Urinary incontinence in the elderly: relation to cognitive and motor function

Urinary incontinence is a common problem in older subjects, very often wrongfully accepted as a normal part of the aging process. A total of 520 subjects (208 males and 312 females; mean age 74.8 +/- 11.8 years), from both private- and nursing-home dwelling populations, were included in this study aimed to estimate the incidence of urinary incontinence and identify factors associated with condition, in aged subjects. The incidence and type of urinary incontinence (stress, urge or mixed incontinence) were assessed by structured questionnaires and diagnosis was confirmed by a seven-day consecutive voiding diary. Assessment of physical, cognitive and emotional functions was performed on each subject using the Mini Mental State Examination (MMSE), Instrumental Activities of Daily Living Scale (IADL), Tinetti Scale (gait), Tinetti Scale (balance) and Geriatric Depression Scale (GDS) instruments. In the total population sample the incidence of urinary incontinence was 47.9%. The incontinence cases were classified, according to the different types, as: stress incontinence (males: 3.4%; females: 8.7%; males+females: 6.5%); urge incontinence (males: 27.4%; females: 31.4%; males+females: 29.8%); mixed incontinence (males: 20.2%; females: 5.8%; males+females: 11.5%). In the total population sample, no significant relationship was found between age and prevalence of urinary incontinence. In the elderly female group, age significantly correlated in a direct manner with urge incontinence (P<0.01) and inversely with stress incontinence (P<0.001). Only in the male sex group age significantly correlated with mixed incontinence (P<0.005). Multiple linear regression analysis showed that the dependent variable 'incontinence' could be predicted by MMSE (P<0.001) in the male sex group and by the Tinetti Scale (gait) (P<0.001) in the female sex group.     

Tumor-derived microvesicles: The metastasomes

Metastasis is the leading cause of cancer death, yet it is mechanistically considered a very inefficient process suggesting the presence of some sort of (e.g. systemic) routes for fuelling the process. The pre-metastatic niche formation is described as one such metastasis promoting route. Now, the emerging potentials of tumor-derived microvesicles (TDMVs), not only in formulating the pre-metastatic niche, but also conferring neoplastic phenotypes onto normal cells, has integrated new concepts into the field. Here, we note as an ancillary proposition that, exerting functional disturbances in other sites, TDMVs (we have termed them metastasomes) may aid foundation of the secondary lesions via two seemingly interrelated models: (i) tumor-organ-training (TOTr), training a proper niche for the growth of the disseminated tumor cells; (ii) tumor-organ-targeting (TOTa), contribution to the propagation of the transformed phenotype via direct or indirect (TOTr-mediated disturbed stroma) transformation and/or heightened growth/survival states of the normal resident cells in the secondary organs. Respecting the high content of the RNA molecules (particularly microRNAs) identified in the secretory MVs, they may play crucial parts in such “malignant trait” spreading system. That is, the interactions between tumor tissue-specific RNA signatures, being transferred via metastasomes, and the cell-type/tissue-specific RNA stockrooms in other areas may settle a unique outcome in each organ. Thus, serving as tumor-organ matchmakers, the RNA molecules may also play substantial roles in the seeding and tropism of the process.     

Novel optimized biopolymer-based nanoparticles for nose-to-brain delivery in the treatment of depressive diseases

A valid option to bypass the obstacle represented by the blood–brain barrier (BBB) in brain delivery is the use of the unconventional intranasal route of administration. The treatment of depressive diseases, resulting from the depletion of a neurotransmitter in the inter-synaptic space, such as serotonin, is indirectly treated using molecules that can permeate the BBB unlike the latter. In the present article, a set of nanovectors were produced using a mucoadhesive biopolymer, i.e. alginate (Alg). Optimizing the reaction, polymeric nanoparticles having diameter of 30–70 nm were produced, and water stable multi-walled carbon nanotubes functionalized (MWCNT-COOH)/Alg complexes were obtained. These nanovectors were loaded with serotonin, evaluating drug loading/release. By means of Raman microscopy, the cellular internalization of the (MWCNT-COOH)/Alg complex was demonstrated. A complete biocompatibility on neuronal cells was proved for the whole set of nanovectors. Finally, a method of self-administration was tested, which involves the use of a household apparatus, such as an aerosol machine, observing a fine particulate, able to deliver the nanovectors through the nose.

A valid option to bypass the obstacle represented by the blood–brain barrier (BBB) in brain delivery is the use of the unconventional intranasal route of administration.     

Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients

Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis.     

Evaluation of Pyrosequencing for Detecting Extensively Drug-Resistant Mycobacterium tuberculosis among Clinical Isolates from Four High-Burden Countries

Reliable molecular diagnostics, which detect specific mutations associated with drug resistance, are promising technologies for the rapid identification and monitoring of drug resistance in Mycobacterium tuberculosis isolates. Pyrosequencing (PSQ) has the ability to detect mutations associated with first- and second-line anti-tuberculosis (TB) drugs, with the additional advantage of being rapidly adaptable for the identification of new mutations. The aim of this project was to evaluate the performance of PSQ in predicting phenotypic drug resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) clinical isolates from India, South Africa, Moldova, and the Philippines. A total of 187 archived isolates were run through a PSQ assay in order to identify M. tuberculosis (via the IS6110 marker), and to detect mutations associated with M/XDR-TB within small stretches of nucleotides in selected loci. The molecular targets included katG, the inhA promoter and the ahpC-oxyR intergenic region for isoniazid (INH) resistance; the rpoB core region for rifampin (RIF) resistance; gyrA for fluoroquinolone (FQ) resistance; and rrs for amikacin (AMK), capreomycin (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing results for performance analysis. The PSQ assay illustrated good sensitivity for the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool that reveals specific nucleotide changes associated with resistance to the first- and second-line anti-TB drug medications. This methodology has the potential to be linked to mutation-specific clinical interpretation algorithms for rapid treatment decisions.