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Efficacy and safety of 5 mg olanzapine combined with aprepitant, granisetron and dexamethasone to prevent carboplatin-induced nausea and vomiting in patients with gynecologic cancer: A multi-institution phase II study.

PURPOSE: The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) to prevent nausea and vomiting in carboplatin (CBDCA) combination therapy for patients with gynecological cancer. METHODS: We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper o

Influence of dissolved organic matter on carbonyl sulfide and carbon disulfide formation from cysteine during sunlight photolysis.

Carbonyl sulfide (COS) and carbon disulfide (CS2) are important atmospheric gases that are formed from organic sulfur precursors present in natural waters when exposed to sunlight. However, it remains unclear how specific water constituents, such as dissolved organic matter (DOM), affect COS and CS2 formation. To better understand the role of DOM, irradiation experiments were conducted in O2-free synthetic waters containing four different DOM isolates, acquired from freshwater to open ocean sources, and the sulfur-based amino acid, cysteine (CYS). CYS is a known natural precursor of COS and CS

Systemic treatment of advanced or recurrent biliary tract cancer.

Biliary tract cancer (BTC) is a disease entity comprising diverse epithelial tumors with features of cholangiocyte differentiation, and it includes cholangiocarcinoma (CCA) and gallbladder cancer (GBC). Depending on its anatomical location, cholangiocarcinoma is categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Nearly two-thirds of patients with biliary tract cancer present with advanced disease at diagnosis and in 68-86% of resections the cancer eventually recurs either locoregionally or at a distance. Chemotherapy is the first-line therapy for advanced or recurrent BTC.

Brain Microbiota in Huntington's Disease Patients.

One of the most important challenges facing medical science is to better understand the cause of neuronal pathology in neurodegenerative diseases. Such is the case for Huntington's disease (HD), a genetic disorder primarily caused by a triplet expansion in the Huntingtin gene (HTT). Although aberrant HTT is expressed from embryogenesis, it remains puzzling as to why the onset of disease symptoms manifest only after several decades of life. In the present study, we investigated the possibility of microbial infection in brain tissue from patients with HD, reasoning that perhaps mutated HTT could

Ventricular geometry-regularized QRSd predicts cardiac resynchronization therapy response: machine learning from crosstalk between electrocardiography and echocardiography.

Up to one-third of patients selected by current guidelines do not respond to cardiac resynchronization therapy (CRT), the aim of this study was to find out novel analytical approaches to improve pre-implantation CRT response prediction. Among 31 pre-implantation features of clinical, laboratory, electrocardiography (ECG), and echocardiography variables in a consecutive cohort of patients receiving a first-time CRT device (CRT-pacemaker or CRT-defibrillator), we developed a machine learning (ML) model with three classification algorithms (support vector machines (SVM), K nearest neighbors, and

Protective Effects of Antioxidants in Huntington's Disease: an Extensive Review.

Huntington's disease (HD) is a hereditary neurodegenerative disease of the central nervous system (CNS). Onset of HD occurs between the ages of 30 and 50 years, although few cases are reported among children and elderly. HD appears to be less common in some populations such as those of Japanese, Chinese, and African descent. Clinical features of HD include motor dysfunction (involuntary movements of the face and body, abnormalities in gait, posture and balance), cognitive impairment (obsessive-compulsive disorder), and psychiatric disorders (dementia). Mutation in either of the two copies of a

Auditory Streaming and Prediction in Tinnitus Sufferers.

