Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.     

Evaluating the efficacy and safety of vascular IPL for treatment of acute cutaneous leishmaniasis: a randomized controlled trial

Lasers in Medical Science - Treatment of cutaneous leishmaniasis (CL) continues to be a health concern, and alternative therapies with fewer side effects are substantially needed. This study aimed...     

Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

Biallelic pathogenic variants in the gene PYROXD1 have recently been described to cause early-onset autosomal recessive myopathy. Myopathy associated with PYROXD1 pathogenic variants is rare and reported in only 17 individuals. Known pathogenic variants in PYROXD1 include missense, insertion and essential splice-site variants. Here we describe a consanguineous family of individuals affected with late-onset myopathy and homozygous PYROXD1 missense variants (NM_024854.5:c.464A>G [p.Asn155Ser]) expanding our understanding of the possible disease phenotypes of PYROXD1-associated myopathy.     

Assessing the role of nocturnal core body temperature dysregulation as a biomarker of neurodegeneration

The vast majority of patients with idiopathic rapid eye movement sleep behaviour disorder will develop a neurodegenerative α‐synuclein‐related condition, such as Parkinson’s disease or dementia with Lewy bodies. The pathology underlying dream enactment overlaps anatomically with the brainstem regions that regulate circadian core body temperature. Previously, nocturnal core body temperature regulation has been shown to be impaired in Parkinson’s disease. However, no study to date has investigated nocturnal core body temperature changes in patients with idiopathic rapid eye movement sleep behaviour disorder, which may prove to be an early objective biomarker for α‐synucleinopathies. Ten healthy controls, 15 patients with idiopathic rapid eye movement sleep behaviour disorder, 31 patients with Parkinson’s disease and six patients with dementia with Lewy bodies underwent clinical assessment and nocturnal polysomnography with core body temperature monitoring. A validated cosinor method was utilised for core body temperature analysis. No differences in mesor, nadir or time of nadir were observed between groups. However, when compared with healthy controls, the amplitude of the nocturnal core body temperature (mesor minus nadir) was significantly reduced in patients with idiopathic rapid eye movement sleep behaviour disorder, Parkinson’s disease with concurrent rapid eye movement sleep behaviour disorder and dementia with Lewy bodies (p < 0.001, p = 0.043 and p = 0.017, respectively). Importantly, this relationship was not seen in those patients with Parkinson’s disease without rapid eye movement sleep behaviour disorder. In addition, there was a significant negative correlation between amplitude of the core body temperature and self‐reported rapid eye movement sleep behaviour disorder symptoms. Changes in thermoregulatory circadian rhythm may be specifically associated with the pathology underlying rapid eye movement sleep behaviour disorder rather than simply that of α‐synucleinopathy. These findings implicate thermoregulatory dysfunction as a potential early biomarker for development of rapid eye movement sleep behaviour disorder‐associated neurodegeneration, and suggest that subpopulations with differing pathological underpinnings might exist in Parkinson’s disease.     

Documentation of Psychiatric Disorders and Related Factors in a Large Sample Population of HIV-Positive Patients in California

This retrospective cohort study examined electronic medical records of HIV-positive patients in California (N = 7,834) to find the prevalence of any psychiatric condition and the associations between several factors and the likelihood of these disorders. Approximately 53 % of the patients in this study had a documented psychiatric condition, including 23 % who had a mood disorder, 19 % who had a substance-related disorder, and 16 % who had an anxiety disorder. After controlling for potential confounders, significant positive associations (p < 0.001) were found between female gender and the presence of any mood disorder (adjusted odds ratio [95 % confidence interval, 95 %CI] = 1.58 [1.26–1.99]) or anxiety disorder (AOR = 1.54 [1.18–2.02]) and between homosexual orientation and the presence of any psychiatric condition (AOR = 1.33 [1.15–1.55]), mood disorder (AOR = 1.71 [1.42–2.07]), or anxiety disorder (AOR = 1.41 [1.22–1.88]). There were also significant negative associations between African-American race and the presence of any psychiatric condition (AOR = 0.68 [0.60–0.77]), mood disorder (AOR = 0.74 [0.64–0.86]), anxiety disorder (AOR = 0.43 [0.36–0.52]), or substance-related disorder (AOR = 0.78 [0.67–0.91]) and between state/federal insurance and the presence of any psychiatric condition (AOR = 0.70 [0.62–0.79]), mood disorder (AOR = 0.71 [0.62–0.80]), or anxiety disorder (AOR = 0.77 [0.66–0.89]).     

Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice

Methimazole is the most widely prescribed antithyroid medication in humans. However, hepatotoxicity is a deleterious adverse effect associated with methimazole administration. No specific protective agent has been developed against this complication yet. This study was designed to investigate the role of taurine as a hepatoprotective agent against methimazole-induced liver injury in mice. Different reactive metabolites were proposed to be responsible for methimazole hepatotoxicity. Hence, methimazole-induced liver injury was investigated in intact and/or enzyme-induced animals in the current investigation. Animals were treated with methimazole (200 mg/kg, by gavage), and hepatic injury induced by this drug was investigated in intact and/or enzyme-induced groups. Markers such as lipid peroxidation, hepatic glutathione content, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in plasma, and histopathological changes in the liver of animals were monitored after drug administration. Methimazole caused liver injury as revealed by increased plasma ALT. Furthermore, a significant amount of lipid peroxidation was detected in the drug-treated animals, and hepatic glutathione reservoirs were depleted. Methimazole-induced hepatotoxicity was more severe in enzyme-induced mice. The above-mentioned alterations in hepatotoxicity markers were endorsed by significant histopathological changes in the liver. Taurine administration (1 g/kg, i.p.) effectively alleviated methimazole-induced liver injury in both intact and/or enzyme-induced animals.     

Resolution of adult respiratory distress syndrome after recovery from fulminant hepatic failure

Adult respiratory distress syndrome (ARDS) complicating the course of fulminant hepatic failure is nearly always fatal without orthotopic liver transplantation. We report the case of a 50-year-old woman with fulminant hepatic failure and ARDS that resolved after her recovery from the acute liver failure without liver transplantation. The pathogenesis is discussed, particularly with regard to liver-lung interactions.