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1.
Lancet ; 403(10429): 862-876, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38340741

ABSTRACT

Since the discovery of norovirus in 1972 as a cause of what was contemporarily known as acute infectious non-bacterial gastroenteritis, scientific understanding of the viral gastroenteritides has continued to evolve. It is now recognised that a small number of viruses are the predominant cause of acute gastroenteritis worldwide, in both high-income and low-income settings. Although treatment is still largely restricted to the replacement of fluid and electrolytes, improved diagnostics have allowed attribution of illness, enabling both targeted treatment of individual patients and prioritisation of interventions for populations worldwide. Questions remain regarding specific genetic and immunological factors underlying host susceptibility, and the optimal clinical management of patients who are susceptible to severe or prolonged manifestations of disease. Meanwhile, the worldwide implementation of rotavirus vaccines has led to substantial reductions in morbidity and mortality, and spurred interest in vaccine development to diminish the impact of the most prevalent viruses that are implicated in this syndrome.


Subject(s)
Enterovirus Infections , Gastroenteritis , Norovirus , Plastic Surgery Procedures , Humans , Gastroenteritis/therapy , Income
2.
BMC Public Health ; 23(1): 674, 2023 04 11.
Article in English | MEDLINE | ID: mdl-37041550

ABSTRACT

BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.


Subject(s)
COVID-19 , Influenza, Human , Humans , Peru , Influenza, Human/epidemiology , Case-Control Studies , SARS-CoV-2 , Fever/epidemiology , Polymerase Chain Reaction , Health Facilities , COVID-19 Testing
3.
J Oral Maxillofac Surg ; 80(6): 1094-1102, 2022 06.
Article in English | MEDLINE | ID: mdl-35405094

ABSTRACT

PURPOSE: It is unclear whether certain bacteria initiate the development of inflammatory jaw conditions, or whether these diseases create a milieu for dysbiosis and secondary colonization of indigenous flora. At present, there are no comparative studies on the types of bacteria that colonize different inflammatory jaw conditions. Accordingly, this study aims to identify and compare the types of bacteria isolated in osteomyelitis, osteoradionecrosis, and MRONJ. METHODS: This is a retrospective cohort study of patients diagnosed with inflammatory jaw conditions. The predictor variables were classification of bacteria as oral flora, categorized herein as resident bacteria, non-resident bacteria, or opportunistic organisms. The outcome variables were a diagnosis of osteomyelitis, osteoradionecrosis, and MRONJ. Covariates were age, sex, penicillin allergy, a diagnosis of diabetes and a history of smoking. Data analysis was performed using ANOVA and chi-squared tests. RESULTS: A total of 105 patients with inflammatory jaw conditions were enrolled. The final sample size was 69 subjects of which 16 were diagnosed with osteomyelitis, 20 with osteoradionecrosis, and 33 with MRONJ. There was no difference in the frequency that resident bacteria were isolated. Non-resident bacteria, which included Staphylococcus and Enterococcus among others, were isolated more frequently at 75% in osteomyelitis compared to 60% in osteoradionecrosis and 48% in MRONJ cases. There is weak evidence of significant difference when comparing osteomyelitis and MRONJ cases (P = .08). Opportunistic organisms, which included Mycobacterium and Candida, were isolated more frequently in osteoradionecrosis at 30% compared to 12.5% in osteomyelitis and 12.12% in MRONJ cases. There is weak evidence of significant difference when comparing osteoradionecrosis and MRONJ cases (P = .1). CONCLUSION: Non-resident bacteria including Staphylococcus and Enterococcus may be more frequently isolated in patients with osteomyelitis, while opportunistic organisms like Mycobacterium and Candida may be more frequently found in patients diagnosed with osteoradionecrosis.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Osteomyelitis , Osteoradionecrosis , Bacteria , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Candida , Humans , Jaw/pathology , Osteomyelitis/pathology , Osteoradionecrosis/diagnosis , Retrospective Studies
4.
Cell Biol Toxicol ; 36(3): 209-221, 2020 06.
Article in English | MEDLINE | ID: mdl-31686351

