Miracle-dz/UniFAR-FTUs huggingface dataset:
Totally laparoscopic aortobifemoral bypass surgery in the treatment of aortoiliac occlusive disease or abdominal aortic aneurysms – a systematic review and critical appraisal of literature

Purpose This systematic review aims to evaluate the published literature regarding totally laparoscopic aortobifemoral bypass (LABF) surgery in the treatment of aortoiliac occlusive disease (AIOD) or abdominal aortic aneurysms (AAA), compared with open aortobifemoral bypass surgery. Materials and methods A systematic review of the medical literature between 1990 and 2016 was performed, searching the medical databases Cochrane Library, OVID Medline, Embase and PubMed. Studies concerning totally LABF with or without control group and containing more than 10 patients were included in the analysis. Operative and aortic cross-clamping times, blood loss, rate of conversion to open surgery, mortality and morbidity within the first 30 postoperative days, hospital stay and primary and secondary patency of the graft were extracted and compared with open surgery when possible. Results Sixty-six studies were deemed eligible for inclusion in this review, 16 of them matched the inclusion criteria for quantitative synthesis. The patient material consisted of 588 patients undergoing totally LABF, 22 due to AAA, and the remaining 566 for AIOD. Five comparative studies regarding AIOD compared 211 totally LABF procedures with 246 open procedures. Only one study concerning AAA was eligible for inclusion, and this study did not provide a comparison against an open group. The operating and aortic cross-clamping times were shorter in the open group. Conversion rates ranged from 0% to 27%. There was no statistically significant difference in mortality between the two groups (p=0.64). Hospital stays ranged from 4.0 to 12.1 and 5.0 to 12.8 days in the laparoscopic group and open group, respectively. Most of the studies provided low levels of evidence, mainly due to lack of blinding, randomization and correction of bias. Conclusion Totally laparoscopic aortoiliac surgery seems to be a feasible technique with unaffected mortality and trend toward benefits in hospital stay and possibly also in complication rates. The literature published this far is sparse and with inconsistent results. More randomized controlled trials are required before this method can be widely implemented.
Mitochondria as a Pharmacological Target

Mitochondria play a central role in energy metabolism within the cell. Mitochondrial dysfunctions lead to various neurodegenerative disorders and to the so-called “mitochondrial diseases”. A vast amount of evidence points to the implication of mitochondria in such complex processes as apoptosis and cardioprotection. The purpose of this review is to present a recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria. These include antitumor, immunosuppressant, and antiviral drugs, potassium channel openers, sulfonylureas, and anesthetics. Some of these substances are specifically designed to affect mitochondrial functions. In other cases, drugs with primary targets in other cellular locations may modify mitochondrial functions as side effects. In any case, identification of mitochondria as primary or secondary targets of a drug may help us to better understand the drug's mechanism of action and open new perspectives for its application. As far as possible, the molecular mechanisms of the interference of particular drugs in the mitochondrial metabolism will be described. In some cases, metabolic routes in which the drugs interfere will also be briefly outlined.
The small heat shock protein B 8 ( HspB 8 ) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis ( ALS )

Dipartimento di Endocrinologia, Fisiopatologia e Biologia Applicata (Center of Excellence on Neurodegenerative Diseases, CEND) and Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita’ degli Studi di Milano, Milano, Italy, Dipartimento di Neuroscienze, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milano, Italy, Department of Cell Biology, Section for Radiation and Stress Cell Biology, University Medical Center Groningen, Groningen, The Netherlands and InterUniversity Center on Neurodegenerative Diseases (CIMN), Universita’ degli Studi di Firenze, Roma ‘Tor Vergata’, Milano, Genova, Italy
Associations Among Vascular Risk Factors, Carotid Atherosclerosis, and Cortical Volume and Thickness in Older Adults

