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pubmed_103_4981
NZ2114 is a promising candidate for therapeutic application owing to potent activity to gram-positive bacterium such as Streptococcus pneumoniae and Staphylococcus aureus. This work is the first report to describe the in vitro and in vivo antibacterial characteristics of NZ2114 against Streptococcus suis. It exhibited strong antimicrobial activity against S. suis type 2 strains CVCC 606, CVCC 3309, and CVCC 3928 at a low minimal inhibitory concentration (MIC) of 0.03-0.06 μM. The NZ2114 killed over 99.9% of tested S. suis CVCC 606 in Mueller-Hinton medium within 4 h when treated with 4 × MIC. It caused only less than 0.25% hemolytic activity in the concentration of 256 μg/ml. Additionally, NZ2114 exhibited potent in vivo activity to S. suis. All mice were survival when the dosage was low to 0.2 mg/kg. Over 99% of S. suis cells were killed within 4 h in blood, lung, liver and spleen with dosage of 10, 20, and 40 mg/kg in mice peritonitis models and no pathogen were detected after 24 h of treatment. Further, no pathological phenomenon in lung and low level of inflammatory cytokines in blood were detected. These results indicate that NZ2114 has the potential to be a new antimicrobial agent candidate for the clinical treatment of infection caused by S. suis type 2.
10.1186/s13568-017-0347-8
pubmed_1033_2254
Mannostatin and aminocyclopentitetrol analogues with various substitutions at the amino function were synthesized. These compounds were tested as inhibitors of human Golgi and lysosomal alpha-mannosidases. Modification of the amine of mannostatin had only marginal effects, whereas similar modifications of aminocyclopentitetrol led to significantly improved inhibitors. Ab initio calculations and molecular docking studies were employed to rationalize the results. It was found that mannostatin and aminocyclopentitretrol could bind to Golgi alpha-mannosidase II in a similar mode to that of the known inhibitor swainsonine. However, due to the flexibility of the five-membered rings of these compounds, additional low-energy binding modes could be adopted. These binding modes may be relevant for the improved activities of the benzyl-substituted compounds. The thiomethyl moiety of mannostatin was predicted to make favorable hydrophobic interactions with Arg228 and Tyr727 that would possibly account for its greater inhibitory activity.
10.1002/cbic.200300842
pubmed_349_11
OBJECTIVE We aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations. METHODS Patients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features. RESULTS A total of 18 patients (including 5 females) were identified. Six had de novo, 5 had maternally inherited mutations, and 7 had chromosomal disruptions. All females had strongly skewed X-inactivation in favor of the abnormal X-chromosome. Symptoms presented in early childhood with delayed motor development alone or in combination with seizures. Intellectual disability was severe in most and moderate in patients with milder mutations. Males with severe intellectual disability had severe, often intractable, epilepsy and exhibited a particular facial dysmorphism. Patients with mutations in exon 9 affecting the protein's PH domain did not develop epilepsy. CONCLUSIONS ARHGEF9 encodes a crucial neuronal synaptic protein; loss of function of which results in severe intellectual disability, epilepsy, and a particular facial dysmorphism. Loss of only the protein's PH domain function is associated with the absence of epilepsy.
10.1212/NXG.0000000000000148
pubmed_83_23111
MicroRNAs (miRNAs) have played a vital role in the regulation of gene expression and have been considered as potential biomarker candidates for early cancer diagnosis. Rapid and sensitive detection of microRNAs is highly desired. Here, we present a new method to rapidly and sensitively determine microRNAs based on the technology of gold nanoparticle catalyzed silver staining enhancement. The new method involves the sandwich hybridization of a capture probe immobilized on a magnetic bead, a reporter probe assembled on gold nanoparticles and a miRNA target, catalytic silver precipitation by gold nanoparticles, magnetic collection of the enhanced sandwich complex, dissolution of the silver precipitation and stripping detection. Using the proposed method the microRNA-7a assay was successfully carried out in less than 70 min and the detection limit was as low as 15 fM. The proposed biosensor may hold great promise in biological monitoring of microRNAs.
10.1039/d0an01606c
pubmed_1066_19796
OBJECTIVE In this review we will focus on doctor-patient communication as one of the most important modifiable factors which may have a significant impact especially on the important transition between the ambulatory and terminal phases of cancer. BACKGROUND High quality communication about prognosis for cancer patients is a critical component of advance care planning, and it plays a critical role among all the complex factors that affect end of life care decisions. In this review we focus on doctor-patient communication as the most important modifiable factor impacting the transitional period between the ambulatory phase and the terminal phase of cancer. We also discuss how prognostic understanding among advanced cancer patients influences decisions in regard to their cancer care. METHODS We investigated studies that examined advanced cancer patients and prognosis-related communication. CONCLUSIONS We believe that oncologists' skills, experience, and comfort level in managing patients' reactions to negative information is a principal barrier that contributes substantially to the deficit of high-quality prognosis-related communication described in the literature. We also believe that it is useful to categorize oncologists with regard to their ability to engage in high quality communication, and we suggest category-specific strategies to improve oncologists' skills to conduct more effective prognosis related communication with their patients.
10.21037/apm-21-142
pubmed_269_25949
Developing articular cartilage substitutes required a combination of high compressive strength, excellent biocompatibility and low friction. Despite great success in tough hydrogels, this combination was hardly realized. Herein, a high strength, low friction, and biocompatible hydrogel was obtained by freezing-thawing polyvinyl alcohol and chitosan aqueous solutions three times, followed with soaking in sodium alginate aqueous solution. Owing to the synergy of crystalline domains, hydrogen bonds, and ionic interactions, the obtained hydrogel exhibited high strength (maximum compressive strength = 141 MPa). Because of the reversible linkages, the gel was also creep-resistant (recovery efficiency = 93%). Benefitted from the negative carboxyl groups from sodium alginate, the water lubrication layer between the gel and the opposing surface was thickened greatly, resulting in a low coefficient of friction (0.044). The biocompatible materials and green progress led to excellent cell compatibility. All these merits made it an ideal substitute for articular cartilage.
10.1016/j.carbpol.2022.119268
pubmed_305_16284
BACKGROUND Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION NCT02614534 ( clinicaltrial.gov ) Nov-2015.
10.1186/s12885-018-4096-0
pubmed_1100_21132
The structure of Scientific Research Institute of Hygiene and Occupational Health includes the attributes of integrated principles installed by S.D. Zaugolnikov in 60-70s and conforms to the tasks of the integrated approach to investigations. The investigations in main fields as toxicology, hygiene and occupational pathology are carried out in conjunction with the auxiliary subdivisions such as laboratories of mathematical and physical modeling, ecology, pathomorphology ets.
pubmed_1100_21132
pubmed_768_11494
We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct. A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor. Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas, accompanied with severe dilatation of the main pancreatic duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We performed distal pancreatectomy and splenectomy. The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant cell type) and adenocarcinoma in the pancreas. There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery. In this case, we could observe a remarkable intraductal tumor growth into the main pancreatic duct. We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth.
10.3748/wjg.v20.i3.852
pubmed_21_2820
We investigated the expression of Src homology 2 domain-containing phosphatase (SHP-2) in laryngeal carcinoma and its clinical significance. Expression of SHP-2 was detected by immunohistochemical staining in normal mucosal tissues and various grades of laryngeal carcinoma. We looked for possible correlations between expression of SHP-2 in laryngeal carcinoma and clinical staging and lymph node metastasis. Immunochemical staining results revealed that the SHP-2 expression was significantly higher (88.24%) in laryngeal carcinoma than in normal mucosal tissue (25%). Additionally, the expression of SHP-2 was significantly correlated with lymph node metastasis, but not with clinical stage and gender of patients with laryngeal carcinoma. Therefore, SHP-2 may be useful as a prognostic marker for laryngeal carcinoma and as a therapeutic target in laryngeal carcinoma treatment.
10.4238/2013.October.7.6
pubmed_183_24870
BACKGROUND/PURPOSE Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations in the DMD gene. We intended to determine the distribution of DMD gene deletions and duplications in local Taiwanese male patients and potential female carriers. METHODS A total of 102 unrelated subjects, including 89 unrelated DMD/BMD male patients and another 13 unrelated potential female carriers, were recruited for this study. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect DMD gene deletions and duplications in the 102 subjects. RESULTS MLPA was informative in 60.7% (54/89) of these patients, identifying deletions in 36.0% (32/89) and duplications in 24.7% (22/89) of these patients. This assay revealed deletions in 30.8% (4/13) and duplications in 30.8% (4/13) of the 13 potential carriers. Deletions and duplications were detected in 35.3% (36/102) and 25.5% (26/102) of a total of 102 affected families, respectively in this series. The "hotspot" regions of the duplications were close to those of the deletions. CONCLUSION MLPA was proven to be a powerful tool for the detection of DMD gene deletions and duplications in male patients and female carriers. There was a relatively lower frequency of deletion and a higher frequency of duplication of DMD gene in this population compared to previous reports.
10.1016/S0929-6646(09)60318-1
pubmed_980_19358
Weaning failure and mortality rates in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supported patients are significant. Small studies suggest the possible usefulness of levosimendan in this environment, especially in postcardiotomy shock. We performed a retrospective analysis of VA-ECMO implants in a referral hospital comparing weaning failure and survival of patients treated with levosimendan with a control group. From 2013 to May 2020, 123 VA-ECMO for several indications were implanted. Levosimendan was administered in 23 patients (18.7%) with good tolerance. Levosimendan was used more frequently in cardiogenic shock due to acute coronary syndrome indication, and in patients with lower left ventricular ejection fraction (LVEF) at the implant. No significant differences were found in success of ECMO weaning (60.9% levosimendan group vs. 44% non-levosimendan group, P = .169) despite worse LVEF in levosimendan group. Survival at follow-up (20.6 [58] months) was higher in the group that received levosimendan, although without finding statistically significant differences (47.8% vs. 32.0%, log rank P = .124). Levosimendan can be safely administered during VA-ECMO support. Patients receiving levosimendan were weaned similarly from circulatory support despite worse LVEF. Its use did not influence in short- and medium-term survival. Randomized studies are needed to evaluate the levosimendan impact in this indication.
10.1111/aor.13899
pubmed_986_8605
1. The effects of neurotransmitter antagonists on spatially linear and non-linear responses of Y cat retinal ganglion cells were studied. 2. The contrast sensitivity of the spatially linear receptive field centre and surround at mesopic and photopic levels of illumination was affected very little by picrotoxin, but the sensitivity of the non-linear subunits was reduced. 3. Picrotoxin also reduced two other non-linear effects: 'shift responses' and the suppression of the response to a centred test flash caused by movement of a peripheral pattern. 4. In contrast to picrotoxin, strychnine decreased the contrast sensitivity of the receptive field centre, and increased the sensitivity of the subunits. 5. The results support the idea that the non-linear responses may all be generated by similar pathways, which are distinct from those which generate linear responses. Because both picrotoxin and strychnine affect subunit responses, cells using gamma-aminobutyric acid (GABA) and glycine as transmitters are probably involved in subunit pathways.
10.1113/jphysiol.1982.sp014116
pubmed_922_9850
In this paper, we construct a piecewise deterministic Markov process to model the membrane voltage fluctuations driven by two ligand-gated channels. The series-solution method is applied to the third-order ordinary differential equations to get its general solutions. Also, the stationary probability density function (PDF) is just the special solution that satisfies certain boundary conditions. The bifurcation conditions of the PDF at the boundary are obtained analytically. As an application, the PDF is used to calculate the power dissipation of the ionic currents in the (nonequilibrium) steady states.
10.1063/1.5096303
pubmed_1061_10588
To address the common challenges in enhanced biological phosphorus removal (EBPR) related to stability and unfavorable influent carbon to phosphorus ratio, a side-stream EBPR (S2EBPR) process that involves a side-stream anaerobic biological sludge hydrolysis and fermentation reactor was proposed as an emerging alternative. In this study, a full-scale pilot testing was performed with side-by-side operation of a conventional anaerobic-anoxic-aerobic (A2O) process versus a S2EBPR process. A comparison of the performance, activity and microbial community between the two configurations was performed. The results demonstrated that, with the same influent wastewater characteristics, S2EBPR configuration showed improved P removal performance and stability than the conventional A2O configuration, especially when the mixers in the side-stream anaerobic reactor were operated intermittently. Mass balance analysis illustrated that both denitrification and EBPR were enhanced in S2EBPR configuration, where return activated sludge was diverted into the anaerobic zone to promote fermentation and enrichment of polyphosphate accumulating organisms (PAOs), and the influent was bypassed to the anoxic zone for enhancing denitrification. A relatively higher PAO activity and total PAO abundance were observed in S2EBPR than in A2O configuration, accompanied by a higher degree of dependence on glycolysis pathway than tricarboxylic acid cycle. No significant difference in the relative abundances of putative PAOs, including Ca. Accumulibacter and Tetrasphaera, were observed between the two configurations. However, higher microbial community diversity indices were observed in S2EBPR configuration than in conventional one. In addition, consistently lower relative abundance of known glycogen accumulating organisms (GAOs) was observed in S2EBPR system. Extended anaerobic retention time and conditions that generate continuous and more complex volatile fatty acids in the side-stream anaerobic reactor of S2EBPR process likely give more competitive advantage for PAOs over GAOs. PAOs exhibited sustained EBPR activity and delayed decay under extended anaerobic condition, likely due to their versatile metabolic pathways depending on the availability and utilization of multiple intracellular polymers. This study provided new insights into the effects of implementing side-stream EBPR configuration on microbial populations, EBPR activity profiles and resulted system performance.
