Epilepsy at a summer camp for children and young adults with developmental disabilities: a 3-year experience.
The comprehensive care of children with epilepsy involves not only the treatment of seizures but also enhancement of their quality of life. Children with developmental disabilities are often unable to attend traditional summer camps because of safety concerns, as their prevalence of epilepsy is high and tends to be more severe. The goal of the current study is to describe our epilepsy experience at a summer camp adapted for children with developmental disabilities, with which the U. S. military has had a long-standing relationship. A retrospective chart review of all children and young adults attending summer sessions between 2008 and 2010 was performed. A total of 1,526 camp sessions were attended by 818 campers (mean 13.7 years), with 32.3% of campers having epilepsy. Of campers with epilepsy, 46.6% had cerebral palsy, 57.6% intellectual disability, and 28.8% autism spectrum disorders. Seizure frequency was at least weekly in 21.2% and at least daily in 13.3%. A history of status epilepticus was reported in 34.9%. There were seven camp infirmary visits because of seizures (incidence 1.4%), including two for status epilepticus. Thus, despite a high prevalence of severe epilepsy, in the setting of appropriate safety precautions, a safe camp experience can be provided, as seizure-related complications are rare.


Cost Analysis of Cervical Cancer Patients with Different Medical Payment Modes Based on Gamma Model within a Grade A Tertiary Hospital.
Cervical cancer shows a growing incidence and medical cost in recent years that has increased severe financial pressure on patients and medical insurance institutions. This study aimed to investigate the medical economic characteristics of cervical cancer patients with different payment modes within a Grade A tertiary hospital to provide evidence and suggestions for inpatient cost control and to verify the application of Gamma model in medical cost analysis. The basic and cost information of cervical cancer cases within a Grade A tertiary hospital in the year 2011-2016 were collected. The Gamma model was adopted to analyze the differences in each cost item between medical insured patient and uninsured patients. Meanwhile, the marginal means of different cost items were calculated to estimate the influence of payment modes toward different medical cost items among cervical cancer patients in the study. A total of 1321 inpatients with cervical cancer between the 2011 and 2016 were collected through the medical records system. Of the 1321 cases, 65.9% accounted for medical insured patients and 34.1% were uninsured patients. The total inpatient medical expenditure of insured patients was RMB 29,509.1 Yuan and uninsured patients was RMB 22,114.3 Yuan, respectively. Payment modes, therapeutic options as well as the recurrence and metastasis of tumor toward the inpatient medical expenditures between the two groups were statistically significant. To the specifics, drug costs accounted for 37.7% and 33.8% of the total, surgery costs accounted for 21.5% and 25.5%, treatment costs accounted for 18.7% and 16.4%, whereas the costs of imaging and laboratory examinations accounted for 16.4% and 15.2% for the insured patient and uninsured patients, respectively. As the effects of covariates were controlled, the total hospitalization costs, drug costs, treatment costs as well as imaging and laboratory examination costs showed statistical significance. The total hospitalization costs, drug costs, treatment costs as well as imaging and laboratory examination costs of insured patient were 1.33, 1.42, 1.52, and 1.44 times of uninsured patients. The analysis of different payment modes toward the medical economic characteristics based on Gamma model is basically rational. Medical payment modes are having certain influence toward the hospitalization expenses of cervical cancer patients in an extent, as drug costs, treatment costs, and examination costs appear to be the main causes.


Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality.
Gastrointestinal complications after kidney transplantation are associated with inferior graft outcomes. We examined the incidence, risk factors, and outcomes of posttransplantation diarrhea. Historic cohort study. We examined first kidney transplant recipients in the United States from 1995 to 2002, with follow-up through December 2002. Recipients of multiple organs were excluded. We limited our study population to Medicare beneficiaries. Recipient, donor, and transplant characteristics were ascertained by means of US Renal Data System database inquiry. Incidence of diarrhea, graft loss, and death after transplantation. First episodes of diarrhea after transplantation were ascertained by using International Classification of Disease, Ninth Revision, Clinical Modification codes using Medicare billing data. Cause of diarrhea was classified as infectious or not and according to specific cause. Graft loss and death were ascertained from the date of the first diarrhea episode. We enrolled 41,442 patients. Mean follow-up was 758 +/- 399 days. We observed 7,103 diarrhea cases and 8,104 graft losses (4,201 deaths). The 3-year cumulative incidence of diarrhea was 22%, with 18% diagnosed as noninfectious diarrhea with an unspecified cause. Using multivariate Cox proportional hazards analysis, factors associated with increased risk of unspecified noninfectious diarrhea were female sex (hazard ratio [HR], 1.40; 95% confidence interval, 1.33 to 1.48), type 1 diabetes (HR, 1.20; 95% confidence interval, 1.06 to 1.37), and regimens containing tacrolimus and mycophenolate mofetil (HR, 1.37; 95% confidence interval, 1.28 to 1.46). Unspecified noninfectious diarrhea was associated with increased risk of graft failure (HR, 2.13; 95% confidence interval, 1.98 to 2.28) and patient death (HR, 2.04; 95% confidence interval, 1.85 to 2.24). Use of claims data to ascertain patient characteristics and events; inability to make causal inference based on retrospective designs. Regimens containing tacrolimus and mycophenolate mofetil were associated with increased risk of noninfectious diarrhea. Episodes of noninfectious diarrhea doubled the hazard of graft loss and patient death.


Client-centered case management. A survey of state programs.
With funding from the Administration on Aging, the National Resource Center: Diversity and Long-Term Care surveyed state administrators of programs serving elders in 24 states in 1994. This survey sought to document what written guidelines and training case managers receive in promoting client autonomy in care planning. In discussions with respondents and review of written materials provided by the states, surveyors explored whether clients received written information about services, the structure for seeking client input into care planning, and the structure for soliciting client feedback once the care plan was in place. Of the states included in this survey, few have developed and implemented guidelines or provide case managers training to promote client autonomy in the care-planning process. After reviewing the survey findings, the authors make two policy recommendations for states to consider in this area.


Congenital myasthenic syndrome due to homozygous CHRNE mutations: report of patients in Arabia.
We describe the clinical characteristics of 3 siblings from 1 family with congenital myasthenic syndrome due to homozygous mutations of the gene coding for the epsilon subunit of the acetylcholine receptor (CHRNE). Onset of symptoms occurred in the first few months of life with ptosis, restricted ocular motility, mild proximal weakness, and difficulty swallowing. Multiple hospital admissions were required due to recurrent pulmonary infections. There was no decremental conduction on repetitive nerve stimulation, but jitter was increased on single fiber electromyographic. Since early childhood, our patients have done well without pulmonary or bulbar symptoms and with partial improvement on pyridostigmine therapy. Response of ptosis to diagnostic ice pack test was striking. Although these siblings have a clinical history and examination findings typical of homozygous CHRNE mutations, the clinical presentation of congenital myasthenia subtypes is variable, and accurate genotyping is essential in choosing the appropriate treatment.


Gene expression of the neurotrophic pigment epithelium-derived factor in the human ciliary epithelium. Synthesis and secretion into the aqueous humor.
To study the expression of the neurotrophic pigment epithelium-derived factor (PEDF), a protein with neurotrophic and neuronal-survival activities, by the human ocular ciliary epithelium. Total RNA extracted from human and bovine ocular tissues were screened by Northern blot analysis with cDNA probes for PEDF. Antibodies to PEDF were used to monitor its synthesis and secretion by metabolically labeling ciliary processes in vitro with 35S-methionine, followed by immunoprecipitation. Pigment epithelium-derived factor antibodies also were used to visualize the cellular distribution of PEDF along the human and bovine ciliary epithelium. Polymerase chain reaction (PCR) and reverse transcription (RT)-PCR was used to screen cDNA libraries of tissue and cell lines derived from the ciliary epithelium to demonstrate PEDF expression. From a subtractive library of the human ocular ciliary body, the authors identified a cDNA clone exhibiting nucleotide homology with the PEDF. Northern blot analysis indicated that PEDF transcripts are present in all the ocular tissues in the human eye; in the bovine eye, it is expressed preferentially in the retinal pigment epithelium. RT-PCR and PCR demonstrated that the PEDF gene is still transcriptionally active in cultured cell lines derived from the bilayer of the ciliary epithelium. Immunoprecipitation and Western blot (immunoblot) analyses with antisera to the PEDF protein demonstrated that a predominant PEDF form of 46 kDa is synthesized in the ciliary body and is secreted as a glycoprotein of 50 kDa. By indirect immunofluorescence and immunocytochemistry, PEDF antibodies decorated both cell types that comprise the ciliary epithelium (nonpigmented and pigmented) and, more distinctively, the plasma-membrane domain of nonpigmented cells in the pars plicata region. These results reveal a new site of synthesis (ciliary epithelium) and accumulation (aqueous humor) of PEDF, and they emphasize its potential importance as a trophic factor in the neuro-differentiated functions of the human ciliary epithelium.


The Clinical Implication of Blood Product Transfusion on Morbidity and Mortality of Ruptured Abdominal Aortic Aneurysm.
Transfusion of blood products occurs frequently in ruptured abdominal aortic aneurysm surgery (rAAA). The aim of this study is to establish the impact of packed red blood cell (PRBC), fresh frozen plasma (FFP), and platelet (PLT) transfusion on the 30-day mortality and morbidity (thrombotic versus non thrombotic complications) of rAAAs. A retrospective study of 90 consecutive rAAAs from November 2007 to June 2015 was conducted. Multivariable regression models were produced to determine blood products associated with 30-day morbidity and mortality post-rAAA. The overall mortality was 14.6%. At multivariable analyses, transfusion with FFP (>3 units) was independently associated with an increased risk of mortality (odds ratio [OR]: 11.27, 95% confidence interval [CI]: 1.13-96.72, P = .027). The overall morbidity was 26.8%, and subgroup analysis (thrombotic vs nonthrombotic complications) demonstrated transfusion of PLTs (>1 pool) to be independently associated with thrombotic events (OR: 4.3, 95% CI: 1.37-13.6, P = .012). Thrombotic events were responsible for 50% (n = 11 of 22) of all morbidities and mortalities (n = 6 of 12). Transfusion of FFP and PLTs may be associated with an increased risk of postoperative morbidity and mortality. The use of these blood components should be considered in the context of the patient's clinical and laboratory data as opposed to a fixed ratio to PRBCs. This may result in the reduction in thrombotic complications emerging in rAAA cohort.


Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?
Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed. In this context, we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid (GLR), a drug used to treat liver diseases (including viral hepatitis) and specific cutaneous inflammation (such as atopic dermatitis) in some countries. The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed. GLR has shown activities against different viruses, including SARS-associated Human and animal coronaviruses. GLR is a non-hemolytic saponin and a potent immuno-active anti-inflammatory agent which displays both cytoplasmic and membrane effects. At the membrane level, GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells. At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1. We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR. The membrane and cytoplasmic effects of GLR, coupled with its long-established medical use as a relatively safe drug, make GLR a good candidate to be tested against the SARS-CoV-2 coronavirus, alone and in combination with other drugs. The rational supporting combinations with (hydroxy)chloroquine and tenofovir (two drugs active against SARS-CoV-2) is also discussed. Based on this analysis, we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19.


[Merosin-positive congenital muscular dystrophy, white matter abnormalities, and bilateral posterior occipital cortical dysplasia].
Congenital muscular dystrophy (CMD) is one of the most frequent dystrophies of childhood, which is commonly characterized by neonatal muscle impairment with or without clinical evidence of central nervous system involvement. CMDs were classified into five clinically distinct forms: the two classical CMDs with and without deficit of the a2 laminin chain (merosin) caused by mutations on chromosome 6q2, the Fukuyama CMD (severe form, initially described in Japanese patients and recently linked to the chromosome 9q31-33), Walker-Warburg syndrome and the muscle-eye-brain disease described in Finnish patients. The majority of these forms have severe clinical and imagiological involvement of SNC. This aspect is rarely observed on classical CMD, particularly in the merosin-positive form. We describe a case of a 28 year-old woman, with clinical and histopathological signs of classical CMD merosin-positive (no deficient), without mental retardation, but with epilepsy. MRI T2 weighted images, revealed diffuse and symetrical high signal white matter of both cerebral hemispheres, affecting corpos calosum, posterior arms of internal capsules and the piramidal tract to mesencephalon. It also disclosed diffuse and symetrical high signal of basal ganglia, specially, the head of caudate nuclei. These were associated with bilateral occipital posterior cortical dysplasia. The observed imagiological pattern could represent a new subtype of CMD, hybrid between classical CMD and the severe forms, however it is not clear where it fits in the spectrum. This case denotes the possible envolvement of SNC in patients merosin-positives. Based on this findings we suggest doing MRI scans to all patients with CMD no deficient in merosin.


Oxidative Stress and Potential Antioxidant Therapies in Vitiligo: A Narrative Review.
Vitiligo is a chronic skin disorder characterised by the loss of melanocytes and subsequent skin depigmentation. Although many theories have been proposed in the literature, none alone explains the pathogenesis of vitiligo. Oxidative stress has been identified as a potential factor in the pathogenesis of vitiligo. A growing body of evidence suggests that antioxidant therapies may offer a promising approach to managing this condition. This review summarises the potential mechanisms of oxidative stress and the types of melanocyte death in vitiligo. We also provide a brief overview of the most commonly studied antioxidants. Melanocytes in vitiligo are thought to be damaged by an accumulation of reactive oxygen species to destroy the structural and functional integrity of their DNA, lipids, and proteins. Various causes, including exogenous and endogenous stress factors, an imbalance between prooxidants and antioxidants, disruption of antioxidant pathways, and gene polymorphisms, lead to the overproduction of reactive oxygen species. Although necroptosis, pyroptosis, ferroptosis, and oxeiptosis are newer types of cell death that may contribute to the pathophysiology of vitiligo, apoptosis remains the most studied cell death mechanism in vitiligo. According to studies, vitamin E helps to treat lipid peroxidation of the skin caused by psoralen ultra-violet A treatment. In addition, Polypodium leucotomos increased the efficacy of psoralen ultra-violet A or narrow-band ultraviolet B therapy. Our review provides valuable insights into the potential role of oxidative stress in pathogenesis and antioxidant-based supporting therapies in treating vitiligo, offering a promising avenue for further research and the development of effective treatment strategies.


Effects of capsaicin on nonadrenergic noncholinergic nerves in the guinea pig atria: role of calcitonin gene-related peptide as cardiac neurotransmitter.
Transmural nerve stimulation (TNS) in vitro produced positive chronotropic and inotropic responses in the spontaneously beating right atria and electrically driven left atria of guinea pigs, respectively. Both the positive responses of the atria were mediated not only by adrenergic but also by nonadrenergic noncholinergic (NANC) nerves. Numerous calcitonin gene-related peptide (CGRP)-like immunoreactive nerves were found in the sinus node and the muscle layers of both atria of guinea pigs. Exogenously applied CGRP produced positive chronotropic and inotropic responses in a dose-dependent manner. In both the right and left atria, capsaicin (10(-5) M) induced positive chronotropic and inotropic responses. The second application of capsaicin did not cause any responses in the atria, indicating a rapid development of tachyphylaxis. When the tissues developed tachyphylaxis to capsaicin, the intensity of CGRP-like immunoreactivity greatly decreased in the sinus node and in both atria. In the atria that developed tachyphylaxis to capsaicin, the positive chronotropic and inotropic responses to NANC nerve stimulation diminished markedly, but the responses to exogenous CGRP and those attributed to adrenergic nerves were not affected. These results suggest that CGRP is the neurotransmitter of intracardiac NANC nerves and that capsaicin produces positive chronotropic and inotropic responses through the release of CGRP from NANC nerves in the guinea pig atria. It is also suggested that capsaicin depletes endogenous CGRP, thereby accounting for the rapid development of tachyphylaxis to capsaicin and the marked and selective diminution of TNS-induced NANC responses following application of capsaicin.


Evaluation of the binding of natural products with thrombin binding aptamer G-quadruplex using electrospray ionization mass spectrometry and spectroscopic methods.
A 15-mer thrombin-binding aptamer (TBA) was discovered with specificity for thrombin. It forms a unique G-quadruplex (G4), which is postulated to be the molecular basis for its binding specificity. Many analytical methods make use of affinity binding between the thrombin and TBA as they form a very stable complex. We develop a strategy to stabilize TBA/G4's structure by introducing G4-interactive molecules, which may enhance its ability to recognize the target. Herein, a fast screening ESI-MS assay was employed to determine potential binding of natural products molecules with the TBA/G4 complex. The experimental results showed that four investigated natural alkaloids had apparent binding affinities. One of them, jatrorrhizine (L1), has been shown to bind strongly to the TBA/G4 mainly in 1:2 M ratio. Once the working conditions were established, the interaction of the jatrorrhizine with the TBA/G4 was explored using a combination of ESI-MS and spectroscopic techniques. Ligand-induced effects on TBA/G4 structure and its stability were examined by means of circular dichroism (CD). Jatrorrhizine inducing the G4 formation seems also to be the more effective in terms of thermal stabilization under the experimental conditions used. Both results of UV and fluorescence experiments undoubtedly showed a good binding affinity with the binding constant around 105 L mol-1. The stacking interactions of jatrorrhizine with the G-tetrads in TBA/G4 were further confirmed by competition experiment. ESI-MS was carried out to determine the coexistence of 1:1 and 1:2 complexes in TBA/G4-L1 system, and showed a dynamical shift from 1:1 to 1:2 complex in minutes.


A personal construct theory approach to the socialization of nursing trainees in two British general hospitals.
Student and pupil nurses (64), from an initial sample of 117, completed repertory grids questionnaires and interviews on the first day of training, at 4 and 18 months. Measures of identification attraction and ideal/actual congruence were derived from the grids. Trainees were found to become more identified with and attracted to medical roles during training and less identified with and attracted to lower-status non-medical roles such as factory worker. Ideal/actual congruence with medical roles other than trainee also increased. Some measures derived from the grids related to trainee 'wastage' and to satisfaction with the hospital.


Morphometrics and lesions of vertebral end plates are associated with lumbar disc degeneration: evidence from cadaveric spines.
Prior studies have suggested that vertebral end plate morphometrics and lesions may play a role in disc degeneration. However, most prior end plate studies have been based on radiographic images, and findings of associations between end plate morphometrics (measurements of size and shape) and disc degeneration remain controversial. The present study investigated the prevalence of vertebral end plate lesions and determined end plate morphometrics through direct measurements of cadaveric spines, and it examined the association of these factors with disc degeneration. We studied 600 vertebral end plates and 313 intervertebral discs from the cadaveric lumbosacral spines of seventy-six men (mean age, fifty-one years). Discography was performed to evaluate disc degeneration as indicated by disruption of the anulus fibrosus. The shape of the vertebral end plate and the presence of any lesions were visually evaluated. Lesions were rated as absent, small to moderate, or large. In addition, each end plate was digitized to quantify its area, circularity, and concavity. The association of end plate morphometrics and lesions with disc degeneration was examined. Vertebral end plate lesions were found in 72% (fifty-five) of the seventy-six lumbar spines and in 32.8% (197) of the 600 end plates. The presence of end plate lesions was associated with disc degeneration, with larger lesions being associated with more severe disc degeneration (odds ratio, 2.31 for small to moderate lesions [p < 0.01] and 3.54 for large lesions [p < 0.001]). Greater end plate area was also associated with more severe disc degeneration (odds ratio, 1.2 per cm2 [p < 0.05]). Vertebral end plate lesions were common and were associated with adjacent disc degeneration, with greater lesion size being associated with more severe disc degeneration. End plate morphometrics, particularly greater end plate size, may also play a role in the pathogenesis of disc degeneration.