OBJECTIVES: The aim of this study was to determine whether auditory streaming (segregation of incoming sounds into separate sound sources) and the ability to anticipate future auditory events are affected in tinnitus sufferers compared with nontinnitus controls with matched levels of hearing. It was hypothesized that tinnitus would result in abnormal electroencephalography responses to tone deviants and tone omissions compared to controls for frequencies near the pitch of tinnitus, and this should correspond with increased levels of cortical γ and θ oscillatory rhythms. DESIGN: Sixteen indivi

Aging-associated genes and let-7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease caused by an abnormal (GCN) triplet expansion within the polyadenylate-binding protein nuclear 1 gene and consequent mRNA processing impairment and myogenic defects. Because a reduced cell proliferation potential and the consequent regeneration failure of aging muscle have been shown to be governed by lethal-7 (let-7) microRNA-mediated mechanisms, in the present study, we evaluated the role of let-7 in the pathogenesis of OPMD. By a multidisciplinary approach, including confocal microscopy, Western blot, and quantitative

Heritability of Age-Related Hearing Loss in Middle-Aged and Elderly Chinese: A Population-Based Twin Study.

OBJECTIVES: The heritability of age-related hearing loss has been studied mostly in developed countries. The authors aimed to estimate the heritability of better ear hearing level (BEHL), defined as hearing level of the better ear at a given frequency, and pure-tone averages at the middle (0.5, 1.0, and 2.0 kHz) and high (4.0, 8.0, and 12.5 kHz) frequencies among middle-aged and elderly Chinese twins, and to explore their genetic correlations. DESIGN: This population-based twin study included 226 monozygotic and 132 dizygotic twin-pairs and 1 triplet (age range, 33 to 80 years; mean age, 51.5

[FMR1 PREMUTATION CARRIERS - ARE THEY REALLY ASYMPTOMATIC?].

Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by a trinucleotide repeat expansion (CGG) in the 5'-untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene located at Xq27.3. Patients with fragile X -related mental retardation, carry the full mutation CGG-repeat expansions (>200 CGG repeats), which are generally accompanied by hypermethylation of the promoter region, with the consequent transcriptional silencing of the FMR1 gene and absence of the encoded FMR1 protein (FMRP). Expansion of the CGG triplet number above the normal range (n=5

Transcriptional profiling of isogenic Friedreich ataxia neurons and effect of an HDAC inhibitor on disease signatures.

Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by transcriptional silencing of the frataxin (FXN) gene, resulting in loss of the essential mitochondrial protein frataxin. Based on the knowledge that a GAA·TTC repeat expansion in the first intron of FXN induces heterochromatin, we previously showed that 2-aminobenzamide-type histone deacetylase inhibitors (HDACi) increase FXN mRNA levels in induced pluripotent stem cell (iPSC)-derived FRDA neurons and in circulating lymphocytes from patients after HDACi oral administration. How the reduced expression of frataxin leads to neurol

Antibodies to human neutrophil antigen HNA-3b implicated in cases of neonatal alloimmune neutropenia.

BACKGROUND: Neonatal alloimmune neutropenia results from maternal alloimmunization to human neutrophil antigens. The alloantibodies involved in neonatal alloimmune neutropenia are against human neutrophil antigens HNA-1a, HNA-1b, HNA-1c, HNA-1d, HNA-2, HNA-3a, HNA-4a, HNA-4b, and HNA-5a; however, to date, antibodies specific to HNA-3b have not been reported. STUDY DESIGN AND METHODS: Blood samples from 10,000 unselected neonates were analyzed, resulting in the selection of 88 neutropenic newborns (neutrophil count <1.5 × 109 /L) from 83 mothers (three pairs of twins and one triplet). HNA-3 ge

Mutant Huntingtin Is Secreted via a Late Endosomal/Lysosomal Unconventional Secretory Pathway.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by the expansion of a CAG triplet in the gene encoding for huntingtin (Htt). The resulting mutant protein (mHtt) with extended polyglutamine (polyQ) sequence at the N terminus leads to neuronal degeneration both in a cell-autonomous and a non-cell-autonomous manner. Recent studies identified mHtt in the extracellular environment and suggested that its spreading contributes to toxicity, but the mechanism of mHtt release from the cell of origin remains unknown. In this study, we performed a comprehensive, unbias

Pain modulation from the brain during diabetic neuropathy: Uncovering the role of the rostroventromedial medulla.

