted to the fetus during pregnancy, labor, delivery or breastfeeding., Methods: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture., Results: Preconception behavioral interventions significantly declines re-infection or new STI rates by 35% (95% CI: 20-47%). Further, condom use has been shown to be the most effective way to prevent HIV infection (85% protection in prospective studies) through sexual intercourse. Intervention trials showed that preconception vaccination against tetanus averted a significant number of neonatal deaths (including those specifically due to tetanus) when compared to placebo in women receiving more than 1 dose of the vaccine (OR 0.28; 95% CI: 0.15-0.52); (OR 0.02; 95% CI: 0.00-0.28) respectively., Conclusion: Preconception counseling should be offered to women of reproductive age as soon as they test HIV-positive, and conversely women of reproductive age should be screened with their partners before pregnancy. Risk assessment, screening, and treatment for specific infections should be a component of preconception care because there is convincing evidence that treatment of these infections before pregnancy prevents neonatal infections.

Introduction: Preconception care recognizes that many adolescent girls and young women will be thrust into motherhood without the knowledge, skills or support they need. Sixty million adolescents give birth each year worldwide, even though pregnancy in adolescence has mortality rates at least twice as high as pregnancy in women aged 20-29 years. Reproductive planning and contraceptive use can prevent unintended pregnancies, unsafe abortions and sexually-transmitted infections in adolescent girls and women. Smaller families also mean better nutrition and development opportunities, yet 222 million couples continue to lack access to modern contraception., Method: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture., Results: Comprehensive interventions can prevent first pregnancy in adolescence by 15% and repeat adolescent pregnancy by 37%. Such interventions should address underlying social and community factors, include sexual and reproductive health services, contraceptive provision; personal development programs and emphasizes completion of education. Appropriate birth spacing (18-24 months from birth to next pregnancy compared to short intervals <6 months) can significantly lower maternal mortality, preterm births, stillbirths, low birth weight and early neonatal deaths., Conclusion: Improving adolescent health and preventing adolescent pregnancy; and promotion of birth spacing through increasing correct and consistent use of effective contraception are fundamental to preconception care. Promoting reproductive planning on a wider scale is closely interlinked with the reliable provision of effective contraception, however, innovative strategies will need to be devised, or existing strategies such as community-based health workers and peer educators may be expanded, to encourage girls and women to plan their families.

Introduction: There is increasingly a double burden of under-nutrition and obesity in women of reproductive age. Preconception underweight or overweight, short stature and micronutrient deficiencies all contribute to excess maternal and fetal complications during pregnancy., Methods: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on maternal, newborn and child health (MNCH) outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture., Results: Maternal pre-pregnancy weight is a significant factor in the preconception period with underweight contributing to a 32% higher risk of preterm birth, and obesity more than doubling the risk for preeclampsia, gestational diabetes. Overweight women are more likely to undergo a Cesarean delivery, and their newborns have higher chances of being born with a neural tube or congenital heart defect. Among nutrition-specific interventions, preconception folic acid supplementation has the strongest evidence of effect, preventing 69% of recurrent neural tube defects. Multiple micronutrient supplementation shows promise to reduce the rates of congenital anomalies and risk of preeclampsia. Although over 40% of women worldwide are anemic in the preconception period, only one study has shown a risk for low birth weight., Conclusion: All women, but especially those who become pregnant in adolescence or have closely-spaced pregnancies (inter-pregnancy interval less than six months), require nutritional assessment and appropriate intervention in the preconception period with an emphasis on optimizing maternal body mass index and micronutrient reserves. Increasing coverage of nutrition-specific and nutrition-sensitive strategies (such as food fortification; integration of nutrition initiatives with other maternal and child health interventions; and community based platforms) is necessary among adolescent girls and women of reproductive age. The effectiveness of interventions will need to be simultaneously monitored, and form the basis for the development of improved delivery strategies and new nutritional interventions.

Introduction: Preconception care includes any intervention to optimize a woman's health before pregnancy with the aim to improve maternal, newborn and child health (MNCH) outcomes. Preconception care bridges the gap in the continuum of care, and addresses pre-pregnancy health risks and health problems that could have negative maternal and fetal consequences. It therefore has potential to further reduce global maternal and child mortality and morbidity, especially in low-income countries where the highest burden of pregnancy-related deaths and disability occurs., Methods: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture., Results: Women who received preconception care in either a healthcare center or the community showed improved outcomes, such as smoking cessation; increased use of folic acid; breastfeeding; greater odds of obtaining antenatal care; and lower rates of neonatal mortality., Conclusion: Preconception care is effective in improving pregnancy outcomes. Further studies are needed to evaluate consistency and magnitude of effect in different contexts; develop and assess new preconception interventions; and to establish guidelines for the provision of preconception care.

