Acupuncture improves immunity and fatigue after chemotherapy in breast cancer patients by inhibiting the Leptin/AMPK signaling pathway.
Acupuncture has become a popular complementary treatment in oncology. This study is based on RNA-Seq transcriptome sequencing technology to investigate the molecular mechanisms underlying the effect of acupuncture-mediated regulation of the Leptin/AMPK signaling pathway on mitochondrial dysfunction-induced fatigue in breast cancer patients after chemotherapy. Peripheral blood samples from 10 patients with post-operative chemotherapy for breast cancer were selected for transcriptome sequencing to screen the key molecular pathways involved in fatigue after chemotherapy in breast cancer patients. Besides, peripheral blood samples were collected from 138 post-operative chemotherapy patients with breast cancer to study the composite fatigue and quality of life scores. Flow cytometry was used to detect T lymphocyte subsets in peripheral blood-specific immune cells. In addition, a blood cell analyzer was used to measure peripheral blood leukocyte counts, and MSP-PCR was used to detect mitochondrial DNA mutations in peripheral blood leukocytes. Transcriptome bioinformatics analysis screened 147 up-regulated mRNAs and 160 down-regulated mRNAs. Leptin protein was confirmed as the key factor. Leptin was significantly higher in the peripheral blood of breast cancer patients who developed fatigue after chemotherapy. Acupuncture treatment effectively improved post-chemotherapy fatigue and immune status in breast cancer patients, suppressed the expression of Leptin/AMPK signaling pathway-related factor and leukocyte counts, and significantly reduced the rate of mitochondrial DNA mutations in peripheral blood leukocytes. The Leptin/AMPK signaling pathway may be the key molecular pathway affecting the occurrence of fatigue after chemotherapy in breast cancer patients. Leptin may improve post-chemotherapy fatigue in breast cancer patients by activating AMPK phosphorylation and alleviating mitochondrial functional impairment.


The morphologic spectrum of infantile lobar emphysema: a study of 33 cases.
Infantile lobar emphysema (ILE) is a relatively uncommon entity characterised by radiologic pulmonary lobar overinflation. The spectrum of underlying pathology in ILE has not been previously detailed. We have reviewed thirty-three cases of ILE accessioned to the Armed Forces Institute of Pathology, Washington D.C., since 1970. Seventeen (51.5%) presented in the first week of life, 27 (81.8%) presented within the first six months, and an additional six cases presented beyond six months including three beyond 18 months of age. Upper lobe involvement occurred in 96.9% cases and multiple lobes were involved in six cases. Nine infants had polyalveolar (hyperplastic) lobes determined on the basis of radial alveolar counts (RACs), while 21 were considered to be "classic ILE" since these showed lobar hyperexpansion without any other abnormality. RACs in infants with classic ILE remained fairly constant irrespective of age unlike a progressive increase seen in normal age-matched controls, suggesting a post-partum arrest of acinar development in ILE. Additional findings included serpiginous bronchioles resembling those seen in extralobar sequestration in two cases, bronchopulmonary dysplasia in two cases, and one case each showing "cystic alveoli" and peripheral subpleural cysts. ILE thus seems to be a composite of various pathologies resulting in a single clinical entity. We hypothesise that the timing of an inciting functional or anatomic bronchial obstruction during in-utero lung development determines morphologic variation in ILE.


Early Prediction of All-Cause Clinical Deterioration in General Wards Patients: Development and Validation of a Biomarker-Based Machine Learning Model Derived From Rapid Response Team Activations.
The aim of the study is to evaluate the performance of a biomarker-based machine learning (ML) model (not including vital signs) derived from reviewed rapid response team (RRT) activations in predicting all-cause deterioration in general wards patients. This is a retrospective single-institution study. All consecutive adult patients' cases on noncritical wards identified by RRT calls occurring at least 24 hours after patient admission, between April 2018 and June 2020, were included. The cases were reviewed and labeled for clinical deterioration by a multidisciplinary expert consensus panel. A supervised learning approach was adopted based on a set of biomarkers and demographic data available in the patient's electronic medical record (EMR). The setting is a 250-bed tertiary university hospital with a basic EMR, with adult (>18 y) patients on general wards. The study analyzed the cases of 514 patients for which the RRT was activated. Rapid response teams were extracted from the hospital telephone log data. Two hundred eighteen clinical deterioration cases were identified in these patients after expert chart review and complemented by 146 "nonevent" cases to build the training and validation data set. None. The best performance was achieved with the random forests algorithm, with a maximal area under the receiver operating curve of 0.90 and F1 score of 0.85 obtained at prediction time T0-6h, slightly decreasing but still acceptable (area under the receiver operating curve, >0.8; F1 score, >0.75) at T0-42h. The system outperformed most classical track-and-trigger systems both in terms of prediction performance and prediction horizon. In hospitals with a basic EMR, a biomarker-based ML model could be used to predict clinical deterioration in general wards patients earlier than classical track-and-trigger systems, thus enabling appropriate clinical interventions for patient safety and improved outcomes.


When to shed? Patterns and drivers of time to first ecdysis in snakes.
Time from birth or hatching to the first shed (postnatal ecdysis) in snakes ranges from about an hour to several weeks depending upon the species. We assessed patterns in time to postnatal ecdysis in 102 snake species for which we could source appropriate information, covering 2.6% of all extant snake species, and related measures to various biological traits. Reconstruction revealed ancestral time to postnatal ecdysis to be 11 days. Since time to postnatal ecdysis can be shorter or longer than the ancestral state, we argue that there are several competing drivers for time to postnatal ecdysis. A reduced time to postnatal ecdysis has evolved in several lineages, commonly in ambush-foraging, viviparous vipers, while extended time to postnatal ecdysis is associated with oviparous species with maternal care. Of central importance is the impact of postnatal ecdysis on the scent levels of neonates, resulting in a reduction of time to postnatal ecdysis in chemically cryptic species, while the pivotal role of scent in mother-neonate recognition has resulted in the retention or extension of time to postnatal ecdysis. We showed that postnatal ecdysis improves chemical crypsis. The patterns revealed in this study suggest that measures of time to postnatal ecdysis can provide insights into the biology of snakes and be used as an indicator of certain life history traits.


A suggestive seizure induction technique protocol in a short EEG in children and adolescents.
The use of a suggestive seizure induction procedure (SSI) in medicine, particularly in the differential diagnosis of psychogenic nonepileptic epileptic seizures (PNES), is well documented. However, there is no description of standardized suggestion procedures used in children and adolescents. The research presents a standardized method of SSI with a cotton swab soaked in water. The protocol was developed based on of 544 placebo trials over ten years in a center for the differential diagnosis of children and adolescents. The protocol is a safe tool that allows inducing specific behavior in children and adolescents in whom there is a well-founded suspicion of PNES.


Cell versus Chemokine Therapy in a Nonhuman Primate Model of Chronic Intrinsic Urinary Sphincter Deficiency.
Mixed efficacy results of autologous skeletal muscle precursor cell therapy in women with chronic intrinsic urinary sphincter deficiency have increased interest in the therapeutic value of alternative regenerative medicine approaches. The goal of this study was to compare the effects of the cell homing chemokine CXCL12 (C-X-C motif chemokine 12) and skeletal muscle precursor cells on chronic urinary sphincter regeneration in chronic intrinsic urinary sphincter deficiency. Five million autologous skeletal muscle precursor cells or 100 ng CXCL12 were injected in the urinary sphincter complex of adult female cynomolgus monkeys with chronic (6-month history) intrinsic urinary sphincter deficiency. These treatment groups of 3 monkeys per group were compared to a group of 3 with no intrinsic urinary sphincter deficiency and no injection, and a group of 3 with intrinsic urinary sphincter deficiency plus vehicle injection. Maximal urethral pressure was measured at rest, during stimulation of the urinary sphincter pudendal nerves at baseline and again 6 months after treatment. The monkeys were then necropsied. The urinary sphincters were collected for tissue analysis of muscle and collagen content, vascularization and motor endplates. CXCL12 but not skeletal muscle precursor cells increased resting maximal urethral pressure in nonhuman primates with chronic intrinsic urinary sphincter deficiency compared to that in monkeys with intrinsic urinary sphincter plus vehicle injection (p >0.05). Skeletal muscle precursor cells and CXCL12 only partially restored pudendal nerve stimulated increases in maximal urethral pressure (p >0.05), sphincter vascularization and motor endplate expression in monkeys with chronic intrinsic urinary sphincter deficiency. Additionally, CXCL12 but not skeletal muscle precursor cell injections decreased collagen and increased the muscle content of urinary sphincter complex in monkeys with chronic intrinsic urinary sphincter deficiency compared to those with intrinsic urinary sphincter plus vehicle injection and no intrinsic urinary sphincter plus no injection (p <0.05 and >0.05, respectively). These results raise questions about cell therapy for chronic intrinsic urinary sphincter deficiency and identify a chemokine treatment (CXCL12) as a potential alternative treatment of chronic intrinsic urinary sphincter deficiency.


Conductive Graphitic Carbon Nitride as an Ideal Material for Electrocatalytically Switchable CO2 Capture.
Good electrical conductivity and high electron mobility of the sorbent materials are prerequisite for electrocatalytically switchable CO2 capture. However, no conductive and easily synthetic sorbent materials are available until now. Here, we examined the possibility of conductive graphitic carbon nitride (g-C4N3) nanosheets as sorbent materials for electrocatalytically switchable CO2 capture. Using first-principle calculations, we found that the adsorption energy of CO2 molecules on g-C4N3 nanosheets can be dramatically enhanced by injecting extra electrons into the adsorbent. At saturation CO2 capture coverage, the negatively charged g-C4N3 nanosheets achieve CO2 capture capacities up to 73.9 × 10(13) cm(-2) or 42.3 wt%. In contrast to other CO2 capture approaches, the process of CO2 capture/release occurs spontaneously without any energy barriers once extra electrons are introduced or removed, and these processes can be simply controlled and reversed by switching on/off the charging voltage. In addition, these negatively charged g-C4N3 nanosheets are highly selective for separating CO2 from mixtures with CH4, H2 and/or N2. These predictions may prove to be instrumental in searching for a new class of experimentally feasible high-capacity CO2 capture materials with ideal thermodynamics and reversibility.


