Minal Patel - Academia.edu (original) (raw)

Papers by Minal Patel

Journal of Food Protection, Oct 1, 2010

An outbreak of Salmonella serotype Montevideo infections associated with multiple locations of re... more An outbreak of Salmonella serotype Montevideo infections associated with multiple locations of restaurant chain A in Phoenix, AZ, was identified in July 2008. One infected individual reported eating at a chain A catered luncheon where others fell ill; we conducted a cohort study among attendees to identify the vehicle. Food and environmental samples collected at six chain A locations were cultured for Salmonella. Restaurant inspection results were compared among 18 chain A locations. Routine surveillance identified 58 Arizona residents infected with the outbreak strain. Three chain A locations, one of which catered the luncheon, were named by two or more case patients as a meal source in the week prior to illness onset. In the cohort study of luncheon attendees, 30 reported illness, 10 of which were later culture confirmed. Illness was reported by 30 (61%) of 49 attendees who ate chicken and by 0 of 7 who did not. The outbreak strain was isolated from two of these three locations from uncooked chicken in marinade, chopped cilantro, and a cutting board dedicated to cutting cooked chicken. Raw chicken, contaminated before arrival at the restaurant, was the apparent source of this outbreak. The three locations where two or more case patients ate had critical violations upon routine inspection, while 15 other locations received none. Poor hygiene likely led to cross-contamination of food and work areas. This outbreak supports the potential use of inspections in identifying restaurants at high risk of outbreaks and the need to reduce contamination of raw products at the source and prevent cross-contamination at the point of service.

Background: In July 2008, the Maricopa County Dept. of Public Health identified an outbreak of Sa... more Background: In July 2008, the Maricopa County Dept. of Public Health identified an outbreak of Salmonella Montevideo infections associated with several Chain A restaurants in Phoenix. An investigation was initiated to identify the source of infections in order to prevent additional illnesses. Methods: Persons infected with S. Montevideo with the outbreak pulsed-field gel electrophoresis pattern from May to November 2008 were interviewed. Routine restaurant inspection data were reviewed. Food and environmental samples were cultured for Salmonella. A cohort of attendees of an event catered by one of the implicated Chain A restaurants was interviewed using an event-specific questionnaire. Results: Fifty-eight persons were confirmed to have been infected with the outbreak strain; 35 (64%) of 55 interviewed patients ate at one of three implicated Chain A restaurants. In the cohort study, 30 (61%) of the 49 persons who ate chicken were ill compared to none of the 7 who did not eat chicken...

Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuc... more Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells.

American Journal of Tropical Medicine and Hygiene, 2015

Approximately 8% of the population in Papua New Guinea (PNG) has chronic hepatitis B virus (HBV) ... more Approximately 8% of the population in Papua New Guinea (PNG) has chronic hepatitis B virus (HBV) infection. To decrease the burden of chronic HBV infection, a national 3-dose infant hepatitis B vaccination program was implemented starting in 1989, with a birth dose (BD) added to the schedule in 1992. To assess the impact of the hepatitis B vaccination program, we conducted a serosurvey among children born after vaccine introduction. During 2012-2013, a cross-sectional stratified four-stage cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children 4-6 years of age. We collected demographic data, vaccination history, and tested children for HBsAg. Of 2,133 participants, 2,130 children had vaccination data by either card or recall: 28% received a BD; 81% received ≥ 3 vaccine doses. Of 2,109 children providing a blood sample, 60 (2.3%) tested positive for HBsAg. This is the largest, most geographically diverse survey of hepatitis B vaccination and HBsAg seroprevalence done in PNG. Progress has been made in PNG toward the Western Pacific Regional goal to reduce the prevalence of chronic HBV infection to < 1% by 2017 among 5-year-old children. Vaccination efforts should be strengthened, including increasing BD coverage and completing the 3-dose series.

Vaccine, 2012

Background: Cambodia is highly endemic for hepatitis B virus (HBV) infection. Preventing perinata... more Background: Cambodia is highly endemic for hepatitis B virus (HBV) infection. Preventing perinatal HBV transmission should be prioritized in health facilities by providing hepatitis B vaccination to all infants within 24 h of birth (timely birth dose coverage). Methods: Teams assessed birth dose policy, practices and coverage in hospitals and health facilities in 10 provinces in Cambodia. Results: Fifty-one sites were assessed. Median (interquartile range) timely birth dose coverage was 66% (48-92%); coverage was 88% (range = 60-96%) in facilities vaccinating on-site and 48% (range = 20-52%) in those referring off-site (p < 0.0001). Overall, 5 (29%) of 16 hospitals that referred vaccination off-site did not tell mothers vaccination should take place within 24 h of birth, and 6 (35%) discharged mothers when no vaccination services were available for infants to receive the birth dose. Conclusions: Newborns can miss a time-sensitive opportunity to be protected against perinatal HBV infection when they are referred for vaccination off-site rather than being vaccinated in the delivery facility. These data support the case to strengthen policies and practices to provide hepatitis B birth dose vaccination in the delivery facility.

