Effects of auditory training in individuals with high-frequency hearing loss

OBJECTIVE:To determine the effects of a formal auditory training program on the behavioral, electrophysiological and subjective aspects of auditory function in individuals with bilateral high-frequency hearing loss.METHOD:A prospective study of seven individuals aged 46 to 57 years with symmetric, moderate high-frequency hearing loss ranging from 3 to 8 kHz was conducted. Evaluations of auditory processing (sound location, verbal and non-verbal sequential memory tests, the speech-in-noise test, the staggered spondaic word test, synthetic sentence identification with competitive ipsilateral and contralateral competitive messages, random gap detection and the standard duration test), auditory brainstem response and long-latency potentials and the administration of the Abbreviated Profile of Hearing Aid Benefit questionnaire were performed in a sound booth before and immediately after formal auditory training.RESULTS:All of the participants demonstrated abnormal pre-training long-latency characteristics (abnormal latency or absence of the P3 component) and these abnormal characteristics were maintained in six of the seven individuals at the post-training evaluation. No significant differences were found between ears in the quantitative analysis of auditory brainstem responses or long-latency potentials. However, the subjects demonstrated improvements on all behavioral tests. For the questionnaire, the difference on the background noise subscale achieved statistical significance.CONCLUSION:Auditory training in adults with high-frequency hearing loss led to improvements in figure-background hearing skills for verbal sounds, temporal ordination and resolution, and communication in noisy environments. Electrophysiological changes were also observed because, after the training, some long latency components that were absent pre-training were observed during the re-evaluation.     

The multiple facets of drug resistance: one history,different approaches

Some cancers like melanoma and pancreatic and ovarian cancers, for example, commonly display resistance to chemotherapy, and this is the major obstacle to a better prognosis of patients. Frequently, literature presents studies in monolayer cell cultures, 3D cell cultures or in vivo studies, but rarely the same work compares results of drug resistance in different models. Several of these works are presented in this review and show that usually cells in 3D culture are more resistant to drugs than monolayer cultured cells due to different mechanisms. Searching for new strategies to sensitize different tumors to chemotherapy, many methods have been studied to understand the mechanisms whereby cancer cells acquire drug resistance. These methods have been strongly advanced along the years and therapies using different drugs have been increasingly proposed to induce cell death in resistant cells of different cancers. Recently, cancer stem cells (CSCs) have been extensively studied because they would be the only cells capable of sustaining tumorigenesis. It is believed that the resistance of CSCs to currently used chemotherapeutics is a major contributing factor in cancer recurrence and later metastasis development. This review aims to appraise the experimental progress in the study of acquired drug resistance of cancer cells in different models as well as to understand the role of CSCs as the major contributing factor in cancer recurrence and metastasis development, describing how CSCs can be identified and isolated.     

Effects of peritoneal dialysis on protein metabolism

Protein-energy wasting is relatively common in renal patients treated with haemodialysis or peritoneal dialysis (PD) and is associated with worse outcome. In this article, we review the current state of our knowledge regarding the effects of PD on protein metabolism and the possible interactions between PD-induced changes in protein turnover and the uraemia-induced alterations in protein metabolism. Available evidence shows that PD induces a new state in muscle protein dynamics, which is characterized by decreased turnover rates and a reduced efficiency of protein turnover, a condition which may be harmful in stress conditions, when nutrient intake is diminished or during superimposed catabolic illnesses. There is a need to develop more effective treatments to enhance the nutritional status of PD patients. New approaches include the use of amino acid/keto acids-containing supplements combined with physical exercise, incremental doses of intraperitoneal amino acids, vitamin D and myostatin antagonism for malnourished patients refractory to standard nutritional therapy.     

ORIGINAL ARTICLE: Leuprolide stimulation testing for the evaluation of early female sexual maturation

