A small exploratory study of the reaction of older people to an episode of delirium.
Delirium or an acute confusional state, occurs as a result of disease or physiological imbalance secondary to impaired brain function. One of its main clinical features is widespread cognitive impairment, which causes patients to become disconnected from their immediate surroundings and misinterpret reality. It has a sudden onset and its duration is relatively brief. Some authors take the view that delirium might be interpreted as a precursor to dementia. The aim of the study was to retrospectively explore older peoples' experience of an episode of delirium. In particular, whether they knew what had caused and cured it; and whether it had left them with any unresolved feelings of anxiety. A cross sectional design using grounded theory methodology was chosen, as being the most appropriate method for exploring this issue. A sample of 19 patients was selected using predetermined criteria, and engaged in a semi-structured interview with the researcher, in the ward environment. The interviews were audiotaped, transcribed, and analysed using the constant comparison method. Those interviewees who had illusions and hallucinations, were often able to describe their experiences in detail. They ranged from being pleasant and entertaining, to horrible and frightening. They were also able to remember short verbal commands from nurses during the episode of altered perception. Others remembered, or chose not to remember, very little. Few interviewees appeared to know exactly what had caused and cured the delirium, although some were able to tentatively connect the experience to their present medical condition. There also appeared to be little evidence of therapeutic communication with nursing staff once the episode of delirium had resolved. Although no one connected the experience with dementia, there did seem to be some evidence of mildly disturbed feelings, on reflecting back over the episode. As interviewees were generally willing to discuss their experiences with the researcher, it suggests that it would be helpful for nurses to provide opportunities to do so. Nevertheless, interviewees appeared to regard the episode simply as a transitory event in the overall context of illness, admission to hospital and their future welfare. The latter was of prime concern; yet again it appeared that they did not always receive the information they required to maintain control over their personal destinies.


Development and Validation of a Novel Scoring System for Noninvasive Nonalcoholic Steatohepatitis Detection in Bariatric Patients.
Nonalcoholic fatty liver disease covers a broad spectrum. Simple steatosis has usually a benign course while nonalcoholic steatohepatitis (NASH) can progress into hepatocellular carcinoma, and cirrhosis. Therefore, differentiating patients with benign steatosis and NASH is crucial. Liver biopsy, the usual gold standard for NASH diagnosis, cannot be used as a screening method due to its associated risks. This is especially problematic for obese patients with a prevalence of nonalcoholic fatty liver disease (NAFLD) in >80% of patients. The aim of this study was therefore to develop and validate a noninvasive NASH screening test in a cohort of high-risk, morbidly obese patients. This prospective study examined diagnostic accuracy in accordance with STARD guidelines. 112 liver biopsies were consecutively assigned to either a training or validation cohort. Using the Bedossa histological scoring system, the cohorts were subdivided into NASH versus NAFLD/No NAFLD. Predictors of NASH were evaluated with receiver operating characteristic (ROC) curves. A model was then constructed using a backward stepwise logistic regression and evaluated in an independent validation cohort. 53.5% of the patients had NASH and 4 patients had cirrhosis. Mean body mass index (BMI) was 49.8 ± 7.5 kg/m2. Backward stepwise logistic regression identified 4 parameters associated with the presence of NASH: alanin-aminotransferase, albumin, BMI, and triglycerides. The noninvasive NASH detection score (NI-NASH-DS) had an ROC of 0.851 and 0.727 in the training and validation cohorts, respectively. Sensitivity and specificity were 77.1% and 88% in the training cohort and 88% and 48% in the validation cohort which was much better than the established noninvasive scores. The NI-NASH-DS is easy-to-use, inexpensive, and noninvasive and can reliably detect NASH in patients with morbid obesity. Due to its simplicity, it can be used frequently and repeatedly.


T cell depletion in bone marrow transplantation for leukemia: current results and future directions.
T cell depletion reduces the incidence and severity of graft-versus-host disease (GVHD) following bone marrow transplantation in man. Graft-versus-host disease of more than grade 2 severity is decreased from about 45% to about 10% in recipients of HLA-identical transplants. However, T cell depletion also increases the frequency of graft failure and leukemia relapse. Graft failure increases from about 1 to 10% following HLA-identical transplants. In patients with acute leukemia in first remission or with chronic myelogenous leukemia in chronic phase, leukemia relapse increases from about 20% to about 40%. Thus, although T cell depletion decreases GVHD, it increases graft failure and leukemia relapse such that survival is not convincingly improved. Several approaches to these problems are possible including increased pre- or post-transplant immune suppression, more effective antileukemia therapy or selective T cell depletion. Preliminary results of these approaches are discussed and new directions suggested.


Eliminating the need for routine monthly postdialysis serum urea nitrogen measurement: A method for monitoring Kt/V and normalized protein catabolic rate using conductivity determined dialyzer clearance.
Many dialysis machines can compute dialyzer sodium clearances at multiple time points during a dialysis treatment using conductivity. For a given treatment, the average dialyzer sodium clearance (K), when combined with treatment time (t), and the estimated urea distribution volume (V, usually based on either anthropometry or bioimpedance), can be used to estimate Kt/V, an important measure of hemodialysis adequacy. While this conductivity-derived value for Kt/V correlates moderately with Kt/V calculated from predialysis and postdialysis serum urea nitrogen (SUN) values (urea reduction ratio, URR), the ultrafiltration volume, and session length it is, unfortunately, not sufficiently accurate to replace URR-based Kt/V. Here we underline the potential utility of an alternative method to estimate Kt/V (a variant of a technique originally proposed by Gotch and Levin and their colleagues) using conductivity-derived sodium clearance (K) that does not require routine measurement of the postdialysis SUN but which should closely track Kt/V computed in the usual fashion. The increased accuracy with the new method is explained by the use of a patient-specific value of V, which is an average value calculated from several dialysis sessions where both conductivity dialyzer clearance and predialysis and postdialysis SUN have been measured. Once this patient-specific conductivity/URR-based value for V has been determined, it can be used to calculate Kt/V for subsequent treatments in which conductivity-based dialyzer clearances are measured, but around which predialysis and postdialysis SUN values have not been obtained. (If the predialysis SUN values for such a subsequent treatment are also measured, then a normalized protein catabolic rate that closely tracks the value from conventional urea modeling, can also be determined.) By reducing the number of postdialysis SUN measurements needed to monitor hemodialysis adequacy this new method of estimating Kt/V by conductivity should save staff time and laboratory costs, increase patient and staff safety, and decrease error rates associated with improper postdialysis blood sampling technique.


LATE MERISTEM IDENTITY2 acts together with LEAFY to activate APETALA1.
The switch from producing vegetative structures (branches and leaves) to producing reproductive structures (flowers) is a crucial developmental transition that significantly affects the reproductive success of flowering plants. In Arabidopsis, this transition is in large part controlled by the meristem identity regulator LEAFY (LFY). The molecular mechanisms by which LFY orchestrates a precise and robust switch to flower formation is not well understood. Here, we show that the direct LFY target LATE MERISTEM IDENTITY2 (LMI2) has a role in the meristem identity transition. Like LFY, LMI2 activates AP1 directly; moreover, LMI2 and LFY interact physically. LFY, LMI2 and AP1 are connected in a feed-forward and positive feedback loop network. We propose that these intricate regulatory interactions not only direct the precision of this crucial developmental transition in rapidly changing environmental conditions, but also contribute to its robustness and irreversibility.


Identification of protease from Euphorbia amygdaloides latex and its use in cheese production.
In this research, protease enzyme was purified and characterized from milk of Euphorbia amygdaloides. (NH4)2SO4 fractionation and CM-cellulose ion exchange chromatography methods were used for purification of the enzyme. The optimum pH value was determined to be 5, and the optimum temperature was determined to be 60 degrees C. The V(max) and K(M) values at optimum pH and 25 degrees C were calculated by means of Linewearver-Burk graphs as 0.27 mg/L min(-1) and 16 mM, respectively. The purification degree was controlled by using SDS-PAGE and molecular weight was found to be 26 kD. The molecular weight of the enzyme was determined as 54 kD by gel filtration chromatography. These results show that the enzyme has two subunits. In the study, it was also researched whether purified and characterized protease can be collapsed to milk. It was determined that protease enzyme can collapse milk and it can be used to produce cheese.


Empowerment through rehabilitation nursing certification.
Certification empowers nurses by validating their clinical competency and continued professional growth. This article discusses the current state of certification in the nursing profession. The potential benefits to the certified nurse and the costs in both time and money needed to achieve and maintain certification are addressed. The article also describes how the nursing department of a 284-bed rehabilitation hospital developed a program to promote specialty certification among its nursing staff. The process and outcome of this program revealed several potential research topics.


Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811.
Pulmonary complications after liver transplantation (LT) often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 μM) for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG) and quarter-size grafts (QSG), respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5-18 h after LT. At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNFα and IL-1β mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT.


Clinical trials and public trust: the geographical shift to the Asia-Pacific region.
Multiple issues surrounding the publication of clinical trials and the conduct of clinical trials, especially those that are industry-sponsored, have raised doubts regarding the integrity of their results, and of the integrity of the medical profession. An appreciation of the historical and economic changes in the relationship between physicians and industry is crucial to the understanding of these issues. Increasingly, as healthcare professionals and centers in the Asia-Pacific region become involved in corporate-funded multi-center drug trials, these ethical issues similarly come into play. It is imperative for medical leaders to take actions ensuring rights of subjects participating in these clinical trials, and to ensure the integrity of physicians and authors of clinical trials from this region of the world.


Profile of reslizumab in eosinophilic disease and its potential in the treatment of poorly controlled eosinophilic asthma.
Eosinophils are important proinflammatory cells that make a major contribution to the inflammation seen in allergic diseases including asthma. Interleukin-5 is central to eosinophil maturation, release from the bone marrow, and subsequent accumulation, activation, and persistence in the tissues. Reslizumab (Cinquil™) is a humanized monoclonal antibody with potent interleukin-5 neutralizing effects, which represents a potential treatment for poorly controlled eosinophilic asthma. This review will consider the current status of the clinical development of reslizumab for asthma and in other inflammatory diseases with a marked eosinophilic component.


