Identification of amylase isoenzymes in intestinal contents.
Samples of intestinal contents were obtained from 16 patients: 5 from the midjejunum, 10 from the distal ileum, and 1 from the cecum. The presence of pancreatic and nonpancreatic isoamylases in these fluids was evaluated by an inhibitor assay (Pharmacia Corporation) and by polyacrylamide gel electrophoresis. In every sample the inhibitor assay detected the presence of pancreatic-type isoamylase but not salivary-type isoamylase. Electrophoresis confirmed that salivary-type isoamylase was totally absent. Therefore, in intestinal disorders which disrupt the intestinal mucosal barrier (such as ischemia, perforation, ulceration, or obstruction), the amylase which escapes from the intestinal lumen and is reabsorbed into the circulation is likely to consist entirely of pancreatic-type isoamylases. In these circumstances, measurement of serum amylase isoenzymes will not distinguish acute pancreatitis from an acute intraabdominal catastrophe requiring surgery.


Validation of a screening kit to identify environmental lead hazards.
In many states, environmental lead hazards are evaluated only after a lead-poisoned child has been identified. This passive approach is problematic because only a small fraction of children are tested for lead and those with elevated blood lead levels may have irreversible developmental damage. In order to reverse this paradigm, a new lead screening kit was developed. In this study, we validated the accuracy of the kit compared to the conventional methods. Forty-five participants used the kit to collect 3 dust, 3 soil and 2 paint samples in their homes. A researcher performed an in-situ analysis of the lead content in the paint and soil using a portable X-ray fluorescence (XRF) spectrometer. The soil, paint, and dust samples collected by the participants were then analyzed by XRF ex-situ. A strong linear correlation was found between the in-situ and ex-situ measurements for soil and dust samples, and a reasonable correlation was obtained for lead content of paint samples. The kit had very high degrees of specificity (true negative rate) and sensitivity (true positive rate) for detecting hazardous levels of lead in soil and dust samples. The agreement was more moderate for paint samples because some of the paint chips provided gave different readings from the front or back surface, but in-situ XRF only reads from the front surface. Overall, the kit gave a sensitivity of 87%, a specificity of 98% and an accuracy of 96% for detection of environmental lead hazards in samples collected from the home by untrained citizens. This suggests that widespread and inexpensive lead screening could be used to successfully identify hazards and ultimately decrease environmental lead exposure in children.


Definitive care for the critically ill during a disaster: current capabilities and limitations: from a Task Force for Mass Critical Care summit meeting, January 26-27, 2007, Chicago, IL.
In the twentieth century, rarely have mass casualty events yielded hundreds or thousands of critically ill patients requiring definitive critical care. However, future catastrophic natural disasters, epidemics or pandemics, nuclear device detonations, or large chemical exposures may change usual disaster epidemiology and require a large critical care response. This article reviews the existing state of emergency preparedness for mass critical illness and presents an analysis of limitations to support the suggestions of the Task Force on Mass Casualty Critical Care, which are presented in subsequent articles. Baseline shortages of specialized resources such as critical care staff, medical supplies, and treatment spaces are likely to limit the number of critically ill victims who can receive life-sustaining interventions. The deficiency in critical care surge capacity is exacerbated by lack of a sufficient framework to integrate critical care within the overall institutional response and coordination of critical care across local institutions and broader geographic areas.


Locomotion of black howlers in a habitat with discontinuous canopy.
The locomotor behaviour of howler monkeys (genus Alouatta) has been the subject of several detailed field studies [1-6]. This paper describes the locomotor behaviour of black howler monkeys (Alouatta caraya) living in a small area of forested habitat characterized by a discontinuous canopy.


Effective Site for the Application of Extracorporeal Shock-Wave Therapy on Spasticity in Chronic Stroke: Muscle Belly or Myotendinous Junction.
To compare the effect of extracorporeal shock-wave therapy (ESWT) applied at the muscle belly and myotendinous junction on spasticity in the upper and lower limbs of chronic stroke patients. Of the 151 patients, a total of 80 patients with stroke-induced spasticity on the elbow flexor and 44 patients on the knee flexor were enrolled for a prospective, randomized clinical trial. The patients were divided into control, muscle belly, and myotendinous junction groups, and a total of three ESWT sessions (0.068-0.093 mJ/mm2, 1,500 shots) were conducted at one per week. A Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS) were collected at the baseline and at 1 week after each session. After interventions, the MAS and MTS of both the belly and the junction groups showed positive effects from the ESWT on spasticity in the elbow and knee flexors, but the control group did not. The results also tended to improve after each session until the entire intervention was completed. However, there was no significant difference between the belly and junction groups. ESWT could be effective for treating chronic spasticity after stroke when applied to muscle belly or myotendinous junction.


