Definitions and epidemiology of the chronically critically ill.
Patients who are chronically critically ill constitute 5-10% of patients with acute respiratory failure but demand a disproportionate share of ICU resources. Epidemiologic studies and clinical trials require definitions for enrollment, and a uniform definition would be ideal to allow comparisons between studies. While a consensus definition exists (≥ 21 consecutive days of mechanical ventilation for ≥ 6 h/d), many study designs have required alternative definitions that include requirement for a tracheostomy, a different period of mechanical ventilation, or admission to a weaning facility. Regardless of definition, studies have indicated that the incidence of chronic critical illness has doubled in recent decades and may double again in the next decade. The overall 1-year survival for chronically critically ill patients is between 40% and 50%, depending on the cohort studied. New clinical prediction rules have been developed to better identify patients who are at high risk and low risk of death. These models could be enhanced by data on functional outcomes for survivors. The healthcare system has been adapting to the increase in chronic critical illness by increasing critical beds in short-term and long-term acute care hospitals, but continued monitoring of resources will be necessary, since the prevalence of chronic critical illness is expected to increase further.


Altered iron metabolism in cystic fibrosis macrophages: the impact of CFTR modulators and implications for Pseudomonas aeruginosa survival.
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in chronic bacterial lung infections and tissue damage. CF macrophages exhibit reduced bacterial killing and increased inflammatory signaling. Iron is elevated in the CF lung and is a critical nutrient for bacteria, including the common CF pathogen Pseudomonas aeruginosa (Pa). While macrophages are a key regulatory component of extracellular iron, iron metabolism has yet to be characterized in human CF macrophages. Secreted and total protein levels were analyzed in non-CF and F508del/F508del CF monocyte derived macrophages (MDMs) with and without clinically approved CFTR modulators ivacaftor/lumacaftor. CF macrophage transferrin receptor 1 (TfR1) was reduced with ivacaftor/lumacaftor treatment. When activated with LPS, CF macrophage expressed reduced ferroportin (Fpn). After the addition of exogenous iron, total iron was elevated in conditioned media from CF MDMs and reduced in conditioned media from ivacaftor/lumacaftor treated CF MDMs. Pa biofilm formation and viability were elevated in conditioned media from CF MDMs and biofilm formation was reduced in the presence of conditioned media from ivacaftor/lumacaftor treated CF MDMs. Defects in iron metabolism observed in this study may inform host-pathogen interactions between CF macrophages and Pa.


Familial polyposis coli in childhood.
Familial polyposis coli has generally been considered a disorder of adulthood that is rarely identified in children. We report 3 affected kindreds in which the disorder was diagnosed in 6 of 11 potentially affected children between 8 and 16 years of age. Experience with these kindreds demonstrates that polyps frequently develop during childhood in affected individuals. Colonoscopy was found to be preferable to the air-contrast barium enema, in that it was as sensitive a technique for detection of adenomas, and in that it also permitted collection of biopsies for histologic confirmation. We recommend that colonoscopy be performed late in the first decade of life before symptoms develop. Total colectomy, rectal mucosectomy, and ileo-anal anastomosis eliminated the risk of malignancy, preserved anal sphincter function by both clinical and manometric assessment, and was readily adapted to by these children.


Chondromyxoid fibroma of a metatarsal and cuneiform.
The occurrence of chondromyxoid fibroma in the foot is relatively rare, and it is highly unusual for the lesion to involve the epiphysis. The authors report a case of a highly aggressive tumor occurring in the first metatarsal bone, crossing the epiphysis and invading the medial cuneiform bone. A literature search did not reveal previous cases of chondromyxoid fibroma in this unusual location.


[Age-related peculiarities of acute cholecystitis].
In the present study the analysis of dynamics of basic laboratory parameters of patients with acute cholecystitis (AC) in the four age groups subdivided according to the WHO classification into young, middle age, elderly and senile was carried out. The most pronounced changes were found in the senile age group in which the AC was accompanied by the decreased number of erythrocytes, low hemoglobin and total protein, leukocytosis, lower percentage of lymphocytes and the highest levels of ALT, AST, bilirubin and urea. Changes in the elderly and senile groups differed and in a number of cases were opposite. In the elderly and especially in the senile group the dynamics of the studied parameters related to surgery, was poorly expressed. These findings can be used in the preparation of the elderly and senile patients for AC surgery.


Marital satisfaction through the lens of Iranian women: a qualitative study.
One of the common concepts to show the happiness and stability of marriage is the concept of marital satisfaction. Marital satisfaction plays an important role in the stability of marriage. This study was conducted to explain the perception of marital satisfaction among Iranian women. This study was conducted between March and September 2015 by common qualitative content analysis approach through semi-structured interviews and 19 participants were selected by purposive sampling. With the analysis of data two themes: (maturity of personality) which included a sub-theme of blossoming of feelings, and (romantic interaction) consisted of three sub-themes of; mutual support, sense of peace and joyful dependence emerged. Marital life can lead to the development of people and lovely interaction between them. Surely it needs to passing of time and self-knowing and couple-knowing of each other. Family consultants need the perception of how couple's interaction is, also they need to understand about couples who can communicate well to each other so they can overcome many life's other deficiencies.


Parafibromin inhibits cancer cell growth and causes G1 phase arrest.
The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation of parafibromin predisposes one to the development of HPT-JT syndrome. To date, the role of parafibromin in tumorigenesis is largely unknown. Here, we report that parafibromin is a nuclear protein that possesses anti-proliferative properties. We show that overexpression of parafibromin inhibits colony formation and cellular proliferation, and induces cell cycle arrest in the G1 phase. Moreover, HPT-JT syndrome-derived mutations in HRPT2 behave in a dominant-negative manner by abolishing the ability of parafibromin to suppress cell proliferation. These findings suggest that parafibromin has a critical role in cell growth, and mutations in HRPT2 can directly inhibit this role.


Successful treatment of thrombotic thrombocytopenic purpura with plasmapheresis and anti-CD20 antibodies in a patient with immune thrombocytopenia and systemic lupus erythematosus: Case report.
Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology with diverse clinical and laboratory manifestations, including thrombocytopenia. About 25% of patients with SLE may be affected by thrombocytopenia, many of whom are asymptomatic. Some patients, however, experience platelet counts that drop quite low and predispose them to bleeding. Thrombotic thrombocytopenic purpura (TTP) is defined with a classic pentad of clinical features, such as thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms and signs, renal symptoms and signs, and fever. The association of TTP and SLE has been sporadically reported in the literature. We describe a 16-year-old girl with SLE and immune thrombocytopenia, in whom TTP was diagnosed. She was treated with pulse methylprednisolone, whose platelet counts normalized after therapy with plasmapheresis and an anti-CD20 monoclonal antibody (rituximab). A pediatric patient with SLE and immune thrombocytopenia in whom TTP developed was treated with plasmapheresis and rituximab therapy successfully, though the patient experienced a disease relapsed after 18 months, which was controlled by the same management.


Interstitial ciliates: benthic microaerophiles or planktonic anaerobes?
We observed marine benthic interstitial ciliates Geleia sp. and Tracheloraphis sp. inhabiting the water column of a chemically stratified salt pond. This habitat is uncharacteristic for interstitial ciliates, yet they displayed active and abundant planktonic populations (up to 800 and 250 cells/liter, respectively) and a well-defined pattern of vertical distribution. Completely absent from the oxygenated epilimnion, they first appeared at the oxic/anoxic interface and were present throughout the anoxic hypolimnion. The data could not be explained by a passive removal (e.g. by currents) of these ciliates from their conventional habitat (soft sediments) to water column. The results suggest that 1) these ciliates favored an anoxic environment, and 2) they switched to a planktonic lifestyle as appropriate conditions (seasonal anoxia) developed in the water column. This sharply contrasts the classic view of these ciliates as specifically benthic and aerobic (albeit microaerophilic) organisms. We hypothesize that Geleia sp. and Tracheloraphis sp. can readily grow in either water column or benthos, but are typically found in sediments simply because they contain their preferred (anoxic) niche.


[Technological evolution of laparoscopic gastrointestinal surgery in China].
After 30 years of development in China, laparoscopic gastrointestinal surgery has been widely accepted and popularized. In recent years, the application of a series of novel technologies, such as 3D laparoscopic system, 4k high-definition laparoscopy, near-infrared fluorescence imaging technique and telesurgery with 5G wireless system has injected new vitality to the laparoscopic gastrointestinal surgery in new era. It also well contributes to the further promotion and standardization of minimally invasive gastrointestinal surgery. This article reviews the application and development of novel techniques in minimally invasive gastrointestinal surgery. It is concluded that great progress has been made in clinical application of minimally invasive gastrointestinal surgery in China. In terms of surgical technology and equipment development, the period of mechanical imitation has passed and a new era focusing on innovation and originality is coming in China. The authors believe that Chinese laparoscopic gastrointestinal surgeons should remember their original intention, insist on the patient-centered concept in diagnosis and treatment, maintain innovative thinking and attitude and thus, push the development of minimally invasive gastrointestinal surgery to a new height in China.


Variable Effects of Autophagy Induction by Trehalose on Herpesviruses Depending on Conditions of Infection.
Trehalose is a non-reducing sugar formed from two glucose units. Trehalose induces abundant autophagy in cultured cells and also reduces the rate of aggregation of the huntingtin protein in the animal model of Huntington disease, a chronic neurological disease in humans. The mechanism of this effect on autophagy is now known to be caused by starvation secondary to inhibition of a family of glucose transporters known as the solute carrier 2 or the glucose transporter family. Variable effects of trehalose treatment have been observed during infections with two herpesviruses-human cytomegalovirus and varicella-zoster virus. The reasons for differing results have now been delineated. These differences are caused by two variables in conditions of infection: timing of addition of trehalose and type of inoculum (cell-free virus vs. infected cells). When monolayers pretreated with trehalose were inoculated with cell-free virus, there was a decline in virus spread by as much as 93 percent when compared with untreated monolayers. However, when monolayers were inoculated with infected cells rather than cell-free virus, there was no decline in virus spread. These results demonstrated that the effect of trehalose was limited to monolayers that were starved when inoculated with cell-free virus. In contrast, sufficient virus was already present in infected cell inocula so as to minimize any inhibitory effect of a starved monolayer. These results also showed that trehalose did not specifically inhibit a herpesvirus; rather, addition of trehalose to cell culture media altered the intracellular environment.


