Advanced telehealth technology improves home-based exercise therapy for people with stable chronic obstructive pulmonary disease: a systematic review.
How effective is home-based exercise therapy delivered using advanced telehealth technology (ATT-ET) for people with chronic obstructive pulmonary disease (COPD) compared with: no exercise therapy (ET), in/outpatient ET, and home-based ET without ATT? Systematic review and meta-analysis of randomised trials. People with stable COPD referred for ET. ATT-ET. Exercise capacity, quality of life, functional dyspnoea, cost-effectiveness and various secondary outcomes. Fifteen eligible trials involved 1,522 participants. Compared with no ET, ATT-ET improved exercise capacity (four studies, 6-minute walk test MD 15 m, 95% CI 5 to 24) and probably improved quality of life (four studies, SMD 0.22, 95% CI 0.00 to 0.43) and functional dyspnoea (two studies, Chronic Respiratory Questionnaire-Dyspnoea MD 2, 95% CI 0 to 4). ATT-ET had a similar effect as in/outpatient ET on functional dyspnoea (two studies, SMD -0.05, 95% CI -0.39 to 0.29) and a similar or better effect on quality of life (two studies, SMD 0.23, 95% CI -0.04 to 0.50) but its relative effect on exercise capacity was very uncertain (three studies, 6-minute walk test MD 6 m, 95% CI -26 to 37). ATT-ET had a similar effect as home-based ET without ATT on exercise capacity (three studies, 6-minute walk test MD 2 m, 95% CI -16 to 19) and similar or better effects on quality of life (three studies, SMD 0.79, 95% CI -0.04 to 1.62) and functional dyspnoea (two studies, Chronic Respiratory Questionnaire-Dyspnoea MD 2, 95% CI 0 to 4). ATT-ET had effects on most secondary outcomes that were similar to or better than each comparator. ATT-ET improves exercise capacity, functional dyspnoea and quality of life compared with no ET, although some benefits may be small. Its benefits are generally similar to in/outpatient ET and similar to or better than home-based ET without ATT. PROSPERO CRD42020165773.


Clinical outcome of long-term renal transplant survivors: a nephrourologic approach.
Long-term renal transplant survivors display high incidences of hypogonadism, neoplasms, erectile dysfunction, and metabolic syndrome. Although the urologist has a major role in the kidney transplantation surgery and treatment of the graft-related surgical complications, the follow-up of these patients is essentially focused on kidney function and the immunosuppressive regimen. We sought to evaluate the role of a nephrourologic follow-up for kidney transplant recipients. We evaluated 27 male patients of mean age of 48.1 +/- 7.5 years and mean renal allograft follow-up of 12.3 +/- 4.3 years. The nephrourologic approach consisted of evaluation of the urinary system, prostate cancer screening, and assessment of voiding function, fertility, erectile dysfunction, hypogonadism, and metabolic syndrome. We also assessed quality of life. Major urologic findings were found in 18 (66.7%) patients. Four patients reported posttransplantation parenthood. The mean serum creatinine was 1.5 +/- 0.6 mg/dL and the calculated clearance, 72.6 +/- 27.4 mL/min/1.73 m(2). Regarding the voiding pattern, 92.6% of patients showed mild to moderate bladder outlet obstruction. Clinically significant increases in prostate volume were observed in 3.7% of patients. Mean serum total prostate-specific antigen was 1.6 +/- 1.5 ng/mL. Erectile dysfunction was displayed by 46.2% and hypogonadism by 74.1% of patients. Metabolic syndrome was diagnosed in 44.4% of patients, and quality of life was generally rated as good (4/5). Long-term renal transplantation survivors show high prevalences of treatable urologic diseases. Thus, we strongly recommend routine complete nephrourologic follow-up of this population.


Preparation and characterization of gelatin/zein nanofiber films loaded with perillaldehyde, thymol, or ɛ-polylysine and evaluation of their effects on the preservation of chilled chicken breast.
Three edible food packaging films loaded with perillaldehyde (P), thymol (T), or ɛ-polylysine (ɛ-PL) in gelatin/zein (G/Z) nanofibers were prepared and characterized. Their effects on the preservation of chilled chicken breast were evaluated. Results showed that the addition of perillaldehyde, thymol, and ɛ-polylysine improved the morphology and diameter of the G/Z. Loading with perillaldehyde improved the elongation and tensile strength of the G/Z/P by 18% and 55%, respectively. The water vapor permeability and oxygen permeability of the G/Z/P were lower than those of the G/Z/T and G/Z/ɛ-PL. X-ray diffraction, differential scanning calorimetry suggested that perillaldehyde enhanced the thermal stability of the G/Z/P. Measurements of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), total volatile basic nitrogen, and total viable bacterial counts demonstrated that the G/Z/P had good bio-compatibility and effectively prolonged the shelf life of chilled chicken breasts by over 6 days. Therefore, the G/Z/P developed herein has potential application in chilled meat packaging.


Real-time tracking and shape analysis of atrial septal defects in 3D echocardiography.
Real-time cardiac ultrasound (US) allows monitoring the heart motion during intracardiac beating heart procedures. Our application assists pediatric atrial septal defect (ASD) closure techniques using real-time 3D US guidance and rigid instruments. ASD tracking is also an important tool for facilitating systematic clinical studies of the dynamic behavior of the intra-atrial communication. One major image processing challenge is associated with the required processing of information at high frame rate, especially given the low image quality. We present an optimization scheme for a block flow technique, which combines the probability-based velocity computation for an entire block (a 3D volume centered on the ASD) with cyclic template matching. The adapted similarity imposes constraints both locally (from frame to frame) to conserve energy, and globally (from a reference template) to minimize cumulative errors. The algorithm is optimized for fast and reliable results. For tests, we use three intra-operational 4D ultrasound sequences of clinical infant beating hearts with ASD. Computing velocity at the block level with an optimized scheme, our technique tracks ASD motion at a frequency of 60 frames/s on clinical 4D datasets. Results are stable and accurate for changes in resolution and block size. In particular, we show robust real-time tracking and preliminary segmentation results of the ASD shape, size and orientation as a function of time. We present an optimized block flow technique for real-time tracking of ASD to assist in minimally invasive beating heart surgery. Our method proposes the standard use of references for processing repetitive data. This paper represents, to our knowledge, the first study on the dynamic morphology of ASD that takes into account the angular effect introduced by the slanted position of the intra-atrial communication with respect to the US probe.


Stroke and Intracranial Hemorrhage in HeartMate II and HeartWare Left Ventricular Assist Devices: A Systematic Review.
Ischemic stroke and intracranial hemorrhage (ICH) following left ventricular assist device (LVAD) placement are major causes of morbidity. The incidence and mortality associated with these events stratified by device type have not been systematically explored. A systematic review of PubMed was conducted from January 2007 through June 2016 for all English-language articles involving HeartMate II (HMII) and HeartWare LVAD patients. Ischemic stroke and/or ICH incidence (events per patient-year) and associated mortality rates were abstracted for each device type. Of 735 articles reviewed, 48 (11,310 patients) met inclusion criteria (33 HMII, six HeartWare, eight both devices, and one unspecified). The median duration of device support was 112 days (total 13,723 patient-years). Overall, ischemic stroke or ICH occurred in 9.8% (1110 persons and 0.08 events per patient year [EPPY]). Ischemic stroke occurred in a median of 6.0% or 0.06 EPPY (range 0-16% or 0-0.21 EPPY) of HMII patients versus 7.5% or 0.09 EPPY (range 4-17.1% or 0.01-0.94 EPPY) of HeartWare patients. ICH occurred in a median of 3.0% or 0.04 EPPY (range 0-13.5% or 0-0.13 EPPY) of HMII and 8.0% or 0.08 EPPY (range 3-23% or 0.01-0.56 EPPY) of HeartWare patients. The median mortality rate for LVAD-associated ischemic stroke was 31% (HMII: 33%, [range 2.4-75%] and HeartWare: 11.5% [range 3.9-40%]), and the median mortality rate following ICH was 71% (HMII: 75%, [range 3.9-100%] and HeartWare: 44%, [range 3.1-88%]). Ischemic stroke and ICH are common after LVAD placement, but heterogeneous event rates are reported in the literature. Given the high associated mortality, further prospective study is warranted.


Crystal structures and Hirshfeld surface analysis of 5-amino-1-(4-meth-oxy-phen-yl)pyrazole-4-carb-ox-ylic acid and 5-amino-3-(4-meth-oxy-phen-yl)isoxazole.
The title compounds, C11H11N3O3, (I), and C10H10N2O2, (II), are commercially available and were crystallized from ethyl acetate solution. The dihedral angle between the pyrazole and phenyl rings in (I) is 52.34 (7)° and the equivalent angle between the isoxazole and phenyl rings in (II) is 7.30 (13)°. In the crystal of (I), the mol-ecules form carb-oxy-lic acid inversion dimers with an R(8) ring motif via pairwise O-H⋯O hydrogen bonds. In the crystal of (II), the mol-ecules are linked via N-H⋯N hydrogen bonds forming chains propagating along [010] with a C(5) motif. A weak N-H⋯π inter-action also features in the packing of (II). Hirshfeld surface analysis was used to explore the inter-molecular contacts in the crystals of both title compounds: the most important contacts for (I) are H⋯H (41.5%) and O⋯H/H⋯O (22.4%). For (II), the most significant contact percentages are H⋯H (36.1%) followed by C⋯H/H⋯C (31.3%).


The distribution of thoracic glomus tissue (aortic bodies) in the rat.
An inventory of the distribution of thoracic glomus tissue (thoracic chemoreceptor tissue, aortic bodies) has been derived from serial sections in foetal, newborn and adult rats. In contrast to other common experimental species, such as the cat and dog, aortic bodies are an inconstant feature and, on the whole, are scarce in the rat. These morphological findings correlate well with experimental studies, indicating an absence or paucity of thoracic chemoreceptor activity in the rat. The results are discussed in terms of their physiological and pathophysiological implications and a revised model of the peripheral arterial chemoreceptor system is presented.