[Pathological and clinical correlations in renal AA amyloidosis: A Moroccan series of 30 cases].
Study of histological and clinical correlations of 30 cases of renal amyloidosis AA diagnosed between November 2010 and December 2012. The main causes associated with amyloidosis AA were represented by chronic infectious diseases (60%). Nephrotic syndrome and renal failure were observed in 94% and 73% respectively. The distribution of amyloid deposits: 90% of patients had a glomerular form and 10% had a vascular form. Inflammatory reaction associated with AA renal amyloidosis was present in 50% of cases. This inflammation was observed near amyloid deposits associated with a deposition of immunoglobulin chains and/or complement factors. Our study confirms the predominance of AA amyloidosis complicating chronic infectious diseases, especially tuberculosis. Our data point out a relationship between the morphology of renal AA amyloidosis, its clinical presentation and prognosis.


Recommendations for risk stratified use of cardiac computed tomography for congenital heart disease during the COVID-19 pandemic.
The impact of the coronavirus disease (COVID-19) pandemic in the United States and around the world has required significant changes to medical practice. Amidst the rapidly evolving public health emergency, hospital centers have been required to postpone elective procedures, preserve personal protective equipment (PPE), practice social distancing and limit staff exposures. Patients with congenital heart disease (CHD) often need urgent evaluation, most commonly for preprocedural evaluation. We have stratified the most common indications for cardiac computed tomography (CCT) imaging in patients with CHD to help guide care for these patients during the COVID-19 pandemic including considerations for reopening.


Current Advances in Endovascular Treatment of Intracranial Atherosclerotic Disease and Future Prospective.
Medical therapy is the first line of treatment for intracranial atherosclerotic disease (ICAD). Percutaneous transluminal angioplasty and stenting (PTAS) are mainly considered for those patients with severe stenosis and recurrent events despite aggressive medical therapy. In this review, we discuss the application of PTAS as a treatment option for ICAD and its future prospect. We did the literature review of the key articles and guidelines to elaborate on the role of PTAS in the management of ICAD based on the current data and expert opinion. We searched PubMed, Google Scholar, and Scopus up to August 2020, and included articles published only in the English language. Since the publication of the results from SAMMPRIS and VISSIT trials, stenting is no longer recommended for secondary stroke prevention in patients with symptomatic ICAD. However, recent clinical studies on intracranial stenting for a subgroup of ICAD patients have shown promising results, likely due to better patient selection and continued advancement of endovascular techniques. There exists a lack of consensus regarding the best endovascular treatment approach (e.g., angioplasty alone or balloon mounted stent vs. self-expanding stent with or without prior angioplasty) or management of in-stent restenosis. Another area of clinical controversy relates to the ideal use and duration of antiplatelet therapy.


Physisporinus vitreus: a versatile white rot fungus for engineering value-added wood products.
The credo of every scientist working in the field of applied science is to transfer knowledge "from science to market," a process that combines (1) science (fundamental discoveries and basic research) with (2) technology development (performance assessment and optimization) and (3) technology transfer (industrial application). Over the past 7 years, we have intensively investigated the potential of the white rot fungus, Physisporinus vitreus, for engineering value-added wood products. Because of its exceptional wood degradation pattern, i.e., selective lignification without significant wood strength losses and a preferential degradation of bordered pit membranes, it is possible to use this fungus under controlled conditions to improve the acoustic properties of tonewood (i.e., "mycowood") as well as to enhance the uptake of preservatives and wood modification substances in refractory wood species (e.g., Norway spruce), a process known as "bioincising." This minireview summarizes the research that we have performed with P. vitreus and critically discusses the challenges encountered during the development of two distinct processes for engineering value-added wood products. Finally, we peep into the future potential of the bioincising and mycowood processes for additional applications in the forest and wood industry.


