Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Incidence of Surgical Site Infection in IBD Patients

BACKGROUND: Surgical site infection is a key hospital-level patient safety indicator. All risk factors for surgical site infection are not always taken into account and adjusted for. OBJECTIVE: This study aimed to measure the impact of IBD in comparison with diverticulitis and colorectal cancer on the national rates of surgical site infection. DESIGN: The American College of Surgeons National Surgical Quality Improvement Project database was queried for all patients undergoing elective colectomy for colon cancer, diverticulitis, and IBD from 2008 through 2012. OUTCOME MEASURES: The association between surgical site infection and IBD patients was assessed. Patient demographics, rates of surgical site infection, wound class, return to operating room, and various patient characteristics were analyzed. Logistic regression was performed to determine the association with surgical site infection. RESULTS: The query yielded 71,845 patients undergoing elective colectomy. Of these patients, 42,132 had colon cancer, 22,143 had diverticulitis, and 7570 had IBD. The rate of surgical site infection was 12.0% for colon cancer, 12.8% for diverticulitis, and 18.0% for IBD. Return to operating room within 30 days was 7.3% for IBD patients, 4.4% for patients with diverticulitis, and 4.9% for patients with colorectal cancer. Return to operating room within 30 days had the highest correlation to surgical site infection in both univariate and multivariable analysis. Other associative factors for surgical site infection common to both analyses included diabetes mellitus, smoking, open procedures, and obesity. LIMITATIONS: This study was limited by the data collection errors inherent to large databases, exclusion of emergent operations, and the inability to identify patients taking immunosuppressive agents. CONCLUSIONS: Patients with IBD undergoing elective colectomy have significantly increased rates of surgical site infection, specifically deep and organ/space infections. Given this information, risk adjustment models for surgical site infection may need to include IBD in their calculation.
Experience with the Nd:YAG Laser in the Treatment of Keloid Scars

Numerous therapeutic modalities have been espoused for the treatment of keloids. In the laboratory, great strides have been made in understanding the connective tissue pathobiology that underhes this problem. Unfortunately, no consistent treatment has been found to prevent the development of surface overhealing. Moreover, all forms of therapy designed to treat this condition have produced inconsistent results. This article documents the use of the Nd: YAG laser in the treatment of 20 patients with keloid scars. Candidates for the study included patients with no previous therapy and those who had prior treatment with steroids and/or surgery with no improvement. Although the use of Nd: YAG laser for keloids continues to be investigational, our results appear promising. Success of therapy was judged by softening and flattening of the scar. Laboratory studies provide a basis for understanding the possible effect of connective tissue metabohsm with the Nd: YAG.
Sensor fusion and computer vision for context-aware control of a multi degree-of-freedom prosthesis

Objective. The aim of the present work was to develop and test a flexible electrotactile stimulation system to provide real-time feedback to the prosthesis user. The system requirements were to accommodate the capabilities of advanced multi-DOF myoelectric hand prostheses and transmit the feedback variables (proprioception and force) using intuitive coding, with high resolution and after minimal training. Approach. We developed a fully-programmable and integrated electrotactile interface supporting time and space distributed stimulation over custom designed flexible array electrodes. The system implements low-level access to individual stimulation channels as well as a set of high-level mapping functions translating the state of a multi-DoF prosthesis (aperture, grasping force, wrist rotation) into a set of predefined dynamic stimulation profiles. The system was evaluated using discrimination tests employing spatial and frequency coding (10 able-bodied subjects) and dynamic patterns (10 able-bodied and 6 amputee subjects). The outcome measure was the success rate (SR) in discrimination.Main results. The more practical electrode with the common anode configuration performed similarly to the more usual concentric arrangement. The subjects could discriminate six spatial and four frequency levels with SR >90% after a few minutes of training, whereas the performance significantly deteriorated for more levels. The dynamic patterns were intuitive for the subjects, although amputees showed lower SR than able-bodied individuals (86%± 10% versus 99%± 3%). Significance. The tests demonstrated that the system was easy to setup and apply. The design and resolution of the multipad electrode was evaluated. Importantly, the novel dynamic patterns, which were successfully tested, can be superimposed to transmit multiple feedback variables intuitively and simultaneously. This is especially relevant for closing the loop in modern multifunction prostheses. Therefore, the proposed system is convenient for practical applications and can be used to implement sensory perception training and/or closed-loop control of myoelectric prostheses, providing grasping force and proprioceptive feedback.
IDL6‐HAE/HSL2 impacts pectin degradation and resistance to Pseudomonas syringae pv tomato DC3000 in Arabidopsis leaves