Context Low concentrations of serum LH and/or oestradiol (E₂) in girls with early physical signs of precocious puberty pose a diagnostic challenge. Objective To assess the diagnostic value of the leuprolide stimulation test in female precocious puberty. Design Retrospective Chart Review. Setting Outpatient clinic. Patients and intervention Thirty‐nine girls, 6·9 (1·4) years, with premature stage II–III breast development, with or without pubarche, underwent stimulation testing with subcutaneous leuprolide (20 μg/kg) with the following hormonal measurements in serum: FSH, LH, oestradiol at baseline; FSH and LH at 1 and 2 h; oestradiol at 24 h. Twelve girls with isolated pubarche were also tested with leuprolide. Main outcome measure A pubertal hormonal pattern was defined as at least one of the following: a baseline serum level of LH ≥ 0·3 U/l, a baseline oestradiol ≥ 37 pmol/l (10 ng/l), a stimulated (peak) LH ≥ 5·0 U/l, a stimulated oestradiol ≥ 184 pmol/l (50 ng/l) to leuprolide. The hormonal response was related to the clinical course during a period of observation of at least 6 months. Results Following leuprolide stimulation, the hormonal response was concordant with pubertal progression (n = 23) or lack thereof (n = 16) in all children. At baseline, pubertal serum concentrations of LH and/or oestradiol were associated with pubertal progression in all, while serum prepubertal LH and/or oestradiol concentrations were associated with pubertal progression in approximately 50% of the patients. Conclusions In girls with early clinical signs of precocious puberty and low serum concentrations of LH and oestradiol in random samples, the LH and oestradiol responses to leuprolide stimulation accurately predict pubertal progression.     

Irs2 Inactivation Suppresses Tumor Progression in Pten+/− Mice

Mutations in the phosphatase and tensin homologue (PTEN)/phosphatidylinositol-3 kinase-α (PI3K) signaling pathway are frequently found in human cancer. In addition, Pten^+/− mice develop tumors in multiple organs because of the activation of the PI3K signaling cascade. Because activation of PI3K signaling leads to feedback inhibition of insulin receptor substrate-2 (IRS2) expression, an upstream activator of PI3K, we therefore anticipated that IRS2 expression would be low in tumors that lack PTEN. Surprisingly, however, an elevation of IRS2 was often detected in tumor samples in which PTEN levels were compromised. To determine the potential contribution of Irs2 to tumor progression, Pten^+/− mice were crossed with Irs2^+/− mice. Deletion of Irs2 did not affect the initiation of neoplasia found in Pten^+/− mice but suppressed cancer cell growth, proliferation, and invasion through the basement membrane. Deletion of Irs2 also attenuated the expression of Myc in prostatic intraepithelial neoplasia in Pten^+/− mice. In addition, the expression levels of IRS2 and MYC were highly correlated in human prostate cancer, and IRS2 could stimulate MYC expression in cultured cells. Our findings provide evidence that the PI3K-activating adaptor Irs2 contributes to tumor progression in Pten^+/− mice by stimulating both Myc and DNA synthesis.     

Orthodeoxia without platypnea from interatrial defect associated with persistent left superior vena cava in the absence of pulmonary hypertension

Orthodeoxia-platypnea is a rare but increasingly recognized syndrome of upright hypoxemia usually associated to breathlessness relieved by recumbency. We report the case of isolated orthodeoxia discovered in a military recruit who referred only fatigability as the clinical symptom after a forced march. Transesophageal echocardiography demonstrated the presence of interatrial defect ostium secundum type with the persistence of left superior vena cava draining into coronary sinus. Right-to-left shunt was visualized by peripheral saline contrast infusion, despite normal right hemodynamics at heart catheterization. Hypoxemia recovered after the percutaneous closure of the interatrial defect. Orthodeoxia and platypnea could occur as separate disease manifestations, the latter probably being a rarer acute event, whereas orthodeoxia was underestimated and potentially earlier screenable.     

High Prevalence of Helicobacter pylori in Liver Cirrhosis (Relationship with Clinical and Endoscopic Features and the Risk of Peptic Ulcer)

In 153 consecutive patients with cirrhosis weassessed: (1) the prevalence of IgG to Helicobacterpylori and compared it with that found in 1010 blooddonors resident in the same area; and (2) therelationships of IgG to Helicobacter pylori with clinical andendoscopic features and with the risk of peptic ulcer.The IgG to Helicobacter pylori prevalence of cirrhoticswas significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was notassociated with sex, cirrhosis etiology, Child class,gammaglobulins and hypertensive gastropathy. In bothgroups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Amongpatients with cirrhosis a significantly higherprevalence of Helicobacter pylori was found in patientswith previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) andpatients with peptic ulcer (P = 0.0004). Multivariateanalysis identified increasing age and male sex as riskfactors for a positive Helicobacter pylori serology and no independent risk factors for pepticulcer. The high prevalence of Helicobacterpylori-positive serology found in the present series isrelated to age and sex and might also be explained byprevious hospital admissions and/or uppergastrointestinal endoscopy. Our results do not confirmthe role of Helicobacter pylori as risk factor forpeptic ulcer in patients with liver cirrhosis.