Publications by authors named "Ali Hadi"

32 Publications

Design and evaluation of a new mobile application to improve the management of minor ailments: a pilot study.

BMC Health Serv Res 2022 Jul 15;22(1):920. Epub 2022 Jul 15.

Clinical Pharmacy Department, College of Pharmacy, University of Basrah, Basrah, Iraq.

Background: Seeking pharmacist advice about minor ailments is a common practice among Iraqi patients because such advice is free and quick. Unfortunately, the assessment and management of minor ailments by Iraqi pharmacists were inappropriate. Therefore, this study aimed to develop a model for a mobile application that can assist community pharmacists in the diagnosis and management of minor ailments.

Methods: The scientific content of the application was based on the information in the symptoms in the pharmacy and British National Formulary books. The design and content of the application were approved by two experts. Thereafter, the application was built for Android mobiles using flutter technology and dart language. A pre-post pilot study was conducted to assess outcomes associated with use of the application, including user acceptance and appropriateness of clinical recommendations. Fifteen students from the College of Pharmacy/University of Baghdad who had an Android mobile participated in this study. Two different scenarios about diarrhea were used during the pilot study, in which the researcher acted as a patient (SP) and the participant student as a pharmacist.

Results: After using the application, the number of questions asked by the participated student to the SP was significantly increased to about double. Additionally, providing the SP with appropriate non-pharmacological and pharmacological therapy along with optimum counseling and education were also significantly improved. All study participants agreed on the application's ease of use and ability to reduce diagnosis and medication errors.

Conclusions: The implementation of the newly developed mobile application, diarrhea management step by step, was associated with improvements in assessment and recommended treatments for diarrhea cases with good acceptance by a pilot sample of pharmacy students at Baghdad University.
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http://dx.doi.org/10.1186/s12913-022-08292-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287937PMC
July 2022

A rare case of acute mesenteric ischaemia and duodenal ulcer perforation together in a single patient in a tertiary care hospital.

J Pak Med Assoc 2022 Apr;72(4):755-757

Department of Surgery, Mayo Hospital, Lahore, Pakistan.

A 57 years old male presented in the emergency department of EAST Surgical Ward, MAYO Hospital Lahore in February 2021 with complaints of abdominal distension, pain and vomiting. He was a chronic smoker and diagnosed hypertensive for the last 14 years but was non-compliant with oral antihypertensive medications. He was a factory worker and took NSAIDs off and on for pain in the knee joint for the last five years. On examination, his abdomen was tense and tender with resonant percussion notes in the right hypogastrium and epigastrium. His chest x-ray showed free gas under the right diaphragm. Diagnosis of a perforated duodenal ulcer was made and exploratory laparotomy was done. Examination revealed a perforated ulcer in the first part of the duodenum with greenish gangrenous patches on the next 3 feet of the small gut. Graham's patch repair and resection of the diseased small gut was done and a jejuno ileostomy was performed. Unfortunately, the patient expired on 2nd postoperative day due to sudden cardiopulmonary arrest.
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http://dx.doi.org/10.47391/JPMA.3716DOI Listing
April 2022

The effect of a dual-wavelength 532 nm and 1064 nm picosecond-domain laser with a fractionated holographic optic on photoaging and patient age perception: A pilot study.

J Cosmet Dermatol 2022 Jan 15;21(1):320-326. Epub 2021 Dec 15.

UnionDerm, New York, New York, USA.

Introduction: This study evaluated the efficacy of a dual-wavelength 532 nm/1064 nm Nd:YAG picosecond-domain laser with a holographic lens array in treating facial photoaging.

Methods: Thirteen subjects were enrolled with 10 completing the study. Receiving three-month treatments, subjects underwent full-face spot treatment of facial lentigines with the 532-nm non-fractionated handpiece, followed by two sequential facial passes of the 1064-nm and the 532-nm fractionated handpieces. Improvement was measured by treating physician evaluation of pigmentation and rhytids as well as blinded reviewer evaluation of pre- and post-treatment image sets taken 12 weeks after the final treatment. Participants completed treatment surveys to assess satisfaction.

Results: Physician grading on a 5-point scale revealed an average improvement of 1.6 in pigmentation (p = 0.0042) and 0.9 in rhytids (p = 0.0196). Blinded physicians appropriately selected baseline images in 44 of 50 (88%) image sets (10 subjects; five reviewers). On an 11-point scale for overall facial photoaging (0 = no change, 1 = 10% improvement, 2 = 20% improvement, etc.) treating physicians scored mean improvement as 3.3 ± 1.83 (95% CI 1.99 to 4.61; range 1-6), while blinded reviewers scored mean improvement as 2.32 ± 2.62 (range % -4 to 8, 95% CI 1.57 to 3.07). The greatest majority (80%) of participants reported satisfaction with the treatment. Adverse events were mild; however, one patient developed hyperpigmentation, consistent with melasma that was successfully treated with topical agents.