Effects of a psychological intervention on depression in infertile couples.
To determine factors affecting depression in infertile couples and the impact of a psychological intervention before or during infertility treatment. In a cross-sectional study with 638 infertile couples assessed for depression, 140 couples with a member who had a Beck Depression Inventory (BDI) score of 17 or higher were randomized to receive psychological treatment either before or during infertility treatment. Logistic regression was performed to eliminate confounding factors. Depression was initially found in 48% of women and 23.8% of men. The mean+/-SD Beck scores fell from 18.7+/-9.7 to 10.7+/-5.8 (P<0.001) in the group psychologically treated before they received infertility treatment. The psychological intervention was found useful in alleviating depression in infertile couples before they received infertility treatment.


Cell-free DNA methylome analysis for early preeclampsia prediction.
Preeclampsia (PE) is a leading cause for peripartal morbidity, especially if developing early in gestation. To enable prophylaxis in the prevention of PE, pregnancies at risk of PE must be identified early-in the first trimester. To identify at-risk pregnancies we profiled methylomes of plasma-derived, cell-free DNA from 498 pregnant women, of whom about one-third developed early-onset PE. We detected DNA methylation differences between control and PE pregnancies that enabled risk stratification at PE diagnosis but also presymptomatically, at around 12 weeks of gestation (range 9-14 weeks). The first-trimester risk prediction model was validated in an external cohort collected from two centers (area under the curve (AUC) = 0.75) and integrated with routinely available maternal risk factors (AUC = 0.85). The combined risk score correctly predicted 72% of patients with early-onset PE at 80% specificity. These preliminary results suggest that cell-free DNA methylation profiling is a promising tool for presymptomatic PE risk assessment, and has the potential to improve treatment and follow-up in the obstetric clinic.


Switching On/Off of a Solvent Coordination in a Au(I)-Pb(II) Complex: High Pressure and Temperature as External Stimuli.
The benzonitrile solvate {[{Au(C6F5)2}2{Pb(terpy)}]·NCPh}n (1) (terpy = 2,2':6',2″-terpyridine) displays reversible reorientation and coordination of the benzonitrile molecule to lead upon external stimuli. High-pressure X-ray diffraction studies between 0 and 2.1 GPa reveal a 100% of conversion without loss of symmetry, which is totally reversible upon decompression. By variable-temperature X-ray diffraction studies between 100 and 285 K, a partial coordination is achieved.


Parental Psychiatric Symptoms and Children's Outcomes: Toward Understanding and Responding to Intergenerational Risk in Child Psychiatry.
Family history of psychiatric illness is a core feature of any competent clinical history taken in a child and adolescent psychiatry clinical setting, and this history is often limited to reviewing caregivers' reports of diagnosed or suspected mental disorders in biological parents and relatives across several generations. Less commonly included is a detailed inquiry into parents' and caregivers' current mental health, including psychiatric symptoms at the time that their child is presenting for evaluation. Recent evidence is a strong reminder that parental mental illness is an important adversity that critically affects lifelong mental well-being in offspring, and that maternal depression in particular is an established factor influencing offspring mental health.1-3 In this issue of the Journal, Wesseldijk et al. present their article "Do Parental Psychiatric Symptoms Predict Outcome in Children With Psychiatric Disorders? A Naturalistic Clinical Study," an effort to examine relationships between parental psychiatric symptoms and clinical outcomes in child psychiatric patients.4 The study moves beyond a focus on maternal depression as a risk factor for offspring psychopathology to include a range of active psychiatric symptomatology in both mothers and fathers at the time that children are presenting for clinical evaluation, and again at follow-up over a year and a half later.


Plasma, cardiac tissue and brain morphine concentrations in acute and chronic morphine-treated rats.
1. The plasma, cardiac tissues and brain morphine concentrations in rats after acute or chronic morphine treatment were measured by high-performance liquid chromatography. 2. Morphine concentrations in plasma and cardiac tissues were found to be significantly higher than those in brain after acute morphine injection. However, after chronic oral administration, morphine concentrations in plasma, cardiac tissues and brain were similar. 3. Brain concentrations of morphine following chronic administration were higher than those obtained after acute administration although concentrations in plasma and cardiac tissues were lower.


Environmental stressors differentially modulate anxiety-like behaviour in male and female zebrafish.
How differently male and female responds in a stressful situation is a matter of curiosity. Apart from curiosity, this opens a new arena to the synthesis of personalized/individualized medications. Here, we used zebrafish, a suitable experimental animal model to study stress and anxiety. We evaluated the differential responses in adult male and female zebrafish on the acute exposure of three different stressors: Caffeine (100 mg/L), Conspecific alarm substance (3.5 ml/L), and sight of sympatric predators (Leaf fish and Snakehead) with the help of two different behavioural paradigms (Novel tank test & Predator exposure). Behavioural responses were captured over 6 minutes and quantified using Smart 3.0. Male zebrafish were found to be more responsive to caffeine treatment. Conspecific alarm substance-challenged males and females showed robust alarm reactions whereas females were found to be more prone to it. Female zebrafish showed statistically significant aversion to the visual representation of sympatric predators. Taken together, each stressor induced differential responses in male and female zebrafish.


Thrombocytopenia is associated with a dysregulated host response in severe COVID-19.
Thrombocytopenia is associated with increased mortality in COVID-19 patients. To determine the association between thrombocytopenia and alterations in host response pathways implicated in disease pathogenesis in patients with severe COVID-19. We studied COVID-19 patients admitted to a general hospital ward included in a national (CovidPredict) cohort derived from 13 hospitals in the Netherlands. In a subgroup, 43 host response biomarkers providing insight in aberrations in distinct pathophysiological domains (coagulation and endothelial cell function; inflammation and damage; cytokines and chemokines) were determined in plasma obtained at a single time point within 48 h after admission. Patients were stratified in those with normal platelet counts (150-400 × 109/L) and those with thrombocytopenia (<150 × 109/L). 6.864 patients were enrolled in the national cohort, of whom 1.348 had thrombocytopenia and 5.516 had normal platelets counts; the biomarker cohort consisted of 429 patients, of whom 85 with thrombocytopenia and 344 with normal platelet counts. Plasma D-dimer levels were not different in thrombocytopenia, although patients with moderate-severe thrombocytopenia (<100 × 109/L) showed higher D-dimer levels, indicating enhanced coagulation activation. Patients with thrombocytopenia had lower plasma levels of many proinflammatory cytokines and chemokines, and antiviral mediators, suggesting involvement of platelets in inflammation and antiviral immunity. Thrombocytopenia was associated with alterations in endothelial cell biomarkers indicative of enhanced activation and a relatively preserved glycocalyx integrity. Thrombocytopenia in hospitalized patients with severe COVID-19 is associated with broad host response changes across several pathophysiological domains. These results suggest a role of platelets in the immune response during severe COVID-19.


Effect of pacifier use on oral breathing in healthy newborn infants.
We tested the hypothesis that the use of a pacifier may affect the ability of some term infants to maintain effective oral breathing during prolonged nasal occlusion. Three nasal occlusion tests without a pacifier and 3 with a pacifier were alternately carried out in 20 healthy term infants (age 2-5 days). Once the infant commenced oral breathing, nasal occlusion was continued for up to 90 sec (prolonged nasal occlusion), provided the infant did not start crying and that arterial oxygen saturation (SaO(2)) did not drop to < or = 80%. The response to nasal occlusion was considered maladaptive if oral breathing was accomplished with signs of upper airway obstruction. After nasal occlusion, the infants succeeded in starting oral breathing in all instances after a delay which was strongly correlated to the drop in SaO(2) (P < 0.001). Once the infants commenced oral breathing, 17/20 infants presented a maladaptive response to 62% of all tests without pacifier, whereas 10/20 infants presented a maladaptive response to 30% of all tests with a pacifier in place (P < 0.001). Following prolonged nasal occlusion, 18 of 19 infants presented a maladaptive response to 84% of all tests without pacifier, whereas 12 of 19 infants presented a maladaptive response to 41% of all tests with a pacifier in place (P < 0.001). Thus, after prolonged nasal occlusion with or without pacifier, the drop in mean SaO(2) from baseline values changed in accordance with an appropriate and maladaptive response (-4 +/- 1 vs. -7 +/- 1; P < 0.001). We conclude that normal term infants often present with a maladaptive response to prolonged nasal occlusion. The use of a pacifier enhances the infant's ability to maintain a more adequate oral air flow.


New insights on circular RNAs and their potential applications as biomarkers, therapeutic agents, and preventive vaccines in viral infections: with a glance at SARS-CoV-2.
The occurrence of viral infections and approaches to handling them are very challenging and require prompt diagnosis and timely treatment. Recently, genomic medicine approaches have come up with the discovery of the competing endogenous RNA (ceRNA) network, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) on the basis of gene silencing. CircRNAs, as a group of non-encoded RNAs, make a loop-like structure by back-splicing through 3' and 5' ends. They are stable, abundant, specific, and highly conserved and can be quickly generated at large scales in vitro. CircRNAs have the potential to contribute in several cellular processes in a way that some serve as microRNA sponges, cellular transporters, protein-binding RNAs, transcriptional regulators, and immune system modulators. CircRNAs can even play an important role in modulating antiviral immune responses. In the present review, circRNAs' biogenesis, function, and biomarker and therapeutic potential as well as their prospective applications as vaccines against viral infections such as SARS-CoV-2 are explained. By considering their unique properties, their potential to be used as novel vaccines, biomarkers, and a therapeutic approach appears possible.


Total circulating red cells versus haematocrit as the primary descriptor of oxygen transport by the blood.
Peripheral haematocrit (PCV) is the traditional target and monitor in many transfusion regimens. Without negating the importance of PCV as a determinant of whole blood viscosity, the present article outlines two important reasons why the red cell volume (RCV) should replace PCV in the central target role during blood transfusion in intensive care and other emergency situations: 1. PCV reflects both RCV and plasma volume (PV) and is therefore not directly proportional to the total blood oxygen carrying capacity. At best, the relationship between PCV and RCV is hyperbolic and this is often overlooked when relating the two parameters in practice. At worst, the hyperbolic relationship is unreliable because PV and RCV can vary independently and the PCV is a fluctuating ratio of variable numbers. 2. PCV is not a good indicator of blood volume (BV), which is another important determinant of oxygen delivery to tissues and a crucial parameter in intensively managed patients. BV is directly proportional to RCV and this relationship also is often overlooked in clinical practice. The recommended values for RCV are 30 ml/kg in men. 25 ml/kg in women and between 30 ml/kg and 45 ml/kg in neonates within the first week of life.