Diabetic neuropathy has a profound impact in the quality of life of patients who frequently complain of pain. The mechanisms underlying diabetic neuropathic pain (DNP) are no longer ascribed only to damage of peripheral nerves. The effects of diabetes at the central nervous system are currently considered causes of DPN. Management of DNP may be achieved by antidepressants that act on serotonin (5-HT) uptake, namely specific serotonin reuptake inhibitors. The rostroventromedial medulla (RVM) is a key pain control center involved in descending pain modulation at the spinal cord through local rel

Recent advances in understanding multiple myeloma.

There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach st

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… Conversely, lenalidomide-based triplets failed to show a PFS or OS benefit over lenalidomide-based doublets in an elderly population 43 . When compared with doublets, triplet therapies are associated with increased toxicity and usually longer PFS but not necessarily OS. … Triplet induction regimens and autologous stem cell transplantation studies in newly diagnosed multiple myeloma. …

Complicated multiple pregnancy referral, treatment and outcomes at the NSW Fetal Therapy Centre.

Objectives: To determine the indications for referral, sonographic workload, diagnoses and outcomes of women with a multiple pregnancy referred to the New South Wales Fetal Therapy Centre (NSW FTC). Methods: Retrospective cohort study of twin and higher order multiple (HOM) pregnancies referred to the NSW FTC at the Royal Hospital for Women (RHW) Department of Maternal Fetal Medicine (MFM), Sydney from January 2007 to December 2009. Results: There were 176 twin pregnancies (138 monochorionic diamniotic, 29 dichorionic diamniotic and nine monoamniotic), and 26 HOMs referred (23 triplet and thre

A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer.

PURPOSE: The doublet gemcitabine and carboplatin is effective for the treatment of recurrent ovarian cancer, while multi-agent chemotherapy with bevacizumab may add additional benefit. This phase II study tested the efficacy and safety of a biweekly gemcitabine, carboplatin, and bevacizumab combination in patients with platinum-sensitive recurrent ovarian, peritoneal, or tubal cancer (ROC). PATIENTS AND METHODS: Eligible patients received concurrent gemcitabine 1000 mg/m(2), carboplatin area under the curve 3, and bevacizumab 10 mg/kg administered intravenously on days 1 and 15 every 28 days

Cigarette smoking, passive smoking, alcohol consumption, and hearing loss.

The objective of this large population-based cross-sectional study was to evaluate the association between smoking, passive smoking, alcohol consumption, and hearing loss. The study sample was a subset of the UK Biobank Resource, 164,770 adults aged between 40 and 69 years who completed a speech-in-noise hearing test (the Digit Triplet Test). Hearing loss was defined as speech recognition in noise in the better ear poorer than 2 standard deviations below the mean with reference to young normally hearing listeners. In multiple logistic regression controlling for potential confounders, current s

The reactions of Cr(CO)6, Fe(CO)5, and Ni(CO)4 with O2 yield viable oxo-metal carbonyls.

Transition metal complexes with terminal oxo and dioxygen ligands exist in metal oxidation reactions, and many are key intermediates in various catalytic and biological processes. The prototypical oxo-metal [(OC)5Cr-O, (OC)4Fe-O, and (OC)3 Ni-O] and dioxygen-metal carbonyls [(OC)5Cr-OO, (OC)4Fe-OO, and (OC)3Ni-OO] are studied theoretically. All three oxo-metal carbonyls were found to have triplet ground states, with metal-oxo bond dissociation energies of 77 (Cr-O), 74 (Fe-O), and 51 (Ni-O) kcal/mol. Natural bond orbital and quantum theory of atoms in molecules analyses predict metal-oxo bond

Usefulness of antiemetic therapy with aprepitant, palonosetron, and dexamethasone for lung cancer patients on cisplatin-based or carboplatin-based chemotherapy.

PURPOSE: The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). METHODS: Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology