Donor facial composite allograft recovery operation: Cleveland and Boston experiences.
Complexity of logistic issues related to facial transplantation includes donor tissue recovery, recipient preparation, and operative execution. Limited information is available on the intricate process associated with facial allograft procurement in the United States. The face transplant teams at the Cleveland Clinic and Brigham and Women's Hospital have combined their experiences regarding collaboration with organ procurement organizations and institutional review boards, and outlined technical and logistic challenges encountered during the process of facial allograft procurement and compared them with those of solid organ procurement. In a collaborative effort, both programs have created comprehensive guidelines for all aspects involved in donor facial allograft procurement. The authors suggest that every face transplant team should develop a thorough understanding of the local and regional legislative issues related to organ and tissue donation and ethical concerns surrounding this procedure. The recovery plan has to be communicated extensively among all members of the team. The Cleveland and Boston teams hope their experiences may help other teams in the process of building new face transplant programs. Therapeutic, V.


Back to the Future: Reflecting on Three Decades of Healthy North Carolina Infant Mortality Goals.
Decreasing infant mortality has been a key objective of Healthy North Carolina task forces since the inaugural 1990 objectives, but the state has frequently failed to reach its infant mortality goal. Minimal infant mortality reductions continue, as does an unacceptable Black-White disparity ratio. More focused efforts are required.


Ototoxicity of topical moxifloxacin in a chinchilla animal model.
Ciprofloxacin is currently the only proven nonototoxic topical antibiotic. However, its widespread use has resulted in the emergence of antimicrobial resistance. There are also concerns that there is currently no safe alternative to ciprofloxacin for patients with a nonintact eardrum. We thus wished to evaluate whether a moxifloxacin solution is ototoxic when used topically in chinchilla ears in the presence of a pressure-equalizing tube (PET). A prospective, randomized, controlled trial was conducted in an animal model. Twenty chinchillas were included in this study. After bilateral insertion of PETs, four drops of a moxifloxacin solution were delivered twice daily for 7 days in the randomly assigned experimental ear. The control ear received an equal amount of a solution of Ringer's lactate. Distortion product otoacoustic emissions (DPOAE) were recorded at baseline (after PET insertion) and at days 1, 3, 7, 14, and 28 after treatment initiation. When baseline DPOAE measurements were compared with the final measurements at day 28, moxifloxacin caused a statistically significant (P < .05) hearing loss (HL) in the experimental ears for the frequencies between 3.7 and 15 kHz. There was no significant change in hearing in the control ears. This represents the first study on the ototoxicity of topical moxifloxacin. Our results demonstrate that moxifloxacin causes HL when used with a nonintact tympanic membrane in a chinchilla animal model.


Examining the Interrelation Among Change Processes: Decentering and Anticipatory Processing Across Cognitive Behavioral Therapy for Social Anxiety Disorder.
As evidence grows supporting certain mechanisms of change in psychological treatments and we improve statistical approaches to measuring them, it is important that we also explore how mechanisms and processes are related to each other, and how they together affect treatment outcomes. To answer these questions about interrelating processes and mechanisms, we need to take advantage of frequent assessment and modeling techniques that allow for an examination of the influence of one mechanism on another over time. Within cognitive behavioral therapy, studies have shown support for both decentering, the ability to observe thoughts and feelings as objective events in the mind, and anticipatory processing, the repetitive thinking about upcoming social situations, as potentially related mechanisms of change. Therefore, the current study examined weekly ratings of decentering and a single-item anticipatory processing question to examine the interrelation among these change mechanisms in 59 individuals who received a 12-weeks of Cognitive Behavioral Group Therapy for social anxiety disorder. Overall, these results found that both anticipatory processing and decentering changed over the course therapy for clients. Change in both anticipatory processing and decentering was related to outcome. The bivariate latent difference score analysis showed that anticipatory processing was a leading indicator of change in decentering, but not the reverse, indicating that change in anticipatory processing is leading to change in decentering. It may be that with the focus on cognitive reappraisal in this treatment, that reducing anticipatory processing is freeing up the cognitive resources for decentering to occur.


Accessory flexor carpi ulnaris: case report and review of the literature.
Most of the accessory muscles of the forearm described in the radiology literature are located either in the radial aspect of the forearm or towards the hypothenar eminence. We present an unusual case of an ulnar-sided distal forearm accessory flexor carpi ulnaris muscle presenting as a "pseudotumour" demonstrated with both ultrasound and MRI, rarely reported in the current surgical and anatomical literature. Given the location and relation to the ulnar nerve towards Guyon's canal, the accessory muscle may also predispose to distal ulnar nerve entrapment.


Catheter ablation of ventricular tachycardia after repair of congenital heart disease: electroanatomic identification of the critical right ventricular isthmus.
Catheter ablation of ventricular tachycardia (VT) after repair of congenital heart disease can be difficult because of nonmappable VTs and complex anatomy. Insights into the relation between anatomic isthmuses identified by delineating unexcitable tissue using substrate mapping techniques and critical reentry circuit isthmuses might facilitate ablation. Sinus rhythm voltage mapping of the right ventricle was performed in 11 patients with sustained VT after repair of congenital heart disease. Unexcitable tissue from patch material, valve annulus, or dense fibrosis, identified from bipolar voltage (<0.5 mV) and pacing threshold (>10 mA), was defined as an anatomic isthmus boundary bordering 4 isthmuses between (1) the tricuspid annulus and scar/patch in the anterior right ventricular outflow, (2) the pulmonary annulus and right ventricular free wall scar/patch, (3) the pulmonary annulus and septal scar/patch, and (4) the septal scar/patch and tricuspid annulus. The reentry circuit isthmuses of all induced 15 VTs (mean cycle length, 276+/-78 ms; 73% poorly tolerated), identified by activation, entrainment, and/or pace mapping, were located in an anatomic isthmus (11 of 15 VTs in anatomic isthmus 1). Transecting the anatomic isthmuses by ablation lesions abolished all VTs. During 30.4+/-29.3 months of follow-up, 91% of patients remained free of VT. Reentry circuit isthmuses in VT late after repair of congenital heart disease are located within anatomically defined isthmuses bordered by unexcitable tissue. The boundaries can be identified with 3-dimensional substrate mapping and connected by ablation lines during sinus rhythm. These findings should facilitate catheter and surgical ablation of stable and unstable VTs.


False positive immunometric assays caused by anti-immunoglobulin antibodies: a case report.
A serological phenomenon causing aberrant results with monoclonal immunoenzymetric assays (IEMA's) is reported. Two different commercial IEMA kits detected low levels of choriogonadotropin (hCG) in the serum of a non-pregnant woman. These assays detected between 32 and 55 IU/l of serum hCG over a 3-wk period; however, an RIA for beta-subunit and two monoclonal immunoradiometric assays (IRMA's) detected no hCG (less than 5 IU/l). An IEMA measurement of creatine kinase MB isozyme was also elevated. Antisera to either human immunoglobulin or specifically to human IgM, added to the serum prior to assay, substantially decreased these IEMA reactions. Addition of either mouse serum or purified mouse IgG totally abolished them. It is concluded that these spurious reactions were most likely caused by an IgM antibody which binds to native and enzyme-labelled mouse IgG, but not to iodinated IgG.


Outdoor and early hour human biting activities of malaria mosquitoes and the suitability of clay pot for outdoor resting mosquito collection in malaria endemic villages of southern Rift Valley, Ethiopia.
Sampling adult Anopheles mosquitoes is important for assessing vector density, estimating the sporozoite infection rate, and quantifying the impact of vector control interventions. The objective of this study was to assess the Anopheles mosquito species composition, and their outdoor and indoor biting activities, and to evaluate the suitability of clay pots for indoor and outdoor resting mosquito collections. Two malaria-endemic villages in the Gamo zone were purposely selected. Forty clay pots were deployed for outdoor resting mosquitoes sampling and another forty for indoor resting sampling. Twenty pit shelters were constructed for outdoor resting mosquito collection. The human landing catch (HLC) technique was employed to collect indoor and outdoor host-seeking mosquitoes in two households in each village. Morphological identification of the Anopheles mosquito was done using an identification key. Enzyme-linked immunosorbent assay technique was used for blood meal origin and circumsporozoite proteins (CSP) test. Speciation of An. gambiae complex was done using polymerase chain reaction. A Chi-square test was used to compare the effectiveness of clay pot and pit shelters for outdoor resting sampling. A total of 904 female Anopheles mosquitoes comprising An. gambiae complex, An. pharoensis, An. tenebrosus, An. dencalicus and An. demelloni were sampled. The majority (64%) of them were sampled by the HLC technique. There was a slight difference between the outdoor clay pot (19%) and pit shelter (17%) collection. No Anopheles mosquitoes were collected indoor using clay pots. All mosquitoes were tested for CSPs, but none of them were found to be positive. Anopheles mosquitoes were tending to bite humans outdoor than indoors, and their peak biting hours was 10-11 pm. The human blood meal index of Anopheles mosquitoes was 0.07 from pit shelters and it was 0.04 from clay pots. The bovine blood meal index was 0.45 for mosquitoes from both pit shelters and clay pot collections. Anopheles arabiensis was the predominant species and it was tending to bite cattle more than humans. Clay pot could be suitable for outdoor resting mosquito collection, but not for indoor resting species.


