Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of Protein Kinase A and A Kinase Anchoring Protein in the Progesterone-Initiated Human Sperm Acrosome Reaction1

Abstract The signal transduction pathways involved in the progesterone (P4)-initiated mammalian sperm acrosome reaction (AR) are not fully understood. To investigate the role of the protein kinase A (PKA) pathway in the P4-initiated AR, we probed this pathway by pretreating capacitated human sperm with reagents designed to either inhibit PKA activation or disrupt PKA/A kinase anchoring protein (AKAP) interactions. Preincubation with the stearated (membrane permeable) PKA inhibitor, PKI α 5-24 (S-PKI α 5-24), significantly inhibited the P4-initiated AR at 10 μM as compared to stearated control peptide. In contrast, preincubation with 100 μM nonstearated PKI α 5-24 did not significantly inhibit versus solvent control. Preincubation with the PKA inhibitor Rp-8-Br-cAMP at 500 μM and 150 μM significantly inhibited the P4-initiated AR versus 8-Br-cAMP and versus solvent. Preincubation with the anchoring inhibitory peptide S-Ht-31 significantly stimulated the P4-initiated AR at 10, 3, and 1 μM versus inactive control peptide. The stimulation of the P4-initiated AR by 3 μM S-Ht31 was significantly inhibited by the addition of 30 μM S-PKI α 5-24 prior to the addition of S-Ht31. Preincubation with S-PKI α 5-24 (30 μM) partially inhibited the ionomycin (50 μM)-initiated AR. A role for PKA in the P4-initiated AR may exist both upstream and downstream of Ca2+ entry. Our studies present the first evidence for the participation of PKA in the P4-initiated AR and also suggest that AKAPs are involved in the PKA-mediated events.
P‐Selectin‐Dependent Monocyte Recruitment Through Platelet Interaction in Intestinal Microvessels of LPS‐Treated Mice

Background: Although platelets or monocytes are thought to be involved in intestinal inflammation, there has been no report on whether platelets can modulate monocyte recruitment in intestinal microvessels. The objective of this study was to determine whether blockade of platelet adhesion attenuates monocyte recruitment in inflamed murine intestinal microvessels. Methods: Monocytes and platelet‐rich plasma were obtained from C57B6/J mice. Interaction of monocytes and platelets with intestinal microvessels was observed under an intravital microscope. Lipopolysaccharide (LPS) was administered intraperitoneally. The effects of anti‐P‐selectin or anti‐platelets antibody treatments or phosphodiesterase (PDE) inhibitors (PDE‐3 and PDE‐2/4 inhibitor) treatments were also studied. Results: LPS‐treatment increased the rolling and adhesion of both platelets and monocytes. Pretreatment with an anti‐P‐selectin antibody inhibited the increased platelet adhesion to venular walls and also attenuated the monocyte adhesion. A PDE‐2/4 inhibitor (ibuzilast) also ameliorated both platelet and monocyte adhesion. A PDE‐3 inhibitor (cilostazol) ameliorated only monocyte adhesion without directly affecting the adhesion of platelets to microvessels. Conclusions: We observed inhibition of platelets adhesion attenuated monocytes recruitment in intestinal microvessels. Attenuation of LPS induced monocyte adhesion by a specific PDE‐3 inhibitor suggests that P‐selectin on activated platelets may play an important role through monocyte and platelet interaction.
Remission in Patients with Crohn's Disease is Associated with Improvement in Employment and Quality of Life and a Decrease in Hospitalizations and Surgeries