10.1016/j.watres.2019.115109
pubmed_34_18480
AIMS Adopting effective injury prevention practices continues to be problematic within snowboarding and the participation of older individuals is associated with an appreciable injury burden. The Haddon Matrix provides an important framework for developing injury prevention interventions. Since prevention behaviour must 'fit' within individual aspirations, our study investigated the meanings and behaviours associated with snowboarding and injury prevention and then applied the findings to the established Haddon Matrix approach. METHODS Nine, older adult recreational participants living in south-west England each contributed two interviews. These progressively focused on experiences and reflections. Verbatim transcripts were analysed and interpreted using the hermeneutic phenomenological themes of time, space, body and human relations. A further wave of analysis reinterpreted the findings in relation to the Haddon Matrix. FINDINGS Snowboarding was conducted within a holiday when participants were seeking happiness by positively re-evaluating their lives. In a frame of connection-and-disconnection, beginners (time) were concerned with being-on the slopes (body and space), while more experienced (body and time) participants blended this with being-in the mountains (space). Snowboarding is a bumps-and-bruises activity and this guided the limited prevention practices. Importantly, all prevention practices were time-limited, due to a concern for learning-by-doing within a holiday. At home, more experienced boarders paid careful attention to fitness, whereas in the resorts they actively selected the soft, off-piste areas and wore protective clothing to cushion their inevitable falls. Group experiences were associated with heightened injury risks. Being seen and judged by others helped to determine the quality of the snowboarding experience. Treatment was avoided for all but the most severe injuries. CONCLUSION The findings confirm the exploratory value of mixing van Manen's four-dimensional approach with Haddon's well-established injury prevention framework. The diverse subjective meanings associated with snowboarding limit the potential for prevention approaches and suggest that resort-based 'injury control' may be more appropriate for addressing the spectrum of prevention in older snowboarders.
10.1177/1466424007079489
pubmed_1093_16045
Recent studies suggest that neuron-glia interactions are involved in multiple aspects of neuronal activity regulation. In the nucleus tractus solitarius (NTS) neuron-glia interactions are thought to participate in the integration of autonomic responses to physiological challenges. However, it remains to be shown whether NTS glial cells might influence breathing and cardiovascular control, and also if they could be integral to the autonomic and respiratory responses to hypoxic challenges. Here, we investigated whether NTS glia play a tonic role in the modulation of central respiratory and sympathetic activities as well as in the changes in respiratory-sympathetic coupling induced by exposure to chronic intermittent hypoxia (CIH), a model of central autonomic and respiratory plasticity. We show that bilateral microinjections of fluorocitrate (FCt), a glial cell inhibitor, into the caudal and intermediate subnuclei of the NTS did not alter baseline respiratory and sympathetic parameters in in situ preparations of juvenile rats. Similar results were observed in rats previously exposed to CIH. Likewise, CIH-induced changes in respiratory-sympathetic coupling were unaffected by FCt-mediated inhibition. However, microinjection of FCt into the ventral medulla produced changes in respiratory frequency. Our results show that acute glial inhibition in the NTS does not affect baseline respiratory and sympathetic control. Additionally, we conclude that NTS glial cells may not be necessary for the continuous manifestation of sympathetic and respiratory adaptations to CIH. Our work provides evidence that neuron-glia interactions in the NTS do not participate in baseline respiratory and sympathetic control.
pubmed_1093_16045
pubmed_250_9996
The role of adiponectin and epicardial adipose tissue in coronary artery disease (CAD) is a subject of debate. Whether plasma adiponectin concentration in the coronary circulation is locally modulated by the epicardial fat is still unexplored. We evaluated the hypothesis whether intracoronary plasma adiponectin levels are related to adiponectin expression in epicardial adipose tissue in vivo in patients with CAD and without CAD (non-CAD). We examined 12 patients with CAD who required CABG and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adiponectin were measured in peripheral vein circulation and in left coronary artery (LCA) during coronary angiography. Epicardial adipose tissue biopsy for adiponectin protein extraction was performed during cardiac surgery in both CAD and non-CAD subjects. Adiponectin protein expression in epicardial adipose tissue was lower in patients with CAD than in those with non-CAD (0.45+/-0.4 vs. 1.1+/-1.0, p<0.05). LCA plasma adiponectin levels significantly correlated with epicardial adipose tissue adiponectin protein expression (r=0.68, p=0.02) in all subjects. Peripheral adiponectin levels and epicardial fat adiponectin protein expression were the best correlates of LCA adiponectin, r (2)=0.49, p<0.01, p<0.05, respectively). Our study showed that intracoronary adiponectin levels reflect systemic adiponectin levels. Epicardial adipose tissue could partially contribute to adiponectin levels in the coronary circulation.
10.1055/s-0028-1100412
pubmed_354_24105
BACKGROUND Chronic kidney disease (CKD) occurs commonly among HIV-infected persons. Statins may delay CKD onset and progression through their cholesterol-lowering and pleiotropic effects. METHODS Among 850 HIV-infected men from the Multicenter AIDS Cohort Study with stored urine samples (2009-2011), we evaluated cross-sectional associations of statin use with urine biomarkers of kidney damage [albumin-to-creatinine ratio (ACR), alpha-1-microglobulin, interleukin-18, kidney injury molecule-1, and procollagen type III N-terminal propeptide] using multivariable linear regression. We evaluated the longitudinal associations of statin use with annual change in estimated glomerular filtration rate by creatinine (eGFR) using linear mixed models, and with incident proteinuria and incident CKD (eGFR <60 mL/min/1.73 m) using Cox proportional hazards regression. We used inverse probability weighting to address potential confounding related to statin use. RESULTS Statin users comprised 30% of participants. In adjusted analyses, each year of cumulative statin use was associated with 4.0% higher baseline ACR levels (P = 0.05), but there was no association with baseline levels of other urine biomarkers. Statin use had no overall association with annual eGFR decline. Among participants with baseline proteinuria, statin use was modestly associated with slower annual eGFR decline compared to non-use (adjusted difference: 1.33 mL/min/1.73 m per year; 95% confidence interval: -0.07 to 2.70). Statin use was not associated with risk of incident proteinuria or incident CKD. CONCLUSIONS Statin use was associated with higher baseline ACR, but not with biomarkers of tubulointerstitial injury. Statin use was associated with modestly slower eGFR decline only among participants with baseline proteinuria. Although these findings may be susceptible to confounding by indication, they suggest a limited effect of statins on CKD risk among HIV-infected men.
10.1097/QAI.0000000000002122
pubmed_629_3864
Three-dimensional domain patterns can self-assemble in a charged colloidal suspension with competing short-range attraction and long-range Yukawa repulsion. Following the investigation of the ground-state domain shapes in our previous paper, we study the stability of isolated spherical, cylindrical, and lamellar domains with respect to shape fluctuations on boundaries. In the framework of the continuum model, we expand the free energy variation to quadratic terms under the constraint of constant volume. For the three shapes (sphere, cylinder, and lamella) discussed, domains with equilibrium sizes are stable with respect to shape fluctuations, and the stability of domains decreases as the spatial symmetry decreases.
10.1021/jp0524431
pubmed_1073_5407
The functions of soft robotics are intimately tied to their form-channels and voids defined by an elastomeric superstructure that reversibly stores and releases mechanical energy to change shape, grip objects, and achieve complex motions. Here, we demonstrate that covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation in soft robots into a mechanochromic, covalent chemical response. A bis-alkene functionalized spiropyran (SP) mechanophore is cured into a molded poly(dimethylsiloxane) (PDMS) soft robot walker and gripper. The stresses and strains necessary for SP activation are compatible with soft robot function. The color change associated with actuation suggests opportunities for not only new color changing or camouflaging strategies, but also the possibility for simultaneous activation of latent chemistry (e.g., release of small molecules, change in mechanical properties, activation of catalysts, etc.) in soft robots. In addition, mechanochromic stress mapping in a functional robotic device might provide a useful design and optimization tool, revealing spatial and temporal force evolution within the robot in a way that might be coupled to autonomous feedback loops that allow the robot to regulate its own activity. The demonstration motivates the simultaneous development of new combinations of mechanophores, materials, and soft, active devices for enhanced functionality.
10.1021/acsami.5b06440
pubmed_36_5008
The present manuscript focuses on a putative natriuretic hormone. It includes the history of a long-term search for the pure molecule, ranging from partial purification to synthesis. It includes a description of seven different bioassay systems used, a resume of the sequential steps in purification, and a summary of a series of experimental protocols employed in the effort to define the biologic properties of the inhibitor of sodium (Na) transport. Two closely related molecules were purified and synthesized. Both are xanthurenic acid derivatives (xanthurenic acid 8-O-β-D-glucoside and xanthurenic acid 8-O-sulfate). It is concluded that one or both of these two low molecular weight compounds (MW: 368 and 284) meet many of the criteria for the final modulator of Na excretion.
10.3389/fendo.2014.00212
pubmed_1025_11751
Stormwater runoff poses a great challenge to the scientific assessment of the effects of diffuse pollution sources on receiving waters. In this study, a self-organizing map (SOM), a research tool for analyzing specific patterns in a large array of data, was applied to the monitoring data obtained from a stormwater monitoring survey to acquire new insights into stream water quality profiles under different rainfall conditions. The components of the input data vectors used by the SOM included concentrations of 10 metal elements, river discharge, and rainfall amount which were collected at the inlet and endpoint of an urban segment of the Yeongsan River, Korea. From the study, it was found that the SOM displayed significant variability in trace metal concentrations for different monitoring sites and rainfall events, with a greater impact of stormwater runoff on stream water quality at the upstream site than at the downstream site, except under low rainfall conditions (≤ 4 mm). In addition, the SOM clearly determined the water quality characteristics for "non-storm" and "storm" data, where the parameters nickel and arsenic and the parameters chromium, cadmium, and lead played an important role in reflecting the spatial and temporal water quality, respectively. When the SOM was used to examine the efficacy of stormwater quality monitoring programs, between 34 and 64% of the sample size in the current data set was shown to be sufficient for estimating the stormwater pollutant loads. The observed errors were small, generally being below 10, 6, and 20% for load estimation, map resolution, and clustering accuracy, respectively. Thus, the method recommended may be used to minimize monitoring costs if both the efficiency and accuracy are further determined by examining a large existing data set.
10.1016/j.watres.2011.05.021
pubmed_123_10208
A new theoretical approach to elaboration of an information-analytical integrated knowledge base containing data on regulation and function of biological systems is presented. The knowledge base incorporates: (i) a reference database containing experimental data on the structural-functional organization of a biological system; (ii) a dynamic mathematical model for analysis of the evolution of the system over time; and (iii) an interpretation module of simulation results. Application of this approach to theoretical investigation of the interferon system in the case of viral infection is discussed. The approach is specific in that it uses mathematical modeling technology, which allows one to generate mathematical models of different degrees of complexity in the analysis of the diverse aspects of biological system behavior. This approach allows one not only to store and to treat available experimental data, but also to acquire new knowledge about the behavior of a biological system. The proposed approach is implemented as a computer system for the IBM PC and compatibles.
10.1093/bioinformatics/11.2.213
pubmed_450_7695
BACKGROUND Although genu recurvatum during walking is a well-known issue in stroke rehabilitation, there are no reliable epidemiological data on its prevalence. The aim of the study was to investigate the prevalence of genu recurvatum during walking and associated knee pain among ambulatory community-dwelling patients with chronic hemiplegic stroke. METHODS Questionnaires were sent to physical therapists working at 223 adult day care facilities in Chiba Prefecture, Japan. The number of all chronic stroke patients attending the day care who could walk without human assistance, including those who used a walking aid and/or an orthosis; the number of patients with genu recurvatum in the paretic limb during walking; and the number of patients with genu recurvatum who had experienced any knee pain in the last month were investigated. Physical therapists were also asked whether they considered genu recurvatum in stroke patients to be problematic. RESULTS Sixty-four facilities (28.7%) responded, providing data on 1110 ambulatory stroke patients, of whom 217 (19.5%) showed genu recurvatum. Of the patients with genu recurvatum, 25 (11.5%) experienced knee pain in the paretic limb. Of 45 physical therapists who gave an opinion on whether genu recurvatum was problematic, 26 (57.8%) thought it was problematic whereas 19 thought it was not problematic. CONCLUSION Rates of genu recurvatum and associated knee pain were relatively low among ambulatory community-dwelling stroke survivors attending adult day care.