Three-dimensional structure of maize alpha-zein proteins studied by small-angle X-ray scattering.
alpha-zeins of maize (Zea mays) that are storage proteins contain nine or ten tandem repeats comprising of about 20 amino acids. Small-angle X-ray scattering (SAXS) of alpha-zeins was measured in 70% (v/v) aqueous ethanol containing beta-mercaptoethanol or without reagent in a protein concentration range of 2.0 to 40.0 mg/ml. The overall radius of gyration of whole particles, Rg, and the corresponding radius of gyration of the cross-section, Rc, of reduced alpha-zeins are 4.00 +/- 0.03 nm and 1.39 +/- 0.05 nm, respectively, in the 70% (v/v) aqueous ethanol containing 2% (v/v) beta-mercaptoethanol. Analyses using the Rg and Rc values indicate that reduced alpha-zeins exist as asymmetric particles with the length of about 13 nm in the solution. A structural model is developed under assumption that each of tandem repeats units forms single alpha-helix and they are joined by glutamine-rich 'turns' or loops, as employed by Argos et al., [Argos, O., Pedersen, K., Marks, M.D. and Larkins, B.A. (1982) J. Biol. Chem. 257, 9984-9990] and Garratt et al. [Garratt, R., Oliva, G., Caracelli, I., Leite, A. and Arruda, P. (1993) Proteins Struc. Func. Genet. 15, 88-99], and that the longest dimension of 13 nm comes from linear stacking of the anti-parallel helices of tandem repeat in the direction perpendicular to the helical axis. The resultant model is presented by an elongated prism-like shape with an approximate axial ratio of 6:1.


[In-vitro evaluation of haemocompatibility of biomaterials].
In-vitro test is usually conducted as a preliminary screening test in the evaluation of the haemocompatibility of biomaterials for its short-term consuming, convenience and less expense. The selection of appropriate model for blood-biomaterial interaction, the choice of sensitive and specific parameters, and the minimization of additional blood activation are most important in the in-vitro test. In addition, the time and the style of blood-biomaterial interaction, the choice of sensitive and specific parameters, and the minimization of additional blood activation are most important in the in-vitro test. In addition, the time and the style of blood-biomaterial interaction, the selection of primary reference materials and the shear rate should be considered. In recent years, though great progress has been made in the in-vitro evaluation of haemocompatibility of biomaterials, all these influencing factor should be standardized for more effective evaluation of the haemocompatibility of biomaterials.


Pulmonary vein flow analysis by transoesophageal echocardiogr phy in patients with chronic atrial fibrillation; 1 year follow-up after cardioversion.
Left and right upper pulmonary vein flow can be adequately recorded by transoesophageal Doppler echocardiography. The aim of this study was to investigate whether analysis of the pulmonary venous flow velocity pattern can predict the long-term maintenance of sinus rhythm after successful cardioversion of chronic atrial fibrillation. Thirty-six consecutive patients, aged 53+/-9 years, with chronic atrial fibrillation of 5.33+/-2 months duration, were subjected to transoesophageal Doppler echocardiography to record left and right upper pulmonary venous flow, 24 h and 3 months following successful cardioversion. One year following cardioversion, 12 patients (33.3%) were in sinus rhythm (sinus rhythm group) while the remaining 24 patients were in atrial fibrillation (atrial fibrillation group). At 24 h following cardioversion, biphasic systolic forward flow in the left and/or right upper pulmonary venous flow velocity was detected in 10 patients of the sinus rhythm group and in four patients of the atrial fibrillation group (P<0001). The systolic fraction was significantly higher in the sinus rhythm group, 0.48+/-0.04 and 0.39+/-0.06, P<0.001 for the left upper pulmonary venous flow, and 0.52+/-0.05 and 0.41+/-0.04, P<0.001 for the right upper pulmonary venous flow, respectively. In patients who displayed a biphasic systolic forward flow and in whom the right upper pulmonary venous flow systolic fraction was higher than 0.50 at 24 h post-cardioversion, the probability of maintenance of sinus rhythm at 1 year exceeded 95%. The detection of a biphasic systolic forward flow in the pulmonary venous flow velocity, and of a right upper pulmonary vein systolic fraction higher than 0.50 as early as 24 h following cardioversion of chronic atrial fibrillation, identifies patients who will remain in sinus rhythm 1 year after cardioversion.


Differences in the economic valuation and determining factors of informal care over time: the case of blood cancer.
To estimate differences in the economic valuation and sociodemographic and clinical factors associated with informal care between phases of the treatment in the case of blood cancer patients. 139 haematological cancer patients who underwent a stem cell transplantation completed a longitudinal questionnaire according to 3 phases of the treatment: short-term (pre-transplant), medium-term (1st year post-transplant) and long-term (2nd-6th year post-transplant). Economic value of informal care was estimated using proxy good and opportunity cost methods. Ordered and binary logistic models were performed to identify factors associated with informal care. 123 patients reported having received informal care. A progressive reduction of the number of hours of care was observed between phases. Monetary value per patient ranged from 1,288 to 3,409; 1,045 to 2,786; and 336 to 854 €/month in the short, medium and long term, respectively. Patients with acute leukaemia and those who received an unrelated allogeneic transplantation were 22% (short-term) and 33.5% (medium-term) more likely to receive more than 8hours/day of care respect to patients diagnosed with lymphoma and autologous transplantation. In the long term, patients with multiple myeloma were more likely to receive more care. Better health status and higher educational level were associated with fewer daily hours of care. Informal care varies greatly between stages of the treatment depending on the clinical and sociodemographic factors. Significant caring time and societal costs are associated with such care in blood cancer patients.


Ultracompact biosensor based on a metalens with a longitudinally structured vector beam.
The refractive index is one of the essential parameters in describing biochemical reactions and biomedical diagnostics, and in situ measurement of the refractive index is very important for the micro total analysis system. We proposed an ultracompact biosensor based on a high numerical aperture metalens that was designed as two parts for generating the Pancharatnam-Berry phase and propagation phase, respectively, by using zinc sulfide nanofins, and nanopillars. Then incident light was modulated into a right-circularly polarized vortex beam and a left-circularly polarized vortex beam in the focal spot. The superposition of both beams can generate a structured vector beam with various polarization states along the focus direction. The polarization is sensitive to the difference of optical path, which has a potential application in index detection and biochemical analysis.


Harnessing mesenchymal stem cell homing as an anticancer therapy.
Mesenchymal stromal cells (MSCs) are non-hematopoietic progenitor cells that have been exploited as vehicles for cell-based cancer therapy. The general approach is based on the innate potential of adoptively applied MSC to undergo facilitated recruitment to malignant tissue. MSC from different tissue sources have been engineered using a variety of therapy genes that have shown efficacy in solid tumor models. In this review we will focus on the current developments of MSC-based gene therapy, in particular the diverse approaches that have been used for MSCs-targeted tumor therapy. We also discuss some outstanding issues and general prospects for their clinical application. The use of modified mesenchymal stem cells as therapy vehicles for the treatment of solid tumors has progressed to the first generation of clinical trials, but the general field is still in its infancy. There are many questions that need to be addressed if this very complex therapy approach is widely applied in clinical settings. More must be understood about the mechanisms underlying tumor tropism and we need to identify the optimal source of the cells used. Outstanding issues also include the therapy transgenes used, and which tumor types represent viable targets for this therapy.


Fluorofenidone Inhibits UUO/IRI-Induced Renal Fibrosis by Reducing Mitochondrial Damage.
Mitochondrial damage contributes to extracellular matrix (ECM) deposition and renal fibrosis. In this study, we aimed (1) to investigate whether fluorofenidone (AKF-PD) can attenuate mitochondrial damage in two renal fibrosis models: unilateral ureteral obstruction (UUO) and renal ischemia-reperfusion injury (IRI), and (2) to explore the underlying mechanism. Mitochondrial damage and renal lesions were analyzed in the UUO and IRI models. Mitochondrial energy metabolism, mitochondrial biogenesis, and oxidative stress were measured to assess the effect of AKF-PD on mitochondrial damage and to explore the underlying mechanism. In addition, HK-2 cells were stimulated with TGF-β with and without AKF-PD. The mitochondrial morphology, mtROS, ATP contents, and redox-related proteins were then examined. In both UUO and IRI models, AKF-PD relieved renal fibrosis, maintained mitochondrial structure, and increased mitochondrial DNA copy numbers. The protection was associated with (1) sustaining mitochondrial energy metabolism, evident by elevations of tricarboxylic acid (TCA) cycle enzymes and mitochondrial respiratory chain complexes; (2) improving mitochondrial biogenesis with increases of TFAM, NRF1, PGC-1α, and SIRT1; and (3) reducing mitochondrial oxidative stress likely via regulating SOD2, SIRT3, and NOX4 expressions. In HK-2 cells treated with TGF-β, AKF-PD protected mitochondria along with improving mitochondrial morphology, enhancing ATP production, reducing mtROS, and regulating SOD2, SIRT3, and NOX4 expression. We demonstrate that AKF-PD inhibited renal fibrosis at least in part via protecting mitochondria from damages developed in the UUO and IRI models. The mitochondrial protection was associated with sustaining mitochondrial energy metabolism, improving mitochondrial biogenesis, and reducing mitochondrial oxidative stress. This research verified the protective effect of AKF-PD on mitochondria in the UUO and IRI models and elaborated the underlying mechanism.


Objective measurement of optical aberrations in myopic eyes.
To determine whether the degree of myopia affects the optical quality of the retinal image after appropriate correction, monochromatic aberrations of the human eye were measured as a function of the degree of myopia. Using a modified Hartmann-Shack method, a population of 27 myopic (up to -9.25 D) and 7 emmetropic optometry students (18-32 years) were objectively evaluated before and after pupil dilation. We then identified for each subject the most influential aberration types, and we calculated the profile of wavefront aberration. To study the behavior of aberration as a function of the degree of myopia, we determined the maximum value of aberration as well as the root mean square (rms) value. It turned out that aberration increases with the refractive error in a quasi-linear relationship for pupil diameters of 5 and 9 mm. This result is valid for both rms and maximum values. We objectively showed that optical quality decreases as myopia increases and as the pupil gets larger. Coma is more frequent in high myopia, and spherical aberration occurs more frequently for dilated pupils.