OBJECTIVES:Hospitalization, surgery, work loss, and impaired quality of life contribute to the cost and burden of care for patients with Crohn's disease. We examined the impact of remission on patients' employment, quality of life, and hospitalization and surgery in a clinical trial to validate clinical remission, as defined by the Crohn's disease activity index (CDAI), as the key treatment goal in managing Crohn's disease.METHODS:ACCENT I evaluated the efficacy and safety of long-term dosing of infliximab compared to a single dose of infliximab in 573 patients with moderately-to-severely active Crohn's disease. At wk 54, employment status was compared between patients in CDAI remission and those not in CDAI remission, for those not employed at baseline. Physical component summary (PCS) and mental component summary (MCS) scores of the SF-36 questionnaire were also compared between these two groups. The numbers of Crohn's-related hospitalizations and surgeries were compared among four groups of patients who spent 0–25%, 25–50%, 50–75%, and 75–100% of time, respectively, in CDAI remission during the study.RESULTS:At baseline, patients had a severely impaired quality of life and a high unemployment rate (38.4%). Among the group of patients who were unemployed at baseline, 31% of those patients who achieved CDAI remission (CDAI < 150) at wk 54 were employed, compared to 16% who were not in CDAI remission at wk 54 (p < 0.05). PCS and MCS scores of patients in CDAI remission at wk 54 were significantly higher (p < 0.0001), indicating better mental and physical functioning, than those of patients not in CDAI remission at wk 54, and were similar to those of the general U.S. population. Hospitalization and surgery rates decreased as the percentage of time patients were in CDAI remission increased (p < 0.01 and p < 0.05, respectively). CONCLUSIONS:CDAI remission is associated with reduced hospitalizations and surgeries, increased employment, and normalized quality of life. Sustained CDAI remission should be the key therapeutic goal in managing Crohn's disease.
Survival implications of sudden functional decline as a sentinel event using the palliative performance scale.

BACKGROUND This retrospective study analyzed sudden functional decline using the Palliative Performance Scale (PPSv2) for patients recently admitted to a palliative care unit (PCU) to determine if this adversely affects survival. There were 3328 patients in the cohort over a 13-year period admitted to a tertiary palliative care bed (71.1%) or a residential hospice bed (28.9%). Patient age ranged from 17-102 years old with 51.9% female and 48.1% male; the majority (88.3%) had a cancer diagnosis. RESULTS Given several limitations noted in the study, six preliminary findings emerged: (1) The lower the initial PPS at PCU admission, the higher the likelihood of an abrupt drop occurring shortly after admission; (2) An abrupt decline in function appears to be associated with smaller survival probabilities; (3) A greater increment change in PPS may be associated with shorter survival probabilities; (4) The lower the PPS on admission, the shorter the survival; (5) When dropping a specific increment amount, the new survival projection appears similar to the PPS level dropped to; and (6) Sudden or abrupt functional decline may be a sentinel event. CONCLUSIONS The data provide evidence that abrupt functional decline implies the likelihood of shorter survival in palliative care patients and may act as a sentinel marker. It is unclear whether these findings would be generalizable outside of a PCU. These results should be interpreted with caution as a prospective evaluation is needed to confirm the results. If substantiated, it may be that incorporating sudden functional decline into palliative prognostic models may increase their predictive accuracy.
IL-12 Decreases Activation-Induced Cell Death in Human Naive Th Cells Costimulated by Intercellular Adhesion Molecule-1. I. IL-12 Alters Caspase Processing and Inhibits Enzyme Function1

Th cells can receive costimulatory signals through the LFA-1/ICAM-1 accessory pathway that are sufficient to induce early Th cell proliferation, but not subsequent cell expansion and maintenance of cell viability. To investigate the regulatory role for IL-12 in ICAM-1-mediated costimulation, human naive Th cells were stimulated with coimmobilized anti-CD3 mAb and ICAM-1 Ig in the presence or absence of IL-12. The ICAM-1-mediated costimulatory signals in this model resulted in early Th cell proliferation followed by cell death that was partially mediated by Fas and involved loss of mitochondrial membrane potential, processing of procaspase-9 and -3, and activation of caspase-3. Addition of IL-12 prevented activation-induced cell death and promoted late proliferation. ICAM-1 + IL-12-costimulated Th cells were resistant to Fas-mediated cell death through a mechanism that did not appear to involve a decrease in either Fas or Fas ligand expression. IL-12 did not inhibit the loss of mitochondrial membrane potential induced by ICAM-1-mediated costimulation, and this finding was consistent with the inability of IL-12 to increase expression of the antiapoptotic Bcl-2 family members, Bcl-2 and Bcl-xL. Interestingly, IL-12 promoted an altered processing of procaspase-9 and -3 and a decrease in the percentage of cells displaying caspase-3 catalytic function. In conclusion, we now describe a novel regulatory function for IL-12 in preventing Th cell death and, as a result, in greatly increasing Th cell viability and expansion. Together, our findings indicate that IL-12 may perform this regulatory role by preventing Fas-mediated activation-induced cell death through inhibition of caspase-3 enzyme activity.
Reducing the Global Burden of Cardiovascular Disease, Part 2: Prevention and Treatment of Cardiovascular Disease