Background: Anaemia during pregnancy can lead to adverse maternal and perinatal outcomes. The WHO recommends that all pregnant women in areas where anaemia is prevalent receive supplements of iron and folic acid. However, due to many factors, the use of iron and folic acid supplementation is still low in many countries. This study was conducted to assess the rates of iron-folic supplementation and the associated factors during pregnancy and the effects of taking iron-folic acid supplementation on rates of maternal anaemia and low birth weight (LBW) infants., Methods: A cross-sectional study was conducted at Khartoum Hospital, Sudan. Enrolled women answered a questionnaire on socio-demographics characteristics, their pregnancy and delivery., Results: Of 856 women, 788 (92.1%) used iron-folic acid supplementation during pregnancy and 65.4% used folic acid. While place of residence, occupation and level of education were not associated with iron-folic acid usage, older age (OR = 3, CI = 1.4-6.3) and use of antenatal care (OR = 14.3, CI = 7.4-27.5) were associated with iron-folic acid use. Primiparity (OR = 3.8, CI = 1.9-7.6), maternal employment (OR = 3.9, CI = 2.25-6.77) and use of antenatal care (OR = 7.9, CI = 4.1-15) were the factors associated with folic acid. Using iron-folic acid was protective against anaemia (OR = 0.39, CI = 0.2-0.7) and LBW infants (OR = 0.3, CI = 0.17-0.68)., Conclusion: There was a high rate of iron-folic acid supplementation use among pregnant women in Khartoum, Sudan, which was beneficial in preventing anaemia in expectant mothers and infants of LBW.

Background: Preeclampsia is a leading cause of maternal and perinatal mortality worldwide. The exact etiology of preeclampsia is unknown, but the inflammatory process is postulated as one of the etiologies. Red blood cell distribution width (RDW) is a measure of anisocytosis (variation of red cell size) and is associated with hypertension and diabetic ketoacidosis. There are few data on the association between RDW and preeclampsia. This study aimed to investigate the association between RDW and preeclampsia., Methods: A case-control study was conducted at Khartoum Hospital, Sudan, during June to August 2012. Cases were women with preeclampsia and healthy women were controls. Sociodemographic characteristics, obstetrics, and clinical data were recorded. The complete blood count, including RDW, was measured using an automated hematology analyzer., Results: The cases and controls (65 women in each arm) were matched in their basic characteristics. There was no difference in the mean (SD) RDW between women with preeclampsia and controls (14.5 ± 1.8% vs. 14.4 ± 1.4%, P = 0.710). There was also no difference in the mean RDW between women with mild and severe preeclampsia (14.7 ± 1.9% vs. 13.9 ± 1.4%, P = 0.144. In logistic regression, there was no association between RDW and preeclampsia (OR = 0.9, CI = 0.7-1.1, P = 0.952)., Conclusions: RDW levels are not associated with the presence or severity of preeclampsia., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1206247718115175.

Background: Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP., Methods: Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A prototype, computerized, cortical impact device was used to create TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was induced (40-45% total blood volume) concurrent with the TBI. After 2 hours of shock, animals were treated with (1) normal saline (NS, n = 5), (2) FFP (n = 5), and (3) LSP (n = 5). The volume of FFP and LSP matched the shed blood volume, whereas NS was 3 times the volume. Six hours after resuscitation, brains were sectioned and stained with TTC (2, 3, 5-Triphenyltetrazolium chloride), and lesion size (mm) and swelling (percent change in volume compared with the contralateral, uninjured side) were measured., Results: This protocol resulted in a highly reproducible brain injury, with clinically relevant changes in blood pressure, cardiac output, tissue hypoperfusion, intracranial pressure, and brain tissue oxygenation. Compared with NS, treatment with LSP significantly (p < 0.05) decreased brain lesion size and swelling (51% and 54%, respectively)., Conclusion: In a clinically realistic combined TBI + HS model, early administration of plasma products decreases brain lesion size and edema. LSP is as effective as FFP, while offering many logistic advantages.