A SEARCH FOR UNHAPPY ABDOMEN: PREVALENCE OF IRRITABLE BOWEL SYNDROME IN GENERAL POPULATION.
The irritable bowel syndrome is the commonest gastrointestinal disorder seen in practice but its exact prevalence in India is not known. This study was carried out to determine the prevalence of symptoms compatible with this diagnosis in general population. A cross sectional random sample survey was conducted in various strata of urban population in Wanoworie area of Pune. Survey utilized personal interviews based on a questionnaire. Symptoms were evaluated as per Manning criteria and the diagnosis of irritable bowel syndrome was defined by Kruis diagnostic index. Of the 1010 subjects interviewed, 370 (37%) reported more than 6 episodes of abdominal pain in previous 6 months, with 333 reporting symptoms consistent with the the diagnosis of irritable bowel syndrome. At least one of the Manning's symptoms was present in 307 out of 370 subjects (83%). The male female ratio was 5.3:1. Among males, 288 (35%) and among females 82 (53.2%) persons had at least some degree of abdominal discomfort. Other common symptoms were: excessive passage of wind (42.2%), irregular bowel habits (33%), excessive belching (30.8%), constipation (27.5) and feeling of incomplete evacuation(28.1%). About one third of the symptomatic subjects (134 or 36.2%) had seen a doctor or wanted to be seen by a specialist. Overall prevalence of the symptoms consistent with irritable bowel syndrome thus, is 33 per cent though only about a third of these may possibly consult a doctor. Follow up of all these patients for a mean duration of 8.3 months showed that no case of organic disease was picked up either by the scoring system or by the gastroenterologist. Symptoms consistent with the diagnosis of irritable bowel syndrome are see in almost one third of the study population residing in Wanoworie area of Pune.


Honokiol suppresses the development of post-ischemic glucose intolerance and neuronal damage in mice.
Honokiol, a constituent of Magnolia obovata, has various pharmacological effects, including protection against cerebral ischemia. However, few studies have been conducted to evaluate the possible neuroprotective effects of honokiol against cerebral ischemia. We recently reported that cerebral ischemic neuronal damage could be triggered by glucose intolerance that develops after the onset of ischemic stress (i.e., post-ischemic glucose intolerance). In addition, suppression of post-ischemic glucose intolerance significantly ameliorated ischemic neuronal damage. Here, we investigated the effects of honokiol on the development of post-ischemic glucose intolerance and neuronal damage. Mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. The development of post-ischemic glucose intolerance on day 1 and neuronal damage on day 3 after MCAO were significantly reduced by intraperitoneal administration of honokiol (10 mg/kg) compared with the vehicle-treated group. Honokiol did not affect serum insulin or adiponectin levels. However, honokiol significantly decreased the expression of phosphoenolpyruvate carboxykinase and increased the expression of 5'-AMP-activated protein kinase (AMPK) on day 1 after MCAO, compared with the vehicle-treated MCAO group. The results of this study suggest that honokiol could prevent post-ischemic glucose intolerance in an AMPK-dependent manner, which may be involved in the neuroprotective effects of honokiol against cerebral ischemia.


Addition of intramuscular to vaginal progesterone for luteal phase support in fresh embryo transfer cycles: A cross-sectional study.
Luteal phase deficiency is common in assisted reproductive technology and is characterized by inadequate progesterone production. Various studies have shown that administration of progesterone in fresh embryo transfer cycles increases the rate of clinical pregnancy and live birth rate. Progesterone administration has variable types: oral, vaginal, oil-based intramuscular, and subcutaneous. This study aims to compare the effect of adding intramuscular progesterone to the vaginal progesterone for luteal phase support in the fresh embryo transfer cycle. This study reviewed the information related to 355 women who had a fresh embryo transfer between March 2020 and February 2021 at the Yazd Reproductive Sciences Institute, Yazd, Iran. The participants population were divided into 2 groups based on the type of luteal phase support regime: group I (n = 173) received 400 mg vaginal progesterone alone twice a day from the day of ovum pick up; and group II (n = 182) received 50 mg IM of progesterone in addition to vaginal progesterone 400 mg twice a day from the day of ovum pick up. Chemical and clinical pregnancy rates were compared between groups. The basic characteristics of groups were statistically similar. The rates of chemical and clinical pregnancy were higher in the vaginal plus IM progesterone group than in the vaginal progesterone group. Moreover, chemical pregnancy showed a significant difference between the groups (p = 0.011). Our findings demonstrated that the addition of IM progesterone to the vaginal progesterone improves the chemical pregnancy rate in fresh embryo transfer.


PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.
Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. The mechanism for tight control of the robust catalytic potential of PARP-1 remains unclear. By monitoring PARP-1 dynamics using hydrogen/deuterium exchange-mass spectrometry (HXMS), we unexpectedly find that a specific portion of the helical subdomain (HD) of the catalytic domain rapidly unfolds when PARP-1 encounters a DNA break. Together with biochemical and crystallographic analysis of HD deletion mutants, we show that the HD is an autoinhibitory domain that blocks productive NAD(+) binding. Our molecular model explains how PARP-1 DNA damage detection leads to local unfolding of the HD that relieves autoinhibition, and has important implications for the design of PARP inhibitors.


The potential of case management for people with dementia: a commentary.
A recent review of studies of case management in dementia argues that lack of evidence of cost-effectiveness should discourage the use of this approach to care. We argue that that this is too conservative a stance, given the urgent need throughout the world to improve the quality of care for people with dementia and their caregivers. We propose a research agenda on case management for people with dementia. A critical comparison was made of the studies identified in two systematic reviews of trials of case management for dementia, with selective inclusion of non-trial studies and economic evaluations. Our interpretation of the literature leads us to four provisional conclusions. First, studies with long follow-up periods tend to show delayed relocation of people with dementia to care homes. Second, the quality of life of people with dementia and their caregivers may also influence the likelihood of relocation. Third, different understandings of what constitutes case management make interpretation of studies difficult. Fourth, we agree that the population most likely to benefit from case management needs to be characterised. Earlier intervention may be more beneficial than intervening when the condition has progressed and the individual's situation is highly complex. However, this runs counter to some definitions of case management as an administrative, professional, and systemic focus on people with high needs and where expensive support is accessed or in prospect. More work needs to be carried out in a more focused way in order to establish the value of case management for people with dementia. Since care home residence is such a sizeable contributor to the costs of dementia care, studies need to be long enough to capture possible postponed relocation. However, case management studies with shorter follow-up periods can still contribute to our understanding, since they can demonstrate improved quality of life. Future research should be built around a common, agreed definition of types of case management.


On the advantage of Folsomia fimetarioides over Isotomiella minor (Collembola) in a metal polluted soil.
Food preference, metal avoidance behaviour and desiccation tolerance were investigated for two collembolan species, Folsomia fimetarioides and Isotomiella minor, in order to test some hypotheses for their different distributions in relation to a heavy metal gradient. F. fimetarioides showed a higher preference for metal tolerant fungi than I. minor when they were offered fungi of different metal tolerance. When they could choose between polluted and unpolluted fungi and substrate, F. fimetarioides significantly avoided the polluted source while I. minor did not. Both species were negatively affected by drought. I. minor was more tolerant than F. fimetarioides when exposed to drought in combination with metal pollution. High supply of preferred fungal species and a better ability to avoid heavy metals favour F. fimetarioides and determine its dominance over I. minor in polluted soils.


[Simulation of the Baird-Parker media formula based on Soviet ingredients for the isolation of Staphylococcus aureus].
A medium has been prepared based on Soviet nutrient agar and reagents supplemented by ingredients from Baird-Parker's medium. Its growth and selective properties are close to those of Baird-Parker's medium. The new selective medium has been recommended for isolation of S. aureus from food products and environment objects.


Plasma insulin-like growth factor-I determinations in patients with cystic fibrosis: Influence of the nutritional and liver status.
Insulin-like growth factor-1 (Igf1), a useful and early marker of undernutrition in inflammatory diseases, is dependent on the calorie and protein content of the diet. In 31 children and adolescents with cystic fibrosis (CF), a chronic inflammatory disease, the influence of the degree of liver dysfunction and the protein and calorie content of the diet on the circulating Igf1 was evaluated. No significant difference in the median plasma Igf1 concentration, measured by RIA, between the CF children (0.80 U/ml) and a for age and puberty matched control group (0.61 U/ml) was found. Expressing the Igf1 concentration as a percentage of normal for age, gave for the CF patients with liver involvement a lower level (median: 76%) than in those without (median: 101%). No correlation existed between the circulating Igf1 levels and the body height SDS, the body weight index and the calorie or protein intake of the patients.


Prenatal prediction of pulmonary hypoplasia.
Pulmonary hypoplasia, although rare, is associated with significant neonatal morbidity and mortality. Conditions associated with pulmonary hypoplasia include those which limit normal thoracic capacity or movement, including skeletal dysplasias and abdominal wall defects; those with mass effect, including congenital diaphragmatic hernia and pleural effusions; and those with decreased amniotic fluid, including preterm, premature rupture of membranes, and genitourinary anomalies. The ability to predict severe pulmonary hypoplasia prenatally aids in family counseling, as well as obstetric and neonatal management. The objective of this review is to outline the imaging techniques that are widely used prenatally to assess pulmonary hypoplasia and to discuss the limitations of these methods.


Dielectric properties of tissues; variation with age and their relevance in exposure of children to electromagnetic fields; state of knowledge.
This paper reviews and summarises the state of knowledge on dielectric properties of tissues; in particular those obtained as a function of age. It also examines the impact of variation in dielectric data on the outcome of recent dosimetric studies assessing the exposure of children to electromagnetic fields.


The effect of the neutrophil elastase inhibitor sivelestat on early injury after liver resection.
The effects of sivelestat on endotoxin-induced lung injury, postperfusion lung injury, and ischemia-reperfusion are known, yet the benefits of sivelestat during liver surgery have yet to be elucidated. The aim of the present study was to assess the effects of sivelestat, with a focus on postoperative chemical data, in hepatectomized patients. A prospective clinical study was conducted in 50 patients undergoing hepatic resection. Patients were randomly assigned to receive Elaspol, sivelestat (ELP group, n = 25) or placebo (control group, n = 25). Perioperative blood chemistry values in both groups, including high-mobility group box 1 (HMGB1) and interleukin (IL)-6, were monitored. The HMGB1 levels increased immediately after the operation (from the intraoperative period to the second postoperative day [POD]) in the control group. Compared to the control group, the levels of HMGB1 in the ELP group were significantly suppressed by the perioperative administration of sivelestat. At POD 1, the levels of IL-6 in the ELP group decreased more rapidly than those before the operation compared to the control group. A human clinical study demonstrated the effect of polymorphonuclear leukocyte elastase inhibitor on the earliest markers of liver injury. The present study showed that patients who received sivelestat had reduced release of HMGB1, and that IL-6 levels decreased more rapidly in patients treated with sivelestat than in those who received the placebo. The most appropriate dose, timing, and duration of sivelestat in humans remain unclear; however, it may have therapeutic potential for various liver injuries.