In this second part of a 2-part series on the global burden of cardiovascular disease, we review the proven, effective approaches to the prevention and treatment of cardiovascular disease. We specifically review the management of acute cardiovascular diseases, including acute coronary syndromes and stroke; the care of cardiovascular disease in the ambulatory setting, including medical strategies for vascular disease, atrial fibrillation, and heart failure; surgical strategies for arterial revascularization, rheumatic and other valvular heart disease, and symptomatic bradyarrhythmia; and approaches to the prevention of cardiovascular disease, including lifestyle factors, blood pressure control, cholesterol-lowering, antithrombotic therapy, and fixed-dose combination therapy. We also discuss cardiovascular disease prevention in diabetes mellitus; digital health interventions; the importance of socioeconomic status and universal health coverage. We review building capacity for conduction cardiovascular intervention through strengthening healthcare systems, priority setting, and the role of cost effectiveness.
Modelling the effectiveness of a natural antimicrobial on Salmonella enteritidis as a function of concentration, temperature and pH, using conductance measurements

The growth of Salmonella enteritidis in a brain heart infusion medium was monitored using the traditional viable count method and by conductance measurements using a Rabit impedance instrument. Growth curves (log10 cfu ml−1vs time) at three different concentrations of oleuropein (0, 0·2 and 0·8%), pH values in the range of 5–8 and incubation temperatures from 22 to 42 °C were modelled using the Gompertz equation. A good correlation between the maximum growth rate from the viable count method and the maximum slope of the conductance curve from the impedance instrument was established. Based on this correlation, the maximum specific growth rate of Salm. enteritidis was modelled as a function of the oleuropein concentration, initial pH values and the incubation temperature with a quadratic equation, using a new, larger dataset of growth measurements by conductance. The developed model was validated by statistical comparison of predicted growth rates with growth rates determined by the viable count method, within the limits of the antimicrobial, pH and temperature domain.
Allometry of thermal variables in mammals: consequences of body size and phylogeny

A large number of analyses have examined how basal metabolic rate (BMR) is affected by body mass in mammals. By contrast, the critical ambient temperatures that define the thermo‐neutral zone (TNZ), in which BMR is measured, have received much less attention. We provide the first phylogenetic analyses on scaling of lower and upper critical temperatures and the breadth of the TNZ in 204 mammal species from diverse orders. The phylogenetic signal of thermal variables was strong for all variables analysed. Most allometric relationships between thermal variables and body mass were significant and regressions using phylogenetic analyses fitted the data better than conventional regressions. Allometric exponents for all mammals were 0.19 for the lower critical temperature (expressed as body temperature ‐ lower critical temperature), −0.027 for the upper critical temperature, and 0.17 for the breadth of TNZ. The small exponents for the breadth of the TNZ compared to the large exponents for BMR suggest that BMR per se affects the influence of body mass on TNZ only marginally. However, the breadth of the TNZ is also related to the apparent thermal conductance and it is therefore possible that BMR at different body masses is a function of both the heat exchange in the TNZ and that encountered below and above the TNZ to permit effective homeothermic thermoregulation.
Methicillin-resistant Staphylococcus aureus: colonization and infection in a long-term care facility.

OBJECTIVE To assess methicillin-resistant Staphylococcus aureus (MRSA) colonization, transmission, and infection over a 1-year period in a long-term care facility with endemic MRSA. DESIGN Monthly surveillance for MRSA colonization of nares, perineum, rectum, and wounds. SETTING Long-term care facility attached to an acute care Veterans Affairs medical center. PATIENTS All 341 patients in the facility had monthly surveillance cultures for 1 year. OUTCOME MEASUREMENTS Colonization and infection with MRSA. MAIN RESULTS The monthly MRSA colonization rate was 23% +/- 1.0%; colonization occurred most commonly in the nares and wounds. Poor functional status was associated with MRSA colonization. Most patients (65%) never acquired MRSA; 25% of patients were already colonized at admission to the facility or at the start of the study, and only 10% of newly admitted patients acquired MRSA while in the facility. These latter patients acquired several different strains in a pattern of acquisition similar to that generally seen within the facility. In the course of 1 year, only nine patients who acquired MRSA had a roommate with the same phage type; no clustering was evident, and none of these patients developed infection. Nine other patients (3%) developed MRSA infection; five of these patients required hospitalization, but none died as a result of infection. CONCLUSIONS In the long-term care facility in which our study took place, MRSA was endemic, and the infection rate was low. In such settings, the cost effectiveness of aggressive management of MRSA (widespread screening for MRSA and eradication with antimicrobial agents) needs to be assessed.
Enzyme-Linked Immunosorbent Assay