10.1016/j.jstrokecerebrovasdis.2016.01.028
pubmed_188_4846
BACKGROUND Ficus vasta Forssk. (Moraceae) is traditionally used for the treatment of various ailments; nonetheless, this species has been poorly studied to date. This work aimed to characterize the phenolic profile and to evaluate the antioxidant and antimicrobial properties of a hydroalcoholic extract obtained from F. vasta leaves collected in Egypt. METHODS The phenolic profile of the extract was characterized by HPLC-PDA/ESI-MS. The antioxidant properties were examined by different in vitro systems: DPPH test, reducing power and metal chelating activity assays. Moreover, the ability of the extract to protect Escherichia coli growth and survival from H2O2-induced oxidative stress was evaluated. The potential toxicity was investigated using Artemia salina lethality bioassay. Finally, the antimicrobial properties against a representative set of Gram-positive and Gram-negative bacterial strains and the yeast C. albicans were assayed by standard methods. RESULTS By HPLC-PDA/ESI-MS analysis 12 compounds belonging to the groups of phenolic acids and flavonoids were identified. The extract exhibited strong radical scavenging activity in DPPH test (IC50 = 0.0672 ± 0.0038 mg/mL), reducing power (3.65 ± 0.48 ASE/mL) and chelating activity (IC50 = 0.801 ± 0.007 mg/mL). A total protection against H2O2-induced damage on E. coli was observed. No toxicity against A. salina was found (LC50 > 1000 μg/mL). The extract exhibited bacteriostatic activity against almost all the bacteria tested (MICs: 250-62.5 μg/mL). CONCLUSIONS The obtained results demonstrate the potential of F. vasta leaves as safe sources of natural antioxidant and antimicrobial compounds.
10.1186/s12906-018-2210-0
pubmed_218_15804
OBJECTIVE To evaluate staged low-dose approaches for coronary CT angiography (CTA) in which a standard sequence was added if the low-dose sequence did not allow reliable rule-out of coronary stenosis. PATIENTS AND METHODS A total of 176 consecutive patients referred for dual-source CTA were randomized to three protocols: group 1 using prospective ECG-triggering (100 kV, 330 mAs), group 2 a retrospectively gated "MinDose" sequence (100 kV, 330 mAs) and group 3 a standard spiral sequence (120 kV, 400 mAs). If image quality in low-dose groups 1 or 2 was non-diagnostic, an additional standard CT examination (as in group 3) was performed. RESULTS Non-diagnostic image quality was found in 11/56, 4/55, and 2/65 patients (46/896, 4/880 and 3/1,040 coronary segments) in groups 1, 2 and 3, respectively. Median (interquartile ranges) volumes of contrast material, CTDI(vol), DLP and effective dose for low-dose groups 1 and 2 and for standard group 3 were 92.5 (11.3), 75.0 (2.5) and 75.0 (9.0) ml; 8.0 (1.4), 16.8 (4.8) and 48.1 (14.2) mGy; 108.0 (27.3), 246.0 (93.0) and 701.0 (207.8) mGy cm; and 1.5 (0.4), 3.4 (1.3) and 9.8 (2.9) mSv, respectively. CONCLUSION A staged coronary CTA protocol with an initial low-dose approach and addition of a standard sequence--should image quality be too low--can lead to a substantial reduction in radiation exposure.
10.1007/s00330-009-1645-6
pubmed_1032_7979
Rumen cannulation is a widely employed technique in ruminant nutrition research. However, the gap between skin and rumen cannula can cause leakage of fermentation gases and influx of atmospheric air, which may adversely affect the anaerobic environment in the rumen. The present study was designed to investigate the effects of rumen cannulation on headspace gases, dissolved gases, fermentation end products, and methanogen community in the rumen of dairy cows. Eight Holstein cows were used in the experiment. Four cows were surgically fitted with rumen cannulas, whereas the other 4 intact cows were used as control. Rumen cannulation decreased gaseous hydrogen and methane concentrations, dissolved carbon dioxide concentration, and relative abundances of Methanosphaera, and increased the saturation factor of dissolved hydrogen and dissolved methane, dissolved methane concentration, volatile fatty acid concentration, 16S ribosomal RNA gene copies of methanogens, and Simpson index of methanogen community. In summary, rumen cannulation causes a reduction in headspace gaseous hydrogen and gaseous methane, which may not decrease dissolved gas concentrations due to an increase in saturation factors. Furthermore, rumen cannulation alters methanogen community with increased methanogen population and decreased relative abundances of Methanosphaera.
10.3168/jds.2018-15187
pubmed_628_10531
STUDY DESIGN A multisurgeon assessment of curve classification, selection of operative approach, and fusion levels via a case study presentation. OBJECTIVES To evaluate the ability of a group of scoliosis surgeons, not involved in the development of a new classification system, to accurately choose the corresponding curve classification of adolescent idiopathic scoliosis (AIS) cases and to evaluate the variability in the selection of operative approaches and both proximal and distal fusion levels in accordance with the new classification system in operative adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA Recent evaluations using the King method for classifying AIS has shown poor intraobserver and interobserver reliability. A new, comprehensive classification system of AIS has been developed, but the result of a scoliosis surgeon's ability to apply the objective classification is unknown. In the surgical treatment of AIS, there are three choices for the operative approach (anterior, posterior, or both) and multiple choices for the selection of fusion levels. METHODS During an AIS roundtable discussion at a spinal surgery meeting, 28 scoliosis surgeons were presented seven cases of operative AIS via good quality slides. Standard preoperative radiographs and clinical photographs were presented, and the reviewers were asked to classify the cases by a new classification system, choose their preferred surgical approach, and classify both proximal and distal fusion levels. RESULTS For the seven cases presented, 84% of the curve types, 86% of lumbar modifiers, and 90% of sagittal thoracic modifiers were classified by the reviewers as described in the new classification. The case study found widely variable operative approaches and fusion levels chosen by the reviewers. There was an average of five different proximal (range, 4-8) and four different distal (range, 3-5) fusion levels chosen by the reviewers for each case. CONCLUSIONS This case study assessment found a relatively high rate (84-90%) of agreement in curve classification of the individual components of a new classification system of AIS. This suggests the ability of a group of scoliosis surgeons to identify the specific criteria necessary for this new classification system of AIS. In addition, the high variability in selection of both operative approach and fusion levels confirms the current lack of standardized treatment paradigms. This further reinforces the need for a method to critically and objectively evaluate these variable treatments to determine the "best" radiographic and clinical results.
10.1097/00007632-200111010-00011
pubmed_196_10196
Poor recognition of other-race faces is ubiquitous around the world. We resolve a longstanding contradiction in the literature concerning whether interracial social contact improves the other-race effect. For the first time, we measure the age at which contact was experienced. Taking advantage of unusual demographics allowing dissociation of childhood from adult contact, results show sufficient childhood contact eliminated poor other-race recognition altogether (confirming inter-country adoption studies). Critically, however, the developmental window for easy acquisition of other-race faces closed by approximately 12 years of age and social contact as an adult - even over several years and involving many other-race friends - produced no improvement. Theoretically, this pattern of developmental change in plasticity mirrors that found in language, suggesting a shared origin grounded in the functional importance of both skills to social communication. Practically, results imply that, where parents wish to ensure their offspring develop the perceptual skills needed to recognise other-race people easily, childhood experience should be encouraged: just as an English-speaking person who moves to France as a child (but not an adult) can easily become a native speaker of French, we can easily become "native recognisers" of other-race faces via natural social exposure obtained in childhood, but not later.
10.1038/s41598-019-49202-0
pubmed_1115_11966
In this article, we discuss the care of newborns and infants in day nurseries. We approach childcare within an historical perspective, emphasizing the current childhood situation. Based on the present conceptions of care and caring, and the Lei das Diretrizes e Bases da Educaçao Nacional n. 9394/96 (Brazilian Guiding and Bases Law for the National Education no. 9394/96) we discuss the childcarers' qualification for attending children up to two years old in day nurseries. Considering the education level currently held by nursing professionals, we consider them qualified for the role of providing day care. In this sense, we identify the day nursery as an important social and political space for nursing.
pubmed_1115_11966
pubmed_411_6051
BACKGROUND Interferon-gamma (IFN-γ) represents a potent inducer for keratinocyte inflammatory and immune activation in vitro. Since tryptophan (trp) conversion to kynurenine (kyn) is involved in inflammation, the topical kyn/trp ratio may serve as a biomarker of skin inflammation. However, the trp metabolism in keratinocytes exposed to IFN-γ is not yet fully understood. OBJECTIVE The aim of this study was to establish a human epidermis model in order to quantify cytokine and kyn/trp secretion from IFN-γ stimulated cells and tissues. Moreover, to compare the cell response of 2D-cultured keratinocytes and the 3D epidermis model. METHODS Polycarbonate filters were used on which primary keratinocytes could attach and stratify in order to form the typical layers of reconstructed human epidermis (RHE). After IFN-γ treatment, secretion of kyn/trp was measured by high performance liquid chromatography. Gene and protein expression of indoleamine 2,3-dioxygenase 1 (IDO) was analyzed with real-time PCR and immunohistochemistry. The secretion of cytokines was quantified with ELISA. RESULTS Trp catabolism to kyn was significantly increased (P < 0.01) in the 2D culture in response to IFN-γ treatment. Before kyn secretion, IDO was strongly upregulated (P < 0.001). IFN-γ treatment also increased the secretion of IL-6 and IL-8 from the keratinocytes. In the RHE, IDO was upregulated by IFN-γ, and kyn secretion could be detected. Interestingly, IDO expression was only present in the basal cells of the RHE. CONCLUSION Our results suggest that IFN-γ acts as an inducer of trp degradation preferentially in undifferentiated keratinocytes, indicated by the IDO expression in the basal layer of the RHE.
10.1016/j.jdermsci.2020.07.005
pubmed_477_6843
The major extracellular, non-fibrous macromolecules in human gingiva are proteoglycans. These sulphated, uronic acid-containing macromolecules are synthesized in vitro by both gingival epithelium and its underlying connective tissue. Biochemical analyses were carried out on cultured human predominantly gingival epithelium and predominantly connective tissue in media containing appropriate radioactive precursor molecules. The proteoglycans were extracted with salt solutions of varying concentration and characterized by means of column chromatography and liquid scintillation counting. The major differences noted between the macromolecules extracted from these closely apposed regions were molecular size, and the ability or not to form large self-aggregatable macromolecules. In general, the epithelial proteoglycans are larger than connective tissue proteoglycans. Proteoglycans from gingival epithelium are able to self-aggregate to form large macromolecules with mol. wt in excess of 2 X 10(6) which are essential for the maintenance of tissue integrity.
10.1016/0003-9969(82)90169-8
pubmed_85_19949
The addition of the reducing agent tris(2-carboxyethyl) phosphine (TCEP) during the formation of α,ω-alkanedithiols monolayers on Au(111) using the immersion method produces the assembly of monolayers with bicoordinated molecules (both S-terminal groups bound to the surface) that have a reductive desorption potential that is more positive than for monolayers with monocoordinated molecules in a standing up configuration. We show that the use of TCEP either during formation of the monolayer or as a post treatment procedure allows the controlled formation of monolayers with bicoordinated or monocoordinated configurations. Density functional theory (DFT) calculations were performed to elucidate the role of TCEP in the formation of the bicoordinated configuration. We investigated the TCEP-dithiol interaction in ethanol solvent as well as the coadsorption of trimethylphosphine with 1,2-ethanedithiol on Au(111). The Brønsted base character of the phosphine facilitates the H exchange from the -SH groups of the dithiol to the phosphorus atom of TCEP with very low activation energy barriers, thus allowing the thiolate groups to bind to the Au(111) surface, thus yielding the bicoordinated configuration. Dithiol lifting mechanisms such as H exchange between S atoms and the formation of intra/inter layer disulfide bonds have much higher energy barriers.
10.1021/acs.langmuir.6b02079
pubmed_700_5151
Dynamic renal scintigraphy is a successful and minimally invasive technique for evaluating renal function. An extension to the basic technique involving fast-frame acquisition and a modified analysis is described which enables ureteric function to be examined. Ureteric peristalsis was assessed in 32 patients using this technique. The results from 5 representative studies are described in detail. Normally functioning ureters exhibit peristaltic contractions at a frequency of up to 3/min. Hyperperistalsis that exceeds 4 contractions/min is associated with obstruction. Peristaltic behaviour in 9 patients examined before and after ESWL was not altered.
10.1111/j.1464-410x.1989.tb05151.x
pubmed_529_9163
We analyzed reaction threshold data from 352 children undergoing open food challenges to hen's egg or cow's milk, either fresh or extensively heated into a muffin. There was no significant shift in dose-distribution curves due to the baking process, implying that existing threshold data for these allergens can be applied to allergen risk management, even when these allergens are heat-processed into baked foods.