Targeting the NF-κB signaling pathway in chronic tendon disease.
Tendon disorders represent the most common musculoskeletal complaint for which patients seek medical attention; inflammation drives tendon degeneration before tearing and impairs healing after repair. Clinical evidence has implicated the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway as a correlate of pain-free return to function after surgical repair. However, it is currently unknown whether this response is a reaction to or a driver of pathology. Therefore, we aimed to understand the clinically relevant involvement of the NF-κB pathway in tendinopathy, to determine its potential causative roles in tendon degeneration, and to test its potential as a therapeutic candidate. Transcriptional profiling of early rotator cuff tendinopathy identified increases in NF-κB signaling, including increased expression of the regulatory serine kinase subunit IKKβ, which plays an essential role in inflammation. Using cre-mediated overexpression of IKKβ in tendon fibroblasts, we observed degeneration of mouse rotator cuff tendons and the adjacent humeral head. These changes were associated with increases in proinflammatory cytokines and innate immune cells within the joint. Conversely, genetic deletion of IKKβ in tendon fibroblasts partially protected mice from chronic overuse-induced tendinopathy. Furthermore, conditional knockout of IKKβ improved outcomes after surgical repair, whereas overexpression impaired tendon healing. Accordingly, targeting of the IKKβ/NF-κB pathway in tendon stromal cells may offer previously unidentified therapeutic approaches in the management of human tendon disorders.


Esmolol reduces anesthetic requirements thereby facilitating early extubation; a prospective controlled study in patients undergoing intracranial surgery.
Adequate cerebral perfusion pressure with quick and smooth emergence from anesthesia is a major concern of the neuroanesthesiologist. Anesthesia techniques that minimize anesthetic requirements and their effects may be beneficial. Esmolol, a short acting hyperselective β-adrenergic blocker is effective in blunting adrenergic response to several perioperative stimuli and so it might interfere in the effect of the anesthetic drugs on the brain. This study was designed to investigate the effect of esmolol on the consumption of propofol and sevoflurane in patients undergoing craniotomy. Forty-two patients that underwent craniotomy for aneurysm clipping or tumour dissection were randomly divided in two groups (four subgroups). Anesthesia was induced with propofol, fentanyl and a single dose of cis-atracurium, followed by continuous infusion of remifentanil and either propofol or sevoflurane. Patients in the esmolol group received 500 mcg/kg of esmolol bolus 10 min before induction of anesthesia, followed by additional 200 mcg/kg/min of esmolol. Monitoring of the depth of anesthesia was also performed using the Bispectral Index-BIS and cardiac output. The inspired concentration of sevoflurane and the infusion rate of propofol were adjusted in order to maintain a BIS value between 40-50. Intraoperative emergence was detected by the elevation of BIS value, HR or MAP. The initial and the intraoperative doses of propofol and sevoflurane were 18-50 mcg/kg/min and 0.2-0.5 MAC respectively in the esmolol group, whereas in the control group they where 100-150 mcg/kg/ and 0.9-2.0 MAC respectively (p = 0.000 for both groups). All procedures were anesthesiologically uneventful with no episodes of intraoperative emerge. Esmolol is effective not only in attenuating intraoperative hemodynamic changes related to sympathetic overdrive but also in minimizing significant propofol and sevoflurane requirements without compromising the hemodynamic status. ClinicalTrials.gov Identifier: NCT02455440 . Registered 26 May 2015.


A PC-based graphical simulator for physiological pharmacokinetic models.
Since many intravenous anesthetic drugs alter blood flows, physiologically-based pharmacokinetic models describing drug disposition may be time-varying. Using the commercially available programming software MATLAB, a platform to simulate time-varying physiological pharmacokinetic models was developed. The platform is based upon a library of pharmacokinetic blocks which mimic physiological structure. The blocks can be linked together flexibly to form models for different drugs. Because of MATLAB's additional numerical capabilities (e.g. non-linear optimization), the platform provides a complete graphical microcomputer-based tool for physiologic pharmacokinetic modeling.


Novel Phocaeicola Strain Ameliorates Dextran Sulfate Sodium-induced Colitis in Mice.
Previously, we isolated a novel Phocaeicola strain, Phocaeicola faecalis FXJYN30E22, from the feces of a healthy human from China. Metagenomic analysis revealed that the distribution of FXJYN30E22 differed in the intestinal tract of different hosts. We aimed to determine whether FXJYN30E22 protects against ulcerative colitis by employing a mouse model. In this study, dextran sulfate sodium was used to construct the UC model. The disease activity index, colon length, body weight changes, and histological scores were used as the pathological indicators to assess the anti-inflammatory effect of P. faecalis FXJYN30E22. Further, cytokine levels, tight junction mRNA expression levels, and short-chain fatty acid (SCFA) concentrations were also analyzed. Phocaeicola faecalis FXJYN30E22 could reduce the DSS-induced increase in DAI score, and enhance the colon length and body weight. Phocaeicola faecalis FXJYN30E22 could enhance TJ protein concentration and modulate the level of cytokines to reach levels close to those of the control group. FXJYN30E22 could also upregulate the concentrations of SCFA, which include acetate and butyrate. Based on the correlation analysis, four factors, including interleukin (IL)-6, IL-10, IL-1β levels, and propionate concentration, were related to the protective roles of FXJYN30E22 in UC mice to different degrees. According to an analysis of the genomic information, the potential protective effects of strain FXJYN30E22 may be associated with the secretion of SCFA by specific genes. These findings suggest that oral P. faecalis FXJYN30E22 could help maintain the epithelial barrier by regulating cytokine levels and secreting SCFA.


Inhibition of Hepatocellular Carcinoma Growth by Ethyl Acetate Extracts of Apulian Brassica oleracea L. and Crithmum maritimum L.
Nowadays, a growing body of evidence supports the view that plants offer an extraordinary opportunity to discover and develop new promising therapeutic strategies for many diseases, including cancer. Here we tested the anticancer action against Hepatocellular carcinoma (HCC) of extracts obtained from two plants harvested in Apulia, namely Brassica oleracea L. and Crithmum maritimum L. B. oleracea was grown in biodynamical agriculture without any agrochemical input, instead C. maritimum was collected on Apulian coasts and is still commonly eaten in Apulia. HCC, one of the most frequent tumors worldwide, is estimated to become the third leading cause of cancer-related deaths in Western Countries by 2030. The approved synthetic drugs for the treatment of HCC are currently inadequate in terms of therapeutic results and tolerability. Hence, aim of the present study was to test the anticancer action against HCC of extracts obtained from Brassica oleracea L. and Crithmum maritimum L. We preliminary prepared extracts from both plants using four solvents with different polarity: hexane, ethyl acetate, methanol and ethanol. Then, we tested the effect of the different fractions in inhibiting HCC cell growth. Finally, we characterized the mechanism of action of the most effective fraction. We found that ethyl acetate fractions from both plants were the most effective in inhibiting HCC growth. In particular, we demonstrated that these fractions effectively reduce HCC growth by exerting, on one hand, a cytostatic effect through their action on the cell cycle, and on the other hand by triggering apoptosis and necrosis. Our findings support the notion that ethyl acetate fractions from Apulian B. oleracea and C. maritimum can be in perspective considered as promising tools to expand the opportunities to identify new and not toxic anticancer therapeutic approaches for HCC. Further pharmacological investigations will shed light on how this could be effectively achieved. Graphical Abstract Experimental workflow for the detection of the ethyl acetate extract of Brassica oleracea L. and Crithmum maritimum L. as an active fraction in inhibiting HCC cell growth.


Quality of Life after Radioembolization for Hepatocellular Carcinoma Using a Digital Patient-Reported Outcome Tool.
Health-related quality of life (HRQoL) measurements are important for patient care, and emerging bundles in value-based care are placing an increasing emphasis on tying reimbursement to patient surveys. A multicenter pilot study was carried out to assess the efficacy of an automated digital patient engagement (DPE) platform for collecting HRQoL measurements at baseline and at 2- to 4-week intervals through 90 days after transarterial radioembolization (TARE) with yttrium-90 (90Y) treatments for hepatocellular carcinoma (HCC). The results revealed a survey completion of 78.4% and demonstrated only 4 of 35 individual symptom instances across all time points of transient worsening relative to baseline. Most importantly, the DPE platform provided an effective means for deploying and collecting patient-reported outcome measures.


Endoscopic retrograde cholangiopancreatography-related adverse events in Korea: A nationwide assessment.
Although endoscopic retrograde cholangiopancreatography (ERCP) is a pivotal procedure for the diagnosis and treatment of a variety of pancreatobiliary diseases, it has been known that the risk of procedure-related adverse events (AEs) is significant. We conducted this nationwide cohort study since there have been few reports on the real-world data regarding ERCP-related AEs. Patients who underwent ERCP were identified between 2012 and 2015 using Health Insurance Review and Assessment database generated by the Korea government. Incidence, annual trends, demographics, characteristics according to the types of procedures, and the risk factors of AEs were assessed. A total of 114,757 patients with male gender of 54.2% and the mean age of 65.0 ± 15.2 years were included. The most common indication was choledocholithiasis (49.4%) and the second malignant biliary obstruction (22.8%). Biliary drainage (33.9%) was the most commonly performed procedure, followed by endoscopic sphincterotomy (27.4%), and stone removal (22.0%). The overall incidence of ERCP-related AEs was 4.7% consisting of post-ERCP pancreatitis (PEP; 4.6%), perforation (0.06%), and hemorrhage (0.02%), which gradually increased from 2012 to 2015. According to the type of procedures, ERCP-related AEs developed the most commonly after pancreatic stent insertion (11.4%), followed by diagnostic ERCP (5.9%) and endoscopic sphincterotomy (5.7%). Younger age and diagnostic ERCP turned out to be independent risk factors of PEP. ERCP-related AEs developed the most commonly after pancreatic stent insertion, diagnostic ERCP and endoscopic sphincterotomy. Special caution should be used for young patients receiving diagnostic ERCP due to increased risk of PEP.


