Relationship of cognitions to fear of somatic symptoms: a test of the cognitive theory of panic.
The relationship between fear of physical anxiety symptoms and cognitive misinterpretation of those symptoms, as measured by responses to the Body Sensations Questionnaire and the Agoraphobic Cognitions Questionnaire, respectively, was examined for two samples of outpatients with panic disorder. Factor analytic and correlational analyses demonstrated that the patients' self-rated fear of specific physical and psychological symptoms was related to the frequency of specific logically related catastrophic thoughts (e.g., fears of heart palpitations or chest pressure with thoughts of a heart attack). This specific relationship between the somatic sensations and the catastrophic thoughts experienced by agoraphobic individuals provides further support for the cognitive theory of panic disorder. When the responses to the two questionnaires were factor-analyzed together, four factors were identified: symptoms and thoughts relevant to cardiovascular, neurological, gastrointestinal, and behavioral control systems, respectively. These findings suggest that the nature of panic-related fears varies across patients, and that the use of specific treatment interventions designed to modify the specific variations in their expression may be advisable.


Cicatricial ectropion in progressive skin diseases.
PURPOSE. To report the clinical course, patient care and treatment of cicatricial ectropion in patients with progressive skin diseases. METHOD. Review and photo series of three typical cases, which were followed for up to 10 years. RESULTS. In certain severe progressive skin diseases, tissue shrinkage may progress permanently. The soft lid tissue cannot withstand the forces of vertical lid traction. As a result, recurrent ectropion occurs. Patients with lamellar ichthyosis and with eruptive Grzybowski-type keratoacanthoma were followed for up to 10 years. Free skin grafts of severely involved donor skin were repeatedly transplanted to the lids. The lid margins were fixed by traction sutures in order to spread out the wound and to allow rapid vascular ingrowth and undisturbed healing. In this way, early wound contracture could be prevented. Nevertheless, follow-up revealed progressive shrinkage of the transplanted lid skin. Eversion of the lacrimal punctum was the first sign of progression. Epiphora was the leading complaint of the patients. Bacterial superinfection of the deepened lacrimal lake was more frequent in advanced ectropion. CONCLUSION. Patients should understand the natural history of their disease in order to accept multiple surgical procedures. Ectropion should be re-operated in time in order to reduce epiphora, to prevent corneal complications, and to avoid metaplasia and keratinization of the conjunctiva and thickening of the lid margin. The elasticity of the lid skin should be improved pharmacologically and by increasing the relative humidity of the home environment, especially in winter. Consistent vertical lid massage can delay recurrence.


Peritoneal fluid and solute transport: influence of treatment time, peritoneal dialysis modality, and peritonitis incidence.
The integrity of the peritoneal membrane in peritoneal dialysis (PD) is of major importance for adequate dialysis and fluid balance. However, alterations in peritoneal fluid transport, such as ultrafiltration failure, often develop during long-term PD. To investigate peritoneal solute and fluid transport and to analyze the influence of treatment time, peritonitis incidence, and PD modality (continuous ambulatory PD [CAPD] or automated PD [APD]), a cross-sectional study with an extended peritoneal transport test that used dextran 70 in 2 L of glucose was performed in 23 nonselected chronic PD patients. Compared were long-term (>40 mo) with short-term PD patients (<40 mo), CAPD with APD patients, and those with a peritonitis incidence of >0.25/yr to those with an incidence of <0.25/yr. Dialysate/plasma (D/P) ratio and mass transfer area coefficient of creatinine, lymphatic absorption rate (LAR), transcapillary ultrafiltration, and effective ultrafiltration were measured. Long-term PD patients had higher D/P ratio of creatinine (73.5 +/- 2.3% versus 65.9 +/- 2.2%; P < 0.01) and higher LAR (243 +/- 69 ml/4 h versus 96 +/- 31 ml/4 h; P < 0.03), both resulting in lower effective ultrafiltration (242 +/- 35 ml/4 h versus 324 +/- 30 ml/4 h; P < 0.05). D/P ratio (r = 0.66) and LAR (r = 0.67) were positively correlated to PD duration. Patients on APD compared with those on CAPD and patients with a history of peritonitis compared with those without did not differ in terms of D/P ratio, mass transfer area coefficient, LAR, transcapillary ultrafiltration, and effective ultrafiltration. Lower ultrafiltration after long-term PD is both the result of increased small solute transport and increased lymphatic absorption. APD or CAPD modality and peritonitis incidence do not have a significant influence on small solute transport or fluid kinetics.


[Generic drugs in psychopharmacology: pros and cons].
Legislation to facilitate process for generic products has been enacted and generic drugs have entered the market soon after the patent for the brand-name agent have expired. In every instance, the rationale has been economic since it is generally assumed that the copies are not only therapeutically equivalent but also a great deal less expensive than the original. Sometimes this may be so. In this short review several comments are made in order to establish the variables that may influence bioequivalence between the brand-name drug and its generics. Among them emphasis is given to the particle sizes, pharmaceutical supply, choice of the right excipient, in order to avoid possible interactions with the drug, ingredient quality and purity, etc. All these variables must be carefully controlled. Even so a patient who is changed from a trade name product to a generic drug (or vice versa) may respond a little differently, which is important in Psychopharmacology. Two or more products should be considered biologically equivalent only when it can demonstrated that they fulfil three conditions: that they have the same pharmaceutical properties; that they are equally effective in therapeutic use and that they are tolerated equally by patients being treated for the indicated uses. Regulatory agencies could require subsequent versions of an original therapeutic product the type of data regarding pharmacology, toxicology and chemical assessment that was mandatory for the introduction of the original.


Correlates of Stress and Coping among Jordanian Nursing Students during Clinical Practice in Psychiatric/Mental Health Course.
Training in psychiatric settings is stressful for nursing students. The purpose of this study was to examine the correlations between the students' characteristics, their stress degrees, stressors and types of coping strategies they experience during training in psychiatric course. A descriptive, correlational, longitudinal design was used. Sixty-five undergraduate nursing students were recruited randomly from five Jordanian universities. Self-report questionnaires were administered at the second semester of the 2012-2013 academic year. The findings showed that students who utilized avoidance or transference strategies reported high stress degrees. Moreover, the results showed that those students who were in the fourth year, with a low family income, who avoid extracurricular activities, with a low academic grade or who registered in other clinical course(s) reported high stress degrees. These findings present a worthy data for the clinical instructors that facilitate students training in psychiatric settings and promote their psychosocial well-being. Copyright © 2014 John Wiley & Sons, Ltd.


Descending interneurons of the stick insect connecting brain neuropiles with the prothoracic ganglion.
Stick insects respond to visual or tactile stimuli with whole-body turning or directed reach-to-grasp movements. Such sensory-induced turning and reaching behaviour requires interneurons to convey information from sensory neuropils of the head ganglia to motor neuropils of the thoracic ganglia. To date, descending interneurons are largely unknown in stick insects. In particular, it is unclear whether the special role of the front legs in sensory-induced turning and reaching has a neuroanatomical correlate in terms of descending interneuron numbers. Here, we describe the population of descending interneurons with somata in the brain or gnathal ganglion in the stick insect Carausius morosus, providing a first map of soma cluster counts and locations. By comparison of interneuron populations with projections to the pro- and mesothoracic ganglia, we then estimate the fraction of descending interneurons that terminate in the prothoracic ganglion. With regard to short-latency, touch-mediated reach-to-grasp movements, we also locate likely sites of synaptic interactions between antennal proprioceptive afferents to the deutocerebrum and gnathal ganglion with descending or ascending interneuron fibres. To this end, we combine fluorescent dye stainings of thoracic connectives with stainings of antennal hair field sensilla. Backfills of neck connectives revealed up to 410 descending interneuron somata (brain: 205 in 19 clusters; gnathal ganglion: 205). In comparison, backfills of the prothorax-mesothorax connectives stained only up to 173 somata (brain: 83 in 16 clusters; gnathal ganglion: 90), suggesting that up to 60% of all descending interneurons may terminate in the prothoracic ganglion (estimated upper bound). Double stainings of connectives and antennal hair field sensilla revealed that ascending or descending fibres arborise in close proximity of afferent terminals in the deutocerebrum and in the middle part of the gnathal ganglia. We conclude that two cephalothoracic pathways may convey cues about antennal movement and pointing direction to thoracic motor centres via two synapses only.


[Colorectal carcinoma with hemiparesis due to isolated brain metastases as an initial symptom - a case report].
We present a rare case of colorectal carcinoma in which hemiparesis was the initial symptom. A 75-year-old woman presented with incomplete left-sided hemiparesis. Brain magnetic resonance imaging(MRI)revealed a 13-mm mass in the right frontal lobe; the mass was resected via craniotomy. Pathological findings, which included the results of immunohistochemical analysis, indicated brain metastasis from colorectal cancer. Colonoscopy revealed advanced colon cancer in the ascending colon, and computed tomography(CT)did not reveal any extracranial metastases. Left-sided hemicolectomy was performed. Whole-brain radiotherapy was scheduled, but before initiation of the therapy, metastases were detected in the neck lymph node and right arm skin, and the brain metastases relapsed. The relapsed brain metastatic lesions were resected, and radiotherapy was administered to the whole brain and the severely painful site of skin metastasis. However, the patient died 201 days after presentation. Historically, systemic chemotherapy was considered ineffective for metastatic brain tumor, and the standard treatments for brain metastasis were surgery and radiotherapy. Although recent advances in systemic chemotherapy for colorectal cancer have resulted in improved patient survival, patients with brain metastases from colorectal cancer still have a poor prognosis. Modern chemotherapeutic agents, including molecularly targeted agents such as bevacizumab, should be validated for the management of brain metastases.


Human locomotion analysis: Identifying a dynamic mapping between upper and lower limb joints using the Koopman operator.
Human locomotion is a complex process that shows some inherent synergies and coordination, also called inter-joint coordination, between the upper and lower limbs. In this paper, we investigate the use of Koopman operator to identify a dynamic mapping between an upper limb and its contra-lateral lower limb in the human locomotion. We perform a human locomotion analysis in the sagittal plane and restrict the study to the forward motion; more specifically, a straight walking task at a constant speed. We use canes as walking aids to provide additional information about the terrain and enforce a frequency locking between the upper and lower body. This mapping will provide a model of the human locomotion.


