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1.
J Urban Health ; 98(6): 711-726, 2021 12.
Article in English | MEDLINE | ID: mdl-34811699

ABSTRACT

Immigrant women represent half of New York City (NYC) births, and some immigrant groups have elevated risk for poor maternal health outcomes. Disparities in health care utilization across the maternity care spectrum may contribute to differential maternal health outcomes. Data on immigrant maternal health utilization are under-explored in the literature. We conducted a cross-sectional analysis of the population-based NYC Pregnancy Risk Assessment Monitoring System survey, using 2016-2018 data linked to birth certificate variables, to explore self-reported utilization of preconception, prenatal, and postpartum health care and potential explanatory pathways. We stratified results by maternal nativity and, for immigrants, by years living in the US; geographic region of origin; and country of origin income grouping. Among immigrant women, 43% did not visit a health care provider in the year before pregnancy, compared to 27% of US-born women (risk difference [RD] = 0.16, 95% CI [0.13, 0.20]), 64% had no dental cleaning during pregnancy compared to 49% of US-born women (RD = 0.15, 95% CI [0.11, 0.18]), and 11% lost health insurance postpartum compared to 1% of US-born women (RD = 0.10, 95% CI [0.08, 0.11]). The largest disparities were among recent arrivals to the US and immigrants from countries in Central America, South America, South Asia, and sub-Saharan Africa. Utilization differences were partially explained by insurance type, paternal nativity, maternal education, and race and ethnicity. Disparities may be reduced by collaborating with community-based organizations in immigrant communities on strategies to improve utilization and by expanding health care access and eligibility for public health insurance coverage before and after pregnancy.


Subject(s)
Emigrants and Immigrants , Maternal Health Services , Cross-Sectional Studies , Female , Humans , Maternal Health , Mothers , New York City/epidemiology , Pregnancy
2.
Cleft Palate Craniofac J ; 55(9): 1191-1199, 2018 10.
Article in English | MEDLINE | ID: mdl-29665339

ABSTRACT

OBJECTIVE: To determine the role of racial background, public health initiatives, and residence on the prevalence of orofacial clefts (OFCs) in New York City (NYC). DESIGN/METHODS: Retrospective review of OFC cases from the New York State Congenital Malformations Registry. PATIENTS/PARTICIPANTS: Patients born with an OFC and all live births to mothers residing in NYC between 1983 and 2010. MAIN OUTCOME MEASURES: Orofacial cleft birth prevalence by cleft type, race, and borough of maternal residence for each year and by time period around the implementation of public health interventions including folate supplementation. RESULTS: A total of 3557 cases were reviewed. The prevalence remained stable for cleft palate and cleft lip with or without cleft palate (CL ± P) in sequential time periods of the study. Among CL ± P cases, cleft lip prevalence decreased early in the study compared to increases in cleft lip and palate prevalence. For most years, the prevalence of OFCs was lower among African Americans than whites. A total of 12% to 26% of mothers in 4 of the NYC boroughs deliver outside of their borough of residence, choosing to give birth in Manhattan most often. No difference in OFC prevalence was shown in any of the 5 NYC boroughs. CONCLUSIONS: The period prevalence remained relatively stable during the time periods before and after the implementation of folate supplementation for OFCs in NYC. Prevalence of OFC subtypes was lower for most time periods during this study among African Americans compared to whites. Several factors may explain the choice of birthplace outside of the mother's borough of residence.


Subject(s)
Cleft Lip/epidemiology , Cleft Palate/epidemiology , Public Health Practice , Residence Characteristics , Cleft Lip/ethnology , Cleft Lip/prevention & control , Cleft Palate/ethnology , Cleft Palate/prevention & control , Female , Humans , Infant, Newborn , Male , New York City , Pregnancy , Prevalence , Registries , Retrospective Studies
3.
J Community Health ; 42(5): 903-910, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28321648