10.1111/all.13198
pubmed_699_22318
BACKGROUND Central venous catheterisation in neonates and infants is challenging because of the small size of the vessels. The curve of the J-tip guidewire causes difficulty when inserting because of the larger radius and the tilted angle of the J-tip. OBJECTIVE We hypothesised that a straight-tip guidewire can facilitate guidewire insertion and improve the first-attempt success rate of central venous catheterisation. DESIGN A randomised controlled study. SETTING This study was performed between September 2018 and July 2021 in tertiary care children's hospital. PATIENTS We enrolled infants weighing less than 5 kg undergoing general anaesthesia. INTERVENTIONS Patients were randomly allocated to the straight-tip or J-tip groups. Ultrasonography-guided catheterisation was performed using the assigned guidewire. MAIN OUTCOME MEASURES The primary outcome was the first-attempt success rate of central venous catheterisation. The secondary outcomes included the number of guidewire insertion attempts, the time required for successful guidewire insertion, and total time for central venous catheter placement. RESULTS Eighty-eight patients were studied. The straight-tip group showed a higher first attempt success rate than the J-tip group (86.3 vs. 61.3%, P  = 0.007, odds ratio 4.0, 95% confidence interval (CI), 1.4 to 11.4]. Guidewire insertion attempts were higher in the J-tip group than in the straight group ( P  = 0.002, odds ratio 9.6, 95% CI, 7.9 to 92.9). Although the guidewire insertion time was longer in the J-tip group ( P  = 0.003, median difference 23.0 s, 95% CI, 7.0 to 48.0), the total catheterisation time was similar owing to the additional guidewire change process in the straight-tip group ( P  = 0.676). CONCLUSION In neonates or infants weighing less than 5 kg, central venous catheterisation using a flexible straight-tip guidewire can improve the first-attempt success rate compared with a J-tip guidewire. TRIAL REGISTRATION ClinicalTrials.gov, identifier: NCT03530618.
10.1097/EJA.0000000000001695
pubmed_275_2147
Drug users in Russia living with HIV/AIDS are often denied basic medical and social services and are systematically excluded from antiretroviral therapy programs. In this presentation to "HIV Treatment for Drug Users--A Realistic Goal," a satellite meeting of the XIV International AIDS Conference held on 15 July 2004, Dmitry Samoilov describes the discrimination faced by people living with HIV/AIDS in general, and HIV-positive drug users in particular. The presentation includes powerful personal testimonials from people living with HIV/AIDS. The author describes the obstacles to drug users' accessing health care, and concludes with suggestions for actions that should be taken to address the problem.
pubmed_275_2147
pubmed_705_11650
We studied the effects of two antiviral agents, human interferon-alpha (IFN-alpha) and ribavirin, on subacute sclerosing panencephalitis (SSPE) virus infections in hamsters. By intracranial administration, IFN-alpha alone improved the survival of infected hamsters by 20% at a dose of 6 x 10(4) IU/kg every other day for 10 days. When the dose of IFN-alpha was increased incrementally to 6 x 10(6) IU/kg, the survival rate increased by 70% in a dose-dependent manner. The combination of IFN-alpha and ribavirin had a synergic inhibitory effect on the replication of SSPE virus in cell culture. Combination of IFN-alpha (at a dose of 6 x 10(5) IU/kg) with ribavirin (at a dose of 1 mg/kg) completely prevented mortality. This was significantly better than either IFN-alpha or ribavirin monotherapy (p < 0.05). Under the conditions used, IFN-alpha did not enhance the toxicity of ribavirin in hamsters. Intraventricular administration of high dose IFN-alpha and ribavirin may have potential usefulness in the treatment of patients with SSPE.
10.1016/s0166-3542(97)00055-7
pubmed_452_10118
Fractional calculus is now a well-established tool in engineering science, with very promising applications in materials modelling. Indeed, several studies have shown that fractional operators can successfully describe complex long-memory and multiscale phenomena in materials, which can hardly be captured by standard mathematical approaches as, for instance, classical differential calculus. Furthermore, fractional calculus has recently proved to be an excellent framework for modelling non-conventional fractal and non-local media, opening valuable prospects on future engineered materials. The theme issue gathers cutting-edge theoretical, computational and experimental studies on advanced materials modelling via fractional calculus, with a focus on complex phenomena and non-conventional media. This article is part of the theme issue 'Advanced materials modelling via fractional calculus: challenges and perspectives'.
10.1098/rsta.2020.0050
pubmed_100_4332
The developmental stage has an influence on the overall responses of plants under biotic or abiotic stress conditions. However, there is a lack of data about the effects of ionizing radiation in plants at different developmental stages. We examined radiation sensitivity of Arabidopsis plants in terms of photosynthetic ability and oxidative stress resistance at two distinct vegetative and reproductive stages, which correspond to 23 and 43 d after seeding (DAS), respectively. When plants were exposed to γ rays at a dose rate 50 Gy h(-1) for 4 h, they were characterized as various common or differential cellular responses depending on the developmental stage. Radial expansion of leaves, inhibition of non-photochemical quenching, and production of •O(2)(-) and H(2)O(2) under methyl viologen-induced photooxidative stress were commonly more conspicuous in the irradiated leaves of both plants than in the respective control. In contrast, the 23 and 43-DAS plants were explicitly discriminated in growth, chloroplast number & ultrastructure, photosynthetic pigment content & activity, and protein damage after γ irradiation. Natural leaf senescence was thereby enhanced in the irradiated leaves of the 23-DAS plants, while it was reversely alleviated in those of the 43-DAS ones. These results suggest that photosynthetic machineries of Arabidopsis plants at the reproductive stage can be relatively tolerant to γ rays of 200 Gy.
10.1269/jrr.10157
pubmed_146_19595
Findings from human experimental studies suggest that mastication positively influences cognitive function. The participants in those studies were relatively young. The goal of this study was to examine the relationship between the functional status of the masticatory system, episodic memory, and executive functions in elderly people. The participants, elderly people living independently at home, were divided into two groups. One group had a full complement of natural teeth (n = 19) and the other group had full dentures (n = 19). The functional status of the masticatory system was assessed by measuring mandibular excursions (i.e. the distances over which the mandible can move in the open, lateral, and forward directions), bite force, number of occluding pairs and complaints of the masticatory system (facial pain, headaches/migraine). Executive functions and episodic memory were assessed by neuropsychological tests. Backward regression analysis showed that only in the group of elderly people with full dentures, 22% of executive functions were predicted by complaints of the masticatory system and 19.4% of episodic memory was predicted by masticatory performance (composed of mandibular excursions and bite force). The conclusion of this study is that only in older persons with full dentures the relationship between mastication, episodic memory, and executive function becomes evident when the functional status of the masticatory system decreases.
10.1111/j.1365-2842.2007.01842.x
pubmed_916_24712
BACKGROUND The Indian Scale for Assessment of Autism (ISAA) was developed to assess the severity of autism among Indian cases. AIMS The present study evaluated the ISAA in relation to the Childhood Autism Rating Scale (CARS) and the Developmental Disability- Children Global Assessment Scale (DD-CGAS). MATERIALS AND METHODS Indian children with ICD 10 diagnoses of Autistic disorder (AD, n = 50), Intellectual Disability (ID, n = 50), Attention Deficit Hyperactivity Disorder (ADHD, n = 26), other psychiatric disorders (PD-N=25) and control children without psychiatric disorders (n = 65) were evaluated using the ISAA, DD-CGAS and the CARS (total n = 216). STATISTICAL ANALYSES In addition to descriptive statistics and correlation, analysis of variance (ANOVA) was used to assess whether the ISAA scores were significantly different across diagnostic groups. RESULTS Total ISAA scores were significantly higher among children diagnosed with autistic disorder compared to four other diagnostic groups. Total ISAA scores were significantly correlated with CARS scores and DD-CGAS scores. Groups sub-divided on the basis of recommended ISAA cutoff points of severity showed significant differences in CARS scores. CONCLUSION The ISAA can thus be used to assess severity of AD among Indian children.
10.4103/0253-7176.155616
pubmed_36_21902
INTRODUCTION Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume-time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS We studied 19 patients (n=8 mild-moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV1 in the whole cohort (r=-0.71, p<0.001) and patients alone (r=-0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=-0.55, p=0.0015) and patients (r=-0.71, p<0.001) and peak exercise tidal volume (r=-0.58, p=0.0062 and r=-0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=-0.65, p<0.001) and patients considered alone (r=-0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=-0.69, p<0.001) and patients (r=-0.62, p<0.001). CONCLUSIONS Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity.
10.1136/thoraxjnl-2014-205940
pubmed_559_19066
Mesenchymal stem cells have been implicated as playing an important role in stem cell engraftment. Recently, a new pluripotent population of umbilical cord blood (UCB) cells, unrestricted somatic stem cells (USSCs), with intrinsic and directable potential to develop into mesodermal, endodermal, and ectodermal fates, has been identified. In this study, we evaluated the capacity of ex vivo expanded USSCs to influence the homing of UCB-derived CD34(+) cells into the marrow and spleen of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. USSCs induced a significant enhancement of CD34(+) cell homing to both bone marrow and spleen (2.2 +/- 0.3- and 2.4 +/- 0.6-fold, respectively; p < .05), with a magnitude similar to that induced by USSCs that had been thawed prior to transplantation. The effect of USSCs was dose-dependent and detectable at USSC:CD34(+) ratios of 1:1 and above. Enhanced marrow homing by USSCs was unaltered by extensive culture passaging of the cells, as similar enhancement was observed for both early-passage (passage 5 [p5]) and late-passage (p10) USSCs. The homing effect of USSCs was also reflected in an increased proportion of NOD/SCID mice exhibiting significant human cell engraftment 6 weeks after transplantation, with a similar distribution of myeloid and lymphoid components. USSCs enhanced the homing of cellular products of ex vivo expanded UCB lineage-negative (lin(-)) cells, generated in 14-day cultures by Selective Amplification. The relative proportion of homing CD34(+) cells within the culture-expanded cell population was unaltered by USSC cotransplantation. Production of stromal-derived factor-1 (SDF-1) by USSCs was detected by both gene expression and protein released into culture media of these cells. Knockdown of SDF-1 production by USSCs using lentiviral-SiRNA led to a significant (p < .05) reduction in USSC-mediated enhancement of CD34(+) homing. Our findings thus suggest a clinical potential for using USSCs in facilitating homing and engraftment for cord blood transplant recipients.
10.1634/stemcells.2005-0639
pubmed_1010_24384
Copy number variation (CNV), a significant source of genetic diversity in the mammalian Y chromosome, is associated with the development of many complex phenotypes, such as spermatogenesis and male fertility. The contribution of Y-linked CNVs has been studied in various species, however, water buffalo has not been explored in this area and the genetic information still remains unknown. The aim of the current study was to investigate the CNVs of four Y-linked genes, including, sex determining Region of Y-Chromosome (SRY), ubiquitously transcribed tetratricopeptide repeat gene protein on the chromosome Y (UTY), DEAD-box helicase 3 Y-linked (DDX3Y, also known as DBY), and oral-facial-digital syndrome 1 Y-linked (OFD1Y) in 254 swamp buffaloes from 15 populations distributed across China, Vietnam, and Laos using quantitative real-time PCR (qPCR). Our results revealed the prevalence of a single-copy UTY gene in buffaloes. The DBY and OFD1Y represented CNVs among and within different buffalo breeds. The SRY showed CNVs only in Vietnamese and Laotian buffaloes. In conclusion, this study indicated that DBY, OFD1Y, and SRY showed CNVs, while the UTY was a single-copy gene in swamp buffaloes.
10.3390/ani10010031
pubmed_484_6052
AIM To investigate the effect of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) as a photosensitizer on the character of infiltration of experimental tumors by different cells of immune system. METHODS The effect of ALA-PDT on subcutaneously implanted Lewis lung carcinoma in c57Bl/6 mice was studied. ALA at a dose of 500 mg/kg was given per os, and 4 h later tumors were subjected to laser irradiation (632 nm, 150 mW/cm(2), 20 min). The evaluation of the tumor infiltration by myelomonocytic and lymphoid cells and oxygen-dependent metabolism of peritoneal macrophages (NBT-test) were carried out. RESULTS It is shown that ALA-PDT resulted in fast and massive infiltration of irradiated tumors by myelomonocytic cells, stimulation of the peritoneal macrophages metabolic activity and augmentation of the content of tumor infiltrating lymphocytes. CONCLUSION The immunomodulation after ALA-PDT occurs via generation of inflammation and direct laser light activation of immune system cells.
pubmed_484_6052
pubmed_603_23157
A novel series of HDAC8 inhibitors without a zinc-chelating hydroxamic acid moiety is reported. Photoaffinity labeling and molecular modeling studies suggest that these ligands are likely to bind in an 'upside-down' fashion in a secondary binding site proximal to the main catalytic site. The most potent ligand in the series exhibits an IC(50) of 28 μM for HDAC8 and is found to inhibit the deacetylation of H4 but not α-tubulin in SH-SY5Y cell line.
pubmed_603_23157
pubmed_335_1233
OBJECTIVE To report the clinical features of 11 patients with metabotropic glutamate receptor 5 (mGluR5) antibody-associated encephalitis, immunoglobulin G (IgG) subclass, and effects of the antibodies on neuronal mGluR5 clusters. METHODS Clinical information was retrospectively obtained from referring physicians. Antibodies to mGluR5 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays. The effects of the antibodies were examined on rat hippocampal neurons with reported techniques. RESULTS From January 2005 to May 2017, 11 patients (median age 29 years, range 6-75 years, 5 female) were identified. The main clinical features were psychiatric (10), cognitive (10), movement disorders (7), sleep dysfunction (7), and seizures (6). Median modified Rankin Scale score at the peak of the disease was 4; 4 patients required intensive care. Five patients had Hodgkin lymphoma, and 1 had small cell lung cancer. CSF showed pleocytosis (median white blood cell count 22 mm3) in all patients; brain MRI was abnormal in 5, involving limbic (1) or extralimbic (4) regions. Treatments included immunotherapy and/or oncologic therapy; at the last follow-up (median 48 months), 6 patients had complete and 5 had partial recovery. Neurologic relapse occurred in 2 patients. Antibodies were IgG1 alone (4 of 9) or in combination with IgG2 (1 of 9), IgG3 (3 of 9), or both (1). Patients' IgG caused a significant and specific decrease of cell-surface synaptic and extrasynaptic mGluR5 without altering the levels of postsynaptic density protein 95. CONCLUSIONS Anti-mGluR5 encephalitis associates with a complex neuropsychiatric syndrome, not restricted to limbic encephalitis, and can occur without tumor. Patients respond to treatment, but relapses can occur. The antibodies have pathogenic effects altering the levels of cell-surface mGluR5.