Effect of reclining and chin-tuck position on the coordination between respiration and swallowing.
Chin-tuck position and reclining posture have been used in dysphagia patients to prevent aspiration during swallowing. However, both behavioural treatments may affect respiratory function. This study was carried out to test the hypothesis that if chin-tuck posture and body reclining affected respiratory function, this would be associated with altered coordination between respiration and swallowing. To investigate this hypothesis, respiratory parameters and manometry were used in each of four combinations of reclining posture and chin-tuck position. In the 60 degrees reclining with 60 degrees chin-tuck position, duration of swallowing apnea (0.89 s.d. 0.17 s) and submental electromyography burst (2.34 s.d. 0.84 s) were significantly longer when compared to both upright sitting and 30 degrees reclining positions. We conclude that 60 degrees reclining from vertical with 60 degrees chin-tuck may affect oral processing stages which delay and reduce a variety of oropharyngeal movements. These in turn significantly influence the coordination between respiration and swallowing.


Hypoxia-targeted bioreductive tyrosine kinase inhibitors with glutathione-depleting function.
Tyrosine kinase inhibitors may serve as ligands for kinases that are involved in normal cell differentiation or repair, thereby leading to toxicity. It may be possible to target such inhibitors to tumor cells by coupling them to hypoxia-activated bioreductive molecules. Such coupling can utilize or incorporate bonds that have a propensity to be preferentially oxidized by thiols such as intracellular glutathione (GSH). The resulting depletion of GSH may increase redox-mediated apoptosis. The resultant molecule is hence projected to act via multiple cell killing mechanisms: (i) inhibition of tumor kinases, (ii) tumor DNA disruption and (iii) causing increased redox-mediated apoptosis.


Effects of anabolic steroids and endurance exercise on cardiac performance.
This study examined the effects of anabolic steroids and exhaustive endurance exercise, and the combination of both treatments on in vitro cardiac contractile function. Fifty-two male Sprague-Dawley rats were randomly assigned, in groups of 13, to one of the four groups: sedentary control (C), steroid-treated (ST), exercise-trained (E), and exercise plus steroid treated (E+S). Nandrolone decanoate was administered to the steroid-treated groups every 7-9 days during the 10 weeks study, while the C and E groups received glycerol injection on these occasions. The exercised rats ran on a treadmill wearing a collar weight (2-3% of body weight) for 50 min, 5 days a week. In vitro ventricular performance was assessed in isolated Langendorff perfused hearts in response to increasing left ventricular balloon volumes. Left ventricular +dP/dt, dP/dt at 60 mmHg developed pressure, tension time index, and Emax (slope of the pressure-volume curves) were significantly (p < 0.05) lowered in the E+S group, as compared to the C, E, or ST group. Meanwhile, the E group exhibited a higher (p < 0.05) left ventricular systolic pressure (LVSP) than the C and E+S groups. No significant differences in dP/dt/P, heart weight (wt), and heart wt to body wt ratio were detected among the four groups. Rats subjected to endurance exercise or anabolic steroid treatment alone exhibited no change in LV function.(ABSTRACT TRUNCATED AT 250 WORDS)


Accumulation of integrase strand transfer inhibitor resistance mutations confers high-level resistance to dolutegravir in non-B subtype HIV-1 strains from patients failing raltegravir in Uganda.
Increasing first-line treatment failures in low- and middle-income countries (LMICs) have led to increased use of integrase strand transfer inhibitors (INSTIs) such as dolutegravir. However, HIV-1 susceptibility to INSTIs in LMICs, especially with previous raltegravir exposure, is poorly understood due to infrequent reporting of INSTI failures and testing for INSTI drug resistance mutations (DRMs). A total of 51 non-subtype B HIV-1 infected patients failing third-line (raltegravir-based) therapy in Uganda were initially selected for the study. DRMs were detected using Sanger and deep sequencing. HIV integrase genes of 13 patients were cloned and replication capacities (RCs) and phenotypic susceptibilities to dolutegravir, raltegravir and elvitegravir were determined with TZM-bl cells. Spearman's correlation coefficient was used to determine cross-resistance between INSTIs. INSTI DRMs were detected in 47% of patients. HIV integrase-recombinant virus carrying one primary INSTI DRM (N155H or Y143R/S) was susceptible to dolutegravir but highly resistant to raltegravir and elvitegravir (>50-fold change). Two patients, one with E138A/G140A/Q148R/G163R and one with E138K/G140A/S147G/Q148K, displayed the highest reported resistance to raltegravir, elvitegravir and even dolutegravir. The former multi-DRM virus had WT RC whereas the latter had lower RCs than WT. In HIV-1 subtype A- and D-infected patients failing raltegravir and harbouring INSTI DRMs, there is high-level resistance to elvitegravir and raltegravir. More routine monitoring of INSTI treatment may be advised in LMICs, considering that multiple INSTI DRMs may have accumulated during prolonged exposure to raltegravir during virological failure, leading to high-level INSTI resistance, including dolutegravir resistance.


Chronic peritoneal dialysis catheters in children: a fifteen-year experience of the Italian Registry of Pediatric Chronic Peritoneal Dialysis.
To analyze data on 503 chronic peritoneal dialysis (CPD) catheters implanted between 1986 and 2000 in pediatric patients enrolled in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (the Registry), comparing three different time periods: 1986-1990, 1991-1995, and 1996-2000. Retrospective study. 23 dialysis centers participating in the Registry. Data were collected from questionnaires filled in every year. The information for each peritoneal catheter included type, site and technique of insertion, exit-site orientation, exit-site care, complications, survival, and reason for removal. 503 catheters were implanted in 363 pediatric patients aged younger than 15 years at the start of CPD: 97 catheters in patients under 2 years of age, 67 in patients aged 2-5 years, and 339 in patients over 5 years of age. Mean patient age at onset of CPD was 8.0 +/- 5.1 years. All catheters were surgically implanted and omentectomy was performed in 82.4% of cases. The catheters used were Tenckhoff [468 (93.0%): 443 double cuff, 25 single cuff] and double-cuffed Valli [35 (7.0%)]. The entry site was in the midline in 153 cases (30.4%) and paramedian in 350 (69.6%). During 9048 dialysis-months we observed 451 catheter-related complications, yielding an incidence of 1 episode/20.1 CPD-months: 330 catheter infections (exit-site and/or tunnel infections), 26 leakages, 26 dislocations, 24 obstructions, 22 cuff extrusions, 6 hemoperitoneums, 17 others. 171 catheters were removed due to catheter-related causes; exit-site and/or tunnel infections were the main cause for removal (75.4%), followed by obstruction, dislocation, outer-cuff extrusion, and leakage. Younger children (< 2 years) had a higher risk of infectious causes of catheter removal compared to children aged 2-5 years (p = 0.004) and over 5 years of age (p = 0.002). During the 15-year observation period, a significant reduction in the incidence of leakage was observed and risk of leakage was lower in catheters with paramedian entry site compared to catheters with midline entry site. Removal and replacement of peritoneal catheters during the same surgical operation was performed in 76.3% of catheter removals. Catheter survival rate was 78.1% at 12 months, 58.5% at 24 months, 43.8% at 36 months, and 34.6% at 48 months. No difference in catheter survival was observed in younger children (< 2 years) compared with the two other age groups: < 2 years versus 2-5 years hazard ratio 0.7, 95% confidence interval (95%CI) 0.4-1.2; < 2 years versus > 5 years hazard ratio 0.8, 95%CI 0.5-1.1. In this survey, we observed better catheter survival in comparison with data reported by the Registry in 1998. Catheter survival improved especially in younger children (< 2 years), a group that previously had a decreased catheter survival rate compared to older age groups. In addition to the progressive increase in experience acquired by dialysis centers, this upward trend may also be related to greater use of double-cuffed catheters, with paramedian exit site, and a higher frequency of omentectomy.


Cloning, overexpression, and properties of a new thermophilic and thermostable esterase with sequence similarity to hormone-sensitive lipase subfamily from the archaeon Archaeoglobus fulgidus.
A new esterase gene from the hyperthermophilic archaeon Archaeoglobus fulgidus, reported to show homology with the mammalian hormone-sensitive lipase (HSL)-like group of the esterase/lipase family, was cloned by means of the polymerase chain reaction from the A. fulgidus genome. In order to compare the biochemical properties of this putative hyperthermophilic enzyme with those of the homologous, thermophilic member of HSL group, namely Alicyclobacillus (formerly Bacillus) acidocaldarius esterase 2 (EST2), an overexpression system in Escherichia coli was established. The recombinant protein, expressed in soluble and active form at 20 mg/liter of E. coli culture, was purified to homogeneity and characterized. The enzyme, a 35.5-kDa monomeric protein, was demonstrated to be a B"-type carboxylesterase (EC 22.214.171.124) on the basis of substrate specificity and the action of inhibitors. Among the p-nitrophenyl (PNP) esters tested the best substrate was PNP-hexanoate with K(m) and k(cat) values of 11 +/- 3 microM (mean +/- SD, n = 3) and 1014 +/- 38 s(-1) (mean +/- SD, n = 3), respectively, at 70 degrees C and pH 7.1. Inactivation by diethylpyrocarbonate, phenylmethylsulfonylfluoride, diisopropylfosfofluoridate (DFP), and physostigmine, as well as labeling with [(3)H]DFP, supported our previous suggestion of a catalytic triad made up of Ser(160)-His(285)-Asp(255). The sequence identity with the thermostable A. acidocaldarius EST2 was 42.5%. The enzyme proved to be much more stable than its Alicyclobacillus counterpart. The conformational dynamics of the two proteins were investigated by frequency-domain fluorometry and anisotropy decay and the activity/stability/temperature relationship was discussed.


Superoxide dismutase mimics, other mimics, antioxidants, prooxidants, and related matters.
A significant number of low molecular weight metal complexes as well as metal-free compounds that are capable of scavenging superoxide and/or other radicals and reactive species in simple systems have been proposed to be used as potential drugs in the case of various diseases and/or as antiaging agents. Some have been used or suggested to be used as diagnostic tools for the involvement of such species in biological processes. In the present work, analysis of such claims indicates that their use as specific detectors of superoxide or of other reactive oxygen species is unsupported and might be confusing. Many of these compounds exert beneficial effects by counteracting the toxic effects of oxidative stress in a significant number of models of pathological processes. However, it is concluded that these actions are more likely due to other effects including prooxidant actions and that their beneficial effects also may be exerted in pathological processes that do not practically involve reactive oxygen species. Adaptation may be a common mode of action explaining a sizable portion of the beneficial effect of the so-called mimics and other compounds including prooxidants.


