Medicine and Health Sciences Commons^™

From Mollusks To Medicine: A Venomics Approach For The Discovery And Characterization Of Therapeutics From Terebridae Peptide Toxins, Aida Verdes, Prachi Anand, Juliette Gorson, Stephen Jannetti, Patrick Kelly, Abba Leffler, Danny Simpson, Girish Ramrattan, Mandë Holford

Publications and Research

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics …

Associations Of Birth Order With Early Adolescent Growth, Pubertal Onset, Blood Pressure And Size: Evidence From Hong Kong’S “Children Of 1997” Birth Cohort, Man Ki Kwok, Gabriel M. Leung, C. Mary Schooling

Publications and Research

Background: Birth order has been proposed as a cardiovascular risk factor, because the lower birth weight and greater infant weight gain typical of firstborns could programme metabolism detrimentally.

Methods: We examined the associations of birth order (firstborn or laterborn) with birth weight-for-gestational age, length/height and body mass index (BMI) z-scores during infancy, childhood, and puberty using generalized estimating equations, with age at pubertal onset using interval- censored regression and with age-, sex- and height-standardized blood pressure, height and BMI z-scores at 13 years using linear regression in a population-representative Chinese birth cohort: “Children of 1997” (n = 8,327).

Results: Compared …

Titanocene−Gold Complexes Containing N‑Heterocyclic Carbene Ligands Inhibit Growth Of Prostate, Renal, And Colon Cancers In Vitro, Yiu Fung Mui, Jacob FernáNdez-Gallardo, Benelita T. Elie, Ahmed Gubran, Irene Maluenda, Mercedes Sanau, Marıá Contel

Publications and Research

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)−N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold−N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer …

Comparative Error-Free And Error-Prone Translesion Synthesis Of N2‑2′-Deoxyguanosine Adducts Formed By Mitomycin C And Its Metabolite, 2,7-Diaminomitosene, In Human Cells, Arindam Bose, Chaitra Surugihalli, Paritosh Pande, Elise Champeil, Ashis K. Basu

Publications and Research

Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates DNA upon reductive activation. 2,7-Diaminomitosene (2,7-DAM) is a major metabolite of MC in tumor cells, which also alkylates DNA. MC forms seven DNA adducts, including monoadducts and inter- and intrastrand cross-links, whereas 2,7-DAM forms two monoadducts. Herein, the biological effects of the dG-N2 adducts formed by MC and 2,7-DAM have been compared by constructing single-stranded plasmids containing these adducts and replicating them in human embryonic kidney 293T cells. Translesion synthesis (TLS) efficiencies of dG-N2-MC and dG-N2-2,7-DAM were 38 ± 3 and 27 …

Tobacco, Alcohol, And Processed Food Industries – Why Do Public Health Practitioners View Them So Differently?, Katherine Smith, Lori Dorfman, Nicholas Freudenberg, Benjamin Hawkins, Shona Hilton, Oliver Razum, Heide Weishaar

Publications and Research

No abstract provided.

Inquiry Into The Implementation Of Bush’S Executive Order 13211 And The Impact On Environmental And Public Health Regulation, Elizabeth Ann Glass Geltman, Gunwant Gill, Miriam Jovanovic

Publications and Research

Executive Order 13211, promulgated in 2001, requires the federal government to consider the impact of federal action on energy independence as part of the George W. Bush’s National Energy Policy. This law review examines whether EO 13211 was used to curtail environmental protection and natural resource conservation. The article begins with a review of the procedure required of federal agencies under EO 13211 and its associated documents. The paper then examines case law and published federal rulemaking proceedings and examines how federal agencies apply tests to evaluate the potential energy effect. The study concludes that EO 13211 strikes a reasonable …

A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin

Publications and Research

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation …

Reducing The Role Of The Food, Tobacco, And Alcohol Industries In Noncommunicable Disease Risk In South Africa, Peter Delobelle, David Sanders, Thandi Puoane, Nicholas Freudenberg