MiR-2425-5p targets RAD9A and MYOG to regulate the proliferation and differentiation of bovine skeletal muscle-derived satellite cells.
Our group previously identified miR-2425-5p, a unique bovine miRNA; however, its biological function and regulation in muscle-derived satellite cells (MDSCs) remain unclear. Herein, stem-loop RT-PCR results showed that miR-2425-5p increased during MDSCs proliferation, but decreased during differentiation. Cell proliferation was examined using EdU assays, cyclin B1 (CCNB1) and proliferating cell nuclear antigen (PCNA) western blot (WB) and flow cytometry analysis. These results showed that miR-2425-5p mimics (miR-2425-M) enhanced MDSCs proliferation, whereas, miR-2425-5p inhibitor (miR-2425-I) had opposite effect. Conversely, cell differentiation studies by desmin (DES) immunofluorescence, myotubes formation, and myosin heavy chain 3 (MYH3) WB analyses revealed that miR-2425-M and miR-2425-I blocked and promoted MDSCs differentiation, respectively. Moreover, luciferase reporter, RT-PCR, and WB assays showed that miR-2425-5p directly targeted the 3'-UTR of RAD9 homolog A (RAD9A) and myogenin (MYOG) to regulate their expression. Rescue experiment showed RAD9A inhibited the proliferation of MDSCs through miR-2425-5p. In addition, we found that miR-2425-5p expression was regulated by its host gene NCK associated protein 5-like (NCKAP5L) rather than being transcribed independently as a separate small RNA. Collectively, these data indicate that miR-2425-5p is a novel regulator of bovine MDSCs proliferation and differentiation and provides further insight into the biological functions of miRNA in this species.


Orientation of lipid tubules by a magnetic field.
Lipid tubules, which are straight hollow cylinders consisting of lipid bilayers, are shown to orient in strong magnetic fields. Birefringence measurements were made of dilute samples of tubules of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC23PC) in magnetic fields of up to 4 T. The tubules were found to orient with their long axes parallel to the field direction, with saturated orientation [P2 (cos theta] approximately greater than 0.95) found at approximately 2 T. From known distributions of lengths and the number of bilayers in the walls, a value delta chi = (-7 +/- 1) X 10(-9) erg cm-3 G-2 was calculated for the tubules, which compares well with some previously reported values for phosphatidylcholines. Magnetic alignment will permit more sophisticated structural studies of monomeric and polymeric tubules, and provide a method of orienting macromolecules in the tubule walls or interior.


Circular dichroic properties of flavan-3,4-diols.
CD data of the eight diastereoisomers of free phenolic and different O-derivatized analogues of a series of flavan-3,4-diols permit assignment of the absolute configuration at the stereocenters of the heterocyclic ring.


Pediatric Ocular Toxocariasis in Costa Rica: 1998-2018 Experience.
To report the epidemiology, clinical characteristics, treatment and outcomes of patients with ocular toxocariasis. Retrospective review of patients diagnosed with ocular toxocariasis at a pediatric referral center from 1998 until 2018 in Costa Rica. 157 patients were diagnosed with ocular toxocariasis with a mean follow-up of 3.1 years. The mean age at presentation was 6.7 years old. The most common causes of consultation included decreased vision (29.9%), strabismus (26.7%), and leukocoria (19.7%). The most common findings included peripheral granuloma, posterior pole granuloma, and chronic endophthalmitis. Sixty-nine (43.9%) eyes had retinal detachment. Patients were managed with a variety of treatments including pars plana vitrectomy, systemic corticosteroids, anti-helminthic drugs or a combination of these. Most eyes did not exhibit functional improvement despite treatment. Most patients with pediatric ocular toxocariasis in Costa Rica often present late and despite treatment, most remain with poor vision in the affected eye.


Parenteral nutrition for hospitalized infants: 20th-century advances in venous access.
To review the literature related to venous access for parenteral infant feeding. Sources included medical, nursing, and nutrition literature from 1900 to 1994. One hundred ten studies were reviewed. Studies were selected based on historical significance and contribution to current practice. Data relating to the development of parenteral nutrients or evolution of parenteral techniques were extracted. The central venous catheter was a significant development in meeting the nutritional needs of hospitalized infants. Delivery of parenteral nutrition through percutaneous, peripherally inserted central venous catheters provides the least trauma and greatest benefit.


Effects of fine carbonaceous particles containing high and low unpaired electron spin densities on lungs of female mice.
The negative impacts on human health that accompany inhalation of atmospheric particles are documented in numerous epidemiologic studies, but the effect of specific chemical properties of the particles is generally unknown. We developed and employed technology for generating inhalable aerosols of carbonaceous air pollution particles that have specific physical and chemical properties. We find that inhaling particles with greater unpaired electron spin (free radical) densities stimulates greater lung inflammatory and oxidative stress responses. Cultured alveolar macrophages take up more particles of greater free radical content, develop mitochondrial abnormalities, and release more leukotriene B(4) (LTB(4)) than alveolar macrophages exposed to lesser free-radical-containing particles in vitro. Mice exposed to high free radical particles in vivo also develop mitochondrial abnormalities in alveolar macrophages and increased oxidative stress, which is reflected by increases in lung nitrotyrosine staining and lung lavage nitrogen oxide levels compared with those of lesser free radical density. These results provide insight for the unexplained geographic differences and have implications for fossil fuel combustion conditions and the impact of fine particles on health and disease.


A live, attenuated pseudorabies virus strain JS-2012 deleted for gE/gI protects against both classical and emerging strains.
Emerging pseudorabies virus (PRV) variant have led to pseudorabies outbreaks in Chinese pig farms. The commercially available PRV vaccine provides poor protection against the PRV variant. In this study, a gE/gI deleted PRV strain JS-2012-△gE/gI was generated from a PRV variant strain using homologous DNA recombination. Compared to the parental strain JS-2012, JS-2012-△gE/gI grew slowly and showed small plaque morphology on Vero cells. The safety and immunological efficacy of JS-2012-△gE/gI was evaluated as a vaccine candidate. JS-2012-△gE/gI was avirulent to suckling piglets, but was able to provide full protection for young piglets against challenge with both the classical virulent PRV and the emerging PRV variant. After sows were vaccinated with the gE/gI-deleted strain, their suckling offspring were resistant to an otherwise lethal challenge with the classical and the variant PRVs. Piglets inoculated with JS-2012-△gE/gI did not develop PRV-specific gE-ELISA antibodies. Thus, JS-2012-△gE/gI appears to be a promising marker vaccine candidate to control PRV variant circulating in pig farms in China.


Urinary kallikrein excretion and plasma DBH activity in hypertension.
Many factors are to be considered in maintaining normal blood pressure. Authors study the behavior of urinary kallikrein (U.K.) and plasma dopamine-beta-hydroxylase (DBH) activity in various forms of hypertension. The values of U.K. excretion in normals were 20.5 +/- 1.8 E.U./24 h. In essential hypertensive patients (9.4 +/- 2.0 E.U./24 h) U.K. decreased, while in secondary hypertension it was significantly higher (33.8 +/- 3.0 E.U./24 h). Plasma DBH activity in essential hypertensive patients (17.72 +/- 2.33 I.U./ml) was similar to controls (20.22 +/- 1.39 I.U./ml); in secondary hypertension the mean values of plasma DBH were decreased (12.31 +/- 2.55 I.U./ml). No correlation between U.K. and plasma DBH activity was observed in normals and in various forms of hypertensive patients. U.K. seems a more reliable factor than plasma DBH in defining the different types of hypertension.


Targeting RNA helicases in cancer: The translation trap.
Cancer cells are reliant on the cellular translational machinery for both global elevation of protein synthesis and the translation of specific mRNAs that promote tumor cell survival. Targeting translational control in cancer is therefore increasingly recognized as a promising therapeutic strategy. In this regard, DEAD/H box RNA helicases are a very interesting group of proteins, with several family members regulating mRNA translation in cancer cells. In this review, we delineate the mechanisms by which DEAD/H box proteins modulate oncogenic translation and how inhibition of these RNA helicases can be exploited for anti-cancer therapeutics.


Anterior segment anomalies of the eye, clefting and skeletal abnormalities in two sibs of consanguineous parents: Michels syndrome or new syndrome?
We report two sibs of consanguineous parents with multiple congenital abnormalities which include prenatal and postnatal growth retardation, anterior segment defects of the eye, arachnodactyly with other skeletal abnormalities, congenital heart disease and early lethality. We think this constellation of anomalies may represent a previously undescribed syndrome. There are some similarities to Michels syndrome from which it should be differentiated.


Genetic mapping of two loci, DXS454 and DXS458, with respect to the X-linked agammaglobulinemia gene locus.
The dinucleotide repeat sequences at the DXS454 and DXS458 loci have been mapped genetically to Xq22, to the interval between DXS3 and DXS17. We have now mapped them with respect to XLA and five other loci, to within the DXS3 to XLA interval. The more precise localisation of these polymorphic loci will be useful for the fine-mapping of disease loci on the long arm of the X chromosome and enable these probes to be used for prenatal diagnosis and carrier status determination in families with XLA.


[Chemical constituents of Chinese medicinal plant Rubus parviforlius L].
Two crystalline components were isolated from the roots of Rubus parviforlius and determined as niga-ichigoside F1 and sauvissimoside R1 by spectroscopic evidences and chemical reactions. They were obtained from the plant for the first time.


Technical report: effects of PUVA treatment on the optical properties of blood/tissue storage bags during extracorporeal photochemotherapy.
Extracorporeal photochemotherapy (photopheresis, ECP) is a novel therapeutic method for patients who do not respond to immunosuppressive medications, and gaining interest in the treatment of Graft-vs-Host Disease. This paper is focused on the optical transmission properties of plastic bags which can be used in an independent (off-line) method of ECP, and reports the results of spectral measurements on various bags of different chemical compositions, with and without PUVA treatment. Regarding their higher and more uniform UVA transmission values, FEP based bags perform superior to the others. Considering its UVB absorption and UVA transmission properties, the EVA bag is a good choice, while Polyimide Kapton-FEP plastic film should not be considered for use in ECP. PUVA treatment of blood bags may affect their optical behaviour, and causes reduction of transmission of the material in UV range of the spectrum.