Magnetic hyperthermia efficiency and (1)H-NMR relaxation properties of iron oxide/paclitaxel-loaded PLGA nanoparticles.
Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar (1)H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger-sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe-NPs in PLGA-NPs also made it possible to maintain Néel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15-20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe-NPs designed for MFH applications.


G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain.
We detected the existence of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in the striatum of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The level of Gi/Go was significantly decreased by 42% in the putamen of the left hemisphere in schizophrenics; caudate head and globus pallidus levels were unchanged. Decreased Gi or Go may underlie enhanced dopamine function in the schizophrenic brain.


Should (Prophylactic) Medications Be Used for the Management of Death Rattle?
Death rattle is a common symptom in the dying phase and has impact on relatives and health care providers. One controversial topic regarding the management of death rattle in the dying phase is whether the symptom should be treated. In this "Controversies in Palliative Care" article, three expert clinicians independently answer this question. Specifically, each group provides a synopsis of the key studies that inform their thought processes, share practical advice on their clinical approach, and highlight the opportunities for future research. The three experts have different opinions on the assessment of death rattle. This seems to depend on the unknown burden of death rattle on the patient. Explanation of the symptom and reassurance could be sufficient. But considering the known burden on some of the relatives, there might be good reasons to use medication to relieve this symptom. Whether this treatment should be performed preventively or only when death rattle develops remains an matter of debate. Further scientific, clinical, and societal debate on the concept of a "good death" for relatives, the meaning of the symptom death rattle, and the impact of medication is needed.


Donor selection for a second allogeneic stem cell transplantation in AML patients relapsing after a first transplant: a study of the Acute Leukemia Working Party of EBMT.
Second allogeneic stem-cell transplantation (SCT2) is a therapeutic option for patients with AML relapsing after a first transplant. Prior studies have shown similar results after SCT2 from the same or different donor; however, there are limited data on second non-T-depleted haplo-identical transplant in this setting. We retrospectively analyzed SCT2 outcomes in 556 patients, median age 46 years, relapsing after first transplant given in CR1. Patients were divided into three groups based on SCT2 donor (donor2): same donor (n = 163, sib/sib-112, UD/UD-51), different matched donor (n = 305, sib/different sib-44, sib/UD-93, UD/different UD-168), or haplo-donor (n = 88, sib/haplo-45, UD/haplo-43). Two-year leukemia-free survival (LFS) rate after SCT2 was 23.5%, 23.7%, and 21.8%, respectively (P = 0.30). Multivariate analysis showed no effect of donor2 type on relapse: hazard ratio (HR) 0.89 (P = 0.57) and 1.11 (P = 0.68) for different donor and haplo-donor compared to same donor, respectively. However, donor2 did predict for non-relapse mortality (NRM) after SCT2: HR 1.21 (P = 0.50) and 2.08 (P = 0.03), respectively, and for LFS: HR 1.00 (P = 0.97) and 1.43 (P = 0.07), respectively. In conclusion, SCT2 with the same or different matched donor is associated with similar outcomes in patients with relapsed AML. Non-T-depleted haplo-identical transplant may be associated with higher NRM, similar relapse rate and with no better results in this setting.


Ileoileal intussusception and ileal stricture associated with necrotizing enterocolitis in a premature infant: report of a case.
A 630-g male infant developed presumed necrotizing enterocolitis (NEC) after fungal enteritis that resulted in subsequent fungal septicemia associated with pneumoperitoneum on the 9th day of life. Urgent percutaneous Penrose drainage was required. During the operation on the 14th day, an ileoileal intussusception and an ileal stricture were found with perforations on each oral side of the lesions. The distinction between NEC and intussusception in premature infants when they coexist can be difficult, as these conditions share common symptoms. The relation between ischemic injury and dysmotility of the intestine is also discussed. The similarity of intrauterine fetal distress and NEC in premature infants, as seen in the present case of the intussusception associated with focal NEC, suggests that mesenteric and enteric vascular ischemia could be one trigger of intussusception in neonates.


Medibots: Dual-Action Biogenic Microdaggers for Single-Cell Surgery and Drug Release.
An innovative concept for the fabrication of dual-action microrobots capable of performing single-cell microsurgery along with a site-directed drug-delivery feature is presented. These multi-action plant-derived biocompatible "medibots" can play a pivotal role in understanding micromotor interactions at the cellular level, aiming toward the destruction of harmful cells (like cancer) among others in living systems.


Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged ≥ 69 referred to colposcopy due to an HPV-positive screening test.
Cervical cancer incidence and mortality rates are high in older women in many developed countries, including Denmark. Therefore, Danish women aged 69 and older were invited for one additional human papilloma virus (HPV) based screening test in 2017. Here, we describe the clinical management and detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) in screen-positive women referred for colposcopy. We conducted an observational study in public gynecology departments in Central Denmark Region, Denmark. Women were eligible for enrolment if they were aged 69 + in 2017, HPV positive on a screening test taken between April 20th, 2017, and December 31st, 2017, and had been referred for direct colposcopy. Data on participants' characteristics, colposcopic findings, and histological outcomes were collected from medical records and the Danish Pathology Databank. We estimated the proportion of women with CIN2 + at the first colposcopy visit and at end of follow up including 95% confidence intervals (CIs). A total of 191 women were included with a median age of 74 years (IQR: 71-78). Most women (74.9%) did not have a fully visible transformation zone at colposcopy. At the first visit 170 women (89.0%) had a histological sample collected, 34 of whom (20.0%, 95% CI 14.3-26.8%) had CIN2 + diagnosed, 19 had CIN3 + , and two had cervical cancer). During follow-up additional CIN2 + were detected resulting in a total of 42 women (24.4%, 95% CI: 18.2-31.5%) being diagnosed with CIN2 + , 25 with CIN3 + , and three with cervical cancer. When restricting to women with paired histologic results (i.e., biopsies and a loop electrosurgical excision procedure (LEEP) specimen), we found that CIN2 + was missed in 17.9% (95% CI 8.9-30.4%) of biopsies compared to the LEEP. Our findings suggest a potential risk of underdiagnosis in older postmenopausal women referred to colposcopy. Future studies should explore potential risk-markers for discrimination of women at increased risk of CIN2 + from those at low risk, as this would reduce risk of underdiagnosis and overtreatment.


Association of CT perfusion parameters with hemorrhagic transformation in acute ischemic stroke.
Prediction of hemorrhagic transformation in acute ischemic stroke could help determine treatment and prognostication. With increasing numbers of patients with acute ischemic stroke undergoing multimodal CT imaging, we examined whether CT perfusion could predict hemorrhagic transformation in acute ischemic stroke. Patients with acute ischemic stroke who underwent CTP scanning within 12 hours of symptom onset were examined. Patients with and without hemorrhagic transformation were defined as cases and controls, respectively, and were matched as to IV rtPA administration and presentation NIHSS score (± 2). Relative mean transit time, relative CBF, and relative CBV values were calculated from CTP maps and normalized to the contralateral side. Receiver operating characteristic analysis curves were created, and threshold values for significant CTP parameters were obtained to predict hemorrhagic transformation. Of 83 patients with acute ischemic stroke, 16 developed hemorrhagic transformation (19.28%). By matching, 38 controls were found for only 14 patients with hemorrhagic transformation. Among the matched patients with hemorrhagic transformation, 13 developed hemorrhagic infarction (6 hemorrhagic infarction 1 and 7 hemorrhagic infarction 2) and 1 developed parenchymal hematoma 2. There was no significant difference between cases and controls with respect to age, sex, time to presentation from symptom onset, and comorbidities. Cases had significantly lower median rCBV (8% lower) compared with controls (11% higher) (P = .009; odds ratio, 1.14 for a 0.1-U decrease in rCBV). There was no difference in median total volume of ischemia, rMTT, and rCBF among cases and controls. The area under the receiver operating characteristic was computed to be 0.83 (standard error, 0.08), with a cutoff point for rCBV of 1.09. Of the examined CTP parameters, only lower rCBV was found to be significantly associated with a relatively higher chance of hemorrhagic transformation.


Country-level factors dynamics and ABO/Rh blood groups contribution to COVID-19 mortality.
The identification of factors associated to COVID-19 mortality is important to design effective containment measures and safeguard at-risk categories. In the last year, several investigations have tried to ascertain key features to predict the COVID-19 mortality tolls in relation to country-specific dynamics and population structure. Most studies focused on the first wave of the COVID-19 pandemic observed in the first half of 2020. Numerous studies have reported significant associations between COVID-19 mortality and relevant variables, for instance obesity, healthcare system indicators such as hospital beds density, and bacillus Calmette-Guerin immunization. In this work, we investigated the role of ABO/Rh blood groups at three different stages of the pandemic while accounting for demographic, economic, and health system related confounding factors. Using a machine learning approach, we found that the "B+" blood group frequency is an important factor at all stages of the pandemic, confirming previous findings that blood groups are linked to COVID-19 severity and fatal outcome.


