Eating disorders as risk factors for osteoporosis

Eating disorders (TCA per its abbreviation in Spanish) are common in young women, with an estimated prevalence of 4-5%. One of the physical complications of eating disorders, especially anorexia nervosa (AN) and eating disorder not otherwise specified (TANE) is bone mass loss, which affects both cortical and trabecular bone. The synergistic effect of malnutrition and estrogen deficiency produces significant bone mass loss, resulting from the uncoupling of bone turnover characterized by a decrease in osteoblastic bone formation and an increase in osteclastic bone resorption. The mechanisms implied in the pathogenesis of bone loss are the hypoestrogenism, hypercortisolism, serum leptin levels and insulin-like growth factor decrease. Severity of bone loss in anorexia nervosa varies depending on duration of illness, the minimal weight ever and sedentarism or strenuous exercise. Long term consequences occur, such as a fracture risk increase in patients who have suffered anorexia nervosa, compared with the general population. The first treatment line to recover bone mass is nutritional rehabilitation together with weight gain. Hormonal replacement therapy may be effective if combined with an anabolic method. Osteopenia and osteoporosis are terms adopted to define the deficiency of bone mass in adults. Authors have used these terms to define densitometric data in young subjects who have not reached their peak bone mass. We suggest the term "hypo-osteogenesia" to define the deficiency in the development of bone mass in adolescents or children.     

Carbohydrate-antigen-125 levels predict hospital stay duration and adverse events at long-term follow-up in Takotsubo cardiomyopathy

The aim of this study is to evaluate the possible role of carbohydrate-antigen(CA)-125 as prognostic marker at short- and long-term follow-up, in subjects with Takotsubo cardiomyopathy (TTC). Sixty-three consecutive subjects with TTC were enrolled in the study and followed for a median 139 days. Circulating levels of CA-125, NT-proBNP, and left ventricular ejection fraction (LVEF) were evaluated at admission. Duration of hospital stay, incidence of death, re-hospitalization and recurrence of TTC during follow-up were recorded. The mean hospital stay was 8.3 days, adverse events occurred during follow up in 17 % of cases. CA-125 levels at admission are inversely related to LVEF (r ?0.30, p < 0.05) and directly related to hospital stay (r 0.29, p < 0.05). CA-125 levels at admission are higher in subjects with adverse events at follow-up (88.9 ± 200.0 vs 20.9 ± 30.0 U/mL, p < 0.05). Rates of incidence of adverse events are proportionally increased with CA-125 tertiles (0, 6, 11 % respectively, p for trend <0.01), at survival analysis (Log Rank p < 0.05) and after correction for age, gender, LVEF and NT-proBNP levels in multivariable Cox analysis (p < 0.05). CA-125 levels <10 U/ml are predictors of adverse events at follow up with 91 % sensitivity, 52 % specificity, 29 % positive predictive power, and 96 % negative predictive power. Increased CA-125 admission levels are associated with a longer hospital stay, a lower LVEF, and a higher risk of adverse events during follow up. CA-125 might be useful for early risk stratification of subjects with TTC.     

Human respiratory syncytial virus N,P and M protein interactions in HEK-293T cells

Characterization of Human Respiratory Syncytial Virus (HRSV) protein interactions with host cell components is crucial to devise antiviral strategies. Viral nucleoprotein, phosphoprotein and matrix protein genes were optimized for human codon usage and cloned into expression vectors. HEK-293T cells were transfected with these vectors, viral proteins were immunoprecipitated, and co-immunoprecipitated cellular proteins were identified through mass spectrometry. Cell proteins identified with higher confidence scores were probed in the immunoprecipitation using specific antibodies. The results indicate that nucleoprotein interacts with arginine methyl-transferase, methylosome protein and Hsp70. Phosphoprotein interacts with Hsp70 and tropomysin, and matrix with tropomysin and nucleophosmin. Additionally, we performed immunoprecipitation of these cellular proteins in cells infected with HRSV, followed by detection of co-immunoprecipitated viral proteins. The results indicate that these interactions also occur in the context of viral infection, and their potential contribution for a HRSV replication model is discussed.     

Default network is not hypoactive in dementia with fluctuating cognition: an Alzheimer disease/dementia with Lewy bodies comparison

Default mode network resting state activity in posterior cingulate cortex is abnormally reduced in Alzheimer disease (AD) patients. Fluctuating cognition and electroencephalogram abnormalities are established core and supportive elements respectively for the diagnosis of dementia with Lewy bodies (DLB). Our aim was to assess whether patients with DLB with both of these features have different default mode network patterns during resting state functional magnetic resonance imaging compared with AD. Eighteen patients with DLB, 18 AD patients without fluctuating cognition, and 15 control subjects were selected after appropriate matching and followed for 2–5 years to confirm diagnosis. Independent component analysis with functional connectivity (FC) and Granger causality approaches were applied to isolate and characterize resting state networks. FC was reduced in AD and DLB patients compared with control subjects. Posterior cingulate cortex activity was lower in AD than in control subjects and DLB patients (p < 0.05). Right hemisphere FC was reduced in DLB patients in comparison with control subjects but not in patients with AD, and was correlated with severity of fluctuations (ρ = −0.69; p < 0.01). Causal flow analysis showed differences between patients with DLB and AD and control subjects.     

Evaluation of the humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> of mice immunized with liposomes containing glycolipids of <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

Mycobacterium smegmati s (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis.     

Evaluation of specific humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> antigens induced in mice immunized with liposomes composed of total lipids extracted from <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.     

In Silico identification of M. TB proteins with diagnostic potential

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.

     

Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial

Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring. We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF). Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access). The primary outcome was adherence to apixaban (2.5 or 5 mg twice daily) at 24 weeks. Patients receiving the educational program were re-randomized (1:1) to continue the program for 24 further weeks or to switch to secondary SOC. Implementation adherence and persistence were reassessed at 48 weeks. In total, 1162 patients were randomized (SOC, 583; educational program, 579). Mean implementation adherence ± standard deviation (SD) at 24 weeks was 91.6% ± 17.1 for SOC and 91.9% ± 16.1 for the educational program arm; results did not differ significantly between groups at any time-point. At 48 weeks, implementation adherence was 90.4% ± 18.0, 90.1% ± 18.6, and 89.3% ± 18.1 for continued educational program, SOC, and secondary SOC, respectively; and corresponding persistence was 86.1% (95% confidence interval [CI] 81.3–89.7), 85.2% (95% CI 81.5–88.2), and 87.8% (95% CI 83.4–91.1). Serious adverse events were similar across groups. High implementation adherence and persistence with apixaban were observed in patients with NVAF receiving apixaban. The educational program did not show additional benefits. This study is registered at ClinicalTrials.gov [NCT01884350].