The mortality of exchange transfusions.
A prospective study of the effect and mortality of exchange transfusion was carried out in the Kandang Kerbau Hospital, Singapore. Altogether 140 exchange transfusions were performed on 122 infants. The exchanges were done for hyperbilirubinaemia due to "idiopathic" jaundice, ABO haemolytic disease, and glucose-6-phosphate dehydrogenase deficiency. Eight infants deteriorated during the exchange, in three of whom the procedure had to be terminated prematurely. Two deaths occurred two days after the exchange--the procedure being partly responsible in one case; necrotizing enterocolitis was present in addition to the kernicterus. Exchange transfusion is not without hazards, and should be performed carefully with close monitoring of the clinical status of the infant during and immediately after the procedure.


Comparison of the behavior of CHO cells during cultivation in 24-square deep well microplates and conventional shake flask systems.
In biopharmaceutical production, the optimization of cell culture media and supplementation is a vital element of process development. Optimization is usually achieved through the screening of multiple media, feed and feeding strategies. However, most screening is performed in shake flasks, which makes the screening process very time consuming and inefficient. The use of small scale culture systems for the screening process can aid in the ability to screen multiple formulations during process development. In order to assess the suitability of 24 deep well (24DW) plates with the Duetz sandwich-covers as a small scale culture system for process development, we have tested growth and production performance of CHO cells in 24DW plates and conventional shake flask cultures. Multiple studies were performed to assess well-to-well and plate-to-plate variability in 24DW plates. Additional studies were performed to determine the applicability of 24DW plates for cell culture medium and supplement screening in batch and fed batch processes. Cultures in 24DW plates exhibited similar kinetics in growth, viability and protein production to those cultured in shake flasks, suggesting that 24DW plates with Duetz sandwich-covers can be effectively used for high throughput cell culture screening.


Tailored release drug delivery system for rifampicin and isoniazid for enhanced bioavailability of rifampicin.
The front line antitubercular drugs rifampicin (RMP) and isoniazid (INH), when co-administered, face the problem of reduced bioavailability of RMP. Stabilization of RMP in the presence of INH under acidic environment may improve the bioavailability of RMP. In vitro degradation studies showed around 15-25% degradation of RMP under the aforesaid conditions if the ratio of RMP: INH is above 1:0.5.This degradation is reduced to less than 10% when the ratio of RMP: INH is below 1:0.25. Based on these findings, an innovative drug delivery system was designed with the immediate release of RMP and tailored prolonged release of INH. The bilayer tablets prepared with this concept were subjected to relative bioavailability studies in healthy human volunteers in an open label, balanced, randomized, single-dose, cross-over study under fasted state. A validated LC-MS/MS bioanalytical method was employed for estimation of RMP and INH in plasma. Bioavailability studies revealed that C(max) and AUC for RMP increased by 18 and 20%, respectively, confirming the above innovative concept. Even in the case of INH, AUC increased significantly by around 30% and thus time above minimum inhibitory concentration (MIC) would also increase, which may result in further improved clinical outcome.


A quantitative hypermorphic CNGC allele confers ectopic calcium flux and impairs cellular development.
The coordinated control of Ca2+ signaling is essential for development in eukaryotes. Cyclic nucleotide-gated channel (CNGC) family members mediate Ca2+ influx from cellular stores in plants (Charpentier et al., 2016; Gao et al., 2016; Frietsch et al., 2007; Urquhart et al., 2007). Here, we report the unusual genetic behavior of a quantitative gain-of-function CNGC mutation (brush) in Lotus japonicus resulting in a leaky tetrameric channel. brush resides in a cluster of redundant CNGCs encoding subunits which resemble metazoan voltage-gated potassium (Kv1-Kv4) channels in assembly and gating properties. The recessive mongenic brush mutation impaired root development and infection by nitrogen-fixing rhizobia. The brush allele exhibited quantitative behavior since overexpression of the cluster subunits was required to suppress the brush phenotype. The results reveal a mechanism by which quantitative competition between channel subunits for tetramer assembly can impact the phenotype of the mutation carrier.


Comparison of early splenic changes associated with replication of viruses in murine monocytic macrophages.
An effect of replication of certain viruses in murine monocytic macrophages was manifested by depletion of cells through degenerative and necrotizing changes in thymus-dependent areas of lymphoid structures. In mice infected with murine hepatitis virus (MHV-3) or lactate dehydrogenase virus, these changes were transient in mice killed on postinoculation day (PID) 2. To study these morphologic changes due to viral replication, adult Swiss specific-pathogen-free homozygous nude mice (nu/nu) and their heterozygous haired littermates (nu/+) were inoculated with 10(5) LD50 of MHV-3, euthanatized, and necropsied on PID 1, 2, 4, 6, 8, and 10 along with noninoculated controls. The nu/+ and nu/nu mice killed on PID 2 had lymphocytic karyorrhexis and depletion of cells in the thymus-dependent area. In the heterozygote, these characteristic lesions were transient; whereas in the homozygote, lesions persisted and were present in survivors euthanatized and necropsied on PID 16. Although the intensity of lesions due to MHV-3 varied between nu/+ and nu/nu mice, virus titers determined on liver homogenates were similar for the homozygote and heterozygote during acute disease. Nude and nonnude mice given lactate dehydrogenase virus and killed on PID 2 had a transient depletion of lymphocytes; whereas mice given lymphocytic choriomeningitis virus and killed on PID 4 had a similar lesion. Lesions neither occurred when mice were treated with silica before inoculation, indicating that functional monocytic macrophages were required, nor occurred when another virus, herpes simplex virus type 1, was given.


[Current pathomorphism and specific features of complex tuberculous uveitis treatment].
The study has indicated that in the 1990th, there has been considerable changes in the clinical picture and course of ocular tuberculous lesions. Their morbidity has tended to increase in children, adolescents, and young individuals. Patients with tuberculous uveitis with posterior eyeball lesions are more than 70%. The specific inflammatory process is primarily exudative and infiltrative, followed by rapid development of complications that prevail over the major focus, prevent treatment and substantially deteriorate visual functions. The findings are important not only for understanding the pathogenetic development of an ocular tuberculous process and they provide evidence for the approach to be used in the treatment of various manifestations of ocular tuberculosis.


How light and biomass density influence the reproduction of delayed Saccharina latissima gametophytes (Phaeophyceae).
Kelp life-cycle transitions are complex and susceptible to various (a)biotic controls. Understanding the microscopic part of the kelp's lifecycle is of key importance, as gametophytes form a critical phase influencing, among others, the distributional limits of the species. Many environmental controls have been identified that affect kelp gametogenesis, whose interactive effects can be subtle and counterintuitive. Here we performed a fully factorial experiment on the (interactive) influences of light intensity, light quality, and the Initial Gametophyte Density (IGD) on Saccharina latissima reproduction and vegetative growth of delayed gametophytes. A total of 144 cultures were followed over a period of 21 d. The IGD was a key determinant for reproductive success, with increased IGDs (≥0.04 mg DW · mL-1 ) practically halting reproduction. Interestingly, the effects of IGDs were not affected by nutrient availability, suggesting a resource-independent effect of density on reproduction. The Photosynthetically Usable Radiation (PUR), overarching the quantitative contribution of both light intensity and light quality, correlated with both reproduction and vegetative growth. The PUR furthermore specifies that the contribution of light quality, as a lifecycle control, is a matter of absorbed photon flux instead of color signaling. We hypothesize that (i) the number of photons absorbed, independent of their specific wavelength, and (ii) IGD interactions, independent of nutrient availability, are major determinants of reproduction in S. latissima gametophytes. These insights help understand kelp gametophyte development and dispersal under natural conditions, while also aiding the control of in vitro gametophyte cultures.


Activation of Notch Signaling by Oocytes and Jag1 in Mouse Ovarian Granulosa Cells.
The Notch pathway plays diverse and complex roles in cell signaling during development. In the mammalian ovary, Notch is important for the initial formation and growth of follicles, and for regulating the proliferation and differentiation of follicular granulosa cells during the periovulatory period. This study seeks to determine the contribution of female germ cells toward the initial activation and subsequent maintenance of Notch signaling within somatic granulosa cells of the ovary. To address this issue, transgenic Notch reporter (TNR) mice were crossed with Sohlh1-mCherry (S1CF) transgenic mice to visualize Notch-active cells (EGFP) and germ cells (mCherry) simultaneously in the neonatal ovary. To test the involvement of oocytes in activation of Notch signaling in ovarian somatic cells, we ablated germ cells using busulfan, a chemotherapeutic alkylating agent, or investigated KitWv/Wv (viable dominant white-spotting) mice that lack most germ cells. The data reveal that Notch pathway activation in granulosa cells is significantly suppressed when germ cells are reduced. We further demonstrate that disruption of the gene for the Notch ligand Jag1 in oocytes similarly impacts Notch activation and that recombinant JAG1 enhances Notch target gene expression in granulosa cells. These data are consistent with the hypothesis that germ cells provide a ligand, such as Jag1, that is necessary for activation of Notch signaling in the developing ovary.


The novel pyrrolopyrimidine PNU-101033-E improves facial motor neuron survival following intracranial axotomy of the facial nerve in the adult rat.
Neuronal survival is important to functional restitution following axotomy. Proximal lesions of the facial nerve, due to head trauma or tumor growth, for example, may cause long-standing or even permanent facial nerve palsy. Betamethasone has been used by several neurosurgical clinics for the treatment of postoperative facial nerve palsy; however, this practice is based only on clinical experience. The aim of the present study was to explore the putative effect on facial motor neuron survival of a novel lazaroid (pyrrolopyrimidine, PNU-101033-E) and furthermore to compare the effects with those of betamethasone, following intracranial transection of the facial nerve in adult rats. Both agents are known to inhibit lipid peroxidation by free radical scavenging. The lesion model used has recently been reported to induce massive neuronal cell death with a relative survival of 26.8 +/- 11.3% 1 month after lesion. Oral administration of lazaroids or daily injections of betamethasone followed surgery for 1 month, after which quantification of motor neuronal profiles was performed in the facial nucleus. Lazaroid-treated animals showed a significantly enhanced neuronal survival (68.0 +/- 9.8%), whereas no significant difference was found in betamethasone-treated animals (33.1 +/- 11.7%). The microglial and astrocytic responses in the facial nucleus were intense on the operated sides in betamethasone-treated as well as lazaroid-treated animals, and no differences in comparison with untreated animals were found. In conclusion, we found that the novel pyrrolopyrimidine PNU-101033-E, but not betamethasone, significantly enhanced nerve cell survival. This agent may therefore serve as a useful neuroprotective agent following intracranial trauma to the facial nerve and should be further evaluated for clinical use.