Background: We have previously shown that the extent of traumatic brain injury (TBI) in large animal models can be reduced with early infusion of fresh frozen plasma (FFP), but the precise mechanisms remain unclear. In this study, we investigated whether resuscitation with FFP or normal saline differed in their effects on cerebral metabolism and excitotoxic secondary brain injury in a model of polytrauma, TBI, and hemorrhagic shock., Methods: Yorkshire swine (n = 10) underwent Grade III liver injury, rib fracture, standardized TBI, and volume-controlled hemorrhage, (40% ± 5%) and were randomly resuscitated with either FFP or normal saline. Hemodynamic parameters and brain oxygenation were continuously monitored, while microdialysis was used to measure the brain concentrations of pyruvate, lactate, glutamate, and glycerol at baseline; 1 hour and 2 hours after shock; immediate postresuscitation (PR); as well as 2, 4, and 6 hours PR. Cells from the injured hemisphere were separated into mitochondrial and cytosolic fractions and analyzed for activity of the pyruvate dehydrogenase complex (PDH)., Results: There were no baseline differences in cerebral perfusion pressure, brain oxygenation, as well as concentrations of pyruvate, lactate, glutamate, and glycerol between the groups. At 2 hours and 4 hours PR, the FFP group had significantly higher cerebral perfusion pressures (52 [5] mm Hg vs. 43 [2] mm Hg, p = 0.016; and 50 [7] mm Hg vs. 37 [1] mm Hg, p = 0.008, respectively). There was a sustained and significant (p < 0.05) drop in the glutamate and glycerol levels in the FFP group, implying a decrease in excitotoxicity and brain damage, respectively. Mitochondrial PDH activity was significantly higher (2,666.2 [638.2] adjusted volume INT × mm vs. 1,293.4 [88.8] adjusted volume INT × mm, p = 0.008), and cytosolic PDH activity was correspondingly lower (671.4 [209.2] adjusted volume INT × mm vs. 3070.7 [484.3] adjusted volume INT × mm, p < 0.001) in the FFP group, suggesting an attenuation of mitochondrial dysfunction and permeability., Conclusion: In this model of TBI, polytrauma, and hemorrhage, FFP resuscitation confers neuroprotection by improving cerebral perfusion, diminishing glutamate-mediated excitotoxic secondary brain injury and reducing mitochondrial dysfunction.

Importance: Reduction in length of hospital stay is a veritable target in reducing the overall costs of health care. However, many existing approaches are flawed because the assumptions of what cause excessive length of stay are incorrect; we methodically identified the right targets in this study., Objective: To identify the causes of excessively prolonged hospitalization (ExProH) in trauma patients., Design: The trauma registry, billing databases, and medical records of trauma admissions were reviewed. Excessively prolonged hospitalization was defined by the standard method used by insurers, which is a hospital stay that exceeds the Diagnosis Related Group-based trim point. The causes of ExProH were explored in a unique potentially avoidable days database, used by our hospital's case managers to track discharge delays., Setting: Level I academic trauma center., Participants: Adult trauma patients admitted between January 1, 2006, and December 31, 2010., Main Outcomes and Measures: Excessively prolonged hospitalization and hospital cost., Results: Of 3237 patients, 155 (5%) had ExProH. The patients with ExProH compared with non-ExProH patients were older (mean [SD] age, 53 [21] vs 47 [22] years, respectively; P = .001), were more likely to have blunt trauma (92% vs 84%, respectively; P = .03), were more likely to be self-payers (16% vs 11%, respectively; P = .02) or covered by Medicare/Medicaid (41% vs 30%, respectively; P = .002), were more likely to be discharged to post-acute care facilities than home (65% vs 35%, respectively; P < .001), and had higher hospitalization cost (mean, $54 646 vs $18 444, respectively; P < .001). Both groups had similar Injury Severity Scores, Revised Trauma Scores, baseline comorbidities, and in-hospital complication rates. Independent predictors of mortality were discharge to a rehabilitation facility (odds ratio = 4.66; 95% CI, 2.71-8.00; P < .001) or other post-acute care facility (odds ratio = 5.04; 95% CI, 2.52-10.05; P < .001) as well as insurance type that was Medicare/Medicaid (odds ratio = 1.70; 95% CI, 1.06-2.72; P = .03) or self-pay (odds ratio = 2.43; 95% CI, 1.35-4.37; P = .003). The reasons for discharge delays were clinical in only 20% of the cases. The remaining discharges were excessively delayed because of difficulties in rehabilitation facility placement (47%), in-hospital operational delays (26%), or payer-related issues (7%)., Conclusions and Relevance: System-related issues, not severity of illness, prolong hospital stay excessively. Cost-reduction efforts should target operational bottlenecks between acute and postacute care.

