Πέμπτη, 2 Μαΐου 2019

Fwd: Nutrition, Pharmacology, Neurological Diseases

Nutrition, Pharmacology, Neurological Diseases

Binge alcohol and HIV: leaky gut and neurodegeneration through the gut–brain axis
Musthafa Mohamed Essa, Byoung-Joon Song, Sulie L Chang

International Journal of Nutrition, Pharmacology, Neurological Diseases 2019 9(1):1-3

Recent Concepts in Nutritional Therapy in Critically Ill Burn Patients
Mariappan Natarajan

International Journal of Nutrition, Pharmacology, Neurological Diseases 2019 9(1):4-36

In developing countries such as India, burn injury is still a major and frequent cause of mortality and morbidity. Nutrition therapy aims to provide adequate and early nutrition for patients suffering from burn injuries. Metabolic support during heightened inflammatory state is essential to make sure adequate treatment of burn patients. It is essential to reduce the force and effects of the hypermetabolic response, aim for healing of wounds, and help to reduce negative catabolism effects. At the same time, care of surgical and medical needs of the patient is crucial for good clinical outcomes. Nutritional sustain is an essential and integral component of burn care that requires an aggressive multifaceted approach. Impaired wound healing, dysfunction of multiple organs, increased chances of infection, and death are largely prevented by an adequate nutrition care along with proper wound management. Catecholamine and corticosteroids, inflammatory mediator levels, are increased, and this hypermetabolic response leads to catastrophic results in the postburn injury period. A shift from preventing malnutrition to disease modulation in nutrition support in critically ill patients is being aimed at present. Uncontrolled inflammation causes severe metabolic derangement in burn patients. Major challenges are assessment of nutritional status of the patient and estimation of nutrient requirements. Careful decision-making for safe use of enteral or parenteral nutrition and an aggressive nutrient delivery are required. The course of disease can be altered favorably to a great extent by supplementation of specific nutrients. Nutritional factors with positive effects on immunity and in cell regulation include glutamine, arginine, and essential fatty acids, known as immunonutrients. They reduce the severity of illness and improve response to treatment of patients. Nutrition support specialists are trying to improve the management protocols and technological advances such as nanotechnology and biomarkers will take the nutrition management to greater advances. 

Ketogenic Diet- An Evidence Based Direction for Seizure Control
Judie Arulappan, Suja Karkada, Sathish Kumar Jayapal, Vidya Seshan

International Journal of Nutrition, Pharmacology, Neurological Diseases 2019 9(1):37-40

The ketogenic diet is a high fat, low carbohydrate and adequate protein diet. This diet is used in treating difficult to control epilepsy in children. The diet helps the body in utilizing fat than carbohydrate. The liver converts fat into fatty acids and ketone bodies. The ketone bodies replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis reduces the frequency of seizure episodes. 

Phoenix dactylifera L. Fruits Date Fruit Ameliorate Oxidative Stress in 3-NP Intoxicated PC12 Cells
Musthafa M Essa, Vandita Singh, Nejib Guizani, Tamilarasan Manivasagam, Arokiasamy J Thenmozhi, Abid Bhat, Bipul Ray, Saravana B Chidambaram

International Journal of Nutrition, Pharmacology, Neurological Diseases 2019 9(1):41-47

Introduction: Date palm fruits (DFs) are reported to possess antimutagenic, antiviral, antifungal, and anti-inflammatory properties. Effect of date fruits in the management of Huntington’s is yet to be studied. Methods: The protective effects of DF were measured in terms of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and reduced glutathione (rGSH), malondialdehyde (MDA) and nitrate/nitrite (NO2/NO3) content in cells. Cellular adenosine triphosphate (ATP) content was also measured. Cytotoxicity assay revealed that DF has the ability to protected cellular viability against 3-NP intoxication. Results: DFs increased the SOD and GPx activities and rGSH content. On the other hand, DF decreased MDA and NO2/NO3 levels in 3-NP intoxicated cells. Interestingly, DF increased ATP content in pheochromocytoma (PC) cells. Conclusion: DF has the ability to encounter 3-NP intoxication induced biochemical changes and improves cellular ATP contents, hence may be an interestingly candidate for further investigations. 

The potency of Pinus merkusii extract nanoparticles as anti Mycobacterium tuberculosis: An in vitro study
Sri Agus Sudjarwo, Giftania Wardani, Koerniasari Eraiko, Koerniasari , Ernawati 

International Journal of Nutrition, Pharmacology, Neurological Diseases 2019 9(1):48-52

Objective: Herbal nanoparticles have gained interest in nanomedicine, and development of new therapeutic with improved bioavailability, increased sensitivity and specificity, and reduced toxicity. The aim of this study was to evaluate the antimycobacterial activity of the Pinus merkusii extract nanoparticle in vitro. Materials and Methods: Ethanolic extract of P. merkusii was set by maceration method. Tripolyphosphate (TPP) was used to make P. merkusii nanoparticles by ionotropic gelation method. The size and morphology of the P. merkusii nanoparticle was analyzed using scanning electron microscope (SEM). The broth microdilution and micro diffusion methods were used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of P. merkusii nanoparticle on strain Mycobacterium tuberculosis H37Rv. Results: The SEM micrographs of the nanoparticle extract of P. merkusii showed that they were approximately uniform spheres with rough surface morphology and a solid dense cubical or rectangular structure. The size of P. merkusii nanoparticle ranged from10 to 800 nm; most were 500 nm. Using the broth microdilution and micro diffusion susceptibility method, P. merkusii nanoparticle was found to have the antimycobacterial effects with a MIC value of 1000 µg/ml and MBCs value of 2000 µg/ml for M. tuberculosis H37Rv. Conclusion: P. merkusii extract nanoparticle has the lead compounds that may be developed further into antimycobacterial drugs. 

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Fwd: Tropical Medicine

Tropical Medicine

Herbal remedies, vaccines and drugs for dengue fever: Emerging prevention and treatment strategies
Rinku Rozera, Surajpal Verma, Ravi Kumar, Anzarul Haque, Anshul Attri

Asian Pacific Journal of Tropical Medicine 2019 12(4):147-152

Dengue fever is a disease that is caused by five dengue virus (DENV) serotypes. It is endemic in more than 128 countries. Millions of people are affected by this disease. But still, there is no specific treatment available till now to combat it. Some of the preventive measures using plant extracts showed certain promising ovicidal activity against Aedes aegypti. There are some vaccines as preventive measure and antiviral agents to cure the dengue fever, which are under clinical trials but their results have not been reported or approved yet. Dengvaxia is the only licensed vaccine to prevent dengue fever in some South American countries, but it is not approved by other regulatory authorities worldwide. Scientific research has been going on to find a permanent cure for dengue fever, but till now, no successful invention has been done. There are some general treatments for dengue patient by employing analgesics and fluid replacement; however, specific treatment is needed to overcome the lethal effect of dengue fever. Since this disease has affected millions of people and not much invention has been made in this field; therefore, advancement in dengue therapy is required for the safety and well-being of dengue patients. Herein we collectively describe the different chemotherapeutics agents, alternative methods like vaccines and antiviral agents to prevent and cure this lethal disease. Furthermore, the future perspective for the treatment of dengue is discussed in this review. 