Attentional bias to smoking and other motivationally relevant cues is affected by nicotine exposure and dose expectancy.
We investigated the effects of acute nicotine dose and expected dose on attentional bias (AB) to smoking and affective cues in overnight nicotine-deprived smokers (n=51; 24 women) using a balanced placebo design, which counterbalanced given nicotine dose (Given-NIC vs. Given-DENIC) with instructed nicotine dose expectancy (Told-NIC vs. Told-DENIC). Before and after smoking a study cigarette, smokers completed a vigilance task where they pressed buttons to every third consecutive even or odd digit, while ignoring intermittent smoking, pleasant, unpleasant, and neutral picture distracters. We examined the early posterior negativity (EPN) and late positive potential (LPP) components of the event-related potentials (ERPs) to the distracters, reaction time (RT) to the target digits, and ratings of the study cigarettes. The EPN was sensitive to both given and instructed nicotine dose, while the instructed dose moderated the impact of given dose for the LPP. The RT metrics were sensitive to given but not to instructed dose. The effects of given dose on ratings following cigarette smoking (e.g. enjoyment) were moderated by the instructed dose. The ERP findings suggest that the anticipated effects of nicotine improve attention much like receiving actual nicotine.


Sexually Transmitted Infection Diagnoses and Access to a Sexual Health Service Before and After the National Lockdown for COVID-19 in Melbourne, Australia.
We aimed to examine the impact of lockdown on sexually transmitted infection (STI) diagnoses and access to a public sexual health service during the coronavirus disease 2019 (COVID-19) pandemic in Melbourne, Australia. The operating hours of Melbourne Sexual Health Centre (MSHC) remained the same during the lockdown. We examined the number of consultations and STIs at MSHC between January and June 2020 and stratified the data into prelockdown (February 3 to March 22), lockdown (March 23 to May 10), and postlockdown (May 11 to June 28), with 7 weeks in each period. Incidence rate ratios (IRRs) and their 95% confidence intervals (CI) were estimated using Poisson regression models. The total number of consultations dropped from 7818 in prelockdown to 4652 during lockdown (IRR, 0.60; 95% CI, 0.57-0.62) but increased to 5347 in the postlockdown period (IRR, 1.15; 95% CI, 1.11-1.20). There was a 68% reduction in asymptomatic screening during lockdown (IRR, 0.32; 95% CI, 0.30-0.35), but it gradually increased during the postlockdown period (IRR, 1.59; 95% CI, 1.46-1.74). Conditions with milder symptoms showed a marked reduction, including nongonococcal urethritis (IRR, 0.60; 95% CI, 0.51-0.72) and candidiasis (IRR, 0.61; 95% CI, 0.49-0.76), during lockdown compared with prelockdown. STIs with more marked symptoms did not change significantly, including pelvic inflammatory disease (IRR, 0.95; 95% CI, 0.61-1.47) and infectious syphilis (IRR, 1.14; 95% CI, 0.73-1.77). There was no significant change in STI diagnoses during postlockdown compared with lockdown. The public appeared to be prioritizing their attendance for sexual health services based on the urgency of their clinical conditions. This suggests that the effectiveness of clinical services in detecting, treating, and preventing onward transmission of important symptomatic conditions is being mainly preserved despite large falls in absolute numbers of attendees.


[Electrodiagnostic evaluation of conservative treatment in carpal tunnel syndrome].
The incidence of carpal tunnel syndrome ranks first by far among all entrapment neuropathies. Many foreign studies have been reported over the years concerning the diagnosis of carpal tunnel syndrome, but very few about its treatment effects. Moreover, data have been based on the patients' subjective reports of their symptoms. Our data, however, are wholly derived from objective electromyographic examination. Five treatment approaches were compared for patients suffering from carpal tunnel syndrome in this study. Ninety-nine hands of 61 patients were divided into five treatment groups vitamins B6 & B12, steroid injection, hand splint, splint combined with vitamins, and splint combined with injection. Each patient was evaluated with electrodiagnostic study before the treatment, and 1 and 2 months after the treatment. Treatment with hand splinting, local injection at wrist, and combined therapies were all superior in effect to vitamins B6 & B12 alone in sensory nerve conduction study. The effects of treatment appeared faster in the groups with local injection and local injection combined with hand splinting in the sensory and motor nerve conduction studies. The results of this study suggest that treatment with vitamins B6 & B12 alone does not suit carpal tunnel syndrome well and that hand splint combined with steroid injection is the better conservative treatment.


Beyond the classroom: self-direction in professional learning.
Against the backdrop of a rapidly changing profession, the context for professional thinking among medical librarians is changing. Competent performance increasingly is linked with the educational efforts of self-directed adult learners. This paper examines strategies that facilitate self-direction, including skills development, organizational learning, learner-based decision making, and alternative teaching models. The analysis provides the basis for a recommended agenda for redesign and development of educational programs.


Intensive care nurses' knowledge of radiation safety and their behaviors towards portable radiological examinations.
Radiological examinations for patients who are hospitalized at intensive care units are usually performed using portable radiography devices. However they may require knowledge and safety precautions of nurses. The aim of the study was to investigate ICU nurses' knowledge of radiation safety and their behaviors towards portable radiological examinations. In total, 44 intensive care nurses were recruited for this cross-sectional descriptive study using census sampling during April and May 2014. The study setting was at intensive care units of Shahid Beheshti Hospital of Kashan, Iran. An eleven-item questionnaire and a five-item checklist were used for evaluating nurses' radiation protection knowledge and behaviors, respectively. An expert panel consisting of ten nursing and radiology faculty members confirmed the content validity of the questionnaire and the checklist. Moreover, a Geiger-Müller counter was used for measuring ionizing radiation during portable radiological examinations. Study data were analyzed using the SPSS software version 13.0. Mean, standard deviation, frequency and one-sample t test were used for description of the data. The level of significance was set at below 0.05. The mean of participants' radiation protection knowledge was 4.77 ± 1.38. The most prevalent radiation protection behavior of nurses was leaving the intensive care unit during portable radiological examinations. Only 6.8% of nurses stayed at the nursing station during radiological examinations. The highest dose of radiation was 0.11 micro Sievert per hour (μSv/h), which was much lower than the highest permitted level of radiation exposure i.e. 0.25 μSv/h. Portable radiological examinations did not expose healthcare providers to high doses of ionizing radiation. Nurses' radiation protection knowledge was limited and hence, they require in-service education programs.


Optical Gain Spectrum and Confinement Factor of a Monolayer Semiconductor in an Ultrahigh-Quality Cavity.
Two-dimensional (2D) semiconductors have attracted great attention as a novel class of gain materials for low-threshold, on-chip coherent light sources. Despite several experimental reports on lasing, the underlying gain mechanism of 2D materials remains elusive due to a lack of key information, including modal gain and the confinement factor. Here, we demonstrate a novel approach to directly determine the absorption coefficient of monolayer WS2 by characterizing the whispering gallery modes in a van der Waals microdisk cavity. By exploiting the cavity's high intrinsic quality factor of 2.5 × 104, the absorption coefficient spectrum and confinement factor are experimentally resolved with unprecedented accuracy. The excitonic gain reduces the WS2 absorption coefficient by 2 × 104 cm-1 at room temperature, and the experimental confinement factor is found to agree with the theoretical prediction. These results are essential for unveiling the gain mechanism in emergent, low-threshold 2D-semiconductor-based laser devices.


Thyroid screening in HIV-infected patients with antiretroviral therapy.
The literature reports an increased incidence of thyroid disorders in human immunodeficiency virus (HIV)-positive persons. We therefore retrospectively analyzed the strategy of collecting thyroid parameters on a routine basis. Overall 410 patients (147 women, 263 men; age, 10-74 years; median age, 45 years) were included. For screening purposes, three parameters were determined; basal thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Descriptive and statistical analyses were performed in the patient groups with increased bTSH (> 4.0 µU/ml) and with decreased fT4 (< 8.9 pg/ml) to evaluate possible correlation with age, gender, duration of antiretroviral therapy (ART), substance classes of ART (nucleosidal reverse transcriptase inhibitors (NRTIs), nonnucleosidal reverse transcriptase inhibitors, and protease inhibitors (PIs)), Centers for Disease Control and Prevention (CDC) disease stage, lowest number of CD4 cells during course of disease, and coexistent hepatitis C. Elevated bTSH was found in 27 patients (median, 5.26 µU/ml), who also showed a correlation with ART duration and NRTI use. Decreased fT4 was seen in 53 persons, and a correlation with PI intake was observed. Of these patients, 31 exhibited normalization in follow-up. Decreased fT3 was observed in eight cases related to nonthyroid illness, and fT3 was elevated in ten patients. No overt hyperthyroidism was noticed; three cases of subclinical hyperthyroidism were transient. In the examined group of patients, the prevalence of abnormal thyroidal parameters was 23 %. Decreased fT4, which does not require therapy, was observed most frequently (12 %) and correlated with PI use. On the other hand, elevated bTSH (6 %) correlated with ART duration and NRTI use. In mild subclinical hypothyroidism as observed in this patient population, thyroxine medication is not indicated in principle. Annual TSH screening is probably sufficient in HIV-infected patients with no clinical symptoms suggestive for thyroid disease.