Formulation and nutritional evaluation of a healthy vegetable soup powder supplemented with soy flour, mushroom, and moringa leaf.
The research study was conducted to develop a healthy vegetables soup powder supplemented with soy flour, mushroom, moringa leaf and compare its nutritional facts with locally available soup powders. Proximate analysis and sensory evaluation were done by standard method. In this study, moisture, ash, protein, fat, fiber, carbohydrate, and energy content were ranged from 2.83% to 5.46%, 9.39% to 16.48%, 6.92% to 16.05%, 4.22% to 6.39%, 0.22% to 1.61%, 58.81% to 75.41%, and 337.42 to 386.72 kcal/100 g, respectively. Highest content of vitamin D, minerals, protein, and fiber and lowest content of moisture, fat, and carbohydrate were found in the presently developed soy-mushroom-moringa soup powder compare to locally available soup powders. Vitamin C was also found significantly higher than locally available soup powders S1, S2, and S3. Heavy metals were not found in any of the soup powders. On the sensory and microbiological point of view, the presently developed soup powder was found highly acceptable up to 6 months. So, the developed soy-mushroom-moringa soup powder is nutritionally superior to locally available soup powders and sufficient to meet day-to-day nutritional requirements as a supplement.


Anesthesia for airway surgeries under the perioperative venovenous extracorporeal membrane oxygenation: Three case reports.
The airway management for patients with critical airway problems continues to be a challenge to the anesthesiologist. In general cases, conventional ventilation techniques have been used successfully. These include fiberoptic bronchoscope guided intubation, supraglottic airway, endotracheal or endobronchial intubation at operative field, high frequency jet ventilation, etc. However, patients with near-fatal airway obstruction or severely depressed pulmonary function that is refractory to conventional ventilation methods also present. In these cases, cardiopulmonary bypass or extracorporeal membrane oxygenation (ECMO) can be used. Although these situations are uncommon indications for ECMO, ECMO can be a potential option for these life threatening conditions. Especially, venovenous (VV) ECMO can be used for pure pulmonary support. We describe three cases of airway surgery requiring ECMO. VV ECMO was established in all cases. ECMO provided adequate temporary pulmonary support and all patients weaned from ECMO successfully without any complication.


[Ductal regeneration in vanishing bile duct syndrome in Hodgkin's lymphoma].
We present the case of a 17-year-old male patient with Hodgkin's lymphoma (nodular sclerosis) in the mediastinum. During the postoperative period treatment with erythromycin was started and the patient developed progressive jaundice and cholestasis. Treatment modified for the lymphoma was initiated, which achieved complete remission and subsequent improvement and resolution of the cholestasis. Histological study of the liver revealed massive loss of bile ducts. After resolution of the cholestasis, consecutive biopsies revealed ductal proliferation. The present report therefore illustrates a case of ductopenia or vanishing bile duct syndrome (VBDS) with ad integrum regeneration of the bile ducts simultaneous with lymphoma remission. Because the 2 possible causes, erythromycin toxicity and Hodgkin's lymphoma, occurred simultaneously, the etiology of the VBDS cannot be definitively established.


Focused scores enable reliable discrimination of small differences in steatosis.
Automated image analysis enables quantitative measurement of steatosis in histological images. However, spatial heterogeneity of steatosis can make quantitative steatosis scores unreliable. To improve the reliability, we have developed novel scores that are "focused" on steatotic tissue areas. Focused scores use concepts of tile-based hotspot analysis in order to compute statistics about steatotic tissue areas in an objective way. We evaluated focused scores on three data sets of images of rodent liver sections exhibiting different amounts of dietary-induced steatosis. The same evaluation was conducted with the standard steatosis score computed by most image analysis methods. The standard score reliably discriminated large differences in steatosis (intraclass correlation coefficient ICC = 0.86), but failed to discriminate small (ICC = 0.54) and very small (ICC = 0.14) differences. With an appropriate tile size, mean-based focused scores reliably discriminated large (ICC = 0.92), small (ICC = 0.86) and very small (ICC = 0.83) differences. Focused scores based on high percentiles showed promise in further improving the discrimination of very small differences (ICC = 0.93). Focused scores enable reliable discrimination of small differences in steatosis in histological images. They are conceptually simple and straightforward to use in research studies.


Computational fluid dynamics study in children with obstructive sleep apnea.
This study aims to identify characteristics in image-based computational fluid dynamics (CFD) in children with obstructive sleep apnea (OSA). Diagnostic study. Hospital-based cohort. Children with symptoms suggestive of OSA were recruited and underwent polysomnography. Three-dimensional models of computational fluid dynamics were derived from cone-beam computed tomography. A total of 68 children participated in the study (44 boys; mean age: 7.8 years), including 34 participants having moderate-to-severe OSA (apnea-hypopnea index [AHI] greater than 5 events/h), and 34 age, gender, and body mass index percentile matched participants having primary snoring (AHI less than 1). Children with moderate-to-severe OSA had a significantly higher total airway pressure (166.3 vs. 39.1 Pa, p = .009), total airway resistance (9851 vs. 2060 Newton-metre, p = .004) and velocity at a minimal cross-sectional area (65.7 vs. 8.8 metre per second, p = .017) than those with primary snoring. The optimal cut-off points for moderate-to-severe OSA were 46.2 Pa in the total airway pressure (area under the curve [AUC] = 73.2%), 2373 Newton-metre in the total airway resistance (AUC = 72.5%) and 12.6 metres per second in the velocity at a minimal cross-sectional area (AUC = 70.5%). The conditional logistic regression model revealed that total airway pressure, total airway resistance and velocity at minimal cross-sectional area were significantly associated with an increased risk of moderate-to-severe OSA. This study demonstrates that CFD could be a useful tool for evaluating upper airway patency in children with OSA.


Evaluation of Racial and Ethnic Disparities in Cardiac Transplantation.
Background Racial and ethnic disparities contribute to differences in access and outcomes for patients undergoing heart transplantation. We evaluated contemporary outcomes for heart transplantation stratified by race and ethnicity as well as the new 2018 allocation system. Methods and Results Adult heart recipients from 2011 to 2020 were identified in the United Network for Organ Sharing database and stratified into 3 groups: Black, Hispanic, and White. We analyzed recipient and donor characteristics, and outcomes. Among 32 353 patients (25% Black, 9% Hispanic, 66% White), Black and Hispanic patients were younger, more likely to be women and have diabetes mellitus or renal disease (all, P<0.05). Over the study period, the proportion of Black and Hispanic patients listed for transplant increased: 21.7% to 28.2% (P=0.003) and 7.7% to 9.0% (P=0.002), respectively. Compared with White patients, Black patients were less likely to undergo transplantation (adjusted hazard ratio [aHR], 0.87; CI, 0.84-0.90; P<0.001), but had a higher risk of post-transplant death (aHR, 1.14; CI, 1.04-1.24; P=0.004). There were no differences in transplantation likelihood or post-transplant mortality between Hispanic and White patients. Following the allocation system change, transplantation rates increased for all groups (P<0.05). However, Black patients still had a lower likelihood of transplantation than White patients (aHR, 0.90; CI, 0.79-0.99; P=0.024). Conclusions Although the proportion of Black and Hispanic patients listed for cardiac transplantation have increased, significant disparities remain. Compared with White patients, Black patients were less likely to be transplanted, even with the new allocation system, and had a higher risk of post-transplantation death.


Optimization and evaluation of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) with reversed-phase protein arrays for protein profiling.
Surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry with protein arrays has facilitated the discovery of disease-specific protein profiles in serum. Such results raise hopes that protein profiles may become a powerful diagnostic tool. To this end, reliable and reproducible protein profiles need to be generated from many samples, accurate mass peak heights are necessary, and the experimental variation of the profiles must be known. We adapted the entire processing of protein arrays to a robotics system, thus improving the intra-assay coefficients of variation (CVs) from 45.1% to 27.8% (p<0.001). In addition, we assessed up to 16 technical replicates, and demonstrated that analysis of 2-4 replicates significantly increases the reliability of the protein profiles. A recent report on limited long-term reproducibility seemed to concord with our initial inter-assay CVs, which varied widely and reached up to 56.7%. However, we discovered that the inter-assay CV is strongly dependent on the drying time before application of the matrix molecule. Therefore, we devised a standardized drying process and demonstrated that our optimized SELDI procedure generates reliable and long-term reproducible protein profiles with CVs ranging from 25.7% to 32.6%, depending on the signal-to-noise ratio threshold used.


Gift authorship: An approach to its frequency in a Peruvian journal
Introduction. Unjustified authorship or "gift authorship" is an inadequate practice of authorship that consists of naming as authors people who do not meet the authorship criteria. Reports of scientific research are often published as original articles in scientific journals and may present these inappropriate practices. Objectives. Determine the prevalence of gift authorship in original articles for publication. Materials and methods. Descriptive study in which the authorship contributions section of all the articles published between 2013 and the first quarter of 2017 in a Peruvian magazine was reviewed. Gift authorship was considered when an author did not meet at least one of the criteria established by the International Committee of Medical Journal Editors (ICMJE). Results. Of the 209 original articles published, 11 were excluded because they did not report authorship contributions. The prevalence of gift authorship was 53.5% (106). The critreria least met were the final approval of the manuscript (23.2%) and the writing and critical review of this manuscript. (16.8%). Conclusions. It is necessary that educational institutions train researchers to distinguish between authorship and contribution. In addition, it is necessary that the journals request and corroborate the reported contributions.


Treatment of the restless legs syndrome with carbamazepine: a double blind study.
One hundred and seventy four patients suffering from the restless legs syndrome were examined in a double blind, between patient, placebo controlled study in general practice for five weeks to investigate the effects of carbamazepine and placebo on the syndrome. The syndrome was more common among middle aged women with relatively low systolic blood pressure. The median haemoglobin concentration was about average for the population, but the severity of the symptoms seemed to increase with decreasing concentrations of haemoglobin. Both placebo and carbamazepine showed a significant therapeutic effect (p less than 0.01). Carbamazepine was significantly more effective than placebo (p less than or equal to 0.03). The significant therapeutic effect of placebo in restless legs showed that only double blind controlled trials can confirm the efficacy of suggested treatments.


