Challenges and opportunities in a tuberculosis outbreak investigation in southern Mississippi, 2005-2007.

OBJECTIVE: Between December 2005 and November 2007, a cluster of 11 tuberculosis (TB) cases emerged in Jackson County, Mississippi. We investigated the potential sources of disease transmission and epidemiologic links in this cluster to prevent future transmission in the community. MATERIALS AND METHODS: Cases of TB reported in Jackson County from December 2005 to November 2007 having matching genotypes or social links to patients with matching genotypes were included in the investigation. We interviewed patients, reviewed medical records, and performed contact investigations. RESULTS: The combined genotyping and epidemiologic data pointed to ongoing TB transmission in this rural community. A combination of patient-specific and programmatic factors, including substance use, delays in TB diagnosis, nonadherence, and TB program staffing cuts, contributed to this outbreak in the context of the 2004 and 2005 Atlantic hurricane seasons. CONCLUSIONS: To eliminate Mycobacterium tuberculosis transmission in this setting, recommendations for the TB program include enhanced coordination with substance abuse programs, community and provider education, and increased outreach capacity.

Priorities and Outcomes for Youth-Adult Transitions in Hospital Care: Perspectives of Inpatient Clinical Leaders at US Children's Hospitals.

OBJECTIVES: Adults with chronic conditions originating in childhood experience ongoing hospitalizations; however, efforts to guide youth-adult transitions rarely address transitioning to adult-oriented inpatient care. Our objectives were to identify perceptions of clinical leaders on important and feasible inpatient transition activities and outcomes, including when, how, and for whom inpatient transition processes are needed. METHODS: Clinical leaders at US children's hospitals were surveyed between January and July 2016. Questionnaires were used to assess 21 inpatient transition activities and 13 outcomes. Perceptions about feasible and important outcome measures and appropriate patients and settings for activities were summarized. Each transition activity was categorized into one of the Six Core Elements (policy, tracking, readiness, planning, transfer, or completion). Associations between perceived transition activity importance or feasibility, hospital characteristics, and transition activity performance were evaluated. RESULTS: In total, 96 of 195 (49.2%) children's hospital leaders responded. The most important and feasible activities were identifying patients needing or overdue for transition, discussing transition timing with youth and/or families, and informing youth and/or families that future stays would be at an adult facility. Feasibility, but not importance, ratings were associated with current performance of transition activities. Inpatient transition activities were perceived to be important for children with medical and/or social complexity or high hospital use. Emergency department visits and patient experience during transition were top outcome measurement priorities. CONCLUSIONS: Children's hospital clinical leaders rated inpatient youth-adult transition activities and outcome measures as important and feasible; however, feasibility may ultimately drive implementation. This work should be used to inform initial research and quality improvement priorities, although additional stakeholder perspectives are needed.

Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006.

BACKGROUND: Almost one-fifth of United States tuberculosis cases are extrapulmonary; unexplained slower annual case count decreases have occurred in extrapulmonary tuberculosis (EPTB), compared with annual case count decreases in pulmonary tuberculosis (PTB) cases. We describe the epidemiology of EPTB by means of US national tuberculosis surveillance data. METHODS: US tuberculosis cases reported from 1993 to 2006 were classified as either EPTB or PTB. EPTB encompassed lymphatic, pleural, bone and/or joint, genitourinary, meningeal, peritoneal, and unclassified EPTB cases. We excluded cases with concurrent extrapulmonary-pulmonary tuberculosis and cases of disseminated (miliary) tuberculosis. Demographic characteristics, drug susceptibility test results, and risk factors, including human immunodeficiency virus (HIV) status, were compared for EPTB and PTB cases. RESULTS: Among 253,299 cases, 73.6% were PTB and 18.7% were EPTB, including lymphatic (40.4%), pleural (19.8%), bone and/or joint (11.3%), genitourinary (6.5%), meningeal (5.4%), peritoneal (4.9%), and unclassified EPTB (11.8%) cases. Compared with PTB, EPTB was associated with female sex (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.7-1.8) and foreign birth (OR, 1.5; CI, 1.5-1.6), almost equally associated with HIV status (OR, 1.1; CI, 1.1-1.1), and negatively associated with multidrug resistance (OR, 0.6; CI, 0.5-0.6) and several tuberculosis risk factors, especially homelessness (OR, 0.3; CI, 0.3-0.3) and excess alcohol use (OR, 0.3; CI, 0.3-0.3). Slower annual decreases in EPTB case counts, compared with annual decreases in PTB case counts, from 1993 through 2006 have caused EPTB to increase from 15.7% of tuberculosis cases in 1993 to 21.0% in 2006. CONCLUSIONS: EPTB epidemiology and risk factors differ from those of PTB, and the proportion of EPTB has increased from 1993 through 2006. Further study is needed to identify causes of the proportional increase in EPTB.