Vaccine, 2013

Hepatitis B virus (HBV) is highly endemic in Cambodia with an estimated pre-vaccine hepatitis B s... more Hepatitis B virus (HBV) is highly endemic in Cambodia with an estimated pre-vaccine hepatitis B surface antigen (HBsAg) prevalence of 9%. By 2005, a hepatitis B vaccination program was implemented to decrease infection rates in children. We conducted a serosurvey to evaluate the impact of the vaccination program in 2011. A cross-sectional two-stage cluster survey was conducted to estimate HBsAg prevalence among children born from 2006 to 2007 in three provinces: Phnom Penh (urban), Kratie (rural), and Ratanakiri (remote). Demographic data, as well as written or oral vaccination history were collected. Children were tested for HBsAg. Factors associated with undervaccination and HBsAg positivity were modeled. Coverage of timely hepatitis B vaccine birth dose (administered at ≤ 24 h) was 55% in Phnom Penh, 36% in Kratie, and 22% in Ratanakiri. Coverage with ≥ 3 hepatitis B vaccine doses (HepB3) was 91% in Phnom Penh, 82% in Kratie, and 64% in Ratanakiri. When compared with children who were born in health facilities with a skilled birth attendant (SBA), children born at home without a SBA were more likely not to have received a timely BD (adjusted relative risk [aRR]=1.94; 95% CI=1.75-2.15) as were children born at home with an SBA (aRR=1.54; 95% CI=1.32-1.80). The proportion of children who tested positive for HBsAg was 0.33% in Phnom Penh, 1.41% in Kratie, and 3.45% in Ratanakiri. In all three provinces, children who received their first dose after 7 days of life and children who never received hepatitis B vaccine had the highest HBsAg prevalence. Progress has been made in Cambodia in decreasing the burden of chronic HBV infection among children. Improvements in vaccination coverage will further decrease the burden of disease.

Stem Cell Reviews and Reports, 2010

Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuc... more Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.

Journal of Allergy and Clinical Immunology, 2010

RATIONALE: Freshwater and marine cyanobacteria and dinoflagelates are known to elaborate toxins w... more RATIONALE: Freshwater and marine cyanobacteria and dinoflagelates are known to elaborate toxins which induce inflammatory rashes and cough in exposed swimmers. The immune mechanism of inflammatory reactions is unknown but clinical symptoms such as erythematous pruritic rashes are common. We used purified marine toxins; debromaplysiatoxins, lyngbyatoxin-a, saxitoxin, and brevatoxin to determine induction of immune activation of human cells ex vivo. METHODS: Meyelomonocytic (U937) cell lines, T-cell (Jurkat) lines, and peripheral mononuclear cells (PBMC) were exposed to the panel of aquatic toxins with lipopolysacchride (LPS) serving as a positive control. Assessment of cell viability and cell cycle analysis was performed using propidium idodide. Elaboration of pro-inflammatory cytokine production by cells cultured with toxins for 48 hours were measured using flow cytometry-based cytokine bead arrays. RESULTS: Toxin concentrations were selected that did not induce cell death. Lyngbyatoxin-a induced G0 cell cycle arrest in U937 cells. When compared to media alone PBMCs exposed to Lyngbyatoxin-a produced significant levels of TNFa, IL-6, IL-1B, IL-10, IL-4, and IL-5 but had no effect on INFg or IL-12 production. The magnitude was similar to PBMC incubated with LPS. None of the other marine toxins tested induced cytokine production by PBMC. CONCLUSIONS: Lyngbyatoxin-a induces macrophage derived pro-inflammatory cytokines and monocyte differentiation ex vivo. The cytokine pattern suggests that it may be mediated through TLR-4 binding. In addition, high levels of the TH2 cytokines IL-4 and IL-5 indicate that these cytokines modulate a TH2 immune response potentially explaining the clinical manifestations seen in individuals following exposure.