Long-term prognostic value for patients with chronic heart failure of estimated glomerular filtration rate calculated with the new CKD-EPI equations containing cystatin C.
Correct estimation of renal function is crucial in assessing prognosis of patients with heart failure (HF). Recently, two new equations have been proposed to calculate estimated glomerular filtration rate (eGFR) with cystatin C alone or both creatinine and cystatin C. We assessed the prognostic value of eGFR estimated by these new equations in outpatients with HF. The study included 879 patients with median age, 70.4 years; main etiology of HF ischemic heart disease, 52.7%; and median LVEF, 34%. eGFR estimates by the new equations correlated significantly with eGFR estimates from previous equations, with the best correlation observed between the 2 equations containing cystatin C [intraclass correlation coefficient 0.95 (95% confidence interval 0.94-0.95)]. During a median follow-up of 3.94 years, 371 patients died. The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations containing cystatin C were found to be best for predicting death [area under the ROC curve 0.685 for CKD-EPI-cystatin C and 0.672 for CKD-EPI-creatinine-cystatin C vs 0.632 for simplified Modification of Diet in Renal Disease Study traceable to isotope dilution mass spectrometry and 0.643 for CKD-EPI (all P < 0.001)]. The CKD-EPI-cystatin C equations also showed significantly better calibration and reclassification measurements for both integrated discrimination improvement and net reclassification improvement in predicting death (P < 0.001). Reclassification with these new equations was particularly better in the subgroup with intermediate eGFR [45-74 mL · min(-1) · (1.73 m(2))(-1)]. The two new CKD-EPI equations containing cystatin C are useful for HF risk stratification and show better prognostic performance than creatinine-only based eGFR equations, mostly in patients with intermediate eGFR. These equations seem appropriate for assessing prognosis of HF patients with moderate renal insufficiency.


Species delimitation of the Hyphydrus ovatus complex in western Palaearctic with an update of species distributions (Coleoptera, Dytiscidae).
The species status of Hyphydrus anatolicus Guignot, 1957 and H. sanctus Sharp, 1882, previously often confused with the widespread H. ovatus (Linnaeus, 1760), are tested with molecular and morphological characters. Cytochrome c oxidase subunit 1 (CO1) was sequenced for 32 specimens of all three species. Gene-trees were inferred with parsimony, time-free bayesian and strict clock bayesian analyses. The GMYC model was used to estimate species limits. All three species were reciprocally monophyletic with CO1 and highly supported. The GMYC species delimitation analysis unequivocally delimited the three species with no other than the three species solution included in the confidence interval. A likelihood ratio test rejected the one-species null model. Important morphological characters distinguishing the species are provided and illustrated. New distributional data are given for the following species: Hyphydrus anatolicus from Slovakia and Ukraine, and H. aubei Ganglbauer, 1891, and H. sanctus from Turkey.


Solitary and Social Drinking in South Korea: An Exploratory Study.
This study aimed to identify differences in drinking norms, heavy drinking, and motives between types of drinkers (abstainers, solitary, and social drinkers) in a representative sample of Korean adults. An online survey of people registered on the electoral roll were randomly invited to be part of the "National Korean Drinking Culture Study" conducted in 2018 (n = 3,015). Participants included 1,532 men and 1,469 women aged 19-60 years. Questions included the number of times they drank in the last month, what they drank, and the volume drank. The amount of pure alcohol consumed was calculated. Drinking norms, motives, and types were determined in the survey questions. Solitary drinkers were more likely to be divorced or separated, less educated, and marginally employed. Solitary drinking peaked in those in their 30s (18.5%) and social drinkers in their 50s (68.1%). Solitary drinkers drank more frequently compared with social drinkers (6.1 vs. 3.6 times per month, p < 0.001), and consumed a significantly larger quantity of alcohol (69.5 g vs. 46.8 g per week). Solitary drinkers were more accepting of drinking-related behaviors in diverse situations compared with social drinkers. The regression analysis revealed that personal drinking motives were the most important factor influencing the frequency and quantity of alcohol consumption in both solitary and social drinking. Solitary drinkers may be more vulnerable to alcohol abuse than social drinkers.


Delayed rather than decreased BOLD response as a marker for early Alzheimer's disease.
Functional MRI (fMRI) in established Alzheimer's disease (AD) shows regionally altered blood oxygenation level dependent (BOLD) responses. Mild cognitive impairment (MCI) is thought to represent an intermediate state between health and early Alzheimer's disease. To study this probable early dementia stage pathology, we studied in detail the BOLD response in MCI during visual encoding. 28 MCI patients, 18 AD patients, and 41 healthy elderly controls performed a face encoding task during fMRI scanning. Data were analyzed using orthogonal regressors, each representing different phases of the BOLD response (from slow to fast). Using a mixed effects model, regressor x group interactions were analyzed applying P < 0.05, corrected. In occipital regions, MCI patients could be distinguished significantly better from controls and AD patients with a regressor of the early phase of the (fast) BOLD response than with the regressor of the late (slow) BOLD phase. Occipitally, the early phase BOLD response was significantly diminished in MCI patients compared to controls, and significantly increased when compared to AD. AD patients showed diminished early phase activation in widespread regions throughout the brain when compared to controls. There were no differences in the late (slow) phase of the BOLD response. This study stresses the importance of analyzing early phase BOLD responses and not only using one model of the BOLD response in neurodegenerative diseases. The increasing delay of the BOLD response from controls to MCI to AD may be consistent with the idea that MCI is a transitional state between healthy aging and dementia. Analyzing differences in different phases of the BOLD response introduces new opportunities to understand changes in regional brain dynamics in MCI and how well this may serve as an early marker of AD pathology.


Nearly unbiased estimator of contemporary effective mother size using within-cohort maternal sibling pairs incorporating parental and nonparental reproductive variations.
In this study, we developed a nearly unbiased estimator of contemporary effective mother size in a population, which is based on a known maternal half-sibling relationship found within the same cohort. Our method allows for variance of the average number of offspring per mother (i.e., parental variation, such as age-specific fecundity) and variance of the number of offspring among mothers with identical reproductive potential (i.e., nonparental variation, such as family-correlated survivorship). We also developed estimators of the variance and coefficient of variation of contemporary effective mother size and qualitatively evaluated the performance of the estimators by running an individual-based model. Our results provide guidance for (i) a sample size to ensure the required accuracy and precision when the order of effective mother size is available and (ii) a degree of uncertainty regarding the estimated effective mother size when information about the size is unavailable. To the best of our knowledge, this is the first report to demonstrate the derivation of a nearly unbiased estimator of effective population size; however, its current application is limited to effective mother size and situations, in which the sample size is not particularly small and maternal half-sibling relationships can be detected without error. The results of this study demonstrate the usefulness of a sibship assignment method for estimating effective population size; in addition, they have the potential to greatly widen the scope of genetic monitoring, especially in the situation of small sample size.


Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2016.
The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma (MM) and AL-amyloidosis) that were presented in the 2016 Annual Meeting of the American Society of Hematology are summarized here. Data from large phase 3 studies for newly diagnosed MM patients who are eligible for autologous transplantation (EMN02, MRC XI and StaMINA trials) are described along with the results of phase 2 studies using novel anti-myeloma drug combinations for induction, consolidation and maintenance as first line therapy. Recent updates of previous important studies in the field of both newly diagnosed (FIRST) and relapsed/refractory MM (POLLUX, CASTOR) are also reported. Moreover, the results of clinical studies with the use of anti-myeloma drugs with new mechanisms of action, including pembrolizumab, selinexor, venetoclax and monoclonal antibodies, are discussed. All these data provide the basis for possible changes in the way we manage myeloma in the near future trying to "cure" the disease.


Sporotrichoid chromomycosis.
Chromomycosis is a chronic fungal skin infection. It manifests frequently by warty or vegetative lesions in exposed areas, most often secondary to trauma. The diagnosis, nevertheless, is confirmed by the presence of fungi in the mycological examination. In fact, the treatment remains a challenge given its recalcitrant nature.


Isotyping and Semi-Quantitation of Monkey Anti-Drug Antibodies by Immunocapture Liquid Chromatography-Mass Spectrometry.
There is an urgent demand to develop new technologies to characterize immunogenicity to biotherapeutics. Here, we developed an immunocapture LC-MS assay to isotype and semi-quantify monkey anti-drug antibodies (ADAs) to fully human monoclonal antibody (mAb) drugs. ADAs were isolated from serum samples using an immunocapture step with the Fab of the full-length mAb cross-linked to magnetic beads to minimize matrix interference. A positive monoclonal antibody control against the human immunoglobulin kappa light chain was used as a calibration standard for ADA quantitation. The final LC-MS method contains 17 multiple reaction monitoring (MRM) transitions and an optimized 15-min LC method. The results suggested that IgG1 was the most abundant isotype in ADA-positive samples. IgG2 and IgG4 were identified at lower levels, whereas IgG3 and IgA levels were only observed at very minor levels. In addition, levels of total ADA measured by the LC-MS assay were comparable to results obtained using a traditional ligand binding assay (LBA). The LC-MS ADA assay enabled rapid immunogenicity assessment with additional isotype information that LBAs cannot provide.


Development of waxy cassava with different Biological and physico-chemical characteristics of starches for industrial applications.
The quality of cassava starch, an important trait in cassava breeding programs, determines its applications in various industries. For example, development of waxy (having a low level of amylose) cassava is in demand. Amylose is synthesized by granule-bound starch synthase I (GBSSI) in plants, and therefore, down-regulation of GBSSI expression in cassava might lead to reduced amylose content. We produced 63 transgenic cassava plant lines that express hair-pin dsRNAs homologous to the cassava GBSSI conserved region under the control of the vascular-specific promoter p54/1.0 from cassava (p54/1.0::GBSSI-RNAi) or cauliflower mosaic virus (CaMV) 35S (35S::GBSSI-RNAi). After the screening storage roots and starch granules from field-grown plants with iodine staining, the waxy phenotype was discovered: p54/1.0::GBSSI-RNAi line A8 and 35S::GBSSI-RNAi lines B9, B10, and B23. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that there was no detectable GBSSI protein in the starch granules of plants with the waxy phenotype. Further, the amylose content of transgenic starches was significantly reduced (<5%) compared with the level in starch granules from the wild-type (about 25%). The inner structure of the waxy starch granules differed from that of the untransformed ones, as revealed by transmission electron microscopy analysis as well as morphological changes in the iodine-starch complex. Endothermic enthalpy was reduced in waxy cassava starches, according to differential scanning calorimeter analysis. Except B9, all waxy starches displayed the A-type X-ray diffraction pattern. Amylogram patterns of the waxy cassava starches were analyzed using a rapid viscosity analyzer and found to have increased values for clarity, peak viscosity, gel breakdown, and swelling index. Setback, consistency, and solubility were notably reduced. Therefore, waxy cassava with novel starch in its storage roots was produced using the biotechnological approach, promoting its industrial utilization.