Publications and Research

Noncommunicable diseases (NCDs) impose a growing burden on the health, economy, and development of South Africa. According to the World Health Organization, four risk factors, tobacco use, alcohol consumption, unhealthy diets, and physical inactivity, account for a significant proportion of major NCDs. We analyze the role of tobacco, alcohol, and food corporations in promoting NCD risk and unhealthy lifestyles in South Africa and in exacerbating inequities in NCD distribution among populations. Through their business practices such as product design, marketing, retail distribution, and pricing and their business practices such as lobbying, public relations, philanthropy, and sponsored research, national and transnational …

The Good Food Jobs Nexus: A Strategy For Promoting Health, Employment, And Economic Development, Nicholas Freudenberg, Michele Silver, Lesley Hirsch, Nevin Cohen

Publications and Research

In the aftermath of the Great Recession, cities have looked to the rapidly growing food sector as a promising source of new employment, and yet most of the sector’s growth has come from low-wage, dead-end food jobs. A strategy to simultaneously increase food employment, improve conditions for food workers, and enhance access to healthy and affordable food to improve public health requires pursuing a “good food jobs” approach that supports policies and programs that advance all three goals. To inform such a strategy, this article analyzes policies and programs to create good food jobs in New York City and discusses …

Awareness Of Rabies And Response To Dog Bites In A Bangladesh Community, Sumon Ghosh, Sukanta Chowdhury, Najmul Haider, Rajub K. Bhowmik, Md. S. Rana, Aung S. Prue Marma, Muhammad B. Hossain, Nitish C. Debnath, Be-Nazir Ahmed

Publications and Research

Community awareness regarding rabies and treatment seeking behaviours are critical both for the prevention and control of the disease in human and animals. We conducted a study to explore people’s awareness about rabies, their attitudes towards dogs and practices associated with treating dog bites in Satkhira Sadar, a southwestern sub-district of Bangladesh. Of the total 3200 households (HHs) surveyed, the majority of the respondents have heard about rabies (73%) and there was a high level of awareness that dog bite is the main cause of rabies (86%), and that rabies can be prevented by vaccination (85%). However, 59% of the …

Craigslist As A Source For Illicit Drugs: A Case Report And Review Of The Literature, Babak Tofighi, Alisha Desai, Christian Grov, Joshua D. Lee

Publications and Research

Introduction: Online drug markets and social media are facilitating the spread of information and sale of illicit substances. Online sites, such as Craigslist and Bluelight, underscore an emerging shift in contemporary drug consumerism.

Case Descriptions: We report on two cases. Case 1 is a 42-year-old male with a history of heroin-use disorder, presented for an initial visit to an office-based buprenorphine program, and reported having acquired heroin from Craigslist. Despite several harrowing experiences, Craigslist remained Patient 1’s primary method of purchasing heroin during a 14-month period. Craigslist ads also redirected the patient to the web site Bluelight, which …

Understanding Differences In Hiv/Hcv Prevalence According To Differentiated Risk Behaviors In A Sample Of Pwid In Rural Puerto Rico, Roberto Abadie, Melissa Welch-Lazoritz, Camila Gelpi-Acosta, Juan Carlos Reyes, Kirk Dombrowski

Publications and Research

Background: Blood contained in needles and injection equipment has been identified as a vector for HIV and HCV transmission among people who inject drugs (PWID). Yet, there is often a wide discrepancy in prevalence for both viruses. While microbiological differences between viruses influence prevalence, other variables associated with the way drugs are acquired and used, also play a role.