[Effect of corundum-vancomycin composite on soft tissue reaction].
The ceramics on the basis of corundum is used for implantation in the form of porous and solid materials. The solid form was used to produce tissue endoprosthesis while porous form is mainly used to fill in the bone defects. The corundum ceramics are also known to be used as coatings for implants in orthopedics and dentistry. On the other hand there is still a need to find out the new way of treatment of the chronic bone infection, during which the traditional way of antibiotics therapy is no more effective. One of the possibly solution is to use the different biomaterials as drug carriers and in the bone surgery one of the best are porous corundum implants, being themselves of high biocompatibility, and additionally containing Vancomycin. The main target of the investigation presented in this paper was the comparative assessment of the corundum ceramics and its composite containing Vancomycin after implantation into back muscle of the total of 15 rats. During the post mortem macroscopic assessment in the tissues which surrounded the implants there were no any inflammatory neither pathological changes observed. In the microscopic findings, in early periods, the observed inflammatory tissue reaction for implants with vancomycin was significantly greater what could be explained by the high concentration of the antibiotic in the given material. On the basis of the results of macroscopic and microscopic findings we can state that the composite material of corundum ceramic containing vancomycin is of high compatibility and could be regarded as the good drug carrier.


While You Don't See Color, I See Bias: Identifying Barriers in Access to Graduate Medical Education Training.
There is a need to acknowledge and address issues of implicit and explicit bias within medical education. These biases can impact standardized test questions and scores, evaluations of clinical performance, and subsequent letters of recommendation, all of which can affect the selection of diverse candidates advancing through medical training. Biased behavior toward trainees can negatively impact their learning environment and career trajectory. This article outlines key definitions related to bias and discusses the ways in which bias potentially impacts selection and entry into Pulmonary and Critical Care Medicine fellowship training. Finally, we will describe some ways to mitigate bias within the fellowship selection process and training programs.


Diastereopure Fe(II) and Zn(II) complexes derived from a tridentate N,N',N-bis(methyl-L-prolinate)-substituted pyridine ligand.
A series of mononuclear iron(II) and zinc(II) complexes of the new chiral Py(ProMe)2 ligand (Py(ProMe)2 = 2,6-bis[[(S)-2-(methyloxycarbonyl)-1-pyrrolidinyl]methyl]pyridine) have been prepared. The molecular geometry in the solid state (X-ray crystal structures) of the complexes [FeCl2(Py(ProMe)2)] (1), [ZnCl2(Py(ProMe)2)] (2), [Fe(OTf)2(Py(ProMe)2)] (3), [Fe(Py(ProMe)2)(OH2)2](OTf)2 (4), and [Zn(OTf)(Py(ProMe)2)](OTf) (5) are reported. They all show a meridional NN'N coordination of the Py(ProMe)2 ligand. The bis-chloride derivatives 1 and 2 represent neutral isostructural five-coordinated complexes with a distorted geometry around the metal center. Unusual seven-coordinate iron(II) complexes 3 and 4 having a pentagonal bipyramidal geometry were obtained using weakly coordinating triflate anions. The reaction of Zn(OTf)2 with the Py(ProMe)2 ligand afforded complex 5 with a distorted octahedral geometry around the zinc center. All complexes were formed as single diastereoisomers. In the case of complexes 3-5, the oxygen atoms of both carbonyl groups of the ligand are also coordinated to the metal. The stereochemistry of the coordinated tertiary amine donors in complexes 3-5 is of opposite configuration as in complexes 1 and 2 as a result of the planar penta-coordination of the ligand Py(ProMe)2. Complexes 1, 2, and 5 have an overall -configuration at their metal center, while the Fe(II) ion in complexes 3 and 4 has the opposite delta-configuration (crystal structures and CD measurements). The magnetic moments of iron complexes 1, 3, and 4 correspond to that of high-spin d6 Fe(II) complexes. The solution structures of complexes 1-5 were characterized by means of UV-vis, IR, conductivity, and CD measurements and their electrochemical behavior. These studies showed that the coordination environment of 1 and 2 observed in the solid state is maintained in solution. In coordinating solvents, the triflate anion (3, 5) or water (4) co-ligands of complexes 3-5 are replaced by solvent molecules with retention of the original pentagonal bipyramidal and octahedral geometry, respectively.


Enhanced Red Emission in Er3+-Sensitized NaLuF4 Upconversion Crystals via Energy Trapping.
Luminescence efficiency of trivalent lanthanide-doped upconversion (UC) materials is significantly limited by luminescence concentration quenching. In this work, red UC emission is dramatically enhanced in Er3+-sensitized NaLuF4 UC crystals through energy trapping under multiple excitation wavelengths. Cross-relaxation quenching and the energy migration to internal lattice defects are simultaneously suppressed by confining the excitation energy in the Er3+ activator after introducing the Tm3+ or Ho3+ energy trapping center. The enhanced red UC emission (Er3+: 660 nm) mainly comes from the effective excitation energy confinement by Tm3+ and Ho3+ trapping centers through an easy energy transfer between Er3+ and Tm3+/Ho3+: 4I11/2 (Er3+) → 3H5 (Tm3+) → 4I13/2 (Er3+) and 4I11/2 (Er3+) → 5I6 (Ho3+) → 4I13/2 (Er3+). It is found that the confining efficiency of excitation energy in Er3+-sensitized NaLuF4 crystals is higher than that in Yb3+/Er3+ cosensitized NaLuF4 crystals, and the luminescence efficiency of Er3+-sensitized NaLuF4 crystals is much higher than that of Er3+-based host sensitization UC crystals (NaErF4). Moreover, Er3+-sensitized UC particles can be efficiently excited by three different wavelengths (808, 980, and 1532 nm), indicating huge advantages for applications in bioimaging, anticounterfeiting, and solar cells.


Sulfation of minoxidil by human platelet sulfotransferase.
In an attempt to determine whether (1) sulfotransferase activity in human platelets would convert minoxidil to minoxidil sulfate and (2) inter-subject variations in this sulfotransferase activity could be noted, platelet homogenates were incubated with minoxidil and 35S-PAPS in HEPES buffer at 37 degrees C for 30 min. Radioactivity which was extracted into ethyl acetate and shown by HPLC to elute with authentic minoxidil sulfate was counted by scintillation counting. Aliquots of the platelet homogenates were also preincubated at 43 degrees C for 15 min to determine the thermal stability of the sulfotransferase activity. Sulfotransferase activity in platelets from 48 adult males ranged from 0.9-13.2 pmol minoxidil sulfate produced/10(7) platelets per 30 min (mean 4.91 +/- 2.84 pmol/10(7) platelets per 30 min +/- SD). Thermal stable sulfotransferase activity ranged from 0.2-7.6 pmol minoxidil produced/10(7) platelets per 30 min and varied from 15 to 57% of the total sulfotransferase activity. Thus, the results indicate that human platelets can effect the sulfation of minoxidil and that sulfotransferase activity does show inter-subject variation.


Generation of 3D skin equivalents fully reconstituted from human induced pluripotent stem cells (iPSCs).
Recent generation of patient-specific induced pluripotent stem cells (PS-iPSCs) provides significant advantages for cell- and gene-based therapy. Establishment of iPSC-based therapy for skin diseases requires efficient methodology for differentiating iPSCs into both keratinocytes and fibroblasts, the major cellular components of the skin, as well as the reconstruction of skin structures using these iPSC-derived skin components. We previously reported generation of keratinocytes from human iPSCs for use in the treatment of recessive dystrophic epidermolysis bullosa (RDEB) caused by mutations in the COL7A1 gene. Here, we developed a protocol for differentiating iPSCs into dermal fibroblasts, which also produce type VII collagen and therefore also have the potential to treat RDEB. Moreover, we generated in vitro 3D skin equivalents composed exclusively human iPSC-derived keratinocytes and fibroblasts for disease models and regenerative therapies for skin diseases, first demonstrating that iPSCs can provide the basis for modeling a human organ derived entirely from two different types of iPSC-derived cells.


Negotiation-centred versus client-centred: which approach should be used?
For nearly 20 years, Canadian occupational therapists have attached great importance to the client-centred approach within their practice. Professionals have agreed to define this approach through a philosophy built around the concepts of respect, power and partnership. But no reported work has really clarified what is meant by these three fundamental concepts. This article attempts to define the concepts of respect and power in the therapist-client relationship through a review of occupational therapy and related health and social sciences literature. It raises the question: "In the professional-client relationship, should the power reside with the client or is a more balanced approach needed?" This paper also proposes using the term negotiation instead of partnership, since negotiation seems to offer more applications for occupational therapy practice. The objective of the authors who advocate for greater negotiation between client and therapist is to stimulate analysis.


Proprioceptive drift without illusions of ownership for rotated hands in the "rubber hand illusion" paradigm.
The rubber hand illusion is one reliable way to experimentally manipulate the experience of body ownership. However, debate continues about the necessary and sufficient conditions eliciting the illusion. We measured proprioceptive drift and the subjective experience (via questionnaire) while manipulating two variables that have been suggested to affect the intensity of the illusion. First, the rubber hand was positioned either in a posturally congruent position, or rotated by 180°. Second, either the anatomically same rubber hand was used, or an anatomically incongruent one. We found in two independent experiments that a rubber hand rotated by 180° leads to increased proprioceptive drift during synchronous visuo-tactile stroking, although it does not lead to feelings of ownership (as measured by questionnaire). This dissociation between drift and ownership suggests that proprioceptive drift is not necessarily a valid proxy for the illusion when using hands rotated by 180°.


A multiscale framework based on the physiome markup languages for exploring the initiation of osteoarthritis at the bone-cartilage interface.
The initiation of osteoarthritis (OA) has been linked to the onset and progression of pathologic mechanisms at the cartilage-bone interface. Most importantly, this degenerative disease involves cross-talk between the cartilage and subchondral bone environments, so an informative model should contain the complete complex. In order to evaluate this process, we have developed a multiscale model using the open-source ontologies developed for the Physiome Project with cartilage and bone descriptions at the cellular, micro, and macro levels. In this way, we can effectively model the influence of whole body loadings at the macro level and the influence of bone organization and architecture at the micro level, and have cell level processes that determine bone and cartilage remodeling. Cell information is then passed up the spatial scales to modify micro architecture and provide a macro spatial characterization of cartilage inflammation. We evaluate the framework by linking a common knee injury (anterior cruciate ligament deficiency) to proinflammatory mediators as a possible pathway to initiate OA. This framework provides a "virtual bone-cartilage" tool for evaluating hypotheses, treatment effects, and disease onset to inform and strengthen clinical studies.