Journal of Allergy and Clinical Immunology, 2010

RATIONALE: Eczema herpeticum (ADEH) is a complication of AD associated with greater disease sever... more RATIONALE: Eczema herpeticum (ADEH) is a complication of AD associated with greater disease severity and increased IgE responses. Interferon regulatory factor 2 (IRF-2) is involved in the modulation of cellular responses to interferons (IFNs) and viral infection. Polymorphisms in IRF2 could therefore contribute to an increased risk of AD, ADEH or disease severity. METHODS: We genotyped 78 IRF2 single nucleotide polymorphisms (SNPs) in European American (N5321) and African American (N5307) patients and controls, in addition to 83 European American patients with ADEH. Single SNP and haplotype analyses were performed using the Cochran-Armitage trend test using PLINK. RESULTS: Significant associations with ADEH were observed for six SNPs among the European population (P50.05-0.0086). Significant associations were also noted for AD and two SNPs (P50.040-0.008) among European Americans and three SNPs (P50.047-0.022) among African Americans. Of interest, an intronic SNP (rs793814) was significantly associated with AD in both the European American and African American groups (P50.0082 and P50.047, respectively), and also for total IgE levels among African Americans (P50.011). The most significant association was for an intronic SNP (rs13119453) and EASI within the European American group (P50.0029). Associations were further enhanced by haplotype analyses, wherein a 5-SNP (CAGGA) haplotype (rs3775552, rs809909, rs7655371, rs6812958, rs2797507) demonstrated the strongest association with ADEH among European Americans (P 5 0.00075). CONCLUSIONS: Our findings suggest IRF2 may be an important candidate gene for AD and ADEH. This study implicates IRF2 as potentially causal gene for AD and its severe complication, ADEH.

Gastrointestinal Endoscopy, 2010

Gastrointestinal Endoscopy, Volume 71, Issue 5, Pages AB242, April 2010, Authors:Minal M. Patel; ... more Gastrointestinal Endoscopy, Volume 71, Issue 5, Pages AB242, April 2010, Authors:Minal M. Patel; Hans Gerdes; Arnold J. Markowitz; Christopher J. Dimaio; Mark A. Schattner.

Gastrointestinal Endoscopy, 2011

European Heart Journal, 2014

Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1... more Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model to develop and evaluate gene-based therapeutics for the treatment of LQTS.

Circulation Research, 2008

Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of... more Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury. We demonstrate the selective role of phosphatidylinositol 3-kinase (PI3K) isoforms in IPC. Hearts from PI3K␥ knockout mice (PI3K␥ Ϫ/Ϫ ) displayed poorer functional recovery and greater tissue injury following IPC compared to wild-type and PI3K␥ ϩ/Ϫ hearts. Examination of the cell-signaling pathways revealed restored phosphorylation levels of Akt and glycogen synthase kinase (GSK)3␤ in wild-type hearts, which were abolished in PI3K␥ Ϫ/Ϫ hearts subjected to IPC. Inhibition of GSK3␤ by LiCl reversed the loss in protection in PI3K␥ Ϫ/Ϫ hearts. In contrast, mice expressing a cardiac-specific kinase-deleted PI3K␣ (PI3K␣DN) were resistant to injury induced by 30 minutes of ischemia followed by 40 minutes of reperfusion. Furthermore, the resistance of PI3K␣DN hearts to ischemia/reperfusion correlated with the persistent expression of p110␥ and was blocked by the PI3K inhibitor wortmannin, suggesting the possible enhanced cell signaling through the PI3K␥ pathway. These results demonstrate the importance of the PI3K␥-Akt-GSK3␤ signaling pathway in IPC. Selective activation of myocardial PI3K␥ may be an attractive target for the treatment of ischemic heart disease. (Circ Res. 2008;103:643-653.)

American Journal of Tropical Medicine and Hygiene, 2012

School-based hygiene and water treatment programs increase student knowledge, improve hygiene, an... more School-based hygiene and water treatment programs increase student knowledge, improve hygiene, and decrease absenteeism, however health impact studies of these programs are lacking. We collected baseline information from students in 42 schools in Kenya. We then instituted a curriculum on safe water and hand hygiene and installed water stations in half ("intervention schools"). One year later, we implemented the intervention in remaining schools. Through biweekly student household visits and two annual surveys, we compared the effect of the intervention on hygiene practices and reported student illness. We saw improvement in proper handwashing techniques after the school program was introduced. We observed a decrease in the median percentage of students with acute respiratory illness among those exposed to the program; no decrease in acute diarrhea was seen. Students in this school program exhibited sustained improvement in hygiene knowledge and a decreased risk of respiratory infections after the intervention.