Preparing the Intensive Care Unit for a Lethal Viral Respiratory Pandemic.
Future pandemics will certainly arise and continue to have a profound impact on health care, including management within the intensive care unit. Robust preparedness plans require specific attention to detail as it pertains to incident management, surge capacity, infection control practices, and the health care workforce. The COVID-19 pandemic highlighted many gaps in prior preparedness efforts, and those lessons learned must be integrated into updated preparedness work. Additionally, ensuring health care workforce wellness, decreasing health care disparities, strengthening networks for rapid research and response, and active roles in dispelling misinformation within the media should be integrated into pandemic preparedness plans.


Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma.
The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC. Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene's methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection. Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARβ), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARβ, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT. The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC.


Thulium fiber laser lithotripsy: Is it living up to the hype?
The holmium:yttrium-aluminium-garnet laser (Ho:YAG) has been the gold standard for laser lithotripsy over the last three decades. After demonstrating good in vitro efficacy, the thulium fiber laser (TFL) has been recently released in the market and the initial clinical results are encouraging. This article aims to review the main technology differences between the Ho:YAG laser and the TFL, discuss the initial clinical results with the TFL as well as the optimal settings for TFL lithotripsy. We reviewed the literature focusing on the technological aspects of the Ho:YAG laser and TFL as well as the results of in vitro and in vivo studies comparing both technologies. In vitro studies show a technical superiority of TFL compared to the Ho:YAG laser and encouraging results have been demonstrated in clinical practice. However, as TFL is a new technology, limited studies are currently available, and the optimal settings for lithotripsy are not yet established. TFL has the potential to be an alternative to the Ho:YAG laser, but more reports are still needed to determine the optimal laser for lithotripsy of urinary tract stones when considering all parameters including effectiveness, safety, and costs.


The use of chest wall muscle flaps to close bronchopleural fistulas: experience with 21 patients.
Nineteen patients with bronchopleural fistulas associated with tuberculosis and 2 patients with fistulas following resection for bronchiectasis underwent closure of the fistulas with pedicled flaps of chest wall muscle. The muscle grafting was combined with a limited thoracoplasty in 13 patients. The initial myoplasty produced prompt fistula closure in 15 patients and delayed closure in 2 others. A repeat myoplasty was successful in 2 patients in whom the initial myoplasty failed. Compared with other methods of treating bronchopleural fistulas used during the same period, muscle grafting carried a higher rate of successful fistula closure and a lower mortality rate.


Pro-Active Fall-Risk Management is Mandatory to Sustain in Hospital-Fall Prevention in Older Patients--Validation of the LUCAS Fall-Risk Screening in 2,337 Patients.
Prevention of in-hospital falls contributes to improvement of patient safety. However, the identification of high-risk patients remains a challenge despite knowledge of fall-risk factors. Hence, objective was to prospectively validate the performance of the LUCAS (Longitudinal Urban Cohort Ageing Study) fall-risk screening, based on routine data (fall history, mobility, mental status) and applied by nurses. Observational study comparing two groups of patients who underwent different fall-risk screenings; the LUCAS screening (2010 - 2011) and the STRATIFY (St. Thomas's Risk Assessment Tool In Falling Elderly Inpatients) (2004 - 2006). Urban teaching hospital. Consecutively hospitalized patients (≥ 65 years old) were screened on admission; LUCAS n = 2,337, STRATIFY n = 4,735. The proportions of fallers were compared between the STRATIFY and the LUCAS time periods. The number of fallers expected was compared to that observed in the LUCAS time period. Standardized fall-incidence recording included case-note checks for unreported falls. Plausibility checks of fall-risk factors and logistic regression analysis for variable fall-risk factors were performed. The proportions of fallers during the two time periods were LUCAS n = 291/2,337 (12.5%) vs. STRATIFY n = 508/4,735 (10.7%). After adjustment for risk-factor prevalence, the proportion of fallers expected was 14.5% (334/2,337), the proportion observed was 12.5% (291/2,337) (p = 0.038). In-hospital fall prevention including systematic use of the LUCAS fall-risk screening reduced the proportion of fallers compared to that expected from the patients' fall-risk profile. Raw proportions of fallers are not suitable to evaluate fall prevention in hospital because of variable prevalence of patients' fall-risk factors over time. Continuous communication, education and training is needed to sustain in-hospital falls prevention.


Luteolin attenuates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via suppression of inflammation response.
Psoriasis is considered as a common chronic immune-mediated skin disorder characterized by abnormal keratinocyte proliferation. Luteolin, an anti-inflammatory natural flavonoid with well-accepted inhibition effect against keratinocyte proliferation, was hypothesized to have a potential therapeutic effect for psoriasis. In this paper, we investigated the relieving effect of luteolin against imiquimod-induced psoriasis-like lesions on BALB/c mice and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated macrophages (RAW264.7 cells). We found that luteolin ameliorated psoriasis-like skin lesions, suppressed the cutaneous infiltration of macrophages, T cells and neutrophils, and downregulated the expression of cytokines like IL-6, IL-1β, TNF-α, IL-17A and IL-23 in both skin lesions and eyeball blood of model mice. In vitro, we observed luteolin significantly suppressed the levels of psoriasis-related pro-inflammatory cytokines, such as IL-17A, IL-6, TNF-α and IL-23, and inflammatory mediators like nitric oxide NO, inducible NOS, COX-2 in RAW264.7 cells. The anti-inflammatory activity was accomplished by inhibiting NF-κB expression and activation. This study demonstrates luteolin is effective in alleviating psoriasis-like skin lesions and downregulating inflammatory response via NF-κB pathway, suggesting luteolin as a potential molecule for further therapeutic research of inflammation-related skin diseases like psoriasis.


Optimal P-wave duration for bedside diagnosis of interatrial block.
Interatrial block (IAB; P wave > or = 110 ms) is highly prevalent and associated with atrial tachyarrhythmias, left atrial electromechanical dysfunction and is a potential risk for embolism. Investigators have often used different parameters for P-wave duration to define IAB, and this causes confusion further adding to clinician ignorance of IAB. We therefore appraised the mode P-wave duration in IAB and evaluated the sensitivity and specificity of using previously used durations. We prospectively evaluated 225 electrocardiograms (ECGs) of patients at a tertiary care general hospital for P-wave duration. Of these, 49 were excluded because of severe motion artifact, errors in lead placement, absence of adequate patient identification, and atrial flutter or fibrillation. Mean, standard error of mean (SEM), standard deviation (SD), mode P-wave duration, specificity, and sensitivity were calculated of the remaining 176 ECGs. From the sample (N = 176; ages 15-95 years; mean +/- SD = 69.15 +/- 16.53 years, female 50.3%), measured P-wave durations ranged from 50 ms to 230 ms (mean +/- SD = 113.75 +/- 30.56 ms, SEM 2.30 ms). 96 patients (54.55%) showed IAB (P wave > or = 110 ms) with the mode P-wave duration being 120 ms. Sensitivity and specificity of using P wave > or = 110 ms is 100% and 88.9%, respectively (accuracy 94.31%), while P wave > or =130 ms yielded 64% and 100%, respectively (accuracy 82.38%). Mode P-wave duration in IAB is 120 ms, and thus, for all practical reasons, it may be used to clinically diagnose IAB using ECGs recorded at the bedside at 25 mm/s with 10 mm/mV standardization.


The standard 'Healthcare Information Systems Architecture' and the DHE middleware.
The integration and evolution of existing systems represents one of the most urgent priorities of health care information systems in order to allow the whole organisation to meet the increasing clinical organisational and managerial needs. This paper discusses how an open architecture, based on the introduction of a middleware of common health care-specific services not only reduces the effort necessary for allowing existing systems to interwork, but also automatically establishes a functional and information basis common to the whole organisation, on top of which also new applications can be rapidly developed, natively integrated with the rest of the system. Such architecture has been already formalised through the European standard, defined by the CEN/TC251 prENV 12967-1 'Architecture for Health care Information Systems' (CEN prENV 12967-1 'Health care Information Systems Architecture'). Thanks to the availability of industrial products conforming to the standard, the effectiveness and the validity of this approach has been already demonstrated in practice. For example, through the Hansa collaboration hospitals and industries from countries of the Western and Eastern Europe, as well as of the Middle East use the same industrial middleware (i.e. 'The DHE middleware-Information view'-SPRI, 1998, 'The DHE middleware-Functional view'-SPRI, 1998) for integrating existing systems as well as for developing new applications.


Glomerulocystic kidney: proposed etiology and pathogenesis.
Glomerulocystic kidney, an unusual lesion seen only in infancy or early childhood, involves cystic dilatation of Bowman's space without evidence of urinary obstruction. This disease may result from intrarenal medullary obstruction in the third trimester of pregnancy because 1) it is similar to the cystic kidney lesion produced by urethral obstruction, 2) patients with glomerulocystic kidney have no evidence of extrarenal urinary tract obstruction and 3) most patients with glomerulocystic kidney have evidence of inflammation and fibrosis in the renal medulla. A prenatal drug history of prolonged maternal ingestion of phenacetin in an infant with glomerulocystic kidney prompted us to submit a possible etiologic source for the hypothesis of intrarenal obstruction.


The effect of different concentrations and temperatures of sodium hypochlorite irrigation on pain intensity following endodontic treatment of mandibular molars with irreversible pulpitis: A randomized, double-blind clinical trial.
This study aimed to determine the severity of pain after endodontic treatment of mandibular molars with irreversible pulpitis following the use of sodium hypochlorite (NaOCl) at different temperatures and concentrations. In this randomized, controlled clinical trial, 72 patients with mandibular molars with irreversible pulpitis were randomly assigned to six groups. The teeth were anesthetized and the root canals were prepared. During the instrumentation, the root canals were irrigated with NaOCl solution at concentrations of 0.5% and 1% and temperatures of 2.5°C, 22°C, and 40°C, 2.5°C were achieved through cryotherapy. Assessment of pain was conducted before, immediately after, and 3, 24, 48, and 72 h after treatment. After obturation, the patients recorded their pain intensity at different time intervals on the visual analog scale (VAS) and reported the number of analgesics tablets they used. The frequency of analgesics tablets and their effect on pain sensation was recorded in the second part of the form. Repeated measures two-way analysis of variance test was used to compare the trend of pain changes over time between two intervals of time in each group. Friedman's nonparametric test was used to compare the intragroup mean score of pain over time and Kruskal-Wallis for comparing the intergroup mean score. Changes in VAS pain scores of all the groups were significant over time (p < .001). Pain in all the groups decreased immediately after treatment and increased 3 h after treatment. There were no significant differences in pain ratings and the number of analgesics tablets used in the groups of NaOCl with different concentrations and temperatures over time. Within the study's limitations, we concluded that there was no significant difference between concentrations of 0.5%, and 1% and temperatures of 2.5°C, 22°C, and 40°C in pain intensity following endodontic treatment of mandibular molars with irreversible pulpitis.