Differential gene expression by Osterix knockdown in mouse chondrogenic ATDC5 cells.
Osterix (Osx) is a transcription factor required for osteoblast differentiation during intramembranous and endochondral ossification. Recently, several reports have described novel functions of Osx in chondrocyte differentiation. In an in vitro study, in which the effects of Osx gene silencing were examined in mouse chondrogenic ATDC5 cells, chondrocyte marker genes were found to be expressionally downregulated and chondrocyte differentiation reduced. On the other hand, in vivo studies based on chondrocyte-specific Osx knockouts demonstrated impaired endochondral bone formation with delayed chondrocyte differentiation and reduced cartilage matrix ossification. However, little is known about the mechanism or targets of Osx involved in the control of chondrocyte differentiation. Here, we attempted to high-density of Affymetrix GeneChip microarray to investigate global gene expression profile changes caused by Osx knockdown in ATDC5 chondrocytes. The mRNA expressions of 112 genes were significantly modified by Osx knockdown: 68 genes were upregulated and 44 genes downregulated. Functional categories of gene expression classified by gene ontology demonstrated that genes related to cell adhesion, development, and signal transduction were highly affected by Osx knockdown. The expressions of differential genes, such as Sfrp2, Sema3a, Nox4, Rgs4, Zfp521, Has2, Sox6, Scn2a1, Sirpa, and Thbs2, were validated by quantitative real-time PCR. This study shows that expression profiling can be used to identify genes that are transcriptionally modified following Osx knockdown and to reveal the molecular mechanism of chondrocyte differentiation regulated by Osx.


The influence of organic-binding metals on the biogas conversion of sewage sludge.
The anaerobic conversion of sewage sludge to methane-rich biogas is an important bioenergy strategy that has been hindered by low conversion efficiency. The poorly understood mechanism of the influence of the key structural component in sludge is responsible for this. The influence of organic-binding metals (OBM), which account for a substantial proportion of metals in sludge, on biogas conversion of both sewage sludge and model sludge were explored in this study. It is observed that the net cumulative methane production of sludge decreased by 23% with the increase of OBM content, implying the crucial role of the OBM in anaerobic sludge digestion. Experimental results showed that the apparent activation energy of sludge organic solubilisation and the median particle size of sludge particulates increased with increasing OBM content, whereas the surface binding sites for enzymes decreased, indicating that the stability of the sludge floc was reinforced by the effect of OBM. Further analyses of the sludge structure revealed that a high OBM content (>2.5% total solids in the present study) compacted the sludge organic matter, restricted the molecular mobility and deteriorated the depolymerisation of the biopolymers by bridging and hydrogen-bonding interactions. This suggests that as a result of the effect of OBM, the hydrolysis and acidification of sludge particulate could be inhibited, resulting in poor biogas conversion. Moreover, it was further authenticated by the results from biochemical methane potential assay process. These findings can deepen the understanding of the role of OBM in sludge for biogas conversion and are important for the improvement of anaerobic sludge digestion.


Vascularized genicular osseous-periosteal flap for pseudarthrosis of the proximal phalanx of the little finger: a case report.
This study describes pseudoarthrosis of the proximal phalanx of the little finger and its successful treatment using a free vascularized genicular osseous-periosteal flap. Since this thin and pliable flap can be harvested as a small vascularized unit, it is ideal for the treatment of phalangeal pseudoarthrosis.


Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial.
There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for the treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high-oleic (HO) peanuts without added DHA (HO-RUTF) or with added DHA (DHA-HO-RUTF), improves cognition when compared with standard RUTF (S-RUTF). A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF: DHA-HO-RUTF, HO-RUTF, and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global z-score and a modified Willatts problem-solving assessment (PSA) intention score for 3 standardized problems, measured 6 mo and immediately after completing RUTF therapy, respectively. MDAT domain z-scores, plasma fatty acid content, anthropometry, and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. Among the 2565 SAM children enrolled, mean global MDAT z-scores were -0.69 ± 1.19 and -0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI: 0.01, 0.38). Children receiving DHA-HO-RUTF had higher gross motor and social domain z-scores than those receiving S-RUTF. The PSA problem 3 scores did not differ by dietary group (OR: 0.92, 95% CI: 0.67, 1.26 for DHA-HO-RUTF). After 4 wk of treatment, plasma phospholipid EPA and α-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared with S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF (P < 0.001). Treatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit 6 mo after completing diet therapy. This treatment should be explored in operational settings. This trial was registered at clinicaltrials.gov as NCT03094247.


