Opa (protein II) influences gonococcal organization in colonies, surface appearance, size and attachment to human fallopian tube tissues

Opa-expressing variants of Neisseria gonorrhoeae strain F62-SF and an Opa- variant, all non-piliated, were examined for differences in the interaction of the bacteria within colonies and in attachment to and damage of human fallopian tube mucosa. Expression of certain Opas was associated with the formation of transparent colonies where the bacteria were tightly packed and evenly spaced within the colonies. Expression of other Opas was associated with the formation of opaque colonies where the gonococci were less tightly packed and were unevenly spaced. Distinct differences in the size of the gonococci and in their surface characteristics were dependent upon the Opa being expressed. Certain Opas were associated with gonococci that had significantly larger cross-sectional areas and bigger perimeters. Scanning electron microscopy showed that OpaC- and OpaD-containing variants yielded greater mucosal damage than OpaB-containing and Opa- variants with the least damage caused by the OpaA-containing variant (clumped bacteria from dark opaque friable colonies). The mucosal damage after 60 min incubation included shortening and decreased numbers of microvilli on non-ciliated cells and invagination and sloughing of ciliated cells. Differences in the interactions of gonococci within colonies and in attachment to fallopian tube mucosa and damage to the mucosal cells occurred with different Opa-expressing variants of N. gonorrhoeae strain F62-SF.     

Trends in Vitamin C Consumption in the United States: 1999–2018

Low intakes of fruits and vegetables have resulted in suboptimal intakes of several micronutrients, including vitamin C. This cross-sectional study used data from 84,902 children/adults (≥1 y) who completed a 24-h dietary recall as part of the United States National Health and Nutrition Examination Survey (1999–2018). Mean vitamin C intakes from foods/beverages were calculated as were trends in major food/beverage sources of vitamin C. Percentages below the Estimated Average Requirement (EAR) were estimated. Overall, mean vitamin C consumption declined by 23% (97–75 mg/d; p-value for trend < 0.001). 100% fruit juice was the leading source of vitamin C (25.6% of total or 21.7mg/d), but this declined by 48% (25–13 mg/d; p-value for trend < 0.001). Whole fruit increased among children/adolescents (+75.8%;10–17 mg/d; p-value for trend < 0.001), but not adults, while the vegetable contribution was generally unchanged. The proportion of the population below the EAR increased by 23.8% on a relative scale or 9 percentage points on an absolute scale (38.3–47.4%). Declines in vitamin C intake is driven largely by decreases in fruit juice coupled with modest increases in whole fruit. Due to associations between vitamin C intake and numerous health outcomes these trends warrant careful monitoring moving forward.     

Clinical Concept-Based Radiology Reports Classification Pipeline for Lung Carcinoma

Rising incidence and mortality of cancer have led to an incremental amount of research in the field. To learn from preexisting data, it has become important to capture maximum information related to disease type, stage, treatment, and outcomes. Medical imaging reports are rich in this kind of information but are only present as free text. The extraction of information from such unstructured text reports is labor-intensive. The use of Natural Language Processing (NLP) tools to extract information from radiology reports can make it less time-consuming as well as more effective. In this study, we have developed and compared different models for the classification of lung carcinoma reports using clinical concepts. This study was approved by the institutional ethics committee as a retrospective study with a waiver of informed consent. A clinical concept-based classification pipeline for lung carcinoma radiology reports was developed using rule-based as well as machine learning models and compared. The machine learning models used were XGBoost and two more deep learning model architectures with bidirectional long short-term neural networks. A corpus consisting of 1700 radiology reports including computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) reports were used for development and testing. Five hundred one radiology reports from MIMIC-III Clinical Database version 1.4 was used for external validation. The pipeline achieved an overall F1 score of 0.94 on the internal set and 0.74 on external validation with the rule-based algorithm using expert input giving the best performance. Among the machine learning models, the Bi-LSTM_dropout model performed better than the ML model using XGBoost and the Bi-LSTM_simple model on internal set, whereas on external validation, the Bi-LSTM_simple model performed relatively better than other 2. This pipeline can be used for clinical concept-based classification of radiology reports related to lung carcinoma from a huge corpus and also for automated annotation of these reports.