Primary plasmacytoma of generalized lymph nodes: a long survivor.
Extramedullary plasmacytomas are occasionally seen in the course of multiple myeloma; however, primary plasmacytomas are unusual. Most of the primary plasmacytomas arise in the upper respiratory system, but a plasmacytoma of the lymph nodes is very rare. A case of a 56-year-old female with primary plasmacytoma in the lower mandibular, cervical, axillary, and para-aortic lymph nodes accompanied by IgA Kappa paraproteinemia is described. After ten courses of combination chemotherapy with cyclophosphamide and prednisolone, she obtained complete response. However, 6 years later, she had a relapse of plasmacytoma in the generalized lymph nodes. She received ten treatments of melphalan-prednisolone and again obtained complete response. She has remained well without chemotherapy or recurrent signs for 9 years. It is considered that conventional chemotherapy can be useful for primary plasmacytoma of generalized lymph nodes.


L and M cone input into spectral sensitivity functions: a reanalysis.
In order to better understand the nature of long-wavelength (L) and middle-wavelength (M) cone input into spectral sensitivity functions and determine the reliability with which it is possible to predict L:M cone inputs, we developed analytical methods to determine confidence intervals for L:M cone input for spectral sensitivity functions or data transformed to cone-contrast space. Spectral sensitivity functions measured by direct heterochromatic brightness matches are dominated by the L/M opponent channel over most of the spectral range. For detection of large/ long test stimuli, spectral sensitivity functions show a characteristic "notch" at the adapting wavelength, with the L/M opponent channel dominating most of the spectral range. Flicker increment threshold (FIT) spectral sensitivity functions display many of the characteristics of the luminance flicker mechanism described by Stromeyer et al. (1987). [Vision Research, 27, 1113-1137]. Previous modelling of FIT spectral sensitivity functions proposed a 2:1 L:M cone input for most of testing conditions. We show that FIT spectral sensitivity functions are dominated by L cones but show L cone suppression under bright red adapting fields. For the fitted spectral sensitivity functions or simulated data sets, we found small confidence intervals for L:M cone input into the L/M opponent channel and conclude that it is possible to reliably predict L:M cone input ratios. However, for similar data sets of additive spectral sensitivity functions, we found large confidence intervals for L:M cone input ratios and conclude that it is not possible reliably predict L:M cone input into the L/M non-opponent channel using available spectral sensitivity functions.


A multi-criteria index for ecological evaluation of tropical agriculture in southeastern Mexico.
The aim of this study was to generate an easy to use index to evaluate the ecological state of agricultural land from a sustainability perspective. We selected environmental indicators, such as the use of organic soil amendments (green manure) versus chemical fertilizers, plant biodiversity (including crop associations), variables which characterize soil conservation of conventional agricultural systems, pesticide use, method and frequency of tillage. We monitored the ecological state of 52 agricultural plots to test the performance of the index. The variables were hierarchically aggregated with simple mathematical algorithms, if-then rules, and rule-based fuzzy models, yielding the final multi-criteria index with values from 0 (worst) to 1 (best conditions). We validated the model through independent evaluation by experts, and we obtained a linear regression with an r2 = 0.61 (p = 2.4e-06, d.f. = 49) between index output and the experts' evaluation.


[A clinical and genetic analysis of a pedigree with two 46,XY patients suffering from 17alpha-hydroxylase deficiency].
To investigate the molecular defects of CYP17A1 gene in a pedigree with two 46,XY patients suffering from 17alpha-hydroxylase deficiency (17-OHD) and explore the steroid biosynthetic difference in carriers of 17-OHD before and after adrenocorticotrophic hormone (ACTH) test. Clinical data and hormone profiles were collected from the members of the pedigree. CYP17A1 genotyping was performed in the patients and family members with PCR-direct sequencing. A short ACTH test was evaluated in some cases. The CYP17 genes of the patients were proved to hold a homozygous mutation with a base deletion and a base transversion (TAC/AA) in exon 6, which produced a missense mutation of Tyr-->Lys at codon 329 and changed the open reading frame following this codon. The hormone response of the carriers after ACTH stimulation was abnormal between the patients and normal controls. 17-OHD in this family was caused by CYP17A1 mutation (TAC329AA); some hormonal response to ACTH stimulation was abnormal in carriers.


Parental concerns' prevalence and socio-demographic variables in general parenting.
The aim of this study was to evaluate parental concerns in general parenting. The participants were 3842 parents of children between 3 and 10 years old, attending public preschools and primary schools, from a stratified random sample of Portuguese parents. Parents completed a parental concerns' scale that comprises five subscales: family and school problems; eating, sleep and physical complaints; preparation; fears; and negative behaviours. The results reported that 93.4 per cent of parents expressed some concern about the issues presented in the scale. Comparative analysis reported significant differences between mothers and fathers; child's gender; child's schooling level; mothers' and fathers' level of education, age at childbirth, marital status, and employment status. These results may indicate that parental concerns are an expected aspect of parenting, and that they should be addressed in family practice. Moreover, the reported differences between groups pointed to the need to develop specific intervention strategies.


Evaluation of patients with COVID-19 diagnosis for chronic diseases.
COVID-19 is one of the most consequential pandemic in world history. Chronic diseases, which are risk factors that increase the case fatality rates, have been the leading cause of death all over the world. This study was aimed at detecting coexisting chronic diseases in patients hospitalized with a diagnosis of COVID-19. The study was carried out with data from 229 patients in an intensive care unit, from June 1st through June 30th. 2020. The inclusion criteria of the study was as follows: (1) having a COVID-19 diagnosis confirmed by PCR test; (2) being hospitalized in the relevant intensive care unit within the dates of the study; and (3) having their data accessible through the hospital automation system. Through literature; chronic diseases of the patients and their effects on the COVID-19 process were evaluated. Statistical analyzes were performed using the Statistical Package for Social Sciences (SPSS) version 24.0 (IBM Corp.; Armonk, NY, USA). The average age of the patients studied were 61.4 years. While the average symptom duration was 8.2 days; total hospitalization period was 13.1 days. The average length of stay of patients (n = 75) who were sent to intensive care unit was 10.1. The most common chronic disease among patients was hypertension with 47.2%. This was followed by diabetes mellitus (32.8%) and heart disease (27.5%), respectively. In the population studied, cough (59.4%), fever (58.5%) and shortness of breath (45.9%) were found to be the most common symptoms. Leukopenia, impairments in liver and muscle enzymes, abnormal C-reactive protein, ferritin and d-dimer levels were the important biochemical tests. Particular attention should be paid to the elderly COVID-19 patients with chronic diseases, especially DM, HT and cancer.


Dynamics of a stoichiometric producer-grazer system with seasonal effects on light level.
Many population systems are subject to seasonally varying environments. As a result, many species exhibit seasonal changes in their life-history parameters. It is quite natural to try to understand how seasonal forcing affects population dynamics subject to stoichiometric constraints, such as nutrient/light availability and food quality. Here, we use a variation of a stoichiometric Lotka-Volterra type model, known as the LKE model, as a case study, focusing on seasonal variation in the producer's light-dependent carrying capacity. Positivity and boundedness of model solutions are studied, as well as numerical explorations and bifurcations analyses. In the absence of seasonal effects, the LKE model suggests that the dynamics are either stable equilibrium or limit cycles. However, through bifurcation analysis we observe that seasonal forcing can lead to complicated population dynamics, including periodic and quasi-periodic solutions.


Potent Inhibition of Biphasic Tubular Reabsorption of Lithium by Acetazolamide and Foscarnet in Rats.
Lithium is mainly excreted into urine, and a large fraction of lithium filtered through glomeruli is reabsorbed in the proximal tubule. However, the mechanisms responsible for lithium reabsorption remain unclear. We previously reported that the reabsorption of lithium was biphasic in rats, and that foscarnet inhibited lithium reabsorption with a high affinity type. We herein evaluated the effects of acetazolamide and foscarnet on the renal excretion of lithium in rats treated with lithium chloride at 2 doses. In rats intravenously injected with a bolus of 25 mg/kg lithium chloride, acetazolamide facilitated the urinary excretion of lithium, and increased the fractional excretion of lithium from 0.446 to 0.953, near the theoretically maximum value. At a dose of 2.5 mg/kg lithium chloride, the fractional excretion of lithium was 0.241 in control rats, 0.420 in rats administered acetazolamide, and 0.976 in rats administered acetazolamide and foscarnet. These results showed the potent inhibition of lithium reabsorption by acetazolamide and foscarnet in rats. And, it was exhibited that the effects of acetazolamide on lithium reabsorption differed with the dosages of lithium administered.


Designing a Hybrid Perovskite with Enlarged Birefringence and Bandgap for Modulation of Light Polarization.
Birefringent crystals have important applications in optoelectronics areas due to their ability to modulate and polarize light. Despite increasing discovery of the birefringence potential of new crystals, it remains a great challenge to optimize both birefringence and bandgap simultaneously. Herein, a 1D chain-like hybrid perovskite birefringent crystal designed by 3D-to-1D dimensional tailoring, (GAM)2 PbI7 ·H2 O (GAM = C5 N10 H10 ), is presented, showing enlarged birefringence of 0.49@550 nm and enlarged optical bandgap (2.48 eV). Consequently, the birefringent quality factor of (GAM)2 PbI7 ·H2 O is up to 2.8 times that of the template MAPbI3 . In particular, the birefringence is much larger than those of commercial birefringent crystals and surpasses that of the vast majority of hybrid perovskite known to date. Theoretical calculations reveal that the strongly anisotropic arrangement of (GAM)2.5+ π-conjugated cations and ordered PbI6 octahedra contributes to the large birefringence and wide bandgap of (GAM)2 PbI7 ·H2 O. It is believed that this work will provide a new pathway toward the rational design and synthesis of hybrid perovskite birefringent crystals for compact wide-bandgap polarization dependent devices.


