Latent tuberculosis infection among patients with and without type-2 diabetes mellitus: results from a hospital case-control study in Atlanta.

OBJECTIVE: The purpose of this study is to compare the prevalence of latent TB infection (LTBI) among patients with type-2 diabetes mellitus (T2DM) to healthy controls without T2DM. To achieve this objective, we conducted a case-control study in a large hospital in Atlanta from 2016 to 2019. RESULTS: We enrolled 98 cases; 119 potential controls were screened, 84 of which had HbA1c ≥ 5.7% and one did not have QFT result, leaving 34 (28.6%) individuals enrolled as controls. LTBI prevalence was 9.2% among cases and 14.7% among controls (crude odds ratio 0.59, 95% CI 0.19-2.04). After adjusting for age and sex, the adjusted odds of LTBI among patients with T2DM was 0.45 (95% CI 0.13, 1.71) times the controls. We did not observe a statistically significant association between LTBI and T2DM. However, we reported a positive correlation between HbA1c level and nil count among individuals with LTBI (R2 = 0.55, p < 0.01). In addition, we reported a high prevalence of LTBI among adults with T2DM and family members without T2DM.

State Variation in Early-Onset Colorectal Cancer in the United States, 1995-2015.

The extent to which the increase in early-onset colorectal cancer (CRC) in the United States varies geographically is unknown. We analyzed changes in CRC incidence and risk factors among people aged 20-49 years by state using high-quality population-based cancer registry data provided by the North American Association of Central Cancer Registries and national survey data, respectively. Early-onset CRC incidence was mostly stable among blacks and Hispanics but increased in 40 of 47 states among non-Hispanic whites, most prominently in western states. For example, rates increased in Washington from 6.7 (per 100 000) during 1995-1996 to 11.5 during 2014-2015 (rate ratio = 1.73, 95% confidence interval = 1.48 to 2.01) and in Colorado from 6.0 to 9.5 (rate ratio = 1.57, 95% confidence interval = 1.30 to 1.91). Nevertheless, current CRC incidence was highest in southern states. From 1995 to 2005, increases occurred in obesity prevalence in all states and heavy alcohol consumption in one-third of states, but neither were correlated with CRC incidence trends. Early-onset CRC is increasing most rapidly among whites in western states. Etiologic studies are needed to explore early life colorectal carcinogenesis.

Contribution of Smoking to Tuberculosis Incidence and Mortality in High-Tuberculosis-Burden Countries.

Globally, 10 million incident cases of tuberculosis (TB) are reported annually, and 95% of TB cases and 80% of tobacco users reside in low- and middle-income countries. Smoking approximately doubles the risk of TB disease and TB mortality. We estimated the proportion of annual incident TB cases and TB mortality attributable to tobacco smoking in 32 high-TB-burden countries. We obtained country-specific estimates of TB incidence, TB mortality, and smoking prevalence from the World Health Organization Global TB Report (2017), tobacco surveillance reports (2015), and the Tobacco Atlas. Risk ratios for the effect of smoking on TB incidence and TB mortality were obtained from published meta-analyses. An estimated 17.6% (95% confidence interval (CI): 8.4, 21.4) of TB cases and 15.2% (95% CI: 1.8, 31.9) of TB mortality were attributable to smoking. Among high-TB-burden countries, Russia had the highest proportion of smoking-attributable TB disease (31.6%, 95% CI: 15.9, 37.6) and deaths (28.1%, 95% CI: 3.8, 51.4). Men had a greater proportion of TB cases attributable to smoking (30.3%, 95% CI: 14.7, 36.6) than did women (4.3, 95% CI: 1.7, 5.7). Our findings highlight the need for tobacco control in high-TB-burden countries to combat TB incidence and TB mortality.

Cross-linked peptide identification: A computational forest of algorithms.

Chemical cross-linking analyzed by mass spectrometry (XL-MS) has become an important tool in unravelling protein structure, dynamics, and complex formation. Because the analysis of cross-linked proteins with mass spectrometry results in specific computational challenges, many computational tools have been developed to identify cross-linked peptides from mass spectra and subsequently interpret the identified cross-links within their structural context. In this review, we will provide an overview of the different tools that are currently available to tackle the computational part of an XL-MS experiment. First, we give an introduction on the computational challenges encountered when processing data from a cross-linking experiment. We then discuss available tools to identify peptides that are linked by intact or MS-cleavable cross-linkers, and we provide an overview of tools to interpret cross-linked peptides in the context of protein structure. Finally, we give an outlook on data management and dissemination challenges and opportunities for cross-linking experiments.