ABSTRACT

Chloropropanols are chemical contaminants that can be formed during industrial processing of foods, such as lipids used in commercially available infant and toddler formula in the USA. Many researchers have studied the most common chloropropanol contaminant, 3-monochloropropane-1,2-diol (3-MCPD), as well as its lipid ester derivatives. A plethora of toxicological outcomes have been described in vivo, including effects on the heart, nervous system, reproductive organs, and kidneys. To better understand the concordance of some of these effects to in vitro outcomes, we focused our research on using an in vitro cellular model to investigate whether the proximal tubule cells of the kidney would be vulnerable to the effects of free 3-MCPD and nine of its common esters in commercial formula. Using the established human kidney proximal tubule cell line, HK-2, we performed 24-h treatments using 3-MCPD and nine mono- or di-esters derived from palmitate, oleate, and linoleate. By directly exposing HK-2 cells at treatment doses ranging from 0 to 100 µM, we could evaluate their effects on cell viability, mitochondrial health, reactive oxygen species (ROS) production, and other endpoints of toxicity. Since chloropropanols reportedly inhibit cellular metabolism through interference with glycolysis, we also tested the extent of this mechanism. Overall, we found mild but statistically significant evidence of cytotoxicity at the highest tested treatment concentrations, which were also associated with mitochondrial dysfunction and transient perturbations in cellular metabolism. Based on these findings, further studies will be required to better understand the effects of these compounds under conditions that are more physiologically relevant to human infant and toddler proximal tubules in order to mimic their exposure to chloropropanol-containing foods.


Subject(s)
Kidney Tubules, Proximal/metabolism , alpha-Chlorohydrin/toxicity , Cell Line , Esters/pharmacology , Fatty Acids , Humans , Kidney/drug effects , Kidney Tubules, Proximal/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , alpha-Chlorohydrin/analogs & derivatives
5.
Metabolomics ; 15(1): 4, 2019 01 03.
Article in English | MEDLINE | ID: mdl-30830465

ABSTRACT

We describe here the agreed upon first development steps and priority objectives of a community engagement effort to address current challenges in quality assurance (QA) and quality control (QC) in untargeted metabolomic studies. This has included (1) a QA and QC questionnaire responded to by the metabolomics community in 2015 which recommended education of the metabolomics community, development of appropriate standard reference materials and providing incentives for laboratories to apply QA and QC; (2) a 2-day 'Think Tank on Quality Assurance and Quality Control for Untargeted Metabolomic Studies' held at the National Cancer Institute's Shady Grove Campus and (3) establishment of the Metabolomics Quality Assurance and Quality Control Consortium (mQACC) to drive forward developments in a coordinated manner.


Subject(s)
Metabolomics/methods , Metabolomics/standards , Humans , Laboratories , Quality Control , Quality Improvement
6.
Neural Comput ; 27(6): 1321-44, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25826019

ABSTRACT

Supervised learning in recurrent neural networks involves two processes: the neuron activity from which gradients are estimated and the process on connection parameters induced by these measurements. A problem such algorithms must address is how to balance the relative rates of these activities so that accurate sensitivity estimates are obtained while still allowing synaptic modification to take place at a rate sufficient for learning. We show how to calculate a sufficient timescale separation between these two processes for a class of contracting neural networks.


Subject(s)
Learning/physiology , Neural Networks, Computer , Algorithms , Animals , Artificial Intelligence , Computer Simulation , Humans , Models, Neurological , Neurons/physiology
7.
BJU Int ; 116(5): 805-14, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25168771