Immune capacity of mice tolerating a weakly incompatible skin allograft. I. Tolerance induction by neonatal skin graft in adult recipients or by neonatal inoculation of adult cells.
An analysis was made of the so-called "tolergenic" effect of neonatal skin grafts which tend to survive longer than control adult grafts and confer this tendency also on simultaneously transplanted adult grafts of the same genotype. When the time interval between the neonatal and adult grafts varied from zero to 150 days, it could be demonstrated that neonatal skin grafts are capable of inducing second-set response comparable to that induced by adult grafts provided that the adult graft is not given simultaneously but only following 20 days or later. Signs of immune erises (i.e. various degrees of a round-cell infiltration) were, however, detected histologically even with shorter intervals of time. The involvement of some non-specific components in the early postgrafting period was indicated by a similar effect of sera from recipients of syngeneic grafts and MSA-incompatible grafts on the survival of grafts across the male-specific antigen barrier. Only long surviving allografts tend to specifically reduce the recipient's immune responsiveness. The possible mechanisms of the specific and non-specific components in the effect of neonatal skin grafts and the factor of time are discussed.


Chronic Ethanol Exposure: Pathogenesis of Pulmonary Disease and Dysfunction.
Ethanol (EtOH) is the world's most commonly used drug, and has been widely recognized as a risk factor for developing lung disorders. Chronic EtOH exposure affects all of the organ systems in the body and increases the risk of developing pulmonary diseases such as acute lung injury and pneumonia, while exacerbating the symptoms and resulting in increased mortality in many other lung disorders. EtOH and its metabolites inhibit the immune response of alveolar macrophages (AMs), increase airway leakage, produce damaging reactive oxygen species (ROS), and disrupt the balance of antioxidants/oxidants within the lungs. In this article, we review the role of EtOH exposure in the pathogenesis and progression of pulmonary disease.


Aggressive leptomeningeal hemangioblastomatosis of the central nervous system in a patient with von Hippel-Lindau disease.
Hemangioblastomas of the central nervous system are the most common tumors seen in patients with von Hippel-Lindau (VHL) disease. A very rare case of diffuse leptomeningeal hemangioblastomatosis obliterating large areas of the subarachnoid space, both intracranial and within the spinal canal, which developed during a relatively short period, in a patient with VHL disease is presented.


Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients.
Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.


An Extraordinarily Stable DNA Minidumbbell.
The minidumbbell (MDB) is a new type of native DNA structure. At neutral pH, two TTTA or CCTG repeats can fold into the highly compact MDB with a melting temperature of ∼22 °C. Owing to the relatively low thermodynamic stability, MDBs have been proposed to be the structural intermediates that lead to efficient DNA repair escape and thus repeat expansions. In this study, we reveal that two CCTG repeats can also form an extraordinarily stable MDB with a melting temperature of ∼46 °C at pH 5.0. This unusual stability predominantly results from the formation of a three hydrogen bond C+·C mispair between the two minor groove cytosine residues. Due to the drastic stability change, the CCTG MDB, when combined with its complementary sequence, shows instant and complete structural conversions when the pH switches between 5.0 and 7.0, making the system serve as a simple and efficient pH-controlled molecular switch.


All ileo-cecal ulcers are not Crohn's: Changing perspectives of symptomatic ileocecal ulcers.
To investigated clinical, endoscopic and histopathological parameters of the patients presenting with ileocecal ulcers on colonoscopy. Consecutive symptomatic patients undergoing colonoscopy, and diagnosed to have ulcerations in the ileocecal (I/C) region, were enrolled. Biopsy was obtained and their clinical presentation and outcome were recorded. Out of 1632 colonoscopies, 104 patients had ulcerations in the I/C region and were included in the study. Their median age was 44.5 years and 59% were males. The predominant presentation was lower GI bleed (55, 53%), pain abdomen ± diarrhea (36, 35%), fever (32, 31%), and diarrhea alone (9, 9%). On colonoscopy, terminal ileum was entered in 96 (92%) cases. The distribution of ulcers was as follows: Ileum alone 40% (38/96), cecum alone 33% (32/96), and both ileum plus cecum 27% (26/96). The ulcers were multiple in 98% and in 34% there were additional ulcers elsewhere in colon. Based on clinical presentation and investigations, the etiology of ulcers was classified into infective causes (43%) and non-infective causes (57%). Fourteen patients (13%) were diagnosed to have Crohn's disease (CD). Non-specific ileocecal ulcers are most common ulcers seen in ileo-cecal region. And if all infections are clubbed together then infection is the most common (> 40%) cause of ulcerations of the I/C region. Cecal involvement and fever are important clues to infective cause. On the contrary CD account for only 13% cases as a cause of ileo-cecalulcers. So all symptomatic patients with I/C ulcers on colonoscopy are not Crohn's.


Can a poor state afford not to expand Medicaid?
Some advocates of the uninsured support expansion of Medicaid programs, while others say that expansions are simply unaffordable, especially in poor states. State-level analyses of the costs and consequences of these expansion programs are infrequent. This study evaluates three programs to expand eligibility for Alabama's Medicaid program. The first two programs would raise the Aid to Families with Dependent Children (AFDC) eligibility threshold to 50 and 100 percent, respectively, of the federal poverty level. The third program, currently not available to the states without a federal waiver, would drop all categorical eligibility requirements and base eligibility solely on whether income is below the federal poverty level. Only 10.7 and 18.3 percent, respectively, of Alabama's uninsured would gain health care coverage under the first two programs. The third program would increase the proportion of Alabamians with health coverage to nearly 50 percent. For all of these programs, front-end state costs would be largely countered by federal funding and offsets, such as reductions in uncompensated hospital care and savings realized by former uninsureds from reductions in out-of-pocket expenditures for health services.


[Informed consent in neurology].
Informed consent has remained in the medical tradition but the scale of values and human rights have changed. Today the emphasis is on a human being's right to autonomy, his personality and power to make decisions. At the same time, the doctor-patient relationship has undergone considerable changes. It has evolved from one of paternalism based on the old idea of charity, to one in which the principle of freedom is prevalent whereby it is the patient who has the right to decide the type of medical procedures to be used on him. This idea is recognized as such in the General Health Act of 1986. It has therefore become obligatory for the medical profession to abide by this Act. To do so the patient must be given sufficient information regarding the medical procedures to be applied in his case in particular, including all the risks and advantages as well as any possible alternatives, so that the patient is able to play a part in choosing the most suitable treatment. By law this information must be written down. This is essential to create protocols or medical guide-lines to orientate both the patient and the judge in the event of a demand action as to whether the medical procedure was in accordance with the lex artis or not in each case (lex artis ad hoc). We wish to encourage our colleagues to create a model such as we present, indicating what we consider to be essential points to be included in guide-lines in order to achieve uniform criteria throughout the country thereby facilitating the work of medical assessors and judges. We encourage the scientific societies involved and the corresponding medical departments to form a working party to draw up these medical guide-lines in order to achieve the maximum agreement possible.


A versatile microfluidic tool for the 3D culture of HepaRG cells seeded at various stages of differentiation.
The development of livers-on-a-chip aims to provide pharmaceutical companies with reliable systems to perform drug screening and toxicological studies. To that end, microfluidic systems are engineered to mimic the functions and architecture of this organ. In this context we have designed a device that reproduces series of liver microarchitectures, each permitting the 3D culture of hepatocytes by confining them to a chamber that is separated from the medium conveying channel by very thin slits. We modified the structure to ensure its compatibility with the culture of hepatocytes from different sources. Our device was adapted to the migratory and adhesion properties of the human HepaRG cell line at various stages of differentiation. Using this device, it was possible to keep the cells alive for more than 14 days, during which they achieved a 3D organisation and acquired or maintained their differentiation into hepatocytes. Albumin secretion as well as functional bile canaliculi were confirmed on the liver-on-a-chip. Finally, an acetaminophen toxicological assay was performed. With its multiple micro-chambers for hepatocyte culture, this microfluidic device architecture offers a promising opportunity to provide new tools for drug screening applications.


Engineering metal-based hydrogel-mediated tertiary lymphoid structure formation via activation of the STING pathway for enhanced immunotherapy.
Tertiary lymphoid structures (TLSs) primarily constructed by multiple immune cells can effectively enhance tumor immune responses, but expediting the formation of TLSs is still an enormous challenge. Herein, a stimulator of interferon gene (STING)-activating hydrogel (ZCCG) was elaborately developed by coordinating Zn2+ with 4,5-imidazole dicarboxylic acid, and simultaneously integrating chitosan (a stimulant of STING pathway activation) and CpG (an agonist of toll-like receptor 9, TLR9) for initiating and activating cGAS-STING and TLR9 pathway-mediated immunotherapy. Moreover, the dual-pathway activation could effectively enhance the infiltration of immune cells and the expression of lymphocyte-recruiting chemokines in the tumor microenvironment (TME), thereby promoting the formation of TLSs and further strengthening tumoricidal immunity. Local administration of the hydrogel could prime systemic immune responses and long-term immune memory and improve the therapeutic effects of programmed death-1 antibody (αPD-1) to inhibit tumor progression, metastasis and recurrence. The engineered hydrogel lays the foundation for tumor immunotherapy strategies based on the enhanced formation of TLSs via the activation of the cGAS-STING and TLR9 pathways.


Comparison of repair of DNA double-strand breaks caused by neutron or gamma radiation in cultured human cells.
The dose-response for the induction of initial double-strand breaks (dsb) in DNA of human epithelioid cells by JANUS 0.85 MeV fission-spectrum neutrons was parabolic as assayed by a calibrated neutral filter elution technique. The relative biological effectiveness (RBE) of these neutrons relative to 60Co gamma-rays was unity. The kinetics of repair after a 60 Gy gamma-ray exposure were biphasic. About 65% of these dsb were rapidly repaired (T 1/2 of approximately 2 min), and the remainder were almost completely removed after 150 min at a slower rate (T 1/2 = 30 min). After the same dose of JANUS neutrons, the rapid repair component was markedly reduced (possibly not a significant repair component), and the bulk of the dsb were sealed more slowly (T 1/2 = 90 min). After 150 min, 25% remained unsealed. Even after a lower neutron dose (20 Gy), a proportion of the dsb were refractory to repair. Thus, unrepaired (or irreparable) dsb induced by high energy neutrons might explain the high RBE of neutrons for cell killing.