Morphometric discrimination between females of two isomorphic sand fly species, Phlebotomus caucasicus and Phlebotomus mongolensis (Diptera: Phlebotominae) in endemic and non-endemic foci of zoonotic cutaneous leishmaniasis in Iran
Azad Absavaran, Mehdi Mohebali, Vahideh Moin-Vaziri, Alireza Zahraei-Ramazani, Amir Ahmad Akhavan, Fariba Mozaffarian, Sayena Rafizadeh, Yavar Rassi

Asian Pacific Journal of Tropical Medicine 2019 12(4):153-162

Objective: To delineate reliable morphological characteristics for identifying and separating female Phlebotomus caucasicus and Phlebotomus mongolensis which exist sympatrically in the main foci of zoonotic cutaneous leishmaniasis in Iran. Methods: Sand flies were collected using sticky trap papers from active colonies of rodent burrows installed from 16 catching sites. Morphometric measurements were analyzed of 87 Phlebotomus caucasicus and 156 Phlebotomus mongolensis. Univariate and multivariate analysis were carried out to determine significant morphometric variables for discrimination of the two species. Finally, seven morphological characteristics of 65 female Phlebotomus caucasicus and 124 female Phlebotomus mongolensis were described. Results: Univariate and multivariate analyses of 10 morphometric variables via Discriminant Function Analysis (DFA) and Principal Component Analysis (PCA) showed that five morphometric variables had an accuracy of 100% for discriminating female Phlebotomus caucasicus and Phlebotomus mongolensis. Moreover, PCA revealed that the five morphometric variables with the highest loadings separated these two species. Morphological studies on antennal flagellum (and its associated structures) and mouth-parts of female specimens demonstrated significant differences in several structures. Conclusions: The results show that morphological and morphometrical features can be used to discriminate two female isomorphic species, Phlebotomus caucasicus and Phlebotomus mongolensis accurately. 

Characterization of the salivary microbiome in healthy Thai children
Izumi Mashima, Citra F Theodorea, Boonyanit Thaweboon, Sroisiri Thaweboon, Tippanart Vichayanrat, Frank A Scannapieco, Futoshi Nakazawa

Asian Pacific Journal of Tropical Medicine 2019 12(4):163-169

Objective: To investigate the composition of the salivary microbiome of 50 healthy Thai children. Methods: A total 76 provinces in Thailand are grouped into 5 geographical clusters based on unique economics, foods and lifestyles. Geographical locations and the results of an oral assessment were also considered. Genomic DNA was extracted from stimulated sdiva samples. Subsequently, amplicon libraries were prepared by 16S Metagenomic Sequencing Library Preparation. The amplicons were sequenced using an Illumina Miseq platform followed by bioinformatics and statistical analyses. Results: The correlation between oral hygiene status and caries history varied from r2=0.887 to r2=0.999 in the geographical groups, suggesting oral hygiene status a strong association between caries history. Twenty taxonomic groups were found in all subjects and constituted 93.6%-96.5% of the microbiome. Of these, genus Veillonella and Prevotella showed significant differences in their proportions between the geographical groups (P<0.05). Furthermore, the proportion of Veillonella parvula, as well as Rothia aeria and Rothia dentocariosa tended to increase with worse oral hygiene status, which was also related to higher dental caries history. Conclusions: The differences in the salivary microbiome as related to geographic regions suggest that environmental factors, which may include dietary habits, could influence the predominant bacteria found in the mouth of Thai children, especially the genus Veillonella and Prevotella. The ratio of Veillonella parvula, Rothia aeria and Rothia dentocariosa may be indicators of worse oral hygiene status and future caries in this population. 

Wild chive oil is an extremely effective larvicide against malaria mosquito vector Anopheles stephensi
Alireza Sanei-Dehkordi, Moussa Soleimani-Ahmadi, Yaser Salim Abadi, Azim Paksa

Asian Pacific Journal of Tropical Medicine 2019 12(4):170-174

Objective: To assess the chemical composition and mosquito larvicidal potentials of essential oil of wild chive (Allium schoenoprasum L.) against Anopheles stephensi. Methods: In the search for an environmentally safer alternative mosquitoes control, the larvicidal efficacy of essential oil obtained from the leaves of Allium schoenoprasum L. against Anopheles stephensi was determined. The composition of chive essential oil was analyzed by gas chromatography–mass spectrometry. Results: In toxicity assays, the essential oil demonstrated substantial larvicidal activity against larvae of Anopheles stephensi with LC50 and LC90 values of 2.60, and 7.31 ppm after 24 h of exposure, respectively. Gas chromatography–mass spectrometry analysis of chive essential oil identified 35 components representing more than 97.31% of the total essential oil. The main constituents were sulfur compounds, including diallyl trisulfide (13.72%), 2-ethyl[1,3]dithiane (8.93%), allyl methyl trisulfide (8.77%), and trimethylene trisulfide (6.64%), respectively. Conclusions: This study demonstrated that wild chive essential oil has a rich source of eco-friendly bioactive compounds for use as a mosquito larvicide. The main reason for its extraordinary properties may be related to the high percentage of sulfur compounds. 

Misinformation on salt water use among Nigerians during 2014 Ebola outbreak and the role of social media
Ahmed Dahiru Balami, Hadiza Umar Meleh

Asian Pacific Journal of Tropical Medicine 2019 12(4):175-180

Objective: To determine the spread of misinformation on salt water among Nigerians, salt water use for Ebola prophylaxis, and the role played by the social media during the 2014 Ebola outbreak. Methods: Information was collected from the general Nigerian population through online Google forms which were majorly disseminated via Facebook and WhatsApp platforms. The data retrieved was analysed using descriptive statistics, Chi-square test and multivariate logistic regression. Results: A total of 703 questionnaires were included in the final analysis. The respondents’ mean age was (30.2±6.7) years, predominantly male (73.2%). Almost all of them (95.0%) had received some message to use salt water, 37.4% of whom received such message on social media. Around a half of them ever made an attempt to verify the health information they received on social media (50.9%), and about a quarter (24.0%) of them had used salt water during the outbreak. Many of them had used salt water because they believed it would not harm them (52.0%). Salt water was less likely to be used by those who had received such message on social media, as well as by those who had received some contrary information to salt use. Conclusions: Social media could serve as an effective tool in propagating health information and should be actively engaged by health agencies, to spread accurate information. 

Latent tuberculosis infection among medical students in Malaysia
Maha Abdullah, Ummi Nadira Daut, Siti Aishah Daud, Nor Afifi Mohd Romli, Marsitah Abdul Jalil, Noorelina Muhammad, Safarina Mohammad Ismuddin, Masriana Hassan

Asian Pacific Journal of Tropical Medicine 2019 12(4):181-184

Objective: This study aimed to determine prevalence of latent tuberculosis infection among medical students and tuberculosis exposure at the health facilities. Methods: A cross-section of study year 1 (n=68) and year 5 (n=75) medical students in a local university were recruited for latent tuberculosis infection testing using QuantiFERON-TB Gold Plus and a questionnaire analyzed for multivariate risk. Results: The majority of the study were vaccinated with BCG. None of year 1 medical students were positive for latent tuberculosis infection, however, six (8.0%) year 5 students were tested positive for latent tuberculosis infection. A higher incidence of year 5 medical students claimed to be exposed to tuberculosis at health facility (65.3% vs. 4.4%) and a higher percentage reported contact with tuberculosis case over the preceding year compared to year 1 students (30.7% vs. 8.8%). Conclusion: We observed a higher incidence of latent tuberculosis infection and higher exposure to tuberculosis in health facilities among year 5 medical students. Baseline screening and monitoring for progression to tuberculosis infection may benefit tuberculosis management programs. 

Disseminated nocardiosis due to Nocardia otitidiscaviarum: A case report and literature review
Shu-Wei Zheng

Asian Pacific Journal of Tropical Medicine 2019 12(4):185-194

Rationale: Disseminated nocardiosis due to Nocardia otitidiscaviarum is rarely reported in immunocompetent hosts. Patient concerns: A 59 year old male patient complained of painful soft tissue swellings and fever for two days. Diagnosis: Disseminated nocardiosis due to Nocardia otitidiscaviarum. Interventions: Initial antimicrobial therapy with imipenem and trimethoprim/sulfamethoxazole was switched to 6 weeks of trimethoprim/sulfamethoxazole, linezolid and tigecycline after sensitivity test results were available. Thereafter, the patient was switched to maintenance trimethoprim/sulfamethoxazole and moxifloxacin. Prednisolone was gradually tapered. Outcomes: Soft tissue swelling and pain disappeared and the patient was discharged uneventfully. Lessons: Disseminated nocardiosis due to Nocardia otitidiscaviarum should be suspected in immunocompetent hosts with risk factors such as medication with prednisolone. Early identification of the causative species and susceptibility results is crucial given the diverse resistance patterns amongst various Nocardia species. 