Morphology of the capsule-like portion of the reactive membranes on intraocular lens implants.
The glass-membrane-like capsules probably are the practically most important part of the separating membranes that typically form on intraocular lens implants in the human eye. With time in the eye, these clear capsules become tougher, more firmly adherent, and less eosinophilic. Their formation occurs early after implantation and is associated with the reactions of intraocular macrophages. Examples of well developed capsules are presented to show that only few cells are needed for their maintenance and that they can be of irregular thickness. Cell life on the film-like capsules is demonstrated using the examples of blood-eating macrophages, epitheliod cells, and melanocytes. Attachment of fibrous structures containing zonular fibers to the haptics is recorded.


A non-parametric grading system for intestinal metaplasia: correlations with gastric tissue enzymes.
A novel method for grading intestinal metaplasia, with general applicability, is described. Highly significant agreement was found by kappa analysis both for intra-observer (k = 0.90) and for inter-observer (k = 0.85) variation, confirming the reproducibility of the method. The ranks derived by this method were correlated with gastric tissue levels of the enzymes beta-glucuronidase, lactic dehydrogenase (LDH), and %m-LDH. A significant (P less than 0.05) positive correlation was found between intestinal metaplasia and %m-LDH, but there was no correlation between intestinal metaplasia and beta-glucuronidase or LDH.


Cardiac resynchronisation therapy: a randomised trial of factory or echocardiographic settings for optimum response.
We aimed to assess whether echocardiographically-optimised atrioventricular (AV) and interventricular (VV) delay programming provided any additional benefit over standard settings following biventricular pacemaker implantation in patients with advanced heart failure. Paired data were collected on 22 patients (aged 67.5 ± 8.3 years, 16 male) with refractory heart failure, NYHA class III/IV symptoms, sinus rhythm, LBBB and a broad QRS complex >120 ms. All patients underwent implantation of a biventricular pacemaker and were randomised to eight weeks of factory pacing mode (Mode 1) or echocardiographically-guided pacing mode (Mode 2), followed by eight weeks in the alternate mode, in a randomised blinded crossover design. Peak oxygen consumption, 6 min walk distance, NYHA class and quality of life scores improved after biventricular pacing, but no significant difference was found between the two modes, with the exception of peak oxygen consumption score (baseline: 14.8 ± 0.9, Mode 1: 14.6 ± 1.2, Mode 2: 16.1 ± 1.2 mL/kg/min), which was better in Mode 2 than Mode 1 (p 0.003). Transthoracic echocardiographic optimisation of AV and VV delays following biventricular pacing may offer additional clinical benefit in an unselected group of patients when compared with factory settings.


M-6 endocarditis: report of an Australian case.
Neisseria elongata subsp. nitroreducens (formerly CDC group M-6) is a newly-recognized cause of particularly destructive endocarditis, frequently requiring valve replacement. We describe an Australian case of endocarditis caused by this organism, summarizing the clinical and microbiological features of this rarely isolated subspecies.


Idiopathic chronic fatigue and myalgia syndrome (myalgic encephalomyelitis): some thoughts on nomenclature and aetiology.
Myalgic encephalomyelitis is a misnomer that describes epidemics of probable hysterical illness and bears no definite relationship to chronic fatigue and myalgia syndrome. The relationship of idiopathic fatigue syndromes to fatigue syndromes after well-defined viral illnesses such as glandular fever is also unclear. Detailed studies of muscle histochemistry and biochemistry in idiopathic chronic fatigue and myalgia syndrome do not support a defect in intermediate metabolism. The aetiology of this syndrome is unknown and it is not yet clear whether it has an organic or a non-organic basis.


Adrenal incidentaloma in pregnancy: clinical, molecular and immunohistochemical findings.
Adrenal incidentalomas detected during pregnancy are very rare, and the natural history of these tumors during gestation is unknown. We report a case of a pregnant woman with an adrenal mass discovered serendipitously, who was followed-up during gestation and underwent adrenalectomy shortly after delivery. This allowed the evaluation of both the clinical outcome and the molecular/immunohistochemical correlates. Estrogens may indeed influence the function and proliferation of human adrenal cells, and a state of circulating estrogen excess can represent an in vivo model to test their effect on the adrenals. No evidence of adrenal change in morphology and function was found in our patient throughout pregnancy, as shown by adrenal ultrasound imaging and adrenal hormone measurements. Four months after delivery, the patient underwent laparoscopic right adrenalectomy, and pathologic analysis revealed a 2.7 cm benign adrenocortical adenoma. The diameter of the adrenal mass at ultrasonography correlated highly with post-partum mass diameter measured by abdominal computed tomography (CT). Quantitative expression of both ERalpha and ERbeta by real-time RT-PCR analysis and Western blotting findings did not differ among adenoma, normal adjacent adrenal and normal adrenal control tissues. This case of an adrenal incidentaloma discovered during pregnancy shows that a close observation with endocrine investigations and ultrasonography could be an appropriate approach, delaying the decision of surgical intervention after delivery. Estrogen receptor mRNA levels in the adrenal mass similar to those observed in normal adrenals suggest that estrogen oversecretion during pregnancy was not a risk factor for tumor progression.


Smoking as a contributing factor for development of polycythemia vera and related neoplasms.
Smoking may be associated with accelerated erythropoiesis, leukocytosis and thrombocytosis, which are also hallmarks in patients with polycythemia vera, essential thrombocythemia and early stages of myelofibrosis (MPNs). The JAK-STAT and NF-κB signaling pathways are activated in both smokers and in patients with MPNs. Additionally, both share elevated levels of several proinflammatory cytokines, in vivo activation of leukocytes and platelets, endothelial dysfunction and increased systemic oxidative stress. Based upon experimental, epidemiological and clinical data it is herein argued and discussed, if smoking may be involved in MPN pathogenesis, considering most recent studies and reviews which are supportive of the concept that chronic inflammation with NF-κB activation and oxidative stress may have a major role - both as triggers but also as the driving force for clonal expansion in MPNs.


Anticholinergic component of the Drug Burden Index and the Anticholinergic Drug Scale as measures of anticholinergic exposure in older people in New Zealand: a population-level study.
Older people are exposed to multiple medicines that possess anticholinergic properties. The use of anticholinergic medicines is associated with the risk of morbidity, mortality and cognitive decline, particularly in older people. Anticholinergic exposure can be measured using tools such as the Drug Burden Index-Anticholinergic component (DBI-ACh) and the Anticholinergic Drug Scale (ADS). The aim of this population-level study was to determine the extent of anticholinergic exposure in older people, particularly among those receiving acetylcholinesterase inhibitors in New Zealand. The study used data extracted from Pharmaceutical Claims Data Mart (Pharms) for the year 2011. A total of 537,387 individuals aged 65 years and older were included in the study, of whom 45.10 % were men. Individuals dispensed donepezil at any time during 2011 were selected as the acetylcholinesterase inhibitor (AChEI) group (n = 4,258) and the remainder were included in the non-acetylcholinesterase inhibitor (non-AChEI) group (n = 533,129). Anticholinergic exposure was measured using the DBI-ACh and the ADS. Analysis of the Pharms dataset revealed that, in 2011, anticholinergic exposure as defined by the DBI-ACh and the ADS was 31.80 % and 52.66 %, respectively. The mean number of medicines dispensed was 5.64 ± 3.91 (± SD) with a 95 % confidence interval of 5.63-5.65. In the AChEI group, anticholinergic exposure using the DBI-ACh and the ADS was 42.93 % (median 0; interquartile range (IQR) 1) and 58.50 % (median 0; IQR 0), respectively. ADS level 3 medicines such as amitriptyline, nortriptyline and oxybutynin were commonly prescribed in both groups. Amitriptyline, nortriptyline, oxybutynin and paroxetine are medicines considered to have significant anticholinergic potency. Of these medicines, nortriptyline and oxybutynin were more frequently prescribed in individuals taking donepezil. A significant proportion of older people are exposed to medicines with anticholinergic properties, including those dispensed acetylcholinesterase inhibitors. Further research is required to explore associations between different measures of anticholinergic exposure and clinically relevant outcomes in older people on a population level.


Association between mask wearing and anxiety symptoms during the outbreak of COVID 19: A large survey among 386,432 junior and senior high school students in China.
To evaluate the association between mask wearing practice and the risk of anxiety symptoms during the COVID-19 epidemic among Chinese students aged 12-18 years old. Totally, 386,432 junior and senior high school students were recruited using a cluster sampling method across three cities of Henan Province in China during February 4-12, 2020. Mask wearing practice was defined according to its type and the behavior exhibited in relation to wearing a mask. Presence of anxiety symptoms was determined by Generalized Anxiety Disorder tool (GAD-7). Multiple logistic regression was performed to estimate the association between mask wearing and anxiety symptoms. Among the participants, compared with students who completely adhered to the all the mask wearing practice, students who did not adhere to all the mask wearing practice had 1.97 times more likely to suffer from anxiety symptoms (adjusted odds ratio (aOR) = 1.97; 95% confidence interval (CI): 1.74-2.22). Furthermore, compared with students who did not know the proper type of mask, students who knew the proper type of mask had a lower risk of anxiety symptoms (aOR = 0.78; 95%CI: 0.76-0.80). Students who adhered to proper behavior of mask wearing was associated with 34% decreased odds for anxiety symptoms (aOR = 0.68; 95%CI: 0.62-0.74). To conclude, proper mask wearing may be an important attribute that play a significant role in reducing the risk of anxiety symptoms among junior and senior school student. However, since this study is a cross-sectional study, prospective studies are needed to further verify.