10.1212/WNL.0000000000005614
pubmed_78_11586
Using historical census microdata, we present a unique analysis of racial and gender disparities in destination selection and an exploration of hypotheses regarding tied migration in the historical context of the Great Migration. Black migrants were more likely to move to metropolitan areas and central cities throughout the period, while white migrants were more likely to locate in nonmetropolitan and farm destinations. Gender differences were largely dependent on marital status. Consistent with the "tied-migration" thesis, married women had destination outcomes that were similar to those of men, whereas single women had a greater propensity to reside in metropolitan locations where economic opportunities for women were more plentiful.
10.1353/dem.2005.0019
pubmed_225_2524
The expression of the murine paired-box-containing gene, Pax2, is examined in the developing central nervous system by in situ hybridization. Pax2 expression is detected along the boundaries of primary divisions of the neural tube. Initially, Pax2 is expressed in the ventricular zone in two compartments of cells on either side of the sulcus limitans and along the entire rhombencephalon and spinal cord. At later times, Pax2 is restricted to progeny cells that have migrated to specific regions of the intermediate zone. In the eye, Pax2 expression is restricted to the ventral half of the optic cup and stalk and later to the optic disc and nerve. In the ear, expression is restricted to regions of the otic vesicle that form neuronal components. The transient and restricted nature of Pax2 expression suggests that this murine segmentation gene homologue may also establish compartmental boundaries and contribute to the specification of neuronal identity, as do certain Drosophila segmentation genes.
10.1242/dev.109.4.797
pubmed_690_17996
We have studied the relation between the structure and the multidrug resistance-reversal activity of a set of diverse chemicals with the MULTICASE structure-activity program. A number of key structural features were identified as being related to multidrug resistance reversal activity. Using these key features, we identified seven new compounds predicted to have substantial activity. These were obtained and tested experimentally on a CHO/CHRC5 cell line derived from the AB1 Chinese hamster ovary line in the presence of vincristine and vinblastine. Of the seven compounds tested so far, four showed substantial reversal activity, the most potent of them exhibiting activity at par with verapamil.
pubmed_690_17996
pubmed_207_11727
Fractal geometry and related concepts have had only a very minor impact on food research. The very few reported food applications deal mainly with the characterization of the contours of agglomerated instant coffee particles, the surface morphology of treated starch particles, the microstructure of casein gels viewed as a product limited diffusion aggregation, and the jagged mechanical signatures of crunchy dry foods. Fractal geometry describes objects having morphological features that are scale invariant. A demonstration of the self-similarity of fractal objects can be found in the familiar morphology of cauliflower and broccoli, both foods. Processes regulated by nonlinear dynamics can exhibit a chaotic behavior that has fractal characteristics. Examples are mixing of viscous fluids, turbulence, crystallization, agglomeration, diffusion, and possibly food spoilage.
10.1080/10408399309527617
pubmed_688_1206
A significant portion of internal medicine residency training in the United States today occurs in general medicine sections of Veterans Administration hospitals. The authors studied the demographic, diagnostic, and prognostic characteristics of the patients treated by house staff members rotating through the general medical wards of the Houston, Texas, Veterans Administration (VA) Medical Center. In 2,131 admissions over 13 months, the most frequent primary causes of admissions included congestive heart failure, pneumonia, exacerbation of chronic obstructive lung disease, and malignancy. In 85 percent of the admissions, two or more chronic diseases were present. In 53 percent of admissions, the patients were deemed to be moderately or severely ill on admission. The data indicate that the residents' experience is representative of problems encountered by practicing internists and that VA hospitals make a significant contribution to internal medicine training and thus to the provision of health care for the nation.
10.1097/00001888-198510000-00004
pubmed_189_19018
Rheumatic diseases are often associated to debilitating chronic pain, which remains difficult to treat and requires new therapeutic strategies. We had previously identified lysophosphatidylcholine (LPC) in the synovial fluids from few patients and shown its effect as a positive modulator of acid-sensing ion channel 3 (ASIC3) able to induce acute cutaneous pain in rodents. However, the possible involvement of LPC in chronic joint pain remained completely unknown. Here, we show, from 2 independent cohorts of patients with painful rheumatic diseases, that the synovial fluid levels of LPC are significantly elevated, especially the LPC16:0 species, compared with postmortem control subjects. Moreover, LPC16:0 levels correlated with pain outcomes in a cohort of osteoarthritis patients. However, LPC16:0 do not appear to be the hallmark of a particular joint disease because similar levels are found in the synovial fluids of a second cohort of patients with various rheumatic diseases. The mechanism of action was next explored by developing a pathology-derived rodent model. Intra-articular injections of LPC16:0 is a triggering factor of chronic joint pain in both male and female mice, ultimately leading to persistent pain and anxiety-like behaviors. All these effects are dependent on ASIC3 channels, which drive sufficient peripheral inputs to generate spinal sensitization processes. This study brings evidences from mouse and human supporting a role for LPC16:0 via ASIC3 channels in chronic pain arising from joints, with potential implications for pain management in osteoarthritis and possibly across other rheumatic diseases.
10.1097/j.pain.0000000000002596
pubmed_113_17442
In the deep sea, the phylogeny and biogeography of only a few taxa have been well studied. Although more than 200 species in 32 genera have been described for the asellote isopod families Desmosomatidae Sars, 1897 and Nannoniscidae Hansen, 1916 from all ocean basins, their phylogenetic relationships are not completely understood. There is little doubt about the close relationship of these families, but the taxonomic position of a number of genera is so far unknown. Based on a combined morphological phylogeny using the Hennigian method with a dataset of 107 described species and a molecular phylogeny based on three markers (COI, 16S, and 18S) with 75 species (most new to science), we could separate Desmosomatidae and Nannoniscidae as separate families. However, we could not support the concept of the subfamilies Eugerdellatinae Hessler, 1970 and Desmosomatinae Hessler, 1970. Most genera of both families were well supported, but several genera appear as para- or even polyphyletic. Within both families, convergent evolution and analogies caused difficulty in defining apomorphies for phylogenetic reconstructions and this is reflected in the results of the concatenated molecular tree. There is no biogeographic pattern in the distribution as the genera occur over the entire Atlantic and Pacific Ocean, showing no specific phylogeographical pattern. Poor resolution at deep desmosomatid nodes may reflect the long evolutionary history of the family and rapid evolutionary radiations. Supplementary Information The online version contains supplementary material available at 10.1007/s13127-021-00509-9.
10.1007/s13127-021-00509-9
pubmed_258_19708
A crucial evolutionary change in vertebrate history was the Palaeozoic (Devonian 419-359 million years ago) water-to-land transition, allowed by key morphological and physiological modifications including the acquisition of lungs. Nonetheless, the origin and early evolution of vertebrate lungs remain highly controversial, particularly whether the ancestral state was paired or unpaired. Due to the rarity of fossil soft tissue preservation, lung evolution can only be traced based on the extant phylogenetic bracket. Here we investigate, for the first time, lung morphology in extensive developmental series of key living lunged osteichthyans using synchrotron x-ray microtomography and histology. Our results shed light on the primitive state of vertebrate lungs as unpaired, evolving to be truly paired in the lineage towards the tetrapods. The water-to-land transition confronted profound physiological challenges and paired lungs were decisive for increasing the surface area and the pulmonary compliance and volume, especially during the air-breathing on land.
pubmed_258_19708
pubmed_773_8720
An immunologic study was made on 170 epileptic patients treated with antiepileptic drugs. The most noteworthy finding was that the serum IgA was decreased in 22 patients, and an IgA deficiency noticed in 12 of them. The blastic transformation rate of lymphocytes in PHA-containing cultures appeared low in seven out of 12 patients. Other findings included decreased serum IgM and IgG in some patients. These abnormalities were not encountered in epileptic patients taking no anti-epileptic drugs. Therefore, they could be considered as the side effects of antiepileptic drugs. In all patients manifesting these abnormalities, diphenylhydantoin was used in common. It was surmised that the above-mentioned immunologic abnormalities caused by anti-epileptic drugs, especially diphenylhydantoin, had resulted from disorders of the antibody producing organs in the bone marrow-thymus-lymphatic system.
10.1111/j.1440-1819.1976.tb00115.x
pubmed_19_21084
While the pharmacology of sugammadex has been extensively reviewed, there is limited literature regarding its use in specific clinical settings. Several case reports describe its use in patients with the potential for postoperative respiratory dysfunction; in the settings of myasthenia gravis, Duchenne muscular dystrophy and myotonic dystrophy. We describe the use of sugammadex in a patient with severe bronchiectasis related to cystic fibrosis who required neuromuscular block for percutaneous endoscopic gastrostomy insertion. The use of rocuronium for neuromuscular block was preferred in order to avoid the potential complications associated with the use of suxamethonium. However we wished to ensure complete neuromuscular block reversal for this short duration procedure in this high-risk patient and also to avoid the side-effects of traditional reversal agents. We therefore planned in advance to use sugammadex for neuromuscular block reversal, and this approach proved successful. Overall, the combination of rocuronium and sugammadex improved perioperative surgical and anaesthetic management in this patient.
10.1177/0310057X1103900223
pubmed_351_15494
Thirty patients with active duodenal ulcer who were Helicobacter pylori positive (HP+) by HLO test and by histology (Giemsa stain) were given omeprazole (OME) 20 mg/d for a two-week period. Estimation of fasting serum gastrin concentration (RIA) was performed before treatment and 24 hours after the last dosage of OME, and HP was searched for an antral biopsies at the end of the treatment as well. Mean fasting serum gastrin concentration increased significantly after treatment in all patients studied (p less than 0.05). However, the increase remained significant only in those patients who continued to be HP+ while no significant increase was observed in those who became HP-. The results could be considered as further evidence of the 'clearing' effect of Omeprazole on HP.
pubmed_351_15494
pubmed_1017_18294
Few research publications have reported on gender-dependent neural correlates of risk decision-making in older adults. In this study, we utilized functional near-infrared spectroscopy (fNIRS) to comprehensively investigate both age- and gender-dependent differences in neural correlates in response to a well-utilized risk decision-making protocol, the Balloon Analog Risk Task (BART). A newly-developed technique, atlas-guided diffuse optical tomography (atlas-DOT), was used to image the prefrontal cortices (PFC) of healthy subjects in two age groups (25-40 years; 60-92 years) using BART stimulation. The behavioral measures and brain activations imaged by atlas-DOT were recorded and compared for both age groups. Three-factor analysis of variance was conducted to include all effects of age (young, old), gender (male, female), case (win, lose) and their interactions for both behavioral and hemodynamic responses. The results indicated age differences in cortical activation patterns, activation amplitudes, and brain-behavior correlations. Larger areas of cortical activation with reduced amplitudes in the PFC were observed in older adults when they performed BART. Brain-behavior correlations indicated that young adults took more risks, whereas older adults were more risk-averse. Results also revealed a gender effect in young adults, but not in older adults. Both male and female older adults demonstrated strong PFC responses and the same risk-averse patterns under lose outcomes. This is the first study to examine the neural correlates of risk decisions in older adults by optical brain imaging.