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Fwd: Pediatric Cardiology

Pediatric Cardiology

High blood pressure in children: The invisible dragon
Sivasubramonian Sivasankaran

Annals of Pediatric Cardiology 2019 12(2):73-76

Improvement of cardiopulmonary function after minimally invasive surgical repair of pectus excavatum (Nuss procedure) in children
Bibhuti B Das, Michael R Recto, Thomas Yeh

Annals of Pediatric Cardiology 2019 12(2):77-82

Background: Severe pectus excavatum in children may result in cardiorespiratory functional impairment; therefore, we evaluated cardiopulmonary response to exercise before and after the Nuss procedure. Methods: Twenty-four physically active pediatric patients aged 9–18 years with severe pectus excavatum (Haller index >3.25) were included in the study. Cardiopulmonary exercise testing using treadmill and modified Bruce protocol was performed before and after the Nuss procedure. Results: Maximal oxygen uptake and oxygen pulse improved by 40.6% (32 ± 13–45 ± 10 ml/kg/min; P = 0.0001) and 44.4% (9 ± 4–13 ± 5 ml/beat; P = 0.03), respectively, after surgical correction of pectus excavatum by Nuss procedure. Significant improvement in maximum voluntary ventilation and minute ventilation after Nuss procedure was also noted. Conclusions: We found that, after repair of pectus excavatum by Nuss procedure, the exercise capacity as measured by maximal oxygen consumption improved significantly primarily due to increase in oxygen pulse, an indirect measurement of stroke volume. 

Modulation of plasma triglycerides concentration by sterol-based treatment in children carrying different genes
Ismael San Mauro Martín, Sara Sanz Rojo, Elena Garicano Vilar, Luis Collado Yurrita, Javier Andrés Blumenfeld Olivares

Annals of Pediatric Cardiology 2019 12(2):83-89

Background: Dyslipidemias have increased during the last decades in children. Aim: The objective of this study was to analyze the influence of different polymorphisms in plasma triglyceride levels of children following a dietary treatment with plant sterols. Design: A randomized, double-blind, crossover, controlled clinical trial was carried out in 26 children (16 women). Materials and Methods: Commercial milk, with 2.24 g sterols, was ingested daily during 3 weeks , and the same amount of skimmed milk without sterols, during the 3 week placebo phase. Both phases were separated by a washout period of 2 weeks. At the beginning and end of each phase, blood draws were performed. Results: Apolipoprotein A5 Ser19Trp (P = 0.002), peroxisome proliferator-activated receptor-alpha L162V (P = 0.003), APOE APOE2/3/4 (P = 0.012), and APOE APOE2,3,4 (P = 0.025) show statistically significant differences between their haplotypes in plasma triglyceride levels. Other genes did not show statistically significant differences. Conclusions: Further studies are needed to establish which genotype combinations would be the most protective against hypertriglyceridemia. 

Prevalence of hypertension and prehypertension in schoolchildren from Central India
Ashish Patel, Anil Bharani, Meenakshi Sharma, Anuradha Bhagwat, Neepa Ganguli, Dharampal Singh Chouhan

Annals of Pediatric Cardiology 2019 12(2):90-96

Background: Epidemiological transition with increasing burden of cardiovascular risk factors is evident not only in adults but also in children. The data on the prevalence of prehypertension and hypertension in children show large regional differences in India and such data are not available from Central India. We, therefore, conducted a large cross-sectional study in Indore to determine the distribution of blood pressure (BP) and the prevalence of hypertension and prehypertension among schoolchildren. Methods: A total of 11,312 children (5305 girls, 6007 boys) aged 5–15 years, drawn from 80 government and private schools in equal proportion, were evaluated. Anthropometric measurements were obtained and BPs were measured using The Fourth Report on The Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents as reference standard. BP ≥90th to <95th percentile for given percentile of height was considered as prehypertension, whereas any BP ≥95th percentile was defined as hypertension. Multiple linear regression analysis was used to find out the determinants of hypertension in these children. Results: Prehypertension was detected in 6.9% and 6.5% and hypertension was found in 6.8% and 7.0% of boys and girls, respectively. Height and weight were found to be a significant predictor of systolic and diastolic BP among both boys and girls. Conclusions: Our results show a high prevalence of prehypertension and hypertension in Indore schoolchildren with age and height being significant determinants. This highlights the need for routine BP measurements in children by pediatricians when they treat them for intercurrent illnesses or vaccinate them. It should also be mandatory as a part of school health checkup programs to detect childhood hypertension for further counseling and therapy. 

Acetaminophen in low doses for closure of the ductus arteriosus of the premature
Adriana Furletti Machado Guimarães, Fátima Derlene Rocha Araújo, Zilda Maria Alves Meira, Henrique Assis Fonseca Tonelli, Guilherme Gomes Duarte, Lívia Castro Ribeiro, Gabriele Queiroz Monteiro Rezende, Sandra Regina Tolentino Castilho

Annals of Pediatric Cardiology 2019 12(2):97-102

Objective: The objective of the study is to report the experience with acetaminophen in low doses as an alternative to the treatment of the ductus arteriosus of the preterm newborn. Materials and Methods: Retrospective study including preterm newborns with patent ductus arteriosus who received oral acetaminophen because treatment with indomethacin had failed or is contraindicated. A dosage consisted of a first dose of 25 mg/kg and maintenance doses of 30 mg/kg/day, for 3 to 7 days. A second cycle was administered in cases of reopening of the ductus arteriosus. The rates of ductal closure and surgery were calculated. Patients were categorized into responder and nonresponder groups for acetaminophen, and the average values of ductal diameter, weight, gestational age, and postnatal age were compared. Results: Eighty-seven preterm newborns, with a postnatal age from 3 to 27 days, with average values of ductus arteriosus equal to 2.5 ± 0.8 mm/kg, gestational age 27.2 ± 1.9 weeks, and birth weight 888.9 ± 241 g, received acetaminophen for 3 to 7 days. A second cycle was administered in 15 preterm newborns. The ductus closure rate, after one or two cycles, was 74.7%, and the recommendations for surgical closure were progressively reduced from 50% in the 1 st year to 6.2% in the past year. Lower ductal closure rate occurred in the group of newborns with the lowest average weight (P = 0.018), the highest average ductal diameter (P = 0.002), and the lowest average gestational age (P = 0.09). Postnatal age at the start of acetaminophen use was shown to be irrelevant regarding the treatment (P = 0.591). Conclusions: Acetaminophen in low doses showed to be an effective alternative for the closure of the ductus arteriosus for preterm newborns in whom treatment with indomethacin or ibuprofen failed or was contraindicated. 

Atrioventricular septal defect and tetralogy of Fallot – A single tertiary center experience: A retrospective review
Khaled A Alhawri, Colin J Mcmahon, Mohammed M Alrih, Yamin Alzein, Asad A Khan, Suhaib K Mohammed, Khaled S Alalwi, Kevin P Walsh, Damien P Kenny, Jonathon G McGuinness, Lars Nolke, John M Redmond

Annals of Pediatric Cardiology 2019 12(2):103-109

Background: Complete atrioventricular septal defect (CAVSD) in association with tetralogy of Fallot is a rare and complex disease that makes its repair more difficult than repair of either lesion alone. We reviewed retrospectively our experience in managing this lesion. Patients and Methods: Between February 2006 and May 2017, 16 patients who underwent repair of CAVSD/tetralogy of Fallot (TOF) were reviewed retrospectively. Fifteen patients had trisomy 21. Five patients underwent primary repair while eleven patients went for staged repair in the form of right ventricular outflow tract (RVOT) stenting (n = 9) or systemic to pulmonary (S-P) surgical shunt (n = 2). RVOT stenting has replaced surgical shunt since 2012 in our center. Early presentation with cyanosis was the main determinant factor for staged versus primary repair. Results: The median age at first palliation was 46 days (range 15–99 days). The median age at total repair for both groups was 6 months (range 3–18 months); the median age for the palliated patients was 6.5 months (range 5–18 months) while the median age for primary repaired patients was 5 months (range 3–11 months). The median weight at final repair was 6.9 kg (3.7–8.2 kg). The pulmonary valve was preserved in five patients (31%), four of them had no prior palliation. Chylothorax occurred in 50% of the patients. One late mortality occurred after final repair due to sepsis. Conclusion: CAVSD/TOF can be repaired with low mortality and morbidity. The use of RVOT stent has replaced the surgical (S-P) shunt with acceptable results in our center. 

