1.Diarrhoea morbidity in children in the Asaro Valley, Eastern Highlands Province, Papua New Guinea
M. Wyrsch ; K. Coakley ; N. Alexander ; G. Saleu ; J. Taime ; M. Kakazo ; P. Howard ; D. Lehmann
Papua New Guinea medical journal 1998;41(1):7-14
A morbidity study of diarrhoea covering 1926 children aged less than 5 years was carried out in Goroka town and the Lowa and Asaro Census Divisions, Eastern Highlands Province between 1986 and 1989. The study involved weekly demographic surveillance of the total population and morbidity surveillance of children by lay reporters who enquired about the presence or absence on any of the preceding 8 days of a range of symptoms associated with diarrhoeal and respiratory diseases. A three-day symptom-free period was used to define distinct episodes of diarrhoea. The average number of episodes/child-year for all children in the study population was 3.0. Boys suffered a significantly higher incidence of diarrhoea under 48 months of age than girls (4.4 episodes compared to 3.6/child-year). Incidence was highest among those aged 6-17 months (5.5/child-year) with a rapid decline after age 35 months. Incidence of diarrhoea was highest in the more remote Asaro Census Division and was higher in periurban areas than in Goroka town. Incidence also varied significantly between villages, some villages experiencing up to 10 times the incidence of diarrhoea found in Goroka town. The incidence of diarrhoea was significantly higher in January than at other times of year. Duration of diarrhoea varied with age, the longest duration being an average of 4.7 days in the 12-17 months age group. In order to reduce diarrhoea morbidity, it is necessary to improve access to water, encourage improved hygiene practices and breastfeeding and warn people about the risks of sleeping with pigs.
PIP: A morbidity study of diarrhea covering 1926 children aged less than 5 years was carried out in Goroka town and the Lowa and Asaro Census Divisions, Eastern Highlands Province between 1986 and 1989. The study involved weekly demographic surveillance of the total population and morbidity surveillance of children by lay reporters who enquired about the presence or absence on any of the preceding 8 days of a range of symptoms associated with diarrheal and respiratory diseases. A 3-day symptom-free period was used to define distinct episodes of diarrhea. The average number of episodes/child-year for all children in the study population was 3.0. Boys suffered a significantly higher incidence of diarrhea under 48 months of age than girls (4.4 episodes/child-year compared to 3.6 episodes/child-year). Incidence was highest among those aged 6-17 months (5.5 episodes/child-year) with a rapid decline after age 35 months. Incidence of diarrhea was highest in the more remote Asaro Census Division and was higher in periurban areas than in Goroka town. Incidence also varied significantly between villages, some villages experiencing up to 10 times the incidence of diarrhea found in Goroka town. The incidence of diarrhea was significantly higher in January than at other times of year. Duration of diarrhea varied with age, the longest duration being an average of 4.7 days in the 12-17 months age group. In order to reduce diarrhea morbidity, it is necessary to improve access to water, encourage improved hygiene practices and breastfeeding and warn people about the risks of sleeping with pigs.
Age Distribution
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Child, Preschool
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Diarrhea - epidemiology
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Female
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Health Surveys
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Papua New Guinea - epidemiology
2.Mitochondrial Genome Editing: Exploring the Possible Relationship of the Atherosclerosis-Associated Mutation m.15059G>A With Defective Mitophagy
Vasily N. SUKHORUKOV ; Victoria A. KHOTINA ; Vladislav A. KALMYKOV ; Alexander D. ZHURAVLEV ; Vasily V. SINYOV ; Daniil Y. POPOV ; Andrey Y. VINOKUROV ; Igor A. SOBENIN ; Alexander N. OREKHOV
Journal of Lipid and Atherosclerosis 2024;13(2):166-183
Objective:
The aim of this study was to evaluate the effect of the m.15059G>A mitochondrial nonsense mutation on cellular functions related to atherosclerosis, such as lipidosis, proinflammatory response, and mitophagy. Heteroplasmic mutations have been proposed as a potential cause of mitochondrial dysfunction, potentially disrupting the innate immune response and contributing to the chronic inflammation associated with atherosclerosis.