AIDS Patient Care and STDs, 2010

Patients with advanced HIV infection commonly present with esophageal symptomatology most frequen... more Patients with advanced HIV infection commonly present with esophageal symptomatology most frequently due to Candida, cytomegalovirus, or herpes simplex virus. We present a case of a 53-year-old man with AIDS and prior esophageal candidiasis and oral aphthous ulcerations, who developed actinomycosis of the esophagus. This article aims to review clinical characteristics of this and seven previously reported cases occurring in HIVinfected patients. Esophageal actinomycosis is frequently preceded by other esophageal disease that likely results in breach of the mucosal barrier, allowing establishment of the infection. Health care providers should be aware of this rare entity, particularly in those with recurring symptoms, so that a timely diagnosis can be made.

Journal of Nanoparticle Research, Jan 20, 2010

In this study, we evaluated the combined effect of a known toxic molecule, cisplatin, in combinat... more In this study, we evaluated the combined effect of a known toxic molecule, cisplatin, in combination with relatively nontoxic nanoparticles, amorphous fumed silica, on chondrocyte cells. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule, and characterized in terms of size, shape, specific surface area, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as-received silica nanoparticles ranged from 7.1 to 61 nm, estimated from measurements of specific surface area, and the primary particles were aggregated. The effects of cisplatin-functionalized silica particles with different specific surface areas (41, 85, 202, 237, and 297 m 2 /g) were compared in vitro on chondrocytes, the parenchymal cell of hyaline cartilage. The results show that adverse effects on cell function, as evidenced by reduced metabolic activity measured by the MTT assay and increased membrane permeability observed using the Live/Dead stain, can be correlated with specific surface area of the silica. Cisplatin-functionalized silica nanoparticles with the highest specific surface area incited the greatest response, which was almost equivalent to that induced by free cisplatin. This result suggests the importance of particle specific surface area in interactions between cells and surface-functionalized nanomaterials.

We have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create nanoco... more We have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create nanocomposites that can be used to repair surgically created orbital floor defects in a rabbit animal model. Nanosized hydroxyapatite particles may improve tissue engineering scaffold properties because they have similar length scale of many cellular and molecular components and therefore can enhance cellular adhesion and migration. We hypothesize that inclusion of nanosized hydroxyapatite particles (20-70 nm) within cyclic acetal hydrogels would support bone defect repair. The objectives of our study include (1) characterization of nanocomposites in vitro, (2) investigation of tissue response and capsule tissue surrounding nanocomposites in vivo, and (3) investigation of the potential of nanocomposites to facilitate bone formation at 7-and 28-day time points in vivo. Experimental nanocomposite groups consisted of 0, 10, and 50 ng=mL nanosized hydroxyapatite. In vitro results indicated uniform dispersion of nanoparticles within nanocomposites and increased compressive moduli of nanocomposites with increase in nanoparticle concentration and bone marrow stromal cell viability within nanocomposites. In vivo results at day 7 indicated a tissue response of mild to increased inflammatory cells and presence of immature fibrous tissue. At day 28, tissue response consisted of mild inflammatory response and mature tissue. Quantitative results at day 7 indicated no difference in total bone percentage area between groups. The results also indicated that the tissue capsule surrounding the 0, 10, and 50 ng group implants had no clear organization. Quantitative results at day 28 indicated that the tissue capsule surrounding the 0, 10, and 50 ng group implants was an organized layer and the bone percentage for the 50 ng group was significantly higher than that of the remaining groups. Initial results indicated that our nanocomposites initiate a positive in vivo response in terms of bone growth. However, the percentage of bone area compared with the total area was low at both time points. Thus, in our study, even after addition of nanoparticles to cyclic acetal hydrogels, their biocompatible properties were maintained. On the other hand, addition of nanoparticles to cyclic acetal hydrogels did not lead to complete restoration of orbital floor defects.

The American journal of clinical nutrition, Jan 10, 2016

Although the use of micronutrient powders (MNPs) is considered the preferred approach for childho... more Although the use of micronutrient powders (MNPs) is considered the preferred approach for childhood anemia control, concerns about iron-related morbidity from clinical trials have challenged programmatic scale-up. We aimed to measure the effects of community-based sales of MNPs on diarrhea-, fever-, cough-, and malaria-morbidity episodes in children 6-35 mo of age. We conducted a cluster-randomized trial in rural Western Kenya where 60 villages were randomly assigned to either intervention or control groups. MNPs (containing iron, vitamin A, zinc, and 11 other micronutrients) and other health products (e.g., insecticide-treated bednets, soap, and water disinfectant) were marketed in 30 intervention villages from June 2007 to March 2008. Household visits every 2 wk were used to monitor self-reported MNP use and morbidity (illness episodes in the previous 24 h and hospitalizations in the previous 2 wk) in both groups. Iron, vitamin A, anemia, malaria, and anthropometric measures were ...