Cancer incidence profile in sub-Saharan African-born blacks in the United States: Similarities and differences with US-born non-Hispanic blacks.

BACKGROUND: Sub-Saharan African-born blacks (ABs) are one of the fastest-growing populations in the United States. However, to the authors' knowledge, data regarding the cancer burden in this group are lacking, which would inform targeted cancer prevention and control. METHODS: The authors calculated age-standardized proportional incidence ratios (PIRs) comparing the frequency of the top 15 cancers in ABs with that of US-born non-Hispanic blacks (USBs) by sex and region of birth using incidence data for 2000 through 2012 from the Surveillance, Epidemiology, and End Results (SEER 17) program. RESULTS: Compared with USBs, ABs had significantly higher PIRs of infection-related cancers (liver, stomach, and Kaposi sarcoma), blood cancers (leukemia and non-Hodgkin lymphoma), prostate cancer, and thyroid cancers (females only). For example, the PIR for Kaposi sarcoma in AB versus USB women was 12.06 (95% confidence interval [95% CI], 5.23-18.90). In contrast, ABs had lower PIRs for smoking-related and colorectal cancers (eg, for lung cancer among men, the PIR was 0.30 [95% CI, 0.27-0.34]). Furthermore, cancer occurrence in ABs versus USBs varied by region of birth. For example, the higher PIRs for liver cancer noted among male ABs (PIR, 3.57; 95% CI, 1.79-5.35) and for thyroid cancer in female ABs (PIR, 3.03; 95% CI, 2.03-4.02) were confined to Eastern African-born blacks, whereas the higher PIR for prostate cancer (PIR, 1.90; 95% CI, 1.78, 2.02) was confined to Western African-born blacks. CONCLUSIONS: The cancer incidence profile of ABs is different from that of USBs and varies by region of birth, suggesting differences in environmental, cultural, social, and genetic factors. The findings of the current study could stimulate etiologic research and help to inform targeted interventions. Cancer 2017;123:3116-24. © 2017 American Cancer Society.

On-farm starling populations and other environmental and management factors associated with the presence of cefotaxime and ciprofloxacin resistant E. coli among dairy cattle in Ohio.

Wild birds that forage around livestock facilities have been implicated as vectors of antimicrobial resistant organisms. Although antimicrobial resistant bacteria have been isolated from European starlings (Sturnus vulgaris), their role in the dissemination of antimicrobial resistant elements in livestock facilities needs further investigation. To determine whether on-farm starling density and other factors were associated with the presence of cefotaxime and ciprofloxacin resistant E. coli among dairy cows in Ohio, bovine fecal pats from 150 farms were tested for the presence of cefotaxime and ciprofloxacin resistant E. coli. Each farm was visited twice (during the summer and fall of 2007-2009). Multi-level logistic regression models with a random intercept to account for fecal pats collected within a specific visit to a farm were used to assess the associations. The percentage of samples with cefotaxime and ciprofloxacin resistant E. coli was 13.4% and 13.6%, respectively. The percentage of farms having at least one sample testing positive for cefotaxime and ciprofloxacin resistant E. coli was 56.7% and 48.7%, respectively. The odds of detecting cefotaxime and ciprofloxacin resistant E. coli in the samples was significantly higher in 2007 compared to 2008 and 2009, in fall compared to summer, and from farms closer than 60km to starling night roost sites compared to the farms further than 60km. The presence of starlings during the day had a negative association with the likelihood of detecting cefotaxime resistant E. coli. Presence of calves also had a negative association with the likelihood of detecting both cefotaxime and ciprofloxacin resistant E. coli. European starlings might play a role in the dissemination of antimicrobial resistant agents in livestock facilities related to their daily population movements rather than the specific density of birds on farm during the day.

Dairy cattle management factors that influence on-farm density of European starlings in Ohio, 2007-2009.

