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Temesgen Sidamo,1 Prakruti S Rao,2 Eleni Aklillu,3 Workineh Shibeshi,1 Yumi Park,4,5 Yong-soon Cho,4,5 Jae-Gook Shin,4,5 Scott K Heysell,2 Stellah G Mpagama,6 Ephrem Engidawork1 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; 3Department of Laboratory of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; 4Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea; 5Center for Personalized Precision Medicine of Tuberculosis (cPMTb), Inje University College of Medicine, Busan, Republic of Korea; 6Kibong’oto Infectious Diseases Hospital, Sanya Juu, TanzaniaCorrespondence: Ephrem Engidawork, Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia, Email ephrem.engidawork@aau.edu.etObjective: This study aimed to explore the population pharmacokinetic modeling (PopPK) of levofloxacin (LFX) and moxifloxacin (MXF), as well as the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24 h and the in vitro minimum inhibitory concentration (AUC0-24/MIC) in Ethiopian multidrug resistant tuberculosis (MDR-TB) patients.Methods: Steady state-plasma concentration of the drugs in MDR-TB patients were determined using optimized liquid chromatography-tandem mass spectrometry. PopPK and simulations were run at various doses, and pharmacokinetic parameters were estimated. The effect of covariates on the PK parameters and PTA for maximum mycobacterial kill and resistance prevention was also investigated.Results: LFX and MXF both fit in a one-compartment model with adjustments. Serum-creatinine (Cr) influenced (p = 0.01) the clearance of LFX, whereas body mass index (BMI) influenced (p = 0.01) the apparent volume of distribution (V) of MXF. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L with the simulated 750 mg, 1000 mg, and 1500 mg doses were 29%, 62%, and 95%, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no change in the PTA for maximum bacterial kill when the MXF dose was increased (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention was improved.Conclusion: The standard doses of LFX and MXF may not provide adequate drug exposure. PopPK of LFX is more predictable for maximum mycobacterial kill, whereas MXF’s resistance prevention target increases with dose. Cr and BMI are likely important covariates for dose optimization in Ethiopian patients.Keywords: population pharmacokinetics, probability of target attainment, moxifloxacin, levofloxacin, MDR-TB patients, Ethiopia

P Syamasundar Rao Department of Pediatrics, University of Texas-Houston McGovern Medical School, Children’s Memorial Hermann Hospital, Houston, TX, USACorrespondence: P Syamasundar RaoEmeritus Chief of Pediatric Cardiology, UT-Houston McGovern Medical School, 6410 Fannin, UTPB Suite # 425, Houston, TX 77030, USATel +1 713-500-5738Fax +1 713-500-5751Email P.Syamasundar.Rao@uth.tmc.eduAbstract: Surgical correction of coarctation of the aorta was described in the mid-1940s and balloon angioplasty was introduced in the early 1980s. Several types of surgical methods were devised to treat native coarctation, but eventually, resection and end-to-end anastomosis became a standard approach with the use of extended end-to-end anastomosis for babies with hypoplasia of the isthmus and/or transverse aortic arch. Balloon angioplasty was considered as a substitute for surgical correction and was so used for some time, but because of high rate of recurrence in the neonate and young infant, most centers have reverted back to surgical correction as a primary mode of treatment of aortic coarctation in the neonate. Further research into feasibility of using stents in the management of coarctation in neonates and young infants are necessary. It is generally agreed that balloon angioplasty is the treatment of choice for post-surgical aortic recoarctations.Keywords: coarctation of the aorta, balloon angioplasty, surgical correction, neonate, stents, post-surgical recoarctation