Hypertension, 2010

ABSTRACT

Journal of Food Protection, Oct 1, 2010

An outbreak of Salmonella serotype Montevideo infections associated with multiple locations of re... more An outbreak of Salmonella serotype Montevideo infections associated with multiple locations of restaurant chain A in Phoenix, AZ, was identified in July 2008. One infected individual reported eating at a chain A catered luncheon where others fell ill; we conducted a cohort study among attendees to identify the vehicle. Food and environmental samples collected at six chain A locations were cultured for Salmonella. Restaurant inspection results were compared among 18 chain A locations. Routine surveillance identified 58 Arizona residents infected with the outbreak strain. Three chain A locations, one of which catered the luncheon, were named by two or more case patients as a meal source in the week prior to illness onset. In the cohort study of luncheon attendees, 30 reported illness, 10 of which were later culture confirmed. Illness was reported by 30 (61%) of 49 attendees who ate chicken and by 0 of 7 who did not. The outbreak strain was isolated from two of these three locations from uncooked chicken in marinade, chopped cilantro, and a cutting board dedicated to cutting cooked chicken. Raw chicken, contaminated before arrival at the restaurant, was the apparent source of this outbreak. The three locations where two or more case patients ate had critical violations upon routine inspection, while 15 other locations received none. Poor hygiene likely led to cross-contamination of food and work areas. This outbreak supports the potential use of inspections in identifying restaurants at high risk of outbreaks and the need to reduce contamination of raw products at the source and prevent cross-contamination at the point of service.

Background: In July 2008, the Maricopa County Dept. of Public Health identified an outbreak of Sa... more Background: In July 2008, the Maricopa County Dept. of Public Health identified an outbreak of Salmonella Montevideo infections associated with several Chain A restaurants in Phoenix. An investigation was initiated to identify the source of infections in order to prevent additional illnesses. Methods: Persons infected with S. Montevideo with the outbreak pulsed-field gel electrophoresis pattern from May to November 2008 were interviewed. Routine restaurant inspection data were reviewed. Food and environmental samples were cultured for Salmonella. A cohort of attendees of an event catered by one of the implicated Chain A restaurants was interviewed using an event-specific questionnaire. Results: Fifty-eight persons were confirmed to have been infected with the outbreak strain; 35 (64%) of 55 interviewed patients ate at one of three implicated Chain A restaurants. In the cohort study, 30 (61%) of the 49 persons who ate chicken were ill compared to none of the 7 who did not eat chicken...

Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuc... more Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells.

American Journal of Tropical Medicine and Hygiene, 2015

Approximately 8% of the population in Papua New Guinea (PNG) has chronic hepatitis B virus (HBV) ... more Approximately 8% of the population in Papua New Guinea (PNG) has chronic hepatitis B virus (HBV) infection. To decrease the burden of chronic HBV infection, a national 3-dose infant hepatitis B vaccination program was implemented starting in 1989, with a birth dose (BD) added to the schedule in 1992. To assess the impact of the hepatitis B vaccination program, we conducted a serosurvey among children born after vaccine introduction. During 2012-2013, a cross-sectional stratified four-stage cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children 4-6 years of age. We collected demographic data, vaccination history, and tested children for HBsAg. Of 2,133 participants, 2,130 children had vaccination data by either card or recall: 28% received a BD; 81% received ≥ 3 vaccine doses. Of 2,109 children providing a blood sample, 60 (2.3%) tested positive for HBsAg. This is the largest, most geographically diverse survey of hepatitis B vaccination and HBsAg seroprevalence done in PNG. Progress has been made in PNG toward the Western Pacific Regional goal to reduce the prevalence of chronic HBV infection to &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 1% by 2017 among 5-year-old children. Vaccination efforts should be strengthened, including increasing BD coverage and completing the 3-dose series.

Vaccine, 2012

Background: Cambodia is highly endemic for hepatitis B virus (HBV) infection. Preventing perinata... more Background: Cambodia is highly endemic for hepatitis B virus (HBV) infection. Preventing perinatal HBV transmission should be prioritized in health facilities by providing hepatitis B vaccination to all infants within 24 h of birth (timely birth dose coverage). Methods: Teams assessed birth dose policy, practices and coverage in hospitals and health facilities in 10 provinces in Cambodia. Results: Fifty-one sites were assessed. Median (interquartile range) timely birth dose coverage was 66% (48-92%); coverage was 88% (range = 60-96%) in facilities vaccinating on-site and 48% (range = 20-52%) in those referring off-site (p < 0.0001). Overall, 5 (29%) of 16 hospitals that referred vaccination off-site did not tell mothers vaccination should take place within 24 h of birth, and 6 (35%) discharged mothers when no vaccination services were available for infants to receive the birth dose. Conclusions: Newborns can miss a time-sensitive opportunity to be protected against perinatal HBV infection when they are referred for vaccination off-site rather than being vaccinated in the delivery facility. These data support the case to strengthen policies and practices to provide hepatitis B birth dose vaccination in the delivery facility.