Summary Plant cell walls undergo dynamic structural and chemical changes during plant development and growth. Floral organ abscission and lateral root emergence are both accompanied by cell‐wall remodeling, which involves the INFLORESCENCE DEFICIENT IN ABSCISSION (IDA)‐derived peptide and its receptors, HAESA (HAE) and HAESA‐LIKE2 (HSL2). Plant cell walls also act as barriers against pathogenic invaders. Thus, the cell‐wall remodeling during plant development could have an influence on plant resistance to phytopathogens. Here, we identified IDA‐like 6 (IDL6), a gene that is prominently expressed in Arabidopsis leaves. IDL6 expression in Arabidopsis leaves is significantly upregulated when the plant is suffering from attacks of the bacterial Pseudomonas syringae pv. tomato (Pst) DC3000. IDL6 overexpression and knockdown lines respectively decrease and increase the Arabidopsis resistance to Pst DC3000, indicating that the gene promotes the Arabidopsis susceptibility to Pst DC3000. Moreover, IDL6 promotes the expression of a polygalacturonase (PG) gene, ADPG2, and increases PG activity in Arabidopsis leaves, which in turn reduces leaf pectin content and leaf robustness. ADPG2 overexpression restrains Arabidopsis resistance to Pst DC3000, whereas ADPG2 loss‐of‐function mutants increase the resistance to the bacterium. Pst DC3000 infection elevates the ADPG2 expression partially through HAE and HSL2. Taken together, our results suggest that IDL6‐HAE/HSL2 facilitates the ingress of Pst DC3000 by promoting pectin degradation in Arabidopsis leaves, and Pst DC3000 might enhance its infection by manipulating the IDL6‐HAE/HSL2‐ADPG2 signaling pathway. Significance Statement During floral abscission a peptide ligand (IDA) and receptor kinases HAESA and HAESA‐LIKE2 act together to promote the activity of cell wall degrading enzymes. Here we show that expression of an IDA‐like peptide, IDL6, is increased upon bacterial pathogen infection and that expression of cell wall degrading enzymes is consequently increased, thus facilitating pathogen entry.
Activation of the ATR Pathway by Human Immunodeficiency Virus Type 1 Vpr Involves Its Direct Binding to Chromatin In Vivo

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) protein Vpr (viral protein R) arrests cells in the G2 phase of the cell cycle, a process that requires activation of the ATR (ataxia-telangiectasia and Rad3-related) pathway. In this study we demonstrate that the expression of Vpr does not cause DNA double-strand breaks but rather induces ATR activation, as indicated by induction of Chk1 phosphorylation and the formation of γ-H2AX and 53BP1 nuclear foci. We define a C-terminal domain containing repeated H(F/S)RIG sequences required for Vpr-induced activation of ATR. Further investigation of the mechanism by which Vpr activates the ATR pathway reveals an increase in chromatin binding of replication protein A (RPA) upon Vpr expression. Immunostaining shows that RPA localizes to nuclear foci in Vpr-expressing cells. Furthermore, we demonstrate direct binding of Vpr to chromatin in vivo, whereas Vpr C-terminal domain mutants lose this chromatin-binding activity. These data support a mechanism whereby HIV-1 Vpr induces ATR activation by targeting the host cell DNA and probably interfering with normal DNA replication.
Alterations in Topoisomerase IV and DNA Gyrase in Quinolone-Resistant Mutants of Mycoplasma hominis Obtained In Vitro