[Isolation and structural elucidation of thermal degradation products of theFusarium mycotoxin nivalenol].
The major class of mycotoxins produced byFusarium moulds are trichothecenes, a large group of sesquiterpenes sharing the same basic chemical structure, a 12,13-epoxytrichothec-9-ene ring system. Their toxicity is attributed to their ability to noncompetitively inhibit the biosynthesis of proteins in eukaryotic cells. Trichothecenes in general are relatively stable substances and their degradation is reported only at high temperatures and prolonged heating time.In an attempt to investigate the stability of the trichothecene nivalenol (NIV) under food processing conditions such as cooking or baking, we performed a number of experiments using a model heating system.Heating of nivalenol, especially under mild alkaline conditions, gave a mixture of four compounds (norNIV A, norNIV B, norNIV C and NIV lactone), which were separated and further analyzed by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). Structure elucidation was achieved by 1D and 2D nuclear magnetic resonance (NMR) experiments.We further demonstrated the formation of these products in heating experiments with spiked flour samples. In a screening of several commercially available products only norNIV B was detected in one of the samples, possibly due to the very low contamination of these particular samples with nivalenol.


Guidance materials from 2014 to 2019 on nutritional care for Ebola patients in Ebola Treatment Units: an analysis.
To evaluate the inclusion and exclusion of nutritional content in guidance materials related to nutritional care for hospitalised Ebola Virus Disease (EVD) patients of any age with the aim to provide recommendations for future revised nutritional care guidelines in Ebola Treatment Units (ETU). Qualitative and quantitative analyses of ETU protocols and other guidance materials were conducted. Materials were obtained from practitioners, their organisations and governments active in EVD outbreaks since 2014. Guinea, Liberia, Sierra Leone and Democratic Republic of Congo. Guidance materials showed a wide variety of topics. Most contained information on different feeding phases during illness, the use of specialised products, what and how to feed children aged 0-23 months, and meal and snack frequency for different age groups. Most materials lacked guidance on how to assess or accommodate patients' dietary preferences, how to obtain feedback on nutritional care from patients or how to assess whether patients need feeding support. These aspects are particularly relevant to prevent deterioration of the patients' nutritional status. There was limited guidance on operational aspects of food preparation and provision. Since 2014, numerous materials have been developed by organisations and governments on nutritional support in ETU. Although every EVD outbreak response must be contextualised because of the complexity of EVD and its case management, it is important to resolve technical differences and to provide comprehensive and more practical guidance. The findings of this study may inform future revised guidelines from normative UN organisations and governments of countries affected by EVD.


Local diversity of drought resistance and resilience in Populus tomentosa correlates with the variation of DNA methylation.
Little information is known about DNA methylation variation in shaping environment-specific drought resistance and resilience for tree adaptation. In this study, we leveraged RNA sequencing and whole-genome bisulfite sequencing data to dissect the distinction of epigenetic regulation under drought stress and rewater condition of Populus tomentosa accessions from three geographical regions. We demonstrated low resistance and high resilience for accessions from South. Non-CG methylation levels in promoter regions of Southern accessions were lower than accessions from higher latitudes and negatively regulated gene expression. CHH context methylation was more sensitive to drought stress, and the geographical-specific differentially methylated regions were scarcely changed by environmental fluctuation. We identified 60 conserved hub genes within the co-expression networks that correlate with photosynthetic and stomatal morphological traits. Epigenome-wide association studies and genome-wide association studies of these 60 hub genes revealed the interdependency between genetic and epigenetic variation in GATA9 and LECRK-VIII.2, which was associated with stomatal morphology and chlorophyll content. The natural epigenetic variation in GATA9 was also faithfully transmitted to progenies in two family-based F1 populations. This study indicates a functional relationship of DNA methylation diversity with drought resistance and resilience which offers new insights into plants' local adaptation to a stressful environment.


Neurologic complaints in young children in the ED: when is cranial computed tomography helpful?
The objective of this study is to describe the use of emergent head computed tomography (CT) in young children and ask in which circumstances scans contributed to immediate management. We reviewed electronic records of children, aged 1 month through 6 years, who received a head CT at a large suburban emergency department between February 2008 and February 2009. Age, sex, chief complaint, history, physical examination, indication for and results of head CT, red flags in history or physical examination, final disposition, and number of head CT scans performed to date were recorded. Abnormalities on CT scans were classified as significant or incidental, and subsequent interventions were documented. Emergent head CTs were performed on 394 children. The most common indications were trauma, 65%; seizure, 11%; and headache, 6%. Computed tomographic abnormalities were found in 40% (154 children): 32 significant findings,104 incidental findings, and 22 preexisting abnormalities. Four children with significant findings required immediate intervention. They all had red flags in both history and physical examination, and 3 of 4 children had known preexisting pathology; 1 child had nonaccidental trauma. Only 1 child had a significantly abnormal CT with no identifiable red flags; this child was admitted for observation and was discharged within 24 hours. Approximately a third of children had no readily identifiable red flag for the CT scans that they received. Of note, 20% of the young children had received more than 1 head CT scan to date, and 6% had between 6 and 20 scans. Every child in this sample who required emergency intervention had red flags on history and physical examination. The 35% of CT scans performed in young children without red flags did not contribute usefully to their acute management.


Early liaisons between cells of the innate immune system in inflamed peripheral tissues.
The crosstalk between natural killer (NK) cells and myeloid dendritic cells (DCs) results in NK-cell activation and DC maturation. Activated NK cells acquire the ability to kill DCs that have failed to undergo complete maturation ('DC editing'). Recent studies have revealed that this crosstalk can be promoted by pathogen-derived products that activate different innate immune cell types directly and simultaneously through their Toll-like receptors (TLRs). These cells include NK cells and DCs, as well as plasmacytoid DCs (PDCs) and mast cells. This crosstalk can have a great impact on the quality and strength of the subsequent adaptive immune response. Thus, NK cells have an important role in the defense against pathogens, acting as regulatory cells as well as effector cells.


Subsegmental approaches to S7: anatomic laparoscopic transdiaphragmatic and nonanatomic robotic transthoracic.
Minimally invasive liver surgery of postero-superior segments (S4a, S7, S8) remains a challenge. The caudal view, an increased distance between trocars and the operative field, and the liver fulcrum limiting the view, contribute to the difficulty [1, 2]. We and other groups have previously reported the use of intercostal trocars to access subdiaphragmatic tumors (transdiaphragmatic approach) [3-5], only few reports on a laparoscopic total transthoracic approach, none (to our knowledge) dynamic manuscripts of a total transthoracic robotic approach, and none (to our knowledge) that use preoperative port site and anatomic modelling exist. Further, we developed a total transthoracic (thoracoscopic) approach to avoid a hostile abdomen, while bringing viewing axis and instruments close to the target [6-10]. In this context, this report details the advantages of a laparoscopic vs. robotic transthoracic approach. According to institutional protocol, reports of individual cases in print or video format do not require institutional review board approval. A 68-year-old male on peritoneal dialysis with left colon adenocarcinoma and a single synchronous liver metastasis in S6-7 close to the root of the right hepatic vein underwent a laparoscopic transdiaphragmatic metastasectomy. Two years later, the patient developed a recurrent 1.5 cm liver metastasis in S7, which lend itself to a robotic transthoracic approach. Following 3-D modelling and virtual port placement planning, the first metastasectomy was performed laparoscopically using a transdiaphragmatic approach. The recurrence was managed transthoracically due to more apical, subdiaphragmatic location. For this operation, a robotic approach was optimal as robotic wrist articulation facilitates manipulation via the limited intercostal space. This was particularly helpful during the diaphragmatic reconstruction. Total transthoracic liver surgery is certainly an advanced procedure requiring superior MIS liver skills. Recommendations for starting with a total transthoracic approach are not unlike from starting a standard, none-transthoracic liver surgery. Early on in the experience we recommend advanced liver MIS skills, and single, small, subdiaphragmatic tumors away from major vessels. Nonetheless, when these recommendations are followed a total transthoracic approach may be safer and result in less access trauma, than traversing a hostile abdomen to reach the posterior-superior liver. Both laparoscopic and robotic transthoracic approaches can facilitate the resection of subdiaphragmatic tumors, especially in patients with hostile abdomens. While the laparoscopic approach has advantages due to a broader spectrum of available surgical tools (flexible tip camera, parenchymal dissection, and energy devices), the robotic wrist articulation facilitates manipulation via the restricted intercostal space.


Schisandrin B ameliorates acute liver injury by regulating EGFR-mediated activation of autophagy.
To investigate the role and possible molecular mechanism of Schisandrin B-induced cell autophagy in the prevention and treatment of APAP-induced liver injury. Molecular docking method was used to predict the interaction between Schisandrin B and the EGFR protein. HepG2 cells were treated with different concentrations of Schisandrin B for 24 h. Schisandrin B-induced autophagy of HepG2 cells was determined using real-time label-free cell analysis (RTCA), flow cytometry, immunofluorescence, PCR, and western blot. Flow cytometry and western blot were used to explore whether Schisandrin B-induced autophagy plays a role in the prevention and treatment of liver injury via the EGFR/TFEB signaling pathway. Schisandrin B treatment of APAP-induced HepG2 cells inhibited the production of TNF-α and IL-1β. Further, Schisandrin B downregulated EGFR protein expression and activated the EGFR/TFEB signaling pathway. Autophagy inhibition promoted APAP-induced apoptosis of HepG2 cells. Moreover, the protein expression levels of TFEB, LC3 and Beclin-1 were upregulated, whereas those of ATG3 and EGFR were downregulated. Schisandrin B can induce autophagy in HepG2 cells. Autophagy may play a role in the prevention and treatment of liver injury via the EGFR/TFEB signaling pathway. Activation of autophagy enhances the effect of Schisandrin B on APAP-induced liver injury.


Analysis of optimal lockdown in integral economic-epidemic model.
We analyze the optimal lockdown in an economic-epidemic model with realistic infectiveness distribution. The model is described by Volterra integral equations and accurately depicts the COVID-19 infectivity pattern from clinical data. A maximum principle is derived, and a qualitative dynamic analysis of the optimal lockdown problem is provided over finite and infinite horizons. We analytically prove and economically justify the possibility of an endemic scenario when the infection rate begins to climb after the lockdown ends.