Pest categorisation of Fusarium oxysporum f. sp. cubense Tropical Race 4.
The EFSA Plant Health Panel performed a pest categorisation of Fusarium oxysporum f. sp. cubense Tropical Race 4 (Foc TR4), an ascomycete fungus causing Fusarium wilt (Panama disease) on Musa spp. Foc TR4 is pathogenic to the commercial banana varieties including those of the 'Cavendish' group and is considered as the most destructive among Foc haplotypes. Uncertainty exists on the host range of Foc TR4, since it has not been demonstrated whether it can infect plant species other than Musa spp., which were previously reported as hosts of other Foc races. Foc TR4 is morphologically and physiologically identical to other representatives of the Fusarium oxysporum Species Complex (FOSC), but all Foc TR4 isolates belong to a single clonal lineage within the vegetative compatibility groups 01213-01216. Several PCR protocols are described in the literature, but their specificity has been questioned as they may generate false positives. The pathogen is not included in EU Commission Implementing Regulation 2019/2072 and is not reported as present in the EU territory. Several potential entry pathways and means of spread were identified, including host plants for planting other than vitroplants, fresh fruits and leaves of host plants, soil and other substrates originating in infested third countries. Host availability and climate suitability occurring in some areas of the EU are favourable for the establishment of Foc TR4. Being a soil-borne pathogen, eradication of Foc TR4 once it enters a new area is very difficult. Therefore, effective quarantine measures are essential in pathogen-free areas. Although not specifically targeting against Foc TR4, phytosanitary measures are currently available to prevent the introduction of the pathogen into the EU. Considering that banana-growing EU countries account for over 12% of the EU banana supply, it is expected that the economic impact of Foc TR4 on the European banana production areas would be devastating. Foc TR4 satisfies the criteria that are within the remit of EFSA to assess for this pathogen to be regarded as a potential Union quarantine pest.


Molecular proximity of Kv1.3 voltage-gated potassium channels and beta(1)-integrins on the plasma membrane of melanoma cells: effects of cell adherence and channel blockers.
Tumor cell membranes have multiple components that participate in the process of metastasis. The present study investigates the physical association of beta1-integrins and Kv1.3 voltage-gated potassium channels in melanoma cell membranes using resonance energy transfer (RET) techniques. RET between donor-labeled anti-beta1-integrin and acceptor-labeled anti-Kv1.3 channels was detected on LOX cells adherent to glass and fibronectin-coated coverslips. However, RET was not observed on LOX cells in suspension, indicating that molecular proximity of these membrane molecules is adherence-related. Several K(+) channel blockers, including tetraethylammonium, 4-aminopyridine, and verapamil, inhibited RET between beta1-integrins and Kv1.3 channels. However, the irrelevant K(+) channel blocker apamin had no effect on RET between beta1-integrins and Kv1.3 channels. Based on these findings, we speculate that the lateral association of Kv1.3 channels with beta1-integrins contributes to the regulation of integrin function and that channel blockers might affect tumor cell behavior by influencing the assembly of supramolecular structures containing integrins.


Gastroenterology service in a teaching hospital in rural New Zealand, 1991-2003.
To retrospectively collect inpatient and outpatient data and to assess the use of endoscopic procedures during the years 1991, 1997 and 2003 to analyse for trends. This retrospective survey was conducted in a University-associated Gastroenterology Unit offering secondary and tertiary health care services for a population of approximately 182,000 people in Southern New Zealand. Data collected included patient contacts (in- and outpatients), gastroscopic and colonoscopic investigations. We observed a significant increase in the absolute numbers of patient contacts over the years (1991: 2308 vs 1997: 2022 vs 2003: 2783, P < 0.0001) with inflammatory bowel disease, other diseases of the colon, anus and rectum and iron studies related disorders decreasing significantly but liver disease and constipation increasing linearly over time. The use of endoscopy services remained relatively stable but colonoscopic investigations for a positive family history of colorectal cancer increased significantly while more gastroscopies were performed for unexplained anaemia. The whole spectrum of gastroenterology contacts was studied. A substantial proportion of colonoscopies and outpatient consultations were undertaken to screen for colorectal cancer. This proportion is likely to grow further. Our findings have implications for the recruitment and training of the next generation of gastroenterologists.


Continuous infusion of endotoxin from an osmotic pump in the conscious, unrestrained rat: a unique model of chronic endotoxemia.
Endotoxin (ET) was administered to conscious, unrestrained rats by continuous intravenous infusion from an Alzet osmotic pump. Delivery of ET was delayed 42 h after surgery by inserting a 100-cm coil of PE-60 tubing between pump and jugular vein. Rats were anorectic following onset of ET delivery; therefore control rats were either fed ad libitum or food-deprived (FD) to match the voluntary consumption of ET rats. Blood was collected from carotid catheters and oxygen consumption determined daily. Body weight, colon temperature, and plasma glucose were similar in ET and FD rats, but ET rats exhibited a transient hyperlactacidemia, progressive leukocytosis, and fall in hematocrit which was not seen in FD rats. Food deprivation resulted in a marked drop in plasma insulin which was not seen in ET rats, despite similar food intake and plasma glucose concentration. Oxygen consumption of ET rats was significantly greater than both fed and FD animals on days 1 and 2 of ET infusion, while mean arterial pressure and heart rate were similar to controls. A unique model of endotoxemia is presented which is characterized by a transient hypermetabolic state, and changes in plasma lactate and insulin levels, white cell count, and hematocrit, which cannot be attributed to food deprivation. The results suggest that ET may be important in the pathogenesis of hypermetabolic sepsis.


Phenotypic and genotypic characterization of serologically atypical strains of Shigella flexneri type 4 isolated in Dhaka, Bangladesh.
Twenty-one atypical Shigella flexneri type 4 strains isolated from patients attending the Dhaka treatment center of the International Centre for Diarrhoeal Disease Research, Bangladesh, were extensively characterized and compared with S. flexneri serotypes 4a and 4b. The atypical strains agglutinated only with the type antigen factor 4 and did not agglutinate with any group factors, thereby excluding their characterization into serotype 4a or 4b. Of the 21 strains, 85.7% did not ferment mannitol but were able to ferment most of the sugars, whereas the remaining 14.3% strains fermented mannitol but were unable to ferment most of the sugars. Most of the strains were resistant to ampicillin, tetracycline, and trimethoprim-sulfomethoxazole. All of the strains harbored the 140-MDa plasmid, had the ipaH gene, had the sen gene (encoding Shigella enterotoxin 2), had the ability to bind Congo red, and were positive for keratoconjunctivitis in the guinea pig eye, attesting their invasive properties. All of the strains contained a middle-range plasmid (35 to 62 MDa) as well as a number of stable small plasmids, yielding mainly two plasmid profiles which were different from those of 4a and 4b strains. Conjugation and curing experiments suggested that the middle-range plasmids harbored a self-transferable multiple antibiotic resistance marker. Pulsed-field gel electrophoresis analysis of all of the tested strains yielded two types with numerous subtypes, whereas ribotyping yielded only two types which were completely different from those of types 4a and 4b. This study concluded that two different clones of atypical S. flexneri type 4 exist and strongly suggests that these are new subserotypes of S. flexneri that await further serological classification.


[Structure and function of otoliths].
Current data on the structure and function of the otoliths are reviewed. The function of the otolith organ in microgravity is discussed. Biophysical approaches to its study are presented. This paper may have theoretical and practical importance since it may help clarify certain aspects of space motion sickness.


Effects of serelaxin on renal microcirculation in rats under control and high-angiotensin environments.
Serelaxin is a novel recombinant human relaxin-2 that has been investigated for the treatment of acute heart failure. However, its effects on renal function, especially on the renal microcirculation, remain incompletely characterized. Our immunoexpression studies localized RXFP1 receptors on vascular smooth muscle cells and endothelial cells of afferent arterioles and on principal cells of collecting ducts. Clearance experiments were performed in male and female normotensive rats and Ang II-infused male rats. Serelaxin increased mean arterial pressure slightly and significantly increased renal blood flow, urine flow, and sodium excretion rate. Group analysis of all serelaxin infusion experiments showed significant increases in GFR. During infusion with subthreshold levels of Ang II, serelaxin did not alter mean arterial pressure, renal blood flow, GFR, urine flow, or sodium excretion rate. Heart rates were elevated during serelaxin infusion alone (37 ± 5%) and in Ang II-infused rats (14 ± 2%). In studies using the in vitro isolated juxtamedullary nephron preparation, superfusion with serelaxin alone (40 ng/ml) significantly dilated afferent arterioles (10.8 ± 1.2 vs. 13.5 ± 1.1 µm) and efferent arterioles (9.9 ± 0.9 vs. 11.9 ± 1.0 µm). During Ang II superfusion, serelaxin did not alter afferent or efferent arteriolar diameters. During NO synthase inhibition (l-NNA), afferent arterioles also did not show any vasodilation during serelaxin infusion. In conclusion, serelaxin increased overall renal blood flow, urine flow, GFR, and sodium excretion and dilated the afferent and efferent arterioles in control conditions, but these effects were attenuated or prevented in the presence of exogenous Ang II and NO synthase inhibitors.