A new low-cost method of virtual cardiac dissection of computed tomographic datasets
Saurabh Kumar Gupta, Diane E Spicer, Robert H Anderson

Annals of Pediatric Cardiology 2019 12(2):110-116

Computed tomography has an established role in the evaluation of a variety of cardiac disorders, including congenital heart diseases. The current generation of high-speed scanners produces volumetric data at low doses of radiation. The interpretation of cardiac anatomy, however, is generally limited to multiplanar assessment of two-dimensional images. The volume rendering technique provides an excellent three-dimensional demonstration of external morphology but offers little information about the intracardiac anatomy. The alternative approach of virtual cardiac dissection, which is a modification of volume rendering, on the other hand, provides crucial insights regarding the intracardiac anatomy. At present, virtual cardiac dissection requires expensive software packages. These software packages are not available in all countries, thus limiting its use in routine clinical care. We present here the details of a newly developed technique that permits virtual cardiac dissection using a personal computer and open-source software. Our technique involves no additional cost and can be achieved in the comfort of the office or operating room of the cardiologist, radiologist, or cardiac surgeon. This enhanced three-dimensional visualization of intracardiac anatomy will surely improve the understanding of the morphological details of both normal and malformed hearts. In addition, by permitting assessment in projections with which modern-day cardiologists and cardiac surgeons are conversant, it is likely to improve clinical decision-making. We illustrate here its potential utility in the morphologic assessment of the atrial septum and its deficiencies, along with malformations of the ventricular outflow tracts, including common arterial trunk. 

Isolation of the left brachiocephalic artery revisited: A 52-year literature review and introduction of a novel anatomic-clinical-prognostic classification
Elaheh Malakan Rad, Hamid Reza Pouraliakbar

Annals of Pediatric Cardiology 2019 12(2):117-129

Isolation of the left brachiocephalic artery (ILBA) is an extremely rare anomaly of aortic arch with diverse manifestations in the neurologic system, heart, and left upper arm. This anomaly is defined as the absence of connection of the left brachiocephalic artery (LBA) to aortic arch and connection of LBA to pulmonary artery (PA) through a patent arterial duct (PAD). However, this definition is not inclusive of all cases. Not only are there inconsistencies in the definition and terminology of this aortic arch anomaly but also there is no classification for this anomaly despite its heterogeneous nature in terms of anatomy, clinical presentation and prognosis. We performed a 52-year comprehensive literature review in the period between 1966 and 2018. Our inclusion criteria were any manuscript that included a case report or case series, with confirmed diagnosis of ILBA. All quantitative data were analyzed using descriptive analysis by SPSS version 21 (IBM SPSS Statistics, USA). Results were presented as mean ± standard deviation and median. Based on the presence or absence of connection of LBA to PA and the number of sources of steal from the LBA, we classified ILBA into three types: single-steal type with no connection of LBA to PA and single source of blood flow steal from LBA through the left subclavian artery (LSCA), double-steal type with connection of LBA to PA through PAD and two sources of steal through LSCA and arterial duct (AD), and triple-steal type with bilateral PADs and therefore, three sources of blood flow steal from LBA including the LSCA and the double ADs. Patients with single-steal type have the best prognosis and present latest with symptoms of cerebrovascular insufficiency or left arm claudication. The oldest reported patient was 69 years of age with symptoms of dizziness and near syncope. No death was reported in these patients. Double-steal type is the most common type and is often associated with genetic syndromes and/or extracardiac anomalies. Triple-steal type is the rarest type with the earliest presentation and worst prognosis. The oldest reported patient was 60 days of age. All reported cases had cardiac symptoms, pulmonary overcirculation, pulmonary hypertension, and fatal outcome. 

Use of the Abbott EnSite Precision three-dimensional mapping system for the placement of an atrial pacemaker lead in a patient with congenital heart disease
Christian Paech, Dirk Schnappauf, Tim Gehre, Franziska Wagner, Roman Antonin Gebauer

Annals of Pediatric Cardiology 2019 12(2):130-131

We report the use of the Abbott three-dimensional mapping system (EnSite Precision) for the placement of an atrial pacemaker lead in a patient after modified Fontan procedure. The mapping system was used for the identification of a promising pacing site in the complexly modified right atrium and to visualize the successful placement of an atrial lead at the same spot. 

The matter of "unbalance" in right dominant atrioventricular septal defect
Ignacio Lugones, María Fernanda Biancolini, Germán Lugones, Julio César Biancolini, Ana M S de Dios

Annals of Pediatric Cardiology 2019 12(2):132-134

Unbalance in atrioventricular septal defect can be found in more than one anatomic level and in different degrees at each level. The definition of “unbalance” has historically been focused in comparing the dimensions of main cardiac structures, such as the atrioventricular valve and the ventricles. However, the hemodynamic aspects of unbalance need to be considered as having, at least, similar relevance. New concepts and already described parameters must be combined and understood as a whole to help the surgical decision-making process. 

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Fwd: Anesthesiology


Ambulatory Surgery Center Medical Director: Visionary Leader

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Michael Guertin, Jarrett Heard, Timothy Del Rosario

Value-Based Payment in Ambulatory Anesthesia: MACRA, MIPS, and More

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Douglas G. Merrill

Outcomes in Ambulatory Anesthesia: Measuring What Matters

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Leopoldo V. Rodriguez, Joshua A. Bloomstone, Gerald A. Maccioli

Quality Improvement in Ambulatory Anesthesia: Making Changes that Work for You

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Christopher J. Jankowski, Michael T. Walsh

Advancing the Safe Delivery of Office-Based Dental Anesthesia and Sedation: A Comprehensive and Critical Compendium

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Mark A. Saxen, James W. Tom, Keira P. Mason

Office-Based Anesthesia: A Comprehensive Review and 2019 Update

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Brian M. Osman, Fred E. Shapiro

Nonoperating Room Anesthesia: Anesthesia in the Gastrointestinal Suite

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Sekar S. Bhavani, Basem Abdelmalak

Pediatric Ambulatory Anesthesia Challenges

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Steven F. Butz

Regional Anesthesia for Ambulatory Anesthesiologists

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Alberto E. Ardon, Arun Prasad, Robert Lewis McClain, M. Stephen Melton, Karen C. Nielsen, Roy Greengrass

Anesthesia for Same-Day Total Joint Replacement

Publication date: June 2019

Source: Anesthesiology Clinics, Volume 37, Issue 2

Author(s): Adam W. Amundson, Jason K. Panchamia, Adam K. Jacob

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Fwd: Health Research and Reviews

Health Research and Reviews

Is coconut oil good for oral health? A review
Faizal C Peedikayil

Journal of Health Research and Reviews 2019 6(1):1-4

Oral health is considered to be of prime importance to all individuals in maintaining good health, and the accepted method of oral hygiene maintenance is mechanical method of tooth cleaning. At present, chemotherapeutic agents are also used as adjutants to reduce plaque formation, but they have their own disadvantage. This has paved the way for the use of natural and plant derivatives as alternatives for chemotherapeutics in dentistry. Coconut oil is considered as a tree of life in ancient literature and is used for any ailments. Coconut oil is edible and is consumed as a part of the staple diet in many countries. It also has medicinal and cosmetic properties. Coconut oil differs from most other dietary oils because of the high content of medium chain fatty acid (MCF), whereas in the majority of other oils, the basic building blocks are almost entirely long chain fatty acids. The MCF in coconut oil such as lauric, caproic, caprylic, myristic, and stearic acid influences the physical and chemical properties. Lauric acid, which is predominant in coconut oil, has proved to have antimicrobial, antiviral, and anti-inflammatory action. Of late, few studies have been conducted by researchers regarding the action of coconut oil on oral health. The review of literature shows excellent results on the use of coconut oil on oral health. This short review discusses the studies conducted on coconut oil on oral microorganisms and anti-inflammatory actions. 