Conclusion: This is the first study to show that picosecond-domain 532 nm/1064 nm laser treatments with combination non-fractionated and fractionated handpieces are well-tolerated, safe, and effective for the treatment of photodamage.
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http://dx.doi.org/10.1111/jocd.14654DOI Listing
January 2022

Evaluation of amikacin dosing schedule in critically ill elderly patients with different stages of renal dysfunction.

Eur J Hosp Pharm 2022 03 29;29(e1):e67-e71. Epub 2021 Sep 29.

Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Objectives: Amikacin is still a widely used aminoglycoside for the treatment of life-threatening infections. The pharmacokinetic parameters of this antibiotic may be altered in critically ill conditions. Moreover, in the elderly population, pathophysiological changes affect these pharmacokinetic variables, making it difficult to predict the appropriate dose and dosing schedule for amikacin. This study aimed to characterise the pharmacokinetics of amikacin in critically ill elderly patients with renal dysfunction, and to evaluate if the available dose adjustment schedules dependent on renal function would be appropriate for empirical dosing.

Methods: Critically ill patients aged >60 years with a creatinine clearance of >20 mL/min in need of treatment with amikacin were randomly enrolled. All the patients received approximately 25 mg/kg amikacin. The patients were then divided into three groups according to the stages of their renal dysfunction based on creatinine clearance, and the optimum time to re-dosing was calculated for each group. The pharmacokinetic parameters of the patients were calculated and estimated as population pharmacokinetic data.

Results: Of 30 patients, only 20% attained the target peak levels of amikacin of >64 mg/L. In addition, the mean volume of distribution was 0.47 L/kg. There was a poor correlation between amikacin clearance and creatinine clearance. The difference in amikacin half-life was not statistically significant among any of the stages of renal impairment.

Conclusions: The initial dosing of amikacin in critically ill elderly patients should not be reduced, even in the context of renal impairment. Regarding the dose adjustment in renal impairment, dosing intervals estimation, no decision can be made based on the creatinine clearance and the first dose individualisation method in terms of the two-sample measurements may be considered as an appropriate strategy.
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http://dx.doi.org/10.1136/ejhpharm-2021-002986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899630PMC
March 2022

Lemierre Syndrome in a Patient With Splenectomy Secondary to Pyruvate Kinase Deficiency, Complicated by Heparin Resistance.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211040635

Kern Medical, Bakersfield, CA, USA.

Lemierre syndrome was first documented in the literature in 1936, and is defined as septic thrombophlebitis of the internal jugular vein. It is typically a result of oropharyngeal infection causing local soft tissue inflammation, which spreads to vasculature, and promotes formation of septic thrombi within the lumen, persistent bacteremia, and septic emboli. We present the case of a 24-year-old incarcerated man, who presented with leukocytosis and a right-sided tender, swollen neck after undergoing left mandibular molar extraction for an infected tooth. Computed tomography revealed a persistent thrombus in the transverse and sigmoid sinuses bilaterally, extending downwards, into the upper jugular veins. He was started on empiric intravenous vancomycin, zosyn, and heparin, but subsequently demonstrated heparin resistance, and was thus anticoagulated with a lovenox bridge to warfarin. Throughout his hospital course, hemocultures demonstrated no growth, so antibiotic treatment was deescalated to oral metronidazole and ceftriaxone. On discharge, the patient was transitioned to oral amoxicillin and metronidazole for an additional 4 weeks with continuation of anticoagulation with warfarin for a total of 3 to 6 months. This case report details a unique presentation of Lemierre syndrome with bilateral transverse sinus, sigmoid sinus, and internal jugular vein thrombosis that was presumably secondary to an odontogenic infectious focus.
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http://dx.doi.org/10.1177/23247096211040635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385586PMC
October 2021

A crossroad between placental and tumor biology: What have we learnt?

Placenta 2021 12 12;116:12-30. Epub 2021 Mar 12.

Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Westernat Ontario, London, Ontario, N6A5C1, Canada. Electronic address:

Placenta in certain species including the human has evolved as a highly invasive tumor-like organ invading the uterus aned its vasculature to derive oxygen and nutrients for the fetus and exchange waste products. While several excellent reviews have been written comparing hemochorial placentation with tumors, no comprehensive review is available dealing with mechanistic insights into what makes them different, and what tumor biologists can learn from placental biologists, and vice versa. In this review, we analyze the structure-function relationship of the human placenta, emphasizing the functional need of the spatio-temporally orchestrated trophoblast invasiveness for fetal development and growth, and pathological consequences of aberrant invasiveness for fetal and maternal health. We then analyze similarities and differences between the placenta and invasive tumors in terms of hallmarks of cancer, some key molecules regulating their invasive functions, and how placental cancers (choriocarcinomas) or other cancers become refractory or even addicted to these invasion-restraining molecules. We cite in vitro models of human trophoblast and choriocarcinoma cell lines utilized to study mechanisms in normal placental development as well as those responsible for tumor progression. We discuss the pathobiology of hyper-invasive placentas and show thattrophoblastic neoplasias are a unique and heterogeneous class of tumors. We delve into the questions as to why metastasis from other organs rarely occurs at the placental site and whether pregnancy makes the mother more or less vulnerable to cancer-related morbidity/mortality. We attempt to compare trophoblast stem cells and cancer stem cells. Finally, we leave the readers with some thoughts as foods of future investigations.
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http://dx.doi.org/10.1016/j.placenta.2021.03.003DOI Listing
December 2021

COVID-19 and Periodontitis: A Reality to Live with.