ABSTRACT

OBJECTIVE: To evaluate functional outcomes of continent cutaneous urinary diversion (CCUD) after radical cystectomy (RC) and to compare diversion-related complications and long-term renal function in a contemporary cohort of patients undergoing urinary diversion with CCUD, orthotopic bladder substitute (OBS) and ileal conduit (IC). PATIENTS AND METHODS: In all, 322 patients underwent RC and CCUD, OBS or IC from January 2002 to June 2013. CCUD was performed using either a modified Indiana pouch or an appendiceal stoma. For patients with CCUD, continence status and time intervals between clean intermittent catheterisations at last follow-up were recorded. For all three diversion types, diversion-related complications and renal function outcome, as determined by the estimated glomerular filtration rate (eGFR) at baseline and at different time intervals after surgery, were evaluated. Multivariate regression analysis was used to evaluate the association of diversion type, baseline variables and diversion-related complications with renal function over time. RESULTS: Of all 322 patients, 73 (23%) received a CCUD, 79 (25%) received an OBS, and 170 (53%) received an IC. After a median follow-up of 36 months, the continence rate for patients with a CCUD was 89%. In all, 64 (88%) patients with a CCUD were able to catheterise every 4-8 h and five (7%) were able to catheterise every 8-10 h. After a median follow-up of 35 months, rates of diversion-related complications were similar among patients who underwent a CCUD, an OBS or an IC. Patients who received an IC had poorer renal function preoperatively than those who received a CCUD or an OBS. However, at 1 year after surgery and thereafter, the three groups had comparable renal function. On multivariate analysis, the type of urinary diversion was not associated with decline in renal function. However, patient age at surgery, diabetes mellitus, baseline eGFR, postoperative non-obstructive hydronephrosis and uretero-enteric stricture were associated with decline in renal function. CONCLUSIONS: A CCUD is associated with excellent functional outcomes. The rates of diversion-related complications and renal function outcomes are comparable with those from an OBS and an IC. A CCUD should be considered a valid alternative for patients who undergo cystectomy and require urinary diversion.


Subject(s)
Cystectomy , Kidney/physiopathology , Urinary Bladder Neoplasms/surgery , Urinary Bladder/surgery , Urinary Diversion , Aged , Aged, 80 and over , Female , Glomerular Filtration Rate , Humans , Kidney Function Tests , Male , Postoperative Complications/etiology , Urinary Bladder/physiopathology , Urinary Bladder Neoplasms/pathology , Urinary Diversion/methods , Urinary Reservoirs, Continent
8.
World J Urol ; 33(9): 1315-21, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25410374

ABSTRACT

PURPOSE: To assess complication rates and early oncological outcomes of patients aged ≥80 years who underwent robot-assisted radical cystectomy (RARC). METHODS: A total of 368 consecutive patients underwent radical cystectomy from April 2001 to September 2013 in a tertiary referral center. Sixty-one patients aged ≥80 years underwent RARC and constitute the cohort of interest. Complications arising within 30 and 90 days of surgery were graded using the modified Clavien classification and were additionally categorized by organ system using a standardized complication reporting system. Recurrence-free survival, disease-specific survival and overall survival were calculated using Kaplan-Meier curves. RESULTS: Median age was 83 years (range 80-94). Twenty-nine (48 %) of all tumor specimens were stage ≥pT3. The median number of nodes removed was 19 (range 6-67). The soft tissue positive margin rate was 10 %. A total of 27 (44 %) patients had complications within 90 days, of which 9 had major complications. Two patients (3 %) died from surgical complications within 90 days. At a median follow-up of 13 months, 12 (20 %) patients had developed recurrent cancer and subsequently died from disease. An additional 13 (21 %) patients died from non-cancer-related causes. The median overall survival time was 36.0 months. At 2 years, recurrence-free, cancer-specific and overall survival rates were 73, 74 and 61 %, respectively. CONCLUSIONS: In patients aged ≥80 years, RARC is feasible with acceptable perioperative morbidity and favorable short-term oncological outcomes. Therefore, RARC should be considered a valid option for carefully selected patients aged ≥80 years with bladder cancer.


Subject(s)
Cystectomy/adverse effects , Neoplasm Recurrence, Local/epidemiology , Postoperative Complications/epidemiology , Robotics/methods , Urinary Bladder Neoplasms/surgery , Age Factors , Aged, 80 and over , Cystectomy/methods , Disease-Free Survival , Female , Follow-Up Studies , Humans , Incidence , Male , Neoplasm Staging , New York/epidemiology , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Survival Rate/trends , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/mortality
9.
Cell Biol Toxicol ; 31(4-5): 221-30, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26377104