Routine gastric suspension technique in single-port sleeve gastrectomy procedure.
Due to limited technical demand, single-port sleeve gastrectomy (SPSG) is a feasible laparoscopic technique for sleeve gastrectomy (SG). Nonetheless, difficulties exist when performing the single-port technique, and in this study, we aim to describe a slight maneuver that can improve the SPSG procedure. Patients who underwent laparoscopic SG between January 2022 and May 2023 at our hospital were included. The patients were classified into two groups: (1) SPSG and (2) multiple-port SG (MPSG). The parameters for this analysis were the patients' age, gender, weight, body mass index (BMI), conversion rate, drainage placement, 30-day readmission rate, and postoperative complications. Postoperative one-month and three-month percentages of total weight loss (%TWL) were calculated and compared. 171 patients were included in this study: (1) the SPSG group (n = 96) and (2) the MPSG group (n = 75). No statistically significant difference was observed within the preoperative (age, gender, height, weight, and BMI) and the perioperative parameters between SPSG and MPSG (operation time, drainage placement, 30-day readmission) (p > 0.05). Per Clavien-Dindo's grading, two patients in the SPSG group suffered grade 1 complications; for the MPSG group, one patient sustained grade 2 and another suffered grade 3b complication. No statistical significance was observed on the %TWL between the two groups (p > 0.05). Our study found that performing SPSG in specific patient is feasible and non-inferior when compared to the MPSG. Further studies will be needed to elucidate better the efficacy and safety of performing SPSG.


On the importance of modeling stent procedure for predicting arterial mechanics.
The stent-artery interactions have been increasingly studied using the finite element method for better understanding of the biomechanical environment changes on the artery and its implications. However, the deployment of balloon-expandable stents was generally simplified without considering the balloon-stent interactions, the initial crimping process of the stent, its overexpansion routinely used in the clinical practice, or its recoil process. In this work, the stenting procedure was mimicked by incorporating all the above-mentioned simplifications. The impact of various simplifications on the stent-induced arterial stresses was systematically investigated. The plastic strain history of stent and its resulted geometrical variations, as well as arterial mechanics were quantified and compared. Results showed the model without considering the stent crimping process underestimating the minimum stent diameter by 17.2%, and overestimating the maximum radial recoil by 144%. It was also suggested that overexpansion resulted in a larger stent diameter, but a greater radial recoil ratio and larger intimal area with high stress were also obtained along with the increase in degree of overexpansion.


Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique.
Prolonged disease-free survival of patients with recurrent or resistant non-Hodgkin's lymphoma (NHL) has been achieved with high-dose therapy followed by autologous bone marrow transplantation (ABMT). A concern with the use of ABMT is that the marrow that is reinfused may contain undetected NHL cells with the potential to reestablish metastatic disease in the recipient. Using a culture technique that is sensitive for detecting occult lymphoma cells in BM, we analyzed histologically normal marrow harvests from 59 consecutive patients with intermediate- or high-grade NHL who were candidates for high-dose therapy and ABMT. The culture results indicated that 22 of the patients had occult lymphoma in their marrow. Forty-three patients underwent high-dose therapy followed by ABMT. Twenty-four achieved a complete clinical remission. Those with occult lymphoma in their harvests (11 patients) continued to relapse for up to 3 years, whereas no relapses were observed beyond 8 months in 13 patients receiving marrow that did not contain detectable lymphoma cells using the culture technique. The relapses in the patients who achieved a complete remission occurred at sites of prior bulky disease rather than at new sites, suggesting that the ability to detect occult lymphoma cells in marrow is a marker of biologic aggressiveness and/or resistance to therapy, or that the reinfused cells could only grow in previously involved sites. The detection of lymphoma cells in marrow used for ABMT is an important adverse prognostic factor, and appears to be independent of other clinical predictors of outcome such as sensitivity or resistance of disease to prior chemotherapy.


Liquid chromatographic method for analysis of All-rac-alpha-tocopheryl acetate and retinyl palmitate in soy-based infant formula using a zero-control reference material (ZRM) as a method development tool.
A liquid chromatographic method is described for analysis of all-rac-alpha-tocopheryl acetate, tocopherols, and retinyl palmitate in soy-based infant formula. The vitamins are extracted in isopropyl alcohol and hexane--ethyl acetate without saponification and quantitated by normal-phase chromatography with fluorescence detection. All-rac-alpha-tocopheryl acetate and retinyl palmitate are quantitated isocratically with mobile phases of 0.5% (v/v) and 0.125% (v/v) isopropyl alcohol in hexane, respectively. Recoveries from zero control reference material soy-based formula averaged 97.2% (n = 25) for retinyl palmitate and 100% (n = 25) for all-rac-alpha-tocopheryl acetate. Coefficients of variation ranged from 1.21 to 2.86% for retinyl palmitate and from 1.49 to 5.16% for all-rac-alpha-tocopheryl acetate. The method provides a rapid, specific, and easily controlled assay for analysis of vitamin A and vitamin E in fortified infant formula. Additionally, the method eliminates use of chlorinated solvents.


A meta-analysis of the relationship between abstinence and neuropsychological functioning in methamphetamine use disorder.
The potential influence of methamphetamine use on neuropsychological functioning is unclear. The aim of this this meta-analysis was to investigate the relationship between abstinence and neuropsychological functioning in people with methamphetamine use disorder. The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018083598). Studies were eligible if they (a) included a group that identified methamphetamine as their primary substance of use, (b) comprised participants who reported a period of abstinence from methamphetamine, (c) included healthy comparison participants, (d) included outcome measures that constituted valid and reliable cognitive tests and, (e) were published in English. The search yielded effect sizes based on 1008 abstinent methamphetamine participants and 984 healthy comparison participants. Findings revealed small-to-moderate effect sizes, indicating that methamphetamine participants performed somewhat below controls on learning efficiency, visual-spatial processing, comprehension knowledge, retrieval fluency, processing speed, and psychomotor speed. Three exceptions, in which performance demonstrated no group effect, were in domains of fluid reasoning, short-term working memory, and reaction and decision speed. The current results support the hypothesis that methamphetamine use is associated with small-to-moderate cognitive sequelae that persist beyond a period of abstinence. However, we cannot determine whether methamphetamine use leads to long-term neuropsychological impairment via structural or functional brain changes, or whether preexisting deficits in neuropsychological performance and cortical integrity are vulnerability factors for methamphetamine use, or both. Taken together, the results suggest that strong statements regarding impaired cognitive functioning in abstinent methamphetamine users are premature. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Retrospective reevaluation of the significance of thyroid microsomal antibody in the treatment of Graves' disease.
The results of treatment were analyzed in relation to serum microsomal antibody (MCAb) titre before treatment in 1185 patients with Graves' disease. The percentage of patients who had ablative therapy because of poor response to antithyroid drug treatment was significantly greater in those with MCAb haemagglutination test (MCHA) titres greater than 1:25,000. With 131I treatment, the patients with MCHA titres greater than 1:6400 responded significantly less to therapy, although the analysis was done in 146 selected patients with certain defined radiation doses and small goitres. With surgical treatment, the percentage of the patients entering into remission was significantly smaller for patients with MCHA titres greater than 1:25,000, because of an increase in both hypothyroidism and relapses. The incidence of hypothyroidism was significantly higher in patients with marked lymphocyte infiltration and/or lymphoid follicles. The degree of these histological findings in Graves' disease was not marked in spite of high MCAb titre and it was significantly different from that in Hashimoto's disease when analyzed in relation to the MCHA titre. These data indicate that in Graves' patients with high MCAb titre, remission is difficult to obtain by treatment, and suggest that the significance of MCAb is different in Graves' disease and Hashimoto's disease. The titre in Graves' disease may be one expression of the activity of this disease.


Evolutionary relationships of Metchnikovella dogieli Paskerova et al., 2016 (Microsporidia: Metchnikovellidae) revealed by multigene phylogenetic analysis.
The species Metchnikovella dogieli (Paskerova et al. Protistology 10:148-157, 2016) belongs to one of the early diverging microsporidian groups, the metchnikovellids (Microsporidia: Metchnikovellidae). In relation to typical ('core') microsporidia, this group is considered primitive. The spores of metchnikovellids have no classical polar sac-anchoring disk complex, no coiled polar tube, no posterior vacuole, and no polaroplast. Instead, they possess a short thick manubrium that expands into a manubrial cistern. These organisms are hyperparasites; they infect gregarines that parasitise marine invertebrates. M. dogieli is a parasite of the archigregarine Selenidium pygospionis (Paskerova et al. Protist 169:826-852, 2018), which parasitises the polychaete Pygospio elegans. This species was discovered in samples collected in the silt littoral zone at the coast of the White Sea, North-West Russia, and was described based on light microscopy. No molecular data are available for this species, and the publicly accessible genomic data for metchnikovellids are limited to two species: M. incurvata Caullery & Mesnil, 1914 and Amphiamblys sp. WSBS2006. In the present study, we applied single-cell genomics methods with whole-genome amplification to perform next-generation sequencing of M. dogieli genomic DNA. We performed a phylogenetic analysis based on the SSU rRNA gene and reconstructed a multigene phylogeny using a concatenated alignment that included 46 conserved single-copy protein domains. The analyses recovered a fully supported clade of metchnikovellids as a basal group to the core microsporidia. Two members of the genus Metchnikovella did not form a clade in our tree. This may indicate that this genus is paraphyletic and requires revision.


RNA polymerase activity associated with bacteriophage phi 6.
The Pseudomonas phaseolicola bacteriophage phi6 incorporated labeled UTP into an acid-insoluble precipitate. Incorporation was dependent on the presence of manganese acetate, ATP, GTP, CTP, and a short heat treatment of the phage; the reaction was stimulated by NH(4)Cl. The substitution of (14)C-ATP, -CTP or -GTP for UTP, together with the appropriate unlabeled ribonucleoside triphosphates, disclosed that CMP was incorporated to the greatest extent followed by GMP, UMP, and AMP. Radioactive RNAs formed by the reaction were resistant to RNases A and T(1) in high salt but susceptible to these nucleases in low salt. The labeled RNA co-sedimented and co-electrophoresed with phi6 double-stranded (ds) RNA. However, the distribution of the radioactivity into the three ds-RNA components varied depending on the (14)C-ribonucleoside triphosphate used in the reaction. The incorporation of UMP was primarily into the two smaller ds-RNA segments, GMP primarily into the large ds-RNA segment, and CMP and AMP were about equally distributed into all three ds-RNA segments.