Epidemiology and antibiotic sensitivity pattern of asymptomatic bacteriuria during pregnancy: A cross-sectional study
Narayana Goruntla, Sandhya Jampala, Vijayajyothi Mallela, Vishnuvandana Bandaru, Rajavardhana Thamineni, Pradeepkumar Bhupalam

Journal of Health Research and Reviews 2019 6(1):5-10

Background: Asymptomatic bacteriuria (ASB) during pregnancy is associated with significant maternal and fetal complications. Continuous monitoring of antibiotic sensitivity pattern of bacterial isolates is required for appropriate management of ASB. Aims: The study aims to assess the prevalence, risk factors, and antibiotic sensitivity profile of ASB during pregnancy. Materials and Methods: A cross-sectional, hospital-based study was conducted in the pregnant women attending Obstetrics and Gynecology Department of a tertiary care hospital. A suitably designed data collection form was used to collect sociodemographic profile, obstetric history, and illnesses suffering from the participants. Urine specimens of the participants were processed for isolation and identification of bacterial species. Kirby–Bauer disc diffusion test was used to screen antibiotic sensitivity of the isolated bacteria. Statistical Analysis: Descriptive statistics were used to represent the sociodemographic data. Chi-square test was used to associate risk factors for the development of ASB during pregnancy. Results: A total of 1332 women were participated in the study. The prevalence of ASB among pregnant women was 86 (6.4%) and Escherichia coli (58; 67.4%) was the most predominant bacteria. Meropenem, cephalosporin's, and gentamycin were shown higher sensitivity in ASB. Advanced age, illiteracy, rural residency, multigravida, multiparity, history of abortion, and medical illnesses were strongly associated to develop ASB during pregnancy. Conclusion: E. coli were the most predominant isolated uropathogen in ASB. The study observed that there is a wide variation in the antibiotic sensitivity pattern of isolated organisms. Hence, there is a need of routine urine culture sensitivity screening in pregnant women for rational use of antibiotics and to reduce the antibiotic resistance. 

A comparative study of the hazards management system associated with laundry operations in secondary and Tertiary Health Facilities in Nigeria
Emmanuel Nosa Omoijiade

Journal of Health Research and Reviews 2019 6(1):11-16

Background: Occupational safety and health hazards in health-care facilities (HCFs) can be grouped according to location or service offered. Contaminated laundry, noise, heat, lifting, sharps, slips, trips, falls, and fire hazards are among those located in the laundry department. Aims: This study sought to assess the measures to reduce workplace hazards, thereby providing information on the hazard management system in various HCFs, as this would prove useful to establish appropriate interventions to further ensure the health and safety of workers in hospital laundries. Materials and Methods: The study was conducted in six hospitals with a laundry department in Benin city, composed of one available tertiary HCF and five secondary HCFs. Data were collected through the hazard identification checklist, which was used to determine the safe/unsafe acts and conditions of the workplaces. Results: The percentage rating for the assessment of the hazard management system in the hospital laundry between the health facility types was 39.57% ± 7.12% for the secondary health facilities, while that of the tertiary health facility was 51.85%. A comparison of the means showed that there was no statistically significant difference in the average rating between secondary and tertiary health facility (P = 0.191), (95% confidence interval = −0.339–0.094). Conclusion: Adverse health and safety effects can be avoided or minimized drastically if the associated hazards are properly managed; however, the hazards management system in the health-care laundries was adjudged to be substandard, in both the tertiary and secondary health facilities. 

Assessment of plasma iron, transferrin alanine, and aspartate transaminase in amoxicillin overdose supplemented with raw cucumber juice
Mathew Folaranmi Olaniyan, Deborah Bukunmi Adepoju

Journal of Health Research and Reviews 2019 6(1):17-21

Background: Raw cucumber (Cucumis sativus) fruit juice contains substances of health-promoting bioactivities. Elevated plasma alanine transaminase (ALT/serum glutamate-pyruvate transaminase), aspartate transaminase (AST/serum glutamic oxaloacetic transaminase), iron, and decreased transferrin could indicate hepatotoxicity, hepatitis, and kidney and liver damage, which could be drug induced. Aim and Objective: This work was designed to determine the benefits of cucumber fruit juice as a natural antidote in amoxicillin-induced hepatotoxicity by assessing the plasma iron, transferrin alanine, and AST in amoxicillin overdose supplemented with raw cucumber juice. Materials and Methods: Fifteen rabbits of the same sex weighing 0.9–1.4 kg divided into three groups of five rabbits each were used for the study. Group A – five control rabbits; Group B – five rabbits given 30 mg/kg body weight (BW) subcutaneous injection of amoxicillin every 24 h for 7 days which was followed by 30 ml raw cucumber fruit juice supplementation for 14 days; and Group C – five rabbits given 30 mg/kg BW subcutaneous injection of amoxicillin every 24 h and raw cucumber fruit juice supplementation for 14 days simultaneously. Plasma ALT, AST, iron, and transferrin were determined in the rabbits by spectrophotometry and enzyme-linked immunosorbent assay. Results: The results obtained showed a significant increase in plasma ALT, AST, and iron and a significant decrease in plasma transferrin when the rabbits in Group B were given 30 mg/kg BW subcutaneous injection of amoxicillin (B2 samples) compared with the results obtained from their basal samples (B1) and control rabbits (A) and when they were given 30 ml of raw cucumber fruit juice supplementation (B3 samples) (P < 0.05). The results obtained showed a significant decrease in plasma ALT, AST, and iron and a significant increase in plasma transferrin when the Group B rabbits were given 30 ml of raw cucumber fruit juice (B3 sample) than when they were given subcutaneous injection of amoxicillin (B2 samples) (P < 0.05). Conclusion: This work revealed significant biochemical alterations in the values of iron, transferrin, AST, and ALT when given 30 mg/kg BW subcutaneous injection of amoxicillin and supplementation of raw cucumber fruit juice. Cucumber juice is therefore beneficial as a possible antidote to amoxicillin-induced hepatotoxicity. 

Analysis of drug utilization pattern of antimicrobials used as surgical prophylaxis for general surgical procedures in a Tertiary Care Hospital of North Karnataka: An observational study
Bhagyashree S Patil, Anant Mahaveer Khot, Aravind V Patil, Akram A Naikwadi

Journal of Health Research and Reviews 2019 6(1):22-25

Background: Surgical site infection (SSI) is an infection presenting within 30 days after the surgical procedure if no prosthetic is placed and up to 1 year if prosthetic is implanted in the patient. Despite standard protocols for preoperative preparation and antimicrobial prophylaxis, the rate of SSI varies from 2.5% to 41.9%. Reasons could be multifactorial, but one among them is lack of adherence to any of the antibiotic policy. To review the drug utilization pattern of antimicrobials in the perioperative period and to study its impact on SSI, the above study has been carried out. Materials and Methods: A cross-sectional, observational study has been carried out in the Department of General surgery of SBM Patil Medical College Hospital. Patients of either sex who underwent surgical procedures such as appendectomy and hernioplasty have been included in the study. Data were collected using a predesigned pro forma. The study was approved by the institutional ethics committee. Results: A total of 140 patients underwent surgical procedures, of which 70 were male and 70 were female. Open appendectomy was the most common procedure performed, followed by hernioplasty in 18 patients. Ceftriaxone–sulbactam was the frequently prescribed antibiotic and six patients developed SSI. Conclusion: Despite use of antibiotics, six patients developed SSI. Hence, auditing of the antimicrobial usage as surgical prophylaxis is need of the hour. Because prescriber's worldwide running out of antibiotic options, it is mandatory for each hospital to have formulary for antibiotic use depending on the pattern of organisms isolated. 