ABSTRACT

Within the United States, alternative tobacco product (ATP) and varies by geographic region, gender and age. Few articles have been published on the usage of these products among the lesbian, gay, bisexual, transgender or queer (LGBTQ) population. A web-based anonymous survey administered through Google Forms, was used to collect data on current tobacco usage, knowledge and beliefs from adult heterosexuals, homosexuals, bisexuals and transgendered persons residing in New York City from May 2014 to July 2014. Sixty-four individuals completed the survey; 30 were heterosexual and 32 identified as either lesbian, gay, bisexual, transgender or queer. Heterosexuals were found to have tried cigarettes, on average, almost a year before the LGBTQ respondents. Social networks were influential to LGBTQ respondents for an introduction to smoking; 48.00% were introduced by friends, 28.00% by family, 12.00% by a significant other and 9.09% by someone else. For heterosexuals, 73.68% reported that friends introduced them to smoking. More heterosexuals reported trying hookah (N = 10), snus (N = 4) and roll your own cigarettes (N = 5). On average respondents knew of eight different tobacco products, regardless of sexual identity. To our knowledge, we present for the first time a comparison of people who tried, current and former users of ATPs, beliefs and knowledge about ATPs, and sources of knowledge of ATPs by sexual identity from NYC. More research is needed to examine the impact of social networks and the upcoming FDA regulations on ATPs have on the overall prevalence of usage among the LGBTQ community.


Subject(s)
Electronic Nicotine Delivery Systems , Health Knowledge, Attitudes, Practice , Sexual and Gender Minorities/psychology , Sexual and Gender Minorities/statistics & numerical data , Water Pipe Smoking , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , New York City , Public Health , Sexuality , Social Support , Young Adult
4.
Biochem J ; 468(1): 17-24, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25940733

ABSTRACT

Catalytically inactive enzymes (also known as pseudoproteases, protease homologues or paralogues, non-peptidase homologues, non-enzymes and pseudoenzymes) have traditionally been hypothesized to act as regulators of their active homologues. However, those that have been characterized demonstrate that inactive enzymes have an extensive and expanding role in biological processes, including regulation, inhibition and immune modulation. With the emergence of each new genome, more inactive enzymes are being identified, and their abundance and potential as therapeutic targets has been realized. In the light of the growing interest in this emerging field the present review focuses on the classification, structure, function and mechanism of inactive enzymes. Examples of how inactivity is defined, how this is reflected in the structure, functions of inactive enzymes in biological processes and their mode of action are discussed.


Subject(s)
Peptide Hydrolases/chemistry , Peptide Hydrolases/metabolism , Animals , Arthropod Proteins/chemistry , Arthropod Proteins/genetics , Arthropod Proteins/metabolism , Aspartic Acid Endopeptidases/chemistry , Aspartic Acid Endopeptidases/genetics , Aspartic Acid Endopeptidases/metabolism , Catalytic Domain/genetics , Cockroaches/enzymology , Cockroaches/genetics , Databases, Protein , Humans , Models, Molecular , Peptide Hydrolases/genetics , Phylogeny , Plasmodium falciparum/enzymology , Plasmodium falciparum/genetics , Protein Conformation , Protozoan Proteins/chemistry , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Sarcoptes scabiei/enzymology , Sarcoptes scabiei/genetics , Structural Homology, Protein
5.
Matern Child Health J ; 19(4): 798-810, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25030701

ABSTRACT

The objective of this study is unknown if fetal sex and race modify the impact of maternal pre-pregnancy body mass index (BMI), and smoking on fetal growth. The authors studied markers of fetal growth in singleton offspring of 8,801 primiparous, normotensive women, enrolled in the Collaborative Perinatal Project. The authors tested for departures from additivity between sex/race and each predictor. The head-to-chest circumference ratio (HCC) decreased more, while birthweight and ponderal index (PI) increased more for each 1 kg/m(2) increase in pre-pregnancy BMI among term females versus males (P = 0.07, P < 0.01 and P = 0.08, interaction respectively). For term offspring of White compared with Black women, smoking independent of "dose" was associated with larger reductions in growth (165 g vs. 68 g reduction in birthweight, P < 0.01, interaction), greater reduction in fetal placental ratio (P < 0.01, interaction), PI (P < 0.01, interaction), and greater increase in HCC (P = 0.02), respectively. The association of BMI and smoking with fetal size appeared to be reversed in term versus preterm infants. Our study provides evidence that the associations of pre-pregnancy BMI and smoking are not constant across sex and race. This finding may be relevant to sex and race differences in neonatal and long term health outcomes.


Subject(s)
Fetal Development , Racial Groups/statistics & numerical data , Adult , Black or African American/statistics & numerical data , Birth Weight/physiology , Body Mass Index , Female , Fetal Development/physiology , Gestational Age , Humans , Male , Maternal Age , Parity , Pregnancy , Pregnancy Complications/epidemiology , Sex Factors , Smoking/adverse effects , Socioeconomic Factors , White People/statistics & numerical data , Young Adult
6.
Cell Tissue Res ; 351(2): 339-52, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22427061

ABSTRACT

Among arthropod pests, mites are responsible for considerable damage to crops, humans and other animals. However, detailed physiological data on these organisms remain sparse, mainly because of their small size but possibly also because of their extreme diversity. Focusing on intestinal proteases, we draw together information from three distinct mite species that all feed on skin but have separately adapted to a free-living, a strictly ecto-parasitic and a parasitic lifestyle. A wide range of studies involving immunohistology, molecular biology, X-ray crystallography and enzyme biochemistry of mite gut proteases suggests that these creatures have diverged considerably as house dust mites, sheep scab mites and scabies mites. Each species has evolved a particular variation of a presumably ancestral repertoire of digestive enzymes that have become specifically adapted to their individual environmental requirements.