ABSTRACT Mycoplasma hominis mutants were selected stepwise for resistance to ofloxacin and sparfloxacin, and their gyrA,gyrB, parC, and parE quinolone resistance-determining regions were characterized. For ofloxacin, four rounds of selection yielded six first-, six second-, five third-, and two fourth-step mutants. The first-step mutants harbored a single Asp426→Asn substitution in ParE. GyrA changes (Ser83→Leu or Trp) were found only from the third round of selection. With sparfloxacin, three rounds of selection generated 4 first-, 7 second-, and 10 third-step mutants. In contrast to ofloxacin resistance, GyrA mutations (Ser83→Leu or Ser84→Trp) were detected in the first-step mutants prior to ParC changes (Glu84→Lys), which appeared only after the second round of selection. Further analysis of eight multistep-selected mutants of M. hominis that were previously described (2) revealed that they carried mutations in ParE (Asp426→Asn), GyrA (Ser83→Leu) and ParE (Asp426→Asn), GyrA (Ser83→Leu) and ParC (Ser80→Ile), or ParC (Ser80→Ile) alone, depending on the fluoroquinolone used for selection, i.e., ciprofloxacin, norfloxacin, ofloxacin, or pefloxacin, respectively. These data indicate that in M. hominis DNA gyrase is the primary target of sparfloxacin whereas topoisomerase IV is the primary target of pefloxacin, ofloxacin, and ciprofloxacin.
SAMPLING AND COUNTING 3-ORIENTATIONS OF PLANAR

Given a planar triangulation, a 3-orientation is an orientation of the internal edges so all internal vertices have out-degree three. Each 3-orientation gives rise to a unique edge coloring known as a Schnyder wood that has proven powerful for various computing and combinatorics applications. We consider natural Markov chains for sampling uniformly from the set of 3-orientations. First, we study a “triangle-reversing” chain on the space of 3-orientations of a fixed triangulation that reverses the orientation of the edges around a triangle in each move. We show that, when restricted to planar triangulations of maximum degree six, this Markov chain is rapidly mixing and we can approximately count 3-orientations. Next, we construct a triangulation with high degree on which this Markov chain mixes slowly. Finally, we consider an “edge-flipping” chain on the larger state space consisting of 3-orientations of all planar triangulations on a fixed number of vertices. We prove that this chain is always rapidly mixing.
New insights on hereditary erythrocyte membrane defects

After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances. New proteins involved in alterations of the red blood cell membrane permeability were recently described. The mechanoreceptor PIEZO1 is the largest ion channel identified to date, the fundamental regulator of erythrocyte volume homeostasis. Missense, gain-of-function mutations in the PIEZO1 gene have been identified in several families as causative of dehydrated hereditary stomatocytosis or xerocytosis. Similarly, the KCNN4 gene, codifying the so called Gardos channel, has been recently identified as a second causative gene of hereditary xerocytosis. Finally, ABCB6 missense mutations were identified in different pedigrees of familial pseudohyperkalemia. New genomic technologies have improved the quality and reduced the time of diagnosis of these diseases. Moreover, they are essential for the identification of the new causative genes. However, many questions remain to solve, and are currently objects of intensive studies.
INTEGRATION OF BACILLUS THURINGIENSIS H-14 FORMULATIONS AND PYRIPROXYFEN FOR THE CONTROL OF LARVAE OF AEDES AEGYPTI AND AEDES ALBOPICTUS