Manipulation of ovarian function influenced glucose metabolism in CBA/J mice.
Menopause is associated with a decline in overall health in women. One health aspect impacted is glucose metabolism. As women experience menopause, their metabolism declines dramatically. The current study addressed the influence of ovarian somatic cells on the improvement of metabolic health through transplantations of young, germ cell-depleted ovaries. The purpose of this study is to expand the understanding of female reproductive health on metabolism. Control mice were grouped by age and treatment mice were age-matched. Treatment mice were placed into one of three groups: 1) mice received germ cell-depleted ovaries, 2) mice received germ cell-containing ovaries, and 3) mice received ovarian somatic cells via injection directly to their original ovary. All mice were subject to a glucose tolerance test, during which a bolus of dextrose was administered, and blood glucose levels were collected and recorded. Mice were euthanized between 680 and 700 days. Metabolic results showed an improvement of glucose metabolism in both germ cell-depleted and germ cell-containing groups compared to controls. No significance difference was noted between the germ cell-containing and germ cell-depleted groups. Somatic cell injection groups also showed improved glucose metabolism compared to controls. This experiment has shown that post-reproductive health is positively influenced by reproductive status. Additionally, somatic cells play an important role in the restoration of health to post-reproductive mice.


Predictors of pleural malignancy in patients with pleural effusion undergoing thoracoscopy.
Thoracoscopic pleural biopsy is highly accurate in the diagnosis of pleural malignancy. However, no scientific evidence is currently available to guide the physician's decision as to when and in which patients with pleural effusion thoracoscopy is indicated. The application of predictive criteria of malignancy might improve the indication of thoracoscopy in patients with undiagnosed pleural effusion. Prospective study of 93 patients referred for thoracoscopy at a tertiary hospital. Clinical variables were obtained prior to thoracoscopy by clinical history and review of previous data, patient interview, and physical examination. Radiologic variables were obtained by evaluation of chest radiograph and chest CT images by two independent readers. After thoracoscopy, all patients without a diagnosis were sent for long-term follow-up. Thoracoscopy demonstrated 94% sensitivity and 100% specificity in the diagnosis of pleural malignancy. Variables, which in a multivariate model are associated with pleural malignancy, include a symptomatic period > 1 month, absence of fever, blood-tinged pleural fluid, and chest CT scan findings suggestive of malignancy. Receiver operating characteristic analysis showed that the use of these four criteria offered adequate classification in 95% of patients. Twenty-eight patients had all four criteria, and all had malignancy; 21 patients had at most one criterion, and none had malignancy. Clinical and radiologic criteria of patients with pleural effusion permit different risk levels for pleural malignancy to be distinguished. Consequently, application of the four proposed criteria permits better indication of thoracoscopy in patients with undiagnosed pleural effusion.


Early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the MACOCHA score in a multicenter cohort study.
Difficult intubation in the intensive care unit (ICU) is a challenging issue. To develop and validate a simplified score for identifying patients with difficult intubation in the ICU and to report related complications. Data collected in a prospective multicenter study from 1,000 consecutive intubations from 42 ICUs were used to develop a simplified score of difficult intubation, which was then validated externally in 400 consecutive intubation procedures from 18 other ICUs and internally by bootstrap on 1,000 iterations. In multivariate analysis, the main predictors of difficult intubation (incidence = 11.3%) were related to patient (Mallampati score III or IV, obstructive sleep apnea syndrome, reduced mobility of cervical spine, limited mouth opening); pathology (severe hypoxia, coma); and operator (nonanesthesiologist). From the β parameter, a seven-item simplified score (MACOCHA score) was built, with an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.85-0.94). In the validation cohort (prevalence of difficult intubation = 8%), the AUC was 0.86 (95% CI, 0.76-0.96), with a sensitivity of 73%, a specificity of 89%, a negative predictive value of 98%, and a positive predictive value of 36%. After internal validation by bootstrap, the AUC was 0.89 (95% CI, 0.86-0.93). Severe life-threatening events (severe hypoxia, collapse, cardiac arrest, or death) occurred in 38% of the 1,000 cases. Patients with difficult intubation (n = 113) had significantly higher severe life-threatening complications than those who had a nondifficult intubation (51% vs. 36%; P < 0.0001). Difficult intubation in the ICU is strongly associated with severe life-threatening complications. A simple score including seven clinical items discriminates difficult and nondifficult intubation in the ICU. Clinical trial registered with www.clinicaltrials.gov (NCT 01532063).


Bullous pemphigoid antibodies. Human skin as a substrate for indirect immunofluorescence assay.
Human skin, the target organ for bullous pemphigoid (BP) antibodies, is thought to be a less sensitive substrate for the indirect immunofluorescence assay of BP antibodies than monkey or guinea pig esophagus. To examine the reasons for this puzzling phenomenon, we compared the titers of BP antibodies obtained when human skin, monkey, and guinea pig esophagus were used as substrates. We found the titers of BP antibodies obtained with human skin from sites commonly involved in BP (flexor arm, flexor thigh, popliteal fossa) were as high and usually higher than those obtained with monkey and guinea pig esophagus. In contrast, much lower titers were obtained with human skin from sites rarely involved in the disease (scalp, face, extensor arm). These findings suggest that human skin as a substrate is at least as sensitive as monkey or guinea pig esophagus for the indirect immunofluorescence assay of BP antibodies when the skin is obtained from regions on the body commonly involved in BP.


Objective evidence for tinnitus from spontaneous emission variability.
Noise exposure is the most common cause for the generation of tinnitus. This study evaluated the variability of spontaneous emissions in industrial workers exposed to noise and reporting the presence of tinnitus in comparison with those exposed to noise but without tinnitus. The assumption being that exposure to noise leads to some instability within the cochlea, which alters the spontaneous emission activity. Thus those experiencing tinnitus may show greater variability than those without tinnitus. 198 mill workers in Poland exposed to noise levels between 85-95dBA for a mean of 12+/-6.6 years, 104 of whom had reported the presence tinnitus and 94 without tinnitus were evaluated for otoscopy, audiometry and otoacoustic emissions. The tests were repeated between 5-10 days in most subjects to check for variability. There were significant differences in the mean age, pure tone average, transient emissions amplitude and variability between groups with and without tinnitus. There were no significant differences between sessions for these measures in either group. Those with tinnitus had poorer thresholds by an average of around 15dB, and reduced TOAE of around 2.6dB compared with those without tinnitus. There are a number of factors such as age, pure tone thresholds and tinntius, which may be responsible for the reduction in emissions. For the purposes of examining SOAE stability, all SOAE peaks were classed as stable if SOAE frequency in the two sessions remained unchanged and variable if SOAE peaks were present in both sessions but shifted in frequency or present in one sessions and absent in the other. SOAE were present in 73.1% of tinnitus group and in 50% of non-tinnitus group. Of these 92% of the tinnitus group had present and variable SOAE whereas 48.9% of the non-tinnitus group did. Thus the positive predictive value was calculated at 65% for those with variable SOAE having tinnitus and significantly higher at 86% negative predictive value for those with stable SOAE having no tinntus. The likelihood ratio of tinnitus being present given that SOAE are present and variable is 1.87 and is significantly reduced for no tinnitus given that SOAE are present and stable at 0.156. This study has clearly demonstrated that the incidence of spontaneous emissions is higher in noise-exposed workers than previously observed and the stability from week to week is significantly lower in those with subjective tinnitus.


[A case of acute sensory and autonomic neuropathy with regression].
The authors report the case of a 24 year old man with no previous disease who presented with a severe autonomic neuropathy. This included major gastrointestinal dysfunction characterised by decreased peristalsis without distension and paralysis of the gall bladder, and orthostatic hypotension with a normal cardiac tachycardia reflex. There was an associated sensory neuropathy affecting heat sensitivity without motor dysfunction and an increased CSF protein content. The proprioceptive nerve fibre conduction was decreased but another nerve conduction was normal initially. The mesenteric plexuses examined during sigmoidectomy performed for peritonitis due to multiple bowel perforations caused by fecoliths, showed no significant changes. Peripheral nerve biopsy revealed massive rarefaction of myelinated fibres which were of small diameter, and of the unmyelinated fibres, mainly due to axonal degeneration. Only two similar cases with incomplete recovery were found in the literature. In our case, a complete recovery was observed. The cause of the condition is unknown.


Controlling the direction of rectification in a molecular diode.
A challenge in molecular electronics is to control the strength of the molecule-electrode coupling to optimize device performance. Here we show that non-covalent contacts between the active molecular component (in this case, ferrocenyl of a ferrocenyl-alkanethiol self-assembled monolayer (SAM)) and the electrodes allow for robust coupling with minimal energy broadening of the molecular level, precisely what is required to maximize the rectification ratio of a molecular diode. In contrast, strong chemisorbed contacts through the ferrocenyl result in large energy broadening, leakage currents and poor device performance. By gradually shifting the ferrocenyl from the top to the bottom of the SAM, we map the shape of the electrostatic potential profile across the molecules and we are able to control the direction of rectification by tuning the ferrocenyl-electrode coupling parameters. Our demonstrated control of the molecule-electrode coupling is important for rational design of materials that rely on charge transport across organic-inorganic interfaces.


Role of Sex Steroids in β Cell Function, Growth, and Survival.
The gonads have long been considered endocrine glands, producing sex steroids such as estrogens, androgens, and progesterone (P4) for the sole purpose of sexual differentiation, puberty, and reproduction. Reproduction and energy metabolism are tightly linked, however, and gonadal steroids play an important role in sex-specific aspects of energy metabolism in various physiological conditions. In that respect, gonadal steroids also influence the secretion of insulin in a sex-specific manner. This review presents a perspective on the physiological roles of estrogens, androgens, and P4 via their receptors in pancreatic β cells in the gender-specific tuning of insulin secretion. I also discuss potential gender-specific therapeutic avenues that this knowledge may open in the future.