Methods:
The human monocytic cell line THP-1 and cytoplasmic hybrid cell line TCHSMAM1 were used. An original approach based on the CRISPR/Cas9 system was developed and used to eliminate mitochondrial DNA (mtDNA) copies carrying the m.15059G>A mutation in the MT-CYB gene. The expression levels of genes encoding enzymes related to cholesterol metabolism were analyzed using quantitative polymerase chain reaction. Proinflammatory cytokine secretion was assessed using enzyme-linked immunosorbent assays. Mitophagy in cells was detected using confocal microscopy.
Results:
In contrast to intact TC-HSMAM1 cybrids, Cas9-TC-HSMAM1 cells exhibited a decrease in fatty acid synthase (FASN) gene expression following incubation with atherogenic low-density lipoprotein. TC-HSMAM1 cybrids were found to have defective mitophagy and an inability to downregulate the production of pro-inflammatory cytokines (to establish immune tolerance) upon repeated lipopolysaccharide stimulation. Removal of mtDNA harboring the m.15059G>A mutation resulted in the re-establishment of immune tolerance and the activation of mitophagy in the cells under investigation.
Conclusion
The m.15059G>A mutation was found to be associated with defective mitophagy, immune tolerance, and impaired metabolism of intracellular lipids due to upregulation of FASN in monocytes and macrophages.
3.Comment on "Long-Term Effects of Diesel Exhaust Particles on Airway Inflammation and Remodeling in a Mouse Model" by Kim et al..
Alexander N LARCOMBE ; Anthony KICIC ; Benjamin J MULLINS
Allergy, Asthma & Immunology Research 2017;9(2):185-186
No abstract available.
Animals
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Inflammation*
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Mice*
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Vehicle Emissions*
4.A survey on surgical site infection among cancer patients at Chong Hua Hospital.
Siguan Stephen SIXTO ; Rafael Jerry U ; Jugao Richard B ; Chu Alexander N ; Sun Cillo M ; Victoria JERRY
Philippine Journal of Surgical Specialties 1994;49(1):15-17
A retrospective descriptive study on the relative frequency of surgical site infection (SSI) among 235 operated cancer patients at Chong Hua Hospital was done covering the period from January 1991 up to May 1993. SSI occurred in 9.4 percent (22/235). There was a significant increase in SSI as the population became older (p=0.01). Dirty operations had a significantly higher infection rate of 50 percent (2/4) compared to 8.7 percent (20/211) for the rest (p=0.45). Clean operations had a significantly lower infection rate of 2.5 percent (3/121) compared to 16.7 percent (19/114) for the rest. There was no difference in SSI between early and late stage cancer cases. Operations in the alimentary tract had a significantly higher infection rate of 19.3 percent (11/57) compared to 6.4 percent (11/172) for operations on the other sites (p=0.004). Operations on solf tissues, breast and thyroid had a signifanctly lower rate of 4.6 percent (4/87) compared to 12.7 percent (18/142) for operations on other sites (p=0.045).(Author)
Human ; Male ; Female ; Aged 80 And Over ; Aged ; Middle Aged ; Surgical Wound Infection ; Thyroid Gland ; Hospitals ; Patients ; Neoplasm
5.Anesthetic considerations for a patient with myasthenia gravis undergoing deep sedation in an outpatient oral surgery setting
Shamit S PRABHU ; Saad A KHAN ; Alexander L DOUDNIKOFF ; Uday N REEBYE
Journal of Dental Anesthesia and Pain Medicine 2019;19(1):67-72
Myasthenia gravis (MG) is a neuromuscular autoimmune disorder which clinically presents as muscular weakness and fatigue due to autoantibody formation against acetylcholine receptors (AChR), leading to their subsequent destruction. Due to the neuromuscular implications of MG, certain considerations must be taken into account when providing anesthesia to MG patients. In the following case report, we have outlined procedural considerations for the anesthetic management of a patient with MG undergoing deep sedation for an elective oral surgery in an outpatient setting, as well as a discussion of relevant literature.
