Trends in sexually transmitted infection screening during COVID-19 and missed cases among adolescents.

OBJECTIVE: The COVID-19 pandemic disrupted sexual health services for young people, with potential consequences of decreasing preventive screening and increasing undiagnosed sexually transmitted infections (STIs). This study aimed to assess trends in asymptomatic screening among patients receiving STI testing and to estimate the number of STI cases that were missed during the early months of the pandemic. STUDY DESIGN: A cross-sectional study of electronic health records for chlamydia, gonorrhea, and trichomonas testing encounters from six pediatric primary care clinics in Philadelphia, July 2014 to November 2020. METHODS: A total of 35,548 testing encounters were analyzed, including 2958 during the pandemic. We assessed whether testing at each encounter was performed as asymptomatic screening, risk-based testing, or symptomatic testing. We evaluated screening trends over time and estimated the number of missed STI cases during the pandemic. RESULTS: The mean monthly testing encounters decreased from 479 per month prepandemic to 329 per month during the pandemic. The percent of tests performed as asymptomatic screening dropped from 72.5% prepandemic to a nadir of 54.5% in April 2020. We estimate that this decrease in asymptomatic screening would represent 159 missed cases (23.8% of expected cases) based on patient volume from the previous year. CONCLUSIONS: During the pandemic, the total volume of STI testing encounters and the proportion of tests performed as asymptomatic screening decreased, potentially resulting in missed diagnoses. Undiagnosed STIs can result in severe sequelae and contribute to community transmission of STIs. Efforts are needed to re-establish and sustain access to STI services for adolescents in response to disruptions caused by the pandemic.

The educational value of using cumulative sum charts.

Various workplace-based assessment tools are available, but none have been shown to improve performance in procedural skills. This study aimed to assess the impact of using one such tool, cumulative sum charts, on procedural skill ability. A single-blind randomised controlled trial was conducted on 82 final year medical students. Control group students received the usual teaching; in addition to this, intervention group students were provided with cumulative sum charts to log their cannulation attempts over a 7-month period. At the end of the year, students from both groups undertook a validated test of automaticity of cannulation skill. Students in the intervention group obtained median (IQR [range]) scores of 68.2 (60.5-74.3 [42.7-81.1]) vs 62.2 (52.2-68.8 [40.7-80.5]) for the control group (p = 0.013). The effect size was moderate (Cohen's d = 0.608). This study therefore provides support for the hypothesis that use of cumulative sum charts improves performance when learning procedural skills.

Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis.

OBJECTIVE: Familial haemophagocytic lymphohistiocytosis (FHL) is a fatal disorder of immune dysregulation with defective cytotoxic lymphocyte function. Disease-causing mutations have been identified in the genes encoding perforin (PRF1), syntaxin-11 (STX11), and Munc13-4 (UNC13D). We screened for UNC13D mutations and studied clinical and functional implications of such mutations in a well defined patient cohort. METHODS: Sequencing of UNC13D was performed in 38 FHL patients from 34 FHL families in which PRF1 and STX11 mutations had been excluded. RESULTS: We identified six different mutations affecting altogether 9/38 individuals (24%) in 6/34 (18%) unrelated PRF1/STX11-negative families. Four novel mutations were revealed; two homozygous nonsense mutations (R83X and W382X), one splice mutation (exon 28), and one missense mutation (R928P). In addition, two known mutations were identified (R214X and a deletion resulting in a frame-shift starting at codon 782). There was considerable variation in the age at diagnosis, ranging from time of birth to 14 years (median 69 days). Three of nine patients (33%) developed central nervous system (CNS) symptoms. Natural killer (NK) cell activity was impaired in all four patients studied. Defective cytotoxic lymphocyte degranulation was evident in the two patients investigated, more pronounced in the patient with onset during infancy than in the patient with adolescent onset. CONCLUSIONS: Biallelic UNC13D mutations were found in 18% of the PRF1/STX11-negative FHL families. Impairment of NK cell degranulation was less pronounced in a patient with adolescent onset. FHL should be considered not only in infants but also in adolescents, and possibly young adults, presenting with fever, splenomegaly, cytopenia, hyperferritinaemia, and/or CNS symptoms.

Estimation of the Stokes radii of serum proteins for a study of protein movement from blood to amniotic fluid.