Panduranga S Rao,1 Julie A Wright Nunes,1 Brenda W Gillespie,2 Rachel L Perlman,1 Rajan Ravichandran3 1Division of Nephrology, Department of Internal Medicine, University of Michigan Health System, 2Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 3Department of Nephrology, Madras Institute of Nephrology, Madras Institute of Orthopedics and Trauma Hospitals, Chennai, India Background: There is a paucity of information on kidney education and screening programs in Indian youth.Methods: Participants (n=2,158) from Chennai colleges were educated about the kidneys and chronic kidney disease (CKD) and screened in a pilot program from April to May 2013. This entailed: 1) a presentation and educational video and 2) an on-site assessment of weight, blood pressure, and demographic information. Urinalysis (UA) kits were distributed and returned in ≤48 hours. We examined participant characteristics and their association with dipstick proteinuria using logistic regression.Results: The mean (standard deviation [SD]) age was 18.9 (1.6) years, and 1,451 (68%) were men. Mean (SD) body mass index (BMI) was 21.9 (4.3) kg/m2; 745 (36%) had a BMI consistent with being overweight or obese. Mean (SD) systolic blood pressure (SBP) was 118.7 (13.1) mm Hg, and 94 (5%) of the participants had SBP ≥140. Mean (SD) diastolic blood pressure (DBP) was 70.9 (11.4) mm Hg, with 119 participants (6%) having ≥90 mm Hg. A total of 136 participants had glycosuria (UA≥1+) and 120 (6%) had proteinuria (UA≥1+). In unadjusted analyses, sex (odds ratio [OR]=1.64 [confidence interval, CI 1.06–2.55]; p=0.026 men vs. women) and age (OR=1.13 per year [CI 1.01–1.26]; p=0.032) were significantly associated with proteinuria. In the analysis adjusted for age, sex, SBP, DBP, glycosuria, and BMI, age remained independently associated with higher odds for proteinuria (OR=1.14 per year [1.02–1.29]; p=0.026). Males showed a trend of higher risk compared with women (OR=1.57 [CI 1.00–2.50]; p=0.051).Conclusion: This education and screening pilot program in a population of college students offers unique opportunities for identification, education, and early intervention for CKD. Keywords: screening, youth, CKD, proteinuria, glycosuria, education, hypertension, BMI, Indian youth

In this piece of work, a numerical investigation of natural convection is carried out on the buoyancy-driven flow of nanofluids and heat transfer through porous media packed inside a wavy cavity. The cavity is placed horizontal, and its right vertical wall is of wavy nature, the bottom and top walls of the cavity are adiabatic, and there is a temperature difference between the left and right vertical wall. The dimensionless governing equations for the flow of nanofluids through the Darcian porous media are solved iteratively by using finite difference method. The study is conducted for wide range of governing parameters, such as Rayleigh-Darcy number (R a = 10 , 10 2 , 10 3) , nanoparticle volume fraction (ϕ = 0 % , 5 % , 10 % , 15 % , 20 %) for three types of nanofluids (A l 2 O 3 - H 2 O , Cu - H 2 O , TiO 2- H 2 O) , the waviness of the vertical wall controlled by dimensionless length of amplitude of the wave (a = 0.05 , 0.15 , 0.25) and number of undulations per unit length (N = 1, 3, 5). The simulated results reveals that the presence of nanoparticles enhances the convective heat transfer process at low Ra, and the wall affects the local convection rate and it also controls the overall heat transfer rate. For a cavity with N = 3, N u ¯ is increased by 33% at Ra = 10, and at R a = 10 3 , N u ¯ has a drop by 10% as the a is increased from 0.05 to 0.25 having 20% of nanoparticles. [ABSTRACT FROM AUTHOR]

In this finite element analysis of natural convection, cooling of a heat source embedded with a wavy porous cavity containing an insulated obstacle is investigated. A heat source is submitted to the left vertical wall, and the wavy right vertical wall is kept at fixed low temperature keeping top and bottom walls as insulated. The insulated obstacle which is placed inside the cavity is either square or circular in shape. The non-dimensional governing equations are solved by Galerkin finite element method and the results are presented in terms of streamlines and isotherms. The parameters considered for the investigation are Rayleigh-Darcy number (R a = 10 , 10 2 , 10 3 ), amplitude of the wavy wall (a = 0.05 , 0.15 , 0.25) , undulation of wavy wall per unit length (N = 3) and shape of the obstacle. From the obtained results, mathematical correlations to calculate the maximum temperature of the heater and average Nusselt number with governing parameters are presented, and it is observed that the presence of a square insulated body reduces the convection process over a circular body; also, for a fixed Ra, the effect of obstacle at a particular portion of the cavity falls off with increment in a. [ABSTRACT FROM AUTHOR]

