Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychic and socioeconomic consequences with diabetes compared to other chronic conditions

The present study relies on data for the years 1988 and 1989 from the Swedish continuous Surveys of Living Conditions (SLC), which are based on random samples from the population among individuals aged 16 through 84 years. We compared the rates of self-reported mental health for subjects reporting diabetes (n = 361), a musculoskeletal condition but without diabetes (n = 2187), hypertension but without diabetes (n = 980), and healthy free from any medical condition (n = 6654). Comparisons are based on age- and gender-standardized rates, using the diabetes group as standard. The results show that more diabetic respondents had psychic symptoms and long-standing psychiatric disorders than the healthy respondents, with otherwise no differences compared to the other chronic conditions. The diabetic respondents had lower mean disposable income, and a higher rate of disability pension than the respondents with hypertension, and than the healthy. They also reported more sick leave days than the healthy respondents.
Polymorphisms in the coding exons of the human luteinizing hormone receptor gene

Four polymorphisms were identified in the coding exons of the human luteinizng hormone/chorionic gonadotropin receptor (hLHR) gene. A CTGCAG insertion occurred after nucleotide 54 in 8 of 34 independent chromosomes examined. The heterozygosity frequency was 0.353. This Leu‐Gln dipeptide insertion in the first Leucine repeat of the hLHR extracellular domain did not affect the ligand binding affinity of the receptor. Among 54 chromosomes analyzed, 64.8% was A and 35.2% was G at nucleotide 872 in exon 10. The heterozygosity frequency was 0.115. The A/G substitution led to the replacement of Asn by Ser in the G alllele and the abolition of a potential N‐glycosylation site. Another polymorphism occurred at nucleotide 935. Fifty nine percent of chromosomes examined were A and 41% were G at this site with the encoded amino acid being Ser in the former and Asn in the latter. The heterozygosity frequency was 0.192. This polymorphism did not have biological consequence. Both of the exon 10 polymorphisms showed ethnic prevalence with the 872 G allele and the 935 A allele predominantly in non‐Caucasians. The fourth polymorphism was neutral and occurred at nucleotide 1065 in exon 11, with C in 60% and T in 40% of the 50 chromosomes examined. These polymorphisms are useful for tracking the inheritance of specific hLHR allele. Hum Mutat 11:333–334, 1998. © 1998 Wiley‐Liss, Inc.
Course and outcome of a pregnancy with a giant fetal cervical teratoma diagnosed prenatally

We report the course and outcome of a pregnancy involving a giant fetal neck teratoma which was diagnosed at 23 weeks of gestation. Sonographic surveillance of the fetal neck revealed continuing growth of the tumor with development of polyhydramnios. Three‐dimensional ultrasound provided additional detailed information on the external extent of the lesion. Color Doppler ultrasound showed intense arterial and venous flow with low resistance indices. Cesarean section under general anesthesia was planned in close cooperation with the neonatologist, pediatric surgeon and anesthesiologist because the size of the neck mass precluded vaginal delivery. Cesarean section was performed at 34 weeks of gestation following preterm rupture of the membranes. Orotracheal intubation was not successful because of compression of the airway and a tracheostomy could not be performed because of the risk of severe fetal hemorrhage from the tumor. The neonate died from respiratory insufficiency 66 min after birth. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology
Cold renal ischemia: comparison of efficacy between two techniques of cooling, in a swine model.

OBJECTIVES In a swine model of renal ischemia, we compared the effectiveness of the transurethral retrograde cold saline perfusion technique to the traditional method of renal cooling with ice slush, in achieving adequate parenchymal temperatures for functional preservation of the organ. Physiological and histological effects were also assessed. METHODS Twenty-four domestic male pigs were sampled into four groups to be submitted to a 60-minute ischemia of the left kidney without cooling, with either one of the two cooling techniques (cold saline retrograde perfusion or ice slush), or sham surgery. All of them had also a concomitant right nephrectomy. Renal cortical and medullary temperatures were recorded throughout the experiment. Urinary output was measured, and serum renal function tests were carried on, pre- and postoperatively. After 5 days, the animals were euthanized and their kidneys were submitted to histological analysis. RESULTS Mean renal temperature fell in both groups submitted to kidney cooling. With ice slush, a faster drop was observed and a lower minimum temperature was achieved (5.0 degrees C in the cortex and 6.3 degrees C in the medulla, vs. 25.4 degrees C and 24.9 degrees C with retrograde cooling). In the other groups, temperature was unchanged. Urinary output and serum creatinine worsened after the experiment, but without significant differences among groups. The histological analysis showed no differences among the four groups, for the studied ischemia time. CONCLUSIONS Ice slush and retrograde perfusion of cold saline are both effective for cooling the kidney during ischemia. Ice slush is faster in doing so, and it allows much lower temperatures to be achieved in the renal parenchyma. With ischemia time of 60 minutes, no significant differences on the occurrence of functional and histological alterations were detected, even for the group without a cooling procedure.
Use of a flexible thiopyrylium photosensitizer and competitive inhibitor for pathogen reduction of viruses and bacteria with retention of red cell storage properties