Background: Heart rate complexity (HRC), commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice has been precluded by the absence of real-time data. This study was conducted to evaluate the utility of real-time, automated, instantaneous, hand-held heart rate entropy analysis in predicting the need for lifesaving interventions (LSIs). We hypothesized that real-time HRC would predict LSIs., Methods: Prospective enrollment of patients who met criteria for trauma team activation was conducted at a Level I trauma center (September 2011 to February 2012). A novel, hand-held, portable device was used to measure HRC (by sample entropy) and time-domain heart rate variability continuously in real time for 2 hours after the moment of presentation. Electric impedance cardiography was used to determine cardiac output. Patients who received an LSI were compared with patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups., Results: Of 82 patients enrolled, 21 (26%) received 67 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. LSI patients had a lower Glasgow Coma Scale (GCS) score (9.2 [5.1] vs. 14.9 [0.2], p < 0.0001). The mean (SD) HRC value on presentation was 0.8 (0.6) in the LSI group compared with 1.5 (0.6) in the non-LSI group (p < 0.0001). With the use of logistic regression, initial HRC was the only significant predictor of LSI. A cutoff value for HRC of 1.1 yields sensitivity, specificity, negative predictive value, and positive predictive value of 86%, 74%, 94%, and 53%, respectively, with an accuracy of 77% for predicting an LSI., Conclusion: Decreased HRC on hospital arrival is an independent predictor of the need for LSI in trauma activation patients. Real-time HRC may be a useful adjunct to standard vital signs monitoring and predicts LSIs., Level of Evidence: Prognostic and diagnostic study, level III.

Background: Therapeutic angioembolization is a relatively new "rescue treatment" modality for gastrointestinal hemorrhage (GIH) for unstable patients who fail primary treatment approaches; however, the effectiveness of this treatment and the incidence of ischemic necrosis following embolization for acute GIH are poorly described. The purpose of this study was to evaluate the effectiveness and safety of "rescue" transcatheter superselective angioembolization (SSAE) for the treatment of hemodynamically unstable patients with GIH., Methods: A 10-year retrospective review of all hemodynamically unstable patients (systolic blood pressure < 90 mm Hg and ongoing transfusion requirement) who underwent "rescue" SSAE for GIH after failed endoscopic management was performed. All patients with evidence of active contrast extravasation were included. Data were collected on demographics, comorbidities, clinical presentation, and type of intravascular angioembolic agent used. Outcomes included technical success (cessation of extravasation), clinical success (no rebleeding requiring intervention within 30 days), and incidence of ischemic complications., Results: Ninety-eight patients underwent SSAE for GIH during the study period; 47 were excluded owing to lack of active contrast extravasation. Of the remaining 51 patients, 22 (43%) presented with a lower GIH and 29 (57%) with upper GIH. The majority underwent embolization with a permanent agent (71%), while the remaining patients received either a temporary agent (16%) or a combination (14%). The overall technical and clinical success rates were 98% and 71%, respectively. Of the 14 patients with technical success but clinical failure (rebleeding within 30 days) and the 1 patient with technical failure, 4 were managed successfully with reembolization, while 2 underwent successful endoscopic therapy, and 9 had surgical resections. Only one patient had an ischemic complication (small bowel necrosis) requiring resection., Conclusion: SSAE, with reembolization if necessary, is an effective rescue treatment modality for hemodynamically unstable patients with active GIH. Of the patients, 20% will fail SSAE and require additional intervention. Ischemic complications are extremely rare., Level of Evidence: Therapeutic study, level IV.