Oxalate excretion in rats injected with xylitol or glycollate: stimulation by phenobarbitone pre-treatment.
The hypothesis that the prior intake of barbiturates may predispose patients to form increased amounts of oxalate following the intravenous infusion of xylitol was investigated in the rat. Phenobarbitone pre-treatment resulted in a 2-3 fold increase in urinary [14C] oxalate concentration following the intraperitoneal injection of [U-14C] xylitol or [l -14C] glycollate. The absence of any marked changes in urine volumes and creatinine excretion implied that this increase in urinary oxalate excretion was due to the enhanced synthesis of oxalate. The activities of key enzymes in hepatic oxalate synthesis, glycollate oxidase, lactate dehydrogenase, catalase and alanine aminotransferase were not altered by phenobarbitone pre-treatment. It is suggested that the increased activity of the microsomal mixed function oxidases, following phenobarbitone treatment, may facilitate the oxidation of glycollate and possibly xylitol. This communication leads experimental support to the concept that the prior intake of drugs, such as barbiturates, may predispose patients to form increased amounts of oxalate.


Synthesis and antibacterial activity of nitroaryl thiadiazole-gatifloxacin hybrids.
A number of gatifloxacin analogues containing a nitroaryl-1,3,4-thiadiazole moiety attached to the piperazine ring at C-7 position were prepared and evaluated as antibacterial agents against a panel of gram-positive and gram-negative bacteria. Among synthesized compounds, nitrofuran analog 6a exhibited more potent inhibitory activity against gram-positive bacteria including Staphylococcus epidermidis (MIC=0.0078 microg/mL), Bacillus subtilis (MIC=0.0039 microg/mL), Enterococcus faecalis (MIC=0.125 microg/mL) and Micrococcus luteus (MIC=0.125 microg/mL), with respect to other synthesized compounds and reference drug gatifloxacin. The target compounds were also assessed for their cytotoxic activity against normal mouse fibroblast (NIH/3T3) cells using MTT assay. The results indicated that these compounds exhibit antibacterial activity at non-cytotoxic concentrations.


Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition and the Future of Lipid Lowering Therapy.
Low-density lipoprotein cholesterol (LDL-C) reduction with statins is the cornerstone of atherosclerotic cardiovascular disease (CVD) prevention. The LDL-C lowering non-statin therapy ezetimibe also modestly reduces CVD risk when added to statin therapy. There remains a clinical need for additional LDL-C lowering agents to reduce CVD risk in patients with genetic hypercholesterolemia, statin intolerance, or who are at high risk due to clinical CVD or diabetes. In clinical trials, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition using monoclonal antibodies has demonstrated robust LDL-C lowering efficacy of 50-65% and a favorable safety profile. These agents are a promising therapeutic strategy for addressing the unmet needs for additional CVD risk reduction. Regulatory approval for PCSK9 monoclonal antibodies may occur in the near future, and additional agents for PCSK9 inhibition are under development. This review focuses on the mechanism of LDL-C reduction using PCSK9 inhibition, as well as the phase I to III clinical trials of PCSK9 inhibitors. Results of the ongoing phase III CVD outcome trials are eagerly awaited.


Laparoscopic Nephro-Sparing Surgery of a Reninoma Tumor in a Pediatric Patient.
Reninoma, or juxtaglomerular cell tumor, is a benign neoplasm which causes severe hypertension with elevated plasma renin activity.1-3 Usually, it is well localized on computed tomography scan or magnetic resonance images, and complete resection of the tumor with renal function preservation is the optimal treatment.2-4 To describe the technique of a transperitoneal nephron-sparing laparoscopic surgery in a pediatric patient. Describe the technique of a minimally invasive nephron-sparing surgery for resection of a reninoma tumor in a child. In a 14-year-old girl with history of severe high blood pressure, ultrasound detected a hypoechoic lesion in right kidney. Angio computed tomography scan confirmed a 20-mm diameter lesion in the anterior surface of the lower pole of right kidney and also informed a lower pole renal artery. Transperitoneal laparoscopic approach was performed using 4 ports. After mobilization of the colon, Gerota's fascia was opened and the tumor identified. Both polar and principal renal arteries were dissected and secured with vessel loops. The tumor was resected using an ultrasonic energy device. Selective clamping of the lower pole renal artery was performed during 8 minutes. The transected renal surface was closed with two continuous barbed sutures and the tumor was removed using a handmade endobag. Perirenal drainage was left for 4 days, there were no perioperative complications and the patient was discharged 2 days after surgery. Pathology confirmed typical reninoma immunohistochemical features. Blood pressure and plasma renin levels returned to normal. Postsurgical scintigraphy informed 40% differential function of the right kidney. Reninoma is a benign renal tumor and because of its nature and localization, minimally invasive nephron-sparing surgery should be considered. Strategic planning of the surgery based on preoperative images is essential. If vessel clamping is imperative, minimizing ischemia time and/or selective clamping, when possible, help preserve renal function.


Acute miliary tuberculosis presenting as acute respiratory failure.
A 42 year old pregnant woman was admitted in acute respiratory failure. Viral pneumonia was suspected and oxygen therapy, CPAP, water restriction and diuretics were started with good response. She remained febrile and had an abnormal chest X-ray, a diagnosis of miliary tuberculosis was confirmed by transbronchial fibreoptic lung biopsy.


Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience.
5-Aminolaevulinic acid (ALA) is a precursor of protoporphyrin IX (Pp IX) in the biosynthetic pathway for haem. Certain types of cells have a large capacity to synthesize Pp IX when exposed to an adequate concentration of exogenous ALA. Since the conversion of Pp IX into haem is relatively slow, such cells tend to accumulate photosensitizing concentrations of Pp IX. Pp IX photosensitization can be induced in cells of the epidermis and its appendages, but not in the dermis. Moreover, since ALA in aqueous solution passes readily through abnormal keratin, but not through normal keratin, the topical application of ALA in aqueous solution to actinic keratoses or superficial basal cell or squamous cell carcinomas induces Pp IX photosensitization that is restricted primarily to the abnormal epithelium. Subsequent exposure to photoactivating light selectively destroys such lesions. In our ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated. The cosmetic results have been excellent, and patient acceptance has been very good.


Race and gender differences in C-reactive protein levels.
This study sought to determine whether there are race and gender differences in the distribution of C-reactive protein (CRP) levels. Few data are available comparing CRP distributions in different race and gender groups. Recent clinical practice recommendations for CRP testing for cardiovascular risk assessment suggest a uniform threshold to define high relative risk (>3 mg/l). We measured CRP in 2,749 white and black subjects ages 30 to 65 participating in the Dallas Heart Study, a multiethnic, population-based, probability sample, and compared levels of CRP between different race and gender groups. Black subjects had higher CRP levels than white subjects (median, 3.0 vs. 2.3 mg/l; p < 0.001) and women had higher CRP levels than men (median, 3.3 vs. 1.8 mg/l; p < 0.001). The sample-weight adjusted proportion of subjects with CRP levels >3 mg/l was 31%, 40%, 51%, and 58% in white men, black men, white women, and black women, respectively (p < 0.05 for each group vs. white men). After adjustment for traditional cardiovascular risk factors, estrogen and statin use, and body mass index, a CRP level >3 mg/l remained more common in white women (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.1 to 2.5) and black women (OR 1.7; 95% CI 1.2 to 2.6) but not in black men (OR, 1.3; 95% CI, 0.8 to 1.9) when compared with white men. Significant race and gender differences exist in the population distribution of CRP. Further research is needed to determine whether race and gender differences in CRP levels contribute to differences in cardiovascular outcomes, and whether thresholds for cardiovascular risk assessment should be adjusted for different race and gender groups.


Art engagement and psychological well-being among community-dwelling older adults in Japan: an observational cross-sectional study.
Art engagement, which includes individual art activities and museum and gallery visits, potentially contributes to improving psychological well-being. However, there is insufficient evidence of its effects on the older population, and few reports are from Asia, including Japan. This study examined the association between art engagement and psychological well-being among older adults in Japan. An observational cross-sectional study design was used. Community-dwelling older adults aged ≥60 years were recruited from the visitors to public facilities (including community centres, sports centres and cultural centres) in Aichi, Japan, in 2022, and completed questionnaires. The psychological well-being assessment included five domains according to Seligman's PERMA framework: Positive emotion, Engagement, Relationship, Meaning and Accomplishment. Regarding art engagement, the frequencies of active art engagement (e.g. activities by individuals and participation in groups, such as music and painting) and receptive art engagement (e.g. visiting museums, galleries and the theatres) were assessed. A total of 522 participants were included in the analysis (mean age = 74.1 years; 78.0% females). Results from the multivariable linear regression analysis, which adjusted for demographic and socio-economic factors, revealed that higher frequencies of active art engagement were significantly associated with higher scores in all five PERMA domain scores. Higher frequencies of receptive art engagement were significantly associated with higher levels of Positive emotion, Engagement and Meaning domain scores, but were only marginally associated with the Accomplishment domain and were not associated with the Relationships domain. This study indicates that art engagement has the potential to enhance psychological well-being among older adults. National and local government strategies to increase accessibility to art and cultural activities for older adults are recommended.


A practical approach to diagnosis and management of functional constipation in adults.
Chronic constipation is a frequently complained condition in clinical practice and may be primary (idiopathic) or due to secondary causes. The definition of the various forms of constipation is presently made according to the Rome III criteria, which recently incorporated also specific diagnostic algorithms. The diagnosis of constipation relies on the patient's history, including use of drugs, physical examination, and specific investigations (transit time, anorectal manometry, balloon expulsion test, defecography). These will often be useful to start a targeted therapeutic schedule that may include fibres, laxatives, biofeedback training and, in extreme cases, a surgical approach. This review will analyse the clinical and diagnostic aspects of chronic constipation in adult patients, with emphasis on recent therapeutic approaches.


Experiences of caregiving and quality of healthcare among caregivers of patients with complex chronic processes: A qualitative study.
Aim To explore the perceptions of main caregivers regarding caring for chronic complex patients in two different regions of Spain. Spain is a country with an ageing population and a high number of people with chronic diseases. It is well known that the role of the caregiver is important to ensure quality of life and appropriate care. Qualitative design using focus groups. Five focus groups, from two different regions, were conducted with 22 caregivers of people with chronic complex diseases to explore their personal experience, examine the quality of care received by the patient and their family and to develop strategies for the improvement of the quality of health care. The focus groups were audio and video recorded. The transcriptions of the focus group sessions were exported to qualitative software analysis MAXQDA 2018.2. The qualitative content analysis was based on different analytical cycles. In general terms, caregivers would refer to accepting the care of their family members, but they highlight many negative aspects such as tiredness, lack of help and overload of care. They indicated general satisfaction with the health system but indicated that help was insufficient and that strategies to better address the situations of the complex chronic patient should be improved. The main categories observed were: Conclusions. Complex chronic illnesses are increasingly common at present, generating important consequences on the lives of patients and that of their caregivers. The design of any health strategy for facing the dilemma of chronic illnesses, must necessarily include the vision of the caregivers.