Methods: Respondent-driven sampling (RDS) methods recruited a sample of 315 current intravenous drug users in rural Puerto Rico. Information about type and frequency of use, HIV and HVC risk behaviors (sharing needles, cookers, cotton, and water), sexual behaviors, and alcohol use …

Parasitic Diseases Of The Central Nervous System: Lessons For Clinicians And Policy Makers, Arturo Carpio, Matthew L. Romo, R.M.E. Parkhouse, Brooke Short, Tarun Dua

Publications and Research

Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, …

Age And Employee Green Behaviors: A Meta-Analysis, Brenton M. Wiernik, Stephan Dilchert, Deniz S. Ones

Publications and Research

Recent economic and societal developments have led to an increasing emphasis on organizational environmental performance. At the same time, demographic trends are resulting in increasingly aging labor forces in many industrialized nations. Commonly held stereotypes suggest that older workers are less likely to be environmentally responsible than younger workers. To evaluate the degree to which such age differences are present, we meta-analyzed 132 independent correlations and 336 d-values based on 4676 professional workers from 22 samples in 11 countries. Contrary to popular stereotypes, age showed small positive relationships with pro-environmental behaviors, suggesting that older adults engaged in these workplace …

Implementing A Minimally Invasive Approach, Diana V. Macri

Publications and Research

The World Health Organization notes that 60% to 90% of children and nearly 100% of adults have a history of dental caries. The caries process begins with the action of organic acids, which are produced by bacteria found in organized dental plaque via the anaerobic metabolism of dietary sugars. When this dental plaque goes undisturbed, organic acids may initiate the early stages of demineralization. Demineralization gradually weakens the tooth structure, making it more susceptible to plaque formation and demineralization. Remineralization is the process by which the damage to these surfaces is repaired by replacing surface minerals utilizing therapies such as …

Pain Management In Dentistry, Diana V. Macri

Publications and Research

The International Association for the Study of Pain (IASP) has defined pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage." The most common dental complaint is pain, accounting for more than 80%of all dental visits. Pain diminishes the quality of life for many people, although it also may be a vital teacher or a warning message to be heeded. How humans process pain is a complicated, individualized process affected by genetics, personality, life experiences and straight forward physiological process.

Chiropractors’ Perception Of Occupational Stress And Its Influencing Factors: A Qualitative Study Using Responses To Open-Ended Questions, Shawn Williams

Publications and Research

Background: Job stress and emotional exhaustion have been shown to have a negative impact on the helping professional. The development and causal relations of job stress and emotional exhaustion are rather unclear in the chiropractic profession. The objective of this study is to understand the main sources of occupational stress and emotional exhaustion among doctors of chiropractic.

Methods: Analysis of the written responses to web-based open-ended questionnaire was performed using an interpretive research methodology. Additionally, cross tabulation and Chi square statistical tests were conducted to match and couple the demographic data with the categorical themes.

Results: Fourteen professional stress categories …

Abnormal Tau Induces Cognitive Impairment Through Two Different Mechanisms: Synaptic Dysfunction And Neuronal Loss, J. Di, L. S. Cohen, C. P. Corbo, Greg R. Phillips, Abdeslem El Idrissi, Alejandra D. Alonso

Publications and Research

The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimerlike dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization …

Drug Repurposing To Target Ebola Virus Replication And Virulence Using Structural Systems Pharmacology, Zheng Zhao, Che Martin, Raymond Fan, Philip E. Bourne, Lei Xie

Publications and Research

Background: The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation.

Results: One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence …

Sexual Behavior Varies Between Same-Race And Different-Race Partnerships: A Daily Diary Study Of Highly Sexually Active Black, Latino, And White Gay And Bisexual Men, Christian Grov, Demetria Cain, H. Jonathan Rendina, Ana Ventuneac, Jeffrey T. Parsons

Publications and Research

Background. Gay and bisexual men (GBM) are at elevated risk for gonorrhea and chlamydia trachomatis (GC/CT). Rectal GC/CT symptoms may be less obvious than urethral, increasing opportunities for undiagnosed rectal GC/CT.

Method. A U.S. national sample of 1,071 GBM completed urethral and rectal GC/CT testing and an online survey.