Effects of two weeks of metformin treatment on whole-body glycocalyx barrier properties in db/db mice.
The anti-diabetic drug metformin has been demonstrated to exert a protective effect against vascular complications in diabetes independent of its glucose lowering action. Since the endothelial glycocalyx has been indicated to have important vasculoprotective properties and to be vulnerable to degradation by hyperglycemic conditions, we evaluated in the current study the effect of short-term metformin treatment on whole-body glycocalyx barrier properties in a mouse model of non-insulin dependent diabetes mellitus (db/db mouse). Glycocalyx barrier properties were measured in an acute experiment in three groups of mice: 1) db/db mice without treatment serving as controls, 2) db/db mice which received metformin for two weeks in the drinking water serving as experimental group, and 3) C57Bl/6 mice serving as reference group. Animals were put under anesthesia (ketamine, medetomidine, and atropine) and carotid artery blood pressure was continuously monitored. To probe the glycocalyx a mixture of the tracers FITC-labeled 70 kDa dextrans (Dex70) or fluorescein-labeled red blood cells (RBCs) versus Texas Red-labeled 40 kDa dextrans (Dex40) was infused and blood samples subsequently collected for 30 min to determine the initial vascular distribution volume and clearance of these tracers. Urine was collected and dry-to-wet weight of heart and kidney were determined after the experiment. Group differences were tested using unpaired t-tests. Metformin treatment did not affect body weight, fasting blood glucose and arterial blood pressure. Compared to C57Bl/6 mice, db/db mice showed a diminished initial exclusion and increased vascular clearance of Dex70 versus Dex40 (P < 0.05), and both were improved by the metformin treatment (P < 0.05). While urine production was higher in the db/db mice compared to C57Bl/6 (P < 0.05), heart and kidney of the metformin treated animals showed comparable dry-to-wet weights compared to the C57Bl/6 mice. Two weeks of metformin in the drinking water is associated with an improvement in glycocalyx barrier properties in db/db mice, as evidence by an enhanced exclusion and retention of 70 kDa dextrans in the vasculature. In addition, metformin improved hydration of heart and kidney. Previous reported cardiovascular benefits of metformin may well involve an improvement of the endothelial glycocalyx.


[Impact of duodenopancreatectomy in elder patients].
The incidence of periampullary neoplasms substantially increases with age. If we take into account that this incidence is higher in the elder patient and that life expectancy is nowadays longer, questioning surgical approach in this group of patients turns out to be controversial. [corrected] Asses if in the elder patients the duodenopancreatectomy has a higher mortality and complications. A retrospective study including patients who underwent duodenopancreatectomy between October 2002 and June 2012 was undertaken to assess whether the elder ones had a higher morbidity and mortality after surgery. Patients were distributed in two groups according to age. The first group included 240 patients younger than 75 years, and the second one included 74 patients older than 75 years. There wasn't NO significant difference in morbidity between the two groups. General mortality for the whole series was 4%. The first group had a 2.9% mortality whereas in the second one mortality reached 4.9%, a significant difference. However, when we changed the reference age from 75 years to 65 or 70 years the difference was not significant any more. From this study we can ascertain that an age more than 75 years significantly increases the mortality risk in duodenopancreatectomy patients. This age, however, doesn't proscribe surgical approach, since surgery is the only choice for curative treatment in patients with this type of cancer.


Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma.
This study aimed to identify the proteomic changes produced by curcumin treatment following stimulation of the host immune system in a rat model of malignant mesothelioma. We analyzed the proteomes of secondary lymphoid organs from four normal rats, four untreated tumor-bearing rats, and four tumor-bearing rats receiving repeated intraperitoneal administrations of curcumin. Cross-comparing proteome analyses of histological sections of the spleen from the three groups first identified a list of eighty-three biomarkers of interest, thirteen of which corresponded to proteins already reported in the literature and involved in the anticancer therapeutic effects of curcumin. In a second step, comparing these data with proteomic analyses of histological sections of mesenteric lymph nodes revealed eight common biomarkers showing a similar pattern of changes in both lymphoid organs. Additional findings included a partial reduction of the increase in spleen-circulating biomarkers, a decrease in C-reactive protein and complement C3 in the spleen and lymph nodes, and an increase in lymph node purine nucleoside phosphorylase previously associated with liver immunodeficiency. Our results suggest some protein abundance changes could be related to the systemic, distant non-target antitumor effects produced by this phytochemical.


QT prolongation and syncopal attacks. A case of the Romano-Ward syndrome.
The Romano-Ward syndrome is very rare as hereditary disease. Only 5 families have been reported in Japan before the present report. The patient, a 15-year-old female, had been treated for epilepsy due to syncopal attacks. Electrocardiography revealed occurrence of an augmented and labile U wave and prolongation of the Q-T interval, with recordings of frequent multifocal extrasystoles and transient ventricular fibrillation. Also noticed was sinus bradycardia. Clinical examinations presented no results coinciding with those specific ECG findings. It was inferred through surveys of her family tree that the present case had an autosomal dominant trait, heterozygously affected through the male line. Severe arrhythmias detected on her ECGs were suppressed by oral administration of 30 mg/day propranolol. Judging from the fact, propranolol may be the first to be administered among a variety of anti-arrhythmic agents in the Romano-Ward syndrome.


Cutoff wavelength of ridge waveguide near field transducer for disk data storage.
The electromagnetic eigenmodes of and light transmission through a C-aperture to the far field, and to a storage medium, have been studied based on the full vectorial finite difference method. It is found that the cutoff wavelength of C-aperture waveguides in a gold film is much longer than that in a perfect electric conductor, and the fundamental mode is confined in the gap and polarized with the electric field along the gap. The light transmission resonance through C-apertures to far field and to a storage medium occurs at wavelengths below the waveguide cutoff wavelength. Measurements on the fabricated C-apertures confirm the mode confinement and transmission resonance.


Wall thickness-based adjustment of ablation index improves efficacy of pulmonary vein isolation in atrial fibrillation: Real-time assessment by intracardiac echocardiography.
Ablation index (AI) linearly correlates with lesion depth and may yield better therapeutic performance in pulmonary vein isolation (PVI) when tailored to a patient's wall thickness (WT) in the left atrium (LA). First study: In paroxysmal atrial fibrillation patients (PAF; n = 20), the average LA WT (mm) in each anatomical segment for PVI was measured by intracardiac echocardiography (ICE) placed in the LA; the optimal AI for creating 1-mm transmural lesion (AI/mm) was calculated. Second study: PAF (n = 80) patients were randomly assigned either to a force-time integral protocol (FTI; 400 g·s, n = 40) or a tailored-AI protocol (TAI; n = 40). In TAI, the LA WT in each segment was individually measured by ICE before starting ablation; a target AI was adjusted according to the individual WT in each segment (AI/mm × WT). The acute procedure outcomes and the 1-year AF-recurrence rate were compared between FTI and TAI. TAI had higher success rate of first-pass isolation (88% vs. 65%) and had lower incidence of residual PV-potentials/conduction-gaps after a circular ablation than FTI (15% vs. 45%). The procedure time to complete PVI decreased in TAI compared to FTI (52 vs. 83 min), being attributed to the increased radiofrequency power and the decreased radiofrequency application time in each point in TAI. TAI had a lower 1-year AF-recurrence rate than FTI. TAI increased acute procedure success, decreased time for PVI, and reduced the 1-year AF-recurrence rate, compared to FTI. Understanding the precise ablation target and tailoring AI would improve the efficacy of PVI.


Cotranslational protein folding--fact or fiction?
Experimentalists have amassed extensive evidence over the past four decades that proteins appear to fold during production by the ribosome. Protein structure prediction methods, however, do not incorporate this property of folding. A thorough study to find the fingerprint of such sequential folding is the first step towards using it in folding algorithms, so assisting structure prediction. We explore computationally the existence of evidence for cotranslational folding, based on large sets of experimentally determined structures in the PDB. Our perspective is that cotranslational folding is the norm, but that the effect is masked in most classes. We show that it is most evident in alpha/beta proteins, confirming recent findings. We also find mild evidence that older proteins may fold cotranslationally. A tool is provided for determining, within a protein, where cotranslation is most evident.


Cardiovascular risk factors in children. Should they concern the pediatrician?
There is evidence that atherosclerosis, coronary artery disease, and essential hypertension begin early in life. The Bogalusa (La) Heart Study has examined cardiovascular risk factors and their determinants during the pediatric age span in a total community study. Reliable measurements were obtained and then analyzed to identify "tracking" of risk factors over time and clusters or aggregations of various risk factors at high levels. Serum lipoprotein levels, obesity, BP, and plasma insulin levels were all correlated after a glucose load, implying causal interrelationships. Although such relationship are only partly elucidated, the associations potentially enhance premature atherosclerosis. Certain kinds of behavior, for example cigarette smoking and type A behavior, may also contribute to early coronary artery disease. Our observations suggest that practicing physicians should assess risk factors in children and encourage changes in life-style to combat the high incidence of coronary artery disease and essential hypertension in the United States.


(-)-Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high-fat diet.
(-)-Epicatechin (EC) is a natural flavanol monomer found in cocoa, green tea, and a variety of other plant foods. In this study, effects of EC on blood lipids and hepatic steatosis, and the underlying mechanisms were investigated. A hyperlipidemic rat model was induced by high-fat, high-cholesterol diet. EC was then administrated to the animals by gavage at doses of 10, 20, 40 mg/kg body weight (BW) for 12 weeks. Simvastatin was included as a positive control. The results showed that EC significantly reduced total cholesterol, LDL cholesterol and triglyceride, alleviated liver fat accumulation, while increased HDL cholesterol, in hyperlipidemic rats. EC also reduced lipid peroxidation, inhibited the pro-inflammatory cytokines, and lowered serum AST and ALT. The potential molecular mechanisms of EC underlying these effects were proposed to be associated to regulating Insig-1-SREBP-SCAP pathway, and other lipid metabolic related genes including LXR-α, FAS, and SIRT1. EC effectively improved blood lipid profile and protected liver from accumulating excessive fat in hyperlipidemic rats. The results shed a light on the potential role of EC as a promising natural product in preventing hyperlipidemia and nonalcoholic fatty liver disease.