Thyrotropin results in euthyroid patients with a past history of hyperthyroidism.
Sensitive TSH levels were measured in 93 euthyroid patients with a past history of hyperthyroidism. Subnormal TSH values were found in 18 out of 75 (24%) patients previously treated with a course of antithyroid drugs, and in 3 out of 18 (17%) post-thyroidectomy patients. These subnormal TSH results are a limitation to the general application of the TSH-first strategy. Twelve months follow-up showed that subnormal TSH values are associated with increased risk of relapse in the antithyroid drug treated group (p less than 0.001). Longer follow-up varies in duration and some late relapses have occurred in drug treated patients with normal baseline TSH levels. To date relapses have occurred in 3 out of 56 normal TSH patients compared with in 6 out of 16 suppressed TSH patients; no thyroidectomy patients have relapsed. Prospective studies are needed to confirm the predictive value of sensitive TSH measurements.


Effect of estradiol on the expression of renal sodium transporters in rats.
Although estradiol has been thought to perform an important role in blood pressure regulation, the effects of estradiol on the expression of renal sodium transporters are not fully understood. Female Sprague-Dawley rats were treated with 17β-estradiol or vehicle for 10 days after ovariectomy, and after both ovariectomy and adrenalectomy to eliminate the effect of aldosterone. In the ovariectomized (OVX) rats, estradiol decreased the abundance of the Na-K-2Cl cotransporter (NKCC2) (31.5% of control (OVX), p < 0.01), Na-Cl cotransporter (NCC) proteins (40.5% of control (OVX), p < 0.01) and α- and γ-subunits of the epithelial sodium channel (ENaC) (44.7% and 11.0% of control (OVX), p < 0.01). Estradiol also reduced plasma aldosterone levels (OVX + 17β-estradiol vs. OVX, 116.3 ± 44.4 vs. 184.2 ± 33.4 pmol/l, p < 0.05) and systolic blood pressure (OVX + 17β-estradiol vs. OVX, 115 ± 4 vs. 132 ± 2 mmHg, p < 0.05). In rats having undergone adrenalectomy and ovariectomy, estradiol did not reduce systolic blood pressure, or the expression of sodium transporters. Estradiol decreased systolic blood pressure, plasma aldosterone levels, and the expression of renal sodium transporters. After aldosterone was eliminated, estradiol did not affect blood pressure or the expression of sodium transporters, which indicates that the effect of estradiol on the renal sodium transporters is at least partly influenced by aldosterone.


Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase). A study in vitro and in two animal species.
A single-chain 55,000-mol wt form of urokinase (UK), similar to that previously isolated from urine, was purified from a transformed kidney cell culture medium and characterized; and its fibrinolytic properties were evaluated. The preparation immunoprecipitated with UK antiserum, had a low intrinsic amidolytic activity that was 0.1% of its active derivative, and resisted diisopropyl fluorophosphate treatment and inactivation by plasma inhibitors. The single-chain UK was therefore designated pro-UK. In the presence of plasmin and during clot lysis, activation by conversion to two-chain, 55,000-mol wt UK (TC-UK) was demonstrated. This did not occur during blood clotting nor on incubation with purified thrombin. Clot lysis in plasma consistently occurred in 2-5 h with 50-100 IU per ml of pro-UK, whereas comparable lysis was inconsistently achieved by 500-1,000 IU of UK. Pro-UK, in sharp contrast to UK, caused no fibrinogen degradation at fibrinolytic concentrations. In the absence of a clot, pro-UK in plasma was stable for more than 2 d. When a clot was added after incubation (37 degrees C) for 50 h, activation to full lytic activity took place. The findings in vivo were comparable but the rapid clearance of pro-UK required that it be given by a constant infusion despite its plasma stability. In rabbits, a UK-resistant species, pro-UK was significantly (P less than 0.001) more efficacious than TC-UK but neither induced significant fibrinogen degradation. In dogs, a more sensitive species, the high specificity of thrombolysis by pro-UK contrasted with the defibrinogenation and uncontrollable bleeding that accompanied thrombolysis by UK. It was concluded that clot lysis by pro-UK is more effective and specific than UK. The advantage of pro-UK is in the limitation of its activation to the site of a clot. This can be explained by an activation mechanism that is dependent, under physiological conditions, on fibrin-stabilized plasmin.


Habitual Physical Activity of People with or at Risk of Diabetes-Related Foot Complications.
Regular physical activity is an important component of diabetes management. However, there are limited data on the habitual physical activity of people with or at risk of diabetes-related foot complications. The aim of this study was to describe the habitual physical activity of people with or at risk of diabetes-related foot complications in regional Australia. Twenty-three participants with diabetes from regional Australia were recruited with twenty-two participants included in subsequent analyses: no history of ulcer (N = 11) and history of ulcer (N = 11). Each participant wore a triaxial accelerometer (GT3X+; ActiGraph LLC, Pensacola, FL, USA) on their non-dominant wrist for 14 days. There were no significant differences between groups according to both participant characteristics and physical activity outcomes. Median minutes per day of moderate-to-vigorous physical activity (MVPA) were 9.7 (IQR: 1.6-15.7) while participants recorded an average of 280 ± 78 min of low-intensity physical activity and 689 ± 114 min of sedentary behaviour. The sample accumulated on average 30 min of slow walking and 2 min of fast walking per day, respectively. Overall, participants spent very little time performing MVPA and were largely sedentary. It is important that strategies are put in place for people with or at risk of diabetes-related foot complications in order that they increase their physical activity significantly in accordance with established guidelines.


Resuscitative endovascular balloon occlusion of the aorta for retroperitoneal hemorrhage and shock after ipsilateral antegrade angioplasty with vascular closure device.
Percutaneous intervention is widely used to treat peripheral vascular disease. Ipsilateral antegrade femoral arterial access for femoropopliteal disease provides a mechanical advantage with regard to wire and stent control; however, it is associated with vascular complications and significant morbidity and mortality secondary to retroperitoneal hemorrhage from a high puncture site or vascular closure device (VCD) failure. Currently, resuscitative endovascular balloon occlusion of the aorta (REBOA) is performed as damage control surgery in patients with non-compressible torso hemorrhage. We describe a patient with hemorrhagic shock secondary to VCD failure, who was successfully treated by REBOA as damage control surgery. To our knowledge, this is the first reported case in the English literature of successful REBOA in a patient with hemorrhagic shock secondary to VCD failure.


Pure spin current in a cobalt phthalocyanine chain induced by the photogalvanic effect.
The development of methods for generating pure spin current at the molecular level is vital. In this work, we investigated how the spin-related photocurrent is produced in a cobalt phthalocyanine chain by the photogalvanic effect (PGE). Depending on how the magnetic moments of the left and right halves of the cobalt phthalocyanine chain are arranged, spin current can be generated. Both charge current and spin current are absent when the magnetic moments are arranged in parallel. Pure spin currents are generated when the magnetic moments are arranged in an antiparallel manner. Importantly, the pure spin current is robust to the polarization type and polarization angle. This characteristic results from the structure's charge density having spatial inversion symmetry but lacking that of the spin density.


The association between women's self-rated health and satisfaction with environmental services in an underserved community in Lebanon.
This research evaluated the association between women's self-rated health and a number of socioeconomic and environmental health indicators relating to drinking water services in an underserved Lebanese community. A population-based, cross-sectional survey using interviews was adopted to obtain information from female homemakers of 2,223 households in the town of Bebnine, Lebanon. The questionnaire included indicators on self-rated health, satisfaction with water quality, source of drinking water, occurrence of diarrhea, and socioeconomic variables, such as education, occupation, and perceived economic status. Self-rated health was categorized as poor, fair, and good. Odds ratios for poor and fair compared to good self-rated health values were calculated using multinomial logistic regression. A total of 712 women (32%) reported poor self-rated health. Women who perceived their household income to be worse than others in town were four times as likely to report poor health. Compared to women who were satisfied with drinking water quality, dissatisfied women were 42% more likely to report poor health. Women living in households reporting recent episodes of diarrheal illness had poorer health ratings than those without. The findings suggest a positive relationship between individual perceptions of water quality and self-rated health. Community concerns over their surrounding environment serve as a primary guide for infrastructural development and government policy.


A comprehensive interaction map of the human survival of motor neuron (SMN) complex.
Assembly of the Sm-class of U-rich small nuclear ribonucleoprotein particles (U snRNPs) is a process facilitated by the macromolecular survival of motor neuron (SMN) complex. This entity promotes the binding of a set of factors, termed LSm/Sm proteins, onto snRNA to form the core structure of these particles. Nine factors, including the SMN protein, the product of the spinal muscular atrophy (SMA) disease gene, Gemins 2-8 and unrip have been identified as the major components of the SMN complex. So far, however, only little is known about the architecture of this complex and the contribution of individual components to its function. Here, we present a comprehensive interaction map of all core components of the SMN complex based upon in vivo and in vitro methods. Our studies reveal a modular composition of the SMN complex with the three proteins SMN, Gemin8, and Gemin7 in its center. Onto this central building block the other components are bound via multiple interactions. Furthermore, by employing a novel assay, we were able to reconstitute the SMN complex from individual components and confirm the interaction map. Interestingly, SMN protein carrying an SMA-causing mutation was severely impaired in formation of the SMN complex. Finally, we show that the peripheral component Gemin5 contributes an essential activity to the SMN complex, most likely the transfer of Sm proteins onto the U snRNA. Collectively, the data presented here provide a basis for the detailed mechanistic and structural analysis of the assembly machinery of U snRNPs.


Repair of soft tissue defects of the fingers with medial plantar venous flap.
To report the surgical procedures and efficacy of using medial plantar venous flap for the repair of soft tissue defects of the fingers. From March 2010 to April 2012, medial plantar venous flaps were harvested to repair the wounds of 31 fingers in 29 cases. Among them, there were 13 middle fingers with defects at the tips in 11 cases, 7 fingers with defects in the dorsal part in 7 cases, and 11 fingers with defects in the finger pulp in 11 cases. The size of the defects ranged from 1.2cm×1.5 cm to 2.5cm × 3.5cm. Medial plantar venous flaps of 1.5cm × 2cm - 3×4 cm were harvested. Full-thickness skin grafts were adopted for the donor areas. All 31 flaps survived, except for 1 flap with arterial crisis and 2 cases with venous crisis. These conditions were timely corrected by secondary anastomosis of artery and vein and the flaps survived. The wounds and the donor areas achieved healing by the first intention. All grafted skins survived. Postoperative follow-up was conducted for 26 fingers in 24 cases for 4-12 months, excluding 5 cases with lost follow-up. The dorsal part of the damaged fingers had normal morphology, and the skin color and texture were similar to those of the normal skin. After the repair of defects in the fingertip and pulp, fingerprints appeared, and the protective sensation was restored. The soft tissue defects of the fingers can be satisfactorily repaired with medial plantar venous flap, and little damage is caused to the donor area. This method is proven effective for the repair of soft tissue defects of the fingers.