Background and Purpose— The purpose of this study was to investigate whether the Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness are associated with cortical volume and thickness. Methods— Consecutive subjects participating in a prospective cohort study of aging and mild cognitive impairment enriched for vascular risk factors for atherosclerosis underwent structural MRI scans at 3-T and 4-T MRI at 3 sites. Freesurfer (Version 5.1) was used to obtain regional measures of neocortical volumes (mm3) and thickness (mm). Multiple linear regression was used to determine the association of Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness with cortical volume and thickness. Results— One hundred fifty-two subjects (82 men) were aged 78 (±7) years, 94 had a clinical dementia rating of 0, 58 had a clinical dementia rating of 0.5, and the mean Mini-Mental State Examination was 28 ± 2. Framingham Cardiovascular Risk Profile score was inversely associated with total gray matter volume and parietal and temporal gray matter volume (adjusted P<0.04). Framingham Cardiovascular Risk Profile was inversely associated with parietal and total cerebral gray matter thickness (adjusted P<0.03). Carotid artery ntima-media thickness was inversely associated with thickness of parietal gray matter only (adjusted P=0.04). Including history of myocardial infarction or stroke and radiological evidence of brain infarction, or apolipoprotein E genotype did not alter relationships with Framingham Cardiovascular Risk Profile or carotid artery intima-media thickness. Conclusions— Increased cardiovascular risk was associated with reduced gray matter volume and thickness in regions also affected by Alzheimer disease independent of infarcts and apolipoprotein E genotype. These results suggest a “double hit” toward developing dementia when someone with incipient Alzheimer disease also has high cardiovascular risk.
[Laparoscopic adrenalectomy].

OBJECTIVE Laparoscopy has become the gold standard for the treatment of adrenal tumours in urology. We evaluate our experience with laparoscopic adrenalectomy (LA) in this work. MATERIAL, METHODS We performed 38 LA between 2003-2008. We use computer tomography (CT) and magnetic resonance imaging (MRI) for the initial evaluation. Indication for procedure is made in cooperation with endocrinologist. We use transperitoneal approach with 3 or 5 ports. RESULTS Mean age was 57.7 +/- 11.7 year (range 32-74.9 year). Nine LA were made in men (24%), in women 29 (76%). Sixteen tumours (42%) were hormonal active (7 pheochromocytoma, 6 primary hyperaldosteronism, 3 peripheral hypercortisolism). Twenty-two tumours were without hormonal activity. Mean tumour size was 4.1 +/- 2 cm (range 1-10.1 cm), mean operation time was 89 +/- 38 minutes (range 32-220 minutes), mean blood loss was 33 +/- 75 ml (range 0-400 ml), mean hospitalization time was 6.1 days (range 3-12 days). There were histologically 15 cortical adenomas, 5 nodular cortical hyperplasia, 1 calcificated hematoma, 3 cysts, 2 potentional malignant tumours on interface between adenoma and carcinoma, 1 cortical carcinoma and 7 pheochromocytoma. We found 3 metastases of renal carcinoma in adrenal gland and one metastasis mesenchymal chondrosarcoma too. Transperitoneal approach was chosen in 20 patients (53%) after previous abdominal operation (open cholecystectomy, appendectomy, transperitoneal nephrectomy, aortofemoral bypass). Complications were in 3 cases from 38 (8%). It was one perforation of diaphragm, which was resolve with laparoscopic suture, one postoperative delirium with fudge and agitation, one abscess in wound after extraction of specimen. We have got any conversion in our collection. The body mass index was higher than 38 in 3 patients. CONCLUSION LA is a quick and safe procedure with minimal morbidity and mortality. This procedure requires very experienced surgeon. Patients profit especially from miniinvasivity and short convalescence. Especially benign tumours of smaller size (by 8 cm) are indicated, extensive and especially malignant tumours remain a domain of open approach. Previous operations in abdominal cavity do not have to be a contraindication for LA and operation is possible in patients with monster obesity.
Family Adjustment and Parenting Stress When an Infant Has Serious Liver Disease: The Australian Experience