Subject(s)
Intestinal Diseases, Parasitic/parasitology , Intestines/parasitology , Mites/enzymology , Animals , Humans , Psoroptidae/enzymology , Pyroglyphidae/enzymology , Scabies/parasitology
7.
Health Lit Res Pract ; 7(3): e119-e129, 2023 07.
Article in English | MEDLINE | ID: mdl-37463292

ABSTRACT

BACKGROUND: Black women experience greater maternal mortality and morbidity than White women. Although there are many causes of this disparity, providing more and better maternal health information to this population may be beneficial. Social media offers a way to easily and quickly disseminate information to empower and educate Black women about health during pregnancy. OBJECTIVE: This study sought to identify social media use patterns to determine what sources Black women used to obtain information about pregnancy and to explore whether health literacy/eHealth literacy influence those patterns. METHODS: This cross-sectional, nationally representative survey panel included 404 Black women. Health literacy was measured by the Single Item Literacy Screener, and eHEALS was used to measure eHealth literacy. We examined participants' social media activity, social media use, social media use for support, and sharing of pregnancy-related health information. Relationships between health literacy, eHealth literacy, and social media use were assessed. KEY RESULTS: Overall, 67.5% of participants had high health literacy, and the average eHealth literacy score was high (34.5). Most women (71.6%) reported using more than three social media accounts as a source for pregnancy information. Women with low health literacy searched social media for general and specific pregnancy health information, reported more social media use during pregnancy in general (p < .001), and more use of social media for giving and getting support (p = .003). Women with higher eHealth literacy were more likely to report more social media use (r = 0.107, p = .039) and often used social media to give and get support (r = 0.197, p = .0001). Women with high health literacy more often reported sharing the pregnancy information they found on social media with their nurse (χ2 = 7.068, p = .029), doula (χ2 = 6.878, p = .032), and childbirth educator (χ2 = 10.289, p = .006). Women who reported higher eHealth literacy also reported more often sharing the pregnancy information they found on social media with their doctor (r = 0.115, p = .030), nurse (r = 0.139, p = .001), coworkers (r = 0.160, p = .004), and family or friends (r = 0.201, p = .0001). CONCLUSION: Substantial numbers of Black women use social media to find pregnancy health information. Future studies should elicit more detailed information on why and how Black women use social media to obtain pregnancy information and support as well as what role health literacy and eHealth literacy may have on birth outcomes. [HLRP: Health Literacy Research and Practice. 2023;7(3):e119-e129.].


Subject(s)
Health Literacy , Social Media , Telemedicine , Humans , Female , Cross-Sectional Studies , Maternal Health
8.
NPJ Vaccines ; 8(1): 9, 2023 Feb 04.
Article in English | MEDLINE | ID: mdl-36739443

ABSTRACT

We have developed a candidate vaccine to protect against multiple strains of Streptococcus pyogenes infections. The candidate vaccine contains two synthetic peptides derived from S. pyogenes proteins: the M-protein epitope, p*17 and the IL-8 degrading S. pyogenes Cell-Envelope Proteinase (SpyCEP) epitope, K4S2. In this study we utilise a rat autoimmune valvulitis model that displays both the cardiac and neurobehavioural pathology associated with post-streptococcal sequelae, to assess if the vaccine candidate antigens induce autoimmune complications and inflammatory pathology. Each antigen was conjugated to carrier protein diphtheria toxoid (DT) and independently assessed for potential to induce autoimmune pathology in female Lewis rats. Rats were administered three subcutaneous doses, and one intranasal dose over a four-week study with a two-week recovery period. A positive control group received recombinant S. pyogenes M5 (rM5) protein, and the negative control group received PBS. Rats that received rM5 developed significant cardiac and neurological pathologies. There was no evidence of these pathologies in the PBS control group, or the rats administered either P*17-DT or K4S2-DT. This study provides further preclinical evidence of the safety of the vaccine candidates p*17 and K4S2 and their appropriateness as candidates in human clinical trials.