BACKGROUND: Progress in developing photochemical methods for pathogen reduction of red blood cells (RBCs) has been hampered by hemolysis. A flexible, nucleic acid‐intercalating thiopyrylium (TP) dye that is only photochemically active in the bound state and a competitive inhibitor of RBC membrane binding, dipyridamole (DP), was used to reduce photoinduced hemolysis stemming from free‐ and membrane‐bound dye.
A Perspective on Ovarian Cancer Biomarkers: Past, Present and Yet-To-Come

The history of biomarkers and ultrasonography dates back over more than 50 years. The present status of biomarkers used in the context of ovarian cancer is addressed. Attention is given to new interpretations of the etiology of ovarian cancer. Cancer antigen 125 (CA125) and multivariate index assays (Ova1, Risk of Ovarian Malignancy Algorithm, Overa) are biomarker-driven considerations that are presented. Integration of biomarkers into ovarian cancer diagnostics and screening are presented in conjunction with ultrasound. Consideration is given to the serial application of both biomarkers and ultrasound, as well as morphology-based indices. Attempts are made to foresee how individualized molecular signatures may be able to both provide an alert of the potential for ovarian cancer and to provide molecular treatments tailored to a personalized genetic signature. In the future, an annual pelvic ultrasound and a comprehensive serum biomarker screening/diagnostic panel may replace the much maligned bimanual examination as part of the annual gynecologic examination. Taken together, it is likely that a new medical specialty for screening and early diagnostics will emerge for physicians and epidemiologists, a field of study that is independent of patient gender, organ, or the subspecialties of today.
Adjunctive &agr;-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study

&agr;-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600–1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.
Mental health in Alberta grain farmers using pesticides over many years.

BACKGROUND Exposure to organophosphates and certain other pesticides has been related to symptoms of mental ill-health. There is particular interest in whether exposure over many years may result in chronic ill-health. AIMS To relate lifetime history of pesticide exposure to symptoms and medical records of mental ill-health in elderly grain farmers in Alberta. METHODS Two populations of grain farmers were identified for study: cohort A (n = 5986), members of an Alberta farm organization in 1983; cohort B (n = 4781), grain farmers registered with the provincial department of agriculture. In 2002-03 both groups completed a questionnaire on lifetime history of pesticide use, physician diagnosed disease and recent neuropsychological symptoms. Durations of exposure to seven pesticide components were calculated and a factor score extracted from responses to the symptom questionnaire. For a sub-cohort surviving to 2009 medical records for mental ill-health were identified. Records and symptom scores were related to pesticide exposures allowing for confounding. RESULTS From cohort A, 1348 and cohort B, 1078 were alive and interviewed (median age 63 years; median duration in farming 40 years): 1371 were linked to the medical records database. Mental ill-health symptom scores were related to duration of exposure to phenoxy compounds (but not to other pesticides) and to mental ill-health in medical records. Those with mental ill-health in hospital discharge records were more likely to have been exposed to phenoxy compounds for ≥35 years. CONCLUSIONS The relationship of long-term exposure to phenoxy herbicides and neuropsychiatric symptoms was unexpected but not explained by measured confounders.
A Redox-Sensitive Cysteine in Zta Is Required for Epstein-Barr Virus Lytic Cycle DNA Replication

ABSTRACT Epstein-Barr virus (EBV) reactivation from latency is known to be sensitive to redox regulation. The immediate-early protein Zta is a member of the basic-leucine zipper (bZIP) family of DNA binding proteins that stimulates viral and cellular transcription and nucleates a replication complex at the viral lytic origin. Zta shares with several members of the bZIP family a conserved cysteine residue (C189) that confers redox regulation of DNA binding. In this work, we show that replacement of C189 with serine (C189S) eliminated lytic cycle DNA replication function of Zta. The mechanistic basis for this replication defect was investigated. We show that C189S was not significantly altered for DNA binding activity in vitro or in vivo. We also show that C189S was not defective for transcription activation of EBV early gene promoters. C189S was deficient for transcription activation of several viral late genes that depend on lytic replication and therefore was consistent with a primary defect of C189S in activating lytic replication. C189S was not defective in binding methylated DNA binding sites and was capable of activating Rta from endogenous latent viral genomes, in contrast to the previously characterized S186A mutation. C189S was slightly impaired for its ability to form a stable complex with Rta, although this did not prevent Rta recruitment to OriLyt. C189S did provide some resistance to oxidation and nitrosylation, which potently inhibit Zta DNA binding activity in vitro. Interestingly, this redox sensitivity was not strictly dependent on C189S but involved additional cysteine residues in Zta. These results provide evidence that the conserved cysteine in the bZIP domain of Zta plays a primary role in EBV lytic cycle DNA replication.
Study on Free Radicals and Pancreatic Fibrosis—Pancreatic Fibrosis Induced by Repeated Injections of Superoxide Dismutase Inhibitor