Partial trisomy 15 in a young girl.
Severe mental retardation, growth failure, microcephaly, micrognathia, cleft palate, hooked nose, low-set thin flabby ears, pronounced elongated philtrum, and generalized decreased subcutaneous tissue characterized a 5 year 9 month old female with karyotype 47,XX,+15,del(15)(q15).


The bleeding child; is it NAI?
As a paediatric haematologist, the question of whether a child has been abused or whether they might have a bleeding diathesis is a question that I am regularly asked. When I first became a consultant, I would often find that not enough information was available; for example, incomplete histories had been taken or investigations were incomplete and difficult to interpret. This inevitably led to delays in confirming the cause of the bleeding and meant that if parents or carers contested a diagnosis of abuse, excluding a bleeding disorder was extremely difficult. I was also aware that carers of several of my patients with haemophilia or other bleeding disorders had initially been under suspicion of abuse, most usually at the time of the first few presentations. By highlighting important questions in history taking, having a specific haematological screen for children being investigated for bleeding in the context of non-accidental injury, and encouraging discussion of abnormal results with a haematologist, these difficulties can, for the most part, be avoided.


Effects of particle size on far infrared emission properties of tourmaline superfine powders.
Tourmaline superfine powders with different particle sizes were prepared by grinding, superfine ball milling, and high-speed centrifugation. The powders were characterized by scanning electron microscopy, X-ray diffraction, dynamic contact angle meter and tensiometry, and Fourier transform infrared spectrometry. The results show that tourmaline powders exhibit improved far infrared emission properties as the particle size decreases. The increased surface free energy and proportion of the polar component are considered to play an important role for their properties. The spontaneous polarization is increased, and the dipole moment of tourmaline is stimulated to a high energy level more easily for the chemical bond vibration, so that the energy is apt to emit by transition. In the range of 2000-500 cm(-1), the emissivity values of the samples with D50 size of 2.67 microm and 0.2 microm are 0.973 and 0.991, respectively.


Untypable genotype restriction patterns and surface gene variants of hepatitis B virus isolates.
Chronic hepatitis B is a global health problem, and is one of the leading causes of cirrhosis and hepatocellular carcinoma. Hepatitis B virus (HBV) genotyping helps in decision making for clinical management of HBV infection, and is important for epidemiological studies. The objectives of this study were to investigate the distribution of HBV genotypes circulating in the Philippines; molecularly characterize untypable genotype restriction patterns; and analyze the presence of surface gene variants. HBV genotypes were determined by restriction fragment length polymorphism (RFLP) and DNA sequencing. Three genotypes, HBV A (76%; 73/96), HBV B (10%; 10/96) and HBV C (14%; 13/96) were detected by RFLP. Out of the 96 isolates, 9% were untypable by RFLP analysis. DNA sequencing followed by phylogenetic analysis revealed that these isolates belonged to HBV genotypes A (67%; 6/9), B (11%; 1/9) and C (22%; 2/9). Out of the 9 isolates, 55% showed single or multiple variations which resulted to amino acid changes. Overall, the identification of untypable genotype can be resolved by sequence and phylogenetic analysis of the S gene and this approach can also be used to detect single or multiple variants. Our findings underscore the importance of accurate genotyping and detection of surface gene variants by DNA sequencing for optimal clinical management.


Testing bioequivalence for multiple formulations with power and sample size calculations.
Bioequivalence (BE) trials play an important role in drug development for demonstrating the BE between test and reference formulations. The key statistical analysis for BE trials is the use of two one-sided tests (TOST), which is equivalent to showing that the 90% confidence interval of the relative bioavailability is within a given range. Power and sample size calculations for the comparison between one test formulation and the reference formulation has been intensively investigated, and tables and software are available for practical use. From a statistical and logistical perspective, it might be more efficient to test more than one formulation in a single trial. However, approaches for controlling the overall type I error may be required. We propose a method called multiplicity-adjusted TOST (MATOST) combining multiple comparison adjustment approaches, such as Hochberg's or Dunnett's method, with TOST. Because power and sample size calculations become more complex and are difficult to solve analytically, efficient simulation-based procedures for this purpose have been developed and implemented in an R package. Some numerical results for a range of scenarios are presented in the paper. We show that given the same overall type I error and power, a BE crossover trial designed to test multiple formulations simultaneously only requires a small increase in the total sample size compared with a simple 2 × 2 crossover design evaluating only one test formulation. Hence, we conclude that testing multiple formulations in a single study is generally an efficient approach. The R package MATOST is available at https://sites.google.com/site/matostbe/.


A novel membrane-bound serine esterase in human T4(+)-lymphocytes is a binding protein of envelope glycoprotein gp120 of HIV-1.
A novel membrane-bound serine esterase, named tryptase TL2, which is immunologically reactive with the antibody inhibiting induction of syncytia by human immunodeficiency virus-1 (HIV-1) (HATTORI, T., KOITO, A., TAKATSUKI, K., KIDO, H., and KATUNUMA, N., 1989, FEBS Lett., 248, 48-52), has been purified from a human T4+ lymphocyte clone. The enzyme has a molecular mass of 198 +/- 15 kDa, and is composed of two subunits of 32 kDa and four subunits of 28 kDa. The enzyme was strongly inhibited by the envelope glycoprotein gp120 of HIV-1, by synthetic peptides of V3 domains of gp120 s with the sequence GPGR in their center, which correspond to the principal neutralizing epitopes of the gp120s of various HIV-1 strains, by Kunitz-type inhibitors with the sequence GPCR in their active site, such as trypstatin, H130, and [Arg15, Glu52] aprotinin and by the microbial inhibitors leupeptin and antipain. This enzyme was specifically bound to the inhibitor V3 domain of gp120 of HIV-1, and this binding was blocked by the inhibitors of tryptase TL2, with a central motif GPCR or GPGR sequence in their center, but not by leupeptin and antipain without the motif. These findings suggest that tryptase TL2 is important in target site recognition and binding of HIV-1 in co-operation with CD4 receptor in the initial process of HIV-1 infection.


[Correlation between D-Dimer/Fibrinogen Ratio and Bleeding in Patients with Newly Diagnosed Acute Promyelocytic Leukemia].
To further explore the better indicators for predicting the degree of bleeding associated with newly diagnosed acute promyelocytic leukemia (APL). A total of 131 patients with newly diagnosed APL were classified according to WHO bleeding scales before treatment and divided into two groups: scales 0, 1 and 2 were included in no severe bleeding group, scales 3 and 4 were included in severe bleeding group. The information of the patients were collected, including sex, age, hemoglobin (Hb), white blood cell (WBC) count and platelet (PLT) count, peripheral blood lymphocyte percentage (LYMPH%), peripheral blood monocyte percentage (MONO%), percentage of leukemic cells in pripheral blood and bone marrow, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, D-dimer (D-D), D-dimer/fibrinogen ratio (DFR). Among 131 patients, 110 were classified as no severe bleeding, and 21 were severe bleeding. The results of univariate analysis showed that patients with severe bleeding had significantly higher percentage of leukemic cells in pripheral blood, WBC, D-D, and DFR, as well as longer PT and lower LYMPH%, compared to those with no severe bleeding. Multivariate analysis revealed that DFR (OR =1.054, 95%CI : 1.024-1.084, P < 0.001) and percentage of peripheral blood leukemic cells (OR=1.026, 95%CI: 1.002-1.051, P =0.033) were independent risk factors for severe bleeding. The area under ROC curve (AUC) of peripheral blood leukemic cells, D-D and DFR were 0.748, 0.736 and 0.809, respectively. There was no statistical difference between the peripheral blood leukemic cells and D-D in diagnostic efficacy (P =0.8708). Compared with D-D, DFR had a higher predictive value (P =0.0302). The optimal cut-off value of DFR was 16.50, with a sensitivity of 90.5% and a specificity of 70.0%. DFR has a significant advantage in predicting the degree of bleeding associated with newly diagnosed APL. The greater the DFR value, the heavier the degree of bleeding. The risk of severe or fatal bleeding increases when DFR is greater than 16.50.


Fear expression is reduced after acute and repeated nociceptin/orphanin FQ (NOP) receptor antagonism in rats: therapeutic implications for traumatic stress exposure.
Evaluation of pharmacotherapies for acute stress disorder (ASD) or post-traumatic stress disorder (PTSD) is challenging due to robust heterogeneity of trauma histories and limited efficacy of any single candidate to reduce all stress-induced effects. Pursuing novel mechanisms, such as the nociceptin/orphanin FQ (NOP) system, may be a viable path for therapeutic development and of interest as it is involved in regulation of relevant behaviors and recently implicated in PTSD and ASD. First, we evaluated NOP receptor antagonism on general behavioral performance and again following a three-species predator exposure model (Experiment 1). Then, we evaluated effects of NOP antagonism on fear memory expression (Experiment 2). Adult, male rats underwent daily administration of NOP antagonists (J-113397 or SB-612,111; 0-20 mg/kg, i.p.) and testing in acoustic startle, elevated plus maze, tail-flick, and open field tests. Effects of acute NOP antagonism on behavioral performance following predator exposure were then assessed. Separately, rats underwent fear conditioning and were later administered SB-612,111 (0-3 mg/kg, i.p.) prior to fear memory expression tests. J-113397 and SB-612,111 did not significantly alter most general behavioral performance measures alone, suggesting minimal off-target behavioral effects of NOP antagonism. J-113397 and SB-612,111 restored performance in measures of exploratory behavior (basic movements on the elevated plus maze and total distance in the open field) following predator exposure. Additionally, SB-612,111 significantly reduced freezing behavior relative to control groups across repeated fear memory expression tests, suggesting NOP antagonism may be useful in dampening fear responses. Other measures of general behavioral performance were not significantly altered following predator exposure. NOP antagonists may be useful as pharmacotherapeutics for dampening fear responses to trauma reminders, and the present results provide supporting evidence for the implication of the NOP system in the neuropathophysiology of dysregulations in fear learning and memory processes observed in trauma- and stress-related disorders.