Vaccine, 2013

Hepatitis B virus (HBV) is highly endemic in Cambodia with an estimated pre-vaccine hepatitis B s... more Hepatitis B virus (HBV) is highly endemic in Cambodia with an estimated pre-vaccine hepatitis B surface antigen (HBsAg) prevalence of 9%. By 2005, a hepatitis B vaccination program was implemented to decrease infection rates in children. We conducted a serosurvey to evaluate the impact of the vaccination program in 2011. A cross-sectional two-stage cluster survey was conducted to estimate HBsAg prevalence among children born from 2006 to 2007 in three provinces: Phnom Penh (urban), Kratie (rural), and Ratanakiri (remote). Demographic data, as well as written or oral vaccination history were collected. Children were tested for HBsAg. Factors associated with undervaccination and HBsAg positivity were modeled. Coverage of timely hepatitis B vaccine birth dose (administered at ≤ 24 h) was 55% in Phnom Penh, 36% in Kratie, and 22% in Ratanakiri. Coverage with ≥ 3 hepatitis B vaccine doses (HepB3) was 91% in Phnom Penh, 82% in Kratie, and 64% in Ratanakiri. When compared with children who were born in health facilities with a skilled birth attendant (SBA), children born at home without a SBA were more likely not to have received a timely BD (adjusted relative risk [aRR]=1.94; 95% CI=1.75-2.15) as were children born at home with an SBA (aRR=1.54; 95% CI=1.32-1.80). The proportion of children who tested positive for HBsAg was 0.33% in Phnom Penh, 1.41% in Kratie, and 3.45% in Ratanakiri. In all three provinces, children who received their first dose after 7 days of life and children who never received hepatitis B vaccine had the highest HBsAg prevalence. Progress has been made in Cambodia in decreasing the burden of chronic HBV infection among children. Improvements in vaccination coverage will further decrease the burden of disease.

Stem Cell Reviews and Reports, 2010

Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuc... more Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.

Journal of Allergy and Clinical Immunology, 2010

RATIONALE: Freshwater and marine cyanobacteria and dinoflagelates are known to elaborate toxins w... more RATIONALE: Freshwater and marine cyanobacteria and dinoflagelates are known to elaborate toxins which induce inflammatory rashes and cough in exposed swimmers. The immune mechanism of inflammatory reactions is unknown but clinical symptoms such as erythematous pruritic rashes are common. We used purified marine toxins; debromaplysiatoxins, lyngbyatoxin-a, saxitoxin, and brevatoxin to determine induction of immune activation of human cells ex vivo. METHODS: Meyelomonocytic (U937) cell lines, T-cell (Jurkat) lines, and peripheral mononuclear cells (PBMC) were exposed to the panel of aquatic toxins with lipopolysacchride (LPS) serving as a positive control. Assessment of cell viability and cell cycle analysis was performed using propidium idodide. Elaboration of pro-inflammatory cytokine production by cells cultured with toxins for 48 hours were measured using flow cytometry-based cytokine bead arrays. RESULTS: Toxin concentrations were selected that did not induce cell death. Lyngbyatoxin-a induced G0 cell cycle arrest in U937 cells. When compared to media alone PBMCs exposed to Lyngbyatoxin-a produced significant levels of TNFa, IL-6, IL-1B, IL-10, IL-4, and IL-5 but had no effect on INFg or IL-12 production. The magnitude was similar to PBMC incubated with LPS. None of the other marine toxins tested induced cytokine production by PBMC. CONCLUSIONS: Lyngbyatoxin-a induces macrophage derived pro-inflammatory cytokines and monocyte differentiation ex vivo. The cytokine pattern suggests that it may be mediated through TLR-4 binding. In addition, high levels of the TH2 cytokines IL-4 and IL-5 indicate that these cytokines modulate a TH2 immune response potentially explaining the clinical manifestations seen in individuals following exposure.