The effective hydrodynamic (Stokes) radii of fifteen serum proteins were estimated by Sephadex G 200 gel filtration and immunochemical methods. The Waldmann-Meyer and Birch equation (Protides Biol. Fluids, Proc. 21st Colloq. (1974) (Peeters, H., ed.), Vol. 21, pp. 653-656, Pergamon Press, Oxford) was used for maximum accuracy. Three replicate column runs were made to assess the precision for the size determinations (coefficients of variation 0.6-2.7(). Quantive two-dimensional immunoelectrophoresis was used to measure eleven proteins in specimens of serum and amniotic fluid collected from twelve normal pregnancies. There was a close inverse linear relationship between the amniotic fluid/serum ratios of the proteins and their Stokes radii. This indicates that the movement of a protein from the blood to amniotic fluid is determined by the size of the protein. The linear correlation of protein amniotic fluid/serum ratio with Stokes radius was better than that with molecular weight. This demonstrates that, as an expression of protein size, Stokes radius should be used in preference to molecular weight when protein filtration systems are being investigated.

Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology?

Glucose-dependent insulinotropic polypeptide (GIP) is said to be a major physiologic factor in the augmentation of the insulin response to oral glucose. Whether GIP promotes insulin release at physiologic concentrations of glucose or GIP, however, is questionable. To investigate this further, volunteers were infused with 10, 20, or 40 g intravenous (i.v.) glucose, with or without simultaneous GIP infusion, to produce plasma levels of GIP or glucose similar to those seen after oral glucose. The effect of 40 g i.v. glucose with three times the original dose of GIP was also investigated. No significant enhancement of glucose-stimulated insulin secretion was seen when GIP was infused with 10 or 20 g i.v. glucose; however, with 40 g a doubling of the insulin response occurred. The higher dose of GIP caused a further increase in insulin response (30-min increment, 972 +/- 191 pmol/L; compared with glucose alone, 356 +/- 100 pmol/L, P less than 0.01; and compared with low GIP, 602 +/- 247 pmol/L, P less than 0.02). The glucose increment after the 40-g i.v. dose was +9.2 mmol/L. The concentration of GIP and glucose required to produce significant potentiation of the insulin response appears to be in the pharmacologic, rather than physiologic, range.

Bombesin, somatostatin and neurotensin-like immunoreactivity in bronchial carcinoma.

Bombesin, a regulatory peptide found in adult lung and in higher concentration during development in the foetal lung, has potent biological actions which include the ability to stimulate the release of a number of hormones. Radioimmunoassay of extracts of tumour, lung and plasma from patients with bronchial carcinoma revealed very high tissue bombesin concentrations in two oat cell carcinomas, with lower levels in two out of six adenocarcinomas exceeding the concentrations found in normal lung. The oat cell carcinomas also contained significant amounts of somatostatin and in one case neurotensin. Neurotensin was further detected in two out of seven squamous tumours and three adenocarcinomas. Secretion of regulatory peptides by bronchial carcinomas may account for some of their ill-understood non-metastatic clinical manifestations.

Influence of dietary intakes of erythorbic acid on plasma vitamin C analyses.

D-Erythorbic acid is an epimer of L-ascorbic acid, but lacks antiscorbutic activity. It is commonly used as a food additive, particularly in processed meat items. Except for high-performance liquid chromatography (HPLC) methodology, the commonly used analytical procedures to measure vitamin C do not distinguish between the two isomers. A study with seven adult women demonstrated that the concentration of erythorbic acid present in food items commonly consumed was sufficient to produce interference in plasma vitamin C analyses. With the meals used, 7-23% of the apparent vitamin C in plasma obtained 2 h after the ingestion of the meals was actually erythorbic acid when analyzed by HPLC. To avoid falsely high plasma-serum vitamin C values as a result of erythorbic acid ingestion, the analyses should be conducted on overnight fasting blood specimens or with the use of an HPLC-amperometric method.

A micro method for the estimation of killing and phagocytosis of Candida albicans by human leucocytes.

A micro method is described for quantitation of the candidacidal and phagocytic capacity of human neutrophils based on previous studies which showed that non-viable Candida albicans are differentially stained by methylene blue. The assay was performed on a microplate using small numbers of phagocytes (2 x 10(3) per well) and Candida albicans (2 x 10(3) or 8 x 10(3) per well) and both the phagocytic and microbicidal activity could be observed in situ within the phagocytic cell. The technique requires small volumes of blood (2 ml) and simple apparatus. Plates may be stored after fixation of stained preparations which makes it particularly suitable as an initial screen of phagocyte function for routine clinical use.

The autopsy. Simple thoughts about the public needs and how to address them.