J Contemp Dent Pract 2020 Dec 1;21(12):1398-1403. Epub 2020 Dec 1.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral and Maxillofacial Pathology, College of Dentistry, Jazan University, Kingdom of Saudi Arabia, Phone: +966507633755, e-mail:

Background: Coronavirus disease-19 (COVID-19) is a r ecent pandemic that is advancing at a r apid r ate. The future course of the disease includes severe r espiratory infection and also leads to death if unattended. Meticulous measures are necessary before attending any patient. The dental operatories and the clinic surroundings must be well sanitized so as to prevent the spread of pandemic.

Aim And Objective: This r eview discusses in brief about the pathophysiology and course of COVID-19. Further, we discussed in detail the management aspects of patients in periodontal perspective and the sanitization procedures required for the dental clinic.

Review Results: The SARS coronavirus enters the human circulation via the angiotensin-converting enzyme (ACE) receptors which are also found on the oral mucosal surfaces. Furin and Cathepsin L are the pro-inflammatory molecules released during pathogenesis of periodontitis and mediate the molecular pathways that help the virus invade into the host. The clinic set-up should be modified to best suit the pandemic conditions. This includes the three phases, i.e., phase I: preparatory phase; phase II: implementation phase; and phase III: follow-up. The patient management is explained based on the emergency needs of the patient based on the recent AAP classification of periodontal diseases and conditions 2017 as emergency, urgent, and elective treatment needs which have been explained in detail.

Conclusion: It can be strongly concluded that there is direct relationship between oral health and systemic health. The treatment procedures and sanitization protocols must be definitely modified. Further consensus and systematic reviews help us arriving at a more standardized protocol.

Clinical Significance: This review would help clinicians modify the way they treat patients in the clinic and provide better services depending upon the emergency needs of the patient.
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December 2020

Methods for Measuring Cardiac Muscle Mechanical Properties.

Front Physiol 2020 8;11:616996. Epub 2021 Jan 8.

Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States and thousands of manuscripts each year are aimed at elucidating mechanisms underlying cardiac disease. The methods for quantifying cardiac performance are quite varied, with each technique assessing unique features of cardiac muscle mechanical properties. Accordingly, in this review, we discuss current methods for quantifying cardiac muscle performance, highlighting what can be learned from each method, and how each technique can be used in conjunction to complement others for a more comprehensive understanding of cardiac function. Importantly, cardiac function can be assessed at several different levels, from the whole organ down to individual protein-protein interactions. Here, we take a reductionist view of methods that are commonly used to measure the distinct aspects of cardiac mechanical function, beginning with whole heart preparations and finishing with the motility assay. While each of the techniques are individually well-documented in the literature, there is a significant need for a comparison of the techniques, delineating the mechanical parameters that can are best measured with each technique, as well as the strengths and weaknesses inherent to each method. Additionally, we will consider complementary techniques and how these methods can be used in combination to improve our understanding of cardiac mechanical function. By presenting each of these methods, with their strengths and limitations, in a single manuscript, this review will assist cardiovascular biologists in understanding the existing literature on cardiac mechanical function, as well as designing future experiments.
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http://dx.doi.org/10.3389/fphys.2020.616996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820907PMC
January 2021

Outcomes Evaluated in Controlled Clinical Trials on the Management of COVID-19: A Methodological Systematic Review.

Life (Basel) 2020 Dec 15;10(12). Epub 2020 Dec 15.

Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK.

It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5 May 2020, and the instruments used to measure these outcomes. Significant heterogeneity was observed in the selection of outcomes and instruments. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality (72.5%) and adverse events (55.6%), while hospital admission (50.8%) and viral detection/load (55.6%) are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed. The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for greater consistency, to enable decision makers to compare and contrast studies.
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http://dx.doi.org/10.3390/life10120350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765224PMC
December 2020

Vascular obliteration because of endothelial and myointimal growth in COVID-19 patients.

Int J Dermatol 2021 Jan 12;60(1):73-80. Epub 2020 Nov 12.

Department of Dermatology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

Background: Coronavirus disease 2019 (COVID-19) is a systemic multi-organ viral illness. Previous studies have found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the damage to vascular tissues are not well-elucidated yet. Histological data in COVID-19 patients are still limited and are mainly focused on post-mortem analysis. Given that the skin is affected by COVID-19 and the relative ease of its histological examination, we aimed to examine the histology of skin lesions in COVID-19 patients to better understand the disease's pathology.