Background: Frequent use of computed tomography (CT) in trauma patients results in frequent detection of non-trauma-related incidental findings (IFs). Inpatient documentation and disclosure at discharge are infrequent, even when they are potentially serious. We aimed to not only identify the incidence of IFs but also to evaluate the effectiveness of an intervention to trigger follow-up., Methods: In this before-after study, all trauma patients evaluated by the trauma surgery service who underwent CT were admitted for >24 h, had at least one IF requiring follow-up, and had a primary care physician (PCP) employed in our health care system were identified. The historical control period was from January 2006 to December 2008. The intervention period was from December 2011 to September 2012. Intervention consisted of notifying the PCP via email or postal letter. The outcome of interest-the rate of follow-up-was compared between both groups., Results: During the historical period, 364 (20.5 %) of 1,774 eligible trauma patients had 434 IFs requiring follow-up. During the study period, 197 (26 %) of 692 trauma patients had 212 IFs requiring follow-up. Overall, 91 % of study patients with postdischarge PCP follow-up had documented follow-up of the IF. There was a significant improvement in the rate of follow-up in the study group compared to that of the control group (51 vs. 11 %; p < 0.0001)., Conclusions: Detection of IFs is common in trauma patients. A dedicated effort of communicating the presence of an IF to the patient's PCP triggered a follow-up for 91 % of patients who saw their PCP after hospital discharge.