Structural zeroes and zero-inflated models.
In psychosocial and behavioral studies count outcomes recording the frequencies of the occurrence of some health or behavior outcomes (such as the number of unprotected sexual behaviors during a period of time) often contain a preponderance of zeroes because of the presence of 'structural zeroes' that occur when some subjects are not at risk for the behavior of interest. Unlike random zeroes (responses that can be greater than zero, but are zero due to sampling variability), structural zeroes are usually very different, both statistically and clinically. False interpretations of results and study findings may result if differences in the two types of zeroes are ignored. However, in practice, the status of the structural zeroes is often not observed and this latent nature complicates the data analysis. In this article, we focus on one model, the zero-inflated Poisson (ZIP) regression model that is commonly used to address zero-inflated data. We first give a brief overview of the issues of structural zeroes and the ZIP model. We then given an illustration of ZIP with data from a study on HIV-risk sexual behaviors among adolescent girls. Sample codes in SAS and Stata are also included to help perform and explain ZIP analyses.


pH-lactate dissociation during anoxic insult: taurine effect.
Taurine, a sulfur amino acid abundant in brain of the fetus and early day neonate, has been postulated to play a major role in mediating the immature brain's unusually high buffering ability for lactic acidosis reported previously. In this study, we directly investigated this 'taurine effect' using a 10-day-old rat pup model and multinuclear (31P and 1H) nuclear magnetic resonance (NMR) in-vivo spectroscopy. Brain of taurine-supplemented pups exhibited significantly higher acid buffering ability against lactic acidosis than age-matched control pups. The study supports the hypothesis that high levels of free cytosolic taurine increase the brain's ability to buffer against lactic acidosis.


Self-assembly of patchy particles into diamond structures through molecular mimicry.
Fabrication of diamond structures by self-assembly is a fundamental challenge in making three-dimensional photonic crystals. We simulate a system of model hard particles with attractive patches and show that they can self-assemble into a diamond structure from an initially disordered state. We quantify the extent to which the formation of the diamond structure can be facilitated by "seeding" the system with small diamond crystallites or by introducing a rotation interaction to mimic a carbon-carbon antibonding interaction. Our results suggest patchy particles may serve as colloidal "atoms" and "molecules" for the bottom-up self-assembly of three-dimensional crystals.


New flow cytometric technologies for the 21st century.
The envelope that defines the limits within which flow cytometry was developed is being rapidly expanded. For example: detection sensitivity has been extended to single molecules, the size range of "particle" analysis now extends from DNA fragments to plankton (1,000.+ microns), cell and chromosome sorting rates are being increased dramatically by using inactivation procedures (50,000 per second versus 2,000 per second), rapid kinetic flow cytometry enables real-time analysis of molecular assembly and cell function in the sub-second time domain, the lifetime of a fluorochrome bound to a single cell can be measured with nsec precision, and classical karyotype information (cell to cell heterogeneity) can be determined in a flow based system. These frontiers have greatly expanded the range of new and exciting flow cytometric based biomedical applications. New enabling technologies have provided the means to measure DNA cleavage by the structure-specific nuclease, human Flap Endonuclease (FEN-1), in the 300 msec time frame. Phase sensitive measurements and fluorescence lifetime are proving to be major advances for understanding molecular environments that change with, for example, the process of apoptosis. The ability to detect single fluorescent molecules has been applied to the analysis of DNA fragments obtained from enzymatic digestion of lambda DNA. This technology is being used to rapidly and very accurately size DNA fragments for the human genome project. Optical chromosome selection is a faster, better, less complex approach to chromosome sorting. This method is based on the induction of specific damage to the DNA of selected chromosomes. Lastly, the miniaturization of a single cell fractionator has made it possible to perform single cell flow cytogenetics.


The antenatal prevention of congenital syphilis in a peri-urban settlement.
The obstetric records of patients from Khayelitsha were examined to assess the efficiency of a system for the antenatal prevention of congenital syphilis, and to identify points of breakdown in the process. Seventy-seven (12.7%) of 607 mothers had serological evidence of syphilis, including 10 (32.3%) of 31 mothers who had received no antenatal care. Of 70 patients who required routine management, only 36 (51.4%) received 3 or more of the recommended 4 penicillin injections. Two main weaknesses in the system were identified. One was the centralisation of serological testing. This delayed results reaching the relevant unit, and was responsible for a high cumulative attrition of patients during the many stages necessitated by the centralised testing. The other was a 24.5% attrition of patients referred from the antenatal clinic to a separate sexually transmitted diseases clinic.


Consequences of anode interfacial layer deletion. HCl-treated ITO in P3HT:PCBM-based bulk-heterojunction organic photovoltaic devices.
In studies to simplify the fabrication of bulk-heterojunction organic photovoltaic (OPV) devices, it was found that when glass/tin-doped indium oxide (ITO) substrates are treated with dilute aqueous HCl solutions, followed by UV ozone (UVO), and then used to fabricate devices of the structure glass/ITO/P3HT:PCBM/LiF/Al, device performance is greatly enhanced. Light-to-power conversion efficiency (Eff) increases from 2.4% for control devices in which the ITO surface is treated only with UVO to 3.8% with the HCl + UVO treatment--effectively matching the performance of an identical device having a PEDOT:PSS anode interfacial layer. The enhancement originates from increases in V(OC) from 463 to 554 mV and FF from 49% to 66%. The modified-ITO device also exhibits a 4x enhancement in thermal stability versus an identical device containing a PEDOT:PSS anode interfacial layer. To understand the origins of these effects, the ITO surface is analyzed as a function of treatment by ultraviolet photoelectron spectroscopy work function measurements, X-ray photoelectron spectroscopic composition analysis, and atomic force microscopic topography and conductivity imaging. Additionally, a diode-based device model is employed to further understand the effects of ITO surface treatment on device performance.


Major groove recognition elements in the middle of the T7 RNA polymerase promoter.
T7 RNA polymerase recognizes a relatively small promoter extending only 17 base pairs upstream from the start site for transcription. A model for this recognition suggests that the enzyme interacts with the major groove of duplex DNA in the region centered at position -9 [Muller, D.K., et al. (1989) Biochemistry 28, 3306-3313], and recent kinetic analyses of promoters containing base analogs at positions -10 and -11 have provided support for this model [Schick, C., & Martin, C.T. (1993) Biochemistry 32, 4275-4280; Schick, C., & Martin, C.T. (1995) Biochemistry 34, 666-672]. In the current work, we extend this analysis across the proposed major groove, identifying specific base functional group contacts at positions -9 through -5. Specifically, the 6-carbonyl of guanine at positions -9 and -7, the 6-amino group of adenine at position -8, the 5-methyl group of thymine at position -6 and the 2-amino group of guanine at position -5 are identified as primary contacts. The results strongly support the model for duplex recognition in this region of the promoter and suggest that recognition continues along one face of the helix beyond the major groove and into the adjoining minor groove at position -5, where helix melting begins.


Hospitalization in Patients with Psoriasis: Impact of Biological Therapies on Temporal Evolution.
Psoriasis is an immunomediated disease mostly controlled at the outpatient level, although there is a low percentage of patients that require systemic drugs or even hospitalization for an adequate control. Biological drugs have represented a turning point in its treatment. So far, despite the growing interest in psoriasis and its management with biological therapies, there is a lack of studies focusing on their impact on hospitalization, a relevant issue to patients and to the sustainability of our healthcare system. In this study, we aimed to describe the temporal evolution of the hospitalizations of patients with psoriasis throughout the period between eight years before the commercialization of the first biological drugs and present, and secondly, whether this market irruption was related to a decrease in the number of admissions. Data was collected retrospectively from the Dermatology department of the Complexo Hospitalario Universitario de Ponte- vedra (CHUP) including patients of all ages with a diagnosis of psoriasis and at least one admission to the department of Dermatology along the study period. We established different time periods for comparing the average hospitalizations per 100,000 inhabitants-year and the average stay, considering that the first biologic drug marketed for the treatment of psoriasis was in 2004. Regression models indicated a significant change in the temporal trend of the hospitalization rate per 100,000 inhabitants-year starting in 2004. In all cases, a gradual and significant decrease in the number of admissions per 100,000 inhabitants-year and in the average hospitalization rate per psoriasis per 100,000 inhabitants-year along the study period were found. There was also a significant decrease in medical hospitalizations and medical hospitalizations excluding psoriasis throughout the study period. In our study population hospitalizations for psoriasis descended progressively and significantly from 2004. So far there are no extensive data on the impact of biological therapies on psoriasis hospitalization. J Drugs Dermatol. 2021;20(2):208-214. doi:10.36849/JDD.4931.


Quantitative Assessment of Protein Adsorption by Combination of the Enzyme-Linked Immunosorbent Assay with Radioisotope-Based Studies.
Protein adsorption at polymer surfaces has been investigated by means of both ELISA and radiolabeling techniques. Most of the data obtained are linearly related to each other for protein concentrations between 0.01 and 1 µg/ml, i.e., the concentration range in which the maximum amount of adsorbed active protein (ELISA) is achieved. The correlation of ELISA data with radioisotope-based measurements allows quantification of the former. Specific correlation factors are described. Adsorption is shown to be strongly dependent on the polymer/protein system. Copyright 1999 Academic Press.


Light-Triggered Adhesive Silk-Based Film for Effective Photodynamic Antibacterial Therapy and Rapid Hemostasis.
Successful control of massive hemorrhage in deep wounds with irregular shape and low elasticity still remains great challenges in the clinic. As the wound sites are usually at risk of bacterial infection, it is necessary to design an ideal hemostatic agent with rapid hemostasis and excellent antibacterial activity. In this study, we developed a light responsive hemostatic film for effective handling of liver bleeding with promising photodynamic therapy against S. aureus onnear infrared (NIR) irradiation. Based on silk fibroin, the film exhibited desirable biocompatibility and mechanical property as a hemostat tape. Significantly, the film tape achieved excellent tissue adhesion and hemostasis in vivo within 2 min of UV exposure, which would have a great potential as a multifunctional biomedical material in the field of tissue repair such as wound healing, bone repair, and nerve regeneration.