[Cyclophosphamide bolus therapy in lupus nephritis--status of the clinical study].
In order to establish a low-dose cumulative cyclophosphamide therapy for lupus nephritis, 21 patients were either randomized for at least 3 i.v. cyclophosphamide pulses until remission occurred or for 12 pulses. 18/21 patients developed a remission after an average of 7.3 pulses and a cumulative cyclophosphamide dose of 9.3 g. Side effects were only mild.


Daily Pad Usage Versus the International Consultation on Incontinence Questionnaire Short Form for Continence Assessment Following Radical Prostatectomy.
Continence assessment is an essential component of follow-up after radical prostatectomy (RP). Several methods exist to assess the severity of urinary incontinence (UI). Our study examined the relationship and degree of agreement between International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) scores and the number of pads used in a 24-hour period in the assessment of UI following RP. Continence was prospectively assessed in 746 men from a Spanish urology clinic 12 months after RP using the ICIQ-SF and pad usage. The relationship between ICIQ-SF scores and pad usage was assessed using Spearman rank correlation coefficients. The Jonckheere-Terpstra trend test was used to determine whether the ICIQ-SF score and the component question scores increased with increasing pad usage. The Bonferroni-corrected pairwise Wilcoxon rank-sum test was used to determine which pairs of pad usage levels differed. The weighted kappa was used to evaluate the agreement between pad usage levels and ICIQ-SF questions. The continence rate was 82% using the "no pad usage" definition of continence versus 78% using the definition of an ICIQ-SF score of 0 (P<0.001). Strong positive correlations were observed between the number of pads and the ICIQ-SF total and component question scores (rs>0.85, P<0.001). The ICIQ-SF total and component question scores increased significantly with increasing pad usage (P<0.001). The ICIQ-SF scores (P<0.018) for all pairs of pad usage levels (0, 1, 2, or 3 or more) differed significantly. The agreement between the ICIQ-SF leakage amount question and pad usage was very good (rs=0.861, P<0.001). At 12 months post-RP, 24-hour pad usage was closely correlated with ICIQ-SF, although the continence rate differed depending on the definition used. Higher levels of pad usage were associated with higher questionnaire scores, more leakage, and poor quality of life (interference with everyday life).


Magnesium sulfate for 6 vs 24 hours post delivery in patients who received magnesium sulfate for less than 8 hours before birth: a randomized clinical trial.
To compare the benefits of magnesium sulfate for 24 h (h) postpartum versus 6 h postpartum in patients who received magnesium sulfate (Mg) for less than 8 h before birth. A randomized, multicenter, open study was conducted between November 2013 and October 2016 in three teaching maternity hospitals in Panama. Pregnant women diagnosed with severe pre-eclampsia or pre-eclampsia with severe features at more than 20 weeks gestation were invited to participate. They were randomized to the following groups in a 1:1 ratio: A- continue Mg for 24 h after birth (control group); and B- receive Mg for 6 h after birth (experimental group). The primary endpoint and variable was seizure (eclampsia) in the first 72 h postpartum. During the study period, 284 patients agreed to participate in the study; 143 were randomized to receive Mg for 24 h postpartum and 141 to receive Mg for 6 h postpartum. There were no significant differences in the baseline characteristics of the two groups studied. There was no eclampsia in the entire population; therefore, there was no significant difference in the primary variable. Two secondary variables showed a significant difference: time to onset of ambulation, which was 14 h shorter (p = 0.0001) in the group that received 6 h of postpartum Mg, and time to initiation of breastfeeding, which was 11 h earlier (p = 0.0001) in the group that received 6 h of postpartum Mg. There were not significant differences between the groups with respect to total complications or any particular complication. There were no cases of maternal death. Maintaining Mg for 6 h postpartum is equally effective in preventing eclampsia as receiving Mg for 24 h postpartum in patients with severe pre-eclampsia who receive less than 8 h of Mg treatment before birth. The onset of maternal ambulation and initiation of breastfeeding are faster in patients who only receive Mg for 6 h postpartum. The study was registered at clinical-trials.gov, number NCT02317146 . Date of registration: December 11, 2014. This study was registered at clinical trials after the beginning of recruitment of patients.


A fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic.
This paper demonstrates a new strategy for developing a fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic. The technique provides amino modified Mn-doped ZnS QDs as fluorescent supports, 4-vinylphenylbronic acid as a covalent monomer, N-isopropyl acrylamide as a thermo-responsive monomer in combination with acrylamide as a non-covalent monomer, and glycosyl moiety of a glycopeptide antibiotic as a template to produce fluorescent molecularly imprinted polymer (FMIP) in aqueous solution. The FMIP can alter its functional moieties and structure with pH and temperature stimulation. This allows recognition of target molecules through control of pH and temperature. The fluorescence intensity of the FMIP was enhanced gradually as the concentration of telavancin increased, and showed selective recognition toward the target glycopeptide antibiotic preferentially among other antibiotics. Using the FMIP as a sensing material, good linear correlations were obtained over the concentration range of 3.0-300.0μg/L and with a low limit of detection of 1.0μg/L. The analysis results of telavancin in real samples were consistent with that obtained by liquid chromatography tandem mass spectrometry.


[Treatment of severe non-cancer pain by oral morphine].
Although the pain-relieving effect of morphine and other opioid analgesics for various conditions (cancer or non-cancer) are established, many physicians hesitate to prescribe them for the patients suffering from severe non-cancer pain. To develop full efficacy of morphine (and other opioids), following procedures are essential for the therapy; detailed explanation about the drugs, careful measures to prevent the adverse effects (nausea, vomiting, constipation, sleepiness, etc.) and prescribing "analgesic dosage" of morphine for the patient. We have been engaged in the control of severe non-cancer pain by self-management of oral morphine, in which patients were supported by telephone instructions when they start the treatment (Yamagata University method). It was confirmed that this self-management of oral morphine regimen was a useful method for the early control of severe non-cancer pain. We recommend expanding application of oral morphine to the treatment of non-cancer severe pain to regain quality of life of the patients.


Blood management in patients with deep prosthetic hip and knee infections.
Patients undergoing treatment for infected hip and knee replacements often have significant blood loss and require allogeneic blood transfusions. In the setting of sepsis, traditional methods of blood management such as preoperative blood donations, cell savers, and reinfusion drains are contraindicated. Pharmacologic agents can minimize transfusion requirements by increasing erythropoiesis, or minimize perioperative blood loss. This article reviews the use of these agents in the management of patients with deep prosthetic hip and knee infections.


[Electroretinographic signs of retinal remodeling after experimental induction of retinal pigment epithelium atrophy].
Various animal models of atrophy of retinal pigment epithelium (RPE) are created in order to study certain aspects of geographical atrophy in humans. To study the effects of new methods of therapy, it is necessary to determine the objective functional markers of structural changes in the retina. To determine the alterations in activity of the retina that characterize its remodeling in induction of RPE atrophy. Full-field electroretinograms (ERG), pattern ERG, and multifocal ERG were recorded according to the ISCEV standards from the right eyes of twenty rabbits of the New Zealand albino breed 6-7 weeks after induction of RPE atrophy by subretinal administration of 0.9% sodium chloride or bevacizumab solution. Characteristic electroretinographic signs of RPE atrophy and retinal remodeling are described. Changes in ERG indicate a predominant inhibition of the functional activity of photoreceptors compared with bipolar cells, which objectively reflects an impairment of their metabolism associated with RPE pathology. With the injection of bevacizumab, a sharp weakening of the functional symbiosis of Mueller cells with bipolar cells was observed. According to pattern ERG, the function of the retinal ganglion cells was reduced. The reaction of the paired eyes after induction of RPE atrophy included a moderate decrease in the amplitude of b-wave of photopic ERG and activation of glia-neuronal relationships. Subretinal injections of 0.9% sodium chloride and bevacizumab trigger changes in the retina that reflect specific remodeling of retinal neurons of the second and third orders, which characterizes the used models of RPE atrophy.


Left-ventricular geometry and risk of sudden cardiac arrest in patients with preserved or moderately reduced left-ventricular ejection fraction.
The majority of sudden cardiac arrests (SCAs) occur in patients with left-ventricular (LV) ejection fraction (LVEF) >35%, yet there are no methods for effective risk stratification in this sub-group. Since abnormalities of LV geometry can be identified even with preserved LVEF, we investigated the potential impact of LV geometry as a novel risk marker for this patient population. In the ongoing Oregon Sudden Unexpected Death Study, SCA cases with archived echocardiographic data available were prospectively identified during 2002-15, and compared with geographical controls. Analysis was restricted to subjects with LVEF >35%. Based on established measures of LV mass and relative wall thickness (ratio of wall thickness to cavity diameter), four different LV geometric patterns were identified: normal geometry, concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. Sudden cardiac arrest cases (n = 307) and controls (n = 280) did not differ in age, sex, or LVEF, but increased LV mass was more common in cases. Twenty-nine percent of SCA cases presented with normal LV geometry, 35% had concentric remodelling, 25% concentric hypertrophy, and 11% eccentric hypertrophy. In multivariate model, concentric remodelling (OR 1.76; 95%CI 1.18-2.63; P = 0.005), concentric hypertrophy (OR 3.20; 95%CI 1.90-5.39; P < 0.001), and eccentric hypertrophy (OR 2.47; 95%CI 1.30-4.66; P = 0.006) were associated with increased risk of SCA. Concentric and eccentric LV hypertrophy, but also concentric remodelling without hypertrophy, are associated with increased risk of SCA. These novel findings suggest the potential utility of evaluating LV geometry as a potential risk stratification tool in patients with preserved or moderately reduced LVEF.