T-Configuration Stent Placement for Carotid Bifurcation Stenosis Co-Existing with Ipsilateral Intracranial Stenosis: A Case Report and Literature Review.
In patients with carotid bifurcation stenosis co-existing with ipsilateral intracranial artery stenosis, combined treatment with carotid artery stenting (CAS)/carotid endarterectomy (CEA) and extracranial-to- intracranial (EC-IC) bypass can be a useful option to prevent future ischemic stroke events. EC-IC bypass requires a sufficient antegrade flow in the ipsilateral external carotid artery. However, standard CAS/CEA occasionally lead to external carotid artery occlusion. Herein, we present a case of successful one-stage endovascular revascularization of both the antegrade internal and external carotid artery flow using the carotid T-stent technique for carotid bifurcation stenosis co-existing with ipsilateral middle cerebral artery stenosis.


The effect of ethanol on platelet function and vascular prostanoids.
The present review will discuss the effects of ethanol on platelet function and vascular prostanoids. Whenever possible we have considered human studies because there are marked species differences in platelet function and vascular prostanoid release even in the absence of ethanol. Because of the specialised nature of some parts of the text, we have included brief introductions to help readers who are not familiar with this field.


Microwave-assisted synthesis of 3,1,2- and 2,1,8-Re(I) and 99mTc(I)-metallocarborane complexes.
Microwave heating was used to prepare eta5-rhenium carborane complexes in aqueous reaction media. For carboranes bearing sterically demanding substituents, isomerization of the cage from 3,1,2 to 2,1,8 derivatives occurred concomitantly with complexation. Microwave heating was equally effective at the tracer level using technetium-99m, affording access to a new class of synthons for designing novel molecular imaging agents.


Indications of different oxygen sources.
Elderly patients with limited prognosis and limited activities are sufficiently supplied by oxygen concentrators with or without portable oxygen gas cylinders. Younger patients with promising life expectancy should be candidates for transtracheal catheter and for liquid oxygen with or without oxygen saving systems.


Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals.
Egr-1 is an immediate-early response gene induced by diverse signals that initiate growth and differentiation. Its cDNA sequence predicts a protein with zinc fingers. We have generated an antiserum to the Egr-1 gene product and identified it as an 80-kilodalton short-lived protein in serum-stimulated mouse fibroblasts. The rat Egr-1 product has also been identified in nerve growth factor-induced PC12 cells. In addition, we show by cell fractionation and immunocytochemistry that the Egr-1 protein is located in the nucleus. We also demonstrate that it is phosphorylated. In vitro-generated Egr-1 protein binds with high affinity to the sequence CGCCCCCGC in a zinc-dependent manner.


First record of Microscapha LeConte from Baltic amber with description of a new species and list of fossil Melandryidae (Coleoptera: Tenebrionoidea).
Microscapha andrzeji sp. nov., the first fossil representative of the genus is described from Eocene Baltic amber. An updated list of fossil Melandryidae (Coleoptera: Tenebrionoidea) is provided. The presence of Microscapha within Baltic amber suggests some potential for palaeoenvironmental inferences based on the melandryid assemblage within the deposit.


Comprehensive treatment of arteriovenous malformations in the oral and maxillofacial region.
Arteriovenous malformations (AVMs) in the oral and maxillofacial region are rare but potentially life-threatening vascular lesions. We report our experience in treating these lesions in the oral and maxillofacial region. Superselective intra-arterial embolization (SIAE), sclerotherapy, bone wax packing of bone cavity and curettage, radiotherapy, and surgical resection were used alone or in combination in 28 patients with AVMs in the oral and maxillofacial region. Among them there are 13 cases involving the soft tissue, 11 cases involving bone, and 4 cases involving both the soft tissue and bone. Follow-up ranged from 3 to 60 months (median, 22 months) after comprehensive treatment. The rates of improvement and cure were 89.3% and 60.7%, respectively. Sclerotherapy in 6 cases of AVMs was ineffective. The rates of improvement and cure in AVMs involving soft tissue treated by surgical resection were 23.1% and 84.6%, respectively. The rates of cure for AVMs involving the jaws treated by SIAE, bone wax packing, curettage, and partial bone resection alone or in combination was 100%. Three cases of AVMs involving both soft tissue and bone treated with SIAE and radiotherapy as well as surgical resection were cured. SIAE was an adjunctive treatment for the AVMs of soft tissue and jaws and for controlling bleeding. Surgical resection was an important treatment modality for AVMs. Bone wax packing of bone cavity and curettage was a simple, safe, and effective method for the treatment of AVMs of the jaws. Radiotherapy and sclerotherapy may not be effective methods for AVMs involving the soft tissue.


Forensic experts' perceptions of expert bias.
How do expert witnesses perceive the possible biases of their fellow expert witnesses? Participants, who were attendees at a workshop at the American Academy of Psychiatry and Law were asked to rate for their biasing potential a number of situations that might affect the behavior of an opposing expert. A Rasch analysis produced a linear scale as to the perceived biasing potential of these different kinds of situations from the most biasing to the least biasing. Working for only one side in both civil and criminal cases had large scaled values and also were the first factor. In interesting contrast, a) an opposing expert also serving as the litigant's treater and b) an opposing expert being viewed as a "hired gun" (supplying an opinion only for money) were two situations viewed as not very biasing. Order of Hierarchical Complexity also accounted for items from the 1st, 2nd and 3rd factors. The result suggests that the difficulty in understanding the conceptual basis of bias underlies the perception of how biased a behavior or a situation is. The more difficult to understand the questionnaire item, the less biasing its behavior or situation is perceived by participants.


Laser ablation of burns: initial clinical trial.
Scanning, high-powered carbon dioxide laser ablation of eschar may facilitate blood conservation in patients with burns. Twenty-one children with full-thickness burns that required serial excisions were enrolled in a Human Studies Committee approved protocol in which a full-thickness wound was ablated with a rapidly scanned continuous wave carbon dioxide laser system. A control wound was sharply excised, and both wounds were immediately autografted. End points were engraftment at 7 days and serial Vancouver scar scores. The children had an average age of 8.3 +/- 1.2 years, weight of 36.3 +/- 4.9 kg, and burn size of 40% +/- 5.1%. The study wounds were ablated with an average energy of 99.2 +/- 5.7 W; there was no bleeding from 19 successfully ablated wounds. Initial engraftment averaged 94.7% +/- 3.5% in the control sites and 94.7% +/- 3.3% in the study sites (P = 1.0). There was no significant difference in Vancouver scar scores at an average follow-up of 32.0 +/- 5.2 weeks. This pilot study follows a successful trial of this concept in a porcine model and demonstrates the technical feasibility of laser vaporization of burn eschar in humans with immediate autografting. Further refinement of the technique is required before it can be generally recommended.


Climbing and the daily energy cost of locomotion in wild chimpanzees: implications for hominoid locomotor evolution.
As noted by previous researchers, the chimpanzee postcranial anatomy reflects a compromise between the competing demands of arboreal and terrestrial locomotion. In this study, we measured the distance climbed and walked per day in a population of wild chimpanzees and used published equations to calculate the relative daily energy costs. Results were used to test hypotheses regarding the arboreal-terrestrial tradeoff in chimpanzee anatomy, specifically whether arboreal adaptations serve to minimize daily locomotor energy costs by decreasing the energy spent climbing. Our results show that chimpanzees spend approximately ten-times more energy per day on terrestrial travel than on vertical climbing, a figure inconsistent with minimizing energy costs in our model. This suggests non-energetic factors, such as avoiding falls from the canopy, may be the primary forces maintaining energetically costly climbing adaptations. These analyses are relevant to anatomical comparisons with living and extinct hominoids.


99mTc-diethyl-HIDA: a contribution to the study of its structure.
Sephadex column chromatography has shown that 99mTc-diethyl-HIDA consists of two clearly separable components. One of them seems to be an intermediate compound changing into the other, almost completely within two hours after reconstitution of the diethyl-HIDA (Solco HIDA) with pertechnetate. The two components could be the mono- and biscomplex of N-(2,6-diethyl-acetanilid)-imino diacetic acid with one atom of technetium. Animal experiments show that there is no important difference in the biological distribution in mice between the two components.


MR hysterosalpingography with an angiographic time-resolved 3D pulse sequence: assessment of tubal patency.
The purpose of our study was to determine if tubal patency can be assessed by MR hysterosalpingography (HSG) using a clinically available MR angiographic sequence (3D time-resolved imaging of contrast kinetics [TRICKS]). This capability would enhance the value of MRI in women with infertility. MR HSG effectively shows tubal patency and can be considered when both conventional HSG and standard MRI are necessary for the evaluation of women with infertility, such as in women with suspected uterine anomalies or extrauterine disease.


Prevalence of moderate or severe left ventricular diastolic dysfunction in obese persons with obstructive sleep apnea.
We investigated prior to gastric bypass surgery the prevalence of left ventricular diastolic dysfunction (LVDD) by Doppler and tissue Doppler echocardiography in 14 obese women and in 6 obese men, mean age 45 years, with a mean body mass index of 49+/-5 kg/m2 who had nocturnal polysomnography for obstructive sleep apnea (OSA). The Doppler and tissue Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether OSA was present or absent. Of 20 patients, 8 (40%) had no OSA, 4 (20%) had mild OSA, and 8 (40%) had moderate or severe OSA. Moderate or severe LVDD was present in 4 of 8 patients (50%) with moderate or severe OSA and in none of 12 patients (0%) with no or mild OSA (p<0.01). Obese patients with moderate or severe OSA have a higher prevalence of moderate or severe LVDD than obese patients with no or mild OSA.