Chronic pelvic ischemia: etiology, pathogenesis, clinical presentation and management.
Overactive Bladder (OAB) and Bladder Pain Syndrome (BPS) although common, are vaguely defined and difficult to diagnose and manage etiologies of storage--type lower urinary tract symptoms (LUTS). The lack of optimal management options is a direct consequence of deficient understanding of the pathophysiologic mechanisms underlying these conditions. These conditions are especially prevalent in females, and cumulative contemporary epidemiological, clinical and laboratory evidence implicates ischemia as one of the key players in the pathophysiologic foundation of both these disorders. Taken together they make up 'the' diagnostic as well as therapeutic black--hole in urologic practice. Much akin to chronic ischemic heart disease, chronic ischemia--reperfusion has been shown to cause degenerative changes at cellular and sub--cellular level in the bladder mucosa, smooth muscle fibers, and vesical neural and microvascular structures leading to a hypersensitive, hyperactive bladder initially, which with time invariably progresses into a failed, fibrotic and pressurized bladder. Diagnosis and management of these diseases are currently symptom focused and remains a source of much frustration. Consideration of role of ischemia connotates hope and could lead to a paradigm shift in the management of these patients with a completely new therapeutic armamentarium attacking the pathology itself.


[Use of "split" courses of combination chemotherapy in breast cancer].
The results of treatment of 110 out-patients with breast metastases, using various repeated schemes of chemotherapy, are discussed. The results and recommendations may be integrated with the procedures of selection of schemes of breast metastasis treatment. Good tolerance, virtual absence of side--effects and complications (e. g. persistent leukopenia) were observed. Integration of the new scheme with antibiotic treatment (carminomycin and adriamycin) is suggested.


Coronary calcium by spiral computed tomography predicts cardiovascular events in high-risk hypertensive patients.
The ability of coronary artery calcium (CAC) to predict coronary events has been shown in several studies. We aimed to investigate the hypothesis that CAC as assessed by dual slice spiral computed tomography (DSCT), is an independent risk factor for cardiovascular events in hypertensive patients. We followed 446 participants of INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy) calcification study, for the incidence of cardiovascular events as a function of CAC and other factors. All were hypertensive, without coronary artery disease (CAD), ages > 55 years and with at least one more major cardiovascular risk factor. All underwent a baseline DSCT and were followed for a mean period of 3.8 +/- 0.4 years. All events were documented while the scheduled visits and confirmed by the INSIGHT critical event committee. Follow-up was conducted on all participants. 294 patients (66%) had CAC at baseline. Forty-seven patients experienced a first cardiovascular event: acute myocardial infarction (MI), 16; sudden cardiac death, two; unstable angina resulting in revascularization, 14; stroke, 15. The incidence of first cardiovascular events was 3.7 times higher among those who had CAC at baseline than among those who had no CAC (14.5% (41 of 294) versus 3.9% (6 of 152)). Patients who experienced an event were more likely to be males, had had higher prevalence of peripheral vascular disease, longer duration of hypertension, and had higher levels of systolic blood pressure (SBP), glucose, creatinine and uric acid. Adjusting for these covariates, CAC (total coronary calcium score (TCS) > 0) independently predicted cardiovascular events with an odds ratio (OR) of 2.76 [95% confidence interval (CI) 1.09-6.99, P = 0.032]. The presence of CAC predicts cardiovascular events in high-risk asymptomatic hypertensive patients.


Dose-response and transmission: the nexus between reservoir hosts, environment and recipient hosts.
Dose is the nexus between exposure and all upstream processes that determine pathogen pressure, and is thereby an important element underlying disease dynamics. Understanding the relationship between dose and disease is particularly important in the context of spillover, where nonlinearities in the dose-response could determine the likelihood of transmission. There is a need to explore dose-response models for directly transmitted and zoonotic pathogens, and how these interactions integrate within-host factors to consider, for example, heterogeneity in host susceptibility and dose-dependent antagonism. Here, we review the dose-response literature and discuss the unique role dose-response models have to play in understanding and predicting spillover events. We present a re-analysis of dose-response experiments for two important zoonotic pathogens (Middle East respiratory syndrome coronavirus and Nipah virus), to exemplify potential difficulties in differentiating between appropriate models with small exposure experiment datasets. We also discuss the data requirements needed for robust selection between dose-response models. We then suggest how these processes could be modelled to gain more realistic predictions of zoonotic transmission outcomes and highlight the exciting opportunities that could arise with increased collaboration between the virology and epidemiology disciplines. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.


Skin-homing, CLA+ memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern: IgG4 counter-regulation by CLA- memory T cells.
Cutaneous lymphocyte-associated Ag (CLA) is a skin-homing receptor displayed by memory/effector T cells recognizing skin-related allergens. Here we demonstrate that peripheral blood CLA+ CD45RO+ T cells in patients with atopic dermatitis (AD) are in vivo activated. They spontaneously proliferate and release an IL-13-dominated Th2 cytokine profile and are capable of inducing IgE in autologous B cells without further activation. The spontaneous cytokine release occurred within the first hour of culture and was not inhibited by cycloheximide or by other immunosuppressive drugs, indicating that cytokine transcription and translation had been completed in vivo. In contrast, the CLA- CD45RO+ T cells from the same patients and from nonatopic controls represented a resting memory T cell subset, secreted borderline quantities of cytokines, and induced IgG4. Polyclonal activation by the anti-CD2/anti-CD3/anti-CD28 mAb mixture generated distinct cytokine patterns in the two memory/effector T cell subsets. CLA+ T cells secreted Th2 cytokines with high IL-13 levels, and the CLA- subset mainly produced IFN-gamma. There was no difference in in vitro activated cytokine pattern between AD patients and nonatopic subjects. These results indicate that the CLA+ memory/effector T cells of AD patients are activated in vivo and play a pivotal role in allergic inflammation by production of IL-13 and induction of IgE Abs. In contrast, the CLA- resting memory T cell population may exert immunoprotective properties toward allergen by high IFN-gamma secretion and induction of IgG4.


Application of the ATC/DDD methodology to monitor antibiotic drug use.
In order to monitor the use of antibiotics, it is essential to have comprehensive data on drug consumption. The findings of drug utilisation studies can serve to describe the pattern of drug use in a particular population, to detect areas of concern, and to evaluate the impact of interventions taken to influence the use of drugs. In the present study, the Anatomical Therapeutical Chemical Classification/Defined Daily Doses (ATC/DDD) system developed by the World Health Organisation was evaluated. The system measures the amount of drug used independent of package size and sales price, which allows comparisons not only within an institution but also within a region, a country, or even internationally. Obviously, there can be no modifications of this system. To illustrate the method, the pattern of quinolone use in the general population, in long-term care facilities, and within a single institution was analysed. These drugs were widely used in long-term care facilities in the Nijmegen region of the Netherlands, accounting for about 30% of the antibiotics used in these settings, whereas in the general population as well as in the University Hospital Nijmegen, these drugs constitute only about 6% of the total antibiotics used. These differences are large enough to warrant closer analysis of patterns of antibiotic usage in different settings to identify the reasons for the use of quinolones and to identify measures that might be taken to rationalise the prescription of these drugs.


An explicit shape-constrained MRF-based contour evolution method for 2-D medical image segmentation.
Image segmentation is, in general, an ill-posed problem and additional constraints need to be imposed in order to achieve the desired segmentation result. While segmenting organs in medical images, which is the topic of this paper, a significant amount of prior knowledge about the shape, appearance, and location of the organs is available that can be used to constrain the solution space of the segmentation problem. Among the various types of prior information, the incorporation of prior information about shape, in particular, is very challenging. In this paper, we present an explicit shape-constrained MAP-MRF-based contour evolution method for the segmentation of organs in 2-D medical images. Specifically, we represent the segmentation contour explicitly as a chain of control points. We then cast the segmentation problem as a contour evolution problem, wherein the evolution of the contour is performed by iteratively solving a MAP-MRF labeling problem. The evolution of the contour is governed by three types of prior information, namely: (i) appearance prior, (ii) boundary-edgeness prior, and (iii) shape prior, each of which is incorporated as clique potentials into the MAP-MRF problem. We use the master-slave dual decomposition framework to solve the MAP-MRF labeling problem in each iteration. In our experiments, we demonstrate the application of the proposed method to the challenging problem of heart segmentation in non-contrast computed tomography data.


Paclitaxel-Nanodiamond Nanocomplexes Enhance Aqueous Dispersibility and Drug Retention in Cells.
Nanodiamonds (NDs) with 5 nm crystalline structures have been recognized as emerging carbon delivery vehicles due to their biocompatible inertness, high surface-to-volume ratio, and energy absorbance properties. In this study, carboxylated nanodiamond (ND-COOH) was reduced to hydroxylated nanodiamond (ND-OH) for stable and pH-independent colloidal dispersity. The poorly water-soluble paclitaxel (PTX) was physically loaded into ND-OH clusters, forming amorphous PTX nanostructure on the interparticle nanocage of the ND substrate. Stable physical PTX loading onto the ND substrate with stable colloidal stability showed enhanced PTX release. ND-OH/PTX complexes retained the sustained release of PTX by up to 97.32% at 70 h, compared with the 47.33% release of bare crystalline PTX. Enhanced PTX release from ND substrate showed low cell viability in Hela, MCF-9, and A549 cancer cells due to sustained release and stable dispersity in a biological aqueous environment. Especially, the IC50 values of ND-OH/PTX complexes and PTX in Hela cells were 0.037 μg/mL and 0.137 μg/mL, respectively. Well-dispersed cellular uptake of suprastructure ND-OH/PTX nanocomplexes was directly observed from the TEM images. ND-OH/PTX nanocomplexes assimilated into cells might provide convective diffusion with high PTX concentration, inducing initial necrosis. This study suggests that poorly water-soluble drugs can be formulated into a suprastructure with ND and acts as a highly concentrated drug reservoir directly within a cell.