Characterization of insulin-like growth factor-binding proteins in human serum from patients with chronic renal failure.
Western ligand blotting of human serum reveals proteins of 41.5, 38, 33, 28, and 23 kD which will specifically bind [125I]insulin-like growth factor-I [( 125I]IGF-I). The relationship of these binding proteins (BPs) to the two serum BP-IGF complexes of 150 and 40 kD and their relationship to the two purified and well characterized IGF-BPs, BP-25 and BP-53, are not clear. The studies reported here used gel filtration, Western ligand blotting, deglycosylation, affinity cross-linking, and immunoprecipitation with antisera against BP-25 and BP-53 to explore the relationship among these IGF-BP forms. Serum from children with chronic renal failure was used for this study, since, by Western ligand blot, it was rich in all five IGF-BPs. The 28- and 33-kD BPs, which were hard to detect in normal serum, were elevated in chronic renal failure serum. Using this serum in each experiment, it was found that the large (150-kD) BP-IGF complex contained only the 41.5- and 38-kD BPs. Both of these BPs were precipitated by anti-BP-53 antiserum, but not by anti-BP-25 antisera, and both BPs were deglycosylated by endoglycosidase-F to a single 31-kD protein which retained the ability to bind IGF-I. This molecular mass of 31 kD is similar to the 28.7-kD mass for nonglycosylated BP-53 predicted by cDNA sequence analysis. In contrast, the 33-, 28-, and 23-kD BPs were only detected in the small (40-kD) BP-IGF complex. None of the three BPs was precipitated by anti-BP-53 antiserum, and none was digested by endoglycosidase-F. The 28-kD BP comigrated with pure BP-25 under all conditions and was precipitated by two independent anti-BP-25 antisera. The 33-kD BP was also precipitated by both anti-BP-25 antisera, while the 23-kD BP was not precipitated by any of the antisera tested. Thus, BP-53 consists of a core protein of 28.7 kD which is differentially glycosylated in serum to form two BPs of 41.5 and 38 kD; these BPs circulate exclusively as part of the large BP-IGF complex. BP-25 circulates in the small BP-IGF complex as a nonglycosylated protein with an apparent mol wt of 28 kD.(ABSTRACT TRUNCATED AT 400 WORDS)


Development of Ir and La-codoped BaTa2O6 photocatalysts using visible light up to 640 nm as an H2-evolving photocatalyst for Z-schematic water splitting.
Ir and La-codoped BaTa2O6 was developed as a novel photocatalyst for H2 evolution utilizing visible light up to 640 nm. The Ir and La-codoped BaTa2O6 with a Ru cocatalyst functioned as an H2-evolving photocatalyst for Z-schematic water splitting under visible light irradiation upon combination with a BiVO4 O2-evolving photocatalyst and a [Co(bpy)3]3+/2+ electron mediator.


Alopecia areata: a clinical study.
100 cases of alopecia areata are examined and the possible relationship with the presumed etiological factors (atopy, autoimmunity and psychosomatics) are looked for. When atopy or autoantibodies are present alopecia areata always runs a serve course. It is, however, impossible to establish a definite etiological relation between atopy or autoimmunity and alopecia areata.


Development of a Comprehensive Trauma Training Curriculum for the Resource-Limited Environment.
The goal of this project was to create a multitiered trauma training curriculum that was designed specifically for the low-resource setting. We developed 2 courses designed to teach principles and skills necessary for trauma care. The first course, "Emergency Ward Management of Trauma (EWMT)," is designed to teach interns the initial assessment and stabilization of trauma patients in the emergency ward. The second course for mid-level surgical residents, "Surgical Techniques and Repairs in Trauma for the Low-resource Environment" (STaRTLE), is a cadaver-based operative trauma course designed to teach surgical exposures and techniques. The courses were rolled out at Mbarara Regional Referral Hospital in the low-income country of Uganda. Precourse and postcourse tests and surveys were administered. This study took place at Mbarara Regional Referral Hospital (MRRH). This is a hospital in southwest Uganda with a subspecialty care, a medical school, nursing school, and multiple residency programs. Students in the EWMT course were interns at MRRH. After 1 year of training, most of these interns will become medical officers as the only provider at a district hospital in Uganda. The students in the STARTLE course were second-year residents in the general surgery program at MRRH. Scores on knowledge based tests improved significantly with both courses. Survey results from the EWMT course suggest that participants feel better prepared to care for the injured patient (median Likert [IQR]: 5.0 [5.0-5.0]) and that their practice improved (5.0 [5.0-5.0]). Similarly, following the STaRTLE course we found participants felt significantly more comfortable with performing 20 of the 22 operative procedures taught. These courses represent a feasible, cost-effective, and resource appropriate trauma education curriculum that if standardized and implemented may improve trauma care and outcomes in the resource-limited setting.


The nature of the pi1 colour mechanism of W.S. Stiles.
The ppi1 colour mechanism was isolated by means of Stile's auxiliary field technique: that it is pi1 which is isolated is proven by both test and field action spectra. 2. The fundamental mechanisms of human trichromatic colour vision must satisfy Grassman's law of additivity. The hypothesis that pi1 is one of the three fundamentals is tested by experiments in which pairs (u1, u2) of monochromatic adapting fields are mixed 3. When two fields with wave-lengths in the neighbourhood of its primary mode (mu1, mu2 less than or equal to 500 nm) are combined, pi1 is field-additive, consistent with the hypothesis that this portion of the pi1 action spectrum is that of the short-wave-length-sensitive photoreceptors. 4. When a short-wave-length adaptation field (mu1 less than or equal to 500 nm) is mixed with a longer wave-length field (mu2 greater than or equal 550 nm) i1 is strongly non-additive. This result proves that the long-wave-length portion of the pi1 field spectrum is generated at least in part by a signal originating in the long- or middle-wave-length sensitive cones. 5. Analysis of the additivity failures supports a model of pi1 in which the signal to be detected is generated in the short-wave-length cones, and must pass serially through two gain stages: the gain in the first stage is controlled by the short-wave-length cones alone; the gain in the second stage is controlled by a signal originating in the middle, or long-wave-length cones, or both.


Insights into the spontaneous multi-scale supramolecular assembly in an ionic liquid-based extraction system.
Herein, we report a four-step mechanism for the spontaneous multi-scale supramolecular assembly (MSSA) process in a two-phase system concerning an ionic liquid (IL). The complex ions, elementary building blocks (EBBs), [EBB]n clusters and macroscopic assembly (MA) sphere are formed step by step. The porous large-sized [EBB]n clusters in the glassy state can hardly stay in the IL phase and they transfer to the IL-water interface due to both electroneutrality and amphiphilicity. Then, the clusters undergo random collision in the interface driven by the Marangoni effect and capillary force thereafter. Finally, a single MA sphere can be formed owing to supramolecular interactions. To our knowledge, this is the first example realizing spontaneous whole-process supramolecular assembly covering microscopic, mesoscopic and macroscopic scales in extraction systems. The concept of multi-scale selectivity (MSS) is therefore suggested and its mechanism is revealed. The selective separation and solidification of metal ions can be realized in a MSSA-based extraction system depending on MSS. In addition, insights into the physicochemical characteristics of ILs from microscopic, mesoscopic to macroscopic scales are provided, and especially, the solvation effect of ILs on the large-sized clusters leading to the phase-splitting is examined. It is quite important that the polarization of uranyl in its complex, the growing of uranyl clusters in an IL as well as the glassy material of uranyl are investigated systematically on the basis of both experiment and theoretical calculations in this work.


Efficacy of diethylcarbamazine and pirimiphos-methyl residual spraying in controlling brugian filariasis.
A control programme against subperiodic brugian filariasis was implemented in three villages, (Kg. Ampungan, Kg. Sebangkoi and Kg. Sebamban) in Sarawak, Malaysia. In Kampong Ampungan, the mass administration of diethylcarbamazine (DEC-citrate) combined with residual house spraying of pirimiphos-methyl reduced microfilarial rate to 8% of the pre-treatment level and microfilarial density (MfD50) to 44% of the pre-treatment level over a period of four years. In Kampong Sebangkoi and Kampong Sebamban, where only mass DEC therapy was applied, the microfilarial rate and MfD50 declined distinctly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. In Kg, Ampungan, we observed a significant reduction of infective biting rate (88.3%), infection rate (62.5%) and transmission potential (88.1%) of Mansonia bonneae at the fourth spray round. The corresponding reduction rates in Kg. Sebangkoi and Kg. Sebamban were 35.3%, 26.7%, 42.2% and 24%, 30.8% and 15.4% respectively. The biting density of the vector was reduced by 79.8% indoors and 31.8% outdoors at the sprayed village, while only a slight decrease in densities (17.9% indoors and 12.4% outdoors) was observed at the unsprayed village. Bioassay tests revealed that pirimiphos-methyl had a substantial fumigant effect on the vector. The integrated control measure in controlling subperiodic brugian filariasis is discussed.


Gold Nanotapes and Nanopinecones in a Quantitative Lateral Flow Assay for the Cancer Biomarker Carcinoembryonic Antigen.
Colorectal cancer is the third most common malignancy and the second leading cause of cancer death globally. Multiple studies have linked levels of carcinoembryonic antigen in patient serum to poor disease prognosis. Hence, the ability to detect low levels of carcinoembryonic antigen has applications in earlier disease diagnosis, assessment, and recurrence monitoring. Existing carcinoembryonic antigen detection methods often require multiple reagents, trained operators, or complex procedures. A method alleviating these issues is the lateral flow assay, a paper-based platform that allows the detection and quantification of target analytes in complex mixtures. The tests are rapid, are point-of-care, possess a long shelf life, and can be stored at ambient conditions, making them ideal for use in a range of settings. Although lateral flow assays typically use spherical gold nanoparticles to generate the classic red signal, recent literature has shown that alternate morphologies to spheres can improve the limit of detection. In this work, we report the application of alternative gold nanoparticle morphologies, gold nanotapes (∼35 nm in length) and gold nanopinecones (∼90 nm in diameter), in a lateral flow assay for carcinoembryonic antigen. In a comparative assay, gold nanopinecones exhibited a ∼2× improvement in the limit of detection compared to commercially available spherical gold nanoparticles for the same antibody loading and total gold content, whereas the number of gold nanopinecones in each test was ∼3.2× less. In the fully optimized test, a limit of detection of 14.4 pg/mL was obtained using the gold nanopinecones, representing a 24-fold improvement over the previously reported gold-nanoparticle-based carcinoembryonic antigen lateral flow assay.


