When should clinicians use the term syndrome?

Medical language provides essential communication with patients and among healthcare providers. Some words appear frequently in this communication, in clinical records, and in the medical literature, and the use of these words assumes that the listener and reader understand their meaning in the context related to their current use. Words, such as syndrome, disorder, and disease, should have obvious definitions but often, in fact, have uncertain meanings. In particular, the word syndrome should imply a definite and stable association between patient characteristics that have implications for treatment, prognosis, pathogenesis, and possibly clinical studies. In many cases the strength of this association is uncertain and the use of the word represents a convenient shorthand which may or may not improve communication with patients or other clinicians. Some astute clinicians have identified associations in their clinical practices, but this is a slow haphazard process. The development of electronic medical records, internet-based communication, and advanced statistical techniques has the potential to clarify important features of syndromes. However, the recent analysis of certain subsets of patients in the ongoing COVID-19 pandemic has demonstrated that even large amounts of information and advanced statistical techniques using clustering or machine learning may not provide precise separation of patients into groups. Clinicians should use the word syndrome carefully.

Electronic cigarette use by and perceptions of middle and high school students in the United States.

Electronic cigarettes (e-cigarettes) provide a novel source of nicotine and may lead to experimentation by adolescents and eventually to their use of conventional cigarettes. The National Youth Tobacco Survey collected information from a nationally representative sample of students in 2016 to determine their experiences with conventional cigarettes and e-cigarettes, their intentions to use these products in the future, and their perceptions of harm and addiction associated with these products. We analyzed these data with ordered probit regression models to determine possible associations with the intention to try e-cigarettes and conventional cigarettes. This survey included 20,520 respondents, 50.6% were male, 5.9% had used conventional cigarettes, and 9.0% had used e-cigarettes. Approximately 10% thought e-cigarettes caused no harm, 3.7% thought that conventional cigarettes caused no harm, and 52.5% thought that e-cigarettes were less harmful than conventional cigarettes. Less than 1% of the students responded "Definitely yes" to the question, "Do you think you will try an e-cig?" The odds ratios for an intention to try e-cigarettes increased as the perception of harm decreased; these ratios increased from 1.0 for "A lot of harm" to 5.85 (95% CI: 3.51, 9.75) for "No harm." In 2016, the majority of students thought that e-cigarettes could cause some harm. This survey indicates that most students have not tried e-cigarettes or conventional cigarettes. The minority of students who think that e-cigarettes pose no harm and students in the ages 14 and 16 are more likely to try them.

Likelihood of Adolescents Trying Conventional or Electronic Cigarettes Varies with Their Use and Perception of Harm and Addictiveness of Other Tobacco Products, Including Cigars.

OBJECTIVES: Developing a comprehensive understanding of tobacco product use among adolescents requires information about the use of conventional cigarettes; electronic cigarettes (e-cigarettes); other tobacco products such as cigars, little cigars, and cigarillos (CCLCs); and smokeless tobacco. In particular, the use of products other than cigarettes may have important implications for additional smoking-related behaviors and the health of students and adolescents. METHODS: The National Youth Tobacco Surveys for 2017, 2018, and 2019 were aggregated to analyze the characteristics of middle school and high school students who had used tobacco products, such as CCLCs. Information collected included age, sex, race, and perceptions about harm and addiction related to tobacco products. Multiple logistic regression models were used to evaluate the associations between having used conventional/e-cigarettes and having used CCLCs, while adjusting for the perceived harm of conventional/e-cigarettes, sex, age, and other risk factors. RESULTS: These combined surveys included 50,172 responses; 6836 respondents (13.6%) had tried CCLCs. Male students used these products more frequently than female students. Students in older age groups (15, 16, 17, and 18 and older,) had used these products more frequently than younger students. The odds for students in this CCLCs subgroup trying conventional cigarettes decreased in those who thought that conventional cigarettes could cause "some harm" or "a lot of harm." The odds for having tried e-cigarettes in the CCLCs subgroup decreased in those who thought that e-cigarettes could cause harm and increased in those who thought that conventional cigarettes could cause "little harm" or "a lot of harm." CONCLUSIONS: More than 10% of middle school and high school students have used CCLCs. The majority of students in this subgroup also have used either conventional cigarettes or e-cigarettes. Understanding possible harm with cigarette use is significantly associated with the reduced use of conventional and e-cigarettes, and using CCLCs independently contributes to the increased risk of using conventional and e-cigarettes. The frequent use of several tobacco products makes surveys in this age group more complicated and indicates that educational efforts and public policies regarding tobacco need to include all tobacco products.