Bone extracellular matrix hydrogel enhances osteogenic differentiation of C2C12 myoblasts and mouse primary calvarial cells.

Hydrogel scaffolds derived from the extracellular matrix (ECM) of mammalian tissues have been successfully used to promote tissue repair in vitro and in vivo. The objective of this study was to evaluate the osteogenic potential of ECM hydrogels prepared from demineralized and decellularized bovine bone in the presence and absence of osteogenic medium. Culture of C2C12 and mouse primary calvarial cells (mPCs) on decellularized bone ECM (bECM) and demineralized bone matrix (DBM) gels resulted in increased expression of osteogenic gene markers, including a 3.6- and 13.4-fold increase in osteopontin and 15.7- and 27.1-fold increase in osteocalcin when mPCs were cultured upon bECM with basal and osteogenic media, respectively. bECM hydrogels stimulated the osteogenic differentiation of C2C12 and mPCs even in the absence of osteogenic medium. These results suggest that bECM hydrogel scaffolds may have great utility in future clinical applications for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 900-908, 2018.

Neuralization of mouse embryonic stem cells in alginate hydrogels under retinoic acid and SAG treatment.

This paper examines the differentiation of a mouse embryonic stem cell line (CGR8) into neurons, under retinoic acid (RA) and smoothened agonist (SAG) treatment. When stem cells underwent through an embryoid body (EB) formation stage, dissociation and seeding on glass coverslips, immunofluorescent labelling for neuronal markers (Nestin, b-Tubulin III, MAP2) revealed the presence of both immature neural progenitors and mature neurons. Undifferentiated CGR8 were also encapsulated in tubular, alginate-gelatin hydrogels and incubated in differentiation media containing retinoic acid (RA) and smoothened agonist (SAG). Cryo-sections of the hydrogel tubes were positive for Nestin, Pax6 and b-Tubulin III, verifying the presence of neurons and neural progenitors. Provided neural induction can be more precisely directed in the tubular hydrogels, these scaffolds will become a powerful model of neural tube development in embryos and will highlight potential strategies for spinal cord regeneration.

What do they do? Interactions between village doctors and medical representatives in Chakaria, Bangladesh.

BACKGROUND: Informally trained village doctors supply the majority of healthcare services to the rural poor in many developing countries. This study describes the demographic and socio-economic differences between medical representatives (MRs) and village doctors in rural Bangladesh, and explores the nature of their interactions. METHODS: This study was conducted in Chakaria, a rural sub-district of Bangladesh. Focus group discussions and in-depth interviews were conducted, along with a quantitative survey to understand practice perceptions. Data analysis was performed using grounded theory and bivariate statistical tests. RESULTS: We surveyed 43 MRs and 83 village doctors through 22 focus group discussions and 33 in-depth interviews. MRs have a higher average per capita monthly expenditure compared to village doctors. MRs are better educated with 98% having bachelor's degrees whereas 84% of village doctors have twelfth grade education or less (p<0.001). MRs are the principal information source about new medications for the village doctors. Furthermore, incentives offered by MRs and credit availability influence the prescription practices of village doctors. CONCLUSIONS: MRs being the key player in providing information about drugs to village doctors might influence their prescription practices. Improvements in the quality of healthcare delivered to the rural poor in informal provider-based health markets require stricter regulations and educational initiatives for providers and MRs.

In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors.

The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-ß3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors.

Backbone dynamics of oxidised and reduced forms of human atrial natriuretic peptide.

The backbone dynamics of the 28 residue 15N-labelled human atrial natriuretic peptide have been examined by 15N NMR methods. 15N R1, R2 and [1H]-15N NOE values were determined for the oxidised and reduced forms of the peptide (ANPox and ANPrd, respectively), and analysed using reduced spectral density mapping and an extended model-free approach. The two forms possessed correlation times for overall molecular motion of 4.7 ns and were highly flexible, with substantial contributions to relaxation processes from internal motions on picosecond to nanosecond time scales. Reduction of the Cys7-Cys23 disulphide bond to form ANPrd produced a very dynamic linear peptide with a mean overall order parameter of 0.2; the intramolecular cross-link in ANPox increased this to a mean value of 0.4. A simple model for segmental backbone motion accounted for the R2 values of both species using only two variable parameters, indicating that relaxation is dominated by interactions with sites <7 residues distant in the covalent network and that changes in the conformation of the disulphide bond lead to significant chemical exchange broadening in ANPox. The contributions of backbone dynamics to configurational entropy were determined and accounted for the different receptor binding affinities of cyclised and linear natriuretic peptides.