Potential dairy farm management and environmental factors that attract European starlings (Sturnus vulgaris) to dairy farms were explored. During the period from 2007 to 2009, 150 dairy farms were each visited twice (once during the summer and again in the fall) and the number of starlings was recorded. Risk factors were assessed for possible association with the number of starlings per milking cow (starling density), using a zero-inflated negative binomial model. Starling density was higher on farms visited in 2007 compared to those visited in 2008 or 2009. The interaction term between feeding method and feeding site was significantly associated with starling density on farm; generally, feeding outdoors was associated with increased starling density. The odds of a zero starling count (compared to a count greater than zero) was higher on farms that removed manure from barns weekly or less frequently than weekly compared to those that removed manure daily or after every milking. The odds of a zero starling count decreased with increasing distance of a farm from the closest night roost. Identifying on farm risk factors that expose farms to starlings will help farmers develop strategies that minimize the number of birds on their farms and thereby reduce physical damage to the farms as well as the potential for pathogen transmission from birds to cattle and humans.

Risk factors associated with the colonization of Ontario layer chicken flocks with Brachyspira species.

Brachyspira species are frequent colonizers of the gastrointestinal tract in a variety of domestic animals, including birds. In chickens, Brachyspira species are associated with a clinical condition known as avian intestinal spirochetosis (AIS), a disease characterized by chronic diarrhoea, weight loss, low egg production, and faecal-stained eggs. The purpose of this study was to identify risk factors associated with the presence of Brachyspira species in Ontario layer chicken flocks. Pooled faecal samples were collected from 89 flocks from 58 farms between August 2010 and February 2011; 52 flocks were classified as dirty flocks (history of downgrades for dirty eggs) and 37 were classified as clean flocks (no history of downgrades for dirty eggs). A questionnaire related to management, biosecurity practices, and antimicrobial use was administered prior to sample collection. Using real-time polymerase chain reaction; 63.5% of the dirty flocks and 24.3% of the clean flocks were positive for Brachyspira species. A logistic regression model with a random effect for farm showed that the odds of Brachyspira species for flocks ≥ 60 weeks of age were higher than for flocks ≤ 34 weeks (OR=9.3; P=0.014). The odds of Brachyspira species in flocks housed in A-frame cages with manure curtains (OR=20.0; P=0.002) and flocks from multi-age farms (OR=8.5; P=0.001) were higher than for flocks in cage-stacked houses and from single-age farms, respectively. The odds of Brachyspira species for flocks housed in barns ≥ 30 years old was lower than for flocks housed in barns ≤ 14 years old (OR=0.1; P=0.002). The calculated intra-class correlation coefficient was 5.6 × 10(-14); the notably low proportion of variation among farms after the fixed effects were included in the model suggests that the farm-level variable (multi-age farm) included in the final model accounted for most of the farm-to-farm variation in Brachyspira presence. Therefore, it is recommended that strict biosecurity, and between-flock decontamination efforts to reduce the infection pressure, be followed on farms with multiple flocks of different ages to avoid transmission of the bacteria between flocks.

Leishmania donovani complex (Kinetoplastida, Trypanosomatidae): comparison of deoxyribonucleic acid based techniques for typing of isolates from Ethiopia.

In Ethiopia, visceral leishmaniasis (VL) is an increasing public health concern. Recently, a new outbreak of VL claimed the lives of hundreds of Ethiopians. Mapping its distribution and the identification of the causative Leishmania species is important for proper use of resources and for control planning. The choice of appropriate typing technique is the key for determining the infecting species. Here we compared three deoxyribonucleic acid (DNA) based markers. We used, for the first time, cpbE and cpbF (cpbE/F) PCR-RFLP and demonstrated that it clearly differentiates Leishmania donovani from Leishmania infantum. The cpbE/F PCR-RFLP gave identical banding pattern for all L. donovani strains irrespective of their geographic origin. With the K26 (primers) PCR-RFLP, the L. donovani strains gave a banding pattern different from L. infantum and showed variation with geographic origin. The Ethiopian isolates typed as L. donovani by the PCR-RFLP of the cpbE/F (gene) and K26 (primers) showed two types of patterns with the T2/B4 (primers) PCR-RFLP; one group with L. infantum-like and the other L. donovani-like pattern. Phylogenetic analysis using cpbE/F sequences showed variation with geographic origin of strains and the African strains of L. donovani are more distantly related to L. infantum. Moreover, the Ethiopian isolates were seen to be closely related to the Sudanese, Kenyan and Indian strains. Thus, we recommend the use of more than one marker to study the population genetics of L. donovani complex.

