Transmissible vaccines whose dissemination rates vary through time,with applications to wildlife

Transmission is a potential property of live viral vaccines that remains largely unexploited but may lie within the realm of many engineering designs. While likely unacceptable for vaccines of humans, transmission may be highly desirable for vaccines of wildlife, both to protect natural populations and also to limit zoonotic transmissions into humans. Defying intuition, transmission alone does not guarantee that a vaccine will perform well: the benefit of transmission over no transmission depends on and increases with the basic reproductive number of the vaccine, $R_0$. The $R_0$ of an infectious agent in a homogeneous population is typically considered to be a fixed number, but some evidence suggests that dissemination of transmissible vaccines may change through time. One obvious possibility is that transmission will be greater from hosts directly vaccinated than from hosts who acquire the vaccine passively, but other types of change might also accrue. Whenever transmission changes over time, the $R_0$ estimated from directly vaccinated hosts will not reflect the vaccine’s long term impact. As there is no theory on the consequences of changing transmission rates for a vaccine, we derive conditions for a transmissible vaccine with varying transmission rates to protect a population from pathogen invasion. Being the first in the transmission chain, the $R_0$ from directly vaccinated hosts has a larger effect than those from later steps in the chain. This mathematical property reveals that a transmissible vaccine with low long term transmission may nonetheless realize a big impact if early transmission is high. Furthermore, there may be ways to artificially elevate early transmission, thereby achieving high herd immunity from transmission while ensuring that the vaccine will ultimately die out.     

A qualitative assessment of diabetes care access and disease management in Central America

BackgroundDiabetes is a growing concern in low-and middle-income countries. Medical missions play a role in increasing access to care and medicines, but often ignore non-communicable disease prevention and advanced management. Increased knowledge of local community needs and resources can lead to the development and implementation of pharmacist-supported interventions to improve diabetes management in rural areas.ObjectivesThe purpose of this study was to 1) understand the availability of monitoring for diabetes locally; and 2) describe knowledge and health beliefs regarding diabetes management for those with diabetes, and prevention among those at high risk of developing diabetes.MethodsThis qualitative evaluation used semi-structured interviews with key informants in a community in rural Honduras. Participants included those with diabetes, those at-risk for developing diabetes, and community leaders. Data was analyzed using thematic content analysis through an iterative process of coding and theme development.ResultsA total of 35 interviews were conducted with five resulting themes: 1) participants identified multiple barriers to diabetes management including access to monitoring, access to certain medications, and access to advanced levels of care; 2) participants acknowledge the relationship between lifestyle choices and diabetes control, but struggled with adherence to a healthy lifestyle; 3) participants identify that they have limited knowledge of diabetes pathophysiology, diabetes management, and strategies to prevent diabetes; 4) participants felt that opportunities existed within the community to support diabetes education and prevention, and 5) providers should integrate culture, societal norms, and religion in diabetes management.ConclusionThis research identifies challenges and resulting opportunities for managing diabetes in rural Honduras. Health care providers including pharmacy personnel should consider strategies to engage communities around self-care and diabetes education. Further, strategies are needed to enhance access to resources and essential medicines for diabetes management. These themes can guide clinicians in supporting communities to enhance diabetes care.     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

Assessment of thyroid disorders in patients with rosacea: a large case-control study