Use of the skeletal survey in the evaluation of child maltreatment.
The radiologic skeletal survey is an important tool for evaluating occult trauma in suspected child abuse. The purposes of this study were: (1) to determine the incidence of clinically unsuspected fractures detected by skeletal survey, and (2) to identify high-risk groups of children who would benefit from skeletal surveys. We retrospectively reviewed the medical records of 203 children admitted over a 30-month period to Children's National Medical Center for alleged physical abuse. Skeletal surveys were ordered based on the treating physicians' clinical suspicions. Patients in whom skeletal surveys were positive for an occult fracture were studied in more detail. There were 96 skeletal surveys performed; of these, 25 were positive for at least 1 clinically unsuspected fracture. Eighty percent of occult fractures were found in children younger than 1 year old. Presenting with a new fracture or an intracranial injury placed the child at higher risk of occult fracture. In contrast, patients with burn injuries had a very low yield of occult fractures. The patient's age and type of suspicious injury can help guide the physician as to when to obtain a skeletal survey.


Chloride channels in renal disease.
Recent studies of hereditary renal tubular disorders have facilitated the identification and roles of chloride channels and cotransporters in the regulation of the most abundant anion, Cl-, in the ECF. Thus, mutations that result in a loss of function of the voltage-gated chloride channel, CLC-5, are associated with Dent's disease, which is characterized by low-molecular weight proteinuria, hypercalciuria, nephrolithiasis, and renal failure. Mutations of another voltage-gated chloride channel, CLC-Kb, are associated with a form of Bartter's syndrome, whereas other forms of Bartter's syndrome are caused by mutations in the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC2) and the potassium channel, ROMK. Finally, mutations of the thiazide-sensitive sodium-chloride cotransporter (NCCT) are associated with Gitelman's syndrome. These studies have helped to elucidate some of the renal tubular mechanisms regulating mineral homeostasis and the role of chloride channels.


Upper GI bleeding among neonates admitted to Mulago Hospital, Kampala, Uganda: a prospective cohort study.
The World Health Organization (WHO) reports estimate that 85% of newborn deaths are due to infections, prematurity and fetal distress. These conditions are risk factors for upper GI bleeding (UGIB) in sick neonates. UGIB is associated with poor neonatal outcomes such as prolonged hospitalisation and poor weight gain. The magnitude of UGIB and its contribution to neonatal morbidity has not been described in most low income countries. To determine the occurrence and factors associated with UGIB among neonates admitted to the Special Care Unit (SCU) of Mulago Hospital. This was a prospective single cohort study where neonates admitted within 24 hours of birth were consecutively enrolled and followed up for seven days. Gastric aspirates from the neonates were examined daily over a period of 7 days using Guaiac and Apt tests for evidence of UGIB. Data on occurrence of UGIB has been presented as proportions and Odds Ratios for associated factors. Out of 191 neonates, 44 (23 %) developed UGIB. Factors independently associated with UGIB included cyanosis in the neonate [OR 5.8; (95% CI; 1.8 - 19.1) p-value 0.004], neonatal seizures [OR 12.6; (95% CI 2.3 - 70.5); p-value 0.004] and birth asphyxia [OR 6.3; (95% CI 1.9 - 21.6); p-value 0.003]. In the first seven days of life, UGIB occurred in 1:4 neonates. Factors independently associated with UGIB included birth asphyxia, cyanosis in the neonate and neonatal seizures.


The transcriptional regulation of pluripotency.
The defining features of embryonic stem cells (ESCs) are their self-renewing and pluripotent capacities. Indeed, the ability to give rise into all cell types within the organism not only allows ESCs to function as an ideal in vitro tool to study embryonic development, but also offers great therapeutic potential within the field of regenerative medicine. However, it is also this same remarkable developmental plasticity that makes the efficient control of ESC differentiation into the desired cell type very difficult. Therefore, in order to harness ESCs for clinical applications, a detailed understanding of the molecular and cellular mechanisms controlling ESC pluripotency and lineage commitment is necessary. In this respect, through a variety of transcriptomic approaches, ESC pluripotency has been found to be regulated by a system of ESC-associated transcription factors; and the external signalling environment also acts as a key factor in modulating the ESC transcriptome. Here in this review, we summarize our current understanding of the transcriptional regulatory network in ESCs, discuss how the control of various signalling pathways could influence pluripotency, and provide a future outlook of ESC research.


Unusual salt stability in highly charged diblock co-polypeptide hydrogels.
The stability and properties of dilute solution hydrogels, synthesized by transition metal mediated polymerization of amino acid N-carboxyanhydrides (NCAs), have been studied in deionized (DI) water as well as various ionic media. These hydrogels are diblock amphiphilic copolymers of hydrophilic, charged segments of poly(l-lysine HBr) or poly(l-glutamic acid sodium salt), and helical, hydrophobic segments of poly(l-leucine). While many of these samples are able to form strong gels in deionized water at polymer concentrations as low as 0.25 wt %, stability in salt or buffer solutions was found to be only achieved at moderately higher polymer concentrations ( approximately 3.0 wt %). We have adjusted relative copolymer compositions and molecular weights to optimize hydrogel strength and polymer solubility in salt concentrations up to 0.5 M NaCl, as well as in cell growth media and aqueous buffers of varying pH. These materials are unique since they do not collapse in high ionic strength media, even though gel formation is contingent upon the presence of highly charged polyelectrolyte segments. The remarkable properties of these hydrogels make them excellent candidates for use as scaffolds in biomedical applications, such as tissue regeneration.


Modified Total Intrinsic Rehabilitation Procedure for Ulnar Palsy.
Tendon transfer for ulnar palsy has been an area of interest for many a stalwart in hand surgery, especially in southeast Asian countries, mainly because of the prevalence of Hansen's disease in these countries. Although the procedures look standardized, there are still many lacunae. Here in this article, we discuss about a surgical technique by which all the motor disabilities evolving due to ulnar nerve paralysis are addressed with three sets of tendon transfers performed in a single stage for: (1) key pinch restoration, (2) claw correction and adduction of fingers, and (3) claw correction and abduction of fingers.


Elevated and accelerated: Locus coeruleus activity and visual search abilities in autistic children.
Autistic individuals excel at visual search, however, the neural mechanism(s) underlying this advantage remain unclear. The locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in sensory perception and selective attention, has been shown to function in a persistently elevated state in individuals on the spectrum. However, the relationship between elevated tonic LC-NE activity and accelerated search in autism has not been explored. To examine the relationship between visual search abilities and resting pupil diameter (an indirect measure of tonic LC-NE activation) in autistic and neurotypical children. Participants were 24 school-aged autistic children and 24 age- and IQ-matched neurotypical children aged 8-15 years. Children completed two tasks: a resting eye-tracking task and a visual search paradigm. For the resting eye-tracking task, pupil diameter was monitored while participants fixated a central crosshair. For the visual search paradigm, participants were instructed to find the target (vertical line) embedded within an array of tilted (10°) distractor lines. The target was present on 50% of trials, and displayed within set sizes of 18, 24, and 36 items. Consistent with previous studies, autistic children had significantly larger resting pupil size and searched faster and more efficiently compared to their neurotypical peers. Eye-tracking findings revealed that accelerated search was associated with fewer, not shorter, fixations in the autism group. Autistic children also showed reduced leftward search bias. Larger resting pupil size, indicative of increased tonic activation of the LC-NE system, was associated with greater search efficiency, longer fixation durations, and reduced leftward bias. Finally, within both groups reduced leftward bias was associated with increased autism symptomatology. Together, these findings add to the existing body of research highlighting superior search in autism, suggest that elevated tonic LC-NE activity may contribute to more efficient search, and link non-social visual-spatial processing strengths to autism symptoms.


Insights on accelerated skeletal repair in Cushing's disease.
Cushing's disease with prolonged exposure to high circulating levels of glucocorticoids is associated with deterioration of the structural integrity of bone, resulting in increased skeletal fragility and fractures. The mechanism of bone repair following successful surgical treatment is poorly understood. A 34-year-old man presented with a tibial fracture and severely low BMD, elevated AM serum cortisol, ACTH, and 24 h urinary free cortisol, which did not suppress with 2 days of high dose dexamethasone. Following transphenoidal resection of a pituitary microadenoma, serum cortisol and ACTH normalized. A repeat DXA at 8 months post-resection showed no change in BMD, however the Trabecular Bone Score (TBS), which reported severe deterioration of trabecular bone architecture at diagnosis, improved to normal. At that time, teriparatide (TPTD) was given for 2 years, which resulted in a 53.9% increase in BMD with only a small improvement in TBS. In this patient, spontaneous recovery of trabecular bone architecture was reflected by the early correction in TBS. Subsequent TPTD treatment was associated with marked improvement in BMD, presumably due to enhanced mineralization. Complete skeletal repair was achieved by this two-step mechanism in a very short time following successful surgical treatment for Cushing's disease.


Associations between violence, criminality, and cognitive control deficits among young men living in low resource communities in South Africa.
Despite empirical support for "Self-control theory" in criminology, there is controversy about how self-control should be operationalized. Working within the framework of "self-control theory," we investigated if violence and criminal behaviors are associated with nine distinct dimensions of cognitive control in a community sample of young men (n = 654) living in peri-urban townships in South Africa. Cognitive control was assessed using the Behavior Rating Inventory of Executive Function. Multivariate statistical analysis was used, to identify associations between violence and criminality, and deaggregated measures of nine distinct components of cognitive control. Fifteen percent of the sample reported recent violence, 27% had been in physical fights with family/friends in the preceding 6 months, 10% reported being arrested, 4% reported forced sexual contact, and 26% reported intimate partner violence (IPV). Controlling for substance use and sociodemographic variables, contact with the criminal justice system and violence were associated with deficits in all domains of cognitive control. Forced sexual contact was associated with behavioral dysregulation. IPV was associated with behavior dysregulation and executive control dysfunction. Future studies might utilize deaggregated measures of self-control to provide further insight into links between particular components of cognitive control and various forms of offending and violence.