Beta-cell function and insulin resistance among First-Degree relatives of persons with type 2 diabetes in a Northwestern Nigerian Population
Yakubu Lawal, Fatima Bello, Felicia Ehusani Anumah, Adamu Girei Bakari

Journal of Health Research and Reviews 2019 6(1):26-30

Background and Aims: Pancreatic beta-cell deficit and insulin resistance (IR) form two major factors in the etiopathogenesis of type 2 diabetes. The aim of this study is to assess beta-cell function and IR among first-degree relatives (FDRs) of persons with type 2 diabetes in a Northwestern Nigerian population. Other objectives include assessing the relationships among HOMA-%B, HOMA-IR, plasma glucose levels, and some obesity indices and to determine whether beta cell function, IR, and some obesity indices are independent determinants of glucose intolerance in the studied population. Materials and Methods: A total of 200 individuals and 200 controls were recruited through cluster sampling from their respective communities after due consent. The relevant biodata was documented and appropriate examinations including anthropometric measurements were carried out. Oral glucose tolerance test was carried out and fasting plasma insulin levels were also measured. IR and beta-cell function were calculated using homeostasis model assessment (HOMA) method. Results: Mean HOMA-IR was higher while HOMA-% B lower among FDRs compared to controls. Significant independent determinants of glucose intolerance with odds ratio (OR) and confidence interval (CI) included age (OR = 1.9, CI 1.9–2.0, P = 0.002), body mass index (OR = 1.9, CI 1.8–2.0, P = 0.032), waist circumference (OR = 2.0, CI 1.9–2.0, P = 0.043), waist-to-hip ratio (OR = 1.1, CI 1.0–15.7, P = 0.022), HOMA-IR (OR = 3.0, CI 2.3–3.3, P < 0.001), and HOMA-B (OR = 0.43, CI 0.24–0.65, P < 0.001) which means HOMA-%B is protective against glucose intolerance with inverse OR of 1/0.43 = 2.3. Conclusions: IR was higher and beta cell functions lower among FDRs compared to controls. IR (HOMA-IR) and some obesity indices were significant determinants of glucose intolerance while HOMA-%B was protective against glucose intolerance in this study. 

Mixed adenoneuroendocrine carcinoma: A report of four cases from South India
Saravanakumari Vijayakumar, Sajini Elizabeth Jacob, Bhawana Ashok Badhe, Bheemanathi Hanuman Srinivas

Journal of Health Research and Reviews 2019 6(1):31-35

Neuroendocrine tumors (NET) are rare. Common sites of NETs are the gastrointestinal tract and pancreas. In 2010, the World Health Organization classified NETs into mixed adenoneuroendocrine carcinoma, neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma (MANEC), tumors that have both exocrine and endocrine components of at least 30% each. Since it is relatively a new entity, only case reports and case series are available. In the past 7 years, there were only eight reports from India. We report a further four cases of this nascent disorder from a single institution, obtained retrospectively. The first includes an elderly man with upper gastrointestinal symptoms and underwent subtotal gastrectomy for antropyloric growth, which was a low-grade MANEC. The second was a female patient with chronic pancreatitis and presented with obstructive jaundice due to an ampullary growth. Whipple's specimen showed an intermediate-grade MANEC. The third case was a 40-year-old female with caecal growth and ovarian mass and was found to have a low-grade MANEC. The fourth, also in a female, was a case of abdominal wall abscess with an intraabdominal connection to the intestine and she had omental deposits and high-grade MANEC. The pathological findings are discussed and compared other reports from the country. 

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Fwd: Applied Hematology

Applied Hematology

Management of Glanzmann's Thrombasthenia – Guidelines based on an expert panel consensus from gulf cooperation council countries
Ahmad Tarawah, Tarek Owaidah, Naima Al-Mulla, Muhammad Faisal Khanani, Jehan Elhazmi, Muneer Albagshi, Yaser Wali, Shikah AlMohareb, Abdulkareem Almomen

Journal of Applied Hematology 2019 10(1):1-9

Glanzmann thrombasthenia is a rare disorder, due to quantitative and/or qualitative abnormalities of the platelet integrin αIIbβ3 and/or αIIbβ3. Although it is considered a rare disorder with a global incidence of 1/1,000,000 population, the case is different at the Gulf Cooperation Council countries, where prevalence rate as high as 1/40,000 in Madinah, Saudi Arabia. This makes it necessary to develop patient's management guidelines. Due to limited resources in the literature, experts' consensus was important to develop such guidelines. Experts panel elected to use recombinant activated factor VII (rFVIIa) as the first line of treatment of acute bleeds and reserve platelets transfusion for nonresponding patients or severe bleeds, rFVIIa at high dose (270 μg/kg body weight) may tried upfront. rFVIIa may be tried as prophylactic treatment in patients with frequents bleeds. Experts panel elected to allow girls with Glanzmann thrombasthenia to have menstruation and to adapt a special protocol for this purpose (Madinah protocol). Pregnancy should be managed carefully, where normal delivery encouraged under coverage of rFVIIa. Risk of bleeding should be expected in neonates. Minor surgeries and dental workup can be managed under coverage of rFVIIa. Glanzmann thrombasthenia patients with severe disease should be encouraged for hematopoietic stem cell transplant.

Preponderant use of fresh-frozen plasma in children despite weaker evidence
Manish Raturi, Shamee Shastry, Poornima B Baliga

Journal of Applied Hematology 2019 10(1):10-14

BACKGROUND: Considering the higher use of fresh-frozen plasma (FFP) in our hospital, we desired to determine the pattern, prevalence, and potential complications of its utilization in new-born and children with the primary aim to observe its effect on the conventional coagulation screening (CCS) parameters. SUBJECTS AND METHODS: Patients' demographics, clinical indications, and pre- and posttransfusion CCS parameters such as the prothrombin time, the international normalized ratio (INR), and partial thromboplastin time were observed over a period of 10 months. Any improvement observed in the laboratory parameters after FFP transfusion was noted. RESULTS: We studied 433 episodes, where 499 FFP units were utilized in 184 patients. Mean age in years was 6 ± 0.16 (new-born to 17). Diagnoses-wise majority had diffuse intravascular coagulation with sepsis 25% (46/184) followed by febrile illness 23% (42/184). Around 46% (84/184) patients had bleeding episodes of which four had known family history of bleeding (three factors IX and one factor XI deficiency). Mean doses of FFP utilized (mL/kg) in children and infants were 12.6 ± 6.3 (n = 297 episodes) and 14.4 ± 6.3 (n = 136 episodes), respectively (P = 0.006). Mean change in INR in the cohort with deranged coagulation parameters against the overtly bleeding cohort was 0.85 versus 0.40 (P = 0.006). CONCLUSION: The study elicits minimal evidence in correcting the coagulation parameters, especially in the infants, whenever FFP was transfused prophylactically. Joint-decision making of the pediatricians and transfusion medicine physician would promote judicious use in children.

Ferritin and Vitamin D levels and its relation to bone diseases in thalassemic adults: A hospital-based retrospective cohort study
Reem Jameel Tharwat, Saud Balilah, Hatem M Habib, Nada H Mahmoud, Fatema S Beek, Fatema K Almadani, Sarah A Elmaghraby, Duha D Al-Loqmani, Hibah A Al-Mahdi

Journal of Applied Hematology 2019 10(1):15-22

BACKGROUND: Thalassemia complications affecting different body systems, including osteoporosis and bone fracture. Although numerous studies are available in the literature, little is known about this subject in Saudi Arabia. OBJECTIVES: The study aimed to describe the characteristics of thalassemia patients in Madinah City, Saudi Arabia and to assess the prevalence of bone disease among them with an emphasis on Vitamin D and Ferritin level. SUBJECTS AND METHODS: A hospital-based retrospective cohort study was designed. The study was carried out on 69 &#946; thalassemia patients from King Fahd Hospital in Madinah, Saudi Arabia from 2015 to 2017. The study extracted patients&#39; data related to their personal, clinical, laboratory, and complications. Data on DEXA scan were also obtained for 20 of the studied patients. The prevalence rate of bone fracture among the studied patients was calculated, and other collected data were tabulated in number and percentage for categorical variables and mean and standard deviation for quantitative variables. RESULTS: All the studied patients were of &#946; thalassemia patients. Two-thirds of them were anemic (66.7&#37;). The prevalence of bone fractures was 14.5&#37; (95&#37; confidence interval &#61; 8.1&#8211;24.7), iron overload of &#62;1000 was found in 62 patients (89.9&#37;) and ferritin level of &#60;10 ng was found in 19 patients (27.5&#37;). Vitamin D level was ranging from 10 to 24 ng in 39.1&#37; and from 25 to 80 ng in 11.6&#37; of studied patients. Furthermore, the Z score value was <&#8722;2 of the spine in 83.7&#37; of 20 patients underwent DEXA scan in our study. Among these 20 patients, the mean Z score value of the femur was &#8722; 2.1. CONCLUSIONS: The prevalence of bone fracture among thalassemia patients in Madinah City, Saudi Arabia was relatively high accounting for 14.5&#37; of the studied patients. Low level of Vitamin D and high iron overload and ferritin level was prevalent among the studied patients. Further studies from multiple centers and cities are needed to more understanding of this important issue.