Anesthesia
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Deep Sedation
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Fatigue
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Humans
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Muscle Weakness
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Myasthenia Gravis
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Outpatients
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Receptors, Cholinergic
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Surgery, Oral
6.Chlorogenic acid ameliorates heart failure by attenuating cardiomyocyte ferroptosis
Kai Huang ; Fanghe Li ; Jiayang Tang ; Haiyin Pu ; Vasily Sukhotukov ; Alexander N Orekhov ; Shuzhen Guo
Journal of Traditional Chinese Medical Sciences 2024;11(2):191-198
Objective:
To elucidate the effects of chlorogenic acid (CGA), a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods, including Lonicera japonica Thunb. (Jin Yin Hua), Eucommia ulmoides Oliv. (Du Zhong Ye), tea, and coffee, on cardiomyocyte ferroptosis and heart failure.
Methods:
We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction (TAC). These indicators included the left ventricular ejection fraction (LVEF), fractional shortening (LVFS), end-systolic volume (LVESV), end-diastolic volume (LVEDV), end-systolic diameter (LVESD), and end-diastolic diameter (LVEDD). An isoprenaline hydrochloride (ISO)-induced H9c2 cardiomyocyte cell model was also established, and the cells were treated with various concentrations of CGA. To assess the effect of CGA on ferroptosis in cardiomyocytes, we measured cell viability and evaluated the levels of intracellular reactive oxygen species (ROS), ferrous ions (Fe2+), and lipid peroxidation using fluorescent staining. To clarify the ferroptosis signaling pathway regulated by CGA, western blotting was used to examine the expression of ferroptosis biomarkers, specifically solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), in H9c2 cardiomyocytes and mouse myocardial tissues.
Results:
CGA significantly enhanced cardiac performance indices such as LVEF, LVFS, LVESV, LVEDV, LVESD, and LVEDD. H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels, Fe2+ content, and lipid peroxidation levels. However, CGA treatment significantly ameliorated these changes. Additionally, in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC, CGA increased the expression of ferroptosis-related proteins, including SLC7A11 and GPX4.
Conclusion
CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway. This process alleviates ferroptosis in cardiomyocytes. These results provide new insights into the clinical use of CGA and the management of heart failure.
7.Mechanisms of the Wnt Pathways as a Potential Target Pathway in Atherosclerosis
Anastasia V. POZNYAK ; Vasily N. SUKHORUKOV ; Mikhail A. POPOV ; Yegor S CHEGODAEV ; Anton Y. POSTNOV ; Alexander N. OREKHOV
Journal of Lipid and Atherosclerosis 2023;12(3):223-236
The proteins of the Wnt family are involved in a variety of physiological processes by means of several canonical and noncanonical signaling pathways. Wnt signaling has been recently identified as a major player in atherogenesis. In this review, we summarize the existing knowledge on the influence of various components of the Wnt signaling pathways on the initiation and progression of atherosclerosis and associated conditions. We used the PubMed database to search for recent papers on the involvement of the Wnt pathways in atherosclerosis. We used the combination of “Wnt” and “atherosclerosis” keywords to find the initial papers, and chose papers published after 2018. In the first section of the paper, we describe the general mechanisms of the Wnt signaling pathways and their components. The next section is dedicated to existing studies assessing the implication of Wnt signaling elements in different atherogenic processes, such as cholesterol retention, endothelial dysfunction, vascular inflammation, and atherosclerotic calcification of the vessels. Lastly, various therapeutic strategies based on interference with the Wnt signaling pathways are considered. We also compare the efficacy and availability of the proposed treatment methods. Wnt signaling can be considered a potential target in the treatment and prevention of atherosclerosis. Therefore, in this review, we reviewed evidences showing that wnt signaling is an important signal for developing appropriate treatment strategies for atherosclerosis.
8.The Effects of Rituximab on Lipids, Arterial Stiffness and Carotid Intima-Media Thickness in Rheumatoid Arthritis.