9.
mBio ; 14(1): e0348822, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36744883

ABSTRACT

Mutation within the Streptococcus pyogenes (Streptococcus group A; Strep A) covR/S regulatory system has been associated with a hypervirulent phenotype resulting from the upregulation of several virulence factors, including the pore-forming toxin, streptolysin O (SLO). In this study, we utilized a range of covR/S mutants, including M1T1 clonal strains (5448 and a covS mutant generated through mouse passage designated 5448AP), to investigate the contribution of SLO to the pathogenesis of covR/S mutant Strep A disease. Up-regulation of slo in 5448AP resulted in increased SLO-mediated hemolysis, decreased dendritic cell (DC) viability post coculture with Strep A, and increased production of tumor necrosis factor (TNF) and monocyte chemoattractant protein 1 (MCP-1) by DCs. Mouse passage of an isogenic 5448 slo-deletion mutant resulted in recovery of several covR/S mutants within the 5448Δslo background. Passage also introduced mutations in non-covR/S genes, but these were considered to have no impact on virulence. Although slo-deficient mutants exhibited the characteristic covR/S-controlled virulence factor upregulation, these mutants caused increased DC viability with reduced inflammatory cytokine production by infected DCs. In vivo, slo expression correlated with decreased DC numbers in infected murine skin and significant bacteremia by 3 days postinfection, with severe pathology at the infection site. Conversely, the absence of slo in the infecting strain (covR/S mutant or wild-type) resulted in detection of DCs in the skin and attenuated virulence in a murine model of pyoderma. slo-sufficient and -deficient covR/S mutants were susceptible to immune clearance mediated by a combination vaccine consisting of a conserved M protein peptide and a peptide from the CXC chemokine protease SpyCEP. IMPORTANCE Streptococcus pyogenes is responsible for significant numbers of invasive and noninvasive infections which cause significant morbidity and mortality globally. Strep A isolates with mutations in the covR/S system display greater propensity to cause severe invasive diseases, which are responsible for more than 163,000 deaths each year. This is due to the upregulation of virulence factors, including the pore-forming toxin streptolysin O. Utilizing covR/S and slo-knockout mutants, we investigated the role of SLO in virulence. We found that SLO alters interactions with host cell populations and increases Strep A viability at sterile sites of the host, such as the blood, and that its absence results in significantly less virulence. This work underscores the importance of SLO in Strep A virulence while highlighting the complex nature of Strep A pathogenesis. This improved insight into host-pathogen interactions will enable a better understanding of host immune evasion mechanisms and inform streptococcal vaccine development programs.


Subject(s)
Streptococcal Infections , Streptococcus pyogenes , Animals , Mice , Virulence/genetics , Streptolysins/genetics , Streptolysins/metabolism , Bacterial Proteins/metabolism , Virulence Factors/metabolism
10.
J Immunol ; 182(12): 7809-17, 2009 Jun 15.
Article in English | MEDLINE | ID: mdl-19494305

ABSTRACT

Infestation of skin by the parasitic itch mite Sarcoptes scabiei afflicts 300 million people worldwide and there is a need for novel and efficient therapies. We have previously identified a multigene family of serine proteases comprising multiple catalytically inactive members (scabies mite-inactivated protease paralogs (SMIPPs)), which are secreted into the gut of S. scabiei. SMIPPs are located in the mite gut and in feces excreted into the upper epidermis. Scabies mites feed on epidermal protein, including host plasma; consequently, they are exposed to host defense mechanisms both internally and externally. We found that two recombinantly expressed SMIPPs inhibited all three pathways of the human complement system. Both SMIPPs exerted their inhibitory action due to binding of three molecules involved in the three different mechanisms which initiate complement: C1q, mannose-binding lectin, and properdin. Both SMIPPs bound to the stalk domains of C1q, possibly displacing or inhibiting C1r/C1s, which are associated with the same domain. Furthermore, we found that binding of both SMIPPs to properdin resulted in prevention of assembly of the alternative pathway convertases. However, the SMIPPs were not able to dissociate already formed convertases. Immunohistochemical staining demonstrated the presence of C1q in the gut of scabies mites in skin burrows. We propose that SMIPPs minimize complement-mediated gut damage and thus create a favorable environment for the scabies mites.