ABSTRACT

A human hepatoma cell line (HuH-7) was evaluated as a metabolically competent cell model to investigate cytochrome P450 3A4 (CYP3A4) inhibition, induction, and hepatotoxicity. First, CYP3A4 gene expression and activity were determined in HuH-7 cells under three culture conditions: 1-week culture, 3-week culture, or 1 % dimethyl sulfoxide (DMSO) treatment. HuH-7 cells treated with DMSO for 2 weeks after confluence expressed the highest CYP3A4 gene expression and activity compared to the other two culture conditions. Furthermore, CYP3A4 activity in DMSO-treated HuH-7 cells was compared to that in a human hepatoma cell line (HepG2/C3A) and human bipotent progenitor cell line (HepaRG), which yielded the following ranking: HepaRG > DMSO-treated HuH-7 >> HepG2/C3A cells. The effects of three known CYP3A4 inhibitors were evaluated using DMSO-treated HuH-7 cells. CYP3A4 enzyme inhibition in HuH-7 cells was further compared to human recombinant CYP3A4, indicating similar potency for reversible inhibitors (IC 50 within 2.5-fold), but different potency for the irreversible inhibitor. Next, induction of CYP3A4 activity was compared between DMSO-treated HuH-7 and HepaRG cells using two known inducers. DMSO-treated HuH-7 cells yielded minimal CYP3A4 induction compared to that in the HepaRG cells after 48-h treatments. Finally, the cytotoxicity of five known hepatotoxicants was evaluated in DMSO-treated HuH-7, HepG2/C3A, and HepaRG cells, and significant differences in cytotoxic sensitivity were observed. Overall, DMSO-treated HuH-7 cells are a valuable model for medium- or high-throughput screening of chemicals for CYP3A4 inhibition and hepatotoxicity.


Subject(s)
Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Dimethyl Sulfoxide/pharmacology , Hepatocytes/drug effects , Hepatocytes/enzymology , Toxicity Tests/methods , Carcinoma, Hepatocellular/enzymology , Cell Line, Tumor , Cytochrome P-450 CYP3A/biosynthesis , Cytochrome P-450 CYP3A/genetics , Gene Expression/drug effects , Hep G2 Cells , Humans , Liver Neoplasms/enzymology
10.
Cell Biol Toxicol ; 31(6): 285-93, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26838987

ABSTRACT

Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.


Subject(s)
Epithelial Cells/drug effects , Mitochondria/drug effects , Plant Extracts/pharmacology , Rauwolfia/chemistry , Reactive Oxygen Species/agonists , Cell Line , Cell Survival/drug effects , Cisplatin/pharmacology , Cystatin C/genetics , Cystatin C/metabolism , Dose-Response Relationship, Drug , Epithelial Cells/cytology , Epithelial Cells/metabolism , Gene Expression Regulation , Hepatitis A Virus Cellular Receptor 1 , Humans , Kidney Tubules, Proximal/cytology , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Membrane Potential, Mitochondrial/drug effects , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism , Receptors, Virus/genetics , Receptors, Virus/metabolism , Valproic Acid/pharmacology , beta 2-Microglobulin/genetics , beta 2-Microglobulin/metabolism
11.
Article in English | MEDLINE | ID: mdl-38555234

ABSTRACT

Epilepsy is one of the most common neurological problems affecting 470,000 children in the United States. While most youth will achieve seizure freedom using medication, up to a third will continue to have seizures and are therefore considered to have drug-resistant epilepsy (DRE). Children and adolescents with epilepsy are at higher risk of behavioral, cognitive, and emotional disorders. Youth with DRE are at even greater risk of behavioral and emotional problems impacting quality of life and may need to pursue surgical interventions, including resective surgery or device implantation. Due to advances in the evaluation of candidates and surgical options, epilepsy surgery is more effective and has become second-line treatment for youth with DRE. This paper highlights the importance of exploring, assessing, and treating psychological and neuropsychological factors throughout the three phases of the epilepsy surgery process and ways pediatricians can support youth and families.

12.
Am J Trop Med Hyg ; 111(1): 80-88, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38806041

ABSTRACT

In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of resistance to benzimidazoles are of concern. In an observational study in Peru, we studied the clinical efficacy of 400 mg of albendazole 20 days after treatment among children aged 2-11 years. Of 426 participants who provided samples, 52.3% were infected with a STH, 144 (33.8%) were positive for Ascaris (41.8% light, 50.8% moderate, and 7.4% heavy infections), 147 (34.5%) were positive for Trichuris (75.2% light, 22.5% moderate, and 2.3% heavy infections), and 1.1% were positive for hookworm species (100% light infections). Additional stool samples were examined at 20, 90, and 130 days after the initial treatment. At 20 days post-administration of albendazole, the cure rate (CR) of Ascaris infection was 80.1% (95% CI: 73.5-86.7), and the egg reduction rate (ERR) was 70.8% (95% CI: 57.8-88.7); the CR for Trichuris infection was 27.1% (95% CI: 20.0-34.3), and the ERR was 29.8% (95% CI: -1.40 to 57.5). Among participants with persistent or recurrent infections with Trichuris, the combined therapy of albendazole (400 mg) and ivermectin at 600 µg/dose increased overall CR for Trichuris infection to 75.2% (95% CI: 67.3-83.2%) with an ERR of 84.2% (95% CI: 61.3-93.8%). Albendazole administration alone for the control of STH was associated with high rates of treatment failure, especially for Trichuris. Combined single doses of albendazole and ivermectin was observed to have improved efficacy.