An oral commensal attenuates Pseudomonas aeruginosa-induced airway inflammation and modulates nitrite flux in respiratory epithelium.
Respiratory infections are a leading cause of morbidity and mortality in people with cystic fibrosis (CF). These infections are polymicrobial in nature with overt pathogens and other colonizing microbes present. Microbiome data have indicated that the presence of oral commensal bacteria in the lungs is correlated with improved outcomes. We hypothesize that one oral commensal, Streptococcus parasanguinis, inhibits CF pathogens and modulates the host immune response. One major CF pathogen is Pseudomonas aeruginosa, a Gram-negative, opportunistic bacterium with intrinsic drug resistance and an arsenal of virulence factors. We have previously shown that S. parasanguinis inhibits P. aeruginosa in vitro in a nitrite-dependent manner through the production of reactive nitrogen intermediates. In this study, we demonstrate that while this mechanism is evident in a cell culture model of the CF airway, an alternative mechanism by which S. parasanguinis may improve outcomes for people with CF is through immunomodulation.


Multi-omics integrative analysis and survival risk model construction of non-small cell lung cancer based on The Cancer Genome Atlas datasets.
Lung cancer is a major cause of cancer-associated mortality worldwide. However, the association between multi-omics data and survival in lung cancer is not fully understood. The present study investigated the performance of the methylation survival risk model in multi-platform integrative molecular subtypes and aimed to identify copy number (CN) variations and mutations that are associated with survival risk. The present study analyzed 439 lung adenocarcinoma cases based on DNA methylation, RNA, microRNA (miRNA), DNA copy number and mutations from The Cancer Genome Atlas datasets. First, six cancer subtypes were identified using integrating DNA methylation, RNA, miRNA and DNA copy number data. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used to extract methylation sites of survival model and calculate the methylation-based survival risk indices for all patients. Survival for patients in the high-risk group was significantly lower compared with that for patients in the low-risk group (P<0.05). The present study also assessed methylation-based survival risks of the six subtypes and analyzed the association between survival risk and non-silent mutation rate, number of segments, fraction of segments altered, aneuploidy score, number of segments with loss of heterozygosity (LOH), fraction of segments with LOH and homologous repair deficiency. Finally, the specific copy number regions and mutant genes associated with the different subtypes were identified (P<0.01). Chromosome regions 17q24.3 and 11p15.5 were identified as those with the most survival risk-associated copy number variation regions, while a total of 29 mutant genes were significantly associated with survival (P<0.01).


RCRA toxicity characterization of discarded electronic devices.
The potential for discarded electronic devices to be classified as toxicity characteristic (TC) hazardous waste under provisions of the Resource Conservation and Recovery Act (RCRA) using the toxicity characteristic leaching procedure (TCLP) was examined. The regulatory TCLP method and two modified TCLP methods (in which devices were disassembled and leached in or near entirety) were utilized. Lead was the only element found to leach at concentrations greater than its TC limit (5 mg/L). Thirteen different types of electronic devices were tested using either the standard TCLP or modified versions. Every device type leached lead above 5 mg/L in at least one test and most devices leached lead above the TC limit in a majority of cases. Smaller devices that contained larger amounts of plastic and smaller amounts of ferrous metal (e.g., cellular phones, remote controls) tended to leach lead above the TC limit at a greater frequency than devices with more ferrous metal (e.g., computer CPUs, printers).


Phycobilisome Structure of Porphyridium cruentum: POLYPEPTIDE COMPOSITION.
Purified phycobilisomes of Porphyridium cruentum were solubilized in sodium dodecyl sulfate and resolved by sodium dodecyl sulfate-acrylamide gel electrophoresis into nine colored and nine colorless polypeptides. The colored polypeptides accounted for about 84% of the total stainable protein, and the colorless polypeptides accounted for the remaining 16%. Five of the colored polypeptides ranging in molecular weight from 13,300 to 19,500 were identified as the alpha and beta subunits of allophycocyanin, R-phycocyanin, and phycoerythrin. Three others (29,000-30,500) were orange and are probably related to the gamma subunit of phycoerythrin. Another colored polypeptide had a molecular weight of 95,000 and the characteristics of long wavelength-emitting allophycocyanin. Sequential dissociation of phycobilisomes, and analysis of the polypeptides in each fraction, revealed the association of a 32,500 molecular weight colorless polypeptide with a phycoerythrin fraction. The remaining eight colorless polypeptides were in the core fraction of the phycobilisome, which also was enriched in allophycocyanin. In addition, the core fraction was enriched in a colored 95,000 dalton polypeptide. Inasmuch as a polypeptide with the same molecular weight is found in thylakoid membranes (free of phycobilisomes), it is suggested that this polypeptide is involved in anchoring phycobilisomes to thylakoid membranes.


Analysis of phenylalanine hydroxylase genotypes and hyperphenylalaninemia phenotypes using L-[1-13C]phenylalanine oxidation rates in vivo: a pilot study.
Hyperphenylalaninemia (HPA) resulting from deficient activity of phenylalanine hydroxylase (PAH) is caused by mutations in the human PAH gene (McKusick 261600). Herein, we report a noninvasive method to: 1) estimate whole-body phenylalanine oxidation in patients with HPA and 2) compare effects of mutant genotypes on phenotypes. We used oral L-[1-13C]phenylalanine as a substrate and measured 13CO2 formation in the first hour as an index of phenylalanine oxidation rates in: 1) patients with PKU (n = 6), variant phenylketonuria (PKU) (n = 7) and non-PKU HPA (n = 4); 2) obligate heterozygotes (n = 18); and 3) controls (n = 8). PAH mutations were identified by PCR, denaturing gradient gel electrophoresis, and DNA sequencing. Phenylalanine oxidation rates demonstrated a gene dosage effect; oxidation in heterozygotes was intermediate between probands and controls. The three classes of HPA had different mean oxidation rates (PKU < variant PKU < non-PKU HPA). The in vivo phenotype (HPA class or whole-body oxidation rate) did not always correspond to prediction from in vitro expression analysis of the mutation effect on enzyme activity. The findings indicate that the in vivo metrical trait (phenylalanine oxidation rate) is not a simple equivalent of phenylalanine hydroxylation activity (unit of protein phenotype) and, as expected, is an emergent property under the control of more than the PAH locus.


Frequency and spectrum of mutations across 94 cancer predisposition genes in African American women with invasive breast cancer.
African American women are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors which are included in current guidelines for identifying women who may benefit from genetic testing. Commercial breast cancer predisposition genetic panels, based largely on data derived from women of European ancestry, may not capture the full spectrum of cancer predisposition genes associated with breast cancer in African American women. Between 2001 and 2018, 488 unselected African American women with invasive breast cancer enrolled in the Clinical Breast Care Project. National Comprehensive Cancer Network (NCCN) Hereditary Cancer testing criteria version 1.2020 were applied to determine genetic risk. Targeted sequencing was performed using the TruSight Cancer panel and variants classified using the ClinVar database. Using NCCN criteria, 64.1% of African American women would be eligible for genetic testing. Fifty pathogenic or likely pathogenic mutations were detected in 19 genes with the highest frequencies in BRCA2 (29.4%) and BRCA1 (15.7%). Mutation frequencies in test-eligible and test-ineligible women were 13.1% and 3.5%, respectively. One-third of women harbored variants that could not be classified. While these data do not suggest a need to expand current commercial gene panels, NCCN criteria would fail to identify 12.5% of African American women with mutations in hereditary cancer predisposing genes.


Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo.
Cells rely on autophagy to clear misfolded proteins and damaged organelles to maintain cellular homeostasis. In this study we use the new autophagy inhibitor PIK-III to screen for autophagy substrates. PIK-III is a selective inhibitor of VPS34 that binds a unique hydrophobic pocket not present in related kinases such as PI(3)Kα. PIK-III acutely inhibits autophagy and de novo lipidation of LC3, and leads to the stabilization of autophagy substrates. By performing ubiquitin-affinity proteomics on PIK-III-treated cells we identified substrates including NCOA4, which accumulates in ATG7-deficient cells and co-localizes with autolysosomes. NCOA4 directly binds ferritin heavy chain-1 (FTH1) to target the iron-binding ferritin complex with a relative molecular mass of 450,000 to autolysosomes following starvation or iron depletion. Interestingly, Ncoa4(-/-) mice exhibit a profound accumulation of iron in splenic macrophages, which are critical for the reutilization of iron from engulfed red blood cells. Taken together, the results of this study provide a new mechanism for selective autophagy of ferritin and reveal a previously unappreciated role for autophagy and NCOA4 in the control of iron homeostasis in vivo.


A perspective on early commercial applications of voice-processing technology for telecommunications and aids for the handicapped.
The Colloquium on Human-Machine Communication by Voice highlighted the global technical community's focus on the problems and promise of voice-processing technology, particularly, speech recognition and speech synthesis. Clearly, there are many areas in both the research and development of these technologies that can be advanced significantly. However, it is also true that there are many applications of these technologies that are capable of commercialization now. Early successful commercialization of new technology is vital to ensure continuing interest in its development. This paper addresses efforts to commercialize speech technologies in two markets: telecommunications and aids for the handicapped.


The Benefits of Physician Training Programs for Rural Communities: Lessons Learned from the Teaching Health Center Graduate Medical Education Program.
Rural communities disproportionately face preventable chronic diseases and death from treatable conditions. Health workforce shortages contribute to limited health care access and health disparities. Efforts to address workforce shortages have included establishing graduate medical education programs with the goal of recruiting and retaining physicians in the communities in which they train. However, rural communities face a number of challenges in developing and maintaining successful residency programs, including concerns over financial sustainability and the integration of resident trainees into existing clinical practices. Despite these challenges, rural communities are increasingly interested in investing in residency programs; those that are successful see additional benefits in workforce recruitment, access, and quality of care that have immediate and direct impact on the health of rural communities. This commentary examines the challenges and benefits of rural residency programs, drawing from lessons learned from the Health Resources and Services Administration's Teaching Health Center Graduate Medical Education program.