Cusum analysis for learning curve of videothoracoscopic lobectomy.
Video assisted thoracoscopic (VATS) lobectomy has a demanding learning curve due to its technical complexity and risk of uncontrollable bleeding. We investigated the case number required for gaining technical proficiency by applying cumulative sum analysis on initial VATS lobectomy operations of a single surgeon. CALGB definition was used for the definition of VATS lobectomy. The data of the initial cases evaluated and cumulative sum (CUSUM) analysis was applied to duration of the operations and length of hospital stay. Fifty-eight patients underwent VATS lobectomy. Of those 51 were malignant and 7 were benign. Fifty-five of the procedures were lobectomy, 2 were inferior bi-lobectomy and 1 was left upper lobectomy with chest wall resection. CUSUM analysis reached to proficiency at 27 cases for duration of the operations. The length of learning curve depends on previous experience of the surgeon on open lobectomy and simpler VATS operations, potential number of VATS lobectomy cases and VATS capability of the surgeon. Depending on these factors, it is possible to obtain technical proficiency with an inferior number of procedures compared with existing literature (50-200).


Virtual Reality as Pain Relief in Burn Care: A Pilot Randomized Controlled Trial on the Effectiveness on Pain During Multiple Dressing Changes.
This pilot Randomized Controlled Trial (RCT) aimed to investigate the effectiveness of Virtual Reality (VR)-distraction on pain during multiple Wound Dressing Changes (WDCs). Furthermore, associations between demographic, clinical, and psychological factors and pain during WDC were determined. Participants were randomized to either the VR-condition or Care As Usual (CAU)-condition. Both groups received standard wound care and pain medication. The VR-group additionally received VR-distraction. The primary outcome measure was pain intensity (VAT 0-10). Secondary outcome measures were pain medication (Fentanyl spray and/or Piritramide) and satisfaction with WDC (VAT 0-10). Only 38 patients (VR-group: n = 21; CAU-group: n = 17) of the 128 intended patients were included during the study period due to several limitations (strict exclusion criteria and restrictions of the VR-equipment). No significant differences were found between both groups on pain intensity and medication. Both groups were also equally satisfied with WDC. Age showed a significant negative correlation with pain during WDC. In view of the small sample size, this study has restricted power and should be considered a pilot. Nevertheless, a RCT with between-subjects design across multiple WDCs was feasible and, given the speed of VR-developments, we expect larger, better powered RCTs to be possible in the near future, for which our experiences and recommendations are relevant.


Neurogenic thoracic outlet syndrome: When to consider the diagnosis and current management options.
Thoracic outlet syndrome (TOS) refers to a group of compressive disorders that occur in the thoracic outlet and can affect the brachial plexus, subclavian artery and vein. Neurogenic TOS (nTOS) is the most common form of TOS, accounting for approximately 97% of cases. nTOS and its resulting compressive brachial plexopathy can lead to potentially disabling symptoms and reduced quality of life. This article reviews the current literature on nTOS and summarises the pathophysiology, diagnostic pathways and the management options for nTOS. nTOS is an uncommon but disabling disorder with no single 'rule-in' test, often resulting in diagnostic delays and late referral. Initial management is non-operative with targeted physiotherapy. If this is unsuccessful, symptoms can be relieved with scalene botulinum toxin injections and surgical intervention.


The Decline of Physical Activity with Age in School-Aged Children with Cerebral Palsy: A Single-Center Cross-Sectional Observational Study.
Maintaining physical activity is important for children with cerebral palsy (CP). This study examined whether age predicted habitual physical activity (HPA) or cardiorespiratory fitness (CRF) in school-aged children with CP and clarified the relationship between HPA and CRF. We utilized cross-sectional data from 39 children with CP (18 girls and 21 boys; mean age 7.44 years; mean body weight 24.76 kg; mean body mass index 15.97 kg/m2; hemiplegic or diplegic CP). The participants wore an accelerometer (ActiGraph) for five days to measure HPA, physical activity energy expenditure (kcal/kg/d), sedentary physical activity (%SPA), light physical activity, moderate-to-vigorous physical activity (%MVPA), and activity counts (counts/min). Participants underwent cardiopulmonary exercise tests on a treadmill using a modified Naughton protocol. Linear regression and correlation analyses were performed. p-value (two-tailed) < 0.05 was considered statistically significant. Age was positively associated with SPA. MVPA negatively correlated with resting heart rate (HR), and activity counts were negatively correlated with resting HR. In conclusion, our study found strong evidence of a negative association between HPA and age in school-aged children with CP. It highlights the importance of creating and improving recreational opportunities that promote physical activity in all children with CP, regardless of whether they are considered therapeutic.


DNA polymorphisms in the psi beta 1- and beta-globin gene regions in Asian macaques.
DNA polymorphisms in the psi beta 1-beta-globin gene region in nine Asian macaques (Macaca fuscata, M. mulatta, M. nemestrina, M. cyclopis, M. fascicularis, M. arctoides, M. radiata, M. maura, and M. assamensis) were examined using several restriction endonucleasese and the human psi beta 1, delta IVS2, and beta IVS2 probes. The BamHI site 3' to the beta-globin gene was polymorphic in M. fuscata and M. mulatta, while the HincII site and the EcoRI site in the psi beta 1-globin gene region was highly polymorphic in M. fuscata and M. mulatta, respectively. These polymorphic sites also seem to be present in other Asian macaques. The present study of the polymorphism at the BamHI site 3' to the beta-globin gene in Asian macaques supports, at the nuclear DNA level, the idea that the fascicularis group including M. fuscata, M. mulatta, M. cyclopis, and M. fascicularis is different from other Asian macaque groups.


The Aryne-Abramov Reaction as a 1,2-Benzdiyne Platform for the Generation and Solvent-Dependent Trapping of 3-Phosphonyl Benzynes.
Synthetic methodology utilizing two aryne intermediates (i.e., a formal benzdiyne) enables the rapid generation of structurally complex molecules with diverse functionality. This report describes the sequential generation of two ortho-benzyne intermediates for the synthesis of 2,3-disubstituted aryl phosphonates. Aryl phosphonates have proven useful in medicinal chemistry and materials science, and the reported methodology provides a two-step route to functionally dense variants by way of 3-phosphonyl benzyne intermediates. The process begins with regioselective trapping of a 3-trifloxybenzyne intermediate by an O-silyl phosphite in an Abramov-like reaction to bond the strained Csp carbons with phosphorus and silicon. Standard aryne-generating conditions follow to convert the resulting 2-silylphenyl triflate into a 3-phosphonyl benzyne, which readily reacts with numerous aryne trapping reactants to form a variety of 2,3-difunctionalized aryl phosphonate products. DFT computational studies shed light on important mechanistic details and revealed that 3-phosphonyl benzynes are highly polarizable. Specifically, the distortion in the internal bond angles at each of the Csp atoms was strongly influenced by both the electronegativity of the phosphonate ester groups as well as the dielectric of the computational solvation model. These effects were verified experimentally as the regioselectivity of benzyl azide trapping increased with more electronegative esters and/or increasingly polar solvents. Conversely, replacing the conventional solvent, acetonitrile, with nonpolar alternatives provided attenuated or even inverted selectivities. Overall, these studies showcase new reactivity of benzyne intermediates and extend the aryne relay methodology to include organophosphonates. Furthermore, this work demonstrates that the regioselectivity of aryne trapping reactions could be tuned by simply changing the solvent.


Using copy milling technology in restorative dentistry.
A technique for the fabrication of copy milled ceramic restorations has been presented. Both direct and indirect fabrication techniques of inlays, onlays, veneers, and crowns are possible. A copy milling machine can mill accurately fitting restorations with a marginal gap of 50 microns. The machine uses premanufactured porcelain blanks, which have improved physical properties over conventional porcelains used in standard techniques. Recently, the ability to mill In-Ceram crowns from presintered alumina blocks and Spinell crowns from alumina/magnesia blocks has been added to the system. The copings are veneered with aluminous porcelain as in the conventional In-Ceram technique.


Embryonic poly(A)-binding protein is differently expressed and interacts with the messenger RNAs in the mouse oocytes and early embryos.
The embryonic poly(A)-binding protein (EPAB) functions in the translational regulation of the maternal messenger RNAs (mRNAs) required during oocyte maturation, fertilization, and early embryo development. Since there is no antibody specific to mammalian EPAB protein, all studies related to the Epab gene could be performed at the mRNA levels except for the investigations in the Xenopus. In this study, we have produced an EPAB-specific antibody. When we examined its expressional distribution in the mouse gonadal and somatic tissues, the EPAB protein was found to be expressed only in the mouse ovary and testis tissues, but it is undetectable level in the somatic tissues including stomach, liver, heart, small intestine, and kidney. Additionally, the spatial and temporal expression patterns of the EPAB and poly(A)-binding protein cytoplasmic 1 (PABPC1) proteins were analyzed in the mouse germinal vesicle (GV) and metaphase II (MII) oocytes, one-cell, and two-cell embryos. While EPAB expression gradually decreased from GV oocytes to two-cell embryos, the PABPC1 protein level progressively increased from GV oocytes to one-cell embryos and remarkably declined in the two-cell embryos ( P < 0.05). We have also described herein that the EPAB protein interacted with Epab, Pabpc1, Ccnb1, Gdf9, and Bmp15 mRNAs dependent upon the developmental stages of the mouse oocytes and early embryos. As a result, we have first produced an EPAB-specific antibody and characterized its expression patterns and interacting mRNAs in the mouse oocytes and early embryos. The findings suggest that EPAB in cooperation with PABPC1 implicate in the translational control of maternal mRNAs during oogenesis and early embryo development.


Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction.
A high-performance liquid chromatography (HPLC) assay was developed for the determination of estazolam in human plasma. Estazolam and alprazolam as an internal standard were detected by ultraviolet absorbance at 240 nm. Estazolam in plasma was extracted by a rapid and simple procedure based on cyanopropyl bonded-phase extraction. Chromatographic separation was achieved with a reversed-phase C8-5 column using a mobile phase of 0.5% potassium dihydrogenphosphate(pH 4.5)-acetonitrile (70:30, v/v). The determination of estazolam was possible in the concentration range of 1.0 - 200.0 ng/mL. The mean recovery of estazolam added to plasma was 96.1 +/- 1.5% with coefficients of variation of less than 5.5%. This method is applicable for accurately monitoring the plasma level of estazolam in healthy subjects participating in scientific research.


The Synthetization and Analysis of Dicyclopentadiene and Ethylidene-Norbornene Microcapsule Systems.
The activities of this paper were focused on an in-situ fabrication process for producing two self-healing systems containing dicyclopentadiene and 5-ethylidene-2-norbornene monomers encapsulated in a urea-formaldehyde shell and integration methods applied in the epoxy matrix to analyse and compare the influences of their integration into the neat epoxy matrix. The self-healing systems were first synthesized according to a literature review, and subsequently, an optimization process was conducted for the fabrication process. Neat epoxy specimens were fabricated as reference specimens and subjected to flexural tests. Several integration methods for incorporating the self-healing systems into the epoxy resin were investigated. The optimal method presenting the best dispersion of the healing system was achieved by reducing the viscosity of the epoxy matrix with 10 vol % acetone solution, the addition of a microcapsule in the matrix, and homogenization at 60 °C at 100 rpm. Thermal analysis was performed in order to observe the mass loss obtained with an increasing temperature and phase changes for both poly-urea-formaldehyde (PUF)-dicyclopentadiene (DCPD) and melamine-urea-formaldehyde (MUF)-5-ethylidene-2-norbornene (ENB) systems. The thermogravimetric analysis performed for the PUF-DCPD system indicates a total loss of mass in the range of 30-500 °C of 72.604% and for the MUF-ENB system, indicates a total mass loss in the range of 30-500 °C of 74.093%. Three-point bending tests showed higher mechanical properties for PUF-DCPD (80%) than MUF-ENB (40%) compared to the neat epoxy systems. Numerical simulations were performed to obtain a better understanding of the microcapsule behavior when embedded in an epoxy matrix.


Evaluation of captopril for the management of hypertension in autonomic dysreflexia: a pilot study.
To evaluate the efficacy of captopril for management of hypertensive urgencies in autonomic dysreflexia. A 1-year, prospective, open-label pilot study. Rehabilitation hospital. Twenty-six consecutive patients older than 15 years with spinal cord injury above T6. During an autonomic dysreflexia episode, captopril 25mg was administered sublingually if systolic blood pressure (SBP) was at or above 150mmHg despite the use of nondrug measures. If SBP remained elevated 30 minutes after captopril administration, 1 dose of immediate-release nifedipine 5mg was given as rescue by the bite and swallow method and repeated, if necessary, in 15 minutes. SBP 30 minutes after captopril administration at initial autonomic dysreflexia episode. A total of 33 autonomic dysreflexia episodes were documented, of which 18 episodes in 5 patients were treated with drug therapy. Captopril alone was effective in 4 of 5 initial episodes (80%). Mean SBPs at baseline and 30 minutes after captopril were 178+/-18mmHg and 133+/-28mmHg, respectively. There were no cases of reactive hypotension. The addition of nifedipine successfully reduced SBP in the remaining patient. Of the combined 18 initial and repeat autonomic dysreflexia episodes, 94% were successfully treated with our protocol. Captopril appears to be safe and effective for autonomic dysreflexia management.


A secure method of nasal endotracheal tube stabilization with suture and rubber tube.
A new method of stabilizing the nasal endotrascheal tube was described. The tube was secured to the anterior portion of the nasal septum with braided silk thread, which was tightened over the rubber tube to keep air route of the cuff open. There found no complications such as unplanned extubation, necrosis and infections of the nasal septum.


[(11)C] Carbon monoxide in selenium-mediated synthesis of (11)C-carbamoyl compounds.
Using either amines, amino alcohols, or alcohols in selenium-mediated synthesis with [(11)C]carbon monoxide, 3 ureas, 6 carbamates, and 1 carbonate were labeled. Tetrabutylammonium fluoride ((TBA)F) was discovered to form a soluble and reactive complex with selenium and drastically increase the radiochemical yields. Of the selected carbamoyl compounds, one was a receptor ligand, one was an enzyme inhibitor, and one was a muscular relaxant pharmaceutical. The (11)C-target compounds were obtained in radiochemical yields ranging from low to almost quantitative and with specific radioactivity up to 1300 GBq/micromol. The radiochemical purity of the final products exceeded 98%. In one case, the corresponding (13)C-substituted compound was produced to verify the position of the (11)C-label. In a typical experiment starting with 16.4 GBq [(11)C]carbon monoxide, 7.0 GBq of LC-purified 5-phenyl-1,3-oxazolidin-[2-(11)C]-2-one was obtained within 20 min from start of the carbonylation reaction (84% decay-corrected radiochemical yield). The presented approach is an interesting alternative to the use of [(11)C]phosgene in labeling chemistry.


Termite-Susceptible Species of Wood for Inclusion as a Reference in Indonesian Standardized Laboratory Testing.
Standardized laboratory testing of wood and wood-based products against subterranean termites in Indonesia (SNI 01.7207-2006) (SNI) has no requirement for the inclusion of a comparative reference species of wood (reference control). This is considered a weakness of the Indonesian standard. Consequently, a study was undertaken to identify a suitable Indonesian species of community wood that could be used as a reference control. Four candidate species of community woods: Acacia mangium, Hevea brasiliensis, Paraserianthes falcataria and Pinus merkusii were selected for testing their susceptibility to feeding by Coptotermes formosanus. Two testing methods (SNI and the Japanese standard method JIS K 1571-2004) were used to compare the susceptibility of each species of wood. Included in the study was Cryptomeria japonica, the reference control specified in the Japanese standard. The results of the study indicated that P. merkusii is a suitable reference species of wood for inclusion in laboratory tests against subterranean termites, conducted in accordance with the Indonesian standard (SNI 01.7207-2006).


Vaccine-hesitant families are more susceptible to verbal communication messaging.
Our survey aims to highlight parents' and healthcare workers' opinions and hesitations regarding children's vaccination, identify the main factors influencing these opinions, and assess the impact of hesitations on immunisation for children, included in the National Immunisation Programme in Lithuania. We used the questionnaire developed by the European Academy of Paediatrics Research in Ambulatory Settings Network (EAPRASnet). This questionnaire is designed to assess attitudes toward vaccination. The study involved parents raising children aged 1-4 years and primary healthcare providers (paediatricians, family doctors and nurses). We analysed the completed questionnaires from a total of 329 parents (142 fathers, 187 mothers) and 386 medical personnel (150 physicians, 236 nurses). Most parents expressed positive opinions about vaccines (> 8 points out of 10 possible), with older parents exhibiting more favourable attitudes. Compared to mothers, fathers showed more criticism regarding the information provided by physicians (p = 0.04). Family doctors and paediatricians were more supportive of vaccination than nurses and homoeopaths (p < 0.001). Parents and healthcare providers with higher education showed statistically significantly stronger opinions about the benefits of vaccines than those with lower education levels (p = 0.01 for parents, p < 0.001 for physicians and nurses). The Internet was identified as the primary source of negative information for both parents (69.6%) and healthcare providers (86%). However, verbal information received from medical staff during patient consultations or informal conversations among colleagues had the greatest impact on parents' opinions (17.3%) and medical personnel (35.5%). Confidential conversations with physicians and nurses remain the most trustworthy sources of information and influential factors shaping opinions. The Internet serves as the primary source of inaccurate information about vaccinations for both parents and medical professionals, although verbal information from primary healthcare providers has a more significant impact on vaccination attitudes. Discrepancies in basic education and specific knowledge about vaccination within the same family can pose additional obstacles to child vaccination.


Arsenic trioxide synergizes with B7H3-mediated immunotherapy to eradicate hepatocellular carcinomas.
Arsenic trioxide (As(2)O(3)), a valuable anticancer drug for the treatment of acute promyelocytic leukemia, may also have therapeutic potential for the treatment of solid tumors. However, its therapeutic efficacy against solid tumors is lacking even at high dosages. Other therapeutic strategies are required to enhance the efficacy of As(2)O(3) against solid tumors such as hepatocellular carcinoma (HCC), which is refractory to chemotherapy. B7H3, a new member of the B7 family, has been shown to induce antitumor immunity. Intratumoral injection of B7H3 plasmids eradicates small EL-4 lymphomas, but monotherapy is ineffective against large tumors. Here we investigated whether As(2)O(3) would synergize with B7H3 immunotherapy to combat HCC. Large subcutaneous H22 HCCs (0.7-0.8 cm in diameter) established in BALB/c mice were rapidly and completely eradicated when intratumoral administration of As(2)O(3) was preceded by in situ gene transfer of B7H3. In contrast, neither As(2)O(3) nor B7H3 monotherapy was effective. The antitumor activity of As(2)O(3) was attributed to increased tumor-cell apoptosis, perhaps as a result of direct cytotoxicity as well as decreased tumor angiogenesis. Combination therapy generated potent systemic antitumor immunity mediated by CD8(+) and NK cells that was effective in combating a systemic challenge of 1 x 10(7) parental H22 cells. It led to the simultaneous and complete regression of multiple distant tumor nodules, concomitant with increased levels of serum IFN-gamma and cytotoxic T lymphocyte (CTL) activity. In conclusion, combining B7H3-mediated immunotherapy with As(2)O(3) warrants investigation as a therapeutic strategy to combat HCC, and other malignancies.