Acyl Radicals from α-Keto Acids Using a Carbonyl Photocatalyst: Photoredox-Catalyzed Synthesis of Ketones.
Acyl radicals have been generated from α-keto acids using inexpensive and commercially available 2-chloro-thioxanthen-9-one as the photoredox catalyst under visible light illumination. These reactive species added to olefins or coupled with aryl halides via a bipyridyl-stabilized Ni(II) catalyst, enabling easy access to a diverse range of ketones. This reliable, atom-economical, and eco-friendly protocol is compatible with a wide range of functional groups.


Clonidine and the hyper-responsiveness of dorsal horn neurones following morphine withdrawal in the spinal cat.
In barbiturate-anaesthetized spinal cats, exaggerated responses of dorsal horn neurones to impulses in unmyelinated primary afferents, were produced by administering naloxone after iontophoretic administration of morphine in the substantia gelatinosa. Clonidine, given both intravenously (5-10 micrograms/kg) and iontophoretically into the substantia gelatinosa, reduced cell responses to pre-naloxone values. The action of clonidine was reversed by idazoxan. This spinal action of clonidine may be an important component in the suppression of the opiate withdrawal syndrome observed in the whole animal.


Prognostic value of long non-coding RNAs in triple negative breast cancer: A PRISMA-compliant meta-analysis.
Triple-negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer. Accumulating evidence showed long non-coding RNAs (lncRNAs) are abnormally expressed in TNBC and could be valuable prognostic tools for TNBC patients. This study aims to research the prognostic value of lncRNAs in TNBC, using the meta-analysis method. We performed a detailed literature search on Pubmed, Scopus, and Web of Science for studies on the prognostic value of lncRNAs in TNBC. The meta-analysis method was used to determine the relationship between lncRNAs expression and survival of TNBC patients. A total of 2803 TNBC patients and 24 lncRNAs from 27 different articles were included in the present study. Subgroup analysis demonstrated that overexpression of lncRNAs in a group that is upregulated in TBNC showed a significant association with poor overall survival (HR = 1.86, 95%CI = 1.45-2.27, I = 41.9%) and disease-free survival (HR = 1.85, 95%CI = 1.37-2.33, I = 0%). Conversely, overexpression of lncRNAs in a downregulation group was markedly related to good overall survival (HR = 0.60, 95%CI = 0.43-0.77, I = 28.6%). Moreover, expression of lncRNA SNHG12, MALAT1, HOTAIR, HIF1A-AS2, HULC, LINC00096, ZEB2-AS1, LUCAT1, and LINC000173 showed a marked correlation with positive lymph node metastasis (LNM), while lncRNA MIR503HG, GAS5, TCONS_l2_00002973 showed the opposite effect. High expression level of MALAT1, HIF1A-AS2, HULC, LINC00096, ADPGK-AS1, ZEB2-AS1, LUCAT1 were positively correlated with distant metastasis (DM), while lncRNA MIR503HG showed the opposite effect. In addition, the mechanisms of lncRNAs in TNBC were summarized. This meta-analysis demonstrated that abnormally expressed lncRNA were significantly associated with the survival of TNBC patients and may serve as biomarkers and therapeutic targets for TNBC prognosis.


A Novel β-Glucosidase From Chryseobacterium scophthalmum 1433 for Efficient Rubusoside Production From Stevioside.
As a natural sweetening and solubilizing agent, rubusoside has great potential in the application of healthy beverages and pharmaceuticals. However, the direct extraction and purification of rubusoside from raw materials is inefficient. In this work, a novel β-glucosidase (CsBGL) was obtained from Chryseobacterium scophthalmum 1433 through screening of the environmental microorganisms. CsBGL markedly hydrolyzed sophorese (Glcβ1-2Glc) and laminaribiose (Glcβ1-3Glc), but for steviol glycosides, it only hydrolyzed the C-13/C-19-linked sophorese, instead of the C-13/C-19-linked Glcβ1-2[Glcβ1-3]Glc trisaccharide and Glcβ1-monosaccharide. It efficiently hydrolyzed stevioside (240 g/L) to produce rubusoside (99% yield) at 47.5°C for 70 min. Even when using a crude steviol glycosides extract (500 g/L) containing ∼226 g/L stevioside as the substrate, CsBGL could also convert stevioside to rubusoside (99% yield) at 47.5°C for 2 h, in which the rubusoside concentration increased from the initial 42 g/L to the final 222 g/L. These results reveal that CsBGL would be a promising biocatalyst for the industry-scale production of rubusoside from stevioside or/and the crude steviol glycosides extract.