Background: Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether this effect was owing to metabolic modulation., Methods: Yorkshire swine (n = 9) underwent a protocol of computer-controlled TBI and 40% hemorrhage and were resuscitated randomly with either fresh frozen plasma equal to the volume of shed blood (FFP; n = 4) or VPA (300 mg/kg) and FFP (FFP+VPA; n = 5). Hemodynamics, brain oxygenation, and blood glucose were monitored continuously for 6 hours after resuscitation. Cerebral microdialysis was used to measure glucose, lactate, pyruvate, glutamate, and glycerol levels at baseline, 1 and 2 hours post-shock, post-resuscitation (PR), and at 2, 4, and 6 hours PR. Brain samples from the injured side were then separated into mitochondrial and cytosolic fractions, and activity of pyruvate dehydrogenase complex (PDH) was measured using a dipstick assay kit., Results: At baseline, there was no difference in brain lactate, pyruvate, glycerol, and glutamate concentrations between the groups. At all time points, there were no differences between the groups in brain oxygenation, cerebral perfusion pressure, or blood and brain glucose concentrations. After VPA infusion (PR time point), however, there was sustained decrease in lactate (0.91 ± 0.47 vs 2.54 ± 0.59 mmol/L; P < .01) and pyruvate (12.80 ± 4.89 vs 46.25 ± 9.22; P < .001) concentrations compared with the FFP alone group, implying superior glucose utilization for ATP production. There was also a decrease in concentrations of glutamate (6.64 ± 3.68 vs 42.25 ± 27.07 mmol/L; P = .02) and glycerol (19.20 ± 6.76 vs 69.75 ± 30.07 mmol/L; P = .01), in the FFP+VPA group, signifying lesser degree of excitotoxicity and brain damage, respectively. Brain PDH activity was greater in the mitochondrial fractions (5,984 ± 504 adjusted volume intensity [INT] × mm(2) vs 4,332 ± 1,055 INT × mm(2); P = .04) and lower in cytosolic fractions in the FFP+VPA group (1,597 ± 1,395 vs 4,026 ± 1,067 INT × mm(2); P = .03), indicating better mitochondrial membrane function and enhanced mitochondrial PDH retention., Conclusion: VPA treatment attenuates perturbation of post-traumatic cerebral metabolism by mitigating mitochondrial dysfunction, and decreases glutamate-mediated excitotoxic damage. These properties could explain its effectiveness in decreasing lesion size and post-traumatic cerebral edema., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Introduction: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert a synergistic effect., Methods: Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. TBI was created through a 20-mm craniotomy using a computer-controlled cortical impactor: 15-mm cylindrical tip impactor at 4 m/s velocity, 100 ms dwell time, and 12-mm penetration depth. The TBI was synchronized with the initiation of volume-controlled hemorrhage (40 ± 5% of total blood volume). After a 2-hour period of shock, animals were randomized to 1 of 3 resuscitation groups (n = 5 per group): (1) 0.9% saline (NS); (2) FFP; and (3) FFP and VPA 300 mg/kg (FFP+VPA). The resuscitative volume for FFP was equivalent to the shed blood, whereas NS was 3 times this volume. VPA treatment was started 1 hour after hemorrhage. Animals were monitored for 6 hours post-resuscitation. At this time the brains were harvested, sectioned into 5-mm slices, and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size (mm(3)) and brain swelling (percent change compared with the uninjured side)., Results: The combined TBI+HS model resulted in a highly reproducible brain injury. Lesion size and brain swelling (mean value ± standard error of the mean) in the FFP+VPA group (1,459 ± 218 mm(3) and 13 ± 1%, respectively) were less than the NS group (3,285 ± 131 mm(3) [P < .001] and 37 ± 2% [P < .001], respectively), and the FFP alone group (2,160 ± 203 mm(3) [P < .05] and 22 ± 1% [P < .001], respectively)., Conclusion: In a large animal model of TBI+HS, early treatment with a combination of FFP and VPA decreases the size of brain lesion and the associated swelling., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Introduction: Traumatic brain injury and shock are among the leading causes of trauma-related mortality. We have previously shown that fresh-frozen plasma (FFP) resuscitation reduces the size of brain lesion and associated swelling compared with crystalloids. We hypothesized that this effect would be associated with an attenuation of circulating nucleosome levels, a biomarker of injury with cytotoxic potential, through reconstitution of circulating deoxyribonuclease-1 (DNAse1), an enzyme identified as critical in nucleosome clearance from the circulation., Methods: Twelve swine underwent a protocol of traumatic brain injury followed by 40% volume-controlled hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for 2 hours before they were resuscitated with normal saline (NS) or FFP. Circulating levels of nucleosomes and DNAse1 were measured whereas extracellular nucleosomes were quantified on brain histology. Lesion size and brain swelling were also quantified., Results: Nucleosome levels were significantly greater in the NS group 6 hours after resuscitation (0.32 mU vs 0.15 mU, P = .030) whereas DNAse1 levels were substantially greater in the FFP group (9.82 ng/mL vs 4.54 ng/mL, P = .010). Circulating nucleosomes levels correlated with lesion size (rho = 0.79, P = .002) as well as brain swelling (rho = 0.89, P < .001) whereas DNAse1 levels correlated with brain swelling (rho = -0.61, P = .036) but not lesion size (rho = -0.47, P = .124). Brain staining revealed nucleosome extracellularization in both groups, but this appeared more frequent in the NS-resuscitated animals., Conclusion: Our results show that resuscitation with FFP attenuates circulating nucleosome levels and prevents DNAse1 depletion. These factors may play a role in the neuroprotective effects observed during early resuscitation with FFP., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury, and that this dysfunction would be associated with early activation, as measured by circulating levels of platelet activation markers., Methods: A total of 33 swine were allocated to TBI and hypotension (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation only). Animals in the TBI/Hemorrhage group were left hypotensive, defined as mean arterial pressure of 35 mm Hg, for 2 hours. Blood samples were drawn at baseline and 3 minutes and 15 minutes following injury as well as following 2 hours of shock. Samples were analyzed for platelet aggregation using impedance aggregometry with agonists collagen, arachidonic acid, and adenosine diphosphate (ADP) and thromboelastography (TEG) and circulating levels of platelet activation markers transforming growth factor-β (TGF-β), CD40 ligand, and sP-selectin., Results: Platelet ADP aggregation was significantly lower in the TBI/Hemorrhage group when compared with the control group 15 minutes following injury (62.4 vs. 80.4 U, p = 0.03) as well as following 2 hours of hypotension (59.9 vs. 73.5 U, p < 0.01). The latter was associated with lower TEG measured clot strength (TEG-MA, 74.1 vs. 79.4 mm, p = 0.05). No difference in collagen or arachidonic acid aggregation was observed. TGF-β levels were significantly higher in the TBI/Hemorrhage group following 2 hours of hypotension (1,764 vs. 1,252 pg/mL, p = 0.01). No differences in CD40 ligand or sP-selectin levels were observed., Conclusion: In this combined model of TBI and hemorrhage, a significantly lower ADP-induced platelet aggregation was detected 15 minutes following injury that was further aggravated during the 2-hour shock period. This dysfunction was associated with an increase in platelet activation marker TGF-β.

Background: Cerebral palsy (CP) is a major cause of childhood disability. There are various maternal and neonatal predictors associated with the development of CP, and they are variable across different populations. This case-control study was designed to investigate maternal and neonatal predictors of CP at Khartoum pediatric neurology clinics. Data (maternal sociodemographic characteristics and neonatal expected predictors) were collected from mothers of children with CP and healthy controls using questionnaires., Results: One hundred and eleven cases of CP and 222 controls were included. Spastic CP was the most common type (69.4%). In logistic regression, maternal age, parity, birth weight, and sex were not associated with CP. However, maternal fever (OR = 8.4, CI = 2.3-30.5; P = 0.001), previous neonatal death (OR = 5.4, CI = 1.8-16.2; P = 0.003), and poor sucking (OR = 30.5, CI = 10.0-93.1; P < 0.001) were predictors of CP., Conclusions: Fever during labor is a significant risk factor for developing CP in children. Further efforts are required for labor management to prevent CP in this setting.