The Management of Women's Health Care by Internists With a Focus on the Utility of Ultrasound.

Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy. Finally, all management decisions need discussions on the potential benefit or harm in each step of a woman's care with an emphasis on personal preferences.

Sleep Patterns and Health Behaviors in Healthcare Students.

OBJECTIVES: Personal health behavior can influence the academic development of healthcare students. This study was designed to evaluate the personal health behavior, including sleep time, of healthcare students at a large health sciences center. METHODS: An anonymous online survey based on standardized questionnaires about sleep, insomnia, depression, alcohol use, and exercise was sent to all of the healthcare students (including medical, nursing, pharmacy, graduate biomedical science, and allied health students) in the Texas Tech University Health Sciences Center graduate education programs in Lubbock. RESULTS: In total, 412 students replied to this survey. Their mean sleep duration during the weekday was 7.5 ± 1.2 hours; 16.5% were short sleepers (<7 hours) during weekdays; 33% of the students woke up "feeling tired or worn out" >15 days during the last month. Many students were either moderately or severely bothered by "the lack of energy" because of poor sleep, and 56.6% of students rated their sleep as either fair or poor. Approximately 35% of students had drinking patterns that qualified as hazardous drinking, 6.3% of students smoked, and 23% of students did not do even mild exercise during the week. Eighty-nine percent of students reported stress in their life, including family stress, job stress, financial stress, legal stress, and other stress. Thirty-five percent of students considered their health as either poor or fair. Approximately 50% of students did not expect any change in their situation during the next 3 to 6 months. CONCLUSIONS: Although most healthcare students report adequate sleep times, more than half of them rate their sleep as fair or poor. In addition, some have poor health habits, including excessive alcohol use. Health science centers should introduce programs to promote healthy behaviors and reduce stress in healthcare students.

Zika Virus: Epidemiology, Pathogenesis and Human Disease.

The Zika virus is a positive sense, single-stranded RNA arbovirus in the Flaviviridae family, genus Flavivirus. This virus was initially isolated in Africa and is transmitted to nonhuman primates and humans by mosquitoes. Initial reports describe sporadic mild viral infection with fever, arthralgia, myalgia and conjunctivitis in Africa and Asia. However, its geographic distribution has significantly increased, and it has caused large outbreaks in the Yap Islands in 2007, in French Polynesia in 2013 and in Brazil in 2015. Multiple cases of Guillain-Barre´ syndrome occurred in French Polynesia and Columbia during outbreaks, and infections in pregnant women in Brazil have been associated with microcephaly and fetal loss. The viremic phase in humans is short, and diagnosis usually depends on positive immunoglobulin M titers with serum neutralization tests for confirmation. Treatment is directed at symptoms; there are no antiviral drugs available. Transmission can also occur through sexual contact with infected men and through blood transfusion. Prevention is important in women and includes limiting travel to endemic areas when possible, control of mosquito populations and condom use when appropriate. The Centers for Disease Control and Prevention is actively involved in tracking these infections and providing up-to-date information.

Engineering of a high lipid producing Yarrowia lipolytica strain.

BACKGROUND: Microbial lipids are produced by many oleaginous organisms including the well-characterized yeast Yarrowia lipolytica, which can be engineered for increased lipid yield by up-regulation of the lipid biosynthetic pathway and down-regulation or deletion of competing pathways. RESULTS: We describe a strain engineering strategy centered on diacylglycerol acyltransferase (DGA) gene overexpression that applied combinatorial screening of overexpression and deletion genetic targets to construct a high lipid producing yeast biocatalyst. The resulting strain, NS432, combines overexpression of a heterologous DGA1 enzyme from Rhodosporidium toruloides, a heterlogous DGA2 enzyme from Claviceps purpurea, and deletion of the native TGL3 lipase regulator. These three genetic modifications, selected for their effect on lipid production, enabled a 77 % lipid content and 0.21 g lipid per g glucose yield in batch fermentation. In fed-batch glucose fermentation NS432 produced 85 g/L lipid at a productivity of 0.73 g/L/h. CONCLUSIONS: The yields, productivities, and titers reported in this study may further support the applied goal of cost-effective, large -scale microbial lipid production for use as biofuels and biochemicals.

Developmental changes in semantic knowledge organization.

Semantic knowledge is a crucial aspect of higher cognition. Theoretical accounts of semantic knowledge posit that relations between concepts provide organizational structure that converts information known about individual entities into an interconnected network in which concepts can be linked by many types of relations (e.g., taxonomic, thematic). The goal of the current research was to address several methodological shortcomings of prior studies on the development of semantic organization, by using a variant of the spatial arrangement method (SpAM) to collect graded judgments of relatedness for a set of entities that can be cross-classified into either taxonomic or thematic groups. In Experiment 1, we used the cross-classify SpAM (CC-SpAM) to obtain graded relatedness judgments and derive a representation of developmental changes in the organization of semantic knowledge. In Experiment 2, we validated the findings of Experiment 1 by using a more traditional pairwise similarity judgment paradigm. Across both experiments, we found that an early recognition of links between entities that are both taxonomically and thematically related preceded an increasing recognition of links based on a single type of relation. The utility of CC-SpAM for evaluating theoretical accounts of semantic development is discussed.

An Investigation of the Variety and Complexity of Statistical Methods Used in Current Internal Medicine Literature.

OBJECTIVES: Accreditation Council for Graduate Medical Education guidelines require internal medicine residents to develop skills in the interpretation of medical literature and to understand the principles of research. A necessary component is the ability to understand the statistical methods used and their results, material that is not an in-depth focus of most medical school curricula and residency programs. Given the breadth and depth of the current medical literature and an increasing emphasis on complex, sophisticated statistical analyses, the statistical foundation and education necessary for residents are uncertain. METHODS: We reviewed the statistical methods and terms used in 49 articles discussed at the journal club in the Department of Internal Medicine residency program at Texas Tech University between January 1, 2013 and June 30, 2013. We collected information on the study type and on the statistical methods used for summarizing and comparing samples, determining the relations between independent variables and dependent variables, and estimating models. We then identified the typical statistics education level at which each term or method is learned. RESULTS: A total of 14 articles came from the Journal of the American Medical Association Internal Medicine, 11 from the New England Journal of Medicine, 6 from the Annals of Internal Medicine, 5 from the Journal of the American Medical Association, and 13 from other journals. Twenty reported randomized controlled trials. Summary statistics included mean values (39 articles), category counts (38), and medians (28). Group comparisons were based on t tests (14 articles), χ2 tests (21), and nonparametric ranking tests (10). The relations between dependent and independent variables were analyzed with simple regression (6 articles), multivariate regression (11), and logistic regression (8). Nine studies reported odds ratios with 95% confidence intervals, and seven analyzed test performance using sensitivity and specificity calculations. These papers used 128 statistical terms and context-defined concepts, including some from data analysis (56), epidemiology-biostatistics (31), modeling (24), data collection (12), and meta-analysis (5). Ten different software programs were used in these articles. Based on usual undergraduate and graduate statistics curricula, 64.3% of the concepts and methods used in these papers required at least a master's degree-level statistics education. CONCLUSIONS: The interpretation of the current medical literature can require an extensive background in statistical methods at an education level exceeding the material and resources provided to most medical students and residents. Given the complexity and time pressure of medical education, these deficiencies will be hard to correct, but this project can serve as a basis for developing a curriculum in study design and statistical methods needed by physicians-in-training.

Modeling the relation between obesity and sleep parameters in children referred for dietary weight reduction intervention.