Revealing the composition-dependent structural evolution fundamentals of bimetallic nanoparticles through an inter-particle alloying reaction.
Alloy nanoparticles represent one of the most important metal materials, finding increasing applications in diverse fields of catalysis, biomedicine, and nano-optics. However, the structural evolution of bimetallic nanoparticles in their full composition spectrum has been rarely explored at the molecular and atomic levels, imparting inherent difficulties to establish a reliable structure-property relationship in practical applications. Here, through an inter-particle reaction between [Au44(SR)26]2- and [Ag44(SR)30]4- nanoparticles or nanoclusters (NCs), which possess the same number of metal atoms, but different atomic packing structures, we reveal the composition-dependent structural evolution of alloy NCs in the alloying process at the molecular and atomic levels. In particular, an inter-cluster reaction can produce three sets of Au x Ag44-x NCs in a wide composition range, and the structure of Au x Ag44-x NCs evolves from Ag-rich [Au x Ag44-x (SR)30]4- (x = 1-12), to evenly mixed [Au x Ag44-x (SR)27]3- (x = 19-24), and finally to Au-rich [Au x Ag44-x (SR)26]2- (x = 40-43) NCs, with the increase of the Au/Ag atomic ratio in the NC composition. In addition, leveraging on real-time electrospray ionization mass spectrometry (ESI-MS), we reveal the different inter-cluster reaction mechanisms for the alloying process in the sub-3-nm regime, including partial decomposition-reconstruction and metal exchange reactions. The molecular-level inter-cluster reaction demonstrated in this study provides a fine chemistry to customize the composition and structure of bimetallic NCs in their full alloy composition spectrum, which will greatly increase the acceptance of bimetallic NCs in both basic and applied research.


Use of electron microscopy and an enzyme-linked immunosorbent assay for the detection of rotaviruses in neonatal calf diarrhea.
Electron microscopy and an enzyme-linked immunosorbent assay were compared for the diagnosis of rotaviruses associated with neonatal calf diarrhea. One hundred percent correlation was observed when 125 samples were tested by both techniques. Both techniques were equally efficient in detecting rotaviruses. The enzyme-linked immunosorbent assay was more sensitive but being specific could not detect other viruses.


Rectal cancer with complete clinical response after neoadjuvant chemoradiotherapy, surgery, or "watch and wait".
The purpose of this study was to compare the outcomes of patients treated with chemoradiotherapy with a complete clinical response followed by either a "watch and wait" strategy or a total mesorectal excision. This was an observational retrospective study from a single institute. Patients with locally advanced rectal cancer following chemoradiotherapy with a complete clinical response from January 1, 2007 to December 31, 2014 were included. The study population consisted of 18 patients who opted for a "watch and wait" policy and 26 patients who underwent radical surgery after achieving a complete clinical response. Patients had no documented treatment complications under the watch and wait policy, while 13 patients who underwent radical surgery experienced significant morbidity. There were two local recurrences in the watch and wait group; both were treated with salvage resection and had no associated mortality. In the radical surgery group, 1 patient showed an incomplete pathologic response (ypT0N1), and the remaining 25 patients showed complete pathologic responses; 1 had a distant recurrence, which was managed non-operatively, and 2 patients died of unrelated causes. The 5-year overall survival rate and median disease-free survival time were 100% and 69.78 months in the watch and wait group and 92.30% and 89.04 months in the radical surgery group. A watch and wait policy avoids the morbidity associated with radical surgery and preserves oncologic outcomes in our retrospective study from a single institute. It could be considered a therapeutic option in patients with locally advanced rectal cancer following chemoradiotherapy with a complete clinical response.