Local nerve damage in leprosy does not lead to an impaired cellular immune response or decreased wound healing in the skin.

This study investigated whether peripheral nerve damage in patients with leprosy impairs local cellular immune responses, thereby reducing wound healing and leading to chronic skin ulceration. Anesthetic and contralateral sensitive skin sites in 42 patients with leprosy were compared for delayed-type hypersensitivity responses to purified protein derivative (PPD) of tuberculin. Leukocyte recruitment, epidermal activation, keratinocyte proliferation, and rates of wound healing after skin biopsy were compared. No significant differences in PPD-induced induration, epidermal activation and thickening or numbers of total T cells, CD8+ T cells, CD1a+ Langerhans cells, and proliferating Ki67+ keratinocytes were observed between anesthetic and sensitive skin sites. Similarly, rates of wound healing over 5 days after skin biopsy did not differ significantly. Thus, local leprosy-associated anesthesia does not appear to contribute to local immune compromise or impaired wound healing. Rather, chronic cutaneous ulceration in leprosy most likely results from repeated trauma associated with loss of sensation.

[Cost of tetanus toxoid injection using a jet-injector (Imule) in collective immunization in Senegal: comparison with injection using a syringe and resterilizable needle]. / Coût de l'injection d'anatoxine tétanique par injecteur sans aiguille(Imule) lors dúne vaccination collective au Sénégal: comparaison avec l'injection par seringues et aiguilles restérilisables.

Needle-less jet injectors were developed by the US army after World War II. Their principal use, however, has been in the administration of lyophilized vaccines from multidose vials to at-risk populations in developing countries. In 1983, a hepatitis B epidemic occurred among customers of a beauty clinic in California (USA) following the use of jet-injectors, demonstrating a clear risk of cross-contamination associated with this technique. As a result, the WHO and Unicef stopped recommending jet-injectors for collective immunizations in developing countries. To eliminate the risk of contamination, Pasteur Mérieux Sérums et Vaccins (now Aventis Pasteur) developed, in 1990, jet-injectors for use with single-use vaccine cartridges. These injectors were tested for tetanus toxoid, DTP, influenza, hepatitis A and typhoid Vi vaccination. The immunogenic reaction was as strong and the injection as well tolerated as for injections using a standard needle and syringe. The additional cost of the Imule technique was evaluated in a district-wide (127,000 inhabitants) tetanus toxoid immunization program at Velingara, Senegal in 1993. The total cost was estimated to be 1.51 FF (76 F CSA, 0.32 US dollars) for one dose of tetanus vaccine given by needle and syringe and 2.41 FF (121 F CSA, 0.56 US dollars) for one dose given by Imule. Thus, the additional cost of injection by ImuleTM was 0.90 FF (45 F CSA, 0.21 US dollars). The cost of cross infection in sub-Saharan Africa has been estimated to be 2.37 FF (118 F CSA, 0.55 US dollars) per injection if injection practices are not supervised. Therefore, the Imule technique may be considered to be cost-effective. However, the technique is still not completely reliable, as shown by the total breakdown of four jet injectors during this vaccination session. Lyophilized vaccines have also not been tested in the field. Vaccinators prefer Imule, training is easy and immunization can be carried out on a day-to-day basis with no vaccine wastage. Imule is not yet in mass production, which would reduce costs. In the face of the ever-increasing risk of cross-contamination during vaccination sessions in sub-Saharan Africa, the Imule technique deserves considerable attention.

Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet-injector and a new single-use cartridge (Imule): comparison with standard syringe injection. Imule Investigators Group.

A new needleless jet-injector, Mini-Imojet, was developed that administers liquid vaccines from a single-use, pre-filled cartridge named Imule, which avoids the risk of cross-contamination. We conducted clinical trials in several settings in France and West Africa to compare the immunogenicity and tolerance of five vaccines (influenza vaccine, Vi capsular polysaccharide typhoid vaccine, tetanus toxoid vaccine, diphtheria-tetanus-whole cell pertussis vaccine, and inactivated hepatitis A vaccine) administered with the Imule system vs standard syringe technique. In each vaccine study, all subjects of either group were tested for serum antibody titres to calculate the geometrical mean titres and seroconversion rates after complete vaccination. Immediate local-reactions were noted after each injection, and local and general reactions were evaluated during a predetermined period of follow-up. When delivered by the Imule technique, all the administered vaccines were of equivalent or superior immunogenicity, compared to the syringe technique. The tolerance to vaccines injected by the Imule system was acceptable in all studies. The most frequently observed reactions were mild (e.g. minor bleeding, superficial papules, erythema and induration) and could be considered to be inherent to the injection technique. The technical and safety advantages of the Mini-Imojet/Imule system, compared to sterilizable, standard disposable or autodestruct syringes and to classical multi-dose vial jet-injectors, reinforces the interest of this new injection technique for collective immunizations.