Preconception care that begins in adolescence and is provided before and between pregnancies has the potential to impact 136 million women who give birth each year and ensure that newborns receive the healthiest start possible. Providing simple interventions before pregnancy can prevent a significant proportion of maternal and neonatal mortality and morbidity. Interventions to promote adolescent health and prevent teenage pregnancies, encourage contraceptive use and appropriate birth spacing, optimize weight and micronutrient status, and screen for and manage chronic conditions have proven efficacy. These interventions must now be scaled up to maximize delivery. Women who receive preconception care are more likely to adopt healthy behaviors, and therefore have better pregnancy outcomes. Preconception care is particularly effective when men are involved and care is provided in the community setting. All healthcare providers can and should begin to provide preconception care to all adolescent girls, women and couples of reproductive age by asking them if they wish to become pregnant or are actively trying to prevent pregnancy., (Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Providing care to adolescent girls and women before and between pregnancies improves their own health and wellbeing, as well as pregnancy and newborn outcomes, and can also reduce the rates of preterm birth. This paper has reviewed the evidence-based interventions and services for preventing preterm births, reported the findings from research priority exercise, and prescribed actions for taking this call further. Certain factors in the preconception period have been shown to increase the risk for prematurity and, therefore, preconception care services for all women of reproductive age should address these risk factors through preventing adolescent pregnancy, preventing unintended pregnancies, promoting optimal birth spacing, optimizing pre-pregnancy weight and nutritional status (including a folic acid-containing multivitamin supplement) and ensuring that all adolescent girls have received complete vaccination. Preconception care must also address risk factors that may be applicable to only some women. These include screening for and management of chronic diseases, especially diabetes; sexually-transmitted infections; tobacco and smoke exposure; mental health disorders, notably depression; and intimate partner violence. The approach to research in preconception care to prevent preterm births should include a cycle of development and delivery research that evaluates how best to scale up coverage of existing evidence-based interventions, epidemiologic research that assesses the impact of implementing these interventions and discovery science that better elucidates the complex causal pathway of preterm birth and helps to develop new screening and intervention tools. In addition to research, policy and financial investment is crucial to increasing opportunities to implement preconception care, and rates of prematurity should be included as a tracking indicator in global and national maternal child health assessments.

Background: The reported prevalence of infertility in Pakistan is approximately 22% with 4% primary and 18% secondary infertility. Infertility is not only a medical but also a social problem in our society as cultural customs and perceived religious dictums may equate infertility with failure on a personal, interpersonal, or social level. It is imperative that people have adequate knowledge about infertility so couples can seek timely medical care and misconceptions can be rectified. We aim to assess the knowledge, perception and myths regarding infertility and suggest ways to improve it., Methods: A cross-sectional survey was carried out by interviewing a sample of 447 adults who were accompanying the patients at two tertiary care hospitals in Karachi, Pakistan. They were interviewed one-on-one with the help of a pretested questionnaire drafted by the team after a thorough literature review and in consultation with infertility specialists., Results: The correct knowledge of infertility was found to be limited amongst the participants. Only 25% correctly identified when infertility is pathological and only 46% knew about the fertile period in women's cycle. People are misinformed that use of IUCD (53%) and OCPs (61%) may cause infertility. Beliefs in evil forces and supernatural powers as a cause of infertility are still prevalent especially amongst people with lower level of education. Seeking alternative treatment for infertility remains a popular option for 28% of the participant as a primary preference and 75% as a secondary preference. IVF remains an unfamiliar (78%) and an unacceptable option (55%)., Conclusions: Knowledge about infertility is limited in the population and a lot of misconceptions and myths are prevalent in the society. Alternative medicine is a popular option for seeking infertility treatment. The cultural and religious perspective about assisted reproductive technologies is unclear, which has resulted in its reduced acceptability.