We developed an antigen capture enzyme-linked immunosorbent assay (ELISA) which does not require purified protective antigen (PA) for detection of human antibodies to Bacillus anthracis PA. Lysates of Spodoptera frugiperda (Sf-9) cells infected with recombinant baculovirus containing the PA gene were used as the source of PA to develop the ELISA. Recombinant PA from crude Sf-9 cell lysates or PA purified from B. anthracis Sterne strain was captured by an anti-PA monoclonal antibody coated onto microtiter plates. We demonstrated that human serum antibody titers to PA were identical in the ELISA whether we used crude Sf-9 cell lysates containing recombinant baculovirus-expressed PA or purified Sterne PA. Finally, false-positive results observed in a direct ELISA were eliminated with this antigen capture ELISA. Thus, the antigen capture ELISA with crude preparations of baculovirus-expressed PA is reliable, safe, and inexpensive for determining anti-PA antibody levels in human sera.
STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation.

OBJECTIVE Older people experience more concurrent illnesses, are prescribed more medications and suffer more adverse drug events than younger people. Many drugs predispose older people to adverse events such as falls and cognitive impairment, thus increasing morbidity and health resource utilization. At the same time, older people are often denied potentially beneficial, clinically indicated medications without a valid reason. We aimed to validate a new screening tool of older persons' prescriptions incorporating criteria for potentially inappropriate drugs called STOPP (Screening Tool of Older Persons' Prescriptions) and criteria for potentially appropriate, indicated drugs called START (Screening Tool to Alert doctors to Right, i.e. appropriate, indicated Treatment). METHODS A Delphi consensus technique was used to establish the content validity of STOPP/START. An 18-member expert panel from academic centers in Ireland and the United Kingdom completed two rounds of the Delphi process by mail survey. Inter-rater reliability was assessed by determining the kappa-statistic for measure of agreement on 100 data-sets. RESULTS STOPP is comprised of 65 clinically significant criteria for potentially inappropriate prescribing in older people. Each criterion is accompanied by a concise explanation as to why the prescribing practice is potentially inappropriate. START consists of 22 evidence-based prescribing indicators for commonly encountered diseases in older people. Inter-rater reliability is favorable with a kappa-coefficient of 0.75 for STOPP and 0.68 for START. CONCLUSION STOPP/START is a valid, reliable and comprehensive screening tool that enables the prescribing physician to appraise an older patient's prescription drugs in the context of his/her concurrent diagnoses.
Aquaporins from pathogenic protozoan parasites: structure, function and potential for chemotherapy

Infectious diseases, caused by protozoa, such as malaria, sleeping sickness, Chagas' disease or leishmaniasis, are a global threat. The increase in the number of affected individuals and the rapid spread of drug‐resistant strains call for specific novel strategies to combat human pathogenic parasites. In the search for novel drug targets, transport proteins for nutrients and metabolites of the parasite—host interface are getting into focus. The present review summarizes and discusses the currently available results on protozoan aquaporins. Various genes coding for aquaporin water and solute channels have been identified in the protozoan genomes and they are probable elements of the parasite's cell membrane. Phylogenetic analysis reveals that individual aquaporin genes are of bacterial or plant origin. So far, six protozoan aquaporins have been cloned and functionally characterized. Typically, these are bifunctional channels and pass water at intermediate to high rates as well as uncharged solutes. In the present review, amino acid compositions of the individual pore entries are compared and permeability properties are attributed to specific protein features. Furthermore, possible physiological roles in osmotic protection and metabolism are discussed. Finally, the potential of protozoan aquaporins for use as a target or entry pathway for chemotherapeutic compounds is reviewed.
Outcome of Noncatheter-Related Thrombosis in Children: Influence of Underlying or Coexisting Factors

