The Bioperl toolkit: Perl modules for the life sciences

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.     

Structure and evolution of the Smith-Magenis syndrome repeat gene clusters, SMS-REPs

An approximately 4-Mb genomic segment on chromosome 17p11.2, commonly deleted in patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with dup(17)(p11.2p11.2) syndrome, is flanked by large, complex low-copy repeats (LCRs), termed proximal and distal SMS-REP. A third copy, the middle SMS-REP, is located between them. SMS-REPs are believed to mediate nonallelic homologous recombination, resulting in both SMS deletions and reciprocal duplications. To delineate the genomic structure and evolutionary origin of SMS-REPs, we constructed a bacterial artificial chromosome/P1 artificial chromosome contig spanning the entire SMS region, including the SMS-REPs, determined its genomic sequence, and used fluorescence in situ hybridization to study the evolution of SMS-REP in several primate species. Our analysis shows that both the proximal SMS-REP (approximately 256 kb) and the distal copy (approximately 176 kb) are located in the same orientation and derived from a progenitor copy, whereas the middle SMS-REP (approximately 241 kb) is inverted and appears to have been derived from the proximal copy. The SMS-REP LCRs are highly homologous (>98%) and contain at least 14 genes/pseudogenes each. SMS-REPs are not present in mice and were duplicated after the divergence of New World monkeys from pre-monkeys approximately 40-65 million years ago. Our findings potentially explain why the vast majority of SMS deletions and dup(17)(p11.2p11.2) occur at proximal and distal SMS-REPs and further support previous observations that higher-order genomic architecture involving LCRs arose recently during primate speciation and may predispose the human genome to both meiotic and mitotic rearrangements.     

Design, testing, and clinical studies of a handheld polarized light camera

Polarized light imaging has been used to detect the borders of skin cancer and facilitate assessment of cancer boundaries. A design for an inexpensive handheld polarized camera is presented and clinical images acquired with this prototype are shown. The camera is built with two universal serial bus (USB) color video cameras, a polarizing beamsplitter cube, and a 4x objective lens. Illumination is provided by three white LEDs and a sheet polarizer. Horizontal and vertical linearly polarized reflected images are processed at 7 frames/s and a resulting polarized image is displayed on screen. We compare the performances of cheap USB camera and a 16-bit electronically cooled camera. Dark noise and image repeatability are compared. In both cases, the 16-bit camera outperforms the USB cameras. Despite these limitations, the results obtained with this USB prototype are very satisfactory. Examples of polarized images of lesions taken prior to surgery are presented.     

Antifluoridationists Persist: the Constitutional Basis for Fluoridation

The controversy surrounding fluoridation persists. In recent years opponents of fluoridation have resorted to the courts with increasing frequency and have achieved a few victories in the trial courts. To date, however, no appellate court has ruled against fluoridation. This article discusses the constitutional basis for the court decisions upholding fluoridation and the main arguments put forth by the antifluoridationists. Five of the more recent cases are summarized, as is the first fluoridation case to be appealed to the US Supreme Court. The article concludes that the legal validity of fluoridation in the United States has been thoroughly tested in the courts and confirmed. It appears that the antifluoridationists will concentrate their future legal attacks on the "harmful effects" of fluoridation on health and the environment. If they can convince the courts that even a few people were truly harmed, the delicate balance between the rights of the state to fluoridate in order to protect the public's health and the rights of the individual not to be harmed could well shift. In closing, the question is raised whether the US Congress has the power to pass legislation either to mandate or forbid fluoridation.     