Background: In the year 1998 WHO proposed that the clinical criteria of counting skin lesions alone should decide whether a patient receives Multibacillary (MB) or Paucibacillary (PB) MDT. There is a concern that a significant number of patients may be incorrectly treated under these guidelines.Aims: This study aims to determine whether the sensitivity and the specificity of the latest WHO criteria, can be enhanced by the addition of nerve examination in the place of slit skin smears.Methods: 150 patients of untreated leprosy reporting at a TLM Hospital in Delhi from January to December 2006 were registered for the study. After physical examination, the number of skin lesions and nerves involved were counted and slit skin smears performed. Two groups were created, those with > 5 skin lesions, and those with 5 or less skin lesions. The diagnostic efficacy of the current WHO classification was calculated with and without the addition of nerve examination.Results: The sensitivity and the specificity of the current WHO operational classification are 76.6%, and 73.7% respectively, using slit skin smear as a standard. When the number of nerves was added to the diagnosis, the sensitivity increased to 94.4%, for more than 5 lesions and to 90.9%, for five or less than five lesions.Conclusions: Nerve examination can significantly improve the sensitivity of the WHO criterion in determination of MB versus PB leprosy. [ABSTRACT FROM AUTHOR]

Recently, a changing pattern of hepatitis A epidemiology has been reported in the Indian population indicating a rise in the rate of hepatitis A infection among adults. The study's objective was to assess anti-HAV prevalence in voluntary blood donors from middle and high socioeconomic strata. Serum samples collected from voluntary blood donors from Pune city and its suburbs in the years 2002 and 2004-2005 were tested for anti-HAV IgG antibodies. Serum samples collected during 2004-2005 were examined for anti-HAV IgM antibodies. Positive samples were tested for HAV-RNA. Agewise anti-HAV positivity was significantly low in adults aged 18-25 years (90.4%) compared to those aged >25 years (97.4%) (P<0.01). A decline in anti-HAV prevalence was significant in 2004-2005 compared to that in 2002 (96.5% vs. 92.1%) (P<0.01). Overall, in both adult age groups, the proportion of anti-HAV positivity was remarkably low in the high socioeconomic group (HSG) (88.96%) compared to that of the middle socioeconomic group (MSG) (95.86%) (P<0.01). Anti-HAV IgM positivity was not significant ( 1%), however, presence of HAV-RNA in one of the samples indicated the possibility of horizontal transmission of HAV. Increase in seronegativity to HAV in HSG implicates a rise in the susceptible pool and indicates the need for vaccination against hepatitis A. [ABSTRACT FROM AUTHOR]

BACKGROUND: A substantial number of patients return to dialysis therapy after a renal transplant fails. It is not clear whether mortality increases among patients with graft failure relative to those on the waiting list who have not yet received a kidney transplant. METHODS: Data from the Scientific Registry of Transplant Recipients were analyzed (N = 175,436). Cox regression with time-dependent covariates was used to compare mortality between post-graft failure dialysis patients and primary transplant candidates on dialysis therapy. Mortality hazard ratios (HRs) were adjusted for age, sex, race, cause of end-stage renal disease, pre-waiting list time on dialysis therapy, calendar year of wait-listing, and organ procurement organization. RESULTS: Overall, the post-graft failure dialysis group experienced a significant 78% greater mortality (HR, 1.78; P < 0.0001) relative to the transplant candidate group. The post-graft failure dialysis/transplant candidate HR was relatively constant across age groups, but significantly greater (P < 0.0001) among patients with diabetes (HR, 1.93) than among those without diabetes (HR, 1.69). The HR was greatest during the first week after graft failure (HR, 13.6; P < 0.0001) and decreased steadily thereafter. However, despite leveling off, the HR remained significantly elevated well after graft failure, including the 5- to 10-year period after graft failure. CONCLUSION: Based on national data, mortality among patients on dialysis therapy after primary graft failure increases significantly relative to mortality among patients still awaiting primary kidney transplantation. Additional studies are urgently needed to define the mechanism of the increased risk and strategies to decrease mortality. Copyright © 2007 by the National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