The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis.
Multidrug resistance mediated by the drug efflux protein, P-glycoprotein (P-gp), is one mechanism that tumor cells use to escape death induced by chemotherapeutic agents. However, the mechanism by which P-gp confers resistance to a large variety of structurally diverse molecules has remained elusive. In this study, classical multidrug resistant human CEM and K562 tumor cell lines expressing high levels of P-gp were less sensitive to multiple forms of caspase-dependent cell death, including that mediated by cytotoxic drugs and ligation of Fas. The DNA fragmentation and membrane damage inflicted by these stimuli were defined as caspase dependent by various soluble peptide fluoromethylketone caspase inhibitors. Inhibition of P-gp function by the anti-P-gp mAb MRK-16 or verapamil could reverse resistance to these forms of cell death. Inhibition of P-gp function also enhanced drug or Fas-mediated activation of caspase-3 in drug-resistant CEM cells. By contrast, caspase-independent cell death events in the same cells, including those mediated by pore-forming proteins or intact NK cells, were not affected by P-gp expression. These observations suggest that, in addition to effluxing drugs, P-gp may play a specific role in regulating some caspase-dependent apoptotic pathways.


Advances in the Development of Biomarkers for Poststroke Epilepsy.
Stroke is the main cause of acquired epilepsy in elderly people. Poststroke epilepsy (PSE) not only affects functional recovery after stroke but also brings considerable social consequences. While some factors such as cortical involvement, hemorrhagic transformation, and stroke severity are associated with increased seizure risk, so far that remains controversial. In recent years, there are an increasing number of studies on potential biomarkers of PSE as tools for diagnosing and predicting epileptic seizures. Biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), glutamate, and S100 calcium-binding protein B (S100B) in blood are associated with the occurrence of PSE. This review is aimed at summarizing the progress on potential biomarkers of PSE.


Recovery From Severe Mental Health Problems: A Systematic Review of Service User and Informal Caregiver Perspectives.
Introduction: The recovery approach aims to have users' perspectives at the heart of service development and research; it is a holistic perspective that considers social needs, personal growth and inclusion. In the last decade recovery-oriented research and practice has increased greatly, however, a comprehensive model of recovery considering exclusively the perspectives of people with lived experience has not been devised. Aims: This review aimed to develop a framework and contextualize service users' and informal caregivers' understanding of recovery from severe mental health problems. Methods: We systematically searched 6 databases including key terms related to knowledge, experience and narratives AND mental health AND personal recovery. The search was supplemented with reference sourcing through gray literature, reference tracking and expert consultation. Data analysis consisted of a qualitative meta-synthesis using constant comparative methods. Results: Sixty-two studies were analyzed. A pattern emerged regarding the recovery paradigms that the studies used to frame their findings. The resulting recovery framework included the domains Social recovery; Prosperity (Legal, political, and economic recovery); Individual Recovery; and Clinical Recovery Experience (SPICE). Service users' definitions of recovery tended to prioritize social aspects, particularly being accepted and connecting with others, while caregivers focused instead on clinical definitions of recovery such as symptom remission. Both groups emphasized individual aspects such as becoming self-sufficient and achieving personal goals, which was strongly linked with having economic means for independence. Conclusions: The recovery model provided by this review offers a template for further research in the field and a guide for policy and practice. Predominant definitions of recovery currently reflect understandings of mental health which focus on an individual perspective, while this review found an important emphasis on socio-political aspects. At the same time, only a small number of studies took place in low-income countries, focused on minoritized populations, or included caregivers' perspectives. These are important gaps in the literature that require further attention. Systematic Review Registration: The review protocol was registered on PROSPERO (CRD42017076450); https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=76450.


SPMM: estimating infection duration of multivariant HIV-1 infections.
Illustrating how HIV-1 is transmitted and how it evolves in the following weeks is an important step for developing effective vaccination and prevention strategies. It is currently possible through DNA sequencing to account for the diverse array of viral strains within an infected individual. This provides an unprecedented opportunity to pinpoint when each patient was infected and which viruses were transmitted. Here we develop a mathematical tool for early HIV-1 evolution within a subject whose infection originates either from a single or multiple viral variants. The shifted Poisson mixture model (SPMM) provides a quantitative guideline for segregating viral lineages, which in turn enables us to assess when a subject was infected. The infection duration estimated by SPMM showed a statistically significant linear relationship with that by Fiebig laboratory staging (P = 0.00059) among 37 acutely infected subjects. Our tool provides a functional approach to understanding early genetic diversity, one of the most important parameters for deciphering HIV-1 transmission and predicting the rate of disease progression. SPMM, webserver, is available at http://www.hayounlee.org/web-tools.html. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


The Proteocephalus Species-Aggregate in Freshwater Centrarchid and Percid Fishes of the Nearctic Region (North America).
In the present paper, species of the Proteocephalus-aggregate de Chambrier, Zehnder, Vaucher, and Mariaux, 2004 (Cestoda: Proteocephalidae) reported from centrarchid and percid fishes in North America are reviewed, and their taxonomic status is critically assessed based on a study of type specimens and new material from Canada and the United States. The following 3 species, supposedly strictly specific to their fish definitive hosts, are recognized as valid: (1) Proteocephalus fluviatilis Bangham, 1925 (new synonyms Proteocephalus osburni Bangham, 1925 and Proteocephalus microcephalus Haderlie, 1953 ; Proteocephalus 'robustus' nomen nudum) from the smallmouth and largemouth bass, Micropterus dolomieu (Lacépède) (type host) and Micropterus salmoides (Lacépède) (both Centrarchidae); (2) Proteocephalus luciopercae Wardle, 1932 (new synonym Proteocephalus stizostethi Hunter and Bangham, 1933 ) from the walleye, Sander vitreus (Mitchill) (type host), and sauger, Sander canadensis (Griffith et Smith) (Percidae); and (3) Proteocephalus pearsei La Rue, 1919 , a parasite of the yellow perch, Perca flavescens Mitchill (Percidae). All species are illustrated based on new, properly heat-fixed material. Scanning electron micrographs of the scoleces of percid tapeworms P. luciopercae and P. pearsei, as well as the bass tapeworms P. fluviatilis and Proteocephalus ambloplitis ( Leidy, 1887 ), the latter of which does not belong to this Proteocephalus-aggregate, are provided for the first time together with a simple key to species identification of proteocephalids from centrarchiform and perciform teleost fishes.


New flavanol and cycloartane glucosides from Landoltia punctata.
Chemical investigation on the constituents of Landoltia punctata led to the isolation and identification of 17 compounds, four of which were new and identified as (3b,24S)-9,19-cycloartane-3,22,24,25-tetraol 3-O-[b-D-glucopyranosyl-(1→2)]-[b-D-glucopyranosyl-(1→6)]-b-D-glucopyranoside (1), (3b,24S)-9,19-cycloartane-3,24,25-triol 3-O-[b-d-glucopyranosyl-(1→2)]-[b-D-glucopyranosyl-(1→6)]-b-D-glucopyranoside (2), 3,4'-dihydroxy-7,3'-dimethoxyflavan-5-O-b-D-glucopyranoside (3) and 3,4'-dihydroxy-4,7,3'-trimethoxyflavan-5-O-b-D-glucopyranoside (4). Their structures were elucidated by spectroscopic, chemical, and biochemical methods. Thus, cycloartane triterpenoids were discovered in the Lemnaceae family for the first time. Compound 3 showed antioxidant capacity in the positively charged 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical (ABTS+•) and superoxide anion radical scavenging assays.


Hepatitis C virus infection and lymphoproliferative diseases in France: a national study. The GERMIVIC Group.
The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenström's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.


Intestinal decompression: preliminary study in the horse.
A technique of nasoduodenal (N-D) intubation and intestinal decompression was developed and used in the horse to explore the prevention of gastric and intestinal distention after abdominal surgical operation. Three styles of tubes (2 single-lumen tubes and 1 double-lumen tube) were positioned in the duodenum of 12 mature horses (10 experimental and 2 clinical) during laparotomy (without enterotomy), and an iatrogenic occlusion at the small intestine was created and later released in the 10 experimental horses. The 2 clinical horses had an exploratory laparotomy to correct a natural obstruction of the small intestine. After each horse recovered from surgical manipulation, suction was used to keep fluids from accumulating in the cranial part of the gastrointestinal tract. In 5 of the 12 horses, the most simple N-D tube was positioned successfully and functioned properly. Three of the 5 horses which were fasted before surgical manipulation (to obtain an empty stomach) survived without postsurgical complications. Volume of reflux material was measured. Clinical data, such as periods of comfort during decompression without giving analgesics, were recorded. Necropsies were done on 10 of the 12 horses (9 experimental and 1 clinical). Although already tested in 2 clinical horses, use of the N-D tube remains experimental, and the N-D tube functioned only in horses which were fasted before surgical manipulation. Perfection of a safe and dependable means of emptying the equine stomach of its solid ingesta before gastrointestinal intubation is done, is the next step in affording greater clinical application of the N-D tube for gastrointestinal decompression.


Xeroderma pigmentosa--a disfiguring disease.
Xeroderma pigmentosa is a rare inherited autosomal recessive disease with the inability to repair DNA damage caused by UV light. Recognized in the late 1800 by Maritz Kaposi it has been reported world wide and in all races with an over prevalence of 1-4 per million population. Kunwar et al. Those affected are extremely sensitive to the UV portion of the light and have a 2000-fold increased risk of skin cancer in the sun exposed skin. Basal cell carcinoma is the most commonly associated carcinoma followed by Squamous cell carcinoma and Melanoma. The pigmentation on the face and the rest of the body can be horribly disfiguring. The recurring cancer occurring on the face and repeated surgical treatment for the ulcerations have important social and psychological implications not encountered with other cancers. We report two cases of BCC and melanoma. The first case is of BCC of the face in a teenaged girl coexisting with xeroderma pigmentosa. The second case presented with melanoma of the scalp in a 10 year old female child. The details of these cases are presented and the management.