     

Whipple's disease in a man with weight loss and diarrhea

In a 45-year-old man with diarrhoea, upper abdominal pain and malabsorption Whipple's disease was diagnosed by gastroduodenoscopy with small bowel biopsies. The disease is rare and can present with gastrointestinal problems but also with cardiac or neurological complaints. Tropheryma whippelii, the aetiological organism, can be demonstrated by pathological investigation of biopsies and with the polymerase chain reaction (PCR). Treatment with trimethoprim-sulfamethoxazole 160-800 mg twice daily is the therapy of choice: it must be continued for a year, otherwise there is a high possibility of relapse. Correct diagnosis, based mostly on gastroduodenoscopy, can lead to the right therapy and recovery of the patient.     

Correlations in uncertainty analysis for medical decision making: an application to heart-valve replacement.

A Monte Carlo uncertainty analysis with correlations between parameters is applied to a Markov-chain model that is used to support the choice of a replacement heart-valve. The objective is to quantify the effects of uncertainty in and of correlations between probabilities of valve-related events on the life expectancies of four valve types. The uncertainty in the logit- and log-transformed parameters-mostly representing probabilities and durations-is modeled as a multivariate normal distribution. The univariate distributions are obtained through values for the median and the 0.975 quantile of each parameter. Correlations between parameters are difficult to quantify. A sensitivity analysis is suggested to study their influences on the uncertainty in valve preference prior to further elicitation efforts. The results of the uncertainty analysis strengthen the conclusions from a preceding study, which did not include uncertainty in the model parameters, where the homograft turned out to be the best choice. It is concluded that the influence of correlations is limited in most cases. Preference statements become more certain when the correlation between valve types increases.     

Measurement of in vitro cellular pharmacokinetics of 5-fluorouracil in human and rat cancer cell lines and rat hepatocytes using a flow-through system

Summary A flow-throught system was used to study the cellular pharmacokinetics of 5-fluorouracil (5-FU) in four human cell lines (squamous-cell carcinoma HEp-2, colon carcinoma WiDr, hepatoma Hep G2, and breast carcinoma MCF-7) as well as in the rat hepatoma H35 cell line and in freshly isolated rat hepatocytes. The system made it possible to restrict the decrease in the concentration of 5-FU in the medium, to keep the volume in which the metabolites accumulated relatively small, and to study the dynamics of a response during and after a change in the composition of the eluent. Clearance of 5-FU from the eluent was achieved predominantly (>95%) by its catabolism to dihydrofluorouracil in the tumor cell lines and to 2-fluoro--alanine in the hepatocytes. Not only rat hepatocytes but also HEp-2 cells showed relatively high clearance values. A concentration-dependent 5-FU elimination was observed, indicating saturation of 5-FU elimination according to Michaelis-Menten kinetics (K_m 14–22 M). The maximal velocity (V_max) values ranged from 0.025 to 0.13 nmol 5-FU/10⁶ cells per minute. For HEp-2 cells, high-concentration pulse injections of 5-FU, thymine, uridine, or uracil immediately led to a reduction in 5-FU conversion, followed by recovery within 5 min. The flow-through system proved to be adequate for the study of the non-linear pharmacokinetics of 5-FU in different intact cells and for the comparison of various manipulations of these pharmacokinetics.Abbreviations 5-FU 5-fluorouracil - FUR 5-fluorouridine - F-DHU dihydrofluorouracil - F--ala 2-fluoro--alanine - F-UPA -fluoroureidopropionic acid - HEPES 4-(2-hydroethyl)-1-piperazine-ethane sulfonic acid - MEM modified minimal essential medium - HBSS Hanks' balanced salt solution - HPLC high-performance liquid chromatography Supported by grant IKA 87-16 from the Netherlands Cancer Foundation. One author (G. J. P.) is the recipient of a senior research fellowship from the Royal Netherlands Academy of Arts and Sciences (KNAW)     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.