Subject(s)
Complement System Proteins/immunology , Sarcoptes scabiei/enzymology , Scabies/immunology , Serine Endopeptidases/metabolism , Animals , Enzyme Activation , Hemolysis , Humans , Protein Binding , Scabies/pathology , Serine Endopeptidases/genetics , Serine Endopeptidases/isolation & purification , Sheep
11.
Sci Rep ; 11(1): 127, 2021 01 08.
Article in English | MEDLINE | ID: mdl-33420258

ABSTRACT

We have developed two candidate vaccines to protect against multiple strains of Strep A infections. The candidates are combinatorial synthetic peptide vaccines composed of a M protein epitope (J8 or p*17) and a non-M protein epitope (K4S2). To enhance immunogenicity, each peptide is conjugated to the carrier protein CRM197 (CRM) and formulated with aluminium hydroxide adjuvant Alhydrogel (Alum) to make the final vaccines, J8-CRM + K4S2-CRM/Alum and p*17-CRM + K4S2-CRM/Alum. The safety and toxicity of each vaccine was assessed. Sprague Dawley rats were administered three intramuscular doses, over a six-week study with a 4-week recovery period. A control group received CRM only formulated with Alum (CRM/Alum). There was no evidence of systemic toxicity in the rats administered either vaccine. There was an associated increase in white blood cell, lymphocyte and monocyte counts, increased adrenal gland weights, adrenocortical hypertrophy, and increased severity of granulomatous inflammation at the sites of injection and the associated inguinal lymph nodes. These changes were considered non-adverse. All rats administered vaccine developed a robust and sustained immunological response. The absence of clinical toxicity and the development of an immunological response in the rats suggests that the vaccines are safe for use in a phase 1 clinical trial in healthy humans.


Subject(s)
Streptococcal Infections/prevention & control , Streptococcal Vaccines/immunology , Streptococcus pyogenes/immunology , Vaccines, Subunit/immunology , Animals , Drug Evaluation, Preclinical , Female , Humans , Immunogenicity, Vaccine , Male , Mice , Mice, Inbred BALB C , Rats , Rats, Sprague-Dawley , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Streptococcal Vaccines/administration & dosage , Streptococcal Vaccines/adverse effects , Streptococcus pyogenes/genetics , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/adverse effects
12.
PLoS Negl Trop Dis ; 15(1): e0008997, 2021 01.
Article in English | MEDLINE | ID: mdl-33406071

ABSTRACT

BACKGROUND: Scabies, a highly contagious skin disease affecting more than 200 million people worldwide at any time, is caused by the parasitic mite Sarcoptes scabiei. In the absence of molecular markers, diagnosis requires experience making surveillance and control challenging. Superficial microthrombi in the absence of vasculitis in scabies-affected skin are a recognised, yet unexplained histopathological differential of scabies infection. This study demonstrates that a family of Scabies Mite Inactivated Cysteine Protease Paralogues (SMIPP-Cs) excreted by the mites plays a role in formation of scabies-induced superficial microthrombi. METHODOLOGY/PRINCIPAL FINDINGS: A series of in vitro and ex vivo experiments involving two representative recombinant SMIPP-Cs was carried out. In the presence of SMIPP-Cs, the thrombin clotting time (TCT), fibrin formation and plasmin induced fibrinolysis were monitored in vitro. The ultrastructure of the SMIPP-C-modulated fibrin was analysed by Scanning Electron Microscopy (SEM). Immuno-histological analyses were performed ex vivo, to localise the SMIPP-C proteins within scabies infected skin biopsies. SMIPP-Cs displayed pro-coagulant properties. They bound calcium ions, reduced the thrombin clotting time, enhanced the fibrin formation rate and delayed plasmin-induced fibrinolysis. The SMIPP-Cs associated with fibrin clots during fibrinogen polymerisation and did not bind to preformed fibrin. Scanning electron microscopy revealed that the fibrin clots formed in the presence of SMIPP-Cs were aberrant and denser than normal fibrin clots. SMIPP-Cs were detected in microthrombi which are commonly seen in scabietic skin. CONCLUSIONS/SIGNIFICANCE: The SMIPP-Cs are the first scabies mite proteins found in sub-epidermal skin layers and their pro-coagulant properties promote superficial microthrombi formation in scabetic skin. Further research is needed to evaluate their potential as diagnostic or therapeutic target.