Effects of DFMO-induced polyamine depletion on human tumor cell sensitivity to antineoplastic DNA-crosslinking drugs

Summary We investigated the effect of pretreatment with difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, on the cytocidal responses of four human adenocarcinoma cell lines to two alkylating and crosslinking agents: chlorambucil and N,N,N-triethylenethio-phosphoramide (thiotepa). The cell lines studied included HuTu-80 (duodenum), HT-29 (colon), ME-180 (cervix), and A-427 (lung). A 48- to 72-h pretreatment with DFMO reduced intracellular putrescine and spermidine contents to <10% and <1% of control levels. This treatment also caused a 30%–70% decline in spermine content. Survival of control and DFMO-pretreated cells after treatment with chlorambucil or thiotepa was measured by a plating efficiency assy. For three of the four lines studied, the DFMO-induced partial polyamine depletion significantly protected cells from the lethal effects of chlorambucil. In ME-180 cultures alone, DFMO pretreatment did not alter the cytocidal efficacy of chlorambucil. Addition of exogenous putrescine to cultures of HuTu-80, HT-29, or A-427 24 h after DFMO addition but 24 h before treatment with chlorambucil reversed the polyamine depletion and its protective effects on chlorambucil-induced cell kill. In contrast to the above observations, DFMO and partial polyamine depletion had no effect on cell survival after thiotepa treatment for any of the cell lines investigated.Abbreviations BCNU 1,3-bis (2-chloroethyl)-1-nitrosourea - CENU chloroethylnitrosourea - cis-Pt (II) cis-diamminedichloroplatinum (II) - DFMO difluoromethylornithine - ODC ornithine decarboxylase - PU putrescine - SD spermidine - SP spermine thiotepa - N,N,N triethylenethiophosphoramide This investigation was supported in part by PHS grant no. CA-32758 awarded by the National Cancer Institute, DHHS; by grant no. 82-6 from the American Cancer Society, Ill. Div., Inc.; and by a Biomedical Research Support Grant to Northwestern University Medical School from the US PHS, NIH (RR-05370)     

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients.MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission.ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07?1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04?1.80; P = 0.026).ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.     

Assessing Diet Quality of Indigenous Food Systems in Three Geographically Distinct Solomon Islands Sites (Melanesia,Pacific Islands)

Indigenous Solomon Islanders, like many living in Pacific Small Island Developing States (PSIDS), are currently experiencing the global syndemic—the combined threat of obesity, undernutrition, and climate change. This mixed-method study aimed to assess nutrition transitions and diet quality by comparing three geographically unique rural and urban indigenous Solomon Islands populations. Participants in rural areas sourced more energy from wild and cultivated foods; consumed a wider diversity of foods; were more likely to meet WHO recommendations of >400 g of non-starchy fruits and vegetables daily; were more physically active; and had significantly lower body fat, waist circumference, and body mass index (BMI) when compared to urban populations. Urban populations were found to have a reduced ability to self-cultivate agri-food products or collect wild foods, and therefore consumed more ultra-processed foods (classified as NOVA 4) and takeout foods, and overall had less diverse diets compared to rural populations. Clear opportunities to leverage traditional knowledge and improve the cultivation and consumption of underutilized species can assist in building more sustainable and resilient food systems while ensuring that indigenous knowledge and cultural preferences are respected.     

Emotional Eating in Adolescence: Effects of Emotion Regulation,Weight Status and Negative Body Image

Emotional eating is associated with an increased risk of binge eating, eating in the absence of hunger and obesity risk. While previous studies with children and adolescents suggest that emotion regulation may be a key predictor of this dysregulated eating behavior, little is known about what other factors may be influencing the link between emotional regulation and emotional eating in adolescence. This multi-method longitudinal study (n = 138) utilized linear regression models to examine associations between childhood emotion regulation, adolescent weight status and negative body image, and emotional eating at age 17. Emotion regulation predicted adolescent emotional eating and this link was moderated by weight status (β = 1.19, p < 0.01) and negative body image (β = −0.34, p < 0.01). Higher engagement in emotional eating was predicted by lower emotional regulation scores among normal-weight teens (β = −0.46, p < 0.001) but not among overweight/obese teens (β = 0.32, p > 0.10). Higher scores on emotion regulation were significantly associated with lower emotional eating at high (β = −1.59, p < 0.001) and low (β = −1.00, p < 0.01) levels of negative body image. Engagement in emotional eating was predicted by higher negative body image among overweight/obese teens only (β = 0.70, p < 0.001). Our findings show that while better childhood emotion regulation skills are associated with lower emotional eating, weight status and negative body image influence this link and should be considered as important foci in future interventions that aim to reduce emotional eating in adolescence.