Methods: Five skin lesions from COVID-19 adult patients were selected for a deep histological tissue examination.

Results: A strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cell growth was identified. Endothelial cell distortion generated vascular lumen obliteration and striking erythrocyte and serum extravasation. Significant deposition of C4d and C3 throughout the vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also observed.

Conclusions: COVID-19 could comprise an obliterative microangiopathy consisting on endothelial and myointimal growth with complement activation. This mechanism, together with the increased vascular permeability identified, could contribute to obliteration of the vascular lumen and hemorrhage in COVID-19. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent increased risk of hemorrhage. Findings of this study could contribute to a better understanding of physiopathological mechanisms underlying COVID-19 on living patients and could help further studies find potential targets for specific therapeutic interventions in severe cases.
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http://dx.doi.org/10.1111/ijd.15300DOI Listing
January 2021

Hidden risks in toys: A systematic review of pediatric toy contact dermatitis.

Contact Dermatitis 2020 May 18;82(5):265-271. Epub 2020 Mar 18.

Department of Dermatology and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Toys are a reflection of the compounds used frequently in manufacturing. Allergic contact dermatitis to potties, metal toys, and children's jewelry is well known, however, there is a broad range of skin risks in toys. With the objective to identify and publicize the associated risk of contact dermatitis in children's toys, we have searched the PubMed database from creation to September 9, 2019. Studies were eligible if they reported a new case of contact dermatitis secondary to interaction with a toy in patients from birth to 18 years of age. A toy was defined as something children interact with for entertainment during leisure time. In this review of the PubMed database we filtered by age and language which may have prevented us from detecting cases in adults that could be extrapolated to children. In addition, several articles were excluded based on title alone. A total of 1312 articles were identified and reviewed manually for inclusion criteria. Review of the articles found 25 original articles for consideration. Several toys were found to be associated with contact dermatitis. These included electronics, toy cars, costume jewelry, bicycles, sqwish balls, slime, Play-Doh, and plasticine. Electronics such as video game controllers, cellphones, iPads, and computers were implicated. In conclusion, there is still an unmet need for observation of this segment of industry for labeling of contents and ongoing surveillance.
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http://dx.doi.org/10.1111/cod.13500DOI Listing
May 2020

Defining decreased protein succinylation of failing human cardiac myofibrils in ischemic cardiomyopathy.

J Mol Cell Cardiol 2020 01 10;138:304-317. Epub 2019 Dec 10.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address:

Succinylation is a post-translational modification of protein lysine residues with succinyl groups derived from succinyl CoA. Succinylation is considered a significant post-translational modification with the potential to impact protein function which is highly conserved across numerous species. The role of succinylation in the heart, especially in heart failure and myofibril mechanics, remains largely unexplored. Mechanical parameters were measured in myofibrils isolated from failing hearts of ischemic cardiomyopathy patients and non-failing donor controls. We employed mass spectrometry to quantify differential protein expression in myofibrils from failing ischemic cardiomyopathy hearts compared to non-failing hearts. In addition, we combined peptide enrichment by immunoprecipitation with liquid chromatography tandem mass spectrometry to quantitatively analyze succinylated lysine residues in these myofibrils. Several key parameters of sarcomeric mechanical interactions were altered in myofibrils isolated from failing ischemic cardiomyopathy hearts, including lower resting tension and a faster rate of activation. Of the 100 differentially expressed proteins, 46 showed increased expression in ischemic heart failure, while 54 demonstrated decreased expression in ischemic heart failure. Our quantitative succinylome analysis identified a total of 572 unique succinylated lysine sites located on 181 proteins, with 307 significantly changed succinylation events. We found that 297 succinyl-Lys demonstrated decreased succinylation on 104 proteins, while 10 residues demonstrated increased succinylation on 4 proteins. Investigating succinyl CoA generation, enzyme activity assays demonstrated that α-ketoglutarate dehydrogenase and succinate dehydrogenase activities were significantly decreased in ischemic heart failure. An activity assay for succinyl CoA synthetase demonstrated a significant increase in ischemic heart failure. Taken together, our findings support the hypothesis that succinyl CoA production is decreased and succinyl CoA turnover is increased in ischemic heart failure, potentially resulting in an overall decrease in the mitochondrial succinyl CoA pool, which may contribute to decreased myofibril protein succinylation in heart failure.
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http://dx.doi.org/10.1016/j.yjmcc.2019.11.159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058372PMC
January 2020

Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease.

Hum Genomics 2019 12 10;13(1):65. Epub 2019 Dec 10.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

Background: Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD boosting supplement to investigate alterations in the pathogenesis of early-stage ALD.

Methods: To examine the impact of NAD therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis.

Results: Our findings reveal that NMN therapy increased hepatic NAD levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression.