Subject(s)
Albendazole , Anthelmintics , Helminthiasis , Ivermectin , Soil , Humans , Albendazole/therapeutic use , Albendazole/administration & dosage , Peru/epidemiology , Child, Preschool , Child , Ivermectin/therapeutic use , Ivermectin/administration & dosage , Male , Female , Soil/parasitology , Helminthiasis/drug therapy , Helminthiasis/epidemiology , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage , Feces/parasitology , Drug Therapy, Combination , Animals , Treatment Outcome , Trichuriasis/drug therapy , Trichuriasis/epidemiology , Ascariasis/drug therapy , Ascariasis/epidemiology , Trichuris/drug effects
13.
Open Forum Infect Dis ; 11(Suppl 1): S121-S128, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38532951

ABSTRACT

Background: The Enterics for Global Health (EFGH) Peru site will enroll subjects in a periurban area of the low Amazon rainforest. The political department of Loreto lags behind most of Peru in access to improved sources of water and sanitation, per capita income, children born <2.5 kg, and infant and child mortality. Chronic undernutrition as manifested by linear growth shortfalls is common, but wasting and acute malnutrition are not. Methods: The recruitment of children seeking care for acute diarrheal disease takes place at a geographic cluster of government-based primary care centers in an area where most residents are beneficiaries of free primary healthcare. Results: Rates of diarrheal disease, dysentery, and Shigella are known to be high in the region, with some of the highest rates of disease documented in the literature and little evidence in improvement over the last 2 decades. This study will update estimates of shigellosis by measuring the prevalence of Shigella by polymerase chain reaction and culture in children seeking care and deriving population-based estimates by measuring healthcare seeking at the community level. Conclusions: Immunization has been offered universally against rotavirus in the region since 2009, and in a context where adequate water and sanitation are unlikely to obtain high standards in the near future, control of principal enteropathogens through immunization may be the most feasible way to decrease the high burden of disease in the area in the near future.

14.
Sci Data ; 10(1): 830, 2023 11 25.
Article in English | MEDLINE | ID: mdl-38007532

ABSTRACT

Prostate cancer is the second most common cancer in men and affects 1 in 9 men in the United States. Early screening for prostate cancer often involves monitoring levels of prostate-specific antigen (PSA) and performing digital rectal exams. However, a prostate biopsy is always required for definitive cancer diagnosis. The Early Detection Research Network (EDRN) is a consortium within the National Cancer Institute aimed at improving screening approaches and early detection of cancers. As part of this effort, the Weill Cornell EDRN Prostate Cancer has collected and biobanked specimens from men undergoing a prostate biopsy between 2008 and 2017. In this report, we describe blood metabolomics measurements for a subset of this population. The dataset includes detailed clinical and prospective records for 580 patients who underwent prostate biopsy, 287 of which were subsequentially diagnosed with prostate cancer, combined with profiling of 1,482 metabolites from plasma samples collected at the time of biopsy. We expect this dataset to provide a valuable resource for scientists investigating prostate cancer metabolism.


Subject(s)
Prostatic Neoplasms , Humans , Male , Biopsy , Prospective Studies , Prostate , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , United States
15.
Am J Cardiol ; 208: 164-170, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37844519