[Uptake HTO from seawater by seashell and formative dynamics of bound tritium in seashell].
Uptake HTO from seawater by five kinds seashell and formative dynamics of bound tritium in organ of seashell are studied by using the isotope-tracer techniques in order to get a better understanding of the marine environmental behavior of HTO. The results show that the tritium in seashell exists in free water tritium and bound tritium form. The free water tritium is main form; its content observed was more than 97.4% of total tritium. The bound tritium content was very lower, only being 0.4% - 2.6% in total tritium. The speed of HTO untaken by seashell is very rapid, specific activity of HTO in three kinds seashell had reached their maximum only 2 h after treatment. The bound tritium in seashell increases slowly with time. The results of analysis of concentration factor (CF) values indicate that HTO would not concentrate in the seashell.


Central Microscotoma: A Rare Presentation of Epiretinal Membranes.
Patients with a symptomatic epiretinal membrane (ERM) typically complain of metamorphopsia and decreased visual acuity. We describe three patients who presented with the single complaint of a central microscotoma due to ERM, an infrequent initial symptom of this entity. This is a retrospective, interventional, non-comparative case series. Three patients with the chief complaint of a central microscotoma related to ERMs who underwent pars plana vitrectomy by a single surgeon experienced full resolution of the preoperative microscotoma. Best-corrected visual acuity, fundus photography, and optical coherence tomography were obtained at each examination. A comprehensive neuro-ophthalmologic evaluation was performed in all cases, including magnetic resonance imaging of the orbits and brain, automated visual fields, multifocal electroretinography, multifocal visually evoked potentials, and blood tests. Three eyes of three patients who presented with the initial sole complaint of a central microscotoma due to ERM are included in this series. A comprehensive neuro-ophthalmologic evaluation ruled out non-retinal etiologies. After months of observation, a pars plana vitrectomy with ERM and internal limiting membrane peeling was performed in all patients. Postoperatively, the patients experienced a complete resolution of their initial, isolated complaint of a central microscotoma. Central microscotoma, as a rare stand-alone presentation of ERM, is described. This symptom resolved after a successful removal of the ERM. A greater awareness among clinicians that ERMs may present in this manner may help avoid excessive and costly medical evaluations.


Vascular homeostasis and angiogenesis determine therapeutic effectiveness in type 2 diabetes.
Under common practice, recognition and treatment of type 2 diabetic nephropathy (DN) are usually revealed at a rather late stage (CKD stages 3-5) due to the insensitiveness of available diagnostic markers. Accumulating data obtained from vascular homeostasis in late stage DN demonstrated (1) a defective angiogenesis and impaired NO production which explains the therapeutic resistance to vasodilators and the inability to correct chronic renal ischemia and (2) an abnormally elevated antiangiogenesis and a progressive vascular disease which correlates with the altered renal hemodynamics characterized by a progressive reduction in renal perfusion as the disease severity progressed. In contract, the vascular homeostasis is adequately functional in early stage DN. Thus, vasodilator treatment at early stage DN (CKD stages 1-2) can enhance renal perfusion, correct the renal ischemia, and restore renal function.


Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein.
The most severe form of congenital adrenal hyperplasia (CAH) is lipoid CAH. It was once thought that this disease was due to mutations in the cholesterol side-chain cleavage enzyme system, thus eliminating the ability to convert cholesterol to pregnenolone, causing a complete absence of steroid hormone production. We recently showed that lipoid CAH is due to mutations in the steroidogenic acute regulatory (StAR) protein, thus preventing acutely stimulated adrenal and gonadal responses to tropic stimulation. However, this lesion may permit low levels of StAR-independent steroidogenesis to persist until the accumulation of intracellular lipid deposits destroys steroidogenic capacity. This model would predict that the steroidogenic cells of the ovaries of affected 46,XX females should remain undamaged until puberty, at which time low levels of StAR-independent estrogen biosynthesis should be detectable. We describe a 15.5-yr-old 46,XX female with a classic history of lipoid CAH who underwent spontaneous feminization and cyclical vaginal bleeding beginning at age 13. Genetic analysis of the patient and her parents showed that she was homozygous for the novel StAR frameshift mutation 261delT. This is the first adolescent female with lipoid CAH who has undergone spontaneous feminization and who has been analyzed genetically. Finding an inactive StAR gene in this patient confirms our two-hit model of the pathogenesis of lipoid CAH, in which loss of StAR activity initially preserves StAR-independent steroidogenesis, which is lost only after cells undergo chronic tropic stimulation and subsequent damage from accumulation of cholesterol esters.


Effect of robotic versus laparoscopic surgery on postoperative wound infection in patients with cervical cancer: A meta-analysis.
The objective of this research is to evaluate the risk of postoperative infection and other risks associated with robotic radical hysterectomy (RRH) compared with laparoscopic radical hysterectomy (LRH). Recent studies on RRH versus LRH have not been conclusive for cervical carcinoma. Our group attempted to use meta-analyses to evaluate the effects of both RRH and LRH on postoperative outcomes in order to make sure that the best operative method was used to prevent wound infections. We looked up Cochrane Library and published databases for this research and found 594 findings. Articles were screened by title and abstract and then carefully examined for inclusion and exclusion criteria. Data extraction was performed independently by two researchers. Comparison studies were used to describe the incidence of wound complications after surgery. The publication bias was assessed using Egger regression correlation analysis. There were six trials eligible for inclusion, of which 491 RRH and 807 LRH. Depending on surgery for cervical carcinoma, it is true that there is a difference in the way that surgery affects the postoperative complications. Our analysis demonstrated that the use of robotic operation can decrease the amount of blood loss during operation as compared with routine laparoscopy (MD, -77.69; 95% CI, -132.08, -23.30; p = 0.005). However, there were no statistical differences in the incidence of postoperative wound infections (OR, 0.54; 95% CI, 0.25, 1.19; p = 0.13) and intraoperative operative time (MD, 13.01; 95% CI, -41.38, 67.41; p = 0.64) among the two procedures. There was no statistically significant difference between these two groups of patients with severe postoperative complications. Unlike other research, the findings of this meta-analysis are not consistent with the findings of the present study, which suggest that robotic operations cannot lower the rate of postoperative wound infections. However, because of the limitations and the retrospective character of the trials covered, these findings should be interpreted with care and more extensive research is required.


Progression of fibrosis in untreated patients with hepatitis C virus infection.
In order to evaluate the progression of liver fibrosis associated with Hepatitis C virus (HCV) infection, two liver biopsy specimens obtained prior to antiviral therapy from 98 patients with HCV were scored and evaluated using statistical methods appropriate for ordered categorical data. Greater progression of fibrosis was seen with increasing time between the biopsies. Likewise, the change in fibrosis score was significantly more pronounced in the 11 patients whose first biopsy was obtained within the first year after acquiring HCV. A multivariate logistic regression analysis of possible explanatory factors for the fibrosis outcome showed that interface hepatitis in both biopsies, the time interval between the biopsies, and age at first biopsy were associated with change in the fibrosis score. In addition we found that higher age at the time of infection was associated with development of cirrhosis, that moderate intake of alcohol was associated with fibrosis progression, and that an inflammatory response in the form of moderate interface hepatitis in the first biopsy was not necessarily associated with greater progression of fibrosis if the second biopsy showed mild interface hepatitis. However, having moderate interface hepatitis later in the course of infection as reflected by the second biopsy may be detrimental. If moderate interface hepatitis early in the course of the disease is followed by less interface hepatitis later there is less fibrosis; and if moderate interface hepatitis persists, there is more fibrosis eventually.


Esophageal perforation--associated risk with balloon tamponade after endoscopic therapy. Myth or reality?
Variceal bleeding is still associated with high mortality and balloon tamponade may be a lifesaving measure when endoscopic therapy is not available or feasible. The risk of esophageal perforation with balloon tamponade after endoscopic therapy is still uncertain. The aims of the study were to investigate balloon tamponade effectiveness and safety after endoscopic therapy. Retrospective analysis of 100 consecutive episodes of acute variceal bleeding treated with the Sengstaken-Blakemore tube. Balloon tamponade had an overall effectiveness of 61%. The Child-Pugh score was significantly higher in patients who failed balloon tamponade. In 48 cases balloon tamponade was preceded by failure of endoscopic therapy. Balloon tamponade was more effective if a previous attempt to perform endoscopic therapy happened (75% vs. 48%; p = 0.006). Aspiration was the most frequent complication. No cases of esophageal perforation were registered. Currently balloon tamponade is only used as a temporary bridge to other strategies, when other forms of hemostatic therapies do not succeed. Balloon tamponade was more effective in patients with less severe hepatic dysfunction. Previous attempts to perform endoscopic therapy may augment tamponade effectiveness without increasing the risk of esophageal perforation.


Dynamic Loss for Robust Learning.
Label noise and class imbalance are common challenges encountered in real-world datasets. Existing approaches for robust learning often focus on addressing either label noise or class imbalance individually, resulting in suboptimal performance when both biases are present. To bridge this gap, this work introduces a novel meta-learning-based dynamic loss that adapts the objective functions during the training process to effectively learn a classifier from long-tailed noisy data. Specifically, our dynamic loss consists of two components: a label corrector and a margin generator. The label corrector is responsible for correcting noisy labels, while the margin generator generates per-class classification margins by capturing the underlying data distribution and the learning state of the classifier. In addition, we employ a hierarchical sampling strategy that enriches a small amount of unbiased metadata with diverse and challenging samples. This enables the joint optimization of the two components in the dynamic loss through meta-learning, allowing the classifier to effectively adapt to clean and balanced test data. Extensive experiments conducted on multiple real-world and synthetic datasets with various types of data biases, including CIFAR-10/100, Animal-10N, ImageNet-LT, and Webvision, demonstrate that our method achieves state-of-the-art accuracy.