Journal of Allergy and Clinical Immunology, 2010

RATIONALE: Eczema herpeticum (ADEH) is a complication of AD associated with greater disease sever... more RATIONALE: Eczema herpeticum (ADEH) is a complication of AD associated with greater disease severity and increased IgE responses. Interferon regulatory factor 2 (IRF-2) is involved in the modulation of cellular responses to interferons (IFNs) and viral infection. Polymorphisms in IRF2 could therefore contribute to an increased risk of AD, ADEH or disease severity. METHODS: We genotyped 78 IRF2 single nucleotide polymorphisms (SNPs) in European American (N5321) and African American (N5307) patients and controls, in addition to 83 European American patients with ADEH. Single SNP and haplotype analyses were performed using the Cochran-Armitage trend test using PLINK. RESULTS: Significant associations with ADEH were observed for six SNPs among the European population (P50.05-0.0086). Significant associations were also noted for AD and two SNPs (P50.040-0.008) among European Americans and three SNPs (P50.047-0.022) among African Americans. Of interest, an intronic SNP (rs793814) was significantly associated with AD in both the European American and African American groups (P50.0082 and P50.047, respectively), and also for total IgE levels among African Americans (P50.011). The most significant association was for an intronic SNP (rs13119453) and EASI within the European American group (P50.0029). Associations were further enhanced by haplotype analyses, wherein a 5-SNP (CAGGA) haplotype (rs3775552, rs809909, rs7655371, rs6812958, rs2797507) demonstrated the strongest association with ADEH among European Americans (P 5 0.00075). CONCLUSIONS: Our findings suggest IRF2 may be an important candidate gene for AD and ADEH. This study implicates IRF2 as potentially causal gene for AD and its severe complication, ADEH.

Gastrointestinal Endoscopy, 2010

Gastrointestinal Endoscopy, Volume 71, Issue 5, Pages AB242, April 2010, Authors:Minal M. Patel; ... more Gastrointestinal Endoscopy, Volume 71, Issue 5, Pages AB242, April 2010, Authors:Minal M. Patel; Hans Gerdes; Arnold J. Markowitz; Christopher J. Dimaio; Mark A. Schattner.

Gastrointestinal Endoscopy, 2011

European Heart Journal, 2014

Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1... more Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model to develop and evaluate gene-based therapeutics for the treatment of LQTS.

Circulation Research, 2008

Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of... more Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury. We demonstrate the selective role of phosphatidylinositol 3-kinase (PI3K) isoforms in IPC. Hearts from PI3K␥ knockout mice (PI3K␥ Ϫ/Ϫ ) displayed poorer functional recovery and greater tissue injury following IPC compared to wild-type and PI3K␥ ϩ/Ϫ hearts. Examination of the cell-signaling pathways revealed restored phosphorylation levels of Akt and glycogen synthase kinase (GSK)3␤ in wild-type hearts, which were abolished in PI3K␥ Ϫ/Ϫ hearts subjected to IPC. Inhibition of GSK3␤ by LiCl reversed the loss in protection in PI3K␥ Ϫ/Ϫ hearts. In contrast, mice expressing a cardiac-specific kinase-deleted PI3K␣ (PI3K␣DN) were resistant to injury induced by 30 minutes of ischemia followed by 40 minutes of reperfusion. Furthermore, the resistance of PI3K␣DN hearts to ischemia/reperfusion correlated with the persistent expression of p110␥ and was blocked by the PI3K inhibitor wortmannin, suggesting the possible enhanced cell signaling through the PI3K␥ pathway. These results demonstrate the importance of the PI3K␥-Akt-GSK3␤ signaling pathway in IPC. Selective activation of myocardial PI3K␥ may be an attractive target for the treatment of ischemic heart disease. (Circ Res. 2008;103:643-653.)

American Journal of Tropical Medicine and Hygiene, 2012

School-based hygiene and water treatment programs increase student knowledge, improve hygiene, an... more School-based hygiene and water treatment programs increase student knowledge, improve hygiene, and decrease absenteeism, however health impact studies of these programs are lacking. We collected baseline information from students in 42 schools in Kenya. We then instituted a curriculum on safe water and hand hygiene and installed water stations in half ("intervention schools"). One year later, we implemented the intervention in remaining schools. Through biweekly student household visits and two annual surveys, we compared the effect of the intervention on hygiene practices and reported student illness. We saw improvement in proper handwashing techniques after the school program was introduced. We observed a decrease in the median percentage of students with acute respiratory illness among those exposed to the program; no decrease in acute diarrhea was seen. Students in this school program exhibited sustained improvement in hygiene knowledge and a decreased risk of respiratory infections after the intervention.