Characterization of Antixenosis in Soybean Genotypes to Bemisia tabaci (Hemiptera: Aleyrodidae) Biotype B.
Bemisia tabaci biotype B (Gennadius) is one of the most important soybean pest worldwide. Herein, 15 soybean genotypes were evaluated, to characterize the occurrence of antixenosis to B. tabaci biotype B. Initially, a multiple-choice test with all genotypes was carried out, evaluating the settling and oviposition preference at 3 d after infestation, and the colonization by nymphs after 48 d of infestation. Subsequently, a no-choice test, using 14 genotypes, was conducted with infested plants individually, and the number of eggs was counted after 72 h. Then, 10 genotypes were selected (indicative of resistance and susceptibility), which were evaluated for whitefly settling 24, 48, and 72 h after infestation and for oviposition 72 h after infestation. The trichomes of the leaflets were characterized for density, size, and inclination to establish possible correlations with the settling and oviposition in the genotypes. In the first multiple-choice test, involving 15 genotypes, 'IAC-17,' 'IAC-19,' and UX-2569-159 expressed antixenosis against B. tabaci. 'Jackson,' 'P98Y11,' and PI-229358 exhibited the same behavior in the no-choice test. In the multiple-choice test, 'Jackson,' 'P98Y11,' and 'TMG1176 RR' were the least attractive and least used for oviposition. The antixenosis shown by 'Jackson,' 'P98Y11,' and PI-229358 may be related to the characteristics of the trichomes (lower density and inclined). Based on the experiments carried out, 'IAC-17,' 'IAC-19,' 'Jackson,' 'P98Y11,' PI-229358, TMG1176 RR, and UX-2569-159 are considered promising for resistance to B. tabaci biotype B and may be exploited in soybean breeding programs for resistance to insects.


Carcinoma of extrahepatic bile ducts and gallbladder metastatic to the ovary: a report of 16 cases.
Information on ovarian metastasis of carcinoma of the extrahepatic bile ducts and gallbladder is limited. Sixteen examples are reported; 3 primary tumors were hilar cholangiocarcinomas, 5 common bile duct carcinomas, and 8 gallbladder carcinomas. The patients ranged from 21 to 87 years (mean, 59 years); 7 presented to gynecologists with nonspecific pelvic symptoms similar to primary ovarian neoplasms. The primary tumor was identified before the detection of the ovarian lesions in 5 cases, was simultaneously detected with the ovarian metastases in 9, and was diagnosed postoperatively in 2. All but one case had bilateral ovarian involvement. The thirty-one ovarian lesions included twenty-nine grossly abnormal ovaries that were enlarged (range, 3.0-16.5 cm, mean, 9.4 cm) and 2 ovaries with only microscopic involvement. The sectioned surface was solid in 9, solid-cystic in 15, and multicystic in 5. Microscopically, ovarian surface implants were seen in 66%, multinodular growth in 58%, and infiltrative stromal invasion in 81%. Mucinous epithelial differentiation was seen in 81%, sometimes with foci of benign-like or borderline-like epithelium simulating primary ovarian mucinous neoplasia. Cystadenoma and cystadenofibroma of nonmucinous type was even mimicked strikingly in some cases because of flattening of epithelium lining glands and cysts. Signet ring cells were present in sufficient quantity for a diagnosis of Krukenberg tumor in four tumors. Colloid-type carcinoma was observed at least focally in 3 tumors. Nonmucinous carcinomatous components included adenocarcinoma with high-grade endometrioid-like morphology in 2 cases, papillary adenocarcinoma simulating mixed müllerian epithelial adenocarcinoma in 1, and undifferentiated carcinoma in 2. Immunohistochemical studies in 8 cases showed a positive reaction for cytokeratin 7 in all and for cytokeratin 20 in 4 cases. The high rate of bilaterality, surface involvement, multinodular growth, and heterogeneity of patterns were the most helpful features for indicating a metastatic nature, with signet ring cells also being helpful in the minority of cases in which they were present. Although the diagnosis of a metastatic tumor to the ovary is possible in most of the cases based on standard diagnostic criteria, problems in the differential diagnosis may be posed by morphologic patterns that overlap strikingly with primary ovarian neoplasms, benign, borderline, and malignant, as discussed herein.


Chronic chest pain and paresthesia after video-assisted thoracoscopy for primary pneumothorax.
This study aims to identify clinical and surgical risk factors for chronic chest pain and paresthesia after video thoracoscopic surgery for primary spontaneous pneumothorax. We retrospectively collected the data of 1,178 consecutive patients <40-years-old undergoing video thoracoscopic surgery for primary spontaneous pneumothorax in 9 Italian centers in 2007-2017. Cases with <2-month follow-up were excluded, leaving 920 patients [80% male; median age: 21 (IQR, 18-27) years] for statistical analysis. The following risk factors for chronic chest pain and chronic paresthesia were assessed by univariable and multivariable Cox regression model: age, gender, cannabis smoking, video thoracoscopy ports number, pleurodesis technique (partial pleurectomy/pleural electrocauterization/pleural abrasion/talc poudrage), chest tube size (24/28 F), postoperative chest tube stay. Blebs/bullae resection with pleurodesis was performed in 732 (80%) cases; pleurodesis alone in 188 (20%). During a median follow-up of 68 (IQR: 42-95) months, chronic chest pain developed in 8% of patients, chronic chest paresthesia in 22%; 0.5% of patients regularly assumed painkillers. Chronic chest pain was independently associated with partial pleurectomy/pleura abrasion (P<0.001) and postoperative chest tube stay (P=0.019). Chronic chest paresthesia was independently associated with pleurodesis by partial pleurectomy (P<0.001), chest tube stay (P=0.035) and 28 F chest tube (P<0.001). After video thoracoscopic surgery for primary spontaneous pneumothorax, the incidence of chronic chest pain and paresthesia was significantly lower when pleurodesis was performed by pleural electrocauterization or talc poudrage, and chest tube was removed early. A 24 F chest tube was associated with lower risk of chronic chest paresthesia.


Closed-Loop Fuzzy Energy Regulation in Patients With Hypercortisolism via Inhibitory and Excitatory Intermittent Actuation.
Hypercortisolism or Cushing's disease, which corresponds to the excessive levels of cortisol hormone, is associated with tiredness and fatigue during the day and disturbed sleep at night. Our goal is to employ a wearable brain machine interface architecture to regulate one's energy levels in hypercortisolism. In the present simulation study, we generate multi-day cortisol profile data for ten subjects both in healthy and disease conditions. To relate an internal hidden cognitive energy state to one's cortisol secretion patterns, we employ a state-space model. Particularly, we consider circadian upper and lower bound envelopes on cortisol levels, and timings of hypothalamic pulsatile activity underlying cortisol secretions as continuous and binary observations, respectively. To estimate the hidden cognitive energy-related state, we use Bayesian filtering. In our proposed architecture, we infer one's cognitive energy-related state using wearable devices rather than monitoring the brain activity directly and close the loop utilizing fuzzy control. To model actuation in the real-time closed-loop architecture, we simulate two types of medications that result in increasing and decreasing the energy levels in the body. Finally, we close the loop using a knowledge-based control approach. The results on ten simulated profiles verify how the proposed architecture is able to track the energy state and regulate it using hypothetical medications. In a simulation study based on experimental data, we illustrate the feasibility of designing a wearable brain machine interface architecture for energy regulation in hypercortisolism. This simulation study is a first step toward the ultimate goal of managing hypercortisolism in real-world situations.


The Muscle Metabolome Differs between Healthy and Frail Older Adults.
Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects, and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference group. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies.


"It brought hope and peace in my heart:" Caregivers perceptions on kangaroo mother care services in Malawi.
Kangaroo mother care (KMC) is an effective intervention for preterm and low birth weight infants. Effective implementation of KMC relies on a multidisciplinary team centering on the newborn's caregiver, who delivers care with support from health care workers. This study explored the experiences of caregivers on the implementation of KMC. We conducted a descriptive qualitative study in the phenomenological tradition, an interpretative approach to describe the caregivers' lived experience with KMC at four health facilities in Malawi from April and June 2019 through 10 non-participatory observations and 24 face-to-face interviews. We drew a purposive sample of 14 mothers, six fathers, three grandmothers, and one grandfather of infants receiving KMC in three secondary and one tertiary level hospitals. Data were analyzed following a thematic approach. Caregivers had limited information on KMC before admission with most of the information learned from peers rather than medical professionals. Stories of positive outcomes following KMC contributed to a shift in perceptions of premature babies and acceptability of KMC as an effective intervention. Unintended consequences resulting from admission due to KMC disrupts responsibilities around the home and disrupts economic activities. Gender division of roles exists with the implementation of KMC and a mother's support networks are crucial. Kangaroo mother care is feasible and acceptable among caregivers. KMC babies are described more positively with the potential to grow into strong and healthy children. KMC remains focused on the mother, which undervalues the important roles of her support network. A change in the nomenclature from kangaroo mother care to kangaroo care would include fathers and others delivering care.


Quantitation of corneal ablation by ultraviolet laser light.
A surgical role has been suggested for the excimer laser. This followed the discovery of precision etching of biological materials by the laser's ultraviolet emissions. In studying the amount of tissue removed as the laser energy density (irradiance) was varied, we found significant differences for the 193-, 249-, and 308-nm laser emission lines. The most efficient cutting irradiance for each pulse appeared to be about 200 millijoules/sq cm for 193 nm, 1,000 millijoules/sq cm for 249 nm, and 1,500 millijoules/sq cm for 308 nm. The flat slope of the etch depth curve for 193 nm suggests it will be a stable frequency when used clinically.


Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism.
Prorenin can be detected in plasma of hypertensive patients. If detected in patients with primary aldosteronism could implicate prorenin in the development of primary aldosteronism. To address this issue, we measured the plasma prorenin levels in primary aldosteronism patients, the expression of the prorenin receptor (PRR) in the normal human adrenocortical zona glomerulosa and aldosterone-producing adenoma (APA), and we investigated the functional effects of PRR activation in human adrenocortical cells. Plasma renin activity, aldosterone, and active and total trypsin-activated renin were measured in primary aldosteronism patients, essential hypertensive patients, and healthy individuals, and then prorenin levels were calculated. Localization and functional role of PRR were investigated in human and rat tissues, and aldosterone-producing cells. Primary aldosteronism patients had detectable plasma levels of prorenin. Using digital-droplet real-time PCR, we found a high PRR-to-porphobilinogen deaminase ratio in both the normal adrenal cortex and APAs. Marked expression of the PRR gene and protein was also found in HAC15 cells. Immunoblotting, confocal, and immunogold electron microscopy demonstrated PRR at the cell membrane and intracellularly. Renin and prorenin significantly triggered both CYP11B2 expression (aldosterone synthase) and ERK1/2 phosphorylation, but only CYP11B2 transcription was prevented by aliskiren. The presence of detectable plasma prorenin in primary aldosteronism patients, and the high expression of PRR in the normal human adrenal cortex, APA tissue, CD56+ aldosterone-producing cells, along with activation of CYP11B2 synthesis and ERK1/2 phosphorylation, suggest that the circulating and locally produced prorenin may contribute to the development or maintenance of human primary aldosteronism.


Preventive health care for pre-school children in Croatia: ongoing trends from 1995 to 2012.
In Croatia, primary health care for pre-school children is organized by pediatricians (PPs) for children in urban and family doctors (FDs) for children in remote areas. This study was undertaken with the aim to determine the trends in preventive activities (general, targeting, and control check-ups and total visits) in both services (FDs, PPs), between 1995 and 2012. The main adapt source was the Croatian Health Service Yearbooks. According to the results, the number and the structure of preventive activities performed by PPs are relatively stable, while those performed by FDs decreased rapidly, primarily because the number of children under the care decreased. It is probable in relations with the regulations to direct the children to PPs and not to the FDs. The average numbers of all preventive activities are under the optimum. There are many similarities between FDs' and PPs', some activities were frequently performed by FDs and others by PPs'.


Genetic divergence between cave and surface populations of Astyanax in Mexico (Characidae, Teleostei).
A study of genetic diversity at microsatellite loci and the mitochondrial DNA (mtDNA) cytochrome b gene was carried out to assess genetic relationships among four Mexican cave (Pachon, Sabinos, Tinaja, Chica) and four surface populations of Astyanax fasciatus (Characidae) from northeast Mexico and the Yucatan. With the exception of Chica, the cave populations were all characterized by extremely low microsatellite variability, which most likely resulted from bottleneck events. Population analyses of the microsatellite data indicated no measurable levels of gene flow between all cave and surface populations (F(ST) > 0.0707). Phylogenetic analyses of mtDNA data showed that only two cave populations - Sabinos and Tinaja - group together to the exclusion of surface populations. From the microsatellite data these cave populations cluster with the Pachon cave fish population. The mtDNA thus appears to have been replaced in Pachon because of introgressive hybridization. It is likely that these three cave populations have descended from a surface ancestor in common with current surface populations, rather than evolving recently from one of the extant surface populations. Like Pachon, the Chica population clustered with the surface populations according to mtDNA data, but was not clearly associated with either the surface or the other cave populations according to the microsatellite data. Our data indicate that the Chica population evolved recently from a surface population, and subsequently hybridized with a phylogenetically older cave population. In conclusion, both the microsatellite and mtDNA data suggest multiple origins of cave populations and the Chica and Sabinos/Tinaja/Pachon were founded after at least two independent invasions from surface populations.


Influence of Patient Characteristics and Psychological Needs on Diabetes Mobile App Usability in Adults With Type 1 or Type 2 Diabetes: Crossover Randomized Trial.
More than 1100 diabetes mobile apps are available, but app usage by patients is low. App usability may be influenced by patient factors such as age, sex, and psychological needs. Guided by Self-Determination Theory, the purposes of this study were to (1) assess the effect of patient characteristics on app usability, and (2) determine whether patient characteristics and psychological needs (competence, autonomy, and connectivity)-important for motivation in diabetes care-are associated with app usability. Using a crossover randomized design, 92 adults with type 1 or 2 diabetes tested two Android apps (mySugr and OnTrack) for seven tasks including data entry, blood glucose (BG) reporting, and data sharing. We used multivariable linear regression models to examine associations between patient characteristics, psychological needs, user satisfaction, and user performance (task time, success, and accuracy). Participants had a mean age of 54 (range 19-74) years, and were predominantly white (62%, 57/92), female (59%, 54/92), with type 2 diabetes (70%, 64/92), and had education beyond high school (67%, 61/92). Participants rated an overall user satisfaction score of 62 (SD 18), which is considered marginally acceptable. The satisfaction mean score for each app was 55 (SD 18) for mySugr and 68 (SD 15) for OnTrack. The mean task completion time for all seven tasks was 7 minutes, with a mean task success of 82% and an accuracy rate of 68%. Higher user satisfaction was observed for patients with less education (P=.04) and those reporting more competence (P=.02), autonomy (P=.006), or connectivity with a health care provider (P=.03). User performance was associated with age, sex, education, diabetes duration, and autonomy. Older patients required more time (95% CI 1.1-3.2) and had less successful task completion (95% CI 3.5-14.3%). Men needed more time (P=.01) and more technical support than women (P=.04). High school education or less was associated with lower task success (P=.003). Diabetes duration of ≥10 years was associated with lower task accuracy (P=.02). Patients who desired greater autonomy and were interested in learning their patterns of BG and carbohydrates had greater task success (P=.049). Diabetes app usability was associated with psychological needs that are important for motivation. To enhance patient motivation to use diabetes apps for self-management, clinicians should address competence, autonomy, and connectivity by teaching BG pattern recognition and lifestyle planning, customizing BG targets, and reviewing home-monitored data via email. App usability could be improved for older male users and those with less education and greater diabetes duration by tailoring app training and providing ongoing technical support.


Intestinal Fatty Acid Binding Protein and Citrulline as Markers of Gut Injury and Prognosis in Patients With Acute Pancreatitis.
Severe acute pancreatitis (AP) is associated with high mortality due to systemic inflammatory response syndrome in the early phase and secondary infection in the later phase. Concomitant intestinal ischemia often results in gut injury. We studied intestinal fatty acid binding protein (IFABP) and citrulline levels as markers of gut injury to predict prognosis in AP. Acute pancreatitis patients at admission and controls were studied. Serum IFABP was measured by enzyme-linked immunosorbent assay and plasma citrulline by high-performance liquid chromatography technique. Ultrastructural changes in duodenal biopsy were also compared between the 2 groups. The IFABP concentration was significantly higher in AP cases (n = 94) compared with controls (n = 100) (mean [standard deviation], 592.5 [753.6] vs 87.8 [67.6] pg/mL; P < 0.001) and in patients with severe AP versus mild AP (738.3 [955.3] vs 404.0 [263.3] pg/ mL, P = 0.03). Citrulline concentration was lower in AP versus controls (29.9 [33.8] vs 83.9 [60.1] μg/L, P < 0.001). We propose a model by which these biomarkers (IFABP >350 pg/mL and citrulline <18 μg/L) are able to predict poor prognosis in 33.9% of patients with AP. The gut injury was also validated via ultrastructural changes. Intestinal fatty acid binding protein is a promising prognostic marker in acute pancreatitis.


Shaping the ultrafast temporal correlations of thermal-like photons.
We show that the temporal correlations between two light beams arising from a broadband thermal-like source can be controlled in the femtosecond regime. Specifically, by introducing spectral phase-only masks in the path of one of the beams, we show that the timing and strength of the photon correlations can be programmed on demand. This example demonstrates that the interbeam second-order coherence function propagates as a phase-sensitive ultrafast wave packet in the path towards the detectors, and is thus, susceptible to be modified by acting on just one of the beams. For quite some time, it has been thought that this could only happen with sources showing time-energy entanglement. Our work shows that such a property is due to the existence of a certain type of correlation, but not necessarily the entanglement.


Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival.
Whether busulphan-treated patients develop blastic transformation earlier than hydroxyurea treated has been a controversial issue. In a randomised prospective study, we examined the busulphan versus hydroxyurea influence on time to blast crisis and on survival. When we opened our study in 1984, the clinical benefit of allogeneic bone marrow transplantation (BMT) was not well known; to follow up the long-time outcome of this treatment was therefore of great interest. Previously untreated CML patients were randomly started on either hydroxyurea (30 mg/kg/day) or busulphan (0.1 mg/kg/day). The end points of the study were overall survival and time to blast crisis. A total of 26 patients subsequently underwent BMT. A total of 179 patients were randomised, 90 of hydroxyurea, and 89 to busulphan treatment. There was no significant difference in survival between hydroxyurea- and busulphan-treated patients (P = 0.46); median survival was 3.5 and 3.2 years, respectively. In all, 85 of the patients were subsequently diagnosed with blast crisis, 41 in the busulphan and 44 in the hydroxyurea group. There was no significant difference between the two groups (P = 0.91). The 26 patients who were allotransplanted survived significantly longer than those who were not transplanted (P = 0.0001). The 5-year-survival rates were 50 and 22% and the 10-year-survival rates were 46 and 2%, respectively. The median survival was 4.7 years for the transplanted and 3.3 years for the nontransplanted patients. We did not find any difference between hydroxyurea and busulphan treatment, either in overall survival or in blast crisis-free survival; transplanted patients survived significantly longer than nontransplanted patients.


Premenstrual exacerbation of asthma.
Questionnaires and twice daily peak expiratory flow measurements were used to evaluate the effects of the menstrual cycle in asthmatic women. Forty per cent of women reported premenstrual deterioration in their symptoms and this was confirmed by peak flow recordings. No correlations were found between premenstrual exacerbation of asthma and symptoms of premenstrual tension, consumption of aspirin, use of the contraceptive pill, cycle length, or behaviour of asthma during pregnancy.