The etiology of Kawasaki disease (KD) remains unknown despite several years of dedicated research in this direction. Recently coronavirus infection and genetic polymorphisms have been implicated. Since first description of the disease there have been few changes in the diagnostic criteria except for newer recommendations of fever of at least 4 instead of 5 days duration. Recently, Echocardiography Criteria and Laboratory Criteria have been added to aid in the diagnosis of incomplete KD where all the historical diagnostic criteria are not present; this is now called the "incomplete form of KD" as opposed to "atypical form of KD". The word "atypical" is reserved for unusual presentations of KD such as those with hemophagocytic syndrome or nerve palsy. The treatment of KD includes infusion of high dose immunoglobulin. Patients non-responsive to immunoglobulin therapy are labeled as having "immunoglobulin resistant KD". The treatment of immunoglobulin resistant KD can be challenging and new therapies that have tried with some success. Late outcomes after 4 decades of treating these patients have recently been published. There has been some concern about increased risk for premature atherosclerosis in patients with childhood KD who had coronary artery abnormalities. [ABSTRACT FROM AUTHOR]

In this review, the clinical features and management of most commonly encountered acyanotic, left-to-right shunt lesions are discussed. Patients with small defects, especially in childhood, are usually asymptomatic while moderate to large defects in infancy may present with symptoms. Hyperdynamic precordium, widely split and fixed second heart sound, ejection systolic murmur at the left upper sternal border and a mid-diastolic flow rumble at the left lower sternal border are present in atrial septal defects, holosystolic murmur at the left lower border is characteristic for a ventricular septal defect whereas a continuous murmur at the left upper sternal border is distinctive for patent ductus arteriosus. Clinical diagnosis is not usually difficult and the diagnosis can be confirmed and quantitated by non-invasive echocardiographic studies. Whereas surgical intervention was used in the past, transcatheter methods are increasingly used for closure of atrial septal defect and patent ductus arteriosus. Small ventricular septal defects may not need to be closed whereas medium and large defects may require surgical closure. Transcatheter closure of both muscular and membranous ventricular septal defects is feasible by transcatheter methodology, but these techniques are experimental at the time of this writing. [ABSTRACT FROM AUTHOR]

In this review, the clinical features and management of most commonly encountered acyanotic obstructive cardiac lesions are discussed. Mild lesions, especially in children are usually asymptomatic while neonates and infants may present with symptoms. Ejection systolic murmurs in patients with pulmonic and aortic stenosis and decreased femoral pulses and blood pressure difference (>20 mmHg) between arms and leg in patients with aortic coarctation are usually seen. Clinical diagnosis is not difficult and the diagnosis can be confirmed and quantitated by non-invasive echocardiographic studies. Whereas surgical intervention was used in the past, balloon dilatation appears to be effective in the treatment of these lesions. [ABSTRACT FROM AUTHOR]

Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15-20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of beta-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169-175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY. [ABSTRACT FROM AUTHOR]

This review summarizes the literature concerning the production of certain anticancer compounds from tissue cultures of medicinal plants. The various problems involved and the possible ways to overcome using biotechnological approaches are discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to examine radiation doses received by infants of less than 750 g birth weight from radiographs. METHODS: We examined the radiology records, including radiograph films, of all 25 surviving infants with birth weight less than 750 g admitted to our center during 1991. The standard method of neonatal radiation dose calculation was modified to consider the body size, postnatal growth, and extramedullary hematopoiesis of the extremely low birth weight infant. To determine overall radiation exposure, we calculated an effective dose equivalent, which is the sum of weighed organ dose equivalents. RESULTS: The infants had a mean of 31 radiographys performed, including 17 chest radiographs, 5 babygrams, and 9 abdominal radiographs. The majority of chest radiographs and babygrams were performed in the first month, whereas abdominal radiographs increased during the second month of life. Total-body radiation dose and total effective dose equivalent by the standard and modified methods, respectively, for single exposures ranged from 0.01 to 0.02 millisieverts (mSv) for a chest radiograph, from 0.02 to 0.04 mSv for a babygram, and from 0.02 to 0.03 mSv for an abdominal radiograph. Surface organs icluding the skin, breast, and thyroid received the largest radiation doses. The effective dose equivalent per infant for all radiographs was 0.72 mSv according to the modified method, compared to a total-body dose of 0.40 mSv using the standard method. However, infants with chronic lung disease or necrotizing enterocolitis received up to 1.5 mSv total-body dose, including 3.3 mSv to the breast, 2.5 mSv to the thyroid, and 2.3 mSv to the testes. CONCLUSIONS: Radiation doses received by infants of less than 750 g birth weight are small in comparison with the range of doses that form the basis of risk estimates for cancer. [ABSTRACT FROM AUTHOR]