Conclusions: These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD-based interventions.
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http://dx.doi.org/10.1186/s40246-019-0251-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902345PMC
December 2019

Pulmonary hemorrhage as the initial presentation of AIDS-related kaposi sarcoma.

Cutis 2019 Oct;104(4):E12-E14

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

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October 2019

Comorbid diseases of vitiligo: A 10-year cross-sectional retrospective study of an urban US population.

J Am Acad Dermatol 2020 Mar 17;82(3):628-633. Epub 2019 Jul 17.

Department of Dermatology, Keck School of Medicine of University of Southern California, Los Angeles, California. Electronic address:

Background: Vitiligo is associated with medical conditions, primarily autoimmune disorders; however, only a few studies in the United States have investigated these associations.

Objective: Our purpose was to investigate the diseases associated with vitiligo in the New York, New York, population and evaluate if these associations differ by race/ethnicity and sex.

Methods: In this retrospective study, we analyzed data collected from the medical records of 1487 vitiligo patients seen at New York University during a 10-year period.

Results: Vitiligo patients had a statistically significant higher prevalence of hypothyroidism, multiple sclerosis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, seronegative arthritis, pernicious anemia, myasthenia gravis, inflammatory bowel disease, lymphoma, and systemic lupus erythematosus. Rates of comorbid autoimmune diseases varied by race and sex.

Limitations: Medical charts did not consistently report race/ethnicity, type of vitiligo, and total body surface area affected. Information from nondermatology medical visits was also included.

Conclusion: This study revealed multiple new disease associations for vitiligo, including multiple sclerosis, idiopathic thrombocytopenic purpura, and lymphoma, as well as confirmed previously reported associations with other autoimmune diseases, the most common being hypothyroidism followed by rheumatoid arthritis. Associations did vary by race/ethnicity and sex.
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http://dx.doi.org/10.1016/j.jaad.2019.07.036DOI Listing
March 2020

Lipid peroxidation derived reactive aldehydes in alcoholic liver disease.

Curr Opin Toxicol 2019 Feb 15;13:110-117. Epub 2018 Oct 15.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO.

Lipid peroxidation is a known consequence of oxidative stress and is thought to play a key role in numerous disease pathologies, including alcoholic liver disease (ALD). The overaccumulation of lipid peroxidation products during chronic alcohol consumption results in pathogenic lesions on protein, DNA, and lipids throughout the cell. Molecular adducts due to secondary end products of lipid peroxidation impact a host of biochemical processes, including inflammation, antioxidant defense, and metabolism. The aggregate burden of lipid peroxidation which occurs due to chronic alcohol metabolism, including downstream signaling events, contributes to the development and progression of ALD. In this current opinion we highlight recent studies and approaches relating cellular mechanisms of lipid peroxidation to the pathogenesis of alcoholic liver disease.
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http://dx.doi.org/10.1016/j.cotox.2018.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602539PMC
February 2019

Real-Time Remote-Health Monitoring Systems: a Review on Patients Prioritisation for Multiple-Chronic Diseases, Taxonomy Analysis, Concerns and Solution Procedure.

J Med Syst 2019 Jun 11;43(7):223. Epub 2019 Jun 11.

Department of Computing, Universiti Pendidikan Sultan Idris, Tanjong Malim, Perak, Malaysia.

Remotely monitoring a patient's condition is a serious issue and must be addressed. Remote health monitoring systems (RHMS) in telemedicine refers to resources, strategies, methods and installations that enable doctors or other medical professionals to work remotely to consult, diagnose and treat patients. The goal of RHMS is to provide timely medical services at remote areas through telecommunication technologies. Through major advancements in technology, particularly in wireless networking, cloud computing and data storage, RHMS is becoming a feasible aspect of modern medicine. RHMS for the prioritisation of patients with multiple chronic diseases (MCDs) plays an important role in sustainably providing high-quality healthcare services. Further investigations are required to highlight the limitations of the prioritisation of patients with MCDs over a telemedicine environment. This study introduces a comprehensive and inclusive review on the prioritisation of patients with MCDs in telemedicine applications. Furthermore, it presents the challenges and open issues regarding patient prioritisation in telemedicine. The findings of this study are as follows: (1) The limitations and problems of existing patients' prioritisation with MCDs are presented and emphasised. (2) Based on the analysis of the academic literature, an accurate solution for remote prioritisation in a large scale of patients with MCDs was not presented. (3) There is an essential need to produce a new multiple-criteria decision-making theory to address the current problems in the prioritisation of patients with MCDs.
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http://dx.doi.org/10.1007/s10916-019-1362-xDOI Listing
June 2019

Quantifying Competition among Mitochondrial Protein Acylation Events Induced by Ethanol Metabolism.

J Proteome Res 2019 04 31;18(4):1513-1531. Epub 2019 Jan 31.

Skaggs School of Pharmacy and Pharmaceutical Sciences , University of Colorado Anschutz Medical Campus , Aurora , Colorado 80045 , United States.