AIDS Patient Care and STDs, 2010

Patients with advanced HIV infection commonly present with esophageal symptomatology most frequen... more Patients with advanced HIV infection commonly present with esophageal symptomatology most frequently due to Candida, cytomegalovirus, or herpes simplex virus. We present a case of a 53-year-old man with AIDS and prior esophageal candidiasis and oral aphthous ulcerations, who developed actinomycosis of the esophagus. This article aims to review clinical characteristics of this and seven previously reported cases occurring in HIVinfected patients. Esophageal actinomycosis is frequently preceded by other esophageal disease that likely results in breach of the mucosal barrier, allowing establishment of the infection. Health care providers should be aware of this rare entity, particularly in those with recurring symptoms, so that a timely diagnosis can be made.

Journal of Nanoparticle Research, Jan 20, 2010

In this study, we evaluated the combined effect of a known toxic molecule, cisplatin, in combinat... more In this study, we evaluated the combined effect of a known toxic molecule, cisplatin, in combination with relatively nontoxic nanoparticles, amorphous fumed silica, on chondrocyte cells. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule, and characterized in terms of size, shape, specific surface area, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as-received silica nanoparticles ranged from 7.1 to 61 nm, estimated from measurements of specific surface area, and the primary particles were aggregated. The effects of cisplatin-functionalized silica particles with different specific surface areas (41, 85, 202, 237, and 297 m 2 /g) were compared in vitro on chondrocytes, the parenchymal cell of hyaline cartilage. The results show that adverse effects on cell function, as evidenced by reduced metabolic activity measured by the MTT assay and increased membrane permeability observed using the Live/Dead stain, can be correlated with specific surface area of the silica. Cisplatin-functionalized silica nanoparticles with the highest specific surface area incited the greatest response, which was almost equivalent to that induced by free cisplatin. This result suggests the importance of particle specific surface area in interactions between cells and surface-functionalized nanomaterials.

We have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create nanoco... more We have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create nanocomposites that can be used to repair surgically created orbital floor defects in a rabbit animal model. Nanosized hydroxyapatite particles may improve tissue engineering scaffold properties because they have similar length scale of many cellular and molecular components and therefore can enhance cellular adhesion and migration. We hypothesize that inclusion of nanosized hydroxyapatite particles (20-70 nm) within cyclic acetal hydrogels would support bone defect repair. The objectives of our study include (1) characterization of nanocomposites in vitro, (2) investigation of tissue response and capsule tissue surrounding nanocomposites in vivo, and (3) investigation of the potential of nanocomposites to facilitate bone formation at 7-and 28-day time points in vivo. Experimental nanocomposite groups consisted of 0, 10, and 50 ng=mL nanosized hydroxyapatite. In vitro results indicated uniform dispersion of nanoparticles within nanocomposites and increased compressive moduli of nanocomposites with increase in nanoparticle concentration and bone marrow stromal cell viability within nanocomposites. In vivo results at day 7 indicated a tissue response of mild to increased inflammatory cells and presence of immature fibrous tissue. At day 28, tissue response consisted of mild inflammatory response and mature tissue. Quantitative results at day 7 indicated no difference in total bone percentage area between groups. The results also indicated that the tissue capsule surrounding the 0, 10, and 50 ng group implants had no clear organization. Quantitative results at day 28 indicated that the tissue capsule surrounding the 0, 10, and 50 ng group implants was an organized layer and the bone percentage for the 50 ng group was significantly higher than that of the remaining groups. Initial results indicated that our nanocomposites initiate a positive in vivo response in terms of bone growth. However, the percentage of bone area compared with the total area was low at both time points. Thus, in our study, even after addition of nanoparticles to cyclic acetal hydrogels, their biocompatible properties were maintained. On the other hand, addition of nanoparticles to cyclic acetal hydrogels did not lead to complete restoration of orbital floor defects.

The American journal of clinical nutrition, Jan 10, 2016

Although the use of micronutrient powders (MNPs) is considered the preferred approach for childho... more Although the use of micronutrient powders (MNPs) is considered the preferred approach for childhood anemia control, concerns about iron-related morbidity from clinical trials have challenged programmatic scale-up. We aimed to measure the effects of community-based sales of MNPs on diarrhea-, fever-, cough-, and malaria-morbidity episodes in children 6-35 mo of age. We conducted a cluster-randomized trial in rural Western Kenya where 60 villages were randomly assigned to either intervention or control groups. MNPs (containing iron, vitamin A, zinc, and 11 other micronutrients) and other health products (e.g., insecticide-treated bednets, soap, and water disinfectant) were marketed in 30 intervention villages from June 2007 to March 2008. Household visits every 2 wk were used to monitor self-reported MNP use and morbidity (illness episodes in the previous 24 h and hospitalizations in the previous 2 wk) in both groups. Iron, vitamin A, anemia, malaria, and anthropometric measures were ...

Hypertension, 2010

ABSTRACT