Subject(s)
Blood Coagulation , Cysteine Proteases/physiology , Fibrinolysin/pharmacology , Fibrinolysis , Sarcoptes scabiei/enzymology , Scabies/parasitology , Skin/blood supply , Animals , Calcium/metabolism , Cysteine Proteases/analysis , Fibrin/biosynthesis , Humans
13.
mBio ; 12(1)2021 02 23.
Article in English | MEDLINE | ID: mdl-33622722

ABSTRACT

Infections with Streptococcus pyogenes and their sequelae are responsible for an estimated 18 million cases of serious disease with >700 million new primary cases and 500,000 deaths per year. Despite the burden of disease, there is currently no vaccine available for this organism. Here, we define a combination vaccine P*17/K4S2 comprising of 20-mer B-cell peptide epitopes, p*17 (a mutant derived from the highly conserved C3-repeat region of the M-protein), and K4S2 (derived from the streptococcal anti-neutrophil factor, Spy-CEP). The peptides are chemically conjugated to either diphtheria toxoid (DT) or a nontoxic mutant form of diphtheria toxin, CRM197. We demonstrate that a prime-pull immunization regimen involving two intramuscular inoculations with P*17/K4S2 adjuvanted with a two-component liposomal adjuvant system (CAF01; developed by Statens Serum Institut [SSI], Denmark), followed by an intranasal inoculation of unadjuvanted vaccine (in Tris) induces peptide- and S. pyogenes-binding antibodies and protects from mucosal and skin infection with hypervirulent covR/S mutant organisms. Prior vaccination with DT does not diminish the response to the conjugate peptide vaccines. Detailed Good Laboratory Practice (GLP) toxicological evaluation in male and female rats did not reveal any gross or histopathological adverse effects.IMPORTANCE A vaccine to control S. pyogenes infection is desperately warranted. S. pyogenes colonizes the upper respiratory tract (URT) and skin, from where it can progress to invasive and immune-mediated diseases. Global mortality estimates for S. pyogenes-associated diseases exceeds 500,000 deaths per year. S. pyogenes utilizes antigenic variation as a defense mechanism to circumvent host immune responses and thus a successful vaccine needs to provide strain-transcending and multicompartment (mucosal and skin) immunity. By defining highly conserved and protective epitopes from two critical virulence factors (M-protein and Spy-CEP) and combining them with a potent immunostimulant, CAF®01, we are addressing an unmet clinical need for a mucosally and skin-active subunit vaccine. We demonstrate that prime-pull immunization (2× intramuscular injections followed by intranasal immunization) promotes high sustained antibody levels in the airway mucosa and serum and protects against URT and invasive disease.


Subject(s)
Bacterial Outer Membrane Proteins/immunology , Epitopes, B-Lymphocyte/immunology , Immunity, Mucosal , Immunization/methods , Liposomes/chemistry , Streptococcal Vaccines/immunology , Streptococcus pyogenes/immunology , Adjuvants, Immunologic/administration & dosage , Animals , Antibodies, Bacterial/blood , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Bacterial Outer Membrane Proteins/administration & dosage , Bacterial Outer Membrane Proteins/genetics , Epitopes, B-Lymphocyte/genetics , Female , Liposomes/administration & dosage , Male , Mice, Inbred BALB C , Rats , Rats, Sprague-Dawley , Streptococcal Infections/prevention & control , Streptococcal Vaccines/administration & dosage , Streptococcus pyogenes/genetics , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology
14.
J Biol Chem ; 284(49): 34413-22, 2009 Dec 04.
Article in English | MEDLINE | ID: mdl-19812030

ABSTRACT

The scabies mite, Sarcoptes scabiei var. hominis, infests human skin, causing allergic reactions and facilitating bacterial infection by Streptococcus sp., with serious consequences such as rheumatic fever and rheumatic heart disease. To identify a possible drug target or vaccine candidate protein, we searched for homologues of the group 3 allergen of house dust mites, which we subsequently identified in a cDNA library. The native protein, designated Sar s 3, was shown to be present in the mite gut and excreted in fecal pellets into mite burrows within the upper epidermis. The substrate specificity of proteolytically active recombinant rSar s 3 was elucidated by screening a bacteriophage library. A preference for substrates containing a RS(G/A) sequence at the P1-P2' positions was revealed. A series of peptides synthesized as internally quenched fluorescent substrates validated the phage display data and high performance liquid chromatography/mass spectrometry analysis of the preferred cleaved substrate and confirmed the predicted cleavage site. Searches of the human proteome using sequence data from the phage display allowed the in silico prediction of putative physiological substrates. Among these were numerous epidermal proteins, with filaggrin being a particularly likely candidate substrate. We showed that recombinant rSar s 3 cleaves human filaggrin in vitro and obtained immunohistological evidence that the filaggrin protein is ingested by the mite. This is the first report elucidating the substrate specificity of Sar s 3 and its potential role in scabies mite biology.