Mitochondrial dysfunction is one of many key factors in the etiology of alcoholic liver disease (ALD). Lysine acetylation is known to regulate numerous mitochondrial metabolic pathways, and recent reports demonstrate that alcohol-induced protein acylation negatively impacts these processes. To identify regulatory mechanisms attributed to alcohol-induced protein post-translational modifications, we employed a model of alcohol consumption within the context of wild type (WT), sirtuin 3 knockout (SIRT3 KO), and sirtuin 5 knockout (SIRT5 KO) mice to manipulate hepatic mitochondrial protein acylation. Mitochondrial fractions were examined by label-free quantitative HPLC-MS/MS to reveal competition between lysine acetylation and succinylation. A class of proteins defined as "differential acyl switching proteins" demonstrate select sensitivity to alcohol-induced protein acylation. A number of these proteins reveal saturated lysine-site occupancy, suggesting a significant level of differential stoichiometry in the setting of ethanol consumption. We hypothesize that ethanol downregulates numerous mitochondrial metabolic pathways through differential acyl switching proteins. Data are available via ProteomeXchange with identifier PXD012089.
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http://dx.doi.org/10.1021/acs.jproteome.8b00800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450748PMC
April 2019

Inadvertent inferior oblique extirpation during orbital decompression.

Eur J Ophthalmol 2019 Jul 1;29(4):NP13-NP15. Epub 2018 Oct 1.

Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Purpose: To report a case of inadvertent inferior oblique extirpation during orbital decompression, its management, and postoperative result.

Methods: A 38-year-old female with thyroid eye disease underwent cosmetic right orbital decompression during whichinferior oblique extirpation was noticed.

Result: The muscle was repaired on the same session (illustrated in the article) with no postoperative diplopia at 3-month follow-up.

Conclusion: Inferior oblique injury should be considered among the uncommon yet important complications of orbital decompression. It can be easily found and repaired in the same session as demonstrated in this case report.
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http://dx.doi.org/10.1177/1120672118803516DOI Listing
July 2019

Systematic Review of an Automated Multiclass Detection and Classification System for Acute Leukaemia in Terms of Evaluation and Benchmarking, Open Challenges, Issues and Methodological Aspects.

J Med Syst 2018 Sep 19;42(11):204. Epub 2018 Sep 19.

Department of Computing, Universiti Pendidikan Sultan Idris, Tanjong Malim, Perak, Malaysia.

This study aims to systematically review prior research on the evaluation and benchmarking of automated acute leukaemia classification tasks. The review depends on three reliable search engines: ScienceDirect, Web of Science and IEEE Xplore. A research taxonomy developed for the review considers a wide perspective for automated detection and classification of acute leukaemia research and reflects the usage trends in the evaluation criteria in this field. The developed taxonomy consists of three main research directions in this domain. The taxonomy involves two phases. The first phase includes all three research directions. The second one demonstrates all the criteria used for evaluating acute leukaemia classification. The final set of studies includes 83 investigations, most of which focused on enhancing the accuracy and performance of detection and classification through proposed methods or systems. Few efforts were made to undertake the evaluation issues. According to the final set of articles, three groups of articles represented the main research directions in this domain: 56 articles highlighted the proposed methods, 22 articles involved proposals for system development and 5 papers centred on evaluation and comparison. The other taxonomy side included 16 main and sub-evaluation and benchmarking criteria. This review highlights three serious issues in the evaluation and benchmarking of multiclass classification of acute leukaemia, namely, conflicting criteria, evaluation criteria and criteria importance. It also determines the weakness of benchmarking tools. To solve these issues, multicriteria decision-making (MCDM) analysis techniques were proposed as effective recommended solutions in the methodological aspect. This methodological aspect involves a proposed decision support system based on MCDM for evaluation and benchmarking to select suitable multiclass classification models for acute leukaemia. The said support system is examined and has three sequential phases. Phase One presents the identification procedure and process for establishing a decision matrix based on a crossover of evaluation criteria and acute leukaemia multiclass classification models. Phase Two describes the decision matrix development for the selection of acute leukaemia classification models based on the integrated Best and worst method (BWM) and VIKOR. Phase Three entails the validation of the proposed system.
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http://dx.doi.org/10.1007/s10916-018-1064-9DOI Listing
September 2018

Erythema elevatum diutinum: a case report and review of literature.

Int J Dermatol 2019 Apr 3;58(4):408-415. Epub 2018 Aug 3.