Local delivery of the topoisomerase I inhibitor camptothecin sodium prolongs survival in the rat intracranial 9L gliosarcoma model.
Camptothecin, a naturally occurring inhibitor of the DNA-replicating enzyme topoisomerase I, demonstrated promising anti-tumor activity in pre-clinical testing; however, because of unexpected toxicity and low anti-tumor effects in the initial clinical trials, further testing was discontinued. We hypothesized that local controlled delivery of camptothecin sodium would achieve effective concentrations in brain tumors without the observed systemic side effects, thereby allowing this novel drug to be used to treat patients with malignant gliomas. To test this hypothesis, we evaluated the sensitivity of rat glioma lines and established human glioma lines to camptothecin in vitro. We found that the LD90 for the established rat and human lines was 0.3 to 1.4 microM after a 1 hr exposure and decreased to less than 0.1 microM after continuous exposure for 7 days. We loaded camptothecin into a controlled-release polymer (ethylene-vinyl acetate co-polymer; EVAc) and showed by high-pressure liquid chromatography that controlled release occurred over at least 21 days. We then tested camptothecin against 9L gliosarcoma, implanted into the brain of Fischer 344 rats. Five days after tumor implantation, animals were treated with camptothecin delivered either systemically or locally by release from EVAc. Local controlled delivery by the polymer significantly extended survival: 59% of the treated animals were long-term survivors (> 120 days) compared to 0% of controls. Systemic administration did not extend survival compared to controls. We compared the efficacy of camptothecin delivered locally with a polymer to camptothecin injected directly into the tumor. Camptothecin increased survival only when delivered locally by polymer.


Gelation, flame retardancy, and physical properties of phosphorylated microcrystalline cellulose aerogels.
Flame-retardant bio-based cellulose aerogels, with abundant renewable sources, are considered as promising sustainable heat-insulation alternatives to conventional petroleum-based foams. An environmentally friendly method was employed to fabricate phosphorylated microcrystalline cellulose (PMCC) aerogel through the gelation of PMCC/H2O dispersion and freeze-drying of PMCC hydrogel. The dispersion stability of PMCC and its readiness to undergo gelation in the aqueous phase were enhanced by increasing the phosphorous content via phosphorylation, thereby effectively weakening the strong intra- and intermolecular hydrogen-bond interactions of the cellulose chains. The morphology of the PMCC aerogel changed from a short rod-shaped and sheet-like aggregation of a three-dimensional skeleton structure to a mostly sheet-like aggregation of a three-dimensional structure with increased phosphate esterification. Remarkably, PMCC aerogels exhibited improved flame retardancy and superior suppression of toxic gas, compared to MCC. This is attributable to the synergic effect of phosphate dehydration, catalytic carbonization, and protection of the aerogel network structure.


Endoleaks with the AneuRx graft: a longer-term, single-center study.
To report the frequency of endoleaks after endovascular aneurysm repair (EVAR) with the AneuRx graft. The study group included 121 consecutive patients treated with the first-generation AneuRx graft before December 2005, which ensured a potential minimum follow-up of 5 years. Thirty-seven patients (31%) had 45 different endoleaks at varying times in their follow-up. There were 18 type I endoleaks (15%), 56% of which developed more than 5 years after EVAR. All 12 type Ia endoleaks were associated with dilation of the neck of the aneurysm by a mean of 8.5 mm at a median follow-up of 4 years. Ten of the 12 type Ia endoleaks were judged to have very favorable necks for EVAR. Five additional patients being followed had documented neck dilation and/or migration without evidence of endoleak or aneurysm enlargement. All type II endoleaks were noted in the first 2 years, and one persisted untreated for 9 years. Type I endoleaks continue to appear over time, and 56% occurred at 5 years or later after EVAR. All were associated with dilation at the attachment site, and all type Ia endoleaks had migration. As type Ia endoleaks may not always be amenable to endovascular repair, EVAR should be considered a less attractive option for some patients whose life expectancy is predicted to exceed 10 years.


Murine hybrid cell lines expressing the NLDC-145 dendritic cell determinant.
Dendritic cells play an important role as accessory cells in the immunological defense system. Investigations into the biological functions of this population have been limited by the difficulties encountered in isolating sufficient numbers of cells, and therefore different approaches have been described to immortalize accessory cell populations. In this report, four murine hybrid cell lines (H1-H4) are described that were produced by fusion of in vitro isolated dendritic cells and a tumor cell. The hybrid lines are characterized by the expression of the dendritic cell specific marker NLDC-145, Ia expression and the absence of macrophage or T cell markers. The cell lines have no phagocytic activity and are functionally active as accessory cells. The expression of the NLDC-145 antigen in vitro was found to be inducible. These NLDC-145-positive cell lines will be useful for the further characterization of the NLDC-145 antigen and in the study of dendritic cell and lymphocyte interactions.


Preliminary examination of the reliability and concurrent validity of the attention-deficit/hyperactivity disorder self-report scale v1.1 symptom checklist to rate symptoms of attention-deficit/hyperactivity disorder in adolescents.
To validate the attention-deficit/hyperactivity disorder (ADHD) Self-Report Scale (ASRS) v1.1 Symptom Checklist versus the clinician-administered ADHD Rating Scale (ADHD-RS) in adolescents with ADHD. A total of 88 adolescents with ADHD aged 13-17 years participated in the study. The study was completed in one or two visits, 1-9 weeks apart. At each visit, participants completed the ASRS v1.1 Symptom Checklist, after which raters administered the ADHD-RS. Internal consistency of the ASRS v1.1 Symptom Checklist was assessed by Cronbach's alpha (Cronbach's α). Concurrent validity between the scales was assessed using Pearson's correlation coefficients. Item-by-item reliability between the scales was assessed by the Kappa coefficient of agreement. The mean age of participants was 14.9±1.5 SD years. 76.1% (n=67) were male. 73.9% (n=65) were currently receiving medication for ADHD. Internal consistency of ASRS v1.1 Symptom Checklist items was high, with Cronbach's α coefficients of 0.93 at Visit 1 and 0.94 at Visit 2. Pearson's correlation coefficients between the ASRS v1.1 Symptom Checklist and ADHD-RS were highly significant at Visit 1 (r=0.72, p<0.0001) and Visit 2 (r=0.73, p<0.0001). There was moderate item-by-item agreement between individual items on the scales (% agreement: 35.2%-63.4%) with statistically significant kappa coefficients for 17 of the 18 items. The ASRS v1.1 Symptoms Checklist showed high internal consistency and high concurrent validity with the clinician-administered ADHD-RS in adolescents with ADHD. Results of this study suggest that the ASRS v1.1 Symptom Checklist is an internally consistent self-report scale for the assessment of adolescent ADHD and is moderately associated with a concurrently administered clinician measure of ADHD symptoms.


Renoprotective role of fenoldopam pretreatment through hypoxia-inducible factor-1alpha and heme oxygenase-1 expressions in rat kidney transplantation.
Donor preconditioning by fenoldopam is demonstrated to improve graft function in recipients. Involvement of hypoxia-inducible factor-1alpha (HIF-1α) and heme oxygenase-1 (HO-1) in renoprotection after fenoldopam pretreatment was investigated. Donor Sprague-Dawley (SD) rats were intravenously treated with fenoldopam (5 μg/kg · min), Sch23390 (10 μg/kg · min), or fenoldopam + Sch23390 for 1 hour. Kidneys experiencing 24 hours of cold preservation were transplanted into syngeneic SD recipients. Ten days after transplantion, serum concentrations of creatinine (sCR), blood urea nitrogen (BUN), interleukin (IL)-8, and tumor necrosis factor (TNF)-α in recipient were determined. Grafts were procured for histopathological examination, apoptosis analysis, and measurements of malondialdehyde and total superoxide dismutase activities; meanwhile, both protein level and mRNA level of HIF-1α and HO-1 were assessed. Fenoldopam preconditioning significantly decreased the serum concentrations of sCR, BUN, IL-8, and TNF-α in recipients. Low apoptosis rate and reduced oxidative stress were found in these grafts. Increased HIF-1α activation and HO-1 expression were observed in fenoldopam pretreatment group. Sch23390 partly inhibited the effects of fenoldopam in the combination group. Donor preconditioning by fenoldopam exerts renoprotection in grafts, at least in part, through HIF-1α activation and HO-1 expression. This provides a preference for further studies.


Lymphangiectasia haemorrhagica conjunctivae.
To re-describe a condition that has not been mentioned in the literature for more than four decades and to outline a new method of treatment of the pathology using an argon laser. Nine patients were identified over a 2 year period who fitted a clinical picture consistent with the features of lymphangiectasia haemorrhagica. Three were treated for frequent recurrent haemorrhages with a newly developed technique using the argon laser and followed for up to 2 years. None of the three treated patients has had a recurrence of the condition to date. In the six untreated patients the condition resolved spontaneously after repeated attacks over between 8 months and 8 years. Lymphangiectasia haemorrhagica conjunctivae is probably more common than expected and may resolve spontaneously, but is readily amenable to treatment with the argon laser if attacks become frequent, uncomfortable or unsightly.


Laser-assisted marking for toric intraocular lens alignment.
We describe a technique of 3-dimensional spectral-domain optical coherence tomography-controlled laser-assisted corneal marking for toric intraocular lens implantation. To facilitate accurate alignment, the technique creates 2 perpendicular intrastromal incisions (width 0.75 mm) using an image-guided femtosecond laser. This was performed in a case series comprising 10 eyes of 10 patients. No posterior corneal perforation or epithelial alterations occurred. The incisions were plainly visible under the operating microscope, and no optical phenomena were reported 6 weeks after surgery. Laser-assisted marking can be performed safely and has the potential to enable precise axis marking. Dr. Dick is a paid consultant to Abbott Medical Optics, Inc. Dr. Schultz has no financial or proprietary interest in any material or method mentioned.


Ganglioside-basic protein interaction: protection of gangliosides against neuraminidase action.
The ability of acidic phospho- and sphingolipids to interact with basic proteins was studied by double diffusion analysis. The phospholipids, tri- and diphosphoinositide, and the sphingolipid, sulfatide, interacted with myelin basic protein as evidenced by precipitin line formation. Of the sialoglycosphingolipids (gangliosides) tested, only the myelin-specific monosialoganglioside, GM4, formed a precipitin line with myelin basic protein. In addition, myelin basic protein retarded the activity of Clostridium perfringens neuraminidase against GM4 and the disialoganglioside, GD1b. Examination of purified rat brain myelin suggested the presence of a neuraminidase activity intrinsic to myelin. This finding, in concert with ganglioside-myelin basic protein complexes which selectively protect against neuraminidase, may provide a physiological explanation for the simplified ganglioside pattern found in myelin.