Purpose To determine the hereditary and nonhereditary risk factors contributing to the development of noncatheter-related thrombosis in children. Patients and Methods Ninety-five children with noncatheter-related thrombosis from a single center were analyzed for clinical manifestations and outcome during a period of 3.5 years. Patients with thrombosis were evaluated for congenital and acquired risk factors, and patients were screened for factor V Leiden, prothrombin 20210A mutations, protein C, protein S, antithrombin III deficiencies, and antiphospholipid antibodies. Results Twelve patients (12.5%) died of thrombosis that was associated with a nonmalignant underlying disorder, and 19 patients (20%) had significant complications, including amputation of extremities, epilepsy, hemiplegia, portal hypertension, recurrence of deep vein thrombosis, and postphlebitic syndrome. Two common mutations (factor V Leiden and prothrombin 20210A) were found in 32.5% of the patients with thrombosis. The most frequent underlying disorder was infection (68%). Ninety-three patients (98%) had one or more risk factors. Conclusions The coexistence of an underlying disorder and the presence of predisposing factors such as infection and the factor V Leiden mutation may cause high rates of death and complications in children with noncatheter-related thrombosis. The results of this study indicate that the underlying disorder and the site of thrombosis determine the rates of death and complications in children with thrombosis.
Predictive value of lymphocytic infiltration and character of invasive margin following total mesorectal excision with sphincter preservation for the high-risk carcinoma of the rectum.

PURPOSE To assess the prognostic significance of clinicopathological factors, especially histological parameters of new Jass classification, following sphincter-sparing total mesorectal excision (TME) for high-risk rectal cancer. MATERIAL AND METHODS Forty-five consecutive patients treated with curative intent in 1998-1999 due to rectal cancer in Dukes stage B and C were studied prospectively. All of them underwent anterior resection with TME technique. Prognostic value was evaluated by the impact on five-year recurrence-free survival (RFS) in uni- and multivariate analysis. Only factors significant in univariate analysis entered the multivariate regression model. P value <0.05 was stated as a significance limit. RESULTS Regarding traditional clinico-pathological factors patient age, tumor site, differentiation grade, mucinous histology and the extent of direct tumor penetration did not significantly affect survival rates. Only the lymph nodes status was associated with prognosis with statistical importance (negative vs positive, RFS: 53.8 +/- 10.0% vs 26.3 +/- 10.4%, respectively). Considering the additional parameters of Jass classification the character of invasive margin of the tumor did not reveal the important predictive value although the lymphocytic tumor infiltration was significantly related to patient outcome (presence vs absence, RFS: 63.6 +/- 15.2% vs 37.5 +/- 8.7%, respectively). In multivariate analysis the only one statistically important and independent predictive parameter was the lymph nodes status. CONCLUSIONS Lymph nodes metastases remain the most important prognostic factor after anterior resection with TME for Dukes B and C rectal cancer. From variables included into Jass classification the absence of lymphocytic infiltration of the tumor can be helpful to identify patients with enhanced risk of oncological relapse.
Biopsychosocial and Spiritual Aspects of Parkinson Disease: An Integrative Review

ABSTRACT The purpose of this study is to systematically examine the scientific literature and report the biopsychosocial and spiritual aspects of persons with Parkinson disease and their adaptation to the disease, to discuss methodological challenges associated with researching this phenomenon, and to propose future research. Synthesis of the literature will reveal the state of the science on the holistic approach to care in persons with Parkinson disease. An exhaustive review of the English language peer-reviewed literature published from January 1961 to July 2011 was conducted utilizing Academic Search Premier, MEDLINE, CINAHL, Psych Articles, Psych Info, PubMed, Wiley InterScience, the Cochrane Center Register for Control Trials, Health and Psychosocial Instruments, and SpringerLink databases. Ninety studies were reviewed. Although numerous medical studies focusing on pharmacological agents for Parkinson disease are reported, there are gaps in the literature on the biopsychosocial, spiritual, and holistic approaches in Parkinson disease care. More research is needed to examine the biopsychosocial and spiritual aspects of persons with Parkinson disease.