Two single-reference approaches to singlet biradicaloid problems: Complex, restricted orbitals and approximate spin-projection combined with regularized orbital-optimized Møller-Plesset perturbation theory.
We present a comprehensive study of two single-reference approaches to singlet biradicaloids. These two approaches are based on the recently developed regularized orbital-optimized Møller-Plesset method (κ-OOMP2). The first approach is to combine Yamaguchi's approximate projection (AP) scheme and κ-OOMP2 with unrestricted (U) orbitals (κ-UOOMP2). By capturing only essential symmetry breaking, κ-UOOMP2 can serve as a suitable basis for AP. The second approach is κ-OOMP2 with complex, restricted (cR) orbitals (κ-cROOMP2). Although its applicability is more limited due to the comparative rarity of cR solutions, κ-cROOMP2 offers a simple framework for describing singlet biradicaloids with complex polarization while removing artificial spatial symmetry breaking. We compare the scope of these two methods with numerical studies. We show that AP+κ-UOOMP2 and κ-cROOMP2 can perform similarly well in the TS12 set, a dataset that includes 12 data points for triplet-singlet gaps of several atoms and diatomic molecules with a triplet ground state. This was also found to be true for the barrier height of a reaction involving attack on a cysteine ion by a singlet oxygen molecule. However, we also demonstrate that in highly symmetric systems like C30 (D5h), κ-cROOMP2 is more suitable as it conserves spatial symmetry. Finally, we present an organic biradicaloid that does not have a κ-cROOMP2 solution in which case only AP+κ-UOOMP2 is applicable. We recommend κ-cROOMP2 whenever complex polarization is essential and AP+κ-UOOMP2 for biradicaloids without essential complex polarization but with essential spin-polarization.


Anatomic double-bundle anterior cruciate ligament reconstruction.
To retrospectively evaluate the early results of anatomic double-bundle anterior cruciate ligament (ACL) reconstruction and compare with the results of native ACL of the contralateral knee. The results of a consecutive series of 118 patients receiving arthroscopic ACL reconstruction were evaluated. Eight patients were lost to the latest follow-up, leaving a total of 110 patients available for study within at least 3 years'clinical follow-up. Among them, 63 patients underwent postoperative MRI and CT scan, as well as clinical evaluation. After reconstruction, the knees were stable and pain-free. Mean postoperative Lysholm score was 95.54 in 110 patients after 3 years. CT and MRI assessment showed that the reconstruction centered in the femoral footprint of ACL (n equal to 63). The sagittal ACL angle in the reconstructed ACL (52.16 degree+/-2.45 degree was much close to that in the contralateral intact ACL (51.31 degree +/-2.18 degree, P larger than 0.05). By ACL-Blumensaat line angle analysis, there was no difference between double-bundle reconstructed knees and their contralateral normal knees (4.67 degree+/-0.43 degree vs. 4.62 degree+/-0.60degree, P larger than 0.05). Anatomic double-bundle ACL reconstruction can place grafts more precisely in the anatomic footprint of the ACL and better restore knee kinematics.


Biomimetic Ag/ZnO@PDMS Hybrid Nanorod Array-Mediated Photo-induced Enhanced Raman Spectroscopy Sensor for Quantitative and Visualized Analysis of Microplastics.
Microplastics are persistent pollutants that accumulate in the environment and can cause serious toxicity to mammals. At present, few technologies are able to quantitatively detect chemicals and provide morphological information simultaneously. Herein, we developed a dragonfly-wing-mimicking ZnO nanorod array decorated with AgNPs on polydimethylsiloxane (PDMS) as a surface-enhanced Raman spectroscopy (SERS) and photo-induced enhanced Raman spectroscopy (PIERS) substrate for trace analysis of microplastics. The Ag/ZnO@PDMS hybrid nanorod array endows the sensor with high sensitivity and signal repeatability (RSD ∼ 5.89%), ensuring the reliable quantitative analysis of microplastics. Importantly, when the noble metal-semiconductor substrate was pre-radiated with ultraviolet light, a surprising PIERS was attained, achieving an additional enhancement of 11.3-fold higher than the normal SERS signal. By combining the PIERS technology with the "coffee ring effect", the sensor successfully discerned microplastics of polyethylene (PE) and polystyrene (PS) at a trace level of 25 μg/mL even with a portable Raman device. It was capable of identifying PS microspheres in contaminated tap water, lake water, river water, and seawater with detection limits of 25, 28, 35, and 60 μg/mL, respectively. The recovery rates of PS microspheres in four water environments ranged from 94.8 to 102.4%, with the RSD ranging from 2.40 to 6.81%. Moreover, quantitative and visualized detection of microplastics was readily realized by our sensor. This portable PIERS sensor represents a significant step toward the generalizability and practicality of quantitative and visual sensing technology.


Object library for a new generation of experiment-controlling applications under the UNIX operating system.
The Interface Object Library based on the Motif extension of the X Windows system and on the ESONE SVIC-VCC Library is presented. Some features of the applications for controlling a synchrotron radiation experiment are discussed. The Interface Object Library is written in the object-oriented C++ language. The library class-hierarchy structure is presented and discussed. Several interfaces were realized in the Interface Object Library: the Windows interface, the CAMAC interface and the interface for supporting the experiment. The behaviour of the objects describing the CAMAC crate and CAMAC block is discussed. The application of these protocols for controlling the fast one-coordinate position-sensitive X-ray detector OD3 is presented.


The association between frequent alcohol drinking and opioid consumption after abdominal surgery: A retrospective analysis.
It is perceived that patients with a history of frequent alcohol consumption require more opioids for postoperative pain control and experience less postoperative nausea and vomiting than patients without such a history. However, there is scarce evidence supporting this notion. The aim of this study was to assess association between frequent alcohol consumption and opioid requirement for postoperative pain control and occurrence of postoperative nausea and vomiting. The medical records for 4143 patients using intravenous patient-control analgesia with opioids after abdominal surgery between January 2010 and September 2013 were obtained, and associations were sought between the cumulative opioid consumption (in intravenous morphine equivalence) per body weight (mg/kg) in the first 2 days after abdominal operation and several demographic and clinical variables by multiple regression analysis. The association between the occurrence of postoperative nausea and vomiting and several demographic and clinical variables was also sought by multiple logistic regression analysis. Frequent alcohol drinking, among other previously reported factors, was associated with increased opioid consumption for postoperative pain control (p < 0.001). The estimate effect of frequent alcohol drinking was 0.117 mg/kg. Frequent alcohol drinking was also associated with decreased risks of postoperative nausea (odds ratio = 0.59, p = 0.003) and vomiting (odds ratio = 0.49, p = 0.026). Frequent alcohol drinking was associated with increased opioid consumption for postoperative pain control and decreased risks of postoperative nausea and vomiting after abdominal surgery.


Case report: A case of hypocalcemic cardiomyopathy with non-reversible cardiac fibrosis.
Hypocalcemic cardiomyopathy is a rare etiology of heart failure. It is considered highly reversible with a relatively favorable prognosis. This case reports a 52-year-old housewife diagnosed with hypocalcemic cardiomyopathy who presented with acute decompensated heart failure and hypocalcemia symptoms with a history of thyroidectomy. Shortness of breath and edema were relieved after diuresis and prompt electrolyte correction. The left ventricular ejection fraction increased from 27% to 53%, and the left ventricular end-diastolic dimension shortened from 58 to 50 mm in echocardiographic re-examinations, while repeat cardiac magnetic resonance imaging revealed evidence of non-reversible cardiac fibrosis after 1-year follow-up. Cardioprotective agents with close follow-ups were called for in this entity of patients.


The value of redundancy in chronic bipolar pacemaker electrode systems.
Bipolar pacing systems, because of the presence of two intracardiac electrodes, provide lead redundancy. This allows conversion of bipolar to unipolar pacing or the reversal of lead polarity. During a 3-year period, this redundancy was utilized in 34 (13.7%) of 248 patients with chronic bipolar lead systems during follow-up pacemaker surgery. Of the 34 patients, elective pulse generator change was the most frequent indication for surgery (23 patients) and in this group redundancy was used most often to select the lead configuration with the highest R-wave amplitude and lowest stimulation threshold, or to solve the problem of weld defects of the connector pins or frayed insulation. The remaining 11 patients underwent surgery for pacemaker system malfunction and in this group redundancy was used to avoid the need for lead repositioning or placement of a new catheter system. Lead redundancy in those patients in whom bipolar pacing has been selected provides flexibility at the time of additional pacemaker surgery, and its use may obviate the need for a change in catheter system when stimulation thresholds are excessive, wire fraction is irreparable, or bipolar sensing signals are inadequate.


Analysis of volumetric and dosimetric changes in mid treatment CT scan in carcinoma nasopharynx: implications for adaptive radiotherapy.
Carcinoma of nasopharynx is a radiosensitive tumor and therapeutic response during radiation treatment can result in dosimetric variations in the delivered dose to the tumor and critical organs. This study was done to evaluate the volumetric and dosimetric changes seen in tumor tissue and organs at risk in a mid treatment planning scan and its implications for adaptive replanning. Twenty patients of locally advanced carcinoma nasopharynx were evaluated. All patients were started on treatment with a baseline treatment plan on SIB-VMAT. To evaluate volumetric and dosimetric changes during treatment, a mid treatment CT scan (MTS) was taken at the 17th fraction of treatment and compared with the baseline planning CT scan (BS). Adaptive treatment plans were generated on the MTS and further treatment was continued on the adaptive plans. The mean weight loss observed at the 17th fraction of treatment was 3.4 ± 2.6 kg(Mean±S.D). The mean neck diameter at C2 level was 14.19±1.02 and 13.29 ± 1.14 cm in the BS and MTS respectively (p=0.001). The GTV 70 volume showed a 29.16% volume loss. The mean doses received by the right and left parotids were 25.45±0.98 and 24.64±3.8 Gy in the baseline treatment plan and 33.21±11.29 (p=0.054) and 31.76±8.44 Gy respectively in the MTS (p=0.016) The mean weight loss showed a statistically significant correlation with increase in the right parotid(p=0.043) and left parotid doses(p=0.024). Weight loss during treatment combined with volume changes in target tissues mandate routine adaptive replanning while treating carcinoma nasopharynx.