Objectives: Parenting stress, problems in family functioning, and lack of fathers’ engagement in treatment are associated with poor quality of life in children with chronic illnesses. The aim of the present study was to examine these characteristics in families of infants with serious liver disease in Australia, to inform the provision of mental health care for these families. Methods: From September 2009 to May 2013, 42 parents of infants recently diagnosed as having serious liver disease (defined as liver disease that may require transplantation in the future) completed questionnaires about family function, impact of the infant's illness on the family, parent stress symptoms, and fathers’ engagement in the care of the child. Participants were recruited from 4 metropolitan children's hospitals in Australia. Results: Parents reported psychological symptoms at similar rates to normative populations. Their reports of family functioning were significantly below mean scores in previously published populations with a medically ill family member (population mean 1.89; mothers mean 1.59; fathers mean 1.61, P < 0.001). Disruption to family roles was significantly correlated with psychological symptoms for mothers (r = 0.48, P < 0.01) and fathers (r = 0.31, P < 0.05). Greater helpfulness of fathers was correlated with lower depression in mothers (r = −0.35, P < 0.05), and fathers’ anxiety was correlated with their increased engagement (r = 0.40, P < 0.01). Conclusions: When parents report the presence of psychological symptoms, symptoms are likely to be present in both parents and are associated with difficulties adjusting to disrupted family roles. Father engagement may be protective of mothers’ mental health.
Carotid Plaque Vulnerability: A Positive Feedback Between Hemodynamic and Biochemical Mechanisms

Background and Purpose— Rupture of atherosclerotic plaques is one of the main causes of ischemic strokes. The aim of this study was to investigate carotid plaque vulnerability markers in relation to blood flow direction and the mechanisms leading to plaque rupture at the upstream side of carotid stenoses. Methods— Frequency and location of rupture, endothelial erosion, neovascularization, and hemorrhage were determined in longitudinal sections of 80 human carotid specimens. Plaques were immunohistochemically analyzed for markers of vulnerability. Plaque geometry was measured to reconstruct shape profiles of ruptured versus stable plaques and to perform computational fluid dynamics analyses. Results— In 86% of ruptured plaques, rupture was observed upstream. In this region, neovascularization and hemorrhage were increased, along with increased immunoreactivity of vascular endothelial and connective tissue growth factor, whereas endothelial erosion was more frequent downstream. Proteolytic enzymes, mast cell chymase and cathepsin L, and the proapoptotic protein Bax showed significantly higher expression upstream as compared with the downstream shoulder of atherosclerotic lesions. Comparison of geometric profiles for ruptured and stable plaques showed increased longitudinal asymmetry of fibrous cap and lipid core thickness in ruptured plaques. The specific geometry of plaques ruptured upstream induced increased levels of shear stress and increased pressure drop between the upstream and the downstream plaque shoulders. Conclusions— Vulnerability of the upstream plaque region is associated with enhanced neovascularization, hemorrhage, and cap thinning induced by proteolytic and proapoptotic mechanisms. These processes are reflected in structural plaque characteristics, analyses of which could improve the efficacy of vascular diagnostics and prevention.
Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain

Adoptive transfer of T lymphocytes transduced with a T cell receptor (TCR) to impart tumor reactivity has been reported as a potential strategy to redirect immune responses to target cancer cells (Schumacher, T.N. 2002. Nat. Rev. Immunol. 2:512–519). However, the affinity of most TCRs specific for shared tumor antigens that can be isolated is usually low. Thus, strategies to increase the affinity of TCRs or the functional avidity of TCR-transduced T cells might be therapeutically beneficial. Because glycosylation affects the flexibility, movement, and interactions of surface molecules, we tested if selectively removing conserved N-glycoslyation sites in the constant regions of TCR α or β chains could increase the functional avidity of T cells transduced with such modified TCRs. We observed enhanced functional avidity and improved recognition of tumor cells by T cells harboring TCR chains with reduced N-glycosylation (ΔTCR) as compared with T cells with wild-type (WT) TCR chains. T cells transduced with WT or ΔTCR chains bound tetramer equivalently at 4°C, but tetramer binding was enhanced at 37°C, predominantly as a result of reduced tetramer dissociation. This suggested a temperature-dependent mechanism such as TCR movement in the cell surface or structural changes of the TCR allowing improved multimerization. This strategy was effective with mouse and human TCRs specific for different antigens and, thus, should be readily translated to TCRs with any specificity.
Psychosocial management of chronic pain in patients with rheumatoid arthritis: challenges and solutions