Clinical performance of the implantable cardioverter-defibrillator.
The automatic implantable cardioverter-defibrillator has been implanted in 276 patients with ventricular tachyarrhythmias refractory to therapy with a follow-up period up to 50 months (average 9.75 months). The functional performance of the device has so far been most encouraging. The risks and complications associated with its use are acceptable and quite similar to those observed in patients with implanted pacemakers. Acceleration of ventricular tachycardia to a faster rhythm or to ventricular fibrillation is dealt with successfully through recycling. Actuarial analysis indicates that the device has a significant impact on the survival rate of the implantees, reducing the one-year mortality rate attributed to arrhythmias to only 2%.


Age estimation accuracies from black South African os coxae.
The accurate estimation of age is considered important from an ethical, legal and archaeological perspective. Among the numerous methods based on macroscopic skeletal studies for age estimation, the Brooks and Suchey (1990) method for aging from the pubic symphysis and the Buckberry and Chamberlain (2002) method for aging from the auricular surface are considered more reliable. However, both these methods have been derived from American populations. Therefore, the following study aimed to assess the accuracy of the estimation of age-at-death from morphological age related changes seen on the pubic symphysis and the auricular surface in a black South African population. A total of 197 individuals of known age of both sexes using both left and right ossa coxae were investigated. Age was estimated using descriptions stipulated by Brooks and Suchey (1990) and Buckberry and Chamberlain (2002). Correlation coefficients, inaccuracies and bias were calculated for both skeletal elements for both sexes and sides. Inaccuracies and bias were lower in the pubic symphysis than in the auricular surface thus making the pubic symphysis a more reliable age estimator. Similarly, males indicated lower inaccuracies and bias than did females. Overall, the pubic symphysis outperformed the auricular surface, even though the method described by Buckberry and Chamberlain (2002) is considered more reliable. It is advised that these two methods be improved to produce better accuracies, particularly when applying the methods to a black South African population.


Effects of diet-induced obesity in the development of lymphedema in the animal model: A literature review.
Obesity poses deleterious consequences on every organ system, especially the lymphatic network. However, the underlying cellular mechanisms through which obesity causes lymphatic dysfunction remains unclear. We aimed to summarize experimental studies that evaluated the effect of obesity on the lymphatic system on animal models. We used the following terms to search the Ovid EMBASE, Ovid MEDLINE(R), Cochrane, and Scopus databases: "lymphedema", "lymphatic diseases", "lymphatic system/complications* ", "lymphatic system/injuries* ", "lymphatic system/abnormalities* ", AND "obesity/complications* ", "diet/high-fat", "adipogenesis" and "lipid metabolism disorder". From a total of 166 articles identified in the initial search, 13 met our eligibility criteria. Long-term exposure to high-fat diet in mice demonstrated significant amount of adipose tissue deposition which sets off an inflammatory cascade resulting in disruption of the chemokine gradient, inhibition of lymphangiogenesis, and changes in gene expression of lymphatic endothelial cells, that alter vessel permeability and induce cell death. Reduced contractile properties of lymphatic collectors, dilated capillaries, increased tissue pressure, and reduced hydraulic conductivity collectively contribute to reduced impaired lymphatic drainage. Aerobic exercise has shown reversal of lymphatic dysfunction in the obese and pharmacological interventions targeting T-cells, iNOS and VEGFR-3 signaling have the potential to combat acquired lymphedema. Scientists should focus their future experiments on developing therapies that regulate expression of T-cell derived cytokines and VEGFR-3 expression whereas clinicians are urged to counsel their patients to reduce weight through aerobic exercise.


Activation of calcium channel by shear-stress in cultured renal distal tubule cells.
Using the patch-clamp technique and the fura-2 fluorescence measurement, we found that flow of a normal solution simultaneously increased both the inward cation (Ca) currents and the cytosolic Ca activity (Cai) in cultured renal distal tubule cells (A6 cells). The activation of these signals was voltage-independent and required a lag period of about 30 s. Flow of a Ca free solution (plus 0.1-0.5 mM EGTA) failed to increase these signals. The Ca current increased and saturated with increasing extracellular Ca concentrations (apparent Km, 1 mM Ca; maximum Ca current, 43 pA). Ni (1 mM) and La (1 mM) inhibited the flow-induced Cai-increase, but nicardipine (50 microM) did not. These results strongly suggest that in A6 cells flow increases Ca-influx through a shear-stress activated Ca-channel and may regulate the cellular transport functions.


Long-term Impact of Continuous Positive Airway Pressure Therapy on Arrhythmia and Heart Rate Variability in Patients With Sleep Apnea.
Autonomic dysfunction can alter heart rate variability and increase the incidence of arrhythmia. We analyzed the impact of continuous positive airway pressure (CPAP) on this pathophysiological phenomenon in patients with severe sleep apnea-hypopnea syndrome. Consecutive patients with recently diagnosed severe sleep apnea-hypopnea syndrome were prospectively considered for inclusion. Incidence of arrhythmia and heart rate variability (recorded on a 24-hour Holter monitoring device) were analyzed before starting CPAP therapy and 1 year thereafter. A total of 26 patients were included in the study. CPAP was administered for 6.6 ± 1.8 hours during Holter monitoring. After starting CPAP, we observed a marginally significant reduction in mean HR (80 ± 9 to 77 ± 11 bpm, p=.05). CPAP was associated with partial modulation (only during waking hours) of r-MSSD (p=.047) and HF (p=.025) parasympathetic parameters and LF (p=.049) sympathetic modulation parameters. None of these parameters returned completely to normal levels (p<.001). The number of unsustained episodes of atrial tachycardia diminished (p=.024), but no clear effect on other arrhythmias was observed. CPAP therapy only partially improves heart rate variability, and exclusively during waking hours, and reduces incidence of atrial tachycardia, both of which can influence cardiovascular morbidity and mortality in sleep apnea-hypopnea syndrome patients.


[Jejuno-ileal short-circuit operations in the treatment of obesity. 16 personal cases (author's transl)].
The authors report a personal experience of 16 cases and in the light of data in the world literature, the authors discuss the controversial method of treatment of very severe obesity when medical treatment has failed. The onset of various complications linked mainly to intestinal malabsorption, should make one careful in the indications for surgery which may, however, be applicable in certain cases.


Sustainable use zoning of land resources considering ecological and geological problems in Pearl River Delta Economic Zone, China.
The Pearl River Delta Economic Zone is one of the fastest growing areas of China's social and economic development. However, the contradiction between people and land, the deterioration of ecological environment and the damage of urban ecological security have become more serious problems. In previous studies there was single land utilization type in small-area and the evaluation method was not suitable to large areas, this study proposes a new method. Firstly, the study implements ecological land zoning from assessing the importance of ecosystem services functional in four aspects: biodiversity, water conservation, soil conservation and coastal protected zone. Then, the suitability evaluation index system of agricultural and construction land is established from the geological environment perspective, and introduces variable weight-analytical hierarchy process-comprehensive index model to evaluate the suitability of agricultural land and construction land. Re-zoning the type of land that has a special effect on the socio-economic, the mining land, protected area of geological relics and groundwater resources, respectively. Finally, considering the actual condition use status and suitability distribution of land, the results of comprehensive zoning of land utilization is got. The results of this study can provide some geological basis for the future land utilization zoning.


Gut microbiota might mediate the benefits of high-fiber/acetate diet to cardiac hypertrophy mice.
Continuously prolonged cardiac hypertrophy results in maladaptive myocardial remodeling, which affects cardiac function and can eventually lead to heart failure. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, have been reported to be associated with cardiovascular diseases (CVD). Gut microbiota may mediate between dietary fiber and SCFA effects on cardiac hypertrophy. The mice model of isoproterenol (ISO)-induced cardiac hypertrophy was constructed and verified for physiological, functional, and fibrotic alterations in this study. Both high-fiber and acetate diet improved physiological indexes, ameliorated cardiac functions, and relieved fibrotic alterations in model mice hearts; collectively, cardiac hypertrophy in mice receiving both high-fiber and acetate diet improved. Following 16s rDNA sequencing and integrative bioinformatics, analyses indicated that both high-fiber and acetate diet caused alterations in mice gut microbiota compared with the ISO group, including OTU composition and abundance. In conclusion, high-fiber and acetate diet improve the physiological status, cardiac functions, and fibrotic alterations in ISO-induced hypertrophic mice. Besides, considering the alterations in mice gut microbiota in response to single ISO, both high-fiber and acetate diet treatment, gut microbiota might mediate the favorable benefits of both high-fiber and acetate diet on cardiac hypertrophy.


Biomarkers for Primary Sjögren's Syndrome.
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with exocrine gland dysfunction and multi-organ involvement. Recent progress in understanding the pathogenesis of pSS offers an opportunity to find new biomarkers for the diagnosis and assessment of disease activity. Screening noninvasive biomarkers from the saliva and tears has significant potential. The need for specific and sensitive biomarker candidates in pSS is significant. This review aims to summarize recent advances in the identification of biomarkers of Sjögren syndrome, trying to identify reliable, sensitive, and specific biomarkers that can be used to guide treatment decisions.


A novel methodology to train and deploy a machine learning model for personalized dose assessment in head CT.
To propose a machine learning-based methodology for the creation of radiation dose maps and the prediction of patient-specific organ/tissue doses associated with head CT examinations. CT data were collected retrospectively for 343 patients who underwent standard head CT examinations. Patient-specific Monte Carlo (MC) simulations were performed to determine the radiation dose distribution to patients' organs/tissues. The collected CT images and the MC-produced dose maps were processed and used for the training of the deep neural network (DNN) model. For the training and validation processes, data from 231 and 112 head CT examinations, respectively, were used. Furthermore, a software tool was developed to produce dose maps from head CT images using the trained DNN model and to automatically calculate the dose to the brain and cranial bones. The mean (range) percentage differences between the doses predicted from the DNN model and those provided by MC simulations for the brain, eye lenses, and cranial bones were 4.5% (0-17.7%), 5.7% (0.2-19.0%), and 5.2% (0.1-18.9%), respectively. The graphical user interface of the software offers a user-friendly way for radiation dose/risk assessment. The implementation of the DNN allowed for a 97% reduction in the computational time needed for the dose estimations. A novel methodology that allows users to develop a DNN model for patient-specific CT dose prediction was developed and implemented. The approach demonstrated herein allows accurate and fast radiation dose estimation for the brain, eye lenses, and cranial bones of patients who undergo head CT examinations and can be used in everyday clinical practice. • The methodology presented herein allows fast and accurate radiation dose estimation for the brain, eye lenses, and cranial bones of patients who undergo head CT examinations and can be implemented in everyday clinical practice. • The scripts developed in the current study will allow users to train models for the acquisition protocols of their CT scanners, generate dose maps, estimate the doses to the brain and cranial bones, and estimate the lifetime attributable risk of radiation-induced brain cancer.