Dialogue regarding the autopsy has been sustained largely by medical students and professionals, and by families of deceased patients. Exclusion of the general public may represent a significant reason for the inexorable decline of autopsy rates and politicoeconomic support. Sensitivity to public concerns regarding the autopsy process carries far-reaching moral and educational significance. A better understanding of the social value of the autopsy will help to ensure its survival in a climate of ever-tightening health-care budgets. Emphasis must be placed on integrating the autopsy process, from the initial request, performance and post-autopsy follow-up with families, to the diagnostic, pathobiologic and epidemiologic interpretation of the results obtained. Opportunities for investigating cause of death currently lie primarily in animal models or in forensic postmortem material where the cause of death is frequently known. Public awareness of the autopsy's special role in the setting of natural and unexplained death is essential if the autopsy is to be retained as a key tool in understanding human disease.

Secondary heterotypic versus homotypic infection by Coxsackie B group viruses: impact on early and late histopathological lesions and virus genome prominence.

The impact of prior exposure to a different or identical strain of Coxsackievirus B (CVB) on murine CVB myocarditis was studied using a susceptible murine host (A/J[H-2a]) and myocarditic CVB3 or avirulent CVB2 as primary or secondary infectants. The effects of secondary heterotypic infection (CVB2 followed by CVB3) and homotypic infection (CVB3 followed by CVB3) 28 days after primary inoculation, versus CVB2 or CVB3 alone, on injury and viral genomic replication, both early (day 7) and late (days 28 and 56), were evaluated. After the primary infection by CVB2, trivial viral RNA was present in the heart and other organs, and a substantial positivity was observed with CVB3 infection. Seven days after secondary heterotypic (CVB2-CVB3) infection, the quantity of CVB genome in heart, pancreas, liver, and spleen was increased compared with the virus genome in the CVB3-CVB3 group and in the group with primary CVB3 infection alone. This phenomenon was seen in the heart and spleen up to day 28 postsecondary infection. Tissue inflammation and necrosis in heart and pancreas were prominent 7 days postsecondary infection with CVB2-CVB3 and correlated well with an increased quantity of CVB genome. Virus genome was present in heart and spleen 28 days after CVB3 infection alone. Serum CVB3 neutralization titer was increased to 1:128 in CVB2-CVB3 group at days 7 and 28 postsecondary infection, and serum completely neutralized cytopathological effects of CVB3 in the CVB3-CVB3 group at day 7 and 28 postsecondary infection. Our results indicate that secondary heterotypic infection by CVB causes increased injury, inflammation, and CVB replication in target organs such as the heart and pancreas, as well as in immune compartments like the spleen. Compared with CVB3 alone, the intense inflammatory infiltriate in the CVB2-CVB3 group is as not due solely to postviral sensitization of the immune system, but rather to the inability of the host to eradicate the virus.

Cardiovascular, biochemical and hormonal changes during food-induced hypotension in chronic autonomic failure.

The cardiovascular, biochemical and hormonal responses to a standard test meal have been investigated in patients with chronic autonomic failure and normal subjects. In autonomic failure there was a rapid (within 15 min), substantial and prolonged fall in blood pressure after the meal. A marked fall in blood pressure also occurred after a liquid meal of similar composition and caloric content, with no change in blood pressure in age-matched subjects with normal autonomic function. In autonomic failure after the test meal the blood pressure reached its nadir (45% fall) after 60 min, and had not returned to pre-meal levels after 3 h. There were no changes in cutaneous and forearm blood flow. In the normal subjects there were no changes in blood pressure after the meal; forearm blood flow fell and cardiac output increased. In autonomic failure there were no changes in plasma noradrenaline levels, unlike the normal subjects. Plasma adrenaline levels were unchanged in both groups. There was a similar rise in levels of plasma renin activity in both groups. The haematocrit and plasma osmolality did not change in either group. Changes in plasma glucose and plasma insulin levels were similar in both groups. The responses of 3 pancreatic gut peptides, neurotensin, pancreatic polypeptide and enteroglucagon, were greater in autonomic failure. Basal levels and responses of vasoactive intestinal polypeptide, cholecystokinin-8 and somatostatin were similar in both groups. The motilin response was greater in normal subjects. We conclude that in patients with autonomic failure there was a rapid, substantial and prolonged fall in blood pressure after a meal. This reduction in blood pressure was not counteracted by an increase in sympathetic nervous activity and other compensatory changes, as occur normally. It was unlikely that osmotic effects of the meal or gut secretions resulted in a significant loss of intravascular fluid into the gut. The fall in blood pressure probably results from vasodilatation within the splanchnic circulation, to which pancreatic and gastrointestinal hormones with vasodilatory actions may contribute.