There are numerous reviews and meta-analyses that confirm that psychological therapy is efficacious for patients with rheumatoid arthritis (RA) in terms of managing pain. Therefore, the literature has moved on to answer additional questions: 1) What types of interventions are most strongly supported by the current evidence? 2) Do different patients benefit from different approaches? 3) When is it best to intervene? 4) What modalities are best for administering the intervention? 5) What model of care should we be proposing that will result in widespread implementation and will ensure access for patients with RA? This review concludes that cognitive behavioral therapy (CBT) is the most efficacious treatment for pain management in RA; however, there are indications that mindfulness may have particular benefits for patients with a history of depression. CBT is most effective when administered early in the course of the disease. However, there is at present little evidence to confirm whether or not psychosocial interventions are effective for patients with comorbid psychological disorders. One of the major challenges is ensuring access to effective interventions for patients, particularly early on in the course of the disease, with a view to preventing physical and psychological morbidity. A stepped-care model is proposed; however, we urgently need more, better-quality trials of minimal interventions, particularly in Internet-delivered CBT, which appears promising and may form the cornerstone of future stepped-care models for providing psychosocial care to patients with RA.
Plankton blooms induced by turbulent flows

Plankton play an important role in the ecology of the ocean and the climate because of their participation in the global carbon cycle at the base of the food chain. However, damaging plankton blooms can sometimes occur and are initially characterized by sudden transient increases in the phytoplankton population. They are thought to be driven by several effects, such as seasonal variations in temperature and salinity, and nutrient mixing. Furthermore, phytoplankton and zooplankton have different buoyancy properties, leading to a differential response in turbulent environments. In this paper, we investigate this effect in a model of advected plankton dynamics. We find that, over a range of parameter values, flows of marine species subjected to inertial/viscous forces naturally lead to patchiness and, in turn, periodically sustained plankton blooms.
SED4 encodes a yeast endoplasmic reticulum protein that binds Sec16p and participates in vesicle formation

SEC16 is required for transport vesicle budding from the ER in Saccharomyces cerevisiae, and encodes a large hydrophilic protein found on the ER membrane and as part of the coat of transport vesicles. In a screen to find functionally related genes, we isolated SED4 as a dosage- dependent suppressor of temperature-sensitive SEC16 mutations. Sed4p is an integral ER membrane protein whose cytosolic domain binds to the COOH-terminal domain of Sec16p as shown by two-hybrid assay and coprecipitation. The interaction between Sed4p and Sec16p probably occurs before budding is complete, because Sed4p is not found in budded vesicles. Deletion of SED4 decreases the rate of ER to Golgi transport, and exacerbates mutations defective in vesicle formation, but not those that affect later steps in the secretory pathway. Thus, Sed4p is important, but not necessary, for vesicle formation at the ER. Sec12p, a close homologue of Sed4p, also acts early in the assembly of transport vesicles. However, SEC12 performs a different function than SED4 since Sec12p does not bind Sec16p, and genetic tests show that SEC12 and SED4 are not functionally interchangeable. The importance of Sed4p for vesicle formation is underlined by the isolation of a phenotypically silent mutation, sar1-5, that produces a strong ER to Golgi transport defect when combined with sed4 mutations. Extensive genetic interactions between SAR1, SED4, and SEC16 show close functional links between these proteins and imply that they might function together as a multisubunit complex on the ER membrane.
Soil warming affects sap flow responses to meteorological conditions for Betula albosinensis at a subalpine wetland in the edge of northeast Qinghai–Tibet Plateau