10.1007/s11682-016-9580-z
pubmed_371_14328
A 61-year-old man with Schnyder's crystalline corneal dystrophy showed a slight reduction in vision during 16 years of observation. Plasma lipoprotein analysis done 10 years after presentation showed type IIA hyperlipoproteinemia, which was also detected in one of four siblings examined, none of whom showed the characteristic corneal dystrophy. Electron microscopic studies on corneal biopsy specimens from the patient showed abundant crystalline material and vacuoles predominantly in the superficial corneal stroma, with occasional keratocytes and rare basal epithelial cells containing laminated structures. The findings of a focal continuity between the trilaminar membrane around some of the stromal vacuoles and the plasmalemma of the keratocytes as well as dissolution of the plasmalemma in other keratocytes are consistent with the hypothesis of a local cellular role in the development of this corneal disorder.
pubmed_371_14328
pubmed_1015_5164
A rapid method for the separation and quantitation of unesterified cholesterol and cholesteryl esters by high-performance liquid chromatography is described. All of the cholesteryl esters typically present in plasma were resolved on Zorbax ODS reversed-phase columns using a linear gradient of water (3%-0%) in acetonitrile-tetrahydrofuran 65:35 (v/v) as eluting solvent. Results obtained by this method show good agreement with chemical and gas-liquid chromatographic methods for quantitation of cholesterol and determination of cholesteryl ester percentage compositions. High-performance liquid chromatography provides the only available method for the separation and quantitation of individual cholesteryl esters from lipid extracts of biological samples.
pubmed_1015_5164
pubmed_1095_17917
OBJECTIVE We present a case of triplet pregnancy with a complete hydatidiform mole, a condition carrying a significant risk to both mother and fetuses and, therefore, raising an important issue on prenatal care. CASE REPORT A 36-year-old patient with gonadal dysgenesis and a 46,XY karyotype successfully conceived a triplet pregnancy after oocyte donation and in vitro fertilization. At mid-trimester, the pregnancy was seen harboring a hydatidiform mole along with two other fetuses by ultrasound. Fetal karyotyping of both fetuses revealed normal results. Serum human chorionic gonadotropin levels were followed up throughout the remainder of pregnancy. At 33 weeks of gestation, preeclampsia ensued with worsening of maternal renal function and high blood pressure, so cesarean section was arranged to deliver a set of two surviving twins. Prophylactic bilateral gonadectomy was done at the same time to curtail the possibility of future malignancy development. Upon pathologic examination of the placentae, hydropic chorionic villi with central cistern formation and nonpolar trophoblastic hyperplasia with atypia and necrosis were found, compatible with complete hydatidiform mole. The gonads showed streaks of fibrous tissue, which resembled ovarian stroma and hilus cells, and an unremarkable tube. Maternal serum human chorionic gonadotropin levels declined gradually to normal level at two months after delivery. CONCLUSION This is the first report of triplet pregnancy complicated with one complete hydatidiform mole and preeclampsia in a 46,XY female with gonadal dysgenesis. Our case demonstrated that prolonged gestation with both surviving fetuses was possible by applying intensive monitoring of the whole pregnancy.
10.1016/S1028-4559(08)60034-0
pubmed_278_10007
Enantioselective nickel-catalyzed reactions of (hetero)arylboronic acids or alkenylboronic acids with substrates containing an alkyne tethered to various acyclic electron-deficient alkenes are described.
10.1039/d1cc01166a
pubmed_889_18513
Gluten-related disorders (GRD) affects approximately 10% of the general population. The only treatment for GRD is still so far is the lifelong complete exclusion of gluten from the daily diet. The correct information about the presence/absence of gluten in food is very important to this group. The present study aimed to evaluate the prevalence of gluten contamination in gluten-free industrial and non-industrial products. In this systematic review, 24 cross-sectional studies were analyzed. The authors developed specific search strategies for Science Direct, Scopus, Web of Science, Google Scholar and ProQuest Dissertations & Theses Global. The authors evaluated the methodological quality of the included studies using criteria from Meta-analysis of Statistics Assessment and Review Instrument (MASTARI). We performed the statistical meta-analysis by metafor package of R program. 95.83% (n = 23) of the studies presented positive results for contamination (over 20 ppm). In industrial food products, studies showed a contamination prevalence of 13.2% (95% CI: 10.8%-15.7%). In non-industrial food products, studies showed a contamination prevalence of 41.5% (95% CI: 16.6%-66.4%). Despite the non-industrial products presented higher contamination prevalence than the industrial products, the difference was not significant (p = 0.072). The findings indicate cross-contamination in industrialized and non-industrialized products. As expected, industrial products labeled as gluten-free showed a lower percentage of gluten-contamination than non-industrialized. Despite that, any contaminated sample found in this group present greater relevance than non-labeled foods. It indicates that foods labeled as "gluten-free" should not be considered safe for patients with GRD since information on the label regarding the presence/absence of gluten is unreliable. Therefore, any gluten-contamination in products labeled as gluten-free is a serious problem to whom present GRD. Further studies are needed to estimate gluten cross-contamination in food service meals and industry better.
10.1080/10408398.2018.1541864
pubmed_214_671
An 87-year-old woman with grade IIIb follicular lymphoma treated with rituximab had presented with nausea, emesis, and chest pain of 1 day duration. She was found to have a contained abdominal aortic rupture secondary to follicular lymphoma invasion. She safely and successfully underwent emergent endovascular aortic repair. We have described a rare case of extranodal disease in follicular lymphoma associated with abdominal aortic pseudoaneurysms, likely due to a combination of malignancy-induced chronic inflammation and radiation therapy and chemotherapy side effects.
10.1016/j.jvscit.2022.03.015
pubmed_32_898
Retrospectively, the first 143 patients who were operated on with bilateral internal thoracic arteries (BITA group) were matched with 143 patients operated on with only one left internal thoracic artery anastomosed on the left anterior descending artery and additional vein grafts (LITA group) and followed up for a maximum of 8 years. At 5 years follow-up there were no significant differences in event-free survival between the groups. After 8 years, the overall survival was 96% and 92% (not significant [NS]), cardiac survival 99% and 97% (NS), angina-free cardiac survival 51% and 35% (NS), infarction-free cardiac survival 95% and 78% (NS), reintervention-free cardiac survival 87% and 88% (NS), and all cardiac event-free survival 49% and 31% (NS) for the BITA and LITA groups, respectively. The incidence of late pulmonary, wound, and other complications was comparable. Cox proportional hazards analysis showed that a higher left ventricular end-diastolic pressure and female sex were predictors of recurrent angina and late cardiac events. During this intermediate-term follow-up, the use of one or two internal thoracic arteries was of no value in predicting angina-free or cardiac event-free survival.
10.1016/0003-4975(95)00183-l
pubmed_130_10671
INTRODUCTION Persistent inflammatory smear is a benign finding on pap test but is associated with premalignant lesion of the cervix. Further evaluation is therefore necessary. This study was done to determine the prevalence of cervical intraepithelial lesions in women with persistent inflammatory smear. METHODS This is descriptive observational study conducted in Department of Obstetrics and Gynaecology of tertiary care centre of Nepal from 15th May 2020 to 14th May 2021 after obtaining ethical clearance from Institutional Review Board (Reference no MEMG/IRC/338/GA). Women with two consecutive pap smear reports showing inflammatory findings were enrolled. Colposcopy was performed and Modified Reid's colposcopic index was used to grade the lesions. Colposcopic guided biopsy was taken and tissue sent for histopathology for abnormal colposcopic lesions. Data analysis was done using Statistical Package for Social Sciences version 21 and frequency and percentages were used to present data. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS Among 115 women, 57 (49.5%) at 95% Confidence Interval (40.37-58.63) had Cervical Intraepithelial lesions. Among them 48 (41.7%) had low grade intraepithelial lesions and 9 (7.8%) had high grade lesions on colposcopy. CONCLUSIONS The prevalence of cervical intraepithelial lesions in women with persistent inflammatory smear on pap was higher in our study compared to other studies.
10.31729/jnma.7011
pubmed_583_14444
This pilot study evaluated the effectiveness of energy conservation training to help post-therapy cancer survivors manage their fatigue. Twelve post-therapy cancer survivors were randomly assigned to an energy conservation training or usual care control (6 in each group). Participants in the intervention group received 1 to 2 hours of individual, face-to-face energy conservation training from an occupational therapist followed by once-a-week telephone monitoring sessions in the subsequent three weeks. Participants in the control group received standard care from their oncologist. Analysis of pre- and post-training data from the Piper Fatigue Scale (PFS) revealed significant reduction only in the sensory subscale of the PFS (Z = 2.21; p = 0.027) for the intervention group; but no significant reduction in the four subscale or total scores of the PFS for the control group. Findings demonstrate partial support for the effectiveness of energy conservation training in helping post-therapy cancer survivors manage their fatigue. Energy conservation training seems to be a viable strategy for managing cancer-related fatigue, though its efficacy is modest. Incorporating specific energy restoration strategies such as relaxation and meditation for future research may help advance the growing body of knowledge in symptom management for post-therapy cancer survivors.
pubmed_583_14444
pubmed_540_6640
Three-dimensional (3D) printing has been gaining attention as a new technological approach to obtain immediate release (IR) dosage forms. The versatility conferred by 3D printing techniques arises from the suitability of using different polymeric materials in the production of solids with different porosities, geometries, sizes, and infill patterns. The appropriate choice of polymer can facilitate in reaching IR specifications and afford other specific properties to 3D printed solid dosage forms. This review aims to provide an overview of the polymers that have been employed in the development of IR 3D printed dosage forms, mainly considering their in vitro drug release behaviour. The physicochemical and mechanical properties of the IR 3D printed dosage forms will also be discussed, together with the manufacturing process strategies. Up to now, methacrylic polymers, cellulosic polymers, vinyl derivatives, glycols and different polymeric blends have been explored to produce IR 3D printed dosage forms. Their effects on drug release profiles are critically discussed here, giving a complete overview to drive formulators towards a rational choice of polymeric material and thus contributing to future studies in 3D printing of pharmaceuticals.
10.1016/j.ijpharm.2022.122066
pubmed_377_10857
A controversy of relevance to the study of biological form involves the concept of adaptation. This controversy is illustrated by the structure and function of the human hand. A review of the principal definitions of adaptation points to two main problems: (1) they are qualitative and make reference to the whole structure (or substructural feature) and (2) they are based on the idea of natural selection as a moulding factor. The first problem would be solved by a definition that encompasses quantitative measures of the effects of selection, drawing on new advances in the comparative method. The second problem is deeper and presents greater conceptual difficulties. I will argue that the idea of natural selection as a moulding factor depends on the notion of a genetic program for development. But regarding the hand, experimental evidence on limb development challenges the idea of a genetic program for skeletal pattern formation, undermining a simple application of standard adaptationist concepts. These considerations lead to a revised definition of adaptation and interpretation of the evolutionary determinants of the hand's form.
10.1007/s12038-011-9102-5
pubmed_1121_2560
The rapid development of Internet of Things mobile terminals has accelerated the market's demand for portable mobile power supplies and flexible wearable devices. Here, an embedded metal-mesh transparent conductive electrode (TCE) is prepared on poly(ethylene terephthalate) (PET) using a novel selective electrodeposition process combined with inverted film-processing methods. This embedded nickel (Ni)-mesh flexible TCE shows excellent photoelectric performance (sheet resistance of ≈0.2-0.5 Ω sq-1 at high transmittance of ≈85-87%) and mechanical durability. The PET/Ni-mesh/polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS PH1000) hybrid electrode is used as a transparent electrode for perovskite solar cells (PSCs), which exhibit excellent electric properties and remarkable environmental and mechanical stability. A power conversion efficiency of 17.3% is obtained, which is the highest efficiency for a PSC based on flexible transparent metal electrodes to date. For perovskite crystals that require harsh growth conditions, their mechanical stability and environmental stability on flexible transparent embedded metal substrates are studied and improved. The resulting flexible device retains 76% of the original efficiency after 2000 bending cycles. The results of this work provide a step improvement in flexible PSCs.
10.1002/adma.202003422
pubmed_892_8045
We developed a scale to measure internalized homophobia in men who have sex with men, which is comprised of items derived from theoretical and clinical reports of internalized homophobia. Two hundred two men who have sex with men and who attend "Man to Man" sexual health seminars in a midwestern U.S. city completed the scale at baseline. Orthogonal factor analysis revealed four dimensions of internalized homophobia: public identification as gay, perception of stigma associated with being homosexual, social comfort with gay men, and the moral and religious acceptability of being gay. Factor scoring of these dimensions indicated that they were associated significantly with relationship satisfaction, duration of longest relationship, extent of attraction to men and women, proportion of social time with gay people, membership of gay/bisexual groups, HIV serostatus, and disclosure of sexual orientation. Internalized homophobia is measurable and consists of four dimensions that are associated significantly with low disclosure, shorter length of and satisfaction with relationships, lower degree of sexual attraction to men and higher degree of attraction to women, and lower social time with gay people.
10.1002/(SICI)1097-4679(199601)52:1<15::AID-JCLP2>3.0.CO;2-V
pubmed_642_5283
Sweet potato virus disease (SPVD) is the most serious viral disease of sweetpotato globally. This disease is caused by the synergistic interaction between the aphid-transmitted potyvirus Sweet potato feathery mottle virus (SPFMV) and the whitefly-transmitted crinivirus Sweet potato chlorotic stunt virus (SPCSV). In sweetpotato, titers of SPFMV have been shown to be significantly enhanced when coinfecting with SPCSV. In this study, the effect of SPCSV on titers of different potyviruses and potyvirus strains infecting sweetpotato in the United States was investigated using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). No significant difference was observed in titers of the russet crack strain of SPFMV (SPFMV-RC), Ipomoea vein mosaic virus (IVMV), and Sweet potato virus G (SPVG) between single and mixed infections. Titers of all potyviruses and potyvirus strains evaluated were enhanced in the presence of SPCSV, suggesting that a conserved mechanism may underlie these interactions. Titers of the common strain of SPFMV (SPFMV-C), which did not cause SPVD-like symptoms when coinfecting with SPCSV, were also significantly enhanced in the presence of SPCSV. Furthermore, titers of SPCSV were found to be lower in treatments involving pairwise infections compared with plants infected by SPCSV alone. The degree of potyvirus titer enhancement did not correspond to the severity of symptoms observed in certain treatments involving pairwise infections.