Comparison of handcrafted features and convolutional neural networks for liver MR image adequacy assessment.
We propose a random forest classifier for identifying adequacy of liver MR images using handcrafted (HC) features and deep convolutional neural networks (CNNs), and analyze the relative role of these two components in relation to the training sample size. The HC features, specifically developed for this application, include Gaussian mixture models, Euler characteristic curves and texture analysis. Using HC features outperforms the CNN for smaller sample sizes and with increased interpretability. On the other hand, with enough training data, the combined classifier outperforms the models trained with HC features or CNN features alone. These results illustrate the added value of HC features with respect to CNNs, especially when insufficient data is available, as is often found in clinical studies.


Computational analyses of JAK1 kinase domain: subtle changes in the catalytic cleft influence inhibitor specificity.
The Janus kinases (JAKs) are a family of intracellular non-receptor tyrosine kinases which transmit signals by phosphorylation of downstream substrates. A myriad of cytokines can trigger the JAK-STAT pathway which influences immune response, embryonic development, and cellular transformation. Here, we built a comparative model for Jak1 based on the crystal structure of Jak2 (PDB code:2B7A) and Jak3 (PDB code: 1YVJ) using the InsightII package. 3D-Profile and stereochemical analysis further verified the validity of the proposed structure. Adenosine 5'-triphosphate (ATP) was then docked into its catalytic cleft. Although the shape of Jak1 kinase cleft is fairly similar to that of Jak3, we observed minute changes in the key residues of the binding interface which influenced the docking of a specific Jak3 inhibitor, WHI-P131. Superimposition of the interface residues suggested that substitution of Asp 99 (Jak3) into Glu 101 (Jak1) generated steric hindrance and a Tyr 91 to Phe 93 switch altered the shape of catalytic cleft which collectively prohibited the inhibitor binding. Furthermore, in-silico mutagenesis of these two residues back to Asp and Tyr enabled Jak1 to accommodate WHI-P131. These results may provide clues for the design and optimization of selective kinase inhibitors.


Modulating the Electron-Donating Ability of Acridine Donor Units for Orange-Red Thermally Activated Delayed Fluorescence Emitters.
The development of thermally activated delayed fluorescence (TADF) emitters with orange-red emission still lags behind that of their blue, green, and yellow counterparts. Recent research to address this problem mainly focused on developing new acceptor units. There were few donor units designed especially for orange-red emitters. Herein, with benzothiophene fused to a diphenylacridine donor unit, a new donor moiety, namely, 5,5-diphenyl-5,13-dihydrobenzo[4,5]thieno[3,2-c]acridine (BTDPAc), was designed and synthesized. Benefiting from the strong electron-donating ability of the new donor moiety, a new TADF emitter, 2-[4'-(tert-butyl)(1,1'-biphenyl)-4-yl]-6-[5,5-diphenylbenzo[4,5]thieno[3,2-c]acridin-13(5H)-yl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (BTDPAc-PhNAI), shows an orange-red emission with a maximum at 610 nm in dilute toluene solution. Also, with the help of the diphenyl rings of the donor unit, high photoluminescence quantum yields were achieved for BTDPAc-PhNAI over a wide concentration range. Consequently, an orange-red organic light-emitting diode based on BTDPAc-PhNAI achieved a high external quantum efficiency of nearly 20 %, which was comparable to state-of-the-art device performances with similar emission spectra.


Surgical treatment of Peyronie's disease: a new approach.
We treated 12 patients with intractable Peyronie's disease with a new approach based on simple incision of the fibrotic plaque(s) and stenting of the corpora with penile implants. Infection in 1 case necessitated removal of the prostheses, while the remaining 11 patients had satisfactory functional and anatomical results. The procedure is indicated for patients with 1) Peyronie's disease and impotency, 2) normal potency and extensive disease and 3) normal potency and localized disease in selective cases. In this series insertion of the penile prostheses did not change sexual prowess in previously potent patients.


Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice.
"Humanized" mice have been widely used for the characterization of human cancer progression and as a powerful preclinical model. Standardization of multicolor phenotyping could help to identify immune cell patterns involved in checkpoint-related complications. Therefore, we applied established protocols for immune cell profiling to our humanized Patient-Derived Xenograft (hPDX) model. hPDX are characterized by the co-existence of a human immune system and a patient-derived tumor transplant. These mice possess a human-like immune system after CD34+ stem cell transplantation while the reconstitution level of the immune system was not related to the quantity of transplanted CD34+ cells. Contamination ≤ 1.2% by CD3+ cells in the hematopoietic stem cell (HSC) transplant did not trigger abnormal T cell maturation. Different B and T cell differentiation stages were identified, as well as regulatory T cells (Tregs) and exhausted T cells that expressed TIGIT, PD-1, or KLRG1. Overall, the application of standardized protocols for the characterization of immune cells using flow cytometry will contribute to a better understanding of immune-oncologic processes.


Delayed in diagnosis of upper aerodigestive tract cancers: A comprehensive review of medical malpractice cases.
Factors that prompt litigation and influence outcomes for malpractice cases involving cancers of the upper aerodigestive tract are incompletely described. Westlaw, a national legal database, was searched for medical malpractice claims related to upper aerodigestive tract cancer for all years available. Of the 122 cases meeting inclusion criteria, 106 (86.9%) involved allegations of failure to diagnose or delay in diagnosis. Tongue, larynx, and nasopharynx cancers were more frequently litigated than would be expected based on their incidence (tongue, 38.7% of aerodigestive tract litigation vs. 26.9% of aerodigestive tract cancers; larynx, 33.0% vs. 22.3%; nasopharynx, 10.4% vs. 4.6%). Payouts were made in over half of diagnosis failure lawsuits (56.6%), which carried an average award of $2840690 [IQR 850219-2537509]. An awareness of litigation on cancers of the upper aerodigestive tract holds the potential to improve patient care and help otolaryngologists avoid potential risks for litigation.


Stationary-phase expression and aminoacylation of a transfer-RNA-like small RNA.
Genome-scale analyses have shown numerous functional duplications in the canonical translational machinery. One of the most striking examples is the occurrence of unrelated class I and class II lysyl-transfer RNA synthetases (LysRS), which together may aminoacylate non-canonical tRNAs. We show that, in Bacillus cereus, the two LysRSs together aminoacylate a small RNA of unknown function named tRNA(Other), and that the aminoacylated product stably binds translation elongation factor Tu. In vitro reconstitution of a defined lysylation system showed that Lys-tRNA(Other) is synthesized in the presence of both LysRSs, but not by either alone. In vivo analyses showed that the class 2 LysRS was present both during and after exponential growth, whereas the class I enzyme and tRNA(Other) were predominantly produced during the stationary phase. Aminoacylation of tRNA(Other) was also found to be confined to the stationary phase, which suggests a role for this non-canonical tRNA in growth-phase-specific protein synthesis.


Pediatric tinea capitis: recognition and management.
Tinea capitis (ringworm of the head) is the most common dermatophytosis of childhood with an increasing incidence worldwide. If suspected clinically, further diagnostic procedures, including direct microscopy and culture, should be performed. Other scalp alterations, such as seborrheic dermatitis, atopic eczema, psoriasis, alopecia areata, folliculitis, and pseudopelade, may mimic ringworm of the head and must be identified. A proven fungal infection of scalp skin and hairs warrants immediate initiation of systemic treatment. At present, only oral griseofulvin is approved for therapy of scalp ringworm in children by health authorities. However, the advent of several newer antifungal agents such as itraconazole, fluconazole, and terbinafine has broadened the therapeutic armamentarium in recent years. These agents offer shorter treatment intervals, and their adverse effects and drug interaction profiles appear to be well within acceptable limits. In patients with tinea capitis, systemic therapy at weight-dependent dosages for an appropriate amount of time in conjunction with topical supportive measures will help to prevent disfiguring hair loss, permanent formation of scar tissue, spread of fungal organisms to other cutaneous regions, and infection of other persons.


Addressing Challenges in Studies of Behavioral Responses of Whales to Noise.
Studying the behavioral response of whales to noise presents numerous challenges. In addition to the characteristics of the noise exposure, many factors may affect the response and these must be measured and accounted for in the analysis. An adequate sample size that includes matching controls is crucial if meaningful results are to be obtained. Field work is thus complicated, logistically difficult, and expensive. This paper discusses some of the challenges and how they are being met in a large-scale multiplatform project in which humpback whales are exposed to the noise of seismic air guns.


The use of His bundle pacing for the treatment of painful left bundle branch block syndrome.
Painful left bundle branch block syndrome is a rare disorder in which patients develop typical angina-like pain without identifiable ischemia. To date, there have been few published cases of effective treatment. In this case report, we describe successful implementation of His bundle pacing for durable symptom resolution in this disorder.


Consumption, behaviour and knowledge with respect to alcoholic drinks in student nurses in the province of Bologna, Italy.
A study was carried out on alcohol intake among the students of the Schools for Trained Nurses in the province of Bologna by means of an anonymous especially prepared questionnaire. The series consisted of 1077 subjects: 753 females and 324 males aged between 16 and 40. 68.2% of males and 56.8% of females drank wine, l'81.3% of males and 61.8% of females drank beer and 65.3% of males and 46.2% of females drank spirits. While beer was the most popular drink, wine was on average drank in greater quantity. Alcohol intake was significantly related to sex (higher among males), area of origin (South) and cigarette smoking. The risk attributable to alcohol abuse are well known to almost all of the sample, above all those in the 2nd and 3rd years of their course. Nevertheless their alcohol consumption was not particularly different from that of students attending other High Schools. Regarding the sources, of their information about the risks, the 'mass media' was more quoted by the oldest students while 'family' was given by the younger students; the Nursing School was more often mentioned by both sexes in the 2nd and 3rd year of course. No relation however was found between the students knowledge of risks and actual consumption.