ABSTRACT

Patients with a single ventricle develop aortopulmonary collaterals (APCs) whose flow has been shown to be inversely proportional to cerebral blood flow (CBF) in a previous cross-sectional study. Longitudinal CBF and APC flow in patients with Fontan physiology adjusting for brain injury (BI) has never been reported. Decreased CBF and BI may adversely impact neurodevelopment. A prospective longitudinal cohort of 27 patients with Fontan physiology (aged 10 ± 1.9 years, 74% male) underwent cardiac and brain magnetic resonance imaging 3 to 9 months and 6.0 ± 1.86 years after Fontan operation to measure the CBF and APC flow and to reassess the BI (focal BI, generalized insult, and hemorrhage). CBF was measured using jugular venous flow and APC flow was measured by the difference between aortic flow and caval return. Multivariate modeling was used to assess the relation between the change in APC flow and BI. A strong inverse relation was found between CBF/aortic flow change and APC flow/aortic flow and APC flow/body surface area change (R2 = 0.70 and 0.72 respectively, p <0.02). Overall, the CBF decreased by 9 ± 11% and the APC flow decreased by 0.73 ± 0.67 l/min/m2. The evolution of CBF and APC flow were significantly and inversely related when adjusting for time since Fontan operation, gender, and BI on the multivariate modeling. Every unit increase in APC flow change was associated with an 8% decrease in CBF change. In conclusion, CBF and APC flow change are inversely related across serial imaging, adjusting for time from Fontan operation, gender, and BI. CBF and APC aortic flow decrease over a 6-year period. This may adversely impact neurodevelopment. Because APCs can be embolized, this may be a modifiable risk factor. Clinical trials numbers: NCT02135081 and NCT02919956.


Subject(s)
Brain Injuries , Fontan Procedure , Heart Defects, Congenital , Humans , Male , Female , Fontan Procedure/methods , Prospective Studies , Pulmonary Circulation , Heart Defects, Congenital/surgery , Cerebrovascular Circulation
16.
Res Sq ; 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37034707

ABSTRACT

Background: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. Methods: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. Discussion: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 hours and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific, prevalent pathogens as a cause of acute illness. Study Registration: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

17.
J Oral Maxillofac Surg ; 70(8): 1854-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22326175

ABSTRACT

PURPOSE: Historically, the identification of microorganisms has been limited to species that could be cultured in the microbiology laboratory. The purpose of the present study was to apply molecular techniques to identify microorganisms in orofacial odontogenic infections (OIs). MATERIALS AND METHODS: Specimens were obtained from subjects with clinical evidence of OI. To identify the microorganisms involved, 16S rRNA sequencing methods were used on clinical specimens. The name and number of the clones of each species identified and the combinations of species present were recorded for each subject. Descriptive statistics were computed for the study variables. RESULTS: Specimens of pus or wound fluid were obtained from 9 subjects. A mean of 7.4 ± 3.7 (standard deviation) species per case were identified. The predominant species detected in the present study that have previously been associated with OIs were Fusobacterium spp, Parvimonas micra, Porphyromonas endodontalis, and Prevotella oris. The predominant species detected in our study that have not been previously associated with OIs were Dialister pneumosintes and Eubacterium brachy. Unculturable phylotypes accounted for 24% of the species identified in our study. All species detected were obligate or facultative anaerobes. Streptococci were not detected. CONCLUSIONS: Molecular methods have enabled us to detect previously cultivated and not-yet-cultivated species in OIs; these methods could change our understanding of the pathogenic flora of orofacial OIs.


Subject(s)
Bacteria/classification , Gram-Negative Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/diagnosis , Tooth Diseases/microbiology , Bacteria/genetics , Bacterial Typing Techniques , Bacteroidaceae Infections/diagnosis , Cohort Studies , Coinfection/diagnosis , Eubacterium/classification , Fusobacterium Infections/diagnosis , Gram-Negative Anaerobic Straight, Curved, and Helical Rods/classification , Humans , Molecular Biology , Peptostreptococcus/classification , Porphyromonas endodontalis/classification , Prevotella/classification , Prospective Studies , RNA, Bacterial/analysis , RNA, Ribosomal, 16S/analysis , Sequence Analysis, RNA
18.
Int Ophthalmol ; 32(5): 471-3, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22581322

ABSTRACT

We describe a patient with severe atopic dermatitis and keratoconjunctivitis, who was prescribed both systemic and topical ciclosporin and who developed ocular surface squamous neoplasia (OSSN). To provide additional information on the incidence of the association between topical ciclosporin use and OSSN, we counted the total prescriptions for topical ciclosporin issued in our hospital between 2003 and 2006 (804 patients) and, for the same period, we reviewed the records of patients with OSSN for a history of treatment with ciclosporin or a history of atopy. No other case of OSSN in a patient with a history of topical ciclosporin use was identified, which makes it difficult to implicate topical ciclosporin as the causative factor.