The Kimberly and Eric J. Waldman Department of Dermatology and Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Erythema elevatum diutinum (EED) is a rare cutaneous leukocytoclastic vasculitis thought to be related to increased levels of circulating antibodies. It has been shown to be associated with HIV infection, tuberculosis, as well as various autoimmune diseases. A retrospective review of all cases of EED indexed in PubMed between 1990 and 2014 was performed. Inclusion criteria for articles was availability of full text in English and a biopsy-confirmed diagnosis of EED. All other articles were excluded. Cases were stratified by age and anatomic location of the lesions. Treatment response was coded as "complete," "partial," and "none." A total of 133 cases of EED with 381 lesions detailed in case reports and case series were included. Twenty-one cases were associated with HIV. Of 47 patients with reported paraproteinemias, IgA paraproteinemia was found in 57.45%, IgG paraproteinemia in 29.8%, IgM paraproteinemia in 10.6%, and IgD paraproteinemia in 2.1% of cases. Of 40 (30.1%) patients with reported comorbid autoimmune disease, rheumatoid arthritis was associated with 10 cases. Cancer was found to be associated with 9.77% of cases. Seventy-five patients were treated with dapsone, with 36 (48%) achieving complete treatment response, 24 (32%) achieving partial response, and seven (9.3%) achieving no response. Keeping the clinical associations of EED in mind, especially malignancy, is critical in management of the disease. More structured studies need to take place in order to fully define the mechanisms and strength of these associations.
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http://dx.doi.org/10.1111/ijd.14169DOI Listing
April 2019

Acquired Idiopathic True Transverse Leukonychia.

Authors:
Ali Hadi Dana Stern

Skinmed 2017;15(4):315-317. Epub 2017 Aug 1.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.

A 34-year-old man from Djibouti presented with a 14-year history of relapsing and remitting transverse white bands on the fingernails with sparing of the toenails. Examination revealed several transverse, white bands following the contour of the lunula on seven of his fingernails that did not fade upon compression of the digits (Figure). There was no onycholysis. No other skin lesions were noted. The patient reported having lived for 4 years (2000-2004) in a house that had well water as its primary water supply. This 4-year period was a stressful point in our patient's life. During that time, he had been a student at university. He had had no reported occupational exposure to arsenic. He reported being a cigarette smoker since 1996 but denied any illicit drug use or alcohol consumption. His past medical history was significant for hepatitis A infection, but he denied any history of systemic illness, including renal disease, heart disease, and lung disease. He denied any family history of leukonychia. He denied any trauma or participation in activities that require excessive use of his hands, and also denied manipulation of the cuticles. The patient's liver function tests, lipid panel, complete blood count, and urinalysis were all within normal limits. A blood test revealed normal arsenic levels. Histologic examination of the nail plate showed segmental parakeratosis, with no evidence of fungal organisms upon PAS staining.
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July 2019

Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation.

Alcohol Clin Exp Res 2017 Oct 14;41(10):1705-1714. Epub 2017 Sep 14.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.

Background: Chronic ethanol (EtOH) consumption is a major cause of liver disease worldwide. Oxidative stress is a known consequence of EtOH metabolism and is thought to contribute significantly to alcoholic liver disease (ALD). Therefore, elucidating pathways leading to sustained oxidative stress and downstream redox imbalances may reveal how EtOH consumption leads to ALD. Recent studies suggest that EtOH metabolism impacts mitochondrial antioxidant processes through a number of proteomic alterations, including hyperacetylation of key antioxidant proteins.

Methods: To elucidate mechanisms of EtOH-induced hepatic oxidative stress, we investigate a role for protein hyperacetylation in modulating mitochondrial superoxide dismutase (SOD2) structure and function in a 6-week Lieber-DeCarli murine model of EtOH consumption. Our experimental approach includes immunoblotting immunohistochemistry (IHC), activity assays, mass spectrometry, and in silico modeling.

Results: We found that EtOH metabolism significantly increased the acetylation of SOD2 at 2 functionally relevant lysine sites, K68 and K122, resulting in a 40% decrease in enzyme activity while overall SOD2 abundance was unchanged. In vitro studies also reveal which lysine residues are more susceptible to acetylation. IHC analysis demonstrates that SOD2 hyperacetylation occurs near zone 3 within the liver, which is the main EtOH-metabolizing region of the liver.

Conclusions: Overall, the findings presented in this study support a role for EtOH-induced lysine acetylation as an adverse posttranslational modification within the mitochondria that directly impacts SOD2 charge state and activity. Last, the data presented here indicate that protein hyperacetylation may be a major factor contributing to an imbalance in hepatic redox homeostasis due to chronic EtOH metabolism.
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http://dx.doi.org/10.1111/acer.13473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626652PMC
October 2017

Advances in Vitiligo: An Update on Medical and Surgical Treatments.

J Clin Aesthet Dermatol 2017 Jan 1;10(1):15-28. Epub 2017 Jan 1.

The Ronald O. Perelman Department of Dermatology, New York University, New York, New York.

Vitiligo is one of the most common cutaneous disorders of depigmentation. Although its underlying causes are still being studied and no definitive cure currently exists, recent research has provided insight into pathogenic mechanisms and new treatment options. The aim of this paper is to provide a comprehensive overview of the medical and surgical therapies for vitiligo with emphasis on the most recent treatment modalities. This review was conducted through a literature search using PubMed and the National institutes of Health's clinicalTrials.gov databases from January 2010 to July 2015. This yielded 86 studies, 12 of which were excluded, and 74 of which were reviewed. Recent studies and ongoing clinical trials indicate that there are many promising new medical and surgical treatment modalities for this chronic condition. A combination of traditional and newer treatments may work synergistically to provide additional improvement in patients' disease state and quality of life.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300730PMC
January 2017

Common conditions in skin of color.