P. falciparum infected erythrocytes are capable of endocytosis.
P. falciparum, an intraerythrocytic parasite, obtains nourishment primarily through phagocytosis of the host cytosol but also through the incorporation of extracellular small molecules which enter through the parasitized red cell's membrane via pores. Normal mature erythrocytes are incapable of endocytosis. Several lines of evidence suggest that extracellular large molecules may be taken up when the mature red cell is parasitized by P. falciparum, but direct evidence has been lacking. We now report the use of ferritin, an electron dense protein, to demonstrate endocytosis in P. falciparum infected red cells. Parasitized red cells incubated with ferritin internalize that macromolecule as demonstrated by electron microscopy. While normal red cells incubated with ferritin took up none of the tracer molecule, parasitized red cells internalized substantial amounts. In addition both ferritin and apoferritin inhibited the growth of P. falciparum in a dose dependent fashion, again indicating endocytosis of a macromolecule. These data indicate that P. falciparum can somehow stimulate the mature erythrocyte to engage in endocytosis. We also note that both infected and non-infected red cells in a culture in which P. falciparum is growing become abnormally sticky for ferritin. Moreover, parasitized red cells bind I125-transferrin while non-parasitized erythrocytes do not. These observations suggest that a soluble parasite product alters the red cell membrane in a non-global manner, causing selective effects in relation to different proteins.


The wood frog (Rana sylvatica): An emerging comparative model for anuran immunity and host-ranavirus interactions.
The wood frog (Rana sylvatica) is widely distributed across North America and is the only amphibian found north of the Arctic Circle due to its remarkable ability to tolerate whole-body freezing. Recent mass mortalities attributable to Ranavirus spp. (family Iridoviridae) in wild juvenile wood frogs, coupled with the apparent high susceptibility of wood frogs to experimental infection with frog virus 3 (FV3), the type species of the Ranavirus genus, or FV3-like isolates underscore the serious threat ranaviruses poses to wood frog populations. Despite the ecological relevance and unique life history of wood frogs, our understanding of the wood frog immune system and antiviral response to ranaviral infections is in its infancy. Here we aim to (1) synthesize the limited knowledge of wood frog immune defences, (2) review recent progress in establishing the wood frog as a study system for ranavirus infection, and (3) highlight the future use of wood frogs as a model anuran to provide insight into the evolution of anuran immune systems and antiviral responses.


Clinicopathological significance of S100 protein expression in cholangiocarcinoma.
Cholangiocarcinoma arising in the large bile ducts undergoes a multistep carcinogenesis process in chronic biliary diseases, and biliary intraepithelial neoplasia is known as a precursor lesion. This study examined the expression of S100 proteins in the multistep cholangiocarcinogenesis to clarify their clinicopathological significance. Immunohistochemical analysis was performed for the expression of S100A2, S100A4, S100A6, and S100P. Bile concentrations of S100P were measured using enzyme-linked immunosorbent assay. The immunohistochemical expression of the S100 proteins was increased in biliary intraepithelial neoplasia as well as invasive adenocarcinoma of perihilar cholangiocarcinoma. Among the proteins, S100P expression was most drastically increased during the multistep carcinogenesis process. In cases with perihilar and extrahepatic cholangiocarcinoma, the immunohistochemical expression of S100A2 in cholangiocarcinoma cells significantly correlated with the histological grade, lymph node metastasis, clinical stage, and a poor survival rate of the patients. The bile levels of S100P were increased significantly in patients with cholangiocarcinoma compared with those in patients with lithiasis. Receiver operating characteristic curve analysis showed that S100P bile concentration was an indicator of cholangiocarcinoma with a sensitivity of 93% and a specificity of 70%. These results suggest that S100P may be useful for the detection of cholangiocarcinoma as tissue and bile biomarkers, and the immunohistochemical expression of S100A2 is a potential prognostic marker in cholangiocarcinoma patients.


Platelet factor 4 enhances fibrin fiber polymerization.
In order to further examine the role of platelet secretory products on fibrin assembly, we have examined the effects of purified platelet factor 4 (PF4) on fibrin formation in vitro. The kinetics of fibrin formation and the structural properties of the resulting fibrin gel are strongly affected by PF4. In the presence of 7.6 ng/mL PF4, the fibrin fiber mass-length ratio increases from 3.5 X 10(12) daltons/cm. These results emphasize the importance of the local microenvironment in clot structure and its subsequent fate at the site of vascular injury.


Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial.
Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D3 (4000 IU) or standard-dose (400 IU) vitamin D3. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks). As compared with standard-dose vitamin D3, high-dose vitamin D3 did not significantly change body weight [-0.7 kg; (95% CI: -3.5, 2.0)], body mass index [-0.2 kg/m2; (95% CI: -1.2, 0.7)], muscle area [-1.7 cm2; (95% CI: -9.6, 6.3)], muscle attenuation [-0.4 HU; (95% CI: -4.2, 3.2)], visceral adipose tissue area [-7.5 cm2; (95% CI: -24.5, 9.6)], or subcutaneous adipose tissue area [-8.3 cm2; (95% CI: -35.5, 18.9)] over the first 8 cycles of chemotherapy. Among patients with advanced or metastatic colorectal cancer, the addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy did not result in any changes in body composition.


Long-term survival (>10 years) of patients >60 years with induction therapy after cardiac transplantation.
Cardiac transplantation has become an established method for end-stage heart disease. Short- and mid-term outcome has been known to be similar between younger and older (>60 years) recipients. So far, nothing is known about long-term outcome of old patients and the potential long-term effects of antibody induction therapy in these patients. The purpose of this study was to analyse long-term outcome of old cardiac transplant recipients who underwent antibody induction therapy. Since 1989, 203 patients (total n = 882) above 60 years have been transplanted at our center. On these patients n = 66 were above 65 years. Survival, incidences of rejection, infection, cancer, graft arteriosclerosis and the amount of renal insufficiency were compared with patients <60 years (n = 679), transplanted during the same period of time. Freedom from specific event was computed by Kaplan-Meier analysis and compared by log-rank test. Ten year survival was similar in all groups (<60 years: 53.7%; 60-64 years: 53.1% and >65 years: 60.2%; P = NS). Causes of death were similar in all patient groups. There were significant fewer rejection episodes in the older patient group (freedom from rejection: 74.9 vs. 83.5 vs. 90.6; P = 0.03). Yet significantly more number of patients >65 years were without steroid maintenance therapy (43.1%) compared to other patient groups (8.2 vs. 9.3%; P < 0.05). There was no difference in overall freedom from severe infection (74.1 vs. 67.7 vs. 85.3%; P = NS), whereas there was a trend towards more CMV disease in the oldest patient group (82.7 vs. 88.6 vs. 70.8%; P=0.06). The incidence of cancer was similar in all groups (freedom from cancer: 82.2 vs. 84.7 vs. 79.1%; P = NS), as well as there was no difference in severe graftsclerosis between all patients (79.2 vs. 93.7 vs. 93.3%; P = NS). There was no difference in development of chronic renal dysfunction (creatinine > 2.0 mg/dl) between the three groups (10 vs. 14 vs. 16%; P = NS). Old recipients of cardiac transplants have a similar long-term outcome than younger recipients. They were less prone to rejections, had a similar incidence of severe infections and showed a trend towards more CMV disease. All patients had a very low rate of graft arteriosclerosis that was similar amongst the groups. Age-related decline of the immune system further enhanced by immunomodulation of antibody induction therapy might be accounted for the results as well as steroid-free immunosuppression.


Comparison of the clinical effectiveness of zanamivir and laninamivir octanoate for children with influenza A(H3N2) and B in the 2011-2012 season.
To evaluate the clinical effectiveness of the two inhaled neuraminidase inhibitors (NAIs), zanamivir (ZN) and laninamivir octate (LO), for influenza A(H3N2) and B virus infections. A prospective, multicenter observational study was conducted from January to April in 2012. Outpatients aged 5-18 years who had a temperature of 37.5°C or higher and were diagnosed as having influenza based on an immunochromatographic assay were enrolled. A total of 338 patients treated with ZN and 314 patients treated with LO were compared. The duration of fever after administration of the first dose of each NAI was evaluated as a primary endpoint. The secondary endpoint was episodes of biphasic fever. No statistically significant difference in the duration of fever was found between the ZN and LO groups (log-rank test, P = 0.117). A logistic regression model showed that episodes of biphasic fever increased by 1.19 times for every decrease of 1 year of age (P = 0.016) and that the number of biphasic fever episodes in patients treated with LO was 5.80-times greater than that in patients treated with ZN (P < 0.001). Although the duration of fever in the LO group was comparable to that in the ZN group, episodes of biphasic fever were more frequent in younger children and in the LO group than in the ZN group.


Moult of overwintering Wood Warblers Phylloscopus sibilatrix in an annual-cycle perspective.
Wood Warblers, an Afro-Palearctic migrant species, are declining steadily in Europe likely due to mortality outside their breeding grounds. However, little is known about their overwintering, and records about the sensitive life-cycle stage of moult in Africa are practically absent. To fill this gap, we report on moult of Wood Warblers captured over two winters (January-February) in 2019-2020 in Cameroon. We caught 14 individuals, of which 12 were monitored for flight feather moult. All inspected individuals showed advanced stages of flight feather renewal. Despite low sample sizes, Underhill-Zucchini moult models aptly explained variation in primary and secondary moult (R 2 = 0.61). Estimated moult onset date was 26 December, completion date was 25 February, and moult duration was 61 days. These findings fit well with experimental data on the annual cycle and the timing of recently published migration tracks of Wood Warblers. Jointly, the data suggest that moult timing is set by an internal programme, which enables Wood Warblers to organise their multi-stage migration such that they reach suitable moulting habitat in time, and can depart in time with a fresh plumage for the breeding grounds. In our study, moult occurred during the peak of the dry season, which in Cameroon nonetheless shows high relative humidity. During our mist-netting on 28 cocoa plantations of varying shade cover, Wood Warblers were caught on 6 farms whose canopies were comparatively open. These data suggest that the birds encounter in Cameroon relatively stable climatic conditions for moult, and do not measurably prefer closed-canopy forests. Our findings are important, because successful moult increases survival prospects and because moult needs to be safely embedded in a migratory life cycle. Hence, information on moult timing and location is essential for identifying year-round vulnerabilities of Wood Warblers.


Incidence of benign and malignant prostate tissue in biopsies of the bladder neck after a radical prostatectomy.
We determined whether bladder neck sparing radical prostatectomy may leave prostate tissue in the unresected bladder neck. We intraoperatively evaluated the presence of prostate tissue in bladder neck biopsy specimens from 73 consecutive patients undergoing bladder neck sparing radical prostatectomy. Of the 73 specimens 14 (19%) contained prostate tissue: 9 (12%) were positive for prostate cancer and 5 (7%) contained benign prostate tissue. All patients with a positive bladder neck biopsy had a positive margin at another site. We recommend routine bladder neck biopsies for patients undergoing a bladder neck sparing procedure.