[Value of aldosterone receptor blockade in diuretic therapy of patients with chronic heart failure].
All forms of chronic heart failure (high-output and low-output failure) are accompanied by an "arterial underfilling" inducing the activation of various neurohumoral systems (renin-angiotensin-aldosterone system, sympathic nervous system, non-osmotic stimulation of vasopressin). Elevated levels of those neurohormones detrimentally modulate renal function. Subsequently, renal salt and volume retention occurs leading to the main symptoms of heart failure, edema formation and dyspnea. Diuretics, which have been discovered more than 40 years ago, beneficially influence renal salt- and volume retention by their effects on tubular sodium reabsorption. While thiazides are recommended in mild forms, loop diuretics are used in severe stages of congestive heart failure. The clinician has to consider the changed pharmacokinetic and -dynamic properties during the application of diuretics in patients with chronic heart failure. In addition, increased sodium reabsorption occurs immediately after cessation of diuretic action often nullifying the preceding diuresis. Thus, salt- and volume restriction should be guaranteed, and a regular application of loop diuretics during the day should be preferred due to the short-acting nature of currently available loop diuretics. Sometimes, diuresis does not longer occur during the treatment with one substance (diuretic resistance), although the therapeutic goals of water excretion have not been achieved. After ruling out factors reducing the actions of diuretics (non-compliance, hyponatremia, etc.), a sequential nephron blockade should be initiated (combination of loop diuretics and a thiazide or an aldosterone-receptor antagonist) to increase diuresis and to elevate symptoms of volume overload. Loop diuretics and thiazides often induce mild hypokalemia, which has been demonstrated to be not as benign as thought before. Chronic treatment with oral potassium supplements has several drawbacks, as urine excretion of potassium is subsequently increased and supplementation is not as effective as believed. Diuretic-induced hypokalemia seems to be aldosterone dependent. As aldosterone levels increase during diuretic therapy even during chronic treatment with an angiotensin-converting enzyme (aldosterone-escape) a combined treatment including an aldosterone-receptor antagonist has been suggested. Beneficial effects of aldosterone-receptor blockade on mortality (RALES trial) appear to be mediated be extrarenal and renal mechanisms. The suggested beneficial renal mechanisms of aldosterone receptor blockade are discussed in detail in the review. In conclusion, diuretic therapy of patients with congestive heart failure is effective to relieve symptoms and, presumably, to prolong life. As renal function and pharmacokinetics and -dynamics of diuretics are changed in heart failure, diuretic treatment has to be adapted to provide optimal treatment. Increased levels of aldosterone appear to play an important role in diuretic-induced hypokalemia, and in the progression of heart and renal failure. Thus, aldosterone receptor antagonists should be used in the treatment of heart failure more frequently.


When are episodes of loss of consciousness life-threatening?
Episodic loss of consciousness is common in the paediatric population. While the majority of cases are due to benign conditions, life-threatening causes must be promptly identified.The present paper presents a case of recurrent loss of consciousness associated with convulsive activity and subsequent cardiac arrest due to a rare inherited ion channel disease known as Brugada syndrome. The case highlights the challenges of distinguishing epilepsy from convulsive syncope and the potentially disastrous consequences of an undiagnosed cardiac etiology. The most important paediatric causes of paroxysmal loss of consciousness and their salient features are reviewed. Clinical features suggesting a cardiac cause are emphasized because early recognition of these cases is critical.


The health care organization of the Dutch East India Company at home.
The Dutch East India Company ('VOC') organized a health care service on board its vessels as well as its home bases and in its factories in Asia. This health care service was based initially on the Dutch navy model. This study addresses the problems manifesting in the VOC health care in the 200 years of its activities, framed within the general concept of the transition during that period from individual to mass health care. It is argued that the service proved inadequate because of a number of factors, chiefly including the inability of the organization to cope with large numbers of people already ill before boarding or falling ill during the Asia-bound voyages; the ignorance of the causes of malnutritional and (tropical) infectious diseases; the training of surgeons (focused on injury-caused disease rather than on systemic disorders); the inordinate frugality of the directors as well as the fear of junior officials to displease the managerial board; and the preoccupation of the VOC board with detail rather than with a policy addressing fundamental health problems.


Novel angular encoder for a quick-extended x-ray absorption fine structure monochromator.
New concepts for time-resolved x-ray absorption spectroscopy using the quick-extended x-ray absorption fine structure (QEXAFS) method are presented. QEXAFS is a powerful tool to gain structural information about, e.g., fast chemical reactions or phase transitions on a subsecond scale. This can be achieved with a monochromator design that employs a channel-cut crystal on a cam driven tilt table for rapid angular oscillations of the Bragg angle. A new angular encoder system and a new data acquisition were described and characterized that were applied to a QEXAFS monochromator to get spectra with a directly measured accurate energy scale. New electronics were designed to allow a fast acquisition of the Bragg angle values and the absorption data during the measurements simultaneously.


[Specific lipids from Mycobacterium ulcerans].
The main lipids synthesized by Mycobacterium ulcerans are specific for the species. Three products were isolated by chromatography. Their structures were determined by means of spectrographic methods performed on the natural substances or on their split products. The most abundant products were phthiodiolone diphthioceranate and phenolphthiodiolone diphthioceranate . These structures have some analogies with those of phthiocerol dimycocerosate synthesized by M. tuberculosis and M. bovis, and with those of phenolphthiocerol mycocerosate synthesized by M. bovis. The reverse configuration of the polymethyl-branched-chain fatty acids isolated from the substances, according to their origin, remains to be pointed out. Little attention has generally been paid to the stereochemistry of such molecules. We verified that the branched-chain fatty acids found in diacyl phthiocerol and in the mycoside of M. leprae have the same configuration as in the analogous molecules isolated from M. tuberculosis or M. bovis, contrary to M. ulcerans. Another peculiarity of phenolphthiodiolone isolated from M. ulcerans is the occurrence of the phenol group in free form.


Probiotic supplementation for preventing invasive fungal infections in preterm neonates--a systematic review and meta-analysis.
Invasive fungal infections (IFI) are associated with significant health burden in preterm neonates. The objective of this study was to systematically review effect of probiotic supplementation (PS) for preventing IFI in preterm neonates. We searched Cochrane Central Register of Controlled Trials, Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, and proceedings of the Pediatric Academic Society meetings in August 2014. Study selection was performed on randomised controlled trials (RCT) of PS in neonates born <37 weeks. Primary outcome of this study was IFI (Isolation of fungus in blood/body fluids) and secondary outcome was fungal gut colonisation. Information on IFI/colonisation was available in 8 of 27 RCT. Meta-analysis (fixed effects model) showed that PS reduced the risk of IFI (RR: 0.50, 95% CI: 0.34, 0.73, I(2) = 39%). Results were not significant with random effects model (RR: 0.64, 95%, CI: 0.30, 1.38, P = 0.25, I(2) = 39%). Analysis after excluding the study with a high baseline incidence (75%) of IFI showed that PS had no significant benefits (RR: 0.89; 95% CI: 0.44, 1.78). Of the five studies reporting on fungal gut colonisation, three reported benefits of probiotics; two did not. Current evidence is limited to derive firm conclusions on the effect of PS for preventing IFI/gut colonisation in preterm neonates.


[Prevalence of sudden cardiac death during sports activities].
Sudden death during sport is a rare and unexpected event. It essentially affects young males, and a cardiomyopathy that had not been diagnosed during medical examinations is present in the majority of cases. In young subjects, there is generally hypertrophic cardiomyopathy or arhythmogenic right ventricular dysplasia. This is revealed during sporting activity, and sudden death is often the first symptom of the disease. Competitive sport increases the relative risk of sudden death to 2.5 compared to the risk in a non-sporting subject. The prevalence of sudden death during competitive sport is poorly understood. From the rare studies available, it could be estimated at 2.3/100,000 athletes per year. In Europe, it essentially occurs during football matches. However, the prevalence of sudden death during so-called 'recreational' sports is not precisely known. It could be much higher because these activities involve a larger number of people, and take place without supervision and usually without a medical examination beforehand. The participants are older, and coronary pathology is usually implicated.


The significance of inadequate transcranial Doppler studies in children with sickle cell disease.
Sickle cell disease (SCD) is a common cause of cerebrovascular disease in childhood. Primary stroke prevention is effective using transcranial Doppler (TCD) scans to measure intracranial blood velocities, and regular blood transfusions or hydroxycarbamide when these are abnormal. Inadequate TCD scans occur when it is not possible to measure velocities in all the main arteries. We have investigated the prevalence and significance of this in a retrospective audit of 3915 TCD scans in 1191 children, performed between 2008 and 2015. 79% scans were normal, 6.4% conditional, 2.8% abnormal and 12% inadequate. 21.6% of 1191 patients had an inadequate scan at least once. The median age of first inadequate scan was 3.3 years (0.7-19.4), with a U-shaped frequency distribution with age: 28% aged 2-3 years, 3.5% age 10 years, 25% age 16 years. In young children reduced compliance was the main reason for inadequate TCDs, whereas in older children it was due to a poor temporal ultrasound window. The prevalence of inadequate TCD was 8% in the main Vascular Laboratory at King's College Hospital and significantly higher at 16% in the outreach clinics (P<0.0001), probably due to the use of a portable ultrasound machine. Inadequate TCD scans were not associated with underlying cerebrovascular disease.


Facile and rapid direct gold surface immobilization with controlled orientation for carbohydrates.
Effective surface immobilization is a prerequisite for numerous carbohydrate-related studies including carbohydrate-biomolecule interactions. In the present work, we report a simple and rapid modification technique for diverse carbohydrate types in which direct oriented immobilization onto a gold surface is accomplished by coupling the amine group of a thiol group-bearing aminophenyl disulfide as a new coupling reagent with an aldehyde group of the terminal reducing sugar in the carbohydrate. To demonstrate the generality of this proposed reductive amination method, we examined its use for three types of carbohydrates: glucose (monosaccharide), lactose (disaccharide), and GM1 pentasaccharide. Through successful mass identifications of the modified carbohydrates, direct binding assays on gold surface using surface plasmon resonance and electrochemical methods, and a terminal galactose-binding lectin assay using atomic force microscopy, we confirmed several advantages including direct and rapid one-step immobilization onto a gold surface and exposure of functional carbohydrate moieties through oriented modification of the terminal reducing sugar. Therefore, this facile modification and immobilization method can be successfully used for diverse biomimetic studies of carbohydrates, including carbohydrate-biomolecule interactions and carbohydrate sensor or array development for diagnosis and screening.