OBJECTIVES: Cross-sectional and longitudinal studies have demonstrated that short sleep periods increase the likelihood of obesity in children. This study was designed to identify other less-clearly defined sleep and behavioral patterns associated with changes in body mass index (BMI) in obese children referred for interventions. METHODS: We retrospectively reviewed the clinic records of children with obesity and children at risk for developing obesity who were referred for counseling and weight loss. Information on sleep habits, pediatric quality of life, pediatric sleep questionnaire (PSQ), and the pediatric daytime sleepiness scale were analyzed, and children were distributed into three behavior groups using cluster analysis. RESULTS: Our sample contained 48 girls and 29 boys with an age range of 2.7 to 16.8 years. The mean BMI was 33.08 ± 7.37 kg/m(2), and mean sleep duration was 9.09 ± 1.09 hours. Multivariate analysis revealed a significant interaction between sleep duration and age when the child was older than 12 years. A 1-hour increase in sleep in older children was associated with a decrease in BMI of 1.263 kg/m(2). Higher (more abnormal) pediatric quality-of-life school scores, higher PSQ1 and PSQ2 scores, and higher pediatric daytime sleepiness scale scores were associated with an increased BMI in univariate analyses but not in the multivariate analysis using the behavior group as an independent predictor. Children who shared a bedroom had a lower BMI in univariate analysis but not in the multivariate analysis. CONCLUSIONS: Longer sleep periods are associated with a decreased BMI, even in children who already meet the criteria for obesity. These children have poor-quality sleep, diurnal behavioral problems, and increased diurnal sleepiness. This study suggests that studies in obese children using questionnaires about sleep habits and quality of life provide useful information that could lead to better weight loss intervention studies.

Structure and mutagenesis of the DNA modification-dependent restriction endonuclease AspBHI.

The modification-dependent restriction endonuclease AspBHI recognizes 5-methylcytosine (5mC) in the double-strand DNA sequence context of (C/T)(C/G)(5mC)N(C/G) (N = any nucleotide) and cleaves the two strands a fixed distance (N12/N16) 3' to the modified cytosine. We determined the crystal structure of the homo-tetrameric AspBHI. Each subunit of the protein comprises two domains: an N-terminal DNA-recognition domain and a C-terminal DNA cleavage domain. The N-terminal domain is structurally similar to the eukaryotic SET and RING-associated (SRA) domain, which is known to bind to a hemi-methylated CpG dinucleotide. The C-terminal domain is structurally similar to classic Type II restriction enzymes and contains the endonuclease catalytic-site motif of DX20EAK. To understand how specific amino acids affect AspBHI recognition preference, we generated a homology model of the AspBHI-DNA complex, and probed the importance of individual amino acids by mutagenesis. Ser41 and Arg42 are predicted to be located in the DNA minor groove 5' to the modified cytosine. Substitution of Ser41 with alanine (S41A) and cysteine (S41C) resulted in mutants with altered cleavage activity. All 19 Arg42 variants resulted in loss of endonuclease activity.

Medical literature searches: a comparison of PubMed and Google Scholar.

BACKGROUND: Medical literature searches provide critical information for clinicians. However, the best strategy for identifying relevant high-quality literature is unknown. OBJECTIVES: We compared search results using PubMed and Google Scholar on four clinical questions and analysed these results with respect to article relevance and quality. METHODS: Abstracts from the first 20 citations for each search were classified into three relevance categories. We used the weighted kappa statistic to analyse reviewer agreement and nonparametric rank tests to compare the number of citations for each article and the corresponding journals' impact factors. RESULTS: Reviewers ranked 67.6% of PubMed articles and 80% of Google Scholar articles as at least possibly relevant (P = 0.116) with high agreement (all kappa P-values < 0.01). Google Scholar articles had a higher median number of citations (34 vs. 1.5, P < 0.0001) and came from higher impact factor journals (5.17 vs. 3.55, P = 0.036). CONCLUSIONS: PubMed searches and Google Scholar searches often identify different articles. In this study, Google Scholar articles were more likely to be classified as relevant, had higher numbers of citations and were published in higher impact factor journals. The identification of frequently cited articles using Google Scholar for searches probably has value for initial literature searches.

Characterization of type II and III restriction-modification systems from Bacillus cereus strains ATCC 10987 and ATCC 14579.