ABSTRACT Studies were carried out on the bioefficacy and residual activity of Bacillus thuringiensis israelensis H-14 (Bti) (water-dispersible granules of VectoBac ABG 6511 and liquid formulations of VectoBac 12AS) and pyriproxyfen (insect growth regulator, Sumilarv 0.5%) as direct applications for control of larvae of Aedes aegypti and Aedes albopictus. Two dosages of each Bti formulation (285 and 570 international toxic units [ITU]/liter) and the integration of both Bti formulations and pyriproxyfen were used for residual tests with 45-liter earthen jars for a period of 4 wk. In 1 test series, the treated water was replenished daily with 6 liters of seasoned untreated water. In the 2nd test series, the water in the jars was topped up to the 40-liter level during evaluation. Neither Bti formulation remained effective for a full week. Water-dispersible Bti granules provided effective initial control activity against Ae. aegypti and Ae. albopictus for both test designs (with replenishment and without replenishment of water). The higher dosage (570 ITU/liter) for both Bti formulations was only partially effective at the end of 1 wk after being diluted. After 1 wk, water-dispersible Bti granules provided greater larval mortality than did liquid Bti formulation against both mosquito species when integrated with pyriproxyfen. Pyriproxyfen (79.5 and 159 mg/liter) on its own showed low larvicidal activity but provided very effective control of adult emergence. In this study, integration of Bti (285 and 570 ITU/liter) with pyriproxyfen (79.5 mg/liter) extended the duration of partial larval control somewhat, but live larvae persisted throughout the 4-wk test. The integration effect was more obvious when water-dispersible Bti granules were integrated with pyriproxyfen than when liquid Bti was used. Integration of Bti with pyriproxyfen had a negative effect on adult emergence, which was completely inhibited by pyriproxyfen after day 1. Daily replenishment of water increased Bti activity and provided slightly better larval control. Aedes albopictus and Ae. aegypti were both completely susceptible to the higher concentration of Bti and pyriproxyfen in both test designs (with replenishment and without replenishment of water).
Ubiquitin-dependent Proteolytic Control of SUMO Conjugates*

Posttranslational protein modification with small ubiquitin-related modifier (SUMO) is an important regulatory mechanism implicated in many cellular processes, including several of biomedical relevance. We report that inhibition of the proteasome leads to accumulation of proteins that are simultaneously conjugated to both SUMO and ubiquitin in yeast and in human cells. A similar accumulation of such conjugates was detected in Saccharomyces cerevisiae ubc4 ubc5 cells as well as in mutants lacking two RING finger proteins, Ris1 and Hex3/Slx5-Slx8, that bind to SUMO as well as to the ubiquitin-conjugating enzyme Ubc4. In vitro, Hex3-Slx8 complexes promote Ubc4-dependent ubiquitylation. Together these data identify a previously unrecognized pathway that mediates the proteolytic down-regulation of sumoylated proteins. Formation of substrate-linked SUMO chains promotes targeting of SUMO-modified substrates for ubiquitin-mediated proteolysis. Genetic and biochemical evidence indicates that SUMO conjugation can ultimately lead to inactivation of sumoylated substrates by polysumoylation and/or ubiquitin-dependent degradation. Simultaneous inhibition of both mechanisms leads to severe phenotypic defects.
Longitudinal study of CD4+ cell counts in HIV-negative pregnant patients

Objective. To evaluate the absolute CD4+, CD8+, and lymphocyte cell counts and percentages from the first trimester through 6–12 weeks post-delivery in normal human immunodeficiency virus (HIV)-negative pregnant patients. Methods. A longitudinal laboratory analysis was performed during pregnancy that involved 51 HIV-negative subjects with blood analysis obtained in all trimesters, at delivery, and 6–12 weeks post-delivery. Twenty-five HIV-negative non-pregnant controls were also evaluated. Blood was analysed for absolute CD4+, CD8+, and lymphocyte cell counts and percentages. Means, standard deviations, trends, and differences were examined. Results. The mean white blood cell (WBC) count is elevated above the non-pregnant state and this parameter increases through the pregnancy up to and including parturition. The mean absolute lymphocyte cell count, lymphocyte percentage, and absolute CD4+ cell count are significantly lower during pregnancy and the progression through pregnancy appears U-shaped. The mean absolute CD8+ cell count is not significantly different. The CD4+ and CD8+ percentages are higher during pregnancy and this elevation persists into the 6–12 week post-delivery time period. A 3-digit drop in CD4+ percentage is common during pregnancy between blood draws; whereas, a 30% decrease or more in absolute CD4+ cell count is rare. Conclusions. By longitudinal analysis, pregnancy appears to significantly elevate the mean values of the WBC count, CD4+ percentage, and CD8+ percentage, but significantly decreases the absolute lymphocyte count, lymphocyte percentage, and absolute CD4+ cell count when compared to non-pregnant controls. The mean absolute CD8+ cell count appears to be unaffected.
Comparison of different aminoglycoside antibiotic treatments to refine ototoxicity studies in adult mice