Suppressive effect of an analog of the antimicrobial peptide of LL‑37 on colon cancer cells via exosome‑encapsulated miRNAs.
Antimicrobial peptides (AMPs) are multifunctional factors with an important role in the innate immune system. Our previous studies revealed that the human cathelicidin LL‑37 and its analog, FF/CAP18, limit the proliferation of colon cancer cell lines. In the present study, the exosomes released by HCT116 cells treated with FF/CAP18 were analyzed. After the treatment, exosomes were isolated from the culture supernatant by ultrafiltration and using the miRCURY™ Exosome Isolation Kit. Membrane vesicles 40‑100‑nm expressing CD63 and CD81 were identified before and after FF/CAP18 treatment. Exosome concentration in the culture supernatant was increased after treatment with FF/CAP18. Exosomes formed in HCT116 cells treated with FF/CAP18 induced growth suppression of the cells in a dose‑dependent manner. By contrast, the exosomes formed in non‑treated HCT116 cells did not affect cell viability. Microarray analysis of miRNA expression indicated that FF/CAP18 treatment induced increases in the expression of three miRNAs (miR‑584‑5p, miR‑1202 and miR‑3162‑5p) in both HCT116 cells and exosomes. These results suggest that FF/CAP18 treatment increases exosome formation, and that exosome‑encapsulated miRNAs suppress HCT116 cell proliferation. Exosomal miRNAs are considered to be involved in the dissemination of cell signals to control local cellular microenvironments. The present findings suggest that FF/CAP18 regulates cancer growth by modulating cell‑to‑cell communication. AMPs localize in the cytoplasm of cancer cells and enhance the expression of growth‑suppressing miRNAs. These miRNAs are also transported to other cancer cells via exosomes. Therefore, transportation of these miRNAs has the potential to suppress cancer growth. AMPs exert their effects directly by targeting cancer cells and indirectly via exosomes.


Skeletal myocyte plasticity: basis for improved therapeutic potential?
Skeletal muscle tissue exhibits a remarkable capacity to regenerate after injury and to adapt its properties in response to altered functional demands or environmental pressure. This potential renders skeletal myocytes especially attractive candidates to be used in therapeutic strategies. Besides the well-described adaptability of skeletal myocytes in terms of contractile function and metabolic profile, more recent research has revealed that the electrophysiological properties of myocytes are also subject to significant changes both under physiological conditions and in pathophysiological situations. A better understanding of skeletal myocyte plasticity, its regulation and its forced induction could improve existing therapeutic approaches and may pave the way for new therapeutic strategies.


Tumor budding in colorectal carcinoma: An institutional interobserver reliability and prognostic study of colorectal adenocarcinoma cases.
Colorectal carcinomas are one of the most commonly diagnosed malignancies. There are many prognostic factors relating to clinical course and disease progression, including tumor stage, metastasis, and tumor budding. In 2016, the International Tumor Budding Consensus Conference (ITBCC) created a system to uniformly assess tumor budding. This system includes a 3-tier system for the grading of tumor budding. In the past, there lacked uniform consensus, however the general grading practice was based on a 2-tiered system. Given that tumor budding is considered to have prognostic value, the accuracy and reproducibility of its assessment is vital. Our study aims to look at interobserver agreement in the scoring of tumor budding. A total of 233 cases of colorectal carcinoma diagnosed in our health system were retrospectively analyzed and routine H&E stained slides of these cases were collected. A representative slide for tumor budding was selected per case. Four investigators with different levels of experience and expertise evaluated the selected slide of each case for tumor budding. Scoring was based on the ITBCC protocol. Clinico-pathological data was collected for each case and analyzed with tumor budding scores. Tumor budding scores per individual investigator and consensus tumor budding score were compared to patient and tumor characteristics including patient survival, tumor grade, tumor stage, and lymph node status. Inter-observer agreement was calculated using Gwet's Agreement Coefficient (AC1) and associated 95% confidence intervals was used to compare the ratings made by 4 pathologists. Overall, there was variation among pathologists in tumor budding score (Gwet's agreement coefficient = 0.25 and 0.326 for 3-tier and 2-tier grading system, respectively). Results show higher reliability with the 2-tier system compared to the 3-tier system. Tumor stage was significantly associated with budding score for all individual investigators and the consensus value (p value < 0.001). There is low inter-observer agreement in the assessment of tumor budding in colorectal carcinoma. This suggests that it is difficult to uniformly grade tumor budding and that our classification system needs improvement. We found that the older 2-tier system (Hase et al.) results in slightly higher inter-observer agreement than the recently proposed 3-tier grading system (ITBCC, 2016), though both systems lead to suboptimal agreement. Worth noting is that observers with subspecialty GI training and more work experience had higher inter-observer agreement. Our results showed that subspecialty training tends to increase agreement more than overall work experience. In addition, our exploratory results showed that there is an association of tumor budding score to tumor stage. While increasing refinement in classification, the 3-tiered system resulted in decreased agreement in tumor budding assessment. Clearly, there is more work to be done in the identification and quantification of tumor buds.


Interpretation of cancer prevention trials.
Principles and methods to guide interpretation require a different emphasis for cancer trials. Assumptions used to design a trial must be validated and modified during the trial to avoid limitations. To maximize information from such trials, recruitment strategies for commonly free-living subjects, measurements of safety and compliance, and ascertainment with pathologic review of endpoints must be obtained. Consideration of multiple endpoints may provide a better interpretation of cancer prevention for skin, colon, and transient occurrences illustrated by cervical dysplasia or biochemical precursors. A careful definition of the limitations of preventive trials is required. These include the actual size of the intervention groups, completeness and duration of follow-up, and comparison between trial participants and a defined source population. To obtain a valid interpretation with adequate precision of intervention effectiveness, time to endpoints should be evaluated using statistical multivariate methods such as Cox proportional hazard or relative risk models. These permit adjustment for important confounding and risk modifiers such as compliance, dietary intake, and drift in control group. The magnitude of the intervention efficacy and the generalizability of results of the trial will be negatively impacted if the intervention has a delayed (latent) effect. Such delay in intervention effect requires added considerations with possible extension of trial duration. Use of confidence limits for intervention effectiveness provides added insight and improved interpretation of prevention trials. The final component of a cancer prevention trial, as with any study, is to interpret and report its results. Providing a valid interpretation with adequate precision to hypotheses of a cancer prevention trial requires added emphasis on the accuracy of the assumptions made to design the trial and the duration of the trial. Design assumptions regarding compliance to the prescribed interventions, time until the experimental intervention achieves full effect, and the frequency of endpoints directly impact on the number of endpoints observed. Terminating a cancer prevention trial before adequate information is obtained, thus severely flawing its interpretation, requires ongoing awareness. Interpretation of a cancer prevention trial should include several added steps: first, investigators to critically review the actual manner in which the trial was conducted; second, carry out an appropriate analysis of the data; and third, review the results and note exceptions or limitations in the data. The results of the trial should be contrasted with previous studies. Implications of the results to future trials should be considered. Finally, these interpretations should be documented in a written report and made available to the scientific community.


The Cosmogonic Experiments of Robert Fludd: A Translation with Introduction and Commentary.
Experientia est etiam stultorum magistra, [but] I will stoop a little, for your better instruction, and more clear information, and elucidate and make plain the abstruse subject we have in hand, by some vulgar or occular demonstrations, which may guide them and persuade them to believe that which may otherwise seem uncredible. That I may therefore proceed more methodically, I will lay down…the chief platform, on which I propose to build such experimental conclusions, as shall direct the misbelievers… Robert Fludd Mosaicall Philosophy.


A non-aggregated zinc(II) phthalocyanine with hexadeca cations for antitumor and antibacterial photodynamic therapies.
With a view to developing highly efficient photosensitizers for both antitumor and antimicrobial photodynamic therapies, herein, we reported a super cationic zinc(II) phthalocyanine (Pc4), which was prepared through the quaternization of the N, N-dimethyl-3-aminophenoxyl-hexadeca-substituted precursor Pc3. Meanwhile, two disubstituted analogues (Pc1 and Pc2) were also prepared as controls. The cationic Pc2 and Pc4 had higher photoactivities including fluorescence and singlet oxygen than the neutral counterparts Pc1 and Pc3, probably because of the inhibition of intramolecular charge transfer (ICT) effect of the amino groups. With the bulky steric effect and high hydrophilicity, Pc4 presented non-aggregated behavior in aqueous solutions. Therefore, it exhibited the highest in vitro photodynamic activity toward HepG2 cancer cells with an IC50 value as low as 0.04 μM. Furthermore, Pc4 showed a highly efficient in vivo PDT effect on H22 tumor-bearing mice with 98.7% tumor growth inhibition. In addition, Pc4 also exhibited an excellent in vitro and in vivo photodynamic inactivation against S. aureus. The results indicate that the non-aggregated hexadeca-cationic Pc4 could serve as a promising photosensitizer for both antitumor and antimicrobial photodynamic therapies.


Haemagglutination assay for HBsAg -- a new approach to reagent preparation.
Human group O rhesus negative erythrocytes were spherocyted and fixed in glutaraldehyde, then coated initially with HBsAg and subsequently with anti-HBs. The resulting reagent was found to agglutinate in the presence of HBsAg positive serum, but not in HBsAg negative serum. The assay was evaluated for blood donor screening (39,962 donations) over a 6-month period, and was compared with Hepatest (RPHA) and AUSRIA-2 (RIA) for the study of two established HBsAg panels.


Cancer researchers' perceptions of the importance of the sex of cell lines, animals, and human samples for cancer biology research.
Sex differences in cancer risk and outcome are currently a topic of major interest in clinical oncology. It is however unknown to what extent cancer researchers consider sex as a biological variable for their research. We conducted an international survey among 1243 academic cancer researchers and collected both quantitative and qualitative data. Although most of the participants indicated that they were familiar with the concept of studying sex differences in cancer biology, they did not think it was important to investigate sex differences in every context of cancer research nor in all tumor types. This is in stark contrast to the current recommendations and guidelines and illustrates the need for increased awareness among cancer researchers regarding the potential impact of the sex of cell lines, animals, and human samples in their studies.


ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy.
Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN. A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA. Expression of ALCAM and S100B in kidney histology from patients with DN was determined by immunohistochemistry. Cell expression of ALCAM and S100B was analyzed through confocal immunofluorescence microscopy. Serum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85±14.99ng/ml vs. 126.88±66.45ng/ml, P<0.0001). Moreover sALCAM correlated positively with HbA1c (R=0.31, P<0.0001), as well as with the stages of chronic kidney disease and negatively correlated with eGFR (R=-0.20, P<0.05). In diabetic patients with normal albuminuria sALCAM was increased compared to patients with DN (126.88±66.45ng/ml vs. 197.50±37.17ng/ml, P<0.0001). In diabetic patients, ALCAM expression was significantly upregulated in both the glomeruli and tubules (P<0.001). ALCAM expression in the glomeruli correlated with presence of sclerosis (R=0.25, P<0.001) and localized mainly in the podocytes supporting the hypothesis that membrane bound ALCAM drives diabetic nephropathy and thus explaining sALCAM decrease in diabetic patients with DN. The expression of S100B was increased significantly in the glomeruli of diabetic patients (P<0.001), but not in the tubules. S100B was as well localized in the podocytes. This study identifies for the first time ALCAM as a potential mediator in the late complications of diabetes in the kidney.


Index finger lengthening by gradual distraction and bone grafting.
We present the case of an 18-year-old woman with a shortened right index finger. The digit was stabilized and lengthened a total of 18 mm by external fixation and iliac bone grafting. A distal interphalangeal fixed flexion deformity of 60 degrees was corrected with external fixation and intermedullary wiring.


[Regulatory interaction between the respiratory chain of mitochondria and the oxidative system of the endoplasmic reticulum].
A regulation mechanism of the interaction of microsomal oxidases and mitochondrial respiratory chain with oxidase substrates is suggested. Quantitative comparison of their affinity to microsomal oxidases and mitochondrial NADH-dehydrogenase is carried out. The interaction with both systems is found to be hydrophobic. It is found that microsomal oxidase substrates inhibit mitochondrial NADH-dehydrogenase at concentrations, which should completely fill the active site of cytochrome P-450. It is suggested that redistribution of reduced equivalents from mitochondria to microsomes and the acceleration of xenobiotic detoxication take place.


Diverse CD1d-restricted reactivity patterns of human T cells bearing "invariant" AV24BV11 TCR.
Human and murine natural T (NT) cells, also referred to as NK1.1+ or NK T cells, express TCR with homologous V regions (hAV24/BV11 and mAV14/BV8, respectively) and conserved "invariant" TCR AVAJ junctional sequences, suggesting recognition of closely related antigens. Murine NT cells recognize CD1-expressing cells and are activated in a CD1-restricted fashion by several synthetic alpha-glycosylceramides, such as alpha-GalCer. Here we studied the reactivity of human T cells against CD1d+ cells pulsed or not with alpha-GalCer and other related ceramides. CD1d-restricted recognition of alpha-GalCer was a general and specific feature of T cell clones expressing both BV11 and canonical AV24AJ18 TCR chains. Besides, human and murine NT cells showed the same reactivity patterns against a set of related glycosylceramides, suggesting a highly conserved mode of recognition of these antigens in humans and rodents. We also identified several AV24BV11 T cell clones self reactive against CD1+ cells of both hemopoietic and nonhemopoietic origin, suggesting the existence of distinct NT cell subsets differing by their ability to recognize self CD1d molecules.


Cerebral amyloid deposition predicts long-term cognitive decline in hemorrhagic small vessel disease.
To investigate the association between cerebral amyloid deposition and long-term cognitive outcomes in patients with hemorrhagic small vessel disease (SVD) and survivors of intracerebral hemorrhage (ICH). Patients experiencing an ICH without overt dementia were prospectively recruited (n = 68) for brain MRI and Pittsburgh compound B (PiB) positron emission tomography scans at baseline. Cognitive function was assessed using the mini-mental status examination (MMSE) and clinical dementia rating after an overall median follow-up of 3.8 years. A positive amyloid scan was defined as a global PiB standardized uptake value ratio >1.2. Associations between follow-up cognitive outcomes and neuroimaging markers were explored using multivariable Cox regression models. PiB(+) patients were older (72.1 ± 7.8 vs. 59.9 ± 11.7, p = .002) and more frequently had cerebral amyloid angiopathy (CAA) (63.6% vs. 15.8%, p = .002) than PiB(-) patients. PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100-person-years, hazard ratio [HR] = 15.7 [3.0-80.7], p = .001) and MMSE score decline (58.8 vs. 9.9 per 100-person-years, HR = 6.2 [1.9-20.0], p = .002). In the non-CAA subgroup (n = 52), PiB(+) remained an independent predictor of dementia conversion, p = .04). In the Cox models, PiB(+) was an independent predictor of dementia conversion (HR = 15.8 [2.6-95.4], p = .003) and MMSE score decline (HR = 5.7 [1.6-20.3], p = .008) after adjusting for confounders. Cerebral amyloid deposition potentially contributes to long-term cognitive decline in SVD-related ICH.


Information on biodiversity and environmental behaviors: A European study of individual and institutional drivers to adopt sustainable gardening practices.
The specific case of home gardening practices is particularly relevant when discussing lifestyle habits and ecological transition, due to the wide range of positive and negative environmental externalities private gardens may generate. However, existing studies usually focus on restricted areas, mostly at a city scale. We provide an original empirical contribution to the literature on individual and institutional drivers regarding ecological transition by exploring the variations of individual behavior between European countries with an appropriate econometric approach. Using a European database (Eurobarometer 83.4), we highlight several interesting results regarding Europeans' adoption of sustainable gardening practices, more particularly on the role of socio-demographic drivers, urban or rural residential location and access to trustworthy biodiversity-related information. In conclusion, we provide recommendations for the design of dedicated public policies, specific to a national or local level of decision.


Behavioral versus Biological Definitions of Dementia Symptoms: Recognizing that Worthwhile Interventions already Exist.
The 2018 Alzheimer's Disease Facts and Figures special report includes two new guidelines for measuring dementia symptoms. The first requires that a biomarker (biological factor) be added to a doctor's clinical judgment of the cause of symptoms when determining whether dementia is present. The second involves identifying four stages of dementia: normal cognition, preclinical, MCI and dementia. Now only those with defining brain pathologies and significant symptoms will be judged to be persons with stage 4 dementia. This article examines the implications of adopting these two new guidelines. The implications are in terms of whether worthwhile dementia interventions can be said to exist, and the extent to which symptoms have to change for an intervention to be judged to have reduced the prevalence of dementia. A cost-benefit framework is used to examine the implications of the new guidelines. To undertake a cost-benefit analysis (CBA) a measure of dementia symptoms change is required for any intervention to be judged effective. A behavioral measure of dementia symptoms is thought more useful than a biological one. The instrument that is recommended and explained is the clinical dementia rating (CDR) scale, which is measured on a 0-to-18 interval. Using this instrument, three CBAs can be shown to exist, and from a contracted version of the CDR, estimates of the prevalence rates for the four stages of dementia are derived. The implications for future dementia research of using the full CDR instrument is presented in the discussion section. The three CBAs that are reported and explained are years of education, Medicare eligibility and hearing aids. For each intervention, the analysis is in terms of demonstrating that it is effective, beneficial and socially worthwhile. By using a behavioral rather than a biological definition of dementia symptoms, we can show that worthwhile interventions already exist.


Current Treatment Strategies Against Multidrug-Resistant Bacteria: A Review.
There are several bacteria called superbugs that are resistant to multiple antibiotics which can be life threatening specially for critically ill and hospitalized patients. This article provides up-to-date treatment strategies employed against some major superbugs, like methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Escherichia coli. The pathogen-directed therapeutics decrease the toxicity of bacteria by altering their virulence factors by specific processes. On the other hand, the host-directed therapeutics limits these superbugs by modulating immune cells, enhancing host cell functions, and modifying disease pathology. Several new antibiotics against the global priority superbugs are coming to the market or are in the clinical development phase. Medicinal plants possessing potent secondary metabolites can play a key role in the treatment against these superbugs. Nanotechnology has also emerged as a promising option for combatting them. There is urgent need to continuously figure out the best possible treatment strategy against these superbugs as resistance can also be developed against the new and upcoming antibiotics in future. Rational use of antibiotics and maintenance of proper hygiene must be practiced among patients.


Treatment of the X-linked lymphoproliferative, Griscelli and Chédiak-Higashi syndromes by HLH directed therapy.
Griscelli syndrome type 2 (GS2), the X-linked lymphoproliferative (XLP) and the Chédiak-Higashi (CHS) syndromes are diseases that all may develop hemophagocytic syndromes. We wanted to investigate whether the treatment protocols for hemophagocytic lymphohistiocytosis (HLH) can also be used for these syndromes. In the HLH-94/HLH-2004 treatment study registries, we evaluated all patients with GS2 (n = 5), XLP (n = 2) or CHS (n = 2) treated between 1994 and 2004. All patients responded to the therapy, and all are alive but one (suffering from CHS), with a mean follow-up of 5.6 years. All GS2, one XLP and one CHS patient underwent hematopoietic stem cell transplant. Mean follow-up post transplant was 6.0 years. Six of the seven transplanted children achieved non-active disease status at the time for SCT. Neurological sequelae were reported in all, except for the XLP patients. Our results indicate that HLH treatment can be an effective first line treatment to induce remission in patients with GS2, XLP and CHS that have developed a hemophagocytic syndrome. We suggest that these patients should be included as a separate cohort in the international HLH study.


Transepidermal water vapour loss is not increased during and following dithranol irritation.
Dithranol is established as a very successful treatment for psoriasis. Its main disadvantages are irritation and staining at sites of application. The aim of the present study was to elucidate further the mechanism of dithranol-induced irritation, in particular to what extent this is related to an impairment of the skin barrier. Dithranol 3% in cream, paste and petrolatum was applied to the forearm skin of 20 volunteers and left in situ for 1 h. Transepidermal water loss (TEWL) was measured during a period of 2 weeks following dithranol application. In addition, a visual scoring system and colorimetry were used to assess erythema. The study showed conclusively that TEWL was not affected by the application of dithranol, even though pronounced erythema occurred.