Vision-Based Contact Adhesion Measurement Method on Soft Matter Surfaces.
Adhesion property measurements contribute to a comprehensive understanding of the mechanical properties of soft matters. Indentation tests are a common method for measuring the adhesion force. However, indenters generally have a large volume and a small sensing angle and, thus, are not conducive to local detection in high-precision environments. Here, we propose a vision-based contact adhesion measurement (VisCAM) method to achieve the contact image and adhesion force on soft matter surfaces from the perspective of indentation direction. The coupling of the 7.6 mm diameter probe and a flexible fiber makes the system similar to a miniaturized endoscope. Classical contact theories and finite element models are used for the contact mechanics analysis of silicone rubber. The image grayscale-load mathematical model is constructed based on the change in contact light spot. Finally, the uncertainty of the system is less than 4%, and the measurement error is 0.04 N. In-vitro kidney indentation experiments showed that the local adhesion force measurement of soft tissues can be completed. Our method provides better solutions for understanding the adhesion properties of soft matters.


Dietary nitrate improves age-related hypertension and metabolic abnormalities in rats via modulation of angiotensin II receptor signaling and inhibition of superoxide generation.
Advanced age is associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed central event is diminished amounts of nitric oxide (NO) due to reduced generation by endothelial NO synthase (eNOS) and increased oxidative stress. In addition, it is widely accepted that increased angiotensin II (ANG II) signaling is also implicated in the pathogenesis of endothelial dysfunction and hypertension by accelerating formation of reactive oxygen species. This study was designed to test the hypothesis that dietary nitrate supplementation could reduce blood pressure and improve glucose tolerance in aged rats, via attenuation of NADPH oxidase activity and ANG II receptor signaling. Dietary nitrate supplementation for two weeks reduced blood pressure (10-15mmHg) and improved glucose clearance in old, but not in young rats. These favorable effects were associated with increased insulin responses, reduced plasma creatinine as well as improved endothelial relaxation to acetylcholine and attenuated contractility to ANG II in resistance arteries. Mechanistically, nitrate reduced NADPH oxidase-mediated oxidative stress in the cardiovascular system and increased cGMP signaling. Finally, nitrate treatment in aged rats normalized the gene expression profile of ANG II receptors (AT1A, AT2, AT1A/AT2 ratio) in the renal and cardiovascular systems without altering plasma levels of renin or ANG II. Our results show that boosting the nitrate-nitrite-NO pathway can partly compensate for age-related disturbances in endogenous NO generation via inhibition of NADPH oxidase and modulation of ANG II receptor expression. These novel findings may have implications for nutrition-based preventive and therapeutic strategies against cardiovascular and metabolic diseases.


Loop-mediated isothermal amplification (LAMP) assay for the rapid detection of the sexually-transmitted parasite, Trichomonas vaginalis.
A loop-mediated isothermal amplification (LAMP) assay was developed to detect the sexually-transmitted parasite, Trichomonas vaginalis in vaginal swabs. The presence of T. vaginalis was detected from 121 female sex workers attending a social hygiene clinic in Balibago, Angeles City, Pampanga, Philippines using culture, polymerase chain reaction (PCR), and the developed LAMP assay. The high analytical sensitivity of LAMP detected a higher prevalence of T. vaginalis (42.06%) compared to culture (8.26%) and PCR (7.44%). Additionally, this assay did not cross-react with DNAs of other trichomonads that can infect humans such as Trichomonas tenax and Pentatrichomonas hominis as well as the pathogens, Candida albicans and Staphylococcus aureus. The LAMP assay developed had a limit of detection (0.036 ng/μl) lower than that of PCR using the primers TvK3 and TvK7 (0.36 ng/μl). Prevalence of T. vaginalis in female sex workers in this area of the Philippines may be higher than previously estimated. Discordant results of PCR and LAMP may be due to different reactions to different kinds of inhibitors in the vaginal swabs.


Access to Drinking Water, Sanitation, and Hand Hygiene Facilities in the Peri-Urban and Informal Settlements of Hosanna Town, Southern Ethiopia.
Access to water, sanitation, and hygiene (WASH) facilities and practices have been extensively studied in urban and rural areas. However, there is a paucity of information on the coverage of water, sanitation, and hygiene facilities in the peri-urban and informal settlement areas, which could potentially exacerbate the spread of water, sanitation, and hygiene-related diseases. Therefore, this study was designed to examine access to drinking water, sanitation, and hand hygiene facilities and their determinant factors in the peri-urban and informal settlements of Hosanna town. A community-based cross-sectional study involving 292 households was conducted in 3 kebeles of Hosanna town. The primary data was collected using a pretested structured questionnaire and an observational checklist. Bivariate and multivariable logistic regressions were used to analyze the data. All the households (100%) had access to piped water on and off-premises, but the reliability of the water sources was a big challenge. Findings revealed that only 35.1% and 16.8% of the households had basic sanitation and basic handwashing facilities, respectively. Households with a middle income were identified as a determinant factor for the presence of piped water on premises (AOR = 2.23; 95% CI = 1.24-4.00), improved sanitation (AOR = 2.17; 95% CI = 1.17-4.03) and handwashing facilities (AOR = 4.36; 95% CI = 1.98-9.62). Piped water on premises was also another strong predictor of the availability of improved sanitation (AOR = 3.34; 95% CI = 1.99-5.62) and handwashing facilities (AOR = 8.18; 95% CI = 4.08-16.42). The majority of the studied households living in the selected peri-urban and informal settlements had access to unreliable drinking water sources. The study also revealed that households had poor access to basic sanitation and basic handwashing facilities. Hence, the findings call for solid government interventions to improve the reliability of the drinking water sources, basic sanitation coverage, and availability of basic handwashing facilities.


Eruption Cyst Treated with Diode Laser: A Case Report.
Eruption cyst or eruption hematoma is a soft tissue cyst of odontogenic origin that occurs in mucosa, which forms shortly before the eruption of the primary or permanent tooth. It is usually found in children. In some cases, it has been seen that it disappears on its own. If there are complications like pain, bleeding or infection, surgical exposure and drainage are necessary. This case is associated with erupting permanent tooth, and its surgical crown exposure has been done by using a diode laser. How to cite this article: Bansal MB, Kumari A, Asrani KH, et al. Eruption Cyst Treated with Diode Laser: A Case Report. Int J Clin Pediatr Dent 2022;15(2):215-217.


Dual Component Passive Icephobic Coatings with Micron-Scale Phase-Separated 3D Structures.
A passive icephobic coating (τice < 20 kPa) is an enabling technology to many industries, including aerospace and energy and power generation, with recent efforts in materials research identifying strategies to achieve this low adhesion threshold. To better meet this need, we have combined low surface energy perfluoropolyether (PFPE) and hydrophilic poly(ethylene glycol) (PEG) species in a segmented polyurethane thermoplastic elastomer. Coating microstructure presents a segregated 3D morphology at the micron-scale (1-100 μm) with discrete PFPE and continuous PEG phases self-similar through the thickness. Spray application produces a solid, mechanically tough film free of additive fluids or sacrificial elements, demonstrating exceptional ice adhesion reduction up to 1000× lower versus aluminum (τice < 1 kPa), as measured under environmentally realistic accretion and centrifugal test shedding conditions. Finally, the modular nature of the synthetic system allows PEG and PFPE to be exchanged for poly(tetramethylene oxide) to investigate performance drivers.


Smart sampling and incremental function learning for very large high dimensional data.
Very large high dimensional data are common nowadays and they impose new challenges to data-driven and data-intensive algorithms. Computational Intelligence techniques have the potential to provide powerful tools for addressing these challenges, but the current literature focuses mainly on handling scalability issues related to data volume in terms of sample size for classification tasks. This work presents a systematic and comprehensive approach for optimally handling regression tasks with very large high dimensional data. The proposed approach is based on smart sampling techniques for minimizing the number of samples to be generated by using an iterative approach that creates new sample sets until the input and output space of the function to be approximated are optimally covered. Incremental function learning takes place in each sampling iteration, the new samples are used to fine tune the regression results of the function learning algorithm. The accuracy and confidence levels of the resulting approximation function are assessed using the probably approximately correct computation framework. The smart sampling and incremental function learning techniques can be easily used in practical applications and scale well in the case of extremely large data. The feasibility and good results of the proposed techniques are demonstrated using benchmark functions as well as functions from real-world problems.


Superexpression of tuberculosis antigens in plant leaves.
Recent developments in genetic engineering allow the employment of plants as factories for 1/foreign protein production. Thus, tuberculosis (TB) ESAT6 antigen was expressed in different plant systems, but the level of vaccine protein accumulation was extremely low. We describe the technology for superexpression of TB vaccine proteins (Ag85B, ESAT6, and ESAT6:Ag85B fusion) in plant leaves which involves: (i) construction of tobacco mosaic virus-based vectors with the coat protein genes substituted by those for TB antigens; (ii) Agrobacterium-mediated delivery to plant leaf tissues of binary vectors containing the cDNA copy of the vector virus genome; and (iii) replication of virus vectors in plant cells under conditions suppressing the virus-induced gene silencing. This technology enables efficient production of the TB vaccine proteins in plants; in particular, the level of Ag85B antigen accumulation was not less than 800 mg/kg of fresh leaves. Expression of TB antigens in plant cells as His(6)-tagged proteins promoted their isolation and purification by Ni-NTA affinity chromatography. Deletion of transmembrane domains from Ag85B caused a dramatic increase in its intracellular stability. We propose that the strategy of TB antigens superproduction in a plant might be used as a basis for the creation of prophylactic and therapeutic vaccine against TB.


Expression, Regulation, and Effects of Interleukin-17f in the Human Ocular Surface.
To evaluate the basal and possibly stimulated expression of interleukin (IL)-17 in the context of the ocular surface and potential downstream effects. Western blot and immunofluorescent staining were used to evaluate IL-17F expression in human cornea/conjunctival tissues and cornea epithelial cell line. Cytokines and matrix metalloproteinase (MMP) transcripts were quantified by qPCR. IL-17F effects on NF-κB were investigated by the secretary alkaline phosphatase assay. IL-17F was expressed in the cytoplasm of human corneal and conjunctival epithelial tissues. In the corneal cell line, exogenous IL-17F did not increase the NF-κB activity, but Pam3CSK4 increased IL-17F transcripts. IL-17F stimulated MMP-9 activity, promoted IL-6, IL-8, tumor necrosis factor-α transcripts levels, and depressed monocyte chemoattractant protein-1 expression, but did not affect transforming growth factor beta-1 transcript levels. Normal corneal/conjunctival epithelial cells express IL-17F. Microbial agents may stimulate IL-17F via the NF-κB pathway. Matrix dissolution stimulated by IL-17F may have a role in the melting and necrosis of cornea in severe inflammation.