Hearing and balance receptors in the inner ear are highly susceptible to damage caused by a wide variety of toxic substances, including aminoglycosides. This class of antibiotics is commonly used in medicine, even though they may produce irreversible bilateral neurosensorial deafness. To identify potential ototoxic agents and novel therapeutic targets, it is necessary to generate standardized animal models of aminoglycoside ototoxicity, which will also serve to explore otic cell repair and regeneration. Although the mouse is the species most often used in biomedical research, due to the genetic information and genetically-modified strains available, there are few standard models of aminoglycoside ototoxicity in adult mice. Most protocols to produce ototoxicity in adult mice employ high doses of aminoglycosides for long periods of time, which causes systemic toxicity, side-effects and high mortality rates. Here, we compare the effects of systemic treatment with four different, yet common, aminoglycoside antibiotics in two mouse strains, evaluating their effects on mortality, cochlear morphology and auditory brainstem responses. Our data indicate that gentamicin and neomycin caused high mortality in the adult mouse without significantly changing the auditory threshold. Amikacin produced a tolerable rate of mortality but at doses that did not exhibit ototoxicity. Finally, intramuscular injection of kanamycin in C57BL/6JOlaHsd mice induced significant dose-dependent bilateral hearing loss with a moderate rate of mortality and less discomfort than following subcutaneous administration.
Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer

BACKGROUND. Long-term thyroid hormone (TH) therapy aiming at the suppression of serum thyrotropin (TSH) has been traditionally used in the management of well differentiated thyroid cancer (ThyrCa). However, formal validation of the effects of thyroid hormone suppression therapy (THST) through randomized controlled trials is lacking. Additionally, the role--if any--of TSH effect at low ambient concentrations upon human thyroid tumorigenesis remains unclear. AIM: Evaluation of the effect of THST on the clinical outcomes of papillary and/or follicular ThyrCa. METHODS. By using a quantitative research synthesis approach in a cumulative ThyrCa cohort, we evaluated the effect of THST on the likelihood of major adverse clinical events (disease progression/recurrence and death). A total of 28 clinical trials published during the period 1934-2001 were identified; only 10 were amenable to meta-analysis. Causality was assessed by Hill criteria. RESULTS: Out of 4, 174 patients with ThyrCa, 2, 880 (69%) were reported as being on THST. Meta-analysis showed that the group of patients who received THST had a decreased risk of major adverse clinical events (RR = 0.73; CI = 0.60-0.88; P < 0.05). Further, by applying a Likert scale, 15/17 interpretable studies showed either a 'likely' or 'questionable' beneficial effect of THST. Assessment of causality between TSHT and reduction of major adverse clinical events suggested a probable association. CONCLUSIONS: THST appears justified in ThyrCa patients following initial therapy. As most primary studies were imperfect, future research will better define the effect of THST upon ThyrCa clinical outcomes.
Political Involvement in the Later Years: A Longitudinal Survey

Three main perspectives have been developed about the political involvement of aging citizens. Disengagement theory suggests declining participation; selective withdrawal points toward ageappropriate emphases, including augmentation; and cohort composition theory posits lower participation among the old as a consequence of their having fewer political resources. These perspectives were explored using a three-wave, 17-year panel study of American adults who aged, on average, from 53 to 70 during the study period. With cohort deprivation ruled out by the panel design and period effects controlled for statistically, effects of aging on participation remained. Although the more passive forms of political involvement remained rather steady, participation in the more demanding modes declined following the transition to old age. Those declines were partly offset by increased involvement of the elderly in age-appropriate activities that can have direct political consequences.
Post‐mortem findings in 10 patients with presumed normal‐pressure hydrocephalus and review of the literature

V. Leinonen, A. M. Koivisto, S. Savolainen, J. Rummukainen, A. Sutela, R. Vanninen, J. E. Jääskeläinen, H. Soininen and I. Alafuzoff (2012) Neuropathology and Applied Neurobiology38, 72–86