Microneedling combined with botulinum toxin-A versus microneedling combined with platelet-rich plasma in treatment of atrophic acne scars: a comparative split face study.
Atrophic post-acne scarring constitutes a troublesome cosmetic concern for both patients and dermatologists. Old and new therapies as well as combinations are being introduced to achieve a satisfactory response. Microneedling has been used either alone or under different combinations for its treatment. The aim was to compare its combination with topical platelet-rich plasma versus its combination with topical Botulinum Toxin-A. 30 subjects with different types and grades of atrophic post-acne scars completed the study. Right side of the face was treated with microneedling and platelet-rich plasma while the left side was treated microneedling and Botox. Response was assessed using two different scales. Patient satisfaction and pain were also assessed. Regarding response to therapy and according to the quartile grading scale, there was no statistically significant difference between the two sides where (23.4% & 13.3%) of the right and left sides, respectively, had an excellent response. Regarding the difference in the qualitative global scarring grading system before and after treatment, there was a highly statistically significant improvement on both sides with higher improvement on the right side than left side but in a non-statistically significant way. Both combinations present efficacious options for treating acne scars with comparable efficacy. Registered and approved prospectively by the ethical review board of the faculty of medicine, Zagazig University.


Relationship of islet cell and islet cell surface antibodies to the presentation and early course of IDDM in childhood.
Islet cell (ICA) and islet cell surface (ICSA) antibodies were measured in 30 children (aged 6-17.7 years) with newly diagnosed insulin-dependent diabetes mellitus (IDDM) to determine the relationship of antibody positivity/negativity to a variety of factors both at presentation (e.g., age, severity of onset, residual insulin secretion, insulin autoantibodies) and during the first year thereafter (HbA1c, insulin antibody binding, residual insulin secretion). At diagnosis, 10 of 30 were ICA (+) and 13 ICSA (+): no differences were found between ICA (+) and (-) subjects at onset; however ICSA (+) children had a lower bicarbonate concentration than those (-) for ICSA (P less than 0.01). During the first year after diagnosis the only significant finding was that in ICA (+) patients insulin dose (units/kg) was lower at both 6 and 12 months (mean +/- SD 0.55 +/- 0.14 and 0.67 +/- 0.12 U/kg, respectively) than ICA (-)'s (0.70 +/- 0.22 and 0.96 +/- 0.38, respectively, both P less than 0.05). Those children positive for both ICA and ICSA did not differ in any way at onset or during the subsequent 12 months from those negative for both antibodies. These results suggest that, except for minor differences, the presentation and course during the first year after diagnosis of IDDM do not differ in those children positive or negative for either or both ICA and ICSA.


The effect of dialyzer reuse on peak expiratory flow rate.
Peak expiratory flow rates were measured during routine haemodialysis in 18 patients with chronic renal failure who were in receipt of thrice weekly haemodialysis treatment, using both a new cuprophan dialyzer and then the same dialyzer after reprocessing. Acetate buffered dialysate was used on both occasions. The peak expiratory flow rates fell by 10 +/- 0.3%, mean +/- sem, during the first hour of treatment with the new dialyzer, and in seven patients (39%) the fall was greater than 15%. Whereas the reduction in peak expiratory flow rates was significantly less with reuse, 4 +/- 0.1% (P less than 0.5). Similarly, the fall in arterial oxygen tension was also reduced on reuse from 28 +/- 1.2% to 14 +/- 1.3% at 30 min (P less than 0.05) and from 30 +/- 1.4% to 18 +/- 3.1% (P less than 0.05) at 60 min of dialysis. There was also a reduction in the fall in the peripheral platelet count at 30 min of dialysis from 14 +/- 0.8% to 9 +/- 0.4% with reuse (P less than 0.05). However, there was no change in dialysis associated leukopenia with reuse of the dialyzer membrane. These results suggest that reprocessing the dialyzer membrane alters its biocompatibility characteristics resulting in an improvement in biocompatibility and further supports the role of inflammatory cell mediator release in the pathogenesis of dialysis associated hypoxaemia and pulmonary dysfunction during the first hour of dialysis treatment.


Degradation of olive mill wastewater by the induced extracellular ligninolytic enzymes of two wood-rot fungi.
Olive mill wastewater (OMWW) is a major problem in olive oil - producing countries, due to its high organic load and concentration in phenols that are toxic for marine life, plants and soil microorganisms. In the present study, two mushroom species were tested in regard to their OMWW's oxidative capacity, Pleurotus citrinopileatus LGAM 28684 and Irpex lacteus LGAM 238. OMWW (25% v/v) degradation was investigated for several culture conditions, namely pH, agitation speed, nitrogen-based supplements and their concentration. The selected values were pH 6, agitation rate 150 rpm, 30 g L-1 corn steep liquor as nitrogen source for P. citrinopileatus and 20 g L-1 diammonium tartrate for I. lacteus. The two strains performed well in cultures supplemented with OMWW, generating very high titers of oxidative enzymes and achieving more than 90% color and phenols reduction within a 24 days cultivation period. In addition, the amount of glucans present in the fungal biomass was assessed. Hence, P. citrinopileatus and I. lacteus appear as potent degraders of OMWW with the ability to use the effluent as a substrate for the production of biotechnologically important enzymes and valuable fungal glucans.


An examination of professional and ethical issues in the fellowship application process in pathology.
Approximately 34 medical specialty and subspecialty fellowship programs in the United States have formalized the application process through the National Resident Matching Program. This approach sets standards for the application process, offers a formalized match similar to that for residency programs, functions within a specific timeline, and establishes binding rules of behavior for both applicants and programs. For fellowship programs that operate outside the National Resident Matching Program, such as those in pathology, no published guidelines exist to help programs and applicants address the many questions and problems that can arise. As a result, programs are free to set their own timelines for interviews, application requirements, contract negotiations and finalizations, and other details. Consequently, applicants often feel pressured to apply earlier and earlier in their residency for competitive fellowship programs, are often required to fill out multiple unique applications, may feel no "loyalty" toward honoring an acceptance without a contract, and often feel disenfranchised by the whole process. This article addresses professional and ethical aspects of the current application process and offers possible solutions for improving it.


Antibody-drug Conjugate PCMC1D3-Duocarmycin SA as a Novel Therapeutic Entity for Targeted Treatment of Cancers Aberrantly Expressing MET Receptor Tyrosine Kinase.
Aberrant expression of the MET receptor tyrosine kinase is an oncogenic determinant and a drug target for cancer therapy. Currently, antibody-based biotherapeutics targeting MET are under clinical trials. Here, we report the preclinical and therapeutic evaluation of a novel anti-MET antibody- drug conjugate PCMC1D3-duocarmycin SA (PCMC1D3-DCM) for targeted cancer therapy. The monoclonal antibody PCMC1D3 (IgG1a/κ), generated by a hybridoma technique and specific to one of the MET extracellular domains, was selected based on its high specificity to human MET with a binding affinity of 1.60 nM. PCMC1D3 was conjugated to DCM via a cleavable valine-citrulline dipeptide linker to form an antibody-drug conjugate with a drug-to-antibody ratio of 3.6:1. PCMC1D3-DCM in vitro rapidly induced MET internalization with an internalization efficacy ranging from 6.5 to 17.2h dependent on individual cell lines. Studies using different types of cancer cell lines showed that PCMC1D3-DCM disrupted the cell cycle, reduced cell viability, and caused massive cell death within 96h after treatment initiation. The calculated IC50 values for cell viability reduction were 1.5 to 15.3 nM. Results from mouse xenograft tumor models demonstrated that PCMC1D3-DCM in a single dose injection at 10 mg/kg body weight effectively delayed xenograft tumor growth up to two weeks without signs of tumor regrowth. The calculated tumoristatic concentration, a minimal dose required to balance tumor growth and inhibition, was around 2 mg/kg body weight. Taken together, PCMC1D3-DCM was effective in targeting the inhibition of tumor growth in xenograft models. This work provides the basis for the development of humanized PCMC1D3-DCM for MET-targeted cancer therapy in the future.


Phase II trial of VEGFR2 inhibitor apatinib for metastatic sarcoma: focus on efficacy and safety.
Apatinib (YN968D1) is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a single-arm, nonrandomized phase II study (NCT03121846) to assess the efficacy and safety of apatinib in patients with stage IV sarcoma. We recruited 64 patients with stage IV sarcoma who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were evaluated. Fifty-nine patients were assessed for efficacy and 64 patients for AEs. The median PFS was 7.93 months. At 12 weeks, the PFR was 74%, the ORR was 16.95% (10/59), and the DCR was 86.44% (51/59). The final ORR was 15.25% (9/59) and the DCR was 57.63% (34/59). Notably, 22 patients (34.38%) who developed hypertension, hand-foot-skin reaction, or proteinuria had significantly longer OS than those without these AEs (18.20 vs. 10.73 months; P = 0.002). We conclude that apatinib is effective and well tolerated in patients with advanced sarcoma. The development of hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in sarcoma patients.


Comparing non-safety with safety device sharps injury incidence data from two different occupational surveillance systems.
The United States Occupational Safety and Health Administration (OSHA) Bloodborne Pathogens Standard as amended by the Needlestick Safety and Prevention Act requiring the use of safety-engineered medical devices to prevent needlesticks and sharps injuries has been in place since 2001. Injury changes over time include differences between those from non-safety compared with safety-engineered medical devices. This research compares two US occupational incident surveillance systems to determine whether these data can be generalized to other facilities and other countries either with legislation in place or considering developing national policies for the prevention of sharps injuries among healthcare personnel.


Human microbial metabolite mimicry as a strategy to expand the chemical space of potential drugs.
The concept of small-molecule mimicry even of weak microbial metabolites present in rodents and humans, as a means to expand drug repertoires, is new. Hitherto, there are few proof-of-concept papers demonstrating utility of this concept. More recently, papers demonstrating mimicry of intestinal microbial metabolites could expand the drug repertoire for diseases such as inflammatory bowel disease (IBD). We opine that, as more functional metabolite-receptor pairings are discovered, small-molecule metabolite mimicry could be a significant effort in drug discovery.