Chromatographic characterisation of neurotensin-like immunoreactivity in plasma and tissue extracts from hepatoma patients.

To determine the nature of the neurotensin-like immunoreactivity produced by some cases of primary liver carcinoma, plasma and tumour neurotensin-like immunoreactivities were characterised in patients with neurotensin-producing hepatoma by chromatographic analysis in conjunction with radioimmunoassay with C- and N-terminally directed antisera. Gel filtration revealed that the majority of neurotensin-like immunoreactivity extracted from the tumour was co-eluted with synthetic neurotensin, whereas a substantial amount of the plasma immunoreactive neurotensin emerged at the void volume. Tumour neurotensin-like immunoreactivity showed a degree of heterogeneity on gel filtration and high pressure liquid chromatography that contrasted with neurotensin-like immunoreactivity extracted from ileal mucosa, suggesting a different post-translational processing of neurotensin within tumour tissue. The ratio of neurotensin 1-8 to neurotensin 1-13 in the patients' plasma suggested that neurotensin was metabolised in a manner similar to that in healthy subjects. The clinical and biological significance of the ectopic production of neurotensin in some hepatomas remains unclear.

Hypoxia response elements.

Hypoxia-inducible factor-1 (HIF-1) has been shown to mediate the transcriptional activation of its target genes in response to oxygen concentration, most likely via a pathway involving a specific oxygen sensor. Molecular cloning of HIF-1 has shown that this widely expressed, DNA binding transcription factor is a heterodimer of two proteins, HIF-1 alpha and HIF-1 beta. A major control of HIF-1 activity by oxygen tension is achieved by changes in the level of the HIF-1 alpha subunit, which complexes with the constitutively expressed HIF-1 beta subunit. Such changes in HIF-1 alpha abundance occur via regulated stability, probably involving proteolysis, rather than at the level of transcription or translation. Further analysis has shown the existence of two separate regulatory domains in the C-terminus of the alpha subunit. Thus, a mechanism of oxygen-regulated HIF-1 activation is proposed, which involves the operation of one inducible domain being amplified by changes in protein level conferred by a second regulatory domain. Evidence for a critical role of HIF-1 in the response of diverse target genes involved in cellular growth and metabolism comes from studies on cultured, mutant mouse cells that lack a functional HIF-1 beta subunit. Furthermore, studies on tumor xenografts derived from the mutant and wild-type cells show that HIF-1 is activated in vivo, and has major effects on gene expression in response to tumor hypoxia. Thus, HIF-1 is a critical component of the oxygen-signaling pathway, and is a prime candidate regulator molecule for the role of coordinating vascular oxygen supply with cellular growth and energy metabolism.

Agent-based computational modeling of wounded epithelial cell monolayers.

Computational modeling of biological systems, or in silico biology, is an emerging tool for understanding structure and order in biological tissues. Computational models of the behavior of epithelial cells in monolayer cell culture have been developed and used to predict the healing characteristics of scratch wounds made to urothelial cell cultures maintained in low- and physiological [Ca2+] environments. Both computational models and in vitro experiments demonstrated that in low exogenous [Ca2+], the closure of 500-microm scratch wounds was achieved primarily by cell migration into the denuded area. The wound healing rate in low (0.09 mM) [Ca2+] was approximately twice as rapid as in physiological (2 mM) [Ca2+]. Computational modeling predicted that in cell cultures that are actively proliferating, no increase in the fraction of cells in the S-phase would be expected, and this conclusion was supported experimentally in vitro by bromodeoxyuridine incorporation assay. We have demonstrated that a simple rule-based model of cell behavior, incorporating rules relating to contact inhibition of proliferation and migration, is sufficient to qualitatively predict the calcium-dependent pattern of wound closure observed in vitro. Differences between the in vitro and in silico models suggest a role for wound-induced signaling events in urothelial cell cultures.

Development and implementation of a human accuracy program in patient foodservice.