CD14 as a potential prognostic factor and Bcl-2 as a therapeutic target in egyptian B-Cell chronic lymphocytic leukemia patients
Mohamed Mahmoud El-Khawanky, Mohamed Hanfy Morsy, Amina Mohamed Elnaggar, Ola Ali Hussin, Mohga Mahmoud Zaewer, Naglaa Ali Khalifa

Journal of Applied Hematology 2019 10(1):23-28

INTRODUCTION: B-cell chronic lymphocytic leukemia (B-CLL) is a unique lymphoproliferative disorder that scarcely occurs under the age of 40. B-CLL represents a neoplastic disorder caused primarily by defective programmed cell death and accompanied by a myriad of cellular and humoral immune defects. AIM: This study aimed to assess Bcl-2 and CD14 expression in B-CLL patients and their study as probable prognostic and therapy targeting factors. PATIENTS AND METHODS: In this study, we assessed Bcl-2 and cluster of differentiation (CD14) expression in a group of Egyptian patients with B-CLL. Forty B-CLL patients and 20 apparently healthy individuals served as the control group were included in this study. STATISTICAL ANALYSIS: SPSS statistical software (IBM SPSS Inc., version 20, Chicago, Illinois, USA) was used for statistical analysis. RESULTS: Aberrant expression of Bcl-2 protein appeared in all B-CLL patients (100&#37;). Bcl-2 expression showed a highly positive correlation with total lymphocyte count and lymphocyte count (P &#61;0.000 for both) and a positive correlation with lactate dehydrogenase (P &#61; 0.044). The expression of myelomonocytic antigen &#8220;CD14&#8221; above the cutoff value 5 &#215; 109/L was reported in 70&#37; (28/40) of B-CLL patients, 55.6&#37; (10/18) of the intermediate-risk group, and 81.8&#37; (18/22) of high-risk group. CONCLUSION: There was a significant increase in Bcl-2 protein and CD14 in B-CLL patients. Bcl-2 was highly increased in all patients and CD14 more observed in the high-risk group than that of the intermediate risk group.

Seroprevalence of hepatitis B virus in blood donors at a large teaching hospital of Pakistan: A potential health policy concern
Sikander Abdullah, Sarmad Zahoor, Muhammad Ahmad Rao, Syed Maaz Abdullah, Sadia Asif, Abdul Wajid, Abdul Rehman Zia Zaidi

Journal of Applied Hematology 2019 10(1):29-32

BACKGROUND: Hepatitis B is an important public health problem for Pakistan. Being asymptomatic in many of the carriers, it needs screening to assess disease burden. Screening blood donors will not only help point out the subliminally diseased individuals but will also offer a boost to treatment rates and preclude the dreaded complications in the affected population. AIM: The aim of this study is to estimate disease burden and depict current trend of Hepatitis B in healthy blood donors by assessing its prevalence at one of the largest hospitals of Pakistan over a 2-year interval. This will serve to offer a direction to health policymakers to channel their resources in an attempt to accelerate diagnostic, preventive, and therapeutic measures against the disease. METHODOLOGY: It is a retrospective single-center cross-sectional study. We screened 76,530 healthy blood donors for hepatitis B virus (HBV) visiting Mayo Hospital, Lahore, Pakistan during 2016 and 2017 with rapid test kits which used lateral flow immunoassay based on the principle of double antibody sandwich technique. RESULTS: Out of 76,530 donors in 2016 and 2017, we detected 1262 donors (1.65&#37;) positive for hepatitis B viral serology. CONCLUSION: We found a positivity rate of 1.65&#37; of hepatitis B in healthy blood donors during 2 years. Although in comparison to 2016, the positivity rate has somewhat declined in 2017, but it remains worrisome. Our findings endorse the need for policy making to sustain and amplify the current HBV screening and treatment strategies and enhance public awareness.

First report of coexistence of sickle cell disease and neurofibromatosis Type 1 in a Saudi patient with family history of neurofibromatosis Type 1
Nawaf Alanazi, Ibrahim Almubarak, Zainab Almoosa, Zafar Iqbal

Journal of Applied Hematology 2019 10(1):33-35

Sickle cell disease is highly prevalent in Saudi Arabia, especially in the eastern and southern regions of the country. Neurofibromatosis Type 1 is one of the most common autosomal dominant disorders. In our case, we report a coexistence of both these diseases in a 15-year-old girl. This coexistence has never been reported in literature. Clinical manifestations of both the diseases and their possible link with each disease are discussed.

Acute myelomonocytic leukemia demonstrating erythrophagocytosis on cerebral spinal fluid cytology
Hiu Lam Agnes Yuen, Jake Shortt

Journal of Applied Hematology 2019 10(1):36-36

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Fwd: Apoptosis


Role of glycogen synthase kinase following myocardial infarction and ischemia–reperfusion

Cellular responses of BRCA1 -defective HCC1937 breast cancer cells induced by the antimetastasis ruthenium(II) arene compound RAPTA-T


An organometallic ruthenium(II) arene compound, Ru(η6-toluene)(PTA)Cl2 (PTA = 1,3,5-triaza-7-phosphaadamantane), termed RAPTA-T, exerts promising antimetastatic properties. In this study, the effects of RAPTA-T on BRCA1-defective HCC1937 breast cancer cells have been investigated, and compared to its effects on BRCA1-competent MCF-7 breast cancer cells. RAPTA-T showed a very low cytotoxicity against both tested cells. Ruthenium is found mostly in the cytoplasmic compartment of both cells. Flow cytometric analysis reveals that the compound arrests the growth of both cells by triggering the G2/M phase that led to the induction of apoptosis. At equimolar concentrations, RAPTA-T causes much more cellular BRCA1 damage in HCC1937 than in MCF-7 cells, suppressing the expression of BRCA1 mRNA in both cell lines with the subsequent down-regulation of the BRCA1 protein. Interestingly, RAPTA-T exhibits an approximately fivefold greater ability to suppress the expression of the BRCA1 protein in HCC1937 than in MCF-7 cells. These data provide insights into the molecular mechanisms by which RAPTA-T exerts its effects on BRCA1-associated breast cancer cells.

Proteasome inhibitors trigger mutations via activation of caspases and CAD, but mutagenesis provoked by the HDAC inhibitors vorinostat and romidepsin is caspase/CAD-independent


Genotoxic anti-cancer therapies such as chemotherapy and radiotherapy can contribute to an increase in second malignancies in cancer survivors due to their oncogenic effects on non-cancerous cells. Inhibition of histone deacetylase (HDAC) proteins or the proteasome differ from chemotherapy in that they eliminate cancer cells by regulating gene expression or cellular protein equilibrium, respectively. As members of these drug classes have been approved for clinical use in recent times, we investigated whether these two drug classes exhibit similar mutagenic capabilities as chemotherapy. The HDAC inhibitors vorinostat/SAHA and romidepsin/FK288 were found to induce DNA damage, and mis-repair of this damage manifested into mutations in clonogenically viable surviving cells. DNA damage and mutations were also detected in cells treated with the proteasome inhibitor bortezomib. Exposure to both drug classes stimulated caspase activation consistent with apoptotic cell death. Inhibition of caspases protected cells from bortezomib-induced acute (but not clonogenic) death and mutagenesis, implying caspases were required for the mutagenic action of bortezomib. This was also observed for second generation proteasome inhibitors. Cells deficient in caspase-activated DNase (CAD) also failed to acquire DNA damage or mutations following treatment with bortezomib. Surprisingly, vorinostat and romidepsin maintained an equivalent level of killing and mutagenic ability regardless of caspase or CAD activity. Our findings indicate that both drug classes harbour mutagenic potential in vitro. If recapitulated in vivo, the mutagenicity of these agents may influence the treatment of cancer patients who are more susceptible to oncogenic mutations due to dysfunctional DNA repair pathways.