10.1094/PD-90-1347
pubmed_680_1092
Intestinal barrier derangement allows intestinal bacteria and their products to translocate to the systemic circulation. Pseudomonas aeruginosa (PA) superimposed infection in critically ill patients increases gut permeability and leads to gut-driven sepsis. PA infections are challenging due to multi-drug resistance (MDR), biofilms, and/or antibiotic tolerance. Inhibition of the quorum-sensing transcriptional regulator MvfR(PqsR) is a desirable anti-PA anti-virulence strategy as MvfR controls multiple acute and chronic virulence functions. Here we show that MvfR promotes intestinal permeability and report potent anti-MvfR compounds, the N-Aryl Malonamides (NAMs), resulting from extensive structure-activity-relationship studies and thorough assessment of the inhibition of MvfR-controlled virulence functions. This class of anti-virulence non-native ligand-based agents has a half-maximal inhibitory concentration in the nanomolar range and strong target engagement. Using a NAM lead in monotherapy protects murine intestinal barrier function, abolishes MvfR-regulated small molecules, ameliorates bacterial dissemination, and lowers inflammatory cytokines. This study demonstrates the importance of MvfR in PA-driven intestinal permeability. It underscores the utility of anti-MvfR agents in maintaining gut mucosal integrity, which should be part of any successful strategy to prevent/treat PA infections and associated gut-derived sepsis in critical illness settings. NAMs provide for the development of crucial preventive/therapeutic monotherapy options against untreatable MDR PA infections.
10.1038/s41467-022-32833-9
pubmed_229_15491
CONTEXT For patients considering elective major surgery, information about operative mortality risks is essential for careful decision making. Because available information is often limited to educated guesses or optimistic data from case series, we examined surgical mortality by using nationwide data. PRACTICE PATTERN EXAMINED Operative mortality in 1.2 million patients in the Medicare system who were hospitalized between 1994 and 1999 for major elective surgery (six cardiovascular procedures and eight major cancer resections). DATA SOURCE MEDPAR file of the National Medicare claims database for patients 65 years of age and older. OUTCOMES Operative mortality, defined as death within 30 days of the operation or death before discharge. RESULTS Overall operative mortality varied widely according to procedure. Procedures associated with relatively low mortality risk included carotid endarterectomy (1.3%) and nephrectomy (2.3%). Overall mortality was greater than 10% for other procedures, such as mitral valve replacement (10.5%), esophagectomy (13.6%), and pneumonectomy (13.7%). In general, mortality risk increased with age. Operative mortality for patients 80 years of age and older was more than twice that for patients 65 to 69 years of age. CONCLUSION Population-based operative mortality for major surgery varies by procedure and patient age and is considerably higher than that typically reported in case series and trials.
pubmed_229_15491
pubmed_835_4502
The study aimed to investigate the association between the estrogen receptor alpha (ERα) polymorphism and the prevalence of metabolic syndrome (MetS) and obesity, as well as the coexistence of MetS and obesity, in peri- and post-menopausal Polish women. The study group consisted of 202 peri-menopausal and 202 post-menopausal women. ERα polymorphism: Xba I and Pvu II, MetS, BMI, and serum estrogen concentration were analyzed. MetS was found in 29% of the peri-menopausal women and in 21% of the post-menopausal women. BMI did not significantly differ between the peri- and post-menopausal women (≈42% were normal weight, ≈40% were overweight, and ≈18% were obese), (p = 0.82). Serum estrogen concentration in the peri-menopausal women was 91 ± 75 pg/mL, while that in the post-menopausal women was 17 ± 9. pg/mL, on average. Peri-menopausal women with AA and TT genotypes of the ERα polymorphism have a lower risk of obesity and MetS and the co-existence of obesity and MetS, whereas those women with the G or C allele have a higher risk of those health problems.
10.3390/metabo12080673
pubmed_947_13613
Herein, Fe-doped CoP nanoparticles (Fe-CoP NPs) encapsulated in porous N-doped carbon (PNC)/carbon nanotubes (CNTs) have been successfully synthesized. The Fe doping and confined structures resulted in enhanced charge transfer and improved active sites for intermediates adsorption. The obtained Fe-CoP@PNC/CNTs materials exhibited superefficient OER performance.
10.1039/d1cc06923c
pubmed_93_25
BACKGROUND Hepatectomy is one of the best curative therapies for hepatocellular carcinoma (HCC). The negative impact of postoperative complications on long-term survival has been investigated in patients with several kinds of cancers. To clarify the impact of postoperative complications on long-term survival in patients who undergo hepatectomy for HCC, we conducted a comparative analysis of 376 patients using the modified Clavien classification and identified the predictors of postoperative complications. METHODS Patients were assigned into two groups: those with (N = 177) and those without complications (N = 199). The clinical data, surgical outcome, and long-term survival of patients were analyzed retrospectively. RESULTS The cumulative overall survival rates of the patients with complications were significantly less than those of the patients without complications (P < 0.01). Multivariate logistic regression analysis revealed that intraoperative blood transfusion (P = 0.04), longer operation time (P = 0.02), use of Pringle's maneuver (P < 0.01), and use of the thoraco-abdominal approach (P = 0.01) were independent risk factors for postoperative complications. CONCLUSIONS Postoperative complications (major or minor) are one of prognostic indicators in hepatectomy for HCC. The present study suggests that high quality surgical technique to minimize complications will improve the prognosis of HCC.
10.1002/jso.21977
pubmed_886_23880
We used two gametocidal (Gc) chromosomes 2C and 3C(SAT) to dissect barley chromosome 4H added to common wheat. The Gc chromosome induced chromosomal structural rearrangements in the progeny of the 4H addition line of common wheat carrying the monosomic Gc chromosome. We conducted in situ hybridization to select plants carrying rearranged 4H chromosomes and characterized the rearranged chromosomes by sequential C-banding and in situ hybridization. We established 60 dissection lines of common wheat carrying single rearranged 4H chromosomes. The rearranged 4H chromosomes had either a deletion or a translocation or a complicated structural change. The breakpoints were distributed in the short arm, centromere and the long arm at a rough ratio of 2:2:1. We conducted PCR analysis using the dissection lines and 93 EST markers specific to chromosome 4H. Based on the PCR result, we constructed a cytological map of chromosome 4H with 18 regions separated by the breakpoints of the rearranged chromosomes. Thirty-seven markers were present in the short arm and 56 in the long arm, and about 70% of the markers were present in no more than the distal 25.6% and 43.1% regions of the short and long arms, respectively. It is noteworthy that nine of the short-arm markers and 13 of the long-arm markers existed in the small subtelomeric regions at both ends characterized by the HvT01 sequences. We reconstructed a genetic map using 38 of the 93 markers that was used to construct the cytological map of chromosome 4H. The order of the markers on the genetic map was almost the same as that on the cytological map. On the genetic map, no markers were available in the pericentromeric region, but on the cytological map, 14 markers were present in the proximal region, and one of the markers was in the centromeric region of the short arm.
10.1266/ggs.85.19
pubmed_422_532
Angiostatin, a potent inhibitor of angiogenesis, tumour growth and metastasis, is a biologically active fragment of plasminogen, containing the kringle domains 1-4. It is generated from plasminogen by limited proteolysis. We show that prostate-specific antigen (PSA), a serine proteinase secreted by human prostate and human prostate cancer cells, is able to convert Lys-plasminogen to biologically active angiostatin-like fragments, containing kringles 1-4, by limited proteolysis of peptide bond Glu439-Ala440 in vitro. In an in vitro morphogenesis assay, the purified angiostatin-like fragments inhibited proliferation and tubular formation of human umbilical vein endothelial cells with the same efficacy as angiostatin. This finding might help to understand growth characteristics of prostate cancer, which usually has low microvessel density and slow proliferation.
10.1038/sj.bjc.6692167
pubmed_1040_3462
Congenital absence of the pericardium, whether partial or total, is a rare abnormality. It can be very difficult to diagnose clinically as well as to confirm radiographically. Plain film fluoroscopy and CT have been shown to be of value in differentiating this entity from others with similar findings. We report a case in which magnetic resonance was utilized to confirm the diagnosis and the findings of this new technique are described.
10.1097/00004728-198505000-00026
pubmed_183_190
An afsA homologue (srrX) and three gamma-butyrolactone receptor gene homologues (srrA, srrB and srrC) are coded on the giant linear plasmid pSLA2-L in Streptomyces rochei 7434AN4, a producer of two polyketide antibiotics, lankacidin and lankamycin. Construction of gene disruptants and their phenotypic study revealed that srrX and srrA make a gamma-butyrolactone receptor system in this strain. Addition of a gamma-butyrolactone fraction to an srrX-deficient mutant restored the production of lankacidin and lankamycin, indicating that the SrrX protein is not necessary for this event. In addition to a positive effect on antibiotic production, srrX showed a negative effect on morphological differentiation. The receptor gene srrA reversed both effects of srrX, while the second receptor gene homologue srrC had only a positive function in spore formation. Furthermore, disruption of the third homologue srrB greatly increased the production of lankacidin and lankamycin. Electron microscopic analysis showed that aerial mycelium formation stopped at a different stage in the srrA and srrC mutants. Overall, these results indicated that srrX, srrA, srrB and srrC constitute a complex regulatory system for antibiotic production and morphological differentiation in S. rochei.
10.1099/mic.0.2006/002170-0
pubmed_1004_23207
An ovarian mature cystic teratoma featuring florid vascular proliferation and Wagner-Meissner-like corpuscles is presented. The vascular proliferation is analogous to that seen in other tumors having a prominent neural component. The Wagner-Meissner-like corpuscles are viewed as evidence of a specialized type of differentiation of this neural component. To the best of our knowledge, they had not been previously reported in this setting.
10.1177/1066896907307306
pubmed_178_4961
Within infected tissue Treponema pallidum shows a characteristic predilection for perivascular areas. After intact capillaries had been prepared from rabbit brain tissue treponemes were incubated with isolated capillaries and visualised by darkfield, phase contrast, and scanning electron microscopy. The organisms rapidly attached to the surface of the capillaries at the tip of the treponeme; attached organisms retained motility for longer periods than unattached organisms. Treponema pertenue also attached to capillaries. Heat-inactivated T pallidum and three non-pathogenic treponemes did not, however, attach to the capillaries. Immune rabbit serum contains a factor that blocks the attachment of T pallidum to capillaries. Compared with cultured mammalian cells capillaries should provide a better tool for investigating host-parasite relationships in syphilis.
10.1136/sti.59.1.11
pubmed_191_18355
Persons with selective IgA deficiency carry an increased risk of coeliac disease, inflammatory bowel disease and perhaps also gastrointestinal malignancies. Inflammatory bowel disease is associated with an increased carriage of adherent and haemolytic Escherichia coli in the intestinal microflora. This study was designed to investigate whether IgA-deficient individuals carry E. coli with virulence-associated properties in their gut flora. The last free-lying colony of E. coli isolates obtained from rectal flora of 25 IgA-deficient and 20 age-matched control individuals was assayed by multiplex PCR for genes for the following adhesins or virulence determinants: P, type 1 and S fimbriae, Dr haemagglutinin, haemolysin, aerobactin and the capsular types K1 and K5. E. coli strains from the intestinal microflora of IgA-deficient individuals more often had the gene for S fimbriae (36% of the strains compared with 0% in control subjects, P=0.003) as well as for haemolysin (40 vs 10% of the strains, P=0.040). IgA-deficient individuals had instead lower frequencies of E. coli carrying genes for type 1 fimbriae in their microflora (68 vs 90%, P=0.14). The results suggest that IgA-deficient individuals carry an increased frequency of E. coli with potentially inflammatogenic properties in their microflora, which may contribute to the development of gastrointestinal disorders such as inflammatory bowel diseases.
10.1006/mpat.2001.0477
pubmed_512_13581
Cheyletus malaccensis is a predatory mite widely distributed in grain storages. It has been regarded as an important biological control agent for pest mites. In this study, we investigated the population genetic structure of C. malaccensis distributed in China based on the partial regions of mitochondrial COI and 12S rRNA genes. We collected 256 individuals of C. malaccensis from stored grain in 34 sites of China. We detected 50 COI gene haplotypes and nine 12S rRNA gene haplotypes. There were three clades in the haplotype network and Bayesian and maximum parsimony phylogenetic trees based on COI sequences, and two based on 12S rRNA sequences. The clustering of haplotypes was not correlated with their geographical distributions. The analysis of molecular variance, AMOVA, indicated that the genetic differentiation between populations was relatively weak. The major genetic differentiation was found within populations. We suggest that the genetic structure of C. malaccensis observed in this study may be the result of long-term climate fluctuations and recent human disturbances.