Described as asymptomatic and an incidental finding on a plain x-ray film, the 'pelvic digit' is a rare congenital anomaly. A 35-year-old man is of a rare symptomatic pelvic digit that warranted surgical excision. Its importance lies in its differentiation from acquired abnormalities due to trauma such as myositis ossificans and avulsion injuries of pelvis. If this entity is kept in mind, unnecessary investigations or interventions can be avoided. [ABSTRACT FROM AUTHOR]

We have previously described that tissue transglutaminase (tTG) is a high level phenotypic biomarker in prostate cancer, which is down regulated in prostate cancer and surrounding premalignant field compared to benign prostate glands. To understand the function of tTG in prostate cancer, we sought to identify proteins that interact with the transglutaminase moiety of tTG using a human prostate cancer complementary deoxyribonucleic acid library in a Yeast 2-Hybrid system. The Yeast 2-Hybrid experiments identified a strong and novel interaction between the transglutaminase moiety and protein kinase A anchor protein 13 (AKAP13), which was quantified by beta-galactosidase assay, confirmed in vitro by immunoprecipitation experiments using PC3 prostate cancer cell lysates, and in vivo colocalization was confirmed by immunofluorescence studies in PC3 cells. Because AKAP plays a major role in protein kinase A and Rho protein mediated signaling, functional studies are underway to elucidate the significance of tTG-AKAP13 interaction in prostate cancer. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This review addresses the diagnosis and management of ventricular septal defects (VSDs). The VSDs are classified on the basis of their size, their number, and their location in the ventricular septum. Natural history of VSDs includes spontaneous closure, development of pulmonary hypertension, onset of infundibular obstruction, and progression to aortic insufficiency. While initial diagnostic approaches such as careful history-taking, physical examination, chest X-rays, and electrocardiograms provide basic information, echo-Doppler studies are essential for assessing the defect's clinical significance and determining the need for intervention. Intervention is usually indicated for symptomatic patients with moderate- to large-sized VSDs. Surgical closure is advised for perimembranous, supracristal and inlet VSDs, and for deficits involving prolapsed aortic valve leaflets. While percutaneous methods to occlude perimembranous VSDs with Amplatzer Membranous VSD Occluder are feasible, they are not recommended due to a notable risk of inducing complete heart block in a significant number of patients. Alternatively, percutaneous and hybrid methods employing the Amplatzer Muscular VSD Occluder are effective for treating large muscular VSDs. The majority of treatment options have demonstrated satisfactory outcomes. However, practitioners are urged to exercise caution in managing small defects to avoid unnecessary procedures and to ensure timely intervention for large VSDs to prevent pulmonary vascular obstructive disease., Competing Interests: The author declares no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Restructured foods are a blend of various ingredients that are dried or fried to obtain a ready-to-eat product. Several frying techniques have been employed viz., deep fat, microwave, vacuum, air, and spray frying. Deep-fat frying is the most common technique used for products that have improved texture and sensory characteristics. It facilitates various transformations that include starch gelatinization, protein denaturation, nutrient loss, non-enzymatic browning, lipid oxidation, etc. This physicochemical change alters both the product and the fried oil quality. The frying conditions will also influence the product characteristics and affect the properties of the fried product. This review focuses on the mechanisms and transformations during deep fat frying. The properties, namely physical, chemical, sensory, thermal, rheological, and microstructural changes of restructured foods were discussed. Thus, a better understanding of mechanisms and properties at optimum frying conditions would yield the desired product quality., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)