The exact mechanisms of the development of pancreatic fibrosis are still unknown. To clarify the relationship between pancreatic fibrosis and free radicals, the effect of the administration of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DDC), on pancreatic fibrosis in rats was studied. A single intraperitoneal injection of 500 mg/kg of DDC significantly reduced SOD activity and significantly increased lipid peroxidation products in the pancreas, showing no histologic changes of inflammation or necrosis. Repeated administration of 500 mg/kg DDC, twice a week, caused inter-and intralobular fibrosis with atrophy of acinar cells in the pancreas for at least 2 weeks without fibrosis of the liver and kidney. Administration of allopurinol showed preventive effects against DDC-induced pancreatic fibrosis. In conclusion, repeated administration of DDC, which caused pancreatic fibrosis, is a new experimental model of pancreatic fibrosis from the viewpoint of oxidative stress.
Monomeric IgG1 Fc molecules displaying unique Fc receptor interactions that are exploitable to treat inflammation-mediated diseases

The IgG1 Fc is a dimeric protein that mediates important antibody effector functions by interacting with Fcγ receptors (FcγRs) and the neonatal Fc receptor (FcRn). Here, we report the discovery of a monomeric IgG1 Fc (mFc) that bound to FcγRI with very high affinity, but not to FcγRIIIa, in contrast to wild-type (dimeric) Fc. The binding of mFc to FcRn was the same as that of dimeric Fc. To test whether the high-affinity binding to FcγRI can be used for targeting of toxins, a fusion protein of mFc with a 38 kDa Pseudomonas exotoxin A fragment (PE38), was generated. This fusion protein killed FcγRI-positive macrophage-like U937 cells but not FcγRI-negative cells, and mFc or PE38 alone had no killing activity. The lack of binding to FcγRIIIa resulted in the absence of Fc-mediated cytotoxicity of a scFv-mFc fusion protein targeting mesothelin. The pharmacokinetics of mFc in mice was very similar to that of dimeric Fc. The mFc's unique FcγRs binding pattern and related functionality, combined with its small size, monovalency and the preservation of FcRn binding which results in relatively long half-life in vivo, suggests that mFc has great potential as a component of therapeutics targeting inflammation mediated by activated macrophages overexpressing FcγRI and related diseases, including cancer.
Profile and treatment outcomes of elderly patients with tuberculosis in Delhi, India: implications for their management.

BACKGROUND Given India's high rate of TB, rising burden of non-communicable diseases (NCDs) and growing elderly population, elderly TB patients may be at higher risk of adverse outcomes including death, loss-to-follow-up (LTFU) and treatment failure. This may call for modifications in their management. This study thus aimed to compare the profile and treatment outcomes between elderly (≥60 years) and non-elderly (15-59 years) TB patients. METHODS This was a retrospective cohort study using routinely-collected programme data from a chest clinic in Delhi, India. It included all elderly and selected non-elderly TB patients registered for treatment between 2005 and 2010. Data on patients' clinical and demographic characteristics and treatment outcomes were analysed. RESULTS There were 812 elderly and 1624 non-elderly TB patients. Elderly patients were more likely to be male (63.2% vs 51.1%) and have smear-positive TB (56.0% vs 47.4%). Adverse outcomes were more frequent among elderly patients (adjusted OR 1.9, 95% CI: 1.5-2.4), specifically deaths (adjusted OR 5.0, 95% CI: 3.1-8.1) and lost-to-follow-up (adjusted OR 1.4, 95% CI: 1.0-1.9). CONCLUSIONS The profile and worse outcomes of elderly Indian TB patients may be indicative of co-existing NCDs. This needs further investigation and likely calls for a more comprehensive and intensive approach to their management.
miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5

Purpose: miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer. Experimental Design: miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation in vitro and in vivo. The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in silico target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments. Results: Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts (P < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration. Conclusions: The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. Clin Cancer Res; 23(17); 5255–66. ©2017 AACR.
Differential expression of the chromosome 11 mucin genes in colorectal cancer