The heart in congenital diaphragmatic hernia: Knowns, unknowns, and future priorities.
There is growing recognition that the heart is a key contributor to the pathophysiology of congenital diaphragmatic hernia (CDH), in conjunction with developmental abnormalities of the lung and pulmonary vasculature. Investigations to date have demonstrated altered fetal cardiac morphology, notably relative hypoplasia of the fetal left heart, as well as early postnatal right and left ventricular dysfunction which appears to be independently associated with adverse outcomes. However, many more unknowns remain, not least an understanding of the genetic and cellular basis for cardiac dysplasia and dysfunction in CDH, the relationship between fetal, postnatal and long-term cardiac function, and the impact on other parts of the body especially the developing brain. Consensus on how to measure and classify cardiac function and pulmonary hypertension in CDH is also required, potentially using both non-invasive imaging and biomarkers. This may allow routine assessment of the relative contribution of cardiac dysfunction to individual patient pathophysiological phenotype and enable better, individualized therapeutic strategies incorporating targeted use of fetal therapies, cardiac pharmacotherapies, and extra-corporeal membrane oxygenation (ECMO). Collaborative, multi-model approaches are now required to explore these unknowns and fully appreciate the role of the heart in CDH.


Discrete breathers in two-dimensional Josephson-junction arrays.
We have proposed theoretically and studied numerically the existence of discrete breathers (intrinsic localized modes) in the dynamics of a two-dimensional Josephson-junction array biased by radio-frequency fields. The solutions are linearly stable in the framework of the Floquet theory and robust in the presence of thermal fluctuations. We have also discussed the conditions for realizing an experimental detection of these modes.


A Case Series on Uterine Arteriovenous Malformations: A Life-Threatening Emergency in Young Women.
Uterine arteriovenous malformation (AVM) is a rare condition, with few cases reported in the literature. Despite being rare, it is a potentially life-threatening condition in women of child-bearing age. It should be considered in the differential diagnosis of prolonged or irregular vaginal bleeding, which, otherwise, can lead to critical complications ending up in severe morbidity and mortality. This case series describes four cases of young Asian women aged between 33 and 38 years who presented with irregular vaginal bleeding. Trans-abdominal ultrasound of the pelvis showed increased vascularity with multi-directional blood flow in the uterus. Magnetic resonance imaging (MRI) confirmed an arteriovenous malformation in all cases. All cases remained stable through the diagnostic journey. Embolization of the arteriovenous malformation was performed successfully in three cases and one case was managed conservatively on hormones. Later, two of them conceived within a year and had live births at term. The aim of reporting these cases is to share the common presentation of this condition and our experience in making the diagnosis and treatment of such patients. Although a few cases are reported world over, none was reported earlier from Pakistani Asian women.


Nanocomposite Architecture for Rapid, Spectrally-Selective Electrochromic Modulation of Solar Transmittance.
Two active electrochromic materials, vacancy-doped tungsten oxide (WO(3-x)) nanocrystals and amorphous niobium oxide (NbOx) glass are arranged into a mesostructured architecture. In a strategy applicable across electrochemical applications, the critical dimensions and interfacial connections in the nanocomposite are designed to optimize pathways for electrochemical charging and discharging. The result is an unprecedented optical range for modulation of visible and near-infrared solar radiation with rapid switching kinetics that indicate the WO(3-x) nanocrystal framework effectively pumps charge out of the normally sluggish NbOx glass. The material is durable for at least 2000 electrochemical cycles.


A Review of Structural Adhesive Joints in Hybrid Joining Processes.
Hybrid joining (HJ) is the combination of two or more joining techniques to produce joints with enhanced properties in comparison to those obtained from their parent techniques. Their adoption is widespread (metal to metal joint, composite to composite and composite to metal) and is present in a vast range of applications including all industrial sectors, from automotive to aerospace, including naval, construction, mechanical and utilities. The objective of this literature review is to summarize the existing research on hybrid joining processes incorporating structural adhesives highlighting their field of application and to present the recent development in this field. To achieve this goal, the first part presents an introduction on the main class of adhesives, subdivided by their chemical nature (epoxy, polyurethane, acrylic and cyanoacrylate, anaerobic and high-temperature adhesives) The second part describes the most commonly used Hybrid Joining (HJ) techniques (mechanical fastening and adhesive bonding, welding processes and adhesive bonding) The third part of the review is about the application of adhesives in dependence of performance, advantage and disadvantage in the hybrid joining processes. Finally, conclusions and an outlook on critical challenges, future perspectives and research activities are summarized. It was concluded that the use of hybrid joining technology could be considered as a potential solution in various industries, in order to reduce the mass as well as the manufacturing cost.


Active specific immunotherapy with an autologous tumor cell vaccine in patients with resected non-small cell lung cancer.
Eighteen postoperative patients with non-small cell lung cancer were actively immunized with a vaccine that included autologous cryopreserved irradiated tumor cells admixed with bacillus Calmette-Guerin. Patients received three weekly intradermal immunizations beginning 1-3 months after surgery (15 patients) or after completion of postoperative radiotherapy (3 patients). There was marked heterogeneity in the relative proportion of tumor cells versus host infiltrating cells within individual vaccines (range of percent tumor cells 7-75%). Five patients exhibited positive delayed cutaneous skin test reactivity (DCR) to autologous irradiated tumor cells prior to immunization, whereas 8 of 13 converted from skin test negative to positive. There were no correlations between DCR reactivity and in vitro lymphoproliferative responses to autologous tumor cells or to clinical outcomes, i.e., freedom from relapse. Possible explanations for the heterogeneity of the lung cancer vaccine and approaches for improving its immunogenicity are discussed.


Absorption characteristics of the lipophilic prodrug of mitomycin C from injected liposomes or an emulsion.
Mitomycin C (MMC) is amphiphilic and so cannot be incorporated into lipoidal delivery systems. To develop a lipoidal delivery system, its prodrug, nonyloxycarbonyl MMC, was formulated in liposomes and in o/w emulsions and the usefulness of these formulations was evaluated. After injection into the rat thigh muscle, MMC was rapidly absorbed regardless of the dosage form. However, the prodrug was retained at the injection site for considerably longer when formulated in a lipid dispersion system. The accumulation of MMC at regional lymph nodes was also investigated and whereas free MMC arrived at and disappeared from the lymph nodes almost immediately after injection, the prodrug arrived at an early stage and its concentration decreased only gradually, remaining fairly high 2 h after injection. Liposomal lipids appeared to accumulate at the lymph nodes to a greater degree than o/w emulsions. It is suggested that the combination of lipidic carrier devices with lipophilic prodrugs may be a useful adjunct to cancer chemotherapy.


Drug addiction: An affective-cognitive disorder in need of a cure.
Drug addiction is a compulsive behavioral abnormality. In spite of pharmacological treatments and psychosocial support to reduce or eliminate drug intake, addiction tends to persist over time. Preclinical and human observations have converged on the hypothesis that addiction represents the pathological deterioration of neural processes that normally serve affective and cognitive functioning. The major elements of persistent compulsive drug use are hypothesized to be structural, cellular and molecular that underlie enduring changes in several forebrain circuits that receive input from midbrain dopamine neurons and are involved in affective (e.g. ventral striatum) and cognitive (e.g. prefrontal cortex) mechanisms. Here we review recent progress in identifying crucial elements useful to understand the pathophysiology of the disease and its treatments. Manipulation of neuropeptides brain systems and pharmacological targeting of κ-opioid receptors and/or drug metabolism may hold beneficial effects at affective and cognitive level. Non-pharmacological, highly innovative approaches such as Transcranial Magnetic Stimulation may reveal unsuspected potential and promise to be the first neurobiology-based therapeutics in addiction.


Oxyalkylation of Lignoboost™ Kraft Lignin with Propylene Carbonate: Design of Experiments towards Synthesis Optimization.
Oxyalkylation with propylene carbonate (PC) is a safe process to convert lignin into a reactive liquid polyol to be used in polyurethane formulations. In this study, the effect of operating conditions of oxyalkylation (temperature, time and quantify of PC) on the quality of lignin-based polyol in terms hydroxyl number (IOH) and viscosity was studied. Full factorial modeling and response surface methodology (RSM) were applied to study the effect and interaction of process variables on the IOH and viscosity of lignin-based polyols. The results revealed that the IOH is highly affected by the reaction time, while the viscosity is affected by the amount of PC. Validation experiments confirmed the model is reliable. Furthermore, RSM optimization allowed to reduce the amount of PC by about 50% and to increase the lignin content in the polyol from 12.5% to 25% (w/w) depending on the temperature and time of the process and also on the purpose of the polyol produced (i.e., application in rigid foams or adhesives).


The Munc13 proteins differentially regulate readily releasable pool dynamics and calcium-dependent recovery at a central synapse.
The Munc13 gene family encodes molecules located at the synaptic active zone that regulate the reliability of synapses to encode information over a wide range of frequencies in response to action potentials. In the CNS, proteins of the Munc13 family are critical in regulating neurotransmitter release and synaptic plasticity. Although Munc13-1 is essential for synaptic transmission, it is paradoxical that Munc13-2 and Munc13-3 are functionally dispensable at some synapses, although their loss in other synapses leads to increases in frequency-dependent facilitation. We addressed this issue at the calyx of Held synapse, a giant glutamatergic synapse that we found to express all these Munc13 isoforms. We studied their roles in the regulation of synaptic transmission and their impact on the reliability of information transfer. Through detailed electrophysiological analyses of Munc13-2, Munc13-3, and Munc13-2-3 knock-out and wild-type mice, we report that the combined loss of Munc13-2 and Munc13-3 led to an increase in the rate of calcium-dependent recovery and a change in kinetics of release of the readily releasable pool. Furthermore, viral-mediated overexpression of a dominant-negative form of Munc13-1 at the calyx demonstrated that these effects are Munc13-1 dependent. Quantitative immunohistochemistry using Munc13-fluorescent protein knock-in mice revealed that Munc13-1 is the most highly expressed Munc13 isoform at the calyx and the only one highly colocalized with Bassoon at the active zone. Based on these data, we conclude that Munc13-2 and Munc13-3 isoforms limit the ability of Munc13-1 to regulate calcium-dependent replenishment of readily releasable pool and slow pool to fast pool conversion in central synapses.