Diana S NOVIKOVA ; Tatiana V POPKOVA ; Galina V LUKINA ; Elena L LUCHIKHINA ; Dmitry E KARATEEV ; Alexander V VOLKOV ; Alexander A NOVIKOV ; Elena N ALEKSANDROVA ; Evgeny L NASONOV
Journal of Korean Medical Science 2016;31(2):202-207
The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (capital ES, CyrillicVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI - reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD.
Antirheumatic Agents/*therapeutic use
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Arthritis, Rheumatoid/complications/*drug therapy/physiopathology
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Biomarkers/blood
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C-Reactive Protein/analysis
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Cardiovascular Diseases/complications
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Carotid Intima-Media Thickness
;
Cholesterol, HDL/blood
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Cholesterol, LDL/blood
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Female
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Humans
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Lipids/*blood
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Middle Aged
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Rituximab/*therapeutic use
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Treatment Outcome
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Triglycerides/blood
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Vascular Stiffness
9.The Effects of Rituximab on Lipids, Arterial Stiffness and Carotid Intima-Media Thickness in Rheumatoid Arthritis.
Diana S NOVIKOVA ; Tatiana V POPKOVA ; Galina V LUKINA ; Elena L LUCHIKHINA ; Dmitry E KARATEEV ; Alexander V VOLKOV ; Alexander A NOVIKOV ; Elena N ALEKSANDROVA ; Evgeny L NASONOV
Journal of Korean Medical Science 2016;31(2):202-207
The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (capital ES, CyrillicVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI - reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD.
Antirheumatic Agents/*therapeutic use
;
Arthritis, Rheumatoid/complications/*drug therapy/physiopathology
;
Biomarkers/blood
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C-Reactive Protein/analysis
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Cardiovascular Diseases/complications
;
Carotid Intima-Media Thickness
;
Cholesterol, HDL/blood
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Cholesterol, LDL/blood
;
Female
;
Humans
;
Lipids/*blood
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Middle Aged
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Rituximab/*therapeutic use
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Treatment Outcome
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Triglycerides/blood
;
Vascular Stiffness
10.Concurrent SHORT syndrome and 3q duplication syndrome
Alexander M BOAZ ; Salvatore A GRASSO ; Michael J DEROGATIS ; Ellis N BEESLEY
Journal of Genetic Medicine 2019;16(1):15-18
SHORT syndrome is an extremely rare congenital condition due to a chromosomal mutation of the PIK3R1 gene found at 5q13.1. SHORT is a mnemonic representing six manifestations of the syndrome: (S) short stature, (H) hyperextensibility of joints and/or inguinal hernia, (O) ocular depression, (R) Rieger anomaly, and (T) teething delay. Other key aspects of this syndrome not found in the mnemonic include lipodystrophy, triangular face with dimpled chin (progeroid facies, commonly referred to as facial gestalt), hearing loss, vision loss, insulin resistance, and intrauterine growth restriction (IUGR). 3q duplication syndrome is rare syndrome that occurs due to a gain of function mutation found at 3q25.31-33 that presents with a wide array of manifestations including internal organ defects, genitourinary malformations, hand and foot deformities, and mental disability. We present a case of a 2 year and 3 month old male with SHORT syndrome and concurrent 3q duplication syndrome. The patient presented at birth with many of the common manifestations of SHORT syndrome such as bossing of frontal bone of skull, triangular shaped face, lipodystrophy, micrognathia, sunken eyes, and thin, wrinkled skin (progeroid appearance). Additionally, he presented with findings associated with 3q duplication syndrome such as cleft palate and cryptorchidism. Although there is no specific treatment for these conditions, pediatricians should focus on referring patients to various specialists in order to treat each individual manifestation.
Chin
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Cleft Palate
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Cryptorchidism
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Depression
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Facies
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Fetal Growth Retardation
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Foot Deformities
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Frontal Bone
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Hand
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Hearing Loss
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Hernia, Inguinal
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Humans
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Insulin Resistance
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Joints
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Lipodystrophy
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Male
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Micrognathism
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Parturition
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Skin
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Skull
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Specialization
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Tooth
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Tooth Eruption