Transpiration in cold‐limited areas is restricted by low soil temperature. However, little is known about the influence of soil warming on tree transpiration under a water logged and cold soil conditions. We aimed to test the hypothesis that an increase in soil temperature in the absence of water stress will lead to increased sap flow of red birch (Betula albosinensis) in a subalpine wetland. Sap flow and relevant environmental data were measured for B. albosinensis in a subalpine wetland in the edge of northeast Qinghai–Tibet Plateau from 2013 to 2016. The cooling and controlling experiments were also conducted in the lab from June to July in 2017. The results showed that meteorological parameters, as well as soil temperature, are important limiting factors for tree transpiration. It was governed by meteorological factors throughout the growing season, whereas we only found a significant increase of sap flow upon soil warming in the mid‐growing season, which may be attributed to warm‐induced hydraulic conductivity. In the early growing season, no warming effect was observed on sap flow. We then concluded that whole‐tree water use may increase with increasing soil temperature and similar precipitation and thus alter the local water balance. These results are essential to understand the response of hydrological processes to future climate warming.
Direct thermal conductance measurements on suspended monocrystalline nanostructures

We describe and demonstrate a new class of devices that enable direct thermal conductance measurements on monocrystalline nanostructures. These are possible through our newly developed techniques for three-dimensional, successive surface nanomachining of GaAs-based heterostructures. Our methods allow the patterning of complex devices comprising electrically insulating, mesoscopic thermal conductors with separate, thermal transducers in situ. Intimate thermal contact between these elements is provided by their epitaxial registry. Low-temperature thermal conductance measurements indicate that phonon boundary scattering in these initial nanometer is scale structures is partially specular. These devices offer promise for ultrasensitive bolometry and calorimetry.
Steroidal regulation of connective tissue growth factor (CCN2; CTGF) synthesis in the mouse uterus

Aims—To determine mechanisms regulating the production of connective tissue growth factor (CCN2; CTGF) and transforming growth factor β1 (TGF-β1) in the mouse uterus. Methods—In situ hybridisation and immunohistochemistry were used to localise CCN2 (CTGF) and TGF-β1 in uteri from sexually mature female mice that had either been (1) mated with sterile males to induce pseudopregnancy or (2) ovariectomised (OVX) and administered estradiol-17β (E2) or progesterone (P4), either alone or in combination. Uteri collected on days 0.5, 1.5, 2.5, 3.5, 4.5, or 5.5 of pseudopregnancy or at one, three, six, 12, or 24 hours after steroid administration were fixed, sectioned, and incubated with specific riboprobes or antibodies to permit detection and localisation of mRNA or protein for CTGF and TGF-β1. Results—On days 0.5–2.5 of pseudopregnancy, CCN2 (CTGF) and TGF-β1 were principally colocalised to uterine epithelial cells, with much smaller amounts in the stroma. On days 3.5–4.5, there was a reduction of CCN2 (CTGF) and TGF-β1 in the epithelium but an increase in stromal and endothelial cells, corresponding to a period of extracellular matrix remodelling and neovascularisation within the endometrium. In OVX mice, epithelial cells were weakly positive for both CCN2 (CTGF) and TGF-β1 in the absence of steroid hormones. Epithelial CTGF mRNA production were strongly but transiently stimulated in OVX mice cells by E2. These effects were antagonised by P4, which itself transiently stimulated epithelial CCN2 (CTGF) production, although less robustly than E2. CTGF and TGF-β1 protein amounts were high in epithelial cells throughout steroid treatment and were increased in the stroma, where they were relatively long lived. Stromal CCN2 (CTGF) and TGF-β1 were lower after co-administration of E2 and P4 than in response to each hormone individually. Although ccn2 (ctgf) is a TGF-β1 inducible gene in other systems, and both growth factors were often co-localised in uterine tissues in these studies, several treatment regimens resulted in high amounts of TGF-β1 protein in stromal cells without the concomitant production of ccn2 (ctgf) mRNA. Conclusions—Maternal factors are principal cues for CCN2 (CTGF) and TGF-β1 production in the uterus because (1) their expression during pseudopregnancy is comparable to that seen in pregnancy and (2) they are regulated by ovarian steroids. TGF-β dependent and independent mechanisms of ccn2 (ctgf) gene transcription exist in the uterus that are variably regulated by steroid hormones. Collectively, the data support a role for CCN2 (CTGF) in mediating the effects of steroid hormones and TGF-β on endometrial function.