Results. In total, 6.2% were GC/CT positive (5.3% rectal, 1.7% urethral). We calculated adjusted (for education, race, age, relationship status, having health insurance, and income) odds ratios for factors associated with rectal and urethral GC/CT diagnoses. Age was inversely associated with urethral and rectal GC/CT. Compared to White men, Latinos had …

Toward Repurposing Metformin As A Precision Anti-Cancer Therapy Using Structural Systems Pharmacology, Thomas Hart, Shihab Dider, Weiwei Han, Hua Xu, Zhongming Zhao, Lei Xie

Publications and Research

Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally …

Hypersexual, Sexually Compulsive, Or Just Highly Sexually Active? Investigating Three Distinct Groups Of Gay And Bisexual Men And Their Profiles Of Hiv-Related Sexual Risk, Jeffrey T. Parsons, H. Jonathan Rendina, Ana Ventuneac, Raymond L. Moody, Christian Grov

Publications and Research

Emerging research supports the notion that sexual compulsivity (SC) and hypersexual disorder (HD) among gay and bisexual men (GBM) might be conceptualized as comprising three groups—Neither SC nor HD; SC only, and Both SC and HD—that capture distinct levels of severity across the SC/HD continuum. We examined data from 370 highly sexually active GBM to assess how the three groups compare across a range of risk factors for HIV infection. Comparisons focused on psychosexual measures—temptation for condomless anal sex (CAS), self-efficacy for avoiding CAS, sexual excitation and inhibition—as well as reports of actual sexual behavior. Nearly half (48.9%) of this …

The Specificity Of Mental Pain In Borderline Personality Disorder Compared To Depressive Disorders And Healthy Controls, Eric A. Fertuck, Esen Karan, Barbara Stanley

Publications and Research

Background: Individuals with Borderline Personality Disorder (BPD) may experience a qualitatively distinct depression which includes “mental pain.” Mental pain includes chronic, aversive emotions, negative self-concept, and a sense of pervasive helplessness. The present study investigated whether mental pain is elevated in BPD compared to Depressive Disorders (DD) without BPD.

Methods: The Orbach and Mikulincer Mental Pain Scale (OMMP) was administered to BPD (N = 57), DD (N = 22), and healthy controls (N = 31). The OMMP assesses total mental pain, comprised of nine subtypes: irreversibility, loss of control, narcissistic wounds, emotional flooding, freezing, self-estrangement, confusion, social distancing, and emptiness. …

An Advertisement And Article Analysis Of Skin Products And Topics In Popular Women’S Magazines: Implications For Skin Cancer Prevention, Corey H. Basch, Jennifer Mongiovi, Grace Clarke Hillyer, Md Fullwood, Danna Ethan, Rodney Hammond

Publications and Research

Background: In the United States, skin cancer is the most commonly diagnosed cancer, with an estimated 5 million people treated per year and annual medical treatment expenditures that exceed 8 billion dollars. The purpose of this study was two-fold: 1) to enumerate the number of advertisements for skin products with and without Sun Protection Factor (SPF) and to further analyze the specific advertisements for sunblock to determine if models, when present, depict sun safe behaviors and 2) to enumerate the number of articles related to the skin for content. Both aims include an assessment for differences in age and in …

The Relationship Between Foot Arch Measurements And Walking Parameters In Children, Simone V. Gill, Sara Keimig, Damian Kelty-Stephen, Ya-Ching Hung, Jeremy M. Desilva

Publications and Research

Background: Walking mechanics are influenced by body morphology. Foot arch height is one aspect of body morphology central to walking. However, generalizations about the relationship between arch height and walking are limited due to previous methodologies used for measuring the arch and the populations that have been studied. To gain the knowledge needed to support healthy gait in children and adults, we need to understand this relationship in unimpaired, typically developing children and adults using dynamic measures. The purpose of the current study was to examine the relationship between arch height and gait in a sample of healthy children …

A Comparison Of Increases In Volume Load Over 8 Weeks Of Low-Versus High-Load Resistance Training, Brad J. Schoenfeld, Dan Ogborn, Bret Contreras, Tom Cappaert, Alex Silva Ribeiro, Brent A. Alvar, Andrew D. Vigotsky

Publications and Research

Background: It has been hypothesized that the ability to increase volume load (VL) via a progressive increase in the magnitude of load for a given exercise within a given repetition range could enhance the adaptive response to resistance training.