The four secretory mucin genes clustered on chromosome 11, MUC2, MUC5AC, MUC5B and MUC6, were screened in 37 patients with cancers in the left hemi‐colon or rectum and 10 normal rectal controls. The mucin genes were detected by in situ hybridization using oligonucleotide probes to the variable number tandem repeat (VNTR) sequences, while the proteins were stained with non‐VNTR (MUC2, MUC5AC and MUC5B) or VNTR (MUC6) antibodies. Low levels of MUC2 mRNA were detected in non‐mucinous adenocarcinomas (5/27) while a higher proportion of mucinous carcinomas (4/9) was positive. All 25 cases of adjacent normal tissue expressed MUC2 mRNA. No transcripts for MUC5AC, MUC5B or MUC 6 were detected in any of these specimens. MUC2 protein product was detected immunohistochemically in 34/36 carcinoma specimens, with no change from normal controls. There was de novo expression of MUC5AC in 23/36 carcinomas. No MUC5B or MUC6 protein was detected. No difference in MUC2 and MUC5AC protein was found between mucinous and non‐mucinous carcinomas. The level of MUC2 was increased in moderately differentiated cancers compared with normal controls and decreased in the poorly differentiated group. Decreased MUC2 was found in poorly differentiated compared with moderately differentiated tumours. More MUC5AC protein was detected in well and moderately differentiated tumours than in poorly differentiated tumours and in all tumours relative to controls. The pattern of MUC2 staining in cancers was different from control tissue, with strong staining in the perinuclear region and none in goblet cell vesicles. MUC5AC staining was mainly detected in the cytoplasm. Poor detection of MUC2 and MUC5AC mRNA and associated strong staining for the total protein suggests altered biosynthesis and processing, leading to the characteristic subcellular distribution. Hence, change in the synthesis of MUC2 and the de novo appearance of MUC5AC in colorectal carcinomas may be significant events in the adenoma‐carcinoma sequence, with possible implications for tumour prognosis. Copyright © 2001 John Wiley & Sons, Ltd.
Mismatch Repair Proteins Are Activators of Toxic Responses to Chromium-DNA Damage

ABSTRACT Chromium(VI) is a toxic and carcinogenic metal that causes the formation of DNA phosphate-based adducts. Cr-DNA adducts are genotoxic in human cells, although they do not block replication in vitro. Here, we report that induction of cytotoxicity in Cr(VI)-treated human colon cells and mouse embryonic fibroblasts requires the presence of all major mismatch repair (MMR) proteins. Cr-DNA adducts lost their ability to block replication of Cr-modified plasmids in human colon cells lacking MLH1 protein. The presence of functional mismatch repair caused induction of p53-independent apoptosis associated with activation of caspases 2 and 7. Processing of Cr-DNA damage by mismatch repair resulted in the extensive formation of γ-H2AX foci in G2 phase, indicating generation of double-stranded breaks as secondary toxic lesions. Induction of γ-H2AX foci was observed at 6 to 12 h postexposure, which was followed by activation of apoptosis in the absence of significant G2 arrest. Our results demonstrate that mismatch repair system triggers toxic responses to Cr-DNA backbone modifications through stress mechanisms that are significantly different from those for other forms of DNA damage. Selection for Cr(VI) resistant, MMR-deficient cells may explain the very high frequency of lung cancers with microsatellite instability among chromate workers.
Cognitive Outcome Following Traumatic Brain Injury

ObjectiveTo determine whether an association exists between traumatic brain injury (TBI) sustained in adulthood and cognitive impairment 6 months or longer after injury. DesignSystematic review of the published, peer-reviewed literature. ResultsFrom 430 articles, we identified 11 primary and 22 secondary studies that examined cognitive impairment by using performance measures for adults who were at least 6 months post-TBI. There was clear evidence of an association between penetrating brain injury and impaired cognitive function. Factors that modified this association included preinjury intelligence, volume of brain tissue lost, and brain region injured. There was also suggestive evidence that penetrating brain injury may exacerbate the cognitive effects of normal aging. We found clear evidence for long-term cognitive deficits associated with severe TBI. There was suggestive evidence that moderately severe brain injuries are associated with cognitive impairments. There was inadequate/insufficient evidence to determine whether an association exists between a single, mild TBI and cognitive deficits 6 months or longer postinjury. ConclusionIn adults, penetrating, moderate, and severe TBIs are associated with cognitive deficits 6 months or longer postinjury. There is insufficient evidence to determine whether mild TBI is associated with cognitive deficits 6 months or longer postinjury.