For many years, industry has utilized the concept of human error rates to monitor and minimize human errors in the production process. A consistent quality-controlled product increases consumer satisfaction and repeat purchase of product. Administrative dietitians have applied the concepts of using human error rates (the number of errors divided by the number of opportunities for error) at four hospitals, with a total bed capacity of 788, within a tertiary-care medical center. Human error rate was used to monitor and evaluate trayline employee performance and to evaluate layout and tasks of trayline stations, in addition to evaluating employees in patient service areas. Long-term employees initially opposed the error rate system with some hostility and resentment, while newer employees accepted the system. All employees now believe that the constant feedback given by supervisors enhances their self-esteem and productivity. Employee error rates are monitored daily and are used to counsel employees when necessary; they are also utilized during annual performance evaluation. Average daily error rates for a facility staffed by new employees decreased from 7% to an acceptable 3%. In a facility staffed by long-term employees, the error rate increased, reflecting improper error documentation. Patient satisfaction surveys reveal satisfaction, for tray accuracy increased from 88% to 92% in the facility staffed by long-term employees and has remained above the 90% standard in the facility staffed by new employees.

Mortality and morbidity of workers exposed to acrylonitrile in fiber production.

This study assessed the risk of cancer mortality and incidence among 2559 employees exposed to acrylonitrile in the production of Orlon at 2 plants in 1944-1991. Latency, duration of exposure, highest level of exposure ever experienced, and cumulative exposure were used as indicators of exposure. The average duration of exposure for the workers was 7.6 years with an average cumulative exposure of 57.6 ppm-years. Overall mortality was lower than expected in a comparison with the United States population and all DuPont employees [454 deaths, standardized mortality ratios (SMR) of 69 and 91, respectively)]. All the cancer death ratios were lower than expected in a similar comparison. The SMR values for specific sites did not differ significantly from the expected values. Mortality from all cancers and from prostate, respiratory, and digestive cancer did not show any significantly associated increases or a consistent pattern suggestive of a dose-response. The cancer morbidity patterns were similarly unremarkable.

The epitheliome: agent-based modelling of the social behaviour of cells.

We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models.

Bacterial adhesion to dental amalgam and three resin composites.

OBJECTIVES: The ability of three oral bacteria to adhere to hydrophobic amalgam (water contact angle 60 degrees) and hydrophobic resin composites (Prisma-AP.H 56 degrees. Herculite XRV 82 degrees and Z100 89 degrees) was compared using an in vitro assay. METHODS AND RESULTS: Following preincubation of the materials with human saliva, X-ray photoelectron spectroscopy showed the surfaces to adsorb carbon and nitrogen-containing compounds in a conditioning film that appeared to block the detection of Na and others in 2100 resin. Hg and Ag in amalgam, Si and Zn in Prisma AP.H resin and Ag and Na in Herculite resin. The precoating of the substrata by a proteinaceous conditioning film led to decreased binding of viable cells of Streptococcus sanguis CH3, Streptococcus salivarius HB and Actinomyces viscosus WG as compared with the adhesion to bare composites. With and without salivary coating, there was a correlation between increased bacterial hydrophobicity and increased retention on the substrata. However, there was no statistical difference in binding to the amalgam compared with the resin composites. In vitro studies showed that the bacteria autoaggregated in the presence of saliva. CONCLUSION: The results indicate the potential ability of normal oral flora to colonize resin composite.

Schistosoma mansoni and S. japonicum worm numbers in 129/J mice of two types and dominance of susceptibility in F1 hybrids.

In a study on the genetics of resistance to schistosomiasis in WEHI 129/J mice, susceptibility to either Schistosoma mansoni or Schistosoma japonicum was shown to be unequivocally dominant in F1 hybrid crosses between genetically resistant WEHI 129/J and susceptible BALB/c mice. The operation of only 1 or 2 genes in the expression of resistance to S. mansoni was suggested by backcross analysis. Thus, approximately 25% of (BALB/c x WEHI 129/J) F1 x WEHI 129/J mice were resistant to S. mansoni infection, whereas resistance was manifest in approximately 50% of WEHI 129/J mice. The data are consistent with resistance being controlled by 1 recessive gene having 50% penetrance. We also report that 129/J mice obtained directly from the Jackson Laboratories (Bar Harbor, Maine) (designated JAX 129/J), differ from locally bred WEHI 129/J in being entirely susceptible to S. mansoni infection. However, both WEHI 129/J and JAX 129/J are relatively resistant to S. japonicum infection.

Clinical pharmacology and general patient care in two teaching hospitals.

The clinical responsibilities and activities over 12-month periods of the Departments of Clinical Pharmacology of two London teaching hospitals have been analysed. The results suggest that clinical pharmacology should not be regarded only as an academic specialty but that it has an important role in patient care.