BackgroundThe frequency of autoimmune diseases and thyroid cancer has been increasingly reported in association with rosacea. However, studies investigating thyroid diseases in rosacea are scarce with conflicting results.ObjectiveTo investigate the relationship between thyroid disorders and rosacea.MethodsA large case-control study on age- and gender-matched 2091 rosacea patients and 9572 controls was conducted. Rosacea patients using the rosacea-specific ICD codes were compiled from the hospital records. Additionally, all participants were evaluated in terms of the presence of hypothyroidism and hyperthyroidism. Conditional logistic regression analysis was used to compute case-control odds ratios (OR) with 95% confidence intervals.ResultsThe analysis comprehended 2091 rosacea patients (1546 female, 545 male; mean 48.73 ± 14.53 years) and 9572 controls (7009 female, 2563 male; mean 48.73 ± 15.1 years). Whereas the rate of hypothyroidism was significantly higher in rosacea patients (OR = 1.3, 95% CI 1.13–1.49, p < 0.001), there was no significant difference in the rate of hyperthyroidism between the groups (OR = 1.12, 95% CI 0.81–1.53, p = 0.497). Stratification for gender revealed a significant association between hypothyroidism and rosacea in females (OR = 1.27, 95% CI 1.1–1.47, p = 0.002) and males (OR = 1.58, 95% CI 1.04–2.4, p = 0.032). The frequency of hypothyroidism in rosacea patients increased towards the age range of 40–49 and then decreased, parallel with the hypothyroidism frequency of the study population.Study limitationsDifferent subtypes and severities of rosacea were not distinguished.ConclusionsHypothyroidism may be a comorbidity of rosacea and investigation for hypothyroidism may be appropriate when evaluating rosacea patients.     

子宫内膜功能亢进性疾病的“异病同治”诊治研究思路＊

笔者根据现代临床子宫内膜的病理演变过程结合中医“异病同治”理念，提出“子宫内膜功能亢进性疾病”概念，涵盖5种常见的子宫内膜疾病：无排卵性异常子宫出血（Abnormal Uterine Bleeding Ovulatory dysfunction，AUB-O），子宫内膜息肉（Endometrial Polyp，EP），子宫内膜异位症（Endometriosis，EMs），子宫腺肌病（Adenomyosis，AM），子宫内膜癌（Endometrial Carcinoma，EC）。基于文献的汇总，分析得到此类疾病的子宫内膜病理演变与中医病因病机的关联性，为寻找关键通路、创新性治疗此类疾病提供了重要的参考方向，对深化中医妇科学常见疾病的共性病因病机提供了理论依据和探索思路。     

Moniletrix of the scalp from almost normal aspect to total alopecia: variable intrafamilial expressiveness

Monilethrix is a rare defect of the hair shaft, with most cases showing an autosomal dominant pattern of inheritance and variable clinical expression. It is characterized by hypotrichosis secondary to hair fragility. The diagnosis is made through trichoscopy, detecting typical findings such as periodic narrowing at regular intervals, giving the hair the appearance of beads in a rosary. This article reports the case of six members of a family diagnosed with monilethrix with alopecia of varying degrees.     

The immediate effects of hallux valgus orthoses: A comparison of orthosis designs

BackgroundHallux valgus orthoses are available in a wide range of designs and materials, but the effects of their design on functional performance have not been fully investigated.Research questionThis present study aims to comprehensively analyze the immediate effects of soft and semi-rigid hallux valgus orthoses on balance, plantar pressure, hallux valgus angle, and subjective sensations.MethodsSixteen female subjects have participated in the study, including 10 subjects with healthy feet and 6 with hallux valgus. Three conditions are tested, including in the barefoot and using two types of commercially available hallux valgus orthoses. The subjects participate in static and dynamic (walking) tests with the use of the Novel Pedar® system. The peak pressure values in the hallux, lateral toes, first metatarsophalangeal joint, 2-4th metatarsal heads, 5th metatarsal head, medial midfoot, lateral midfoot and rearfoot in the various foot conditions are examined and compared. The hallux valgus angle of each subject is measured based on their footprint. Their subjective feelings towards the orthoses are also evaluated. A repeated-measures analysis of variance, and independent-sample t-test are performed.ResultsThe correction of the hallux valgus angle is statistically significant when the subjects with hallux valgus use the orthoses. In comparing the two types of orthoses, the use of the orthosis made of soft materials results in correction in the hallux valgus angle and higher wear comfort, and lower plantar pressure in hallux area.SignificanceThe results provide insights into the design of hallux valgus orthoses, thus offering practical reference for the selection of hallux valgus orthosis with compromise between functional performance and wear comfort.     

Bile acid indices as biomarkers for liver diseases I: Diagnostic markers

BACKGROUNDHepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis.AIMTo discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile.METHODSWe analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases.RESULTSTotal and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases.CONCLUSIONBA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.