Can I order a burger at rnacdonalds.com? Visual similarity effects of multi-letter combinations at the early stages of word recognition.
Previous research has shown that early in the word recognition process, there is some degree of uncertainty concerning letter identity and letter position. Here, we examined whether this uncertainty also extends to the mapping of letter features onto letters, as predicted by the Bayesian Reader (Norris & Kinoshita, 2012). Indeed, anecdotal evidence suggests that nonwords containing multi-letter homoglyphs (e.g., rn→m), such as docurnent, can be confusable with their base word. We conducted 2 masked priming lexical decision experiments in which the words/nonwords contained a middle letter that was visually similar to a multi-letter homoglyph (e.g., docurnent [rn-m], presiclent [cl-d]). Three types of primes were employed: identity, multi-letter homoglyph, and orthographic control. We used 2 commonly used fonts: Tahoma in Experiment 1 and Calibri in Experiment 2. Results in both experiments showed faster word identification times in the homoglyph condition than in the control condition (e.g., docurnento-DOCUMENTO faster than docusnento-DOCUMENTO). Furthermore, the homoglyph condition produced nearly the same latencies as the identity condition. These findings have important implications not only at a theoretical level (models of printed word recognition) but also at an applied level (Internet administrators/users). (PsycINFO Database Record


Hemorrhagic retinopathy in newborns: frequency, form of presentation, associated factors and significance.
During the first 72 hours of their lives, 420 neonates were checked for retinal hemorrhages and macular affection. The neonate's gestational age, birth weight, and Apgar scores and maternal data (nulliparty, fetal presentation, duration of labor and delivery, induction of labor and obstetric technique) were all recorded. In 81 cases (19.2%), retinal hemorrhages were found. No significant relation was established with any of the associated factors, except for a significantly lower frequency of hemorrhages in cases of cesarean delivery (p < 0.01) and a significantly longer expulsive phase in the group with hemorrhages (p < 0.05). In follow-up examination 3 to 4 months later, neither the infants with hemorrhages nor the control group presented alterations.


Gastrointestinal endoscopy training in India.
A structured endoscopy training program with clear goals for proper teaching and evaluation serves to alleviate apprehensions in the minds of trainees regarding this crucial area. It also ensures that training is acquired not in isolation but in the setting of ongoing patient care, so that the emphasis is on how the procedure fits into the overall management plan for the patient. By specifying the details of the endoscopy unit set-up, the qualifications of the trainer and the number of procedures to be performed by the trainee, it is hoped that uniformity will be produced in the quality of training imparted, whether it be in a teaching or a non-teaching hospital. The end-product of such training, through the DM/MCh or the DNB stream, is a gastroenterologist who is also a certified endoscopist, capable of performing all standard diagnostic and therapeutic procedures. A further period of focused training for 1 to 2 years is required to achieve the level of competence expected of an advanced therapeutic endoscopist. There is little room for short-term training courses in endoscopy for the basic training of an endoscopist, although such courses are useful as CME activities, for the maintenance and renewal of skills of the trained endoscopist, as well as providing him with exposure to new and evolving therapeutic techniques. Efforts at improving and standardizing the training and practice of GI endoscopy in India are likely to remain exercises in futility without the active and dynamic involvement of all the leading professional societies in the country. The need of the hour is the establishment of technical committees for laying down standards in training and practice of GI endoscopy that should be voluntarily approved by all these societies so that they may then be implemented by the State medical councils and the MCI. A move in this direction from within the profession is far more appropriate and is also likely to find greater acceptance than such moves imposed from above, at the behest of judicial authorities. A system of hospital accreditation committees for large public and private sector hospitals offering endoscopy services, supervised by the accreditation committee of the State medical council, needs to be established. Clinics and nursing homes offering these services also need to be approved by the same committee after meeting standards similar to those laid down for larger hospitals. Mechanisms for audits of performance and outcome of endoscopic procedures as well as periodic participation in CME activities for maintenance of skills and expertise need to be established and linked to periodic renewal of credentials for practising GI endoscopy. Procedures for credentialing for new endoscopic techniques need to be established. The path ahead is long and arduous but we must tread it for it will only become more difficult if we procrastinate.


Barriers and enablers to implementing tuberculosis control strategies in EU and European Economic Area countries: a systematic review.
Meeting the 2035 WHO targets of reducing tuberculosis incidence by 90% from 2015 levels requires the implementation of country-specific tuberculosis control strategies. This systematic review aims to identify factors that facilitate or impede the implementation of such strategies in EU and European Economic Area (EEA) settings. Focusing on providers of care, health system constraints, and social and political factors, this Review complements available evidence on the accessibility of tuberculosis services to recipients of care. Databases were searched for EU and EEA articles published between Jan 1, 1997, and Nov 6, 2020, that presented empirical data on tuberculosis policies, strategies, guidelines, or interventions. 2061 articles were screened and 65 were included. The most common barrier to tuberculosis control strategies described the divergence of health-care practices from guidelines, often related to inadequate knowledge or perceived usefulness of the guidelines by clinicians. The most commonly identified enabler to tuberculosis control strategies was the documented positive attitudes of health-care workers towards tuberculosis programmes. Divergence between clinical practice and guidelines was described in most EU and EEA settings, indicating the need for a focused review of guideline adherence. Strengths of this study involve its broad inclusion criteria and wide range of tuberculosis control strategies analysed.


Quality of reporting of integrative Chinese and Western medicine intervention in randomized controlled trials of ulcerative colitis: a review.
Integrative Chinese and Western medicine (ICWM) is commonly used for the treatment of ulcerative colitis (UC) in clinical practice. However, it is unclear whether the details of ICWM interventions, such as selection rationale, implementation design, and potential interactions, were adequately reported. Therefore, this study aimed to assess the quality of reporting in the ICWM interventional randomized controlled trials (RCTs) of UC and to identify the common problems if any. Through a search of 10 international electronic databases, we identified RCTs of UC with ICWM interventions published in English or Chinese from the inception date of each database up to 16 June 2023. Literature screening was strictly conducted based on the inclusion and exclusion criteria of the Population, Concept, and Context (PCC) framework. The general characteristics of the included studies were described. The quality of reporting was assessed according to three checklists, including the CONSORT (Consolidated Standards of Reporting Trials) with 36 items (except for one item 1b about abstract), the CONSORT for Abstracts (17 items), and a self-designed ICWM-related checklist (27 items covering design rationale, intervention details, outcome assessments, and analysis). The reporting scores of RCTs published before and after 2010 were compared. A total of 1458 eligible RCTs were included. For the reporting compliance, the median score (interquartile ranges) of the CONSORT (72 score in total), the CONSORT for Abstract (34 score), and ICWM-related (54 score) items was 21 (18-25), 13 (12-15), and 18 (15-21), respectively. Although the time period comparisons showed that reporting quality of included publications improved significantly after the CONSORT 2010 issued (P < 0.01), more than 50% of items were evaluated as poor quality (reporting rate < 65%) among each checklist, especially in the CONSORT for Abstract and ICWM-specific items. Although CONSORT appears to have enhanced the reporting of RCTs in UC, the quality of ICWM specifics is variable and in need of improvement. Reporting guidelines of the ICWM recommendations should be developed to improve their quality.


The solvation effect on the rattling behaviour of the hydrated excess proton in water.
The solvation effect on the kinetic rattling behaviour of the hydrated excess proton H+(aq) in water is theoretically modeled by using density functional theory (DFT) and the quantum chemical cluster model (CM). To test the solvation effects on the proton morphology and rattling kinetics, different solvation models for the proton are constructed based on the gas phase (GP) Zundel cation, which include the gas phase-polarizable continuum model (GP-PCM), the gas phase-supermolecule model (GP-SM), and the gas phase-supermolecule-polarizable continuum model (GP-SM-PCM). These solvation models consider either one or both of the short- and long-range solute-solvent interactions. Meanwhile, 1 to 6 explicit solvent water molecules (Nm' = 1-6) are added around the GP Zundel cation to test different explicit solvation environments. The calculation results show that the solvation environment has an important influence on the morphology and rattling kinetics of H+(aq). The proton rattling pathways are obtained only under the condition that both symmetrical explicit solvation environments and implicit bulk solvents are present. The zero-point contribution reduces the reaction energy barrier and enables the rattling to occur spontaneously at room temperature. The theoretical modeling results provide new insights into the microscopic kinetic behaviour of proton rattling in water at the molecular level, which are helpful in studying the proton transfer mechanism in aqueous systems.


RNA structure determination using SAXS data.
Exploiting the experimental information from small-angle X-ray solution scattering (SAXS) in conjunction with structure prediction algorithms can be advantageous in the case of ribonucleic acids (RNA), where global restraints on the 3D fold are often lacking. Traditional usage of SAXS data often starts by attempting to reconstruct the molecular shape ab initio, which is subsequently used to assess the quality of a model. Here, an alternative strategy is explored whereby the models from a very large decoy set are directly sorted according to their fit to the SAXS data. For rapid computation of SAXS patterns, the method developed here makes use of a coarse-grained representation of RNA. It also accounts for the explicit treatment of the contribution to the scattering of water molecules and ions surrounding the RNA. The method, called Fast-SAXS-RNA, is first calibrated using a tRNA (tRNA-val) and then tested on the P4-P6 fragment of group I intron (P4-P6). Fast-SAXS-RNA is then used as a filter for decoy models generated by the MC-Fold and MC-Sym pipeline, a suite of RNA 3D all-atom structure algorithms that encode and exploit RNA 3D architectural principles. The ability of Fast-SAXS-RNA to discriminate native folds is tested against three widely used RNA molecules in molecular modeling benchmarks: the tRNA, the P4-P6, and a synthetic hairpin suspected to assemble into a homodimer. For each molecule, a large pool of decoys are generated, scored, and ranked using Fast-SAXS-RNA. The method is able to identify low-rmsd models among top ranking structures, for both tRNA and P4-P6. For the hairpin, the approach correctly identifies the dimeric state as the solution structure over the monomeric state and alternative secondary structures. The method offers a powerful strategy for recognizing native RNA conformations as well as multimeric assemblies and alternative secondary structures, thus enabling high-throughput RNA structure determination using SAXS data.