10.1007/s10493-016-0028-3
pubmed_93_23151
The genetic influence of single nucleotide polymorphisms (SNPs) on antidepressant efficacy has been previously demonstrated. To evaluate whether there are ethnic differences, we compared the allele frequencies of antidepressant efficacy-related SNPs between the Taiwanese population and four other populations in the HapMap database. We recruited 198 Taiwanese major depression patients and 106 Taiwanese controls. A panel of possible relevant SNPs (in brain-derived neurotrophic factor, 5-hydroxytryptamine receptor 2A, interleukin 1 beta, and G-protein beta 3 subunit genes) was selected for comparisons of allele frequencies using the χ(2) test. Our results suggested no difference between Taiwanese patients and controls, but there were significant differences among Taiwanese controls and the other four ethnic groups in brain-derived neurotrophic factor, 5-hydroxytryptamine receptor 2A, interleukin 1 beta and G-protein beta 3 subunit genes. We conclude that there are ethnic differences in the allele frequencies of antidepressant efficacy-related SNPs, and that the degree of variations is consistent with geographic distances. Further investigation is required to verify the attribution of genetic differences to ethnic-specific antidepressant responses.
10.1016/S0929-6646(11)60071-5
pubmed_399_9271
Specimens of tenosynovial sheath in 80 patients affected with carpal tunnel syndrome were studied histologically and by ultrastructural methods. The specimens were obtained from patients who had been submitted to decompression with neurolysis of the median nerve and synovectomy of the flexor tendons. They were divided into two groups. The first group, consisting of patients with irritative or compressive symptomatology of recent occurrence, presented thickened and oedematous synovial sheaths, with histological inflammatory features and deposits of Types 1 and 2 collagen in the perivascular and interstitial sites. Ultrastructural analysis revealed deficits in the synovial sheath cells in addition to interstitial collagen deposits. The second group of longstanding carpal tunnel syndrome with severe signs of compression presented diffuse thickening of the sheaths, with extensive fibrosis associated with hyalinosis, and Type 3 collagen deposit which at times was amyloid. It is suggested that thickening of the synovial sheaths in carpal tunnel syndrome occurs in successive stages of a proliferative nature and successively of a regressive type, with extensive fibro-hyalinosis.
pubmed_399_9271
pubmed_99_4247
Forty consecutive cases of causalgia treated during a 7-year period are presented. The patients ranged in age between 17 and 55 years, and all patients were males who received their nerve injuries from missile or shrapnel wounds. The greater occipital nerve was involved in two cases, median nerve in 10, sciatic nerve in 12, brachial plexus in seven, cauda equina in five, and multiple nerves in four cases. Each patient was treated with phenoxybenzamine, a postsynaptic alpha 1-blocker and presynaptic alpha 2-blocking agent. The drug was given orally in gradually increasing increments until a maximum daily dose of 40 to 120 mg was reached. Duration of treatment was usually 6 to 8 weeks. Total resolution of pain was achieved in all cases. The follow-up period ranged between 6 months and 6 years. Side effects of phenoxybenzamine were minimal and transient, consisting primarily of mild orthostatic hypotension and ejaculatory problems. We conclude that oral phenoxybenzamine is a simple, safe, and effective treatment of causalgia.
10.3171/jns.1984.60.6.1263
pubmed_879_6468
ASD genetic diagnosis has dramatically improved due to NGS technologies, and many new causative genes have been discovered. Consequently, new ASD phenotypes have emerged. An extensive exome sequencing study carried out by the Autism Sequencing Consortium (ASC) was published in February 2020. The study identified 102 genes which are de novo mutated in subjects affected by autism spectrum disorder (ASD) or similar neurodevelopmental disorders (NDDs). The majority of these genes was already known to be implicated in ASD or NDDs, whereas approximately 30 genes were considered "novel" as either they were not previously associated with ASD/NDDs or very little information about them was present in the literature. The aim of this work is to review the current literature since the publication of the ASC paper to see if new data mainly concerning genotype-phenotype correlations of the novel genes have been added to the existing one. We found new important clinical and molecular data for 6 of the 30 novel genes. Though the broad and overlapping neurodevelopmental phenotypes observed in most monogenic forms of NDDs make it difficult for the clinical geneticist to address gene-specific tests, knowledge of these new data can at least help to prioritize and interpret results of pangenomic tests to some extent. Indeed, for some of the new emerging genes analyzed in the present work, specific clinical features emerged that may help the clinical geneticist to make the final diagnosis by associating the genetic test results with the phenotype. The importance of this relatively new approach known as "reverse phenotyping" will be discussed.
10.3390/jcm10215060
pubmed_131_13260
Studies conducted on three normally menstruating women demonstrated a distinct cyclic variation in adherence of group B streptococcus type III to vaginal epithelial cells. This cyclic variation consisted of a gradual rise in adherence during the first half of the menstrual cycle, reaching a maximum on day 14, followed by a sharp decline to low levels of adherence that persisted through the second half of the cycle. These changes in adherence correlated directly with the variation in the pyknotic index of the vaginal epithelial cells, suggesting that hormonal factors played a role in adherence of group B streptococci to vaginal epithelium.
10.1016/0002-9378(81)90030-2
pubmed_868_3248
p40 is selective for ΔNp63 isoforms and appears to be more specific for squamous differentiation than p63. Its performance as a basal/myoepithelial marker in salivary gland tumors has only rarely been addressed in the literature. We thus compared the performance of p63 and p40 (ΔNp63) immunohistochemical stain as markers of basal, squamoid, and myoepithelial differentiation in 105 salivary gland tumors selected from our archives. The neoplasms were categorized according to their presumed phenotype as ductoacinar (n=45), biphasic (dual ductal and myoepithelial/basal differentiation, n=44), purely myoepithelial (n=5), and excretory duct phenotype (n=11). Only nuclear staining for p63 and p40 was considered positive. Distribution of staining was scored as: 0 (no staining), 1+ (1% to 25%), 2+ (26% to 50%), 3+ (51% to 75%), and 4+ (76% to 100%). Intensity was scored as weak, moderate, or strong. p63 and p40 highlighted the basal and myoepithelial cells in normal salivary gland tissue as well as basal/myoepithelial/squamoid elements in biphasic tumors, purely myoepithelial tumors, and excretory duct type tumors (4+ with strong staining for p63, and moderate staining for p40). All ductal tumors were negative for p40. However, 13/13 polymorphous low-grade adenocarcinoma/cribriform adenocarcinomas of salivary gland, 7/9 canalicular adenomas, and 3/5 mammary analog secretory carcinomas showed some degree of p63 staining. Thus, we confirm that p40 is a more specific basal/myoepithelial/squamoid marker than p63 in salivary gland tumors. A subset of ductal tumors show a discordant p63+/p40- immunoprofile that can be a pitfall if not recognized, but may also help distinguish these tumors from truly biphasic tumors and myoepithelial tumors.
10.1097/PAI.0000000000000222
pubmed_349_11718
BACKGROUND Ethiopia is embarking upon a ground-breaking plan to address the high levels of unmet need for mental health care by scaling up mental health care integrated within primary care. Health system governance is expected to impact critically upon the success or otherwise of this important initiative. The objective of the study was to explore the barriers, facilitators and potential strategies to promote good health system governance in relation to scale-up of mental health care in Ethiopia. METHODS A qualitative study was conducted using in-depth interviews. Key informants were selected purposively from national and regional level policy-makers, planners and service developers (n = 7) and district health office administrators and facility heads (n = 10) from a district in southern Ethiopia where a demonstration project to integrate mental health into primary care is underway. Topic guide development and analysis of transcripts were guided by an established framework for assessing health system governance, adapted for the Ethiopian context. RESULTS From the perspective of respondents, particular strengths of health system governance in Ethiopia included the presence of high level government support, the existence of a National Mental Health Strategy and the focus on integration of mental health care into primary care to improve the responsiveness of the health system. However, both national and district level respondents expressed concerns about low baseline awareness about mental health care planning, the presence of stigmatising attitudes, the level of transparency about planning decisions, limited leadership for mental health, lack of co-ordination of mental health planning, unreliable supplies of medication, inadequate health management information system indicators for monitoring implementation, unsustainable models for specialist mental health professional involvement in supervision and mentoring of primary care staff, lack of community mobilisation for mental health and low levels of empowerment and knowledge undermining meaningful involvement of stakeholders in local mental health care planning. CONCLUSIONS To support scale-up of mental health care in Ethiopia, there is a critical need to strengthen leadership and co-ordination at the national, regional, zonal and district levels, expand indicators for routine monitoring of mental healthcare, promote service user involvement and address widespread stigma and low mental health awareness.
10.1186/s13033-017-0144-4
pubmed_748_8784
Patients with neurodegenerative diseases by definition, experience slowly progressive aggravation of their condition; in the terminal stage many patients need some special management, tube feeding or suction, and thus home care is often difficult. For home care management, communication among all those involved, namely, medical staff, patients and their families, home doctor, nurse, physical therapist, helper and hospital, is very important. The results of a questionnaire we sent to the patients' families, clearly showed that they would hope to take home care as long as possible, be able to consult the specialists any time and have a reliable care-manager.
pubmed_748_8784
pubmed_52_13823
A 63-year-old male patient with locally advanced stage giant squamous cell skin cancer in the back was admitted to our clinic. He was treated by radiotherapy with palliative intent and achieved a nearly complete response. However, the tumor recurred 3 times after various palliative treatments (surgery, chemotherapy). The tumor finally progressed and the patient died 28 months after his first admission to the clinic. We present this case because of the unexpectedly excellent response to radiotherapy and achievement of successful palliation with other treatment modalities.
pubmed_52_13823
pubmed_306_15035
To test if proteolysis is involved in tumor cell extravasation, we developed an in vitro model where tumor cells cross an endothelial monolayer cultured on a basement membrane. Using this model we classified the ability of the cells to transmigrate through the endothelial cell barrier onto the underlying matrix, and scored this invasion according to the stage of passage through the endothelium. Metalloproteinase inhibitors reduced tumor cell extravasation by at least 35%. Visualization of protease and cell adhesion molecules by confocal microscopy demonstrated the cell surface localization of MMP-2, MMP-9, MT1-MMP, furin, CD44 and αvβ3, during the process of transendothelial migration. By the addition of inhibitors and bio-modulators we assessed the functional requirement of the aforementioned molecules for efficient migration. Proteolytic digestion occurred at the cell-matrix interface and was most evident during the migratory stage. All of the inhibitors and biomodulators affected the transition of the tumor cells into the migratory stage, highlighting the most prevalent use of proteolysis at this particular step of tumor cell extravasation. These data suggest that a proteolytic interface operates at the tumor cell surface within the tumor-endothelial cell microenvironment.
10.1371/journal.pone.0078413
pubmed_722_6267
Fingolimod (FTY720, Gilenya, 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol) is a novel drug recently approved in the United States for the oral treatment of relapsing multiple sclerosis. The compound is eliminated predominantly by ω-hydroxylation, followed by further oxidation. The ω-hydroxylation was the major metabolic pathway in human liver microsomes (HLM). The enzyme kinetics in HLM were characterized by a Michaelis-Menten affinity constant (K(m)) of 183 μM and a maximum velocity (V(max)) of 1847 pmol/(min · mg). Rates of fingolimod metabolism by a panel of HLM from individual donors showed no correlation with marker activities of any of the major drug-metabolizing cytochrome P450 (P450) enzymes or of flavin-containing monooxygenase (FMO). Among 21 recombinant human P450 enzymes and FMO3, only CYP4F2 (and to some extent CYP4F3B) produced metabolite profiles similar to those in HLM. Ketoconazole, known to inhibit not only CYP3A but also CYP4F2, was an inhibitor of fingolimod metabolism in HLM with an inhibition constant (K(i)) of 0.74 μM (and by recombinant CYP4F2 with an IC(50) of 1.6 μM), whereas there was only a slight inhibition found with azamulin and none with troleandomycin. An antibody against CYP4F2 was able to inhibit the metabolism of fingolimod almost completely in HLM, whereas antibodies specific to CYP2D6, CYP2E1, and CYP3A4 did not show significant inhibition. Combining the results of these four enzyme phenotyping approaches, we demonstrated that CYP4F2 and possibly other enzymes of the CYP4F subfamily (e.g., CYP4F3B) are the major enzymes responsible for the ω-hydroxylation of fingolimod, the main elimination pathway of the drug in vivo.
10.1124/dmd.110.035378
pubmed_794_2837
Avoidance of civilian casualties increasingly affects the political calculus of legitimacy in armed conflict. "Collateral damage" is a problem that can be managed through the material production of precision, but it is also the case that precision is a problem managed through the cultural production of collateral damage. Bearing decisively on popular perceptions of ethical conduct in recourse to political violence, childhood is an important site of meaning-making in this process. In pop culture, news dispatches, and social media, children, as quintessential innocents, figure prominently where the dire human consequences of imprecision are depicted. Children thus affect the practical "precision" of even the most advanced weapons, perhaps precluding a strike for their presence, potentially coloring it with their corpses. But who count as children, how, when, where, and why are not at all settled questions. Drawing insights from what the 2015 film, Eye in the Sky, reveals about a key social technology of governance we have already internalized, I explore how childhood is itself a terrain of engagement in the (un)making of precision.
10.1177/00108367211050274