The role of the Lumina intense pulsed light system in the treatment of port wine stains--a case controlled study.
The pulsed dye laser has been the treatment of choice for port wine stains over the past 20 years. In the past 5 years there has been increasing discussion of the role of other light treatments, such as the intense pulsed light system in the treatment of port wine stains. These systems use high-energy lamps, which emit noncoherent broad-spectrum light. Cut off filters are applied depending on the treatment modality to limit the wavelengths emitted. We present the results of a 3-year prospective within patient controlled clinical trial using an intense pulsed light system called the Lumina, developed by Lynton Lasers of Cheshire, England. Our aims and objectives were to assess the effectiveness of the system in the treatment of port wine stains in a human model and to record the optimum treatment parameters and the incidence of side effects. Following ethical approval 12 subjects were enrolled into the trial. In order to meet the requirements of the local ethics committee these were all adults with port wine stains located in less visible areas of the body. The results showed that eight of the 12 subjects had some degree of fading of their port wine stain as measured on a percentage scoring system. Of the four who failed to show any response, all had pink port wine stains. It did seem the case that the darker the port wine stain, the better the fading seen. Furthermore, the more distal lesions tended to be less responsive than those situated closer to the head area. However, it is difficult to draw any definitive statistical conclusions due to the small number of patients in the trial.


Respiratory Mechanics and Outcomes in Immunocompromised Patients With ARDS: A Secondary Analysis of the EFRAIM Study.
In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement. This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [ΔPrs]). This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, ΔPrs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality. Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.01-2.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher ΔPrs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: ΔPrs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality. In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.


Correlated product of experts for sparse Gaussian process regression.
Gaussian processes (GPs) are an important tool in machine learning and statistics. However, off-the-shelf GP inference procedures are limited to datasets with several thousand data points because of their cubic computational complexity. For this reason, many sparse GPs techniques have been developed over the past years. In this paper, we focus on GP regression tasks and propose a new approach based on aggregating predictions from several local and correlated experts. Thereby, the degree of correlation between the experts can vary between independent up to fully correlated experts. The individual predictions of the experts are aggregated taking into account their correlation resulting in consistent uncertainty estimates. Our method recovers independent Product of Experts, sparse GP and full GP in the limiting cases. The presented framework can deal with a general kernel function and multiple variables, and has a time and space complexity which is linear in the number of experts and data samples, which makes our approach highly scalable. We demonstrate superior performance, in a time vs. accuracy sense, of our proposed method against state-of-the-art GP approximations for synthetic as well as several real-world datasets with deterministic and stochastic optimization. The online version contains supplementary material available at 10.1007/s10994-022-06297-3.


Feeding NOD mice with pig splenocytes induces transferable mechanisms that modulate cellular and humoral xenogeneic reactions against pig spleen or islet cells.
We have reported previously that oral administration of pig cells to NOD mice modified xenogeneic cellular response against pig islet cells (PICs), and hypothesized that it may have induced active suppression. This preliminary report evaluated only the effect of feeding pig cells by 'primary' proliferation, i.e. when splenocytes from fed mice are confronted with pig cells in vitro. The present study also considered 'secondary' proliferation and cytokine production after feeding and subsequent in vivo graft of pig cells. Additionally, serum IgM and IgG isotypes were quantified by ELISA using pig target cells. Induction of active mechanism by feeding was hypothetical, which led us here to transfer splenocytes from mice fed pig spleen cells (PSC) and evaluate 'primary' (after transfer) and 'secondary' (after transfer and subsequent graft of pig cells) proliferations and cytokine secretions in recipient mice. We also determined whether the effects of feeding pig cells persisted after depression of suppressor mechanisms by cyclophosphamide. Mice fed with PSC displayed increased 'primary' splenocyte proliferation to PSC or PIC (P < 0.0001), while 'secondary' responses were decreased (P < 0.03) in those fed PSC and subsequently grafted with PSC. The increased 'primary' and decreased 'secondary' proliferations were reduced (P < 0.04) by pretreatment with cyclophosphamide. The IL-10/ and IL-4/IFNgamma ratios produced in response to PSC increased (P < 0.04) in mice fed and grafted with PSC compared to those grafted only with PSC. IgM and IgG levels against pig cells were, respectively, increased (P < 0.04) and decreased (P < 0.04) in mice fed and grafted with PSC. IgG2a and IgG2b, but not IgG1, levels were lower (P < 0.01). These effects of feeding PSC on 'secondary' proliferation, cytokine and antibody productions, were not detected when mice were fed PSC only after graft with PSC. Transfer with splenocytes from mice fed PSC increased 'primary' proliferation of splenocytes from recipient mice in response to PSC (P < 0.02) or PIC (P < 0.05). After transfer with splenocytes from PSC-fed mice and graft with PSC, 'secondary' proliferation to pig cells were reduced (P < 0.04), and the IL-10/IFNgamma ratio produced in response to PSC was increased fourfold. Thus, oral administration of PSC induces active transferable mechanisms, characterized by a biphasic pattern with early increased 'primary' xenogeneic cellular reactions to both PSC and PIC, followed by decreased 'secondary' responsiveness and a concomitant shift of the Th1/Th2 balance towards greater Th2 influence. Decreased responsiveness may be due to active suppression, even though induction of anergy or deletion cannot be excluded.


[The gastrulation in Cnidaria: A key to understanding phylogeny or the chaos of secondary modifications?].
The data revealed by comparative embryology of the basal (diploblastic) metazoans is traditionally considered a valuable potential source of information on the origin and early evolution of the animal kingdom and its major clades. Special attention is paid to the fundamental morphogenetic process of gastrulation during which the cells of the early embryo differentiate into the germ layers and the primary body plan is formed. Comparative analysis of gastrulation in different cnidarian taxa reveals high level of intergroup, intragroup, and individual variation. With few exceptions, there is no robust correlation between the type of gastrulation and the taxon. Current data do not support the idea that morphogenetic processes underlying cnidarian gastrulation can be divided into several distinct types. Rather, there is a continuum of equifinal ontogenetic trajectories. In cnidarians, the mode of gastrulation apparently depends less on the macroevolutionary history of the species than on various evolutionary plastic features, such as the oocyte size, the amount of yolk, the number of cells at the blastula (or morula) stage, the presence of phototrophic symbionts, or the ecology of the larva. Thus, in cnidarians, morphogenetic basis of gastrulation contains only a very weak phylogenetic signal and can have only limited application in phylogenetic reconstructions. On the other hand, comparative studies of the ontogeny of the basal metazoans shed light on the general rules of the evolution of morphogenetic processes that is crucial for understanding the early history of the animal kingdom.


Impact of rate versus rhythm control on quality of life in patients with persistent atrial fibrillation. Results from a prospective randomized study.
Despite the high prevalence of atrial fibrillation (AF), there are only limited data on quality of life (QoL) stemming from prospective trials comparing rate versus rhythm control. This prospective study evaluated QoL in patients with symptomatic persistent AF randomized to therapy aiming at rate versus rhythm control. Patients with symptomatic persistent AF (7 to 360 days duration) were prospectively randomized to ventricular rate control (n=125) or to cardioversion and maintenance of sinus rhythm (n=127). QoL was assessed by the Medical Outcomes Study Short Form health survey (SF-36) at baseline and during 1 year of follow-up. Changes in QoL were compared on an intent-to-treat basis, and subsequently between patients in sinus rhythm versus AF. At baseline, all SF-36 scales were reduced compared to healthy controls. At 1 year, six of eight items had improved significantly in patients assigned to rate control, and five of eight items on rhythm control (p=ns). The physical component summary showed a comparable increase with both treatment strategies (rate control: p=0.004; rhythm control: p<0.001) whereas no significant changes were found for the mental component summary. At 1 year, 55% of patients reported a positive health transition with no inter-group differences. There were no significant differences in QoL in patients in sinus rhythm or AF at the end of the observation period. In patients with symptomatic persistent AF, the two treatment strategies of rate versus rhythm control are associated with similar improvements in QoL.


Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects.
The phosphodiesterase (PDE) type 5 inhibitor is a widely used agent that facilitates penile erection. Udenafil is newly developed as a PDE-5 inhibitor. This is the first study to determine the safety, tolerability and pharmacokinetics of udenafil in healthy subjects. Udenafil was safe and well tolerated in healthy Korean subjects. The AUC and C(max) of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations. To evaluate the safety, tolerability and pharmacokinetics (PK) of udenafil, a novel phosphodiesterase type 5 inhibitor. A double-blind, randomized, placebo-controlled, dose-rising, parallel-group, single- and multiple-dose study was conducted in healthy Korean subjects. The subjects were allocated to single-dose groups of 25, 50, 100, 200 or 300 mg (eight subjects in each dose group, including two placebos), or to multiple-dose groups of 100 or 200 mg (once-daily dosing for 7 days; nine subjects in each dose group, including three placebos). Serial samples of blood and urine were collected after oral administration and the drug concentrations in plasma and urine were determined by high-performance liquid chromatography. Safety and tolerability were evaluated by monitoring clinical laboratory parameters and adverse events. Udenafil reached peak plasma concentrations at 0.8-1.3 h, and then declined mono-exponentially with a terminal half-life of 7.3-12.1 h in the single-dose study. The area under the time-concentration curves (AUC) and maximum plasma concentrations (C(max)) increased supraproportionally with increasing dose in the single-dose study. During multiple dosing, a steady state was reached at 5 days and little accumulation occurred after repeated dosing for 7 days. Udenafil was generally well tolerated in these healthy subjects, and no serious adverse events occurred. Udenafil was safe and well tolerated in healthy volunteers. The AUC and C(max) of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations.