Subject(s)
Antigens, Dermatophagoides/chemistry , Sarcoptes scabiei/chemistry , Serine Proteases/chemistry , Animals , Bacteriophages/metabolism , Female , Filaggrin Proteins , Humans , Hydrogen-Ion Concentration , Intermediate Filament Proteins/chemistry , Mice , Mice, Inbred C57BL , Mites , Peptide Library , Pichia/metabolism , Recombinant Proteins/chemistry , Substrate Specificity
15.
Article in English | MEDLINE | ID: mdl-33053737

ABSTRACT

Triclosan was introduced into the market in the 1970s and has since been used as an antimicrobial agent in a diverse array of consumer and personal care products. Although it has been widely used over a number of years, there is growing concern and debate over its safety and efficacy and its potential as an endocrine disruptor. Although prior animal toxicology studies have shown an association between triclosan and decreased testosterone levels, human studies have been limited, particularly for adult men. Using the National Health and Nutrition Examination Survey data (NHANES, 2011-2012), we examined the association of urinary triclosan on testosterone levels in adult men 18-65 years of age. Multivariable linear regression analysis failed to show an association between triclosan and serum testosterone (ß = 0.0003, p = 0.98, 95% CI = -0.024, 0.025). The results suggest there is no association or that triclosan concentrations are too low to cause a significant impact on testosterone levels. Additionally, longitudinal studies would provide a more comprehensive understanding of the direction of change and magnitude of causal relationships over time.


Subject(s)
Endocrine Disruptors , Testosterone , Triclosan , Adolescent , Adult , Aged , Endocrine Disruptors/toxicity , Endocrine Disruptors/urine , Humans , Linear Models , Male , Middle Aged , Nutrition Surveys , Testosterone/blood , Triclosan/toxicity , Triclosan/urine , Young Adult
17.
NPJ Vaccines ; 5(1): 74, 2020.
Article in English | MEDLINE | ID: mdl-32802413

ABSTRACT

We evaluated vaccination against Streptococcus pyogenes with the candidate vaccine, J8-DT, delivered by a high-density microarray patch (HD-MAP). We showed that vaccination with J8-DT eluted from a coated HD-MAP (J8-DT/HD-MAP), induced similar total IgG responses to that generated by vaccination with J8-DT adjuvanted with Alum (J8-DT/Alum). We evaluated the effect of dose reduction and the number of vaccinations on the antibody response profile of vaccinated mice. A reduction in the number of vaccinations (from three to two) with J8-DT/HD-MAP induced comparable antibody responses to three vaccinations with intramuscular J8-DT/Alum. Vaccine-induced protection against an S. pyogenes skin challenge was assessed. J8-DT/HD-MAP vaccination led to a significant reduction in the number of S. pyogenes colony forming units in skin (92.9%) and blood (100%) compared to intramuscular vaccination with unadjuvanted J8-DT. The protection profile was comparable to that of intramuscular J8-DT/Alum. J8-DT/HD-MAP induced a shift in the antibody isotype profile, with a bias towards Th1-related isotypes, compared to J8-DT/Alum (Th2 bias). Based on the results of this study, the use of J8-DT/HD-MAP should be considered in future clinical development and control programs against S. pyogenes. Furthermore, the innate characteristics of the technology, such as vaccine stability and increased coverage, ease of use, reduction of sharp waste and the potential reduction of dose may be advantageous compared to current vaccination methods.

18.
PLoS Negl Trop Dis ; 14(10): e0008720, 2020 10.
Article in English | MEDLINE | ID: mdl-33001992

ABSTRACT

The parasitic mite Sarcoptes scabiei is an economically highly significant parasite of the skin of humans and animals worldwide. In humans, this mite causes a neglected tropical disease (NTD), called scabies. This disease results in major morbidity, disability, stigma and poverty globally and is often associated with secondary bacterial infections. Currently, anti-scabies treatments are not sufficiently effective, resistance to them is emerging and no vaccine is available. Here, we report the first high-quality genome and transcriptomic data for S. scabiei. The genome is 56.6 Mb in size, has a a repeat content of 10.6% and codes for 9,174 proteins. We explored key molecules involved in development, reproduction, host-parasite interactions, immunity and disease. The enhanced 'omic data sets for S. scabiei represent comprehensive and critical resources for genetic, functional genomic, metabolomic, phylogenetic, ecological and/or epidemiological investigations, and will underpin the design and development of new treatments, vaccines and/or diagnostic tests.