17-Aminogeldanamycin selectively diminishes IRE1α-XBP1s pathway activity and cooperatively induces apoptosis with MEK1/2 and BRAF V600E inhibitors in melanoma cells of different genetic subtypes


Outcomes of melanoma patient treatment remain unsatisfactory despite accessibility of oncoprotein-targeting drugs and immunotherapy. Here, we reported that 17-aminogeldanamycin more potently activated caspase-3/7 in BRAFV600E melanoma cells than geldanamycin, another inhibitor of heat shock protein 90 (HSP90). 17-aminogeldanamycin alleviated self-triggered compensatory increase in HSP70 mRNA level and induced endoplasmic reticulum (ER) stress, which was followed by selective diminution of cytoprotective IRE1α-XBP1s pathway activity of unfolded protein response (UPR), inhibition of ERK1/2 activity and induction of apoptosis. Concomitantly, ATF6/p50 level and expression of PERK-dependent genes, CHOP and BIM, remained unaltered. This might result from an inframe deletion in EIF2AK3 leading to a PERKL21del variant revealed by whole-exome sequencing in melanoma cell lines. 17-aminogeldanamycin exhibited similar activity in NRASQ61R melanoma cells that harbored a heterozygous inactivating variant of NAD(P)H:quinone oxidoreductase 1 (NQO1P187S). In addition, 17-aminogeldanamycin acted cooperatively with trametinib (an inhibitor of MEK1/2) and vemurafenib (an inhibitor of BRAFV600E) in induction of apoptosis in melanoma cell lines as evidenced by in-cell caspase-3/7 activation and PARP cleavage that occurred earlier compared with either drug used alone. As trametinib and vemurafenib did not significantly affect HSP70 and GRP78 transcript levels, cooperation of MEK/BRAFV600E inhibitors and 17-aminogeldanamycin might result from a concurrent inhibition of the RAS/RAF/MEK/ERK cascade and IRE1α-dependent signaling, and cell-intrinsic ER homeostasis can determine the extent of the drug cooperation. Our study indicates that 17-aminogeldanamycin takes several advantages compared with other HSP90-targeting compounds, and can complement activity of BRAF/MEK inhibitors in melanoma cells of different genetic subtypes.

Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound


Apoptosis is a mechanism to remove unwanted cells in the tissue. In diabetic wound, which is characterized by delayed healing process, excessive apoptosis is documented and plays a crucial role. Matrix metalloproteinase 9 (MMP9), which is elevated in non-healed diabetic wound, is necessary for healing process but its abnormality resulted in a delayed healing. The classical function of MMP9 is the degradation of extracellular matrix (ECM). However, there is some literature evidence that MMP9 triggers cell apoptosis. Whether the excessive MMP9 contributes to epidermis cell apoptosis in delayed healing diabetic wound and the underlying mechanisms is not clear. In this study, we aimed to explore whether MMP9 induced keratinocyte apoptosis and investigate the plausible mechanisms. Our in vitro study showed that advanced glycation end products (AGEs) induced keratinocyte apoptosis and enhanced MMP9 level. Besides, MMP9, both intra-cellular expressions and extra-cellular supplement, promoted cell apoptosis. Further, MMP9 resulted in an increased expression of FasL, other than Fas and p53. These findings identified a novel effect that MMP9 exerted in delayed diabetic wound healing, owing to a pro-apoptotic effect on keratinocyte, which was mediated by an increase of FasL expression. This study increases understanding of elevated MMP9 which is involved in diabetic wound repair and offers some insights into novel future therapies.

Recombinant human lactoferrin induces apoptosis, disruption of F-actin structure and cell cycle arrest with selective cytotoxicity on human triple negative breast cancer cells


Breast cancer is the most frequently diagnosed cancer among women worldwide. Here, recombinant human lactoferrin (rhLf) expressed in Pichia pastoris was tested for its potential cytotoxic activity on a panel of six human breast cancer cell lines. The rhLf cytotoxic effect was determined via a live-cell HTS imaging assay. Also, confocal microscopy and flow cytometry protocols were employed to investigate the rhLf mode of action. The rhLf revealed an effective CC50 of 91.4 and 109.46 µg/ml on non-metastatic and metastatic MDA-MB-231 cells, with favorable selective cytotoxicity index values, 11.68 and 13.99, respectively. Moreover, rhLf displayed satisfactory SCI values on four additional cell lines, MDA-MB-468, HCC70, MCF-7 and T-47D (1.55–3.34). Also, rhLf provoked plasma membrane blebbing, chromatin condensation and cell shrinkage in MDA-MB-231 cells, being all three apoptosis-related morphological changes. Also, rhLf was able to shrink the microfilaments, forming a punctuated cytoplasmic pattern in both the MDA-MB-231 and Hs-27 cells, as visualized in confocal photomicrographs. Moreover, performing flow cytometric analysis, rhLf provoked significant phosphatidylserine externalization, cell cycle arrest in the S phase and apoptosis-induced DNA fragmentation in MDA-MB-231 cells. Hence, rhLf possesses selective cytotoxicity on breast cancer cells. Also, rhLf caused apoptosis-associated morphologic changes, disruption of F-actin cytoskeleton organization, phosphatidylserine externalization, DNA fragmentation, and arrest of the cell cycle progression on triple-negative breast cancer MDA-MB-231 cells. Overall results suggest that rhLf is using the apoptosis pathway as its mechanism to inflict cell death. Findings warranty further evaluation of rhLf as a potential anti-breast cancer drug option.

Correction to: MiRNA-126 expression inhibits IL-23R mediated TNF-α or IFN-γ production in fibroblast-like synoviocytes in a mice model of collagen-induced rheumatoid arthritis

The authors would like to add an article note stating that "The authors Jie Gao and Ruina Kong have equally contributed to the article".

Potential role of anastasis in cancer initiation and progression

Cell death rocks

Ultraspiracle-independent anti-apoptotic function of ecdysone receptors is required for the survival of larval peptidergic neurons via suppression of grim expression in Drosophila melanogaster


In Drosophila melanogaster a significant number of heterogenous larval neurons in the central nervous system undergo metamorphosis-associated programmed cell death, termed metamorphoptosis. Interestingly distinct groups of doomed larval neurons are eliminated at different metamorphic phases. Although ecdysone hormonal signaling via nuclear ecdysone receptors (EcRs) is known to orchestrate the neuronal metamorphoptosis, little is known about how this signaling controls such diverse neuronal responses. Crustacean cardioactive peptide (CCAP)-producing neurons in the ventral nerve cord are developmentally programmed to die shortly after adult emergence. In this study, we show that disruption of endogenous EcR function by ectopic expression of dominant negative forms of EcRs (EcRDN) causes premature death of larval CCAP neurons in a caspase-dependent manner. This event is rescued by co-expression of individual EcR isoforms. Furthermore, larval CCAP neurons are largely normal in ecr mutants lacking either EcR-A or EcR-B isoforms, suggesting that EcR isoforms redundantly function to protect larval CCAP neurons. Of surprise, a role of Ultraspiracle (Usp), a canonical partner of EcR, is dispensable in the protection of CCAP neurons, whereas both EcR and Usp are required for inducing metamorphoptosis of vCrz neurons shortly after prepupal formation. As a downstream, grim is an essential cell death gene for the EcRDN-mediated CCAP neuronal death, while either hid or rpr function is dispensable. Together, our results suggest that Usp-independent EcR actions protect CCAP neurons from their premature death by repressing grim expression until their normally scheduled apoptosis at post-emergence. Our studies highlight two opposite roles played by EcR function for metamorphoptosis of two different peptidergic neuronal groups, proapoptotic (vCrz) versus antiapoptotic (CCAP), and propose that distinct death timings of doomed larval neurons are determined by differential signaling mechanisms involving EcR.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Δημοφιλείς αναρτήσεις