Extracellular polymeric substances trigger an increase in redox mediators for enhanced sludge methanogenesis.
Artificial redox mediators can be employed to improve the electron transfer efficiency during sludge methanogenesis, whereas these artificial redox mediators have possible deficiencies, such as high cost and non-biodegradability. For large-scale commercial applications, more cost-effective and environmentally friendly alternatives should be developed. Herein, the potential of extracellular polymeric substances (EPS) as natural redox mediators to improve methanogenesis was investigated. Compared to the control test without EPS addition, the methane (CH4) production yield was increased by 83.5 ± 2.4% with an EPS dosage of 0.50 g/L and the lag phase duration was shortened by 45.6 ± 7.0%, along with the enhanced sludge dewaterability. Spectroelectrochemical measurements implied that EPS addition notably changed the intensities of different redox-active groups, which decreased the charge transfer resistance and enhanced the extracellular electron transfer efficiency. These redox-active groups were mainly from the solubilization and hydrolysis of sludge protein due to increased protease activities, thereby leading to a higher acetate concentration during the acidification step. Further investigation showed that EPS addition also improved the activities of both acetotrophic and hydrogenotrophic methanogens, as indicated by a higher abundance of alpha subunit of methyl coenzyme M reductase (mcrA) genes, enhancing CH4 production. This work provides an innovative strategy for improving sludge anaerobic digestion with efficient additives.


The ATPase activity in isometric and shortening skeletal muscle fibres.
Muscle proteins utilise the hydrolysis of ATP to provide the energy for force development and the production of mechanical work. We have developed a technique with high sensitivity and time resolution to probe as directly as possible the link between ATPase activity, force development and muscle shortening. The ATPase activity was recorded in real time during contraction and shortening of permeabilised muscle fibres of rabbit skeletal muscle by measuring fluorescence changes associated with the binding of inorganic phosphate, a product of ATPase activity, to a genetically engineered phosphate binding protein labelled with a coumarin fluorophore. The muscle shortening velocity was found to affect directly the ATPase activity, with up to a five-fold increase during shortening at moderate velocities, and a decrease in activity during slow stretch.


Inhibition of Wnt and PI3K signaling modulates GSK-3beta activity and induces morphological changes in cortical neurons: role of tau phosphorylation.
Glycogen synthase kinase GSK-3beta has been identified as one of the major candidates mediating tau hyperphosphorylation at the same sites as those present in tau protein in brain from Alzheimer's disease (AD) patients. However, the signal transduction pathways involved in the abnormal activation of GSK-3beta, have not been completely elucidated. GSK-3beta activity is repressed by the canonical Wnt signaling pathway, but it is also modulated through the PI3K/Akt route. Recent studies have suggested that Wnt signaling might be involved in the pathophysiology of AD. On the other hand, modulators of the PI3K pathway might be reduced during aging leading to a sustained activation of GSK-3beta, which in turn would increase the risk of tau hyperphosphorylation. The role of Wnt and PI3K signaling inhibition on the extent of tau phosphorylation and neuronal morphology has not been completely elucidated. Thus, in the present investigation we analyzed the effects of different negative modulators of the Wnt and the PI3K pathways on GSK-3beta activation and phosphorylation of tau at the PHF-1 epitope in cortical cultured neurons and hippocampal slices from adult rat brain. Changes in the microtubule network were also studied. We found that a variety of Wnt and PI3K inhibitors, significantly increased tau phosphorylation at the PHF-1 site, induced the disarrangement of the microtubule network and the accumulation of tau within cell bodies. These changes correlated with alterations in neuronal morphology.


Citation Skew in Plastic Surgery Journals: Does the Journal Impact Factor Predict Individual Article Citation Rate?
Citation skew refers to the unequal distribution of citations to articles published in a particular journal. We aimed to assess whether citation skew exists within plastic surgery journals and to determine whether the journal impact factor (JIF) is an accurate indicator of the citation rates of individual articles. We used Journal Citation Reports to identify all journals within the field of plastic and reconstructive surgery. The number of citations in 2018 for all individual articles published in 2016 and 2017 was abstracted. Thirty-three plastic surgery journals were identified, publishing 9823 articles. The citation distribution showed right skew, with the majority of articles having either 0 or 1 citation (40% and 25%, respectively). A total of 3374 (34%) articles achieved citation rates similar to or higher than their journal's IF, whereas 66% of articles failed to achieve a citation rate equal to the JIF. Review articles achieved higher citation rates (median, 2) than original articles (median, 1) (P < 0.0001). Overall, 50% of articles contributed to 93.7% of citations and 12.6% of articles contributed to 50% of citations. A weak positive correlation was found between the number of citations and the JIF (r = 0.327, P < 0.0001). Citation skew exists within plastic surgery journals as in other fields of biomedical science. Most articles did not achieve citation rates equal to the JIF with a small percentage of articles having a disproportionate influence on citations and the JIF. Therefore, the JIF should not be used to assess the quality and impact of individual scientific work.


A novel opioid structure which accepts protonated as well as non-protonated nitrogen: a family of pure, delta receptor selective antagonists.
Conventional opioids including opioid peptides require an "opioid" nitrogen which exists in protonated state while interacting with the receptor. In the present paper we demonstrate that the Tyr-Pro-Gly-Phe-Leu-Thr hexapeptide sequence accepts N-terminal substituents such as N-t-Boc, N-phenylacetyl and N-diphenylacetyl where the N cannot become protonated, as well as "traditional" substitutions such as N,N-diallyl, where protonation is likely under physiological conditions. The opioid peptides bearing these substituents are pure antagonists of medium affinity (Ke values in the mouse vas deferens bioassay against [Met5]-enkephalin are in the 3 x 10(-7)-4 x 10(-6) M range) with a high delta receptor preference (50-350-fold delta over mu selectivity ratios).


Absence of HHV-8 DNA in hobnail hemangiomas.
Hobnail hemangioma (HH) is a rare subtype of hemangioma that shares the morphological feature of hobnail endothelia with retiform hemangioendothelioma (RHE) and has to be considered in the differential diagnosis of Kaposi sarcoma. Since DNA of the human herpesvirus type 8 (HHV-8) has been detected in more than 90% of Karposi sarcomas and could recently be demonstrated in RHE, we sought to detect HHV-8 DNA in HH. DNA from 12 HH was extracted and subjected to polymerase chain reaction analysis for HHV-8 DNA using two independent protocols with a single set of primers and a nested PCR approach, respectively. PCR amplification was performed using the LightCycler as well as using a thermocycler. HHV-8 DNA could not be detected in HH, although each sample contained DNA adaequately preserved for PCR reactions, as determined by amplification of the beta actin gene. HHV-8 appears to play no rule in the pathogenesis of HH. Absence of HHV-8 DNA in HH might be important in the differential diagnosis to other vascular tumours, in particular Kaposi sarcoma.


Complex and region-specific changes in astroglial markers in the aging brain.
Morphological aging of astrocytes was investigated in entorhinal cortex (EC), dentate gyrus (DG), and cornu ammonis 1 (CA1) regions of hippocampus of male SV129/C57BL6 mice of different age groups (3, 9, 18, and 24 months). Astroglial profiles were visualized by immunohistochemistry by using glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and s100β staining; these profiles were imaged using confocal or light microscopy for subsequent morphometric analysis. GFAP-positive profiles in the DG and the CA1 of the hippocampus showed progressive age-dependent hypertrophy, as indicated by an increase in surface, volume, and somata volume at 24 months of age compared with 3-month-old mice. In contrast with the hippocampal regions, aging induced a decrease in GFAP-positive astroglial profiles in the EC: the surface, volume, and cell body volume of astroglial cells at 24 months of age were decreased significantly compared with the 3-month group. The GS-positive astrocytes displayed smaller cellular surface areas at 24 months compared with 3-month-old animals in both areas of hippocampus, whereas GS-positive profiles remained unchanged in the EC of old mice. The morphometry of s100β-immunoreactive profiles revealed substantial increase in the EC, more moderate increase in the DG, and no changes in the CA1 area. Based on the morphological analysis of 3 astroglial markers, we conclude that astrocytes undergo a complex age-dependent remodeling in a brain region-specific manner.


Differential diagnosis of pancreatic mass lesion with percutaneous fine-needle aspiration biopsy under ultrasonic guidance.
Ultrasonically guided percutaneous fine-needle aspiration biopsy for cytological diagnosis was performed on 28 patients with ultrasonically scanned solid mass lesions of the pancreas in an attempt to make a differential diagnosis between pancreatic cancer and chronic pancreatitis. In 25 of the 28 patients, enough cells were aspirated to enable a cytological diagnosis to be made. In 19 of these 25 patients, malignant cells were obtained, while the aspirates from 6 patients contained only normal pancreatic cells. In 3 of the 28 patients, insufficient numbers of cells were obtained to allow the establishment of a cytological diagnosis. Pancreatic cancers were present in 22 of the 28 patients, and among these a positive diagnosis of cancer was made by aspiration biopsy in 86.4% (19/22). The technique resulted in no false positive diagnoses of cancer among 6 patients with chronic pancreatitis. No complications, such as bleeding, fistula formation, and elevation of the serum amylase, followed the procedure. This new method appears to be extremely useful in the diagnosis of pancreatic mass lesions.


Regulatory risks associated with bacteria as biostimulants and biofertilizers in the frame of the European Regulation (EU) 2019/1009.
Agriculture represents an important mechanism for the reduction in plant, animal and microbial biodiversity and the alteration of the environment. The high pressure to cope with increasing demands of food for the human population intensifies the environmental impact and requires alternative ways to produce more food and to minimize the decrease in biodiversity. The use of biostimulants and biofertilizers could represent one of such alternatives. However, we need to guarantee that their use does not result in a greater damage for human health and for the environment. The European authorities try to protect humans, plants, animals and the environment by developing the recent European Regulation (EU) 2019/1009 on biostimulants. In the present study, we discuss the taxonomic approach of the EU to limit the use of microorganisms as biostimulants. We also propose an alternative method to evaluate the safety of microorganisms that are used as biostimulants and biofertilizers. That is, we suggest the use of panels of bioassays on model organisms and potential improvements on this system to evaluate the risks associated with the use of microorganisms as biostimulants and biofertilizers.