The genomes of two Bacillus cereus strains (ATCC 10987 and ATCC 14579) have been sequenced. Here, we report the specificities of type II/III restriction (R) and modification (M) enzymes. Found in the ATCC 10987 strain, BceSI is a restriction endonuclease (REase) with the recognition and cut site CGAAG 24-25/27-28. BceSII is an isoschizomer of AvaII (G/GWCC). BceSIII cleaves at ACGGC 12/14. The BceSIII C terminus resembles the catalytic domains of AlwI, MlyI, and Nt.BstNBI. BceSIV is composed of two subunits and cleaves on both sides of GCWGC. BceSIV activity is strongly stimulated by the addition of cofactor ATP or GTP. The large subunit (R1) of BceSIV contains conserved motifs of NTPases and DNA helicases. The R1 subunit has no endonuclease activity by itself; it strongly stimulates REase activity when in complex with the R2 subunit. BceSIV was demonstrated to hydrolyze GTP and ATP in vitro. BceSIV is similar to CglI (GCSGC), and homologs of R1 are found in 11 sequenced bacterial genomes, where they are paired with specificity subunits. In addition, homologs of the BceSIV R1-R2 fusion are found in many sequenced microbial genomes. An orphan methylase, M.BceSV, was found to modify GCNGC, GGCC, CCGG, GGNNCC, and GCGC sites. A ParB-methylase fusion protein appears to nick DNA nonspecifically. The ATCC 14579 genome encodes an active enzyme Bce14579I (GCWGC). BceSIV and Bce14579I belong to the phospholipase D (PLD) family of endonucleases that are widely distributed among Bacteria and Archaea. A survey of type II and III restriction-modification (R-M) system genes is presented from sequenced B. cereus, Bacillus anthracis, and Bacillus thuringiensis strains.

An overview of clustering applied to molecular biology.

In molecular biology, we are often interested in determining the group structure in, e.g., a population of cells or microarray gene expression data. Clustering methods identify groups of similar observations, but the results can depend on the chosen method's assumptions and starting parameter values. In this chapter, we give a broad overview of both attribute- and similarity-based clustering, describing both the methods and their performance. The parametric and nonparametric approaches presented vary in whether or not they require knowing the number of clusters in advance as well as the shapes of the estimated clusters. Additionally, we include a biclustering algorithm that incorporates variable selection into the clustering procedure. We finish with a discussion of some common methods for comparing two clustering solutions (possibly from different methods). The user is advised to devote time and attention to determining the appropriate clustering approach (and any corresponding parameter values) for the specific application prior to analysis.

Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation.

BACKGROUND: Histone acetyltransferase enzymes (HATs) are implicated in regulation of transcription. HATs from different families may overlap in target and substrate specificity. RESULTS: We isolated the elp3+ gene encoding the histone acetyltransferase subunit of the Elongator complex in fission yeast and characterized the phenotype of an Deltaelp3 mutant. We examined genetic interactions between Deltaelp3 and two other HAT mutants, Deltamst2 and Deltagcn5 and used whole genome microarray analysis to analyze their effects on gene expression. CONCLUSIONS: Comparison of phenotypes and expression profiles in single, double and triple mutants indicate that these HAT enzymes have overlapping functions. Consistent with this, overlapping specificity in histone H3 acetylation is observed. However, there is no evidence for overlap with another HAT enzyme, encoded by the essential mst1+ gene.

Schizosaccharomyces pombe histone acetyltransferase Mst1 (KAT5) is an essential protein required for damage response and chromosome segregation.

Schizosaccharomyces pombe Mst1 is a member of the MYST family of histone acetyltransferases and is the likely ortholog of Saccharomyces cerevisiae Esa1 and human Tip60 (KAT5). We have isolated a temperature-sensitive allele of this essential gene. mst1 cells show a pleiotropic phenotype at the restrictive temperature. They are sensitive to a variety of DNA-damaging agents and to the spindle poison thiabendazole. mst1 has an increased frequency of Rad22 repair foci, suggesting endogenous damage. Two-hybrid results show that Mst1 interacts with a number of proteins involved in chromosome integrity and centromere function, including the methyltransferase Skb1, the recombination mediator Rad22 (Sc Rad52), the chromatin assembly factor Hip1 (Sc Hir1), and the Msc1 protein related to a family of histone demethylases. mst1 mutant sensitivity to hydroxyurea suggests a defect in recovery following HU arrest. We conclude that Mst1 plays essential roles in maintenance of genome stability and recovery from DNA damage.