The biosynthesis of cyclic carotenes.
1. The incorporation of (3RS)-[2-(14)C,(4R)-4-(3)H(1)]mevalonic acid into various cyclic carotenes in the fruit of the tomato mutant delta has been studied. The results confirm our previous view that the alpha-ionone ring of alpha-carotene does not arise by isomerization of a beta-ionone residue, and show that the same is also true for the alpha-ionone ring of delta- and in-carotene and alpha-zeacarotene. 2. The incorporation of (3RS)-[2-(14)C,2-(3)H(2)]mevalonic acid into alpha- and beta-carotene in carrot roots has been studied. The results show that the beta-ionone ring of beta-carotene does not arise by isomerization of the alpha-ionone residue of alpha-carotene. 3. These experiments show that alpha- and beta-ionone rings in cyclic carotenes are formed independently, probably by elimination of different protons from the same carbonium ion intermediates.


Psychotropic medication in adolescents: a review.
All published articles of double-blind, controlled studies of drug treatment of mental disorders in adolescents are reviewed. The evidence for efficacy ranges from suggestive to nonexistent, without any match of drug and disorder showing definitive evidence, either because of the limited number of studies available or because these studies have less than clear findings. Special considerations in the study of adolescent psychopharmacology are addressed, and a practical approach to drug treatment making the best use of the limited information available is offered.


Diabetes-specific preventive-care practices among adults in a managed-care population -- Colorado, Behavioral Risk Factor Surveillance System, 1995.
The prevalence of diagnosed diabetes in the United States is 3%; however, diabetes accounts for approximately 15% of total U.S. health-care expenditures. Preventive-care practices (e.g., glycemic control and regular foot and ophthalmic examinations) can reduce the occurrence and progression of diabetic complications. Although managed-care organizations (MCOs) have assessed the use of such practices through chart reviews, telephone surveys of MCO patients with diabetes are a less expensive method for collecting accurate data. The ongoing, state-based Behavioral Risk Factor Surveillance System (BRFSS) telephone survey can be used to assess levels of care provided by MCOs and self-care practices among persons with diabetes in MCO populations. In 1995, a Colorado-based MCO collaborated with the Colorado Diabetes Control Program (CDCP) to use the state-based BRFSS to assess care practices among MCO enrollees. This report presents findings from the CDCP analysis of data on MCO enrollees aged > or = 30 years who had diabetes; the findings indicate that, although approximately three fourths of enrollees reported most preventive-care practices, two thirds had never heard the term hemoglobin "A-one-C," one fourth had not had their feet examined during the preceding year, and nearly one fifth did not receive an annual dilated-eye examination.


Oral estramustine therapy in serum chromogranin A-positive stage D3 prostate cancer patients.
Neuroendocrine (NE) differentiation in prostate cancer (PC) has attracted much attention since it has been shown to be associated with androgen independence and bad prognoses. In this study 34 patients with hormone refractory prostate cancer and elevated Chromogranin A (CgA) serum values were treated with estramustine for 15 months. The results were evaluated by analyzing clinical data and the serially measured total PSA and Chromogranin A serotest concentration, as well as bone scan recordings. In responders to therapy a sharp decline in CgA level was recorded as well as a slight decrease in the number of metastatic lesions in the bone. However, in 6- and 12-month nonresponders, supranormal serum CgA concentrations were measured (mean 305 +/- 122 ng/ml/ and 284 +/- 101 ng/ml, respectively). Statistical significance was found between neither of these groups (p > 0.05). Mean bone lesions data were practically identical in nonresponding groups (9.6 and 9.5) but were much lower in the respective responders (4.9 and 4.1). Twelve patients were found to be nonresponders 3 months after therapy initiation (12 out of 34, 35.3%). From the remaining 22 studied subjects a positive response patients continued in 17 patients during the next 3 months or overall in a six-month period (17 out of 34, 50%, or 17 out of 22, 77.3% from 3-month responders). After 9 months of therapy, 15 responding, patients were found (15 out of 34, 44.1%, or 15 out of 17, 88.2% from 6-month responders) while, after a full year of estramustine administration, 8 patients responded to therapy (8 out of 34, 23.5%, or 8 out of 15, 53.3% from responders after 9 months of treatment). Finally, after 15 months of treatment, only 3 responding patients found (3 out of 34, 8.8% or 3 out of 8, 37.5% from responders after 12 months of treatment). Mean response periods after 12 and 15 months of estramustine treatment were 5.5 and 5.7 months, respectively. In conclusion, the reported results indicate a 12-15 month responding period for estramustine therapy in patients with a slight initial elevation in CgA serotest (up to 150 ng/ml) and less than 10 metastatic osseous lesions. Thus, serum CgA assessment has definitely found a role in monitoring PC patients with NE positive stage D3 disease. This specially holds true as the population of aged men is rapidly increasing, posing a great challenge to urologists and oncologists in treating difficult-to-manage hormone-independent prostatic carcinoma.


The Expression and Prognostic Value of ILK and YAP1 in Glioma.
Integrin-linked kinase (ILK) is a widely expressed serine/threonine-protein kinase that has been implicated in cancer development, progression, and metastasis. Yes-associated protein (YAP), as the most important effector of Hippo signaling pathway, which is considered to be a tumor suppressor pathway, acts as an oncogene in a variety of human cancers. The present study aimed to explore the expression of ILK and YAP1, the relationship between them, and the effect of ILK, YAP1 on prognosis in gliomas. Immunohistochemistry was used to examine the expression of ILK and YAP1. The χ2 test analyzes the relationship between ILK, YAP1, and pathologic parameters. The Spearman correlation analyzes the relationship between ILK and YAP1. Survival analysis was used to investigate the effect of ILK and YAP1 on prognosis. High expression of ILK was associated with the age above 50 (P=0.003), higher World Health Organization (WHO) grade (P<0.001), recurrence (P<0.001), and Ki-67 expression≥10% (P<0.001). High expression of YAP1 was associated with higher WHO grade (P<0.001), recurrence (P=0.043), and Ki-67 expression ≥10% (P=0.037). In lower grade gliomas, the high expression rate of ILK in isocitrate dehydrogenase 1 wild-type was higher than that in isocitrate dehydrogenase 1 mutant (P=0.048). The high expression rate of YAP1 in 1p19q non-codeletion was higher than that in 1p19q codeletion (P=0.022). There was a positive correlation between ILK and YAP1 (r=0.344). The patients with high expression of ILK and YAP1 had worse OS and PFS. As an upstream factor of the Hippo signaling pathway, ILK may affect the development and prognosis of gliomas by regulating YAP1.


Familial posterior helical ear pits and Wiedemann-Beckwith syndrome.
Multiple cases of posterior helical ear pits (PHEP) with apparent autosomal dominant inheritance in a very large family are reported. There are at least 2 cases of Wiedemann-Beckwith syndrome (WBS) within this family. Three other instances of familial PHEP and/or WBS are presented. An individual with a somewhat atypical osteopetrosis and PHEP is described. The previous literature of PHEP and the association with WBS is reviewed.


Biochemical characterization of a psychrophilic and halotolerant α-carbonic anhydrase from a deep-sea bacterium, Photobacterium profundum.
Prokaryotic α-carbonic anhydrases (α-CA) are metalloenzymes that catalyze the reversible hydration of CO2 to bicarbonate and proton. We had reported the first crystal structure of a pyschrohalophilic α-CA from a deep-sea bacterium, Photobacterium profundum SS9. In this manuscript, we report the first biochemical characterization of P. profundum α-CA (PprCA) which revealed several catalytic properties that are atypical for this class of CA's. Purified PprCA exhibited maximal catalytic activity at psychrophilic temperatures with substantial decrease in activity at mesophilic and thermophilic range. Similar to other α-CA's, Ppr9A showed peak activity at alkaline pH (pH 11), although, PprCA retained 88% of its activity even at acidic pH (pH 5). Exposing PprCA to varying concentrations of oxidizing and reducing agents revealed that N-terminal cysteine residues in PprCA may play a role in the structural stability of the enzyme. Although inefficient in CO2 hydration activity under mesophilic and thermophilic temperatures, PprCA exhibited salt-dependent thermotolerance and catalytic activity under extreme halophilic conditions. Similar to other well-characterized α-CA's, PprCA is also inhibited by monovalent anions even at low concentrations. Finally, we demonstrate that PprCA accelerates CO2 biomineralization to calcium carbonate under alkaline conditions.


Diagnostic significance of serum galectin-3 levels in heart failure with preserved ejection fraction.
Galectin-3, reflecting cardiac fibrosis, is a promising biomarker in early detection of heart failure with preserved ejection fraction (HFpEF). We aimed to clarify the clinical utility of galectin-3 levels in the diagnosis of HFpEF and to compare galectin-3 with N-terminal pro-brain-type natriuretic peptide (NT-proBNP) levels. The study included 44 HFpEF patients (mean age 60 ± 6.78 years, 24 men) and 38 control subjects (mean age 57 ± 8.98 years, 20 men). Galectin-3 and NT-proBNP levels were assessed by the ELISA kits. The receiver operating characteristics (ROC) curve was used to examine the diagnostic performance of galectin-3 and NT-proBNP in HFpEF. Galectin-3 and NT-proBNP levels were significantly increased in patients with HFpEF compared to controls [5.35 ng/ml (0.86 – 14.90) vs 0.51 ng/ml (0.15 – 1.71) P < 0.0001, 617.75 ± 271.30 pg/ml vs 66.35 ± 54.01 pg/ml P < 0.0001, respectively]. Galectin-3 correlated with NT-proBNP, left atrial volume index, left ventricular mass index, and E/E' (r = 0.90, P < 0.0001; r = 0.75, P = 0.0001; r = 0.86, P = 0.0001; r = 0.80, P = 0.0001; respectively). The area under the ROC curve was 0.98 for galectin-3 and 1.0 for NT-proBNP. Our results support that, in addition to NT-proBNP, galectin-3 is also a valuable biomarker for the diagnosis of patients with HFpEF.