A randomized double-blind, placebo-controlled study of omalizumab for idiopathic anaphylaxis.
Idiopathic anaphylaxis (IA) is a diagnosis of exclusion, thus taking away the option of therapeutic management focused on eliminating the inciting agent. Epinephrine and antihistamines followed by systemic corticosteroids are the mainstays of therapy for acute events. There is no prophylactic therapy that reliably prevents anaphylaxis. We sought to determine the efficacy of omalizumab in the management of patients with frequent episodes of IA in a double-blind, placebo-controlled trial. We prospectively enrolled 19 patients with frequent IA (≥6 episodes/y) who then underwent a medical evaluation that included a serum tryptase determination, mutational analysis for KIT D816V, and bone marrow evaluation to rule out a clonal mast cell disorder. Computer-generated random numbers were provided by the study pharmacist. The primary end point was anaphylactic events in the 6 months after baseline. Sixteen patients completed the primary trial. No statistically significant difference was demonstrated between the placebo and treated groups. There was a trend for efficacy in the treatment group, particularly after 60 days. Overall, the safety profile was favorable without long-term side effects. Omalizumab was safely administered to a difficult-to-treat patient population with IA. The efficacy results trended modestly in favor of the treatment group, but no statistically significant differences were detected.


Sister chromatid exchange assay as a predictor of tumor chemoresponse.
Sister Chromatid Exchanges (SCEs) are known to enhance as a consequence of exposure to various mutagenic agents and appear to indicate DNA damaging effects and/or subsequent repair by homologous recombination (HR). DNA damage plays an interesting role in the majority of mechanisms underlying the effects of antitumor drugs, since the genetic activity of the plethora of these agents is due to their ability to damage the DNA. The DNA-effects of antitumor agents towards normal cells (genotoxicity) are great drawbacks of antitumor therapy and are connected to important adverse health effects in cancer patients undergoing chemotherapy. On the other hand, failure of chemotherapy in many cases is due to the DNA repair ability which cancer, like normal cells, also possess. As both DNA repair and genotoxic exposure are expected to vary among patients, correlating SCEs frequencies with only individual repair capacity may be feasible to predict. Cancer risk has not been observed to be associated with high SCEs levels. Since the administration of effective antitumor drugs with limited adverse effects is of great importance in the success of anticancer therapy, a lot of interest has been directed toward the development of methods and approaches that would enable the correct selection of appropriate drugs prior to the initiation of therapy on an individual basis. To this effect, more than 30 years ago, an investigation of the ability of the in vitro and the in vivo SCEs-assay to predict the in vitro and in vivo sensitivity of tumor cells to newly synthesized drugs or to those already in use began. In this short review a critical appraisal of the SCEs-assay as an important biomarker used for predicting cancer chemo-response as well as a summary of the key findings from several studies published within the last 20 years in this field is performed.


Thoracic and lumbar spinal impact tolerance.
Thoracolumbar injuries resulting from motor vehicle accidents, falls, and assaults have a high risk of morbidity and mortality. However, there are no biomechanically based standards that address this problem. This study used four cadaveric porcine specimens as a model for direct spinal impact injuries to humans to determine an appropriate injury tolerance value. The anthropometric parameters of these specimens are compared with values found in a large human cadaveric dataset. Each specimen was subjected to five impacts on the dorsal surface of the lower thorax and abdomen. The injuries ranged from mild spinous process fractures to endplate fractures with anterior longitudinal ligament (ALL) transactions with a maximum AIS=3. The average peak reaction force for the thoracic failure tests was 4720+/-1340 N, and the average peak reaction force for the lumbar failure tests was 4650+/-1590 N. When scaled to human values using anthropometric parameters determined in this study, the force at which there is a 50% risk of injury is 10,200+/-3900 N. This value favorably compares to that found in the existing literature on isolated vertebral segments. After demonstrating that the porcine model can be used as a spinal impact model for the human, the resulting injury risk value can be used in determining new standards for human injury risk or in guiding the design of safety equipment for the back.


FDA approval summary: Crizotinib for pediatric and young adult patients with relapsed or refractory systemic anaplastic large cell lymphoma.
In January 2021, the U.S. Food and Drug Administration (FDA) approved crizotinib for pediatric patients 1 year and older and young adults with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). This is the first approval for pediatric sALCL. Approval was based on a single-arm trial of crizotinib monotherapy that included 26 patients, aged 1-20 years, with previously treated sALCL. Efficacy was based on centrally assessed objective response rate (88%) and duration of response. Herein, we highlight unique aspects of the regulatory review, including extension of the indication to young adults, postmarketing safety, and dose optimization strategies.


Effects of human growth hormone on fuel utilization and mineral balance in critically ill patients on full intravenous nutritional support.
The effects of recombinant human growth hormone (GH) on fuel utilization, mineral and fluid balance in critically ill patients were studied. Twenty patients requiring mechanical ventilation and receiving standard parenteral nutrition were studied. GH 0.1 mg/kg/day (n = 10) or placebo (n = 10) was administered as continuous intravenous infusion for 3 days. Plasma mineral levels, urinary nitrogen, and mineral excretion were measured. Indirect calorimetry was used to calculate energy production rate and fuel utilization. Insulin-like growth factor I concentrations increased: day 4 GH, 18.9 +/- 7.0 ng/mL; controls 11.6 +/- 3.2 ng/mL (P < .05). During GH administration, the nitrogen balance became zero, whereas it remained negative in controls (P = .03). Fuel utilization did not differ between the groups. Neither did oxygen consumption, carbon dioxide production, or the respiratory quotient (RQ). Nonprotein RQ showed a tendency to decrease in the GH group, whereas an increase was present in controls. Mineral balance improved in both groups. Phosphate balance improved by 250% in the GH group (P = .054). GH administration in critically ill patients reduces nitrogen loss and improves phosphate retention but does not have an important effect on fuel utilization.


Facilitation of memory consolidation by vasopressin: mediation by terminals of the dorsal noradrenergic bundle?
Administration of arginine-vasopressin (AVP, 5 micrograms, s.c.) immediately after the learning trial results in a long-term facilitation of a one-trial learning passive avoidance response. This effect of AVP is absent in animals with prior destruction of the ascending dorsal noradrenergic bundle by bilateral microinjection of 6-hydroxydopamine (6-OHDA). Postlearning local microinjection of a minute amount of AVP via chronically implanted cannulae into the locus coeruleus did not influence passive avoidance behavior. Upon injection into the midbrain dorsal raphe nucleus, however AVP facilitated passive avoidance behavior. This effect, however, was absent in rats receiving previous microinjection of 5,6-dihydroxytryptamine (5,6-DHT) or of 6-OHDA into the dorsal raphe nucleus. Bilateral 6-OHDA-induced lesions of the nucleus accumbens or 5,6-DHT-induced destruction of the dorsal raphe nucleus did not prevent the effect of AVP administered subcutaneously. The data suggest that vasopressin facilitates memory consolidation processes by modulating noradrenergic neurotransmission in terminals of the dorsal noradrenergic bundle. The serotoninergic neuronal network originating from the dorsal raphe nucleus has a secondary--norepinephrine-mediated--influence upon these processes.


Development of a novel anoxic/oxic fed-batch membrane bioreactor (AFMBR) based on gravity-driven and partial aeration modes: A pilot scale study.
A novel pilot gravity-driven anoxic/oxic fed-batch membrane bioreactor (AFMBR) was developed to treat real domestic wastewater. In this process, the anoxic and oxic stages created favorable conditions for stable and continuous nitritation-denitritation/denitrification-nitrification links without adding external carbon source. Excellent removals of organic carbon/nitrogen (NH4+-N: 71-97%, COD: 78-96%, UV254: 70-95%, TN: 20-60%) and spontaneous permeability recovery were achieved simultaneously. It was assessed at micro levels by characterizing sludge particle morphologies, microbiota functional evolutions, fouling layer properties and energy consumptions. It was demonstrated that the aerobic granular sludge (AGS) was cultivated successfully. Notable differences of microbial diversity were observed in different regions of AFMBR. The SEM and AFM spectra suggested the loose cake layers can shed automatically due to low pressure and continue flushing. The energy consumption in AFMBR was around 0.042 kWh/m3, far lower than that of conventional MBR. Overall, the AFMBR has a potential on improvement of domestic wastewater treatment.


Computational model of interstitial transport in the spinal cord using diffusion tensor imaging.
Local drug delivery methods, including convection-enhanced delivery (CED), are being used to increase distribution in selected regions of nervous tissue. There is a need for 3D models that predict spatial drug distribution within these tissues. A methodology was developed to process magnetic resonance microscopy (MRM) and diffusion tensor imaging (DTI) scans, segment gray and white matter regions, assign tissue transport properties, and model the interstitial transport of macromolecules. Fiber tract orientation was derived from DTI data and used to assign directional dependence of hydraulic conductivity, K, and tracer diffusivity, Dt, transport tensors. Porous media solutions for interstitial fluid pressure, velocity, and albumin distribution were solved using a finite volume method. To test this DTI-based methodology, a rat spinal cord transport model was developed to simulate CED into the dorsal white matter column. Predicted distribution results correspond well with small volume (approximately 1 microl) trends found experimentally, although albumin loss was greater at larger infusion volumes (>2 microl). Simulations were similar to those using fixed transport properties due to the bulk alignment of white matter fibers along the cord axis. These findings help to validate the DTI-based methodology which can be applied to modeling regions where fiber tract organization is more complex, e.g., the brain.


Modulation of sympathetic transmission by neuronally-released dopamine.
1 When rabbits were pretreated with Fla-63, there was a marked inhibition of dopamine-beta-hydroxylase such that, after incubation of the ear arteries with [3H]-dopamine 47.2% of the tritium in the tissue was retained as unchanged dopamine. 2 [3H]-dopamine was released by stimulation of the sympathetic nerves in ear arteries taken from rabbits pretreated with Fla-63 and incubated with [3H]-dopamine. 3 The dopamine antagonists metoclopramide (1.0 microM) and ergometrine (1.0 microM) enhanced the stimulation-induced efflux of tritium in ear arteries taken from rabbits pretreated with Fla-63 and incubated with [3H]-dopamine, but not when the arteries were incubated with [3H]-noradrenaline. 4. These results suggest that if dopamine is present in the transmitter stores, it can be released by stimulation of the sympathetic nerves, and if the amount is adequate, it can activate an inhibitory feedback loop where prejunctional dopamine receptors are present.