Short sleep times predict obesity in internal medicine clinic patients.

STUDY OBJECTIVES: Epidemiological studies have demonstrated an association between short sleep times and obesity as defined by body mass index (BMI). We wanted to determine whether this association occurs in patients with chronic medical diagnoses since the number of confounding factors is likely higher in patients than the general population. METHODS: Two hundred patients attending internal medicine clinics completed a survey regarding sleep habits, lifestyle characteristics, and medical diagnoses. An independent surveyor collected the information on the questionnaires and reviewed the medical records. Height and weight were measured by clinic personnel. Data were analyzed with multivariate logistic regression. RESULTS: Subjects with short sleep times (< 7 hours) had an increased likelihood of obesity as defined by a BMI > or = 30 kg/m2 when compared to the reference group of (8, 9] hours (odds ratio 2.93; 95% confidence interval, 1.06-8.09). There was a U-shaped relationship between obesity and sleep time in women but not in men. Young age (18 to 49 years), not smoking, drinking alcohol, hypertension, diabetes, and sleep apnea were also associated with obesity in the overall model. CONCLUSIONS: This study demonstrates an association between short sleep times and obesity in undifferentiated patients attending an internal medicine clinic using models adjusting for age, lifestyle characteristics, and some medical diagnoses. The U-shaped relationship in women suggests that sleep patterns may have gender specific associations. These observations provide the background for therapeutic trials in weight loss in patients with established medical problems.

Functional characterization of the conserved amino acids in Pop1p, the largest common protein subunit of yeast RNases P and MRP.

RNase P and RNase MRP are ribonucleoprotein enzymes required for 5'-end maturation of precursor tRNAs (pre-tRNAs) and processing of precursor ribosomal RNAs, respectively. In yeast, RNase P and MRP holoenzymes have eight protein subunits in common, with Pop1p being the largest at >100 kDa. Little is known about the functions of Pop1p, beyond the fact that it binds specifically to the RNase P RNA subunit, RPR1 RNA. In this study, we refined the previous Pop1 phylogenetic sequence alignment and found four conserved regions. Highly conserved amino acids in yeast Pop1p were mutagenized by randomization and conditionally defective mutations were obtained. Effects of the Pop1p mutations on pre-tRNA processing, pre-rRNA processing, and stability of the RNA subunits of RNase P and MRP were examined. In most cases, functional defects in RNase P and RNase MRP in vivo were consistent with assembly defects of the holoenzymes, although moderate kinetic defects in RNase P were also observed. Most mutations affected both pre-tRNA and pre-rRNA processing, but a few mutations preferentially interfered with only RNase P or only RNase MRP. In addition, one temperature-sensitive mutation had no effect on either tRNA or rRNA processing, consistent with an additional role for RNase P, RNase MRP, or Pop1p in some other form. This study shows that the Pop1p subunit plays multiple roles in the assembly and function of of RNases P and MRP, and that the functions can be differentiated through the mutations in conserved residues.

Attenuation of social class and reproductive risk factor associations for Hodgkin lymphoma due to selection bias in controls.

OBJECTIVE: Hodgkin lymphoma (HL) risk has been linked with higher social class and lower parity, but our prior population-based case-control study in adult women had unexpected null findings for these variables. Because subject participation was 87% for cases but 65% for random digit-dialing (RDD) controls, we examined representativeness of our controls and the impact of detected bias on prior results. METHODS: Using data from RDD enumeration, abbreviated interviews with nonparticipating controls, and the US census, we compared participating and nonparticipating RDD controls across several age groups and then recomputed odds ratios for risk factor associations adjusted for bias. RESULTS: The 325 RDD control participants were younger, more likely to be white, better educated, and of lower birth order and lower parity than the nonparticipants. Adjustment of odds ratios for bias strengthened previously null findings for education and for parity, breast-feeding and miscarriages in young adult women; these latter changes eliminated previously apparent age modification of risks. CONCLUSIONS: Selection bias in female RDD controls resulted from differential participation by socioeconomic factors, varied with age, and produced underestimations of several associations in young women, including reproductive factors. Thus, our prior conclusions of etiologic irrelevance for some study variables may have been inaccurate.