Motility of the large intestine of piebald-lethal mice.
In normal siblings of piebald mice, artificial fecal pellets were propelled by peristaltic activity through the large intestine in vitro and were expelled at the anal end. Peristalsis was blocked by lidocaine. Artificial fecal pellets were propelled in the dilated region of the megacolon, but were not propelled in the terminal hypoganglionic segment of the intestine of piebald mice. Retropulsion of artificial fecal pellets occurred in vitro in normal bowel obstructed by a ligature, in the bowel of piebald mice with a narrowed terminal segment, and in the intestine of mice with imperforate anus. The results indicate that the distended portion of the colon of piebald mice is capable of coordinated peristalsis and that accumulation of feces and megacolon are secondary to the terminal obstruction that results from absence of coordinated propulsive activity in the hypoganglionic terminal segment. Reverse peristalsis may be a general response to a distal obstruction.


Delaying weed adaptation to herbicide by environmental heterogeneity: a simulation approach.
Environmental heterogeneity in space or time can drive the evolutionary trajectory of an adaptive trait. This concept could be of practical significance in pesticide resistance management that aims to delay the evolution of a resistance allele. Using a population genetics model, the dynamics of herbicide resistance in a weed species was simulated in a heterogeneous environment with alternation of two unrelated herbicides in time, in space or in both time and space. The level of the environmental heterogeneity (habitat grain) was simulated by a variation in the size of the herbicide-treated areas. The model confirms that several strategies based on habitat heterogeneity efficiently slow down and even prevent resistance evolution. For a recessive resistant trait in outcrossing species, a medium level of environmental heterogeneity (intermediate habitat grain) was found to be the best for delaying herbicide resistance, as previously observed for insecticide resistance management. In selfing species or for a dominant resistant trait in outcrossing species, a low level of environmental heterogeneity (coarse-grained habitat) was more efficient in delaying resistance evolution when heterogeneity in both space and time were considered. This model suggests that the choice of optimal tactics for delaying herbicide resistance by enhanced heterogeneity in space or time firstly depends on the interactions between the breeding system and the dominance of the resistance allele in the presence of herbicide, then on the value of the fitness cost and lastly on the dominance of this fitness cost.


Identity of antibody to hepatitis B e/1 antigen as an atypical rheumatoid factor.
Chronic carriers of hepatitis B surface antigen (HBsAg) who were positive for antibody to hepatitis B e antigen were tested for precipitating specificities of the antibody and for rheumatoid factor (RF) over a two-year period. Twenty-one of 69 carriers were RF-positive by the latex-RF test with human IgG, but all were negative by the hemagglutination-RF test with rabbit IgG. Antibody to e/1 antigen was identified as an IgM antibody reactive in the latex-RF test, whereas antibody to e/2 antigen belonged to the IgG class and showed no RF reactivity. Antibody production seems to follow a sequential evolution: antibody to e/1 antigen appears early and that to e/2 antigen follows shortly thereafter. Antibody to e/2 antigen remains as the permanent antibody, whereas that to e/1 antigen sometimes disappears. The fact that antibody to e/1antigen is present only in certain chronic carriers of HBsAg would account for discrepancies in reported results of RF test in viral hepatitis.


Functional innervation of Guinea-pig bladder interstitial cells of cajal subtypes: neurogenic stimulation evokes in situ calcium transients.
Several populations of interstitial cells of Cajal (ICC) exist in the bladder, associated with intramural nerves. Although ICC respond to exogenous agonists, there is currently no evidence of their functional innervation. The objective was to determine whether bladder ICC are functionally innervated. Guinea-pig bladder tissues, loaded with fluo-4AM were imaged with fluorescent microscopy and challenged with neurogenic electrical field stimulation (EFS). All subtypes of ICC and smooth muscle cells (SMC) displayed spontaneous Ca(2+)-oscillations. EFS (0.5 Hz, 2 Hz, 10 Hz) evoked tetrodotoxin (1 µM)-sensitive Ca(2+)-transients in lamina propria ICC (ICC-LP), detrusor ICC and perivascular ICC (PICC) associated with mucosal microvessels. EFS responses in ICC-LP were significantly reduced by atropine or suramin. SMC and vascular SMC (VSM) also responded to EFS. Spontaneous Ca(2+)-oscillations in individual ICC-LP within networks occurred asynchronously whereas EFS evoked coordinated Ca(2+)-transients in all ICC-LP within a field of view. Non-correlated Ca(2+)-oscillations in detrusor ICC and adjacent SMC pre-EFS, contrasted with simultaneous neurogenic Ca(2+) transients evoked by EFS. Spontaneous Ca(2+)-oscillations in PICC were little affected by EFS, whereas large Ca(2+)-transients were evoked in pre-EFS quiescent PICC. EFS also increased the frequency of VSM Ca(2+)-oscillations. In conclusion, ICC-LP, detrusor ICC and PICC are functionally innervated. Interestingly, Ca(2+)-activity within ICC-LP networks and between detrusor ICC and their adjacent SMC were synchronous under neural control. VSM and PICC Ca(2+)-activity was regulated by bladder nerves. These novel findings demonstrate functional neural control of bladder ICC. Similar studies should now be carried out on neurogenic bladder to elucidate the contribution of impaired nerve-ICC communication to bladder pathophysiology.


Intrinsically disordered caldesmon binds calmodulin via the "buttons on a string" mechanism.
We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain (residues 636-771, CaD136) are intrinsically disordered proteins. The computational and experimental analyses of the wild type CaD136 and series of its single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan mutant (W674A/W707A) suggested that although the interaction of CaD136 with calmodulin (CaM) can be driven by the non-specific electrostatic attraction between these oppositely charged molecules, the specificity of CaD136-CaM binding is likely to be determined by the specific packing of important CaD136 tryptophan residues at the CaD136-CaM interface. It is suggested that this interaction can be described as the "buttons on a charged string" model, where the electrostatic attraction between the intrinsically disordered CaD136 and the CaM is solidified in a "snapping buttons" manner by specific packing of the CaD136 "pliable buttons" (which are the short segments of fluctuating local structure condensed around the tryptophan residues) at the CaD136-CaM interface. Our data also show that all three "buttons" are important for binding, since mutation of any of the tryptophans affects CaD136-CaM binding and since CaD136 remains CaM-buttoned even when two of the three tryptophans are mutated to alanines.


[Lung lipoproteinosis--diagnostic problems].
Pulmonary alveolar proteinosis is a very rare disease, first described by Rosen in 1958. It is characterized by the accumulation of lipoproteins in the pulmonary alveoli. Clinical and radiologic presentations are typical for the interstitial lung disease. Only few cases of this disease have been described in the Polish literature. A patient with disseminated lesions to the lungs is presented. A diagnosis was possible after an analysis of BAL fluid and histological examination of the lung tissue collected by the transbronchial biopsy.


Effect of orthotopic liver transplantation on the progression of familial amyloidotic polyneuropathy.
Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disease associated with a mutant form of the protein transthyretin (TTR). It is characterized clinically by the systemic deposition of amyloid fibrils resulting in organ dysfunction and, ultimately, death. The majority of TTR is produced in the liver, and transplantation of the liver has been shown to ameliorate this source of mutant TTR, arresting the progression of this fatal disease. Thirteen patients with FAP have undergone successful liver transplant surgery at our center since 1992. The impact of liver transplantation on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal dysfunction is reported in this study. Three patients who died before cardiovascular and neurological follow-up are excluded from the analysis. Ten of 13 patients (77%) remain alive an average of 49 months (range, 17-64 months) after transplantation. Three patients suffered sudden death, with autopsy documentation of amyloid deposits involving the conduction system of the heart. Liver transplantation was performed more quickly, required less blood, and a shorter postoperative hospital stay in these patients, compared with patients with cirrhosis. Neurological and nutritional symptoms improved in the majority of affected patients. Those patients with echocardiographic evidence of ventricular wall and valve thickening before transplantation progressed postoperatively despite neurologic improvement. Liver transplantation offers the only cure for the genetic defect causing FAP and appears to result in subjective and objective improvement in neurological dysfunction. Patients with preexisting cardiovascular abnormalities progress despite transplantation; therefore, consideration for combined heart-liver transplantation may be warranted in this subset of patients.


[Familial aortic dissection in a young woman. A clinical case and review of the literature].
A case report of aortic dissecting aneurysm in a 29-years-old woman is described. The father died of rupture of a dissecting aneurysm with acute hemopericardium at the age of 46 years. Histologic examination of the aortic wall revealed a loss of mucopolysaccharide-like material in the media and cystic medial changes. This dramatic familial cluster of aortic dissecting aneurysm suggests a genetically inherited disease although the basic defect remains to be found out.


DNA fragmentation in leukocytes following repeated low dose sarin exposure in guinea pigs.
The objective of this study was to determine levels of DNA fragmentation in blood leukocytes and parietal cortex from guinea pigs following repeated low-level exposure to the chemical warfare nerve agent (CWNA) sarin. Guinea pigs were injected (s.c.) once a day for 10 days with saline, or 0.1, 0.2, or 0.4 LD50 (50% mean lethal dose) sarin dissolved in sterile physiological saline. Blood and parietal cortex was collected after injection at 0, 3, and 17 days recovery and evaluated for DNA fragmentation using single-cell gel electrophoresis (Comet assay). Cells were imaged using comet analysis software and three parameters of DNA fragmentation measured: tail length, percent DNA in the tail, and tail moment arm. Repeated low-dose exposure to sarin produced a dose-dependent response in leukocytes at 0 and 3 days post-exposure. There was a significant increase in all measures of DNA fragmentation at 0.2 and 0.4 LD50, but not at 0.1 LD50. There was no significant increase in DNA fragmentation in any of the groups at 17 days post-exposure. Sarin did not produce a systematic dose-dependent response in parietal cortex at any of the time points. However, significant increases in DNA fragmentation at 0.1 and 0.4 LD50 were observed at 0 and 3 days post-exposure. All measures of DNA fragmentation in both leukocytes and neurons returned to control levels by 17 days post-exposure, indicating a small and non-persistent increase in DNA fragmentation following repeated low-level exposure to sarin.