Subject(s)
Sarcoptes scabiei/genetics , Scabies/parasitology , Swine/parasitology , Animals , Genome Size , Host-Parasite Interactions , Mass Spectrometry , Phylogeny , Skin/immunology , Skin/parasitology
19.
Am J Health Promot ; 32(5): 1178-1186, 2018 06.
Article in English | MEDLINE | ID: mdl-28318307

ABSTRACT

PURPOSE: This study contributes to the emerging literature on lesbian, gay, bisexual, transgendered, and queer (LGBTQ) health disparities and tobacco use by examining the motivations for smoking among the New York City (NYC) LGBTQ population. APPROACH: We used grounded theory and blended methods from 3 grounded theorists-Strauss, Corbin, and Charmaz-for data collection, coding, and analysis. SETTING: NYC has extensive legislation to prevent smoking; however, the current smoking prevalence of homosexuals is double that of heterosexuals. PARTICIPANTS: Study participants were leaders from 23 NYC LGBTQ organizations. Leaders were chosen to establish a relationship with community and to ensure cultural sensitivity. Eligibility criteria required holding a leadership position in an organization serving the NYC LGBTQ community. METHODS: Interviews were transcribed verbatim and uploaded into Dedoose for analysis. An initial code list was developed from the interview guide. Key themes were identified as the themes with the most number of quotes. RESULTS: Three key themes emerged from our interviews: image, socializing, and stress. Smoking was reported to be a socialization aid and a maladaptive coping technique for stress arising from interactions of conflicting identities. CONCLUSION: Future smoking cessation interventions among the LGBTQ community should equip smokers with healthy coping mechanisms that address the stressors that arise from the intersections of smokers' many identities.


Subject(s)
Heterosexuality/psychology , Motivation , Sexual and Gender Minorities/psychology , Social Behavior , Stress, Psychological/complications , Tobacco Smoking/psychology , Transgender Persons/psychology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , New York City/epidemiology , Sexual and Gender Minorities/statistics & numerical data , Tobacco Smoking/epidemiology , Transgender Persons/statistics & numerical data
20.
Parasit Vectors ; 11(1): 301, 2018 05 16.
Article in English | MEDLINE | ID: mdl-29769145

ABSTRACT

BACKGROUND: Scabies is worldwide one of the most common, yet neglected, parasitic skin infections, affecting a wide range of mammals including humans. Limited treatment options and evidence of emerging mite resistance against the currently used drugs drive our research to explore new therapeutic candidates. Previously, we discovered a multicopy family of genes encoding cysteine proteases with their catalytic sites inactivated by mutation (SMIPP-Cs). This protein family is unique in parasitic scabies mites and is absent in related non-burrowing mites. We postulated that the SMIPP-Cs have evolved as an adaptation to the parasitic lifestyle of the scabies mite. To formulate testable hypotheses for their functions and to propose possible strategies for translational research we investigated whether the SMIPP-Cs are common to all scabies mite varieties and where within the mite body as well as when throughout the parasitic life-cycle they are expressed. RESULTS: SMIPP-C sequences from human, pig and dog mites were analysed bioinformatically and the phylogenetic relationships between the SMIPP-C multi-copy gene families of human, pig and dog mites were established. Results suggest that amplification of the SMIPP-C genes occurred in a common ancestor and individual genes evolved independently in the different mite varieties. Recombinant human mite SMIPP-C proteins were produced and used for murine polyclonal antibody production. Immunohistology on skin sections from human patients localised the SMIPP-Cs in the mite gut and in mite faeces within in the epidermal skin burrows. SMIPP-C transcription into mRNA in different life stages was assessed in human and pig mites by reverse transcription followed by droplet digital PCR (ddPCR). High transcription levels of SMIPP-C genes were detected in the adult female life stage in comparison to all other life stages. CONCLUSIONS: The fact that the SMIPP-Cs are unique to three Sarcoptes varieties, present in all burrowing life stages and highly expressed in the digestive system of the infective adult female life stage may highlight an essential role in parasitism. As they are excreted from the gut in scybala they presumably are able to interact or interfere with host proteins present in the epidermis.


Subject(s)
Cysteine Proteases/genetics , Gene Expression , Life Cycle Stages/genetics , Phylogeny , Sarcoptes scabiei/enzymology , Sarcoptes scabiei/genetics , Animals , Catalytic Domain , Computational Biology , Cysteine Proteases/metabolism , Digestive System/enzymology , Dogs , Feces/parasitology , Female , Host-Parasite Interactions , Humans , Mice , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Sarcoptes scabiei/anatomy & histology , Scabies/parasitology , Sequence Alignment , Skin/enzymology , Skin/immunology , Swine
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