Subject(s)
Carcinoma, Squamous Cell/etiology , Conjunctiva/pathology , Conjunctival Neoplasms/etiology , Immunocompromised Host , Keratoconjunctivitis/complications , Carcinoma, Squamous Cell/diagnosis , Conjunctival Neoplasms/diagnosis , Diagnosis, Differential , Female , Humans , Keratoconjunctivitis/diagnosis , Keratoconjunctivitis/immunology , Middle Aged , Photomicrography
19.
Article in English | MEDLINE | ID: mdl-20940664

ABSTRACT

PURPOSE: Lid contour is important for eyelid symmetry, but clinical quantification can be difficult. The marginal peak is a major determinant of upper eyelid contour, and its horizontal position, relative to the mid-pupillary line, may be used as a measure of symmetry after surgery. This study used digital image analysis to assess the peak position in patients who had undergone levator aponeurosis repair. METHODS: An unselected group of patients underwent anterior-approach levator aponeurosis repair, performed under local anesthesia by a single surgeon, using 3 6/0 Vicryl sutures to reattach the levator aponeurosis to the upper tarsus. Both before and 2-3 weeks after ptosis repair, digital photographs were taken in a fixed format and the images analyzed using NIH imaging software to assess the position of the upper eyelid peak. Comparisons were made between the pre- and postoperative measurements in the operated eye and between the operated eye and its fellow eye. RESULTS: Twenty people (8 male; 40%) underwent unilateral levator muscle resection (9 right eyes; 45%). In eyes before ptosis surgery, the peak was significantly more medially placed (median +0.17 mm) as compared with that of fellow eyes (median +0.80 mm) (p = 0.023). There was a significant temporal shift of the median peak after surgery, from +0.17 mm to +0.92 mm (p = 0.029). Although there was a minor nasal shift of peak in the unoperated eyes after contralateral surgery (median +0.80 mm to +0.64 mm), the peak positions for the 2 eyes were not significantly different at 2-3 weeks after aponeurosis repair (p = 0.22). CONCLUSIONS: Digital image analysis allows an objective assessment of the upper eyelid marginal contour after ptosis repair. A nasal shift in the upper eyelid marginal peak has been identified in ptotic eyes (as compared with the contralateral side) and, after successful ptosis repair, there is a significant temporal shift to match the unoperated fellow eye.


Subject(s)
Blepharoptosis/diagnosis , Eyelids/pathology , Image Processing, Computer-Assisted , Oculomotor Muscles/pathology , Suture Techniques , Anesthesia, Local , Blepharoplasty , Blepharoptosis/surgery , Eyelids/surgery , Female , Humans , Male , Oculomotor Muscles/surgery , Photography , Reproducibility of Results
20.
Facial Plast Surg Aesthet Med ; 23(5): 339-343, 2021 09.
Article in English | MEDLINE | ID: mdl-33710909

ABSTRACT

Importance: A centralized repository of clinically applicable facial images with unrestricted use would facilitate facial aesthetic research. Objective: Using a machine learning neural network, we aim to (1) create a repository of synthetic faces that can be used for facial aesthetic research and (2) analyze synthetic faces according to contemporary aesthetic principles. Design, Setting, and Participants: Synthetic facial images were generated using an open source generative adversarial network. Images were refined and then analyzed using computer vision technology. Interventions: Not applicable. Main Outcomes and Measures: Synthetic facial images were created for use as a facial aesthetic research data set. Results: One thousand synthetic images were generated, and 60 images underwent analysis. Image attributes, including age, gender, image principle axis, facial emotion, and facial landmark points, were attained. Images demonstrated accordance with contemporary aesthetic principles of horizontal thirds and vertical fifths. Images demonstrated excellent correspondence when compared with real human facial photographs. Conclusions and Relevance: We have generated realistic synthetic facial images that have potential as a valuable research tool and demonstrate similarity to real human photographs while adhering to contemporary aesthetic principles.


Subject(s)
Esthetics , Face/anatomy & histology , Image Processing, Computer-Assisted , Machine Learning , Photography , Adult , Biomedical Research , Female , Humans , Male , Middle Aged
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