Chromosome size affects sequence divergence between species through the interplay of recombination and selection.
The structure of the genome shapes the distribution of genetic diversity and sequence divergence. To investigate how the relationship between chromosome size and recombination rate affects sequence divergence between species, we combined empirical analyses and evolutionary simulations. We estimated pairwise sequence divergence among 15 species from three different mammalian clades-Peromyscus rodents, Mus mice, and great apes-from chromosome-level genome assemblies. We found a strong significant negative correlation between chromosome size and sequence divergence in all species comparisons within the Peromyscus and great apes clades but not the Mus clade, suggesting that the dramatic chromosomal rearrangements among Mus species may have masked the ancestral genomic landscape of divergence in many comparisons. Our evolutionary simulations showed that the main factor determining differences in divergence among chromosomes of different sizes is the interplay of recombination rate and selection, with greater variation in larger populations than in smaller ones. In ancestral populations, shorter chromosomes harbor greater nucleotide diversity. As ancestral populations diverge, diversity present at the onset of the split contributes to greater sequence divergence in shorter chromosomes among daughter species. The combination of empirical data and evolutionary simulations revealed that chromosomal rearrangements, demography, and divergence times may also affect the relationship between chromosome size and divergence, thus deepening our understanding of the role of genome structure in the evolution of species divergence.


Aflatoxins in human breast milk.
Breast milk from 99 Sudanese mothers was analysed for aflatoxins. Aflatoxins M1 and/or M2 were detected in 37 of the milks. No other aflatoxin was detected. M1 occurred alone in 13 milks, (mean 19.0 pg/ml), M2 in 11 milks (mean 12.2 pg/ml), and in 13 samples both M1 and M2 were detected. There appeared to be a linear relationship between M1 and M2 where both were excreted. No aflatoxin was detected in subcutaneous abdominal wall fat removed during Caesarian section from 15 women, but was present in three out of 14 bloods taken during anaesthesia. The presence of aflatoxins in mothers' milk showed no correlation with duration of lactation, the infants' nutrition, presence of aflatoxin in mothers' blood, or the infant's blood and urine. It is concluded that some Sudanese women excrete aflatoxins in breast-milk at levels similar to or higher than those considered safe in animal milk, for human consumption.


Prion protein codon 129 polymorphism modifies age at onset of frontotemporal dementia with the C.709-1G>A progranulin mutation.
Frontotemporal lobar degeneration because of mutations in the progranulin (PGRN) gene presents a high variability both in the clinical phenotype and age of onset of disease. Factors that influence this variability remain largely unknown. The aim of our study was to determine whether selected genetic variables modify age at onset of disease in our series of 21 patients with a single splicing mutation (c.709-1G>A) in the PGRN gene, all of whom were of Basque descent. In our analysis, we included the following genetic variables: PGRN rs5848 and rs9897526 polymorphisms, APOE and microtubule-associated protein tau genotypes, and PRNP codon 129 polymorphism. We found no association between PGRN polymorphisms, APOE and microtubule-associated protein tau genotypes, and age at onset of the disease; whereas we report evidence for an association between PRNP codon 129 polymorphism and age at onset of disease in frontotemporal dementia-PGRN(+) patients. MM homozygous carriers presented onset of disease on average 8.5 years earlier than patients who carried at least 1 valine on their PRNP codon 129 (MV or VV). The biological justification for this association remains speculative.


Imbalance of cusp width and aortic regurgitation associated with aortic cusp prolapse in ventricular septal defect.
The Doppler echocardiograms of the aortic valve and associated aortic regurgitation (AR) were reviewed in 72 patients with a ventricular septal defect (VSD). Group I comprised 13 patients without any deformity of the aortic cusp for > or = 10 years, group 2 included 35 patients who did not develop AR for > or = 10 years after right coronary cusp prolapse (RCCP) was first detected, group 3 comprised 11 patients with RCCP and AR in whom the AR remained subclinical for > or = 10 years, and group 4 was 13 patients who underwent surgical treatment because of moderate to severe AR. The cusp imbalance index [width of right (R) or non- (N) coronary cusp/width of left coronary cusp (L)] was compared among the 4 groups. R/L or N/L was larger in group 4 than in groups 1-3; R/L exceeded 1.30 in all the patients in group 4, whereas it was less than 1.30 in all the atients in groups 1-3. Two patients in group 4 with non-coronary cusp prolapse had an N/L greater than 1.50. No other patients in any group had an N/L larger than 1.20. An imbalance of cusp width may predict possible progressive deterioration of AR.


Midwifery basics. Antenatal care--the booking history.
Joannna is in the first trimester of her first pregnancy. She has seen her General Practitioner who gave her some general advice about what she should and should not be eating. Aware of her previous medical history, the GP told Joanna to go to the reception desk and to make an appointment for the community midwife to visit her at home to undertake the 'booking'. A week later she received a package of information and a letter from the midwife confirming the appointment time and asking Joanna to produce an early morning specimen of urine (EMSU) on the day of the visit.


Interdisciplinary treatment of an end-to-end occlusion due to congenitally missing maxillary lateral incisors.
Odontogenic aplasia, or the congenital absence of permanent teeth, is relatively common. When the missing teeth include the maxillary lateral incisors, treatment considerations must reconcile both esthetic and functional objectives. In developing dentition, erupting adjacent teeth can drift from their intended positions into the edentulous space created by the congenitally missing tooth. When this movement happens (e.g., cuspids shifting more mesially than normal), esthetic and functional problems occur. A restorative solution for missing maxillary lateral incisors subsequent to the loss of the maxillary incisor spaces is presented while highlighting the use of a leucite-reinforced material. This approach allowed for a minimal preparation design and conservation of tooth structure, providing an optimal bond.


Bangkok: the end of broken promises? XV International AIDS Conference, 2004.
The global community has again failed to significantly confront the AIDS crisis. In the context of a worsening HIV pandemic, the conference highlighted the shortfall in funding, the soaring infection rate in Asia, the need to integrate prevention and treatment and the difficulties in coordinating a global response. To overcome AIDS, the global community must put aside ideology and honour its commitments.


Relative ineffectiveness of ultrabrief right unilateral versus bilateral electroconvulsive therapy in depression.
Bilateral (BL) electrode placement delivered at 2.5 times the initial seizure threshold (ST; 2.5 x ST) is the gold standard method for seizure delivery during electroconvulsive therapy (ECT). However, there is a growing interest in using a high dose (6 x ST) with ultrabrief right unilateral (UB-RUL) electrode placement to reduce the incidence of possible short-term memory problems associated with BL ECT. Although studies have found UB-RUL ECT to have similar effectiveness to BL ECT, the objective of this study was to determine potential differences in efficiency (ie, the number of treatments needed to reach remission). Electroconvulsive therapeutic data for 56 patients with depression treated during 2006 and 2007 were analyzed via retrospective chart review. A total of 26 patients were started on UB-RUL ECT, whereas 30 patients were started on brief pulse BL ECT. The patients started on high-dose UB-RUL ECT required significantly more treatments than the patients started on BL ECT (9.4 [3.3] vs 7.7 [2.8] treatments). Of the 26 patients started on UB-RUL ECT, 12 (46%) experienced a lack of effectiveness and/or insufficient seizure induction and were thus switched to BL ECT; the 8 patients switched because of lack of effectiveness received a mean (SD) of 12.2 (2.9) treatments, whereas the 4 patients switched because of insufficient seizure induction received a mean (SD) of 11.3 (3.6) treatments. These findings add to an emerging story of reduced efficiency of UB-RUL versus BL electrode placement for an index course of ECT for the treatment of depression.


Replacing Synthetic Ingredients by Sustainable Natural Alternatives: A Case Study Using Topical O/W Emulsions.
With the increasing debate on sustainability, there is a strong market trend to formulate more sustainable products for topical application. Several studies emphasize the potential applications of natural, organic, or green chemistry-derived ingredients, but comparative studies between conventional ingredients and sustainable alternatives are lacking. This type of study is considered an excellent baseline and time-saving strategy for future studies. In addition, one of the main challenges of replacing ingredients by sustainable alternatives in topical vehicles is to maintain high-quality products. Thus, the main goal of this research study was to create a well-defined strategy supported by specific experimental data for the development of sustainable topical vehicles with high-quality standards. The study was designed to evaluate the effects of replacing conventional ingredients (e.g., hydrocarbons, silicones, and preservatives) by sustainable ones on the physical, chemical, and microbiological features of topical emulsions. Additionally, in vivo assessment studies were performed to evaluate the safety, biological efficacy, and sensorial aspects of the developed formulations. The results obtained showed that the replacement of ingredients by sustainable alternatives has an effective impact on the physicochemical and structural properties of the emulsions, mainly on their rheological behavior. However, using appropriate strategies for ingredient selection and rheological adjustment, it is possible to overcome some barriers created by the use of natural raw materials, thus developing appealing and high-quality sustainable topical vehicles.


The Impact of Racial and Non-racial Discrimination on Health Behavior Change Among Visible Minority Adults During the COVID-19 Pandemic.
Pre-pandemic health behavior has been put forward as a reason for excess COVID-19 infection and death in some racialized groups. At the same time, scholars have labeled racism the other pandemic and argued for its role in the adverse COVID-19 outcomes observed. The purpose of this study was to examine the impact of discrimination on health behavior change among racialized adults in the early stages of the pandemic. Data were collected from 210 adults who identified as a visible minority in Alberta, Canada, in June 2020. The Everyday Discrimination Scale (Short Version) was adapted to examine past-month experiences. Four questions asked if alcohol/cannabis use and stress eating had significantly increased, and if sleep and exercise had significantly decreased in the past month. Logistic regression models examined associations between discrimination attributed to racial and non-racial causes and health behavior change adjusted for covariates. The majority of adults (56.2%) reported past-month discrimination including 26.7% who attributed it to their race. Asian adults reported more racial discrimination and discrimination due to people believing they had COVID-19 than other visible minorities. Racial discrimination during the pandemic was strongly associated with increased substance use (OR: 4.0, 95% CI 1.2, 13.4) and decreased sleep (OR: 7.0, 95% CI 2.7, 18.4), and weakly associated with decreased exercise (OR: 2.2, 95% CI 1.1, 4.5). Non-racial discrimination was strongly associated with decreased sleep (OR: 4.8, 95% CI 1.8, 12.5). Racial discrimination may have a particularly important effect on intensifying adverse health behavior changes among racialized adults during a time of global crisis.


Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.
Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model.


Thymolipoma.
Although the diagnosis of thymolipoma has improved with the introduction of computerized tomography (CT), variations in CT appearance are still being described; this paper describes a case which resembled a lipoma. The CT features of thymolipoma are discussed with special reference to the differential diagnosis. Surgical excision should be considered for patients who are found to exhibit a fatty intrathoracic mass on CT.