Cytochrome P450 catalyzes the oxidation of N omega-hydroxy-L-arginine by NADPH and O2 to nitric oxide and citrulline.

Rat liver microsomes catalyze the oxidative denitration of N omega-hydroxy-L-arginine (NOHA) by NADPH and O2 with formation of citrulline and nitrogen oxides like NO and NO2-. Besides NO2- and citrulline, whose simultaneous formation is linear for at least 20 min, the formation of NO could be detected under the form of its P450 and P420-Fe(II) complexes by UV-visible and EPR spectroscopy. Classical inhibitors of NO-synthases, like N omega-methyl-and N omega-nitro-arginine, fail to inhibit the microsomal oxidation of NOHA to citrulline and NO2-. On the contrary classical inhibitors of hepatic cytochromes P450 like CO, miconazole, dihydroergotamine and troleandomycin, strongly inhibit this monooxygenase reaction. These results show that the oxygenation of NOHA by NADPH and O2 with formation of citrulline and NO can be efficiently catalyzed by cytochromes P450 (with rates up to 1.5 turnovers per min for the cytochromes of the 3A subfamily).

Formation of nitrogen oxides and citrulline upon oxidation of N omega-hydroxy-L-arginine by hemeproteins.

HRP catalyzes the oxidation of N omega-hydroxy-L-arginine (NOHA) by H2O2 with formation of citrulline and NO2- with initial rates of about 0.7 and 0.2 nmol per nmol HRP per min. In the same manner, cytochromes P450 from rat liver microsomes catalyze the oxidation of NOHA to citrulline and NO2- by cumylhydroperoxide. Inhibitors of these hemeproteins (N3- and CN- for HRP and miconazole for P450) strongly inhibit both citrulline and NO2- formation. Rates of NOHA oxidation by these hemeproteins markedly decrease with time presumably because of their denaturation by nitrogen oxides and of the formation of hemeprotein-iron-NO complexes. These results suggest that NO (and other nitrogen oxides) could be formed from oxidation of NOHA by other enzymes than NO-synthases.

[Sickle-cell cardiomegaly in children. Study of 13 cases]. / Les cardiomégalies drépanocytaires de l'enfant. Etude de 13 observations.

Thirteen children, aged 18 months to 14 years and presenting with sickle cell anemia and cardiomegaly (Cardiothoracic ratio greater than or equal to 0.55) were investigated by echocardiography and radio-isotopic measurement of the cardiac output. Eight children presented with one or several criteria of anemic cardiopathy: left ventricular dilatation and hyperkinesia, increased cardiac index. On the contrary, 2 children presented with left ventricular dilatation and decreased contractility, without increase in the cardiac index; 3 children presented with echocardiographic findings similar to those of controls and a normal cardiac index, which is unusual in cases with chronic anemia. These results show that the cardiovascular system of children with sickle cell anemia does not always behave as one would expect in chronic anemia. They also suggest the possible early occurrence of cardiomyopathy, as already described in adults with sickle cell anemia.

[Isotopic radiocardiography as a method for hemodynamic investigation in pediatric cardiology (author's transl)]. / Le radiocardiogramme isotopique comme méthode d'exploration hémodynamique en cardiologie infantile.

In 22 children with acquired or malformative heart diseases catheterization and radiocardiography (RCG) investigations were performed. The results obtained with this method of hemodynamic investigation, in which the dilution curve of a short-lived isotope (Indium 113) is detected externally and recorded, were compared with the catheterization data. There is a significant correlation between the pulmonary arterial and capillary pressures obtained with RCG and those measured by catheterization in non cyanotic heart diseases. In addition, morphological analysis of RCG curves may provide information concerning the anatomic diagnosis of some heart diseases.