Objectives: The purpose of this study was to compare changes in volume load (VL) over eight weeks of resistance training (RT) in high-versus low-load protocols.

Materials and Methods: Eighteen well-trained men were matched according to baseline strength were randomly assigned to either a low-load RT(LOW,n= 9) where 25 - 35 repetitions were performed per exercise, or a high-load RT (HIGH,n= 9) …

How Different Are Men Who Do Not Know Their Hiv Status From Those Who Do? Results From An U.S. Online Study Of Gay And Bisexual Men, Christian Grov, H. Jonathon Rendina, Jeffrey T. Parsons

Publications and Research

We compared self-described HIV-positive (31.6%, n=445), HIV-negative (56.8%, n=801), and HIV-unknown (11.6%, n=164) gay and bisexual men (GBM) on sociodemographic and behavioral characteristics. Participants from across the U.S. were enrolled via a popular sexual networking website to complete an online survey. In total, 44.8% of HIV-negative and HIV-unknown men said they had not been tested for HIV in the CDC-recommended last 6 months. HIV-unknown men significantly differed from HIV-negative and HIV-positive men in sexual behavior and HIV status disclosure patterns. HIV-unknown men were more willing than HIV-negative men to take PrEP; however, HIV-unknown men were significantly less likely than others …

Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response To Pulmonary Tuberculosis In A Rabbit Model, Selvakumar Subbian, Liana Tsenova, Jennifer Holloway, Blas Peixoto, Paul O'Brien, Veronique Dartois, Vikram Khetani, Jerome B. Zeldis, Gilla Kaplan

Publications and Research

Objectives: Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB).We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection.

Methods: A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with orwithout CC-11050, starting at fourweeks post infection. The …

Reorienting Adolescent Sexual And Reproductive Health Research: Reflections From An International Conference, Kristien Michielsen, Sara De Meyer, Olena Ivanova, Ragnar Anderson, Peter Decat, Céline Herbiet, Caroline W. Kabiru, Evert Ketting, James Lees, Caroline Moreau, Deborah L. Tolman, Ine Vanwesenbeeck, Bernardo Vega, Elizabeth Verhetsel, Venkatraman Chandra-Mouli

Publications and Research

On December 4th 2014, the International Centre for Reproductive Health (ICRH) at Ghent University organized an international conference on adolescent sexual and reproductive health (ASRH) and well-being. This viewpoint highlights two key messages of the conference - 1) ASRH promotion is broadening on different levels and 2) this broadening has important implications for research and interventions – that can guide this research field into the next decade. Adolescent sexuality has long been equated with risk and danger. However, throughout the presentations, it became clear that ASRH and related promotion efforts are broadening on different levels: from risk to well-being, from …

The Human Disease-Associated Ab Amyloid Core Sequence Forms Functional Amyloids In A Fungal Adhesin, Rachele D. Rameau, Desmond N. Jackson, Audrey Beaussary, Yves F. Dufrêne, Peter N. Lipke

Publications and Research

There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains form through interactions that have amyloid-like properties: binding of amyloid dyes, perturbation by antiamyloid agents, and interaction with homologous sequences. To test whether these functional interactions are mediated by typical amyloid interactions, we substituted an amyloid core sequence, LVFFA, from human A protein for the native sequence IVIVA in the 1,419-residue Candida albicans adhesin Als5p. The chimeric protein …