Feasibility of using solid sampling graphite furnace atomic absorption spectrometry for preparation of spiked filter papers with Cu and Zn as standards for direct solid analysis.
An approach was developed for the preparation of cryogenic ground spiked filter papers with Cu and Zn for use as synthetic calibrating standards for direct solid microanalysis. Solid sampling graphite furnace atomic absorption spectrometry was used to evaluate the microhomogeneity and to check the applicability of the synthetic calibrating standards for the direct determination of Cu and Zn in vegetable certified reference materials. The found concentrations presented no statistical differences at the 95% confidence level. The homogeneity factors ranged from 2.7 to 4.2 for Cu and from 6.4 to 11.5 for Zn.


Dose and time related effects of T-2 toxin on mitogenic response of murine splenic cells in vitro.
The effects of T-2 toxin in vitro on murine splenic cells were investigated. Cells from syngeneic male NFS/N mice were cultured with three concentrations of either lipopolysaccharide (LPS), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), or concanavalin A (Con A), for 48 h. T-2 toxin (10(-12)-10(-8)M) was added at the beginning or 24 h after initiation of the cultures. Exposure to T-2 toxin (10(-11)-10(-10)M) after 24 h increased 3H-thymidine uptake by splenic cells. Stimulation by PWM increased dramatically while the response to LPS was increased to a lesser extent in this system. Conversely, exposure to T-2 toxin decreased T-cell responses to both PHA and Con A. Exposing cells to T-2 toxin at the initiation of culture increased Con A stimulation; LPS and PWM responses decreased following 48 h exposure. When splenic cells were pre-treated for 60 or 90 min at 0 degrees C with 10(-9)M T-2 toxin the responses to both PWM and LPS increased. Increased 3H-thymidine uptake was also observed following 90 min exposure to T-2 toxin alone at either 0 or 37 degrees C. The increased PWM response and the mitogenic phenomenon observed when cells were exposed only to T-2 toxin were consistent with previously observed effects of in vivo T-2 toxin exposure.


Appendicitis: evaluation by Tc-99m leukocyte scan.
Diagnosing appendicitis may be difficult. We report the use of a new technetium-99m-albumin colloid white blood cell (TAC-WBC) scan in the evaluation of appendicitis. In a synthesis requiring 75 minutes, autologous neutrophils and macrophages from 40 mL of whole blood were labelled with technetium-99m-albumin colloid and administered to 100 patients with possible appendicitis. The entire process, from labelling the cells to completion of the scan took a maximum of 5 1/4 hours. Two patients had second scans on separate hospitalizations. Twenty-six patients had appendicitis; 12 had perforations, five of whom had an abscess. Eighty-five scans were read as either positive or negative for appendiceal pathology with a sensitivity of 89%, a specificity of 92%, and an accuracy of 92% in diagnosing appendicitis. Seventeen scans were indeterminant; eight of these patients had appendicitis. The value of the TAC-WBC scan in the evaluation of appendicitis lies in its ability to be used emergently, its high negative predictive value for men and women (NPV = 97%), and its high positive predictive value for men (PPV = 93%). At present, the scan does not appear to be reliable in diagnosing appendicitis in women (PPV = 43%). It is most useful in those patients in whom diagnosis is uncertain, and should not be used in patients with clear-cut appendicitis in whom its use will delay definitive surgical care.


Effective immobilization of lactate dehydrogenase onto mesoporous silica.
This study presents that covalent immobilization technique has been utilized for the immobilization of l-lactate dehydrogenase (l-LDH) from porcine on mesoporous silica. To develop mesoporous silica as support material for use in l-LDH immobilization, the particle surfaces were functionalized with 3-aminopropyltrimethoxysilane and further conjugated with glutaraldehyde. The effect of some parameters such as glutaraldehyde concentration, immobilization pH, initial enzyme concentration, and immobilization time was investigated and the optimum conditions for these parameters were determined as 1% (w/v), pH 8.0, 1 mg/ml, and 120 min, respectively. The maximum working pH and temperature for the oxidation of lactate to pyruvate reaction were determined as 10.0 and 35°C for free and 9.0 and 40°C for immobilized l-LDH, respectively. The kinetic parameters (Km and Vmax ) of l-LDH for the oxidation of lactate to pyruvate reaction were examined as 1.02 mM and 7.58 U/mg protein for free and 0.635 mM and 1.7 U/mg protein for immobilized l-LDH, respectively. Moreover, the immobilized l-LDH was 1.3-fold more stable than free l-LDH at 25°C according to calculated t1/2 values. The immobilized l-LDH retained 80% of its initial activity in a batch reactor after 14 reuses.


The role of osteotomy in the anterior cruciate ligament-deficient knee.
Whether the ACL-deficient knee actually causes osteoarthritis is unclear. What is clear is that the two conditions can exist simultaneously. Treatment of these patients must be individualized based on their activities, symptoms, and findings. In the unusual patient with significant instability and moderate medial compartment osteoarthritis, a combined valgus osteotomy and ACL reconstruction may be appropriate. The authors emphasize that this is a salvage procedure, not intended to return the athlete to competition. Although the short-term results are promising, the long-term results of this treatment are unknown.


Lactulose ameliorates cerebral ischemia-reperfusion injury in rats by inducing hydrogen by activating Nrf2 expression.
Molecular hydrogen has been proven effective in ameliorating cerebral ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen species. Lactulose can produce a considerable amount of hydrogen through fermentation by the bacteria in the gastrointestinal tract. To determine the neuroprotective effects of lactulose against cerebral I/R injury in rats and explore the probable mechanisms, we carried out this study. The stroke model was produced in Sprague-Dawley rats through middle cerebral artery occlusion. Intragastric administration of lactulose substantially increased breath hydrogen concentration. Behavioral and histopathological verifications matched biochemical findings. Behaviorally, rats in the lactulose administration group won higher neurological scores and showed shorter escape latency time in the Morris test. Morphologically, 2,3,5-triphenyltetrazolium chloride showed smaller infarction volume; Nissl staining manifested relatively clear and intact neurons and TUNEL staining showed fewer apoptotic neurons. Biochemically, lactulose decreased brain malondialdehyde content, caspase-3 activity, and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine concentration and increased superoxide dismutase activity. The effects of lactulose were superior to those of edaravone. Lactulose orally administered activated the expression of NF-E2-related factor 2 (Nrf2) in the brain as verified by RT-PCR and Western blot. The antibiotics suppressed the neuroprotective effects of lactulose by reducing hydrogen production. Our study for the first time demonstrates a novel therapeutic effect of lactulose on cerebral ischemia/reperfusion injury and the probable underlying mechanisms. Lactulose intragastrically administered possessed neuroprotective effects on cerebral I/R injury in rats, which could be attributed to hydrogen production by the fermentation of lactulose through intestinal bacteria and Nrf2 activation.


Ultrastructure of the anterior sense organs of adult Gastromermis Boophthorae (Nematoda: Mermithidae).
The amphids of adult Gastromermis boophthorae exhibit an organization unlike any previously reported. Each amphid consists of a distal cuticular channel which opens to the exterior, and a proximal amphidial gland. The cuticular channel is double and 15-18 cilia are held in a tight bundle by the inner channel. The amphidial gland contains an extensive reticulum, and the nerve axons which give rise to the amphidial cilia are arranged around the outside of the gland; anteriorly these axons are characteristically flattened. A granular secretion is produced by the amphidial gland and passes via the reticulum to the double cuticular channel, thus bathing the ciliary bundle. The ultrastructure of the amphids is discussed in relation to functional considerations.


Should I use steroid injections to treat shoulder pain during the COVID-19 pandemic?
Corticosteroid (CS) injections are commonly used both in primary and secondary care in the management of chronic shoulder pain. On March 11, 2020, the World Health Organization declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the causative virus for COVID-19) outbreak a pandemic and global health emergency. There was initial concern with the use of CS injections during the COVID-19 pandemic because of the increased potential for adrenal insufficiency and altered immune response. This led to the publication of guidelines from societies around the world. The aim of this article is to critically appraise the evidence that form the rationale behind these guidelines and to review the alternative treatment options for the management of shoulder pain during the COVID-19 pandemic.


Patient perspectives of prostate cancer screening vary by race following 2018 guideline changes.
The 2018 US Preventive Services Task Force guidelines recommend individualizing prostate cancer screening in 55- to 69-year-old men. Given the higher incidence of prostate cancer in African American (AA) compared to non-Hispanic White (NHW) men, this study compared reported rates of prostate-specific antigen (PSA) screening hypothesizing that it would not be commensurate with the relative risk between these two groups. Using the 2020 Behavioral Risk Factor Surveillance System, we identified 43,685 men (40,301 NHW and 3384 AA) interviewed about PSA screening. AA men had an odds ratio (OR) of 0.80 (95% confidence interval [CI], 0.69-0.93; p = .004) of reporting PSA screening; sequentially correcting for access to care, smoking, and age had minimal effect on this finding, but when correcting for income significantly attenuated this difference (OR, 0.95; 95% CI, 0.81-1.12). Further adding education level eliminated the effect size of AA race entirely with OR, 0.99 (95% CI, 0.84-1.17; p = .91). Further analysis found significant interaction between education and race, with college-educated AA men having 1.42 OR of receiving screening compared to college-educated NHW men. Despite prostate cancer being more common and having higher population-level mortality in AA than NHW men, PSA screening and education patterns do not reflect this increased risk even when adjusting for health access disparities. The authors' findings of significant effect from both income and education suggest that systemic racism is an important factor in the observed difference in PSA screening between AA men and NHW men. In the United States, prostate cancer is more common in African American men New guidelines from 2018 encourage physicians to consider risk factors in deciding whether or not to recommend screening, but overall African American men continue to be screened at a lower rate than non-Hispanic White men This effect disappears when correcting for income and education level, suggesting that several factors including systemic racism, medical mistrust, and self-advocacy may impact this observed difference.