Semin Cutan Med Surg 2016 Dec;35(4):184-190

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.

The skin of color population is rapidly growing in the United States. This population has numerous unique and more commonly occurring dermatologic conditions. Additionally, certain cutaneous conditions can present differently in darker versus lighter skin types. This paper provides an up-to-date overview of common conditions that occur in skin of color, including their clinical presentations, pathogenesis, differential diagnoses, and treatments.
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http://dx.doi.org/10.12788/j.sder.2016.065DOI Listing
December 2016

Efficacy of Varicocele Repair in Different Age Groups.

Urology 2015 Aug;86(2):273-5

School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

Objective: To compare semen parameters and spouse pregnancy rates after varicocele repair in 2 age groups.

Materials And Methods: Mean changes in spermatozoa concentration, motility, and morphology after varicocele repair in 83 patients were compared between patients aged 30 years or younger (group 1) and those older than 30 years (group 2). Spouse pregnancy rates were compared between the 2 age groups.

Results: The mean sperm concentration increased significantly in both groups (P <.05). The percentage of motile sperm increased from 48.2% to 56.6% in group 1 and from 47.2% to 53.2% in group 2 one year after varicocele repair. The increase in motility was statistically significant for both groups (P <.05), but there was no statistically significant difference in the increase in sperm motility between the 2 groups (P = .01). The percentage of sperm with abnormal morphology decreased significantly in both groups 12 months postoperatively (from 62.7% to 59.6% in group 1 and from 61.3% to 58% in group 2; P = .03). However, there was no statistically significant difference in the improvement in sperm morphology between the 2 groups (P >.05). The pregnancy rates in the patients' spouses were 51.1% and 44.7% in groups 1 and 2, respectively. This difference was not statistically significant (P = .9).

Conclusion: There was no statistically significant difference in semen parameter improvement and spouse pregnancy rates after varicocelectomy in the 2 age groups.
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http://dx.doi.org/10.1016/j.urology.2015.05.004DOI Listing
August 2015

Questions regarding the diagnosis of malignant hyperthermia.

Anesthesiology 2015 Sep;123(3):731-2

North Shore University Hospital, Manhasset, New York (A.J.B.).

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http://dx.doi.org/10.1097/ALN.0000000000000760DOI Listing
September 2015

An improved high yield total synthesis and cytotoxicity study of the marine alkaloid neoamphimedine: an ATP-competitive inhibitor of topoisomerase IIα and potent anticancer agent.

Mar Drugs 2014 Sep 19;12(9):4833-50. Epub 2014 Sep 19.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Recently, we characterized neoamphimedine (neo) as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been access to sufficient amounts of material for biological testing. Although there are two reported syntheses of neo, both require 12 steps with low overall yields (≤6%). In this article, we report an improved total synthesis of neo achieved in 10 steps with a 25% overall yield. In addition, we report an expanded cytotoxicity study using a panel of human cancer cell lines, including: breast, colorectal, lung, and leukemia. Neo displays potent cytotoxicity (nM IC50 values) in all, with significant potency against colorectal cancer (lowest IC50 = 6 nM). We show that neo is cytotoxic not cytostatic, and that neo exerts cytotoxicity by inducing G2-M cell cycle arrest and apoptosis.
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http://dx.doi.org/10.3390/md12094833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178486PMC
September 2014

Design of an amide N-glycoside derivative of β-glucogallin: a stable, potent, and specific inhibitor of aldose reductase.

J Med Chem 2014 Jan 23;57(1):71-7. Epub 2013 Dec 23.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Science, University of Colorado Anschutz Medical Campus , Aurora, Colorado 80045, United States.

β-Glucogallin (BGG), a major component of the Emblica officinalis medicinal plant, is a potent and selective inhibitor of aldose reductase (AKR1B1). New linkages (ether/triazole/amide) were introduced via high yielding, efficient syntheses to replace the labile ester, and an original two-step (90%) preparation of BGG was developed. Inhibition of AKR1B1was assessed in vitro and using transgenic lens organ cultures, which identified the amide linked glucoside (BGA) as a stable, potent, and selective therapeutic lead toward the treatment of diabetic eye disease.
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http://dx.doi.org/10.1021/jm401311dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956592PMC
January 2014

Combined and independent impact of diabetes mellitus and chronic kidney disease on residual platelet reactivity.

Thromb Haemost 2013 Jul 16;110(1):118-23. Epub 2013 May 16.

Cardiac Catheterization Laboratory, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029, USA.

Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4-6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 - 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.
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http://dx.doi.org/10.1160/TH13-01-0004DOI Listing
July 2013
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