Background: Melanomas within the alimentary tract are usually metastatic in origin. On the other hand, primary melanomas of the gastrointestinal tract are relatively uncommon. There are several published reports of melanomas occurring in the esophagus, stomach, small bowel, and anorectum. The occurrence of primary melanoma of the colon has, however, only been rarely reported. The optimum modus operandi for the management of primary colonic melanoma remains nebulous due to the limited number of reports in literature., Methods: A comprehensive search of Medline, Cochrane and Highwire was performed using the following keywords: 'melanoma', 'malignant melanoma', 'primary melanoma', 'colon', 'gastrointestinal tract', 'alimentary tract', 'digestive tract', and 'large bowel'. All patients with primary melanoma localized to the colon were included in the review. Patients with metastatic melanomas to the gastrointestinal (GI) tract and primary melanomas localized to the GI tract in anatomic locations other than colon were excluded., Results: There have been only 12 reported cases of primary melanoma of the colon to date. The average age of patients on presentation was 60.4 years without any significant gender predilection. Right colon (33%) and cecum (33%) were the most common sites for the occurrence of primary colonic melanoma while abdominal pain (58%) and weight loss (50%) were the most common presenting complaints. Colonoscopy is the most reliable diagnostic investigation and offers the additional advantage of obtaining tissue for diagnosis. S-100 and HMB-45 are highly sensitive and specific for the diagnosis of this malignancy. For primary colonic melanomas that have not metastasized to any distant parts of the body, surgical resection with wide margins appears to be the treatment of choice. Although the management was individualized in every case, most of the authors preferred traditional hemicolectomy as the favored surgical approach. Chemotherapeutic agents including interferons, cytokines, biological agents and radiation therapy for brain metastases have been reported as adjuvant and palliative options while considering malignant melanomas in general. The average recurrence-free interval was 2.59 years. Nine of the 12 reports documented follow-up in their patients. Two of these 9 (22.2%) patients died., Conclusions: Primary melanoma of the colon is a rare clinical entity. Whenever a seemingly primary melanoma is detected in an atypical location such as the colon, it is prudent to conduct a thorough clinical investigation to consider the possibility of metastatic disease. Further studies are needed to document the long term follow-up, survival advantage and safety of the management approaches employed in patients with primary colonic melanoma. Based on current data, surgical resection appears to be appropriate management for primary colonic melanomas; unless the disease has metastasized to distant sites where surgery may have a limited palliative role.

Objective: To investigate mother's perception and practices about breastfeeding and their socio-demographic correlate in infants equal to or less than 6 months., Methods: A cross-sectional study was carried out on 200 mother-infant pairs who visited the health care centers, Bilal Colony (semi-urban) and the Aga Khan University (urban), for their well baby follow-ups and vaccination using convenient sampling. Frequencies and percentages were computed and Chi-square was used to find associations between socio-demographics of mothers and their perception and practices about breastfeeding., Results: Exclusive breastfeeding was reported by about 54% of the mothers. Thirty-five percent of the mothers gave prelacteal feed, 14% discarded colostrum and 43% woke up their infant to feed if time had exceeded 2 hours. Majority of the females were aware of the advantages (92%) and the disadvantages (85%) of breastfeeding. However, the awareness of positive feedback relationship of milk production and sucking was lacking and breast feeding was considered to cause weakness in mothers., Conclusion: Despite the efforts of health policy makers, the results show a situation that is not improving. Women were aware of the advantages and disadvantages of breast and bottle feeding but a disparity was observed between their perception and practices.

Objective: To assess the knowledge and practice of risk factors, symptoms and screening for breast cancer among health care professionals., Methods: A cross sectional study was carried out at The Aga Khan University Hospital from January 2008 to March 2008. A total of 336 health care workers including consultants (48), fellows (17), residents (76), medical officers (14), interns (37), nurses (94) and fourth and final year medical students (50) were requested to fill a questionnaire designed to assess the knowledge about the risk factors, signs and symptoms, screening tools, breast self examination (BSE) and treatment., Results: More than two third participants had good knowledge about the risk factors and signs of breast cancer except some dissociation regarding association of menarche status and smoking. Majority was aware of the benefits of mammography. More than 80% had the consensus that breast cancer is curable if detected early and more than 50% thought that a surgeon should be consulted first if lump is palpable., Conclusions: This study reveals that health care professionals have fairly good awareness regarding the risk factors, symptoms and role of mammography. But some are still deficient in their knowledge regarding screening modalities and BSE method and time and role of chemotherapy. And this can be improved with further education.