Does Oxidative Stress Along with Dysbiosis Participate in the Pathogenesis of Asthma in the Obese?
The most important environmental factor that can play a key role in the development of asthma in the obese is overproduction of reactive oxygen species (ROS). The aim of the study was to examine changes in the concentration of oxidative stress parameters in the lungs, bronchoalveolar lavage (BAL) fluid and blood of mice in models of asthma or/and obesity caused by high-fat diet (HFD). The concentrations of 4-HNE and isoprostanes in the lungs of the animals were measured. BAL fluid levels of hydrogen peroxide were marked. Additionally, thiobarbituric acid reactive substances (TBARS) and ferric reducing ability of plasma (FRAP) were used as biomarkers of oxidative stress in the blood. Administration of lipoic acid (LA), a probiotic with standard-fat diet (SFD, 10% fat) and low-fat diet (LFD, 5% fat) significantly decreased the concentration of 4-HNE as compared to the OVA (ovalbumin) + HFD group (p < 0.05). Treatment with low-fat diet or LFD in combination with apocynin insignificantly decreased H2O2 values as compared to the OVA + HFD group. Supplementation of probiotic with SFD and LFD significantly decreased the concentration of TBARS as compared to the OVA + SFD and saline + HDF groups (p < 0.05). Significantly lower concentrations of TBARS were also observed in the LA plus LFD group (p < 0.05) as compared to the OVA + HFD group. Low-fat diet with probiotic significantly increased the concentration of FRAP as compared to the obese mice (p = 0.017). Treatment with LFD in combination with LA significantly increased FRAP values as compared to the obese and obese asthmatic mice (p < 0.001).


Role of the physician in bereavement.
The purpose of this article is to set forth a clear and concise guide for physicians to use in their treatment of the bereaved. The physician's attitudes toward death and dying, as well as normal and abnormal grief reactions, are reviewed. The role of the physician prior to the time of death, at the time of death, and after the death are discussed. Models of hospital-based programs that can be of significant help to physicians in treating the bereaved are presented also.


The association between parent-reported provider communication quality and child obesity status: Variation by parent obesity and child race/ethnicity.
To examine the association between healthcare provider communication quality and child obesity status, and the role of parent obesity and child race/ethnicity regarding this association. We conducted a cross-sectional secondary data analysis with the 2011-2013 Medical Expenditures Panel Survey of parents with children ages 6-12 (n=5390). We used multivariable logistic regression to examine the association of parent-reported healthcare provider communication quality (explaining well, listening carefully, showing respect, and spending enough time) with child obesity status, and effect modification by parent obesity and child race/ethnicity. Parents of obese children were more likely to report that their child's healthcare provider listened carefully (OR=1.41, p=0.002) and spent enough time (OR=1.33, p=0.022) than parents of non-obese children. Non-obese parents of obese children experienced better communication in the domains of listening carefully (p<0.001) and spending enough time (p=0.007). Parents of obese non-Hispanic Asian children and non-Hispanic Black children were more likely to report that providers explained things well (p=0.043) and listened carefully (p=0.012), respectively. Parents of obese children experienced better communication if parents were non-obese or children were non-Hispanic Black or Asian. Healthcare providers should ensure effective communication with obese parents of obese children.


Comparison of DVH parameters and loading patterns of standard loading, manual and inverse optimization for intracavitary brachytherapy on a subset of tandem/ovoid cases.
Comparison of inverse planning with the standard clinical plan and with the manually optimized plan based on dose-volume parameters and loading patterns. Twenty-eight patients who underwent MRI based HDR brachytherapy for cervix cancer were selected for this study. Three plans were calculated for each patient: (1) standard loading, (2) manual optimized, and (3) inverse optimized. Dosimetric outcomes from these plans were compared based on dose-volume parameters. The ratio of Total Reference Air Kerma of ovoid to tandem (TRAK(O/T)) was used to compare the loading patterns. The volume of HR CTV ranged from 9-68 cc with a mean of 41(±16.2) cc. Mean V100 for standard, manual optimized and inverse plans was found to be not significant (p=0.35, 0.38, 0.4). Dose to bladder (7.8±1.6 Gy) and sigmoid (5.6±1.4 Gy) was high for standard plans; Manual optimization reduced the dose to bladder (7.1±1.7 Gy p=0.006) and sigmoid (4.5±1.0 Gy p=0.005) without compromising the HR CTV coverage. The inverse plan resulted in a significant reduction to bladder dose (6.5±1.4 Gy, p=0.002). TRAK was found to be 0.49(±0.02), 0.44(±0.04) and 0.40(±0.04) cGy m(-2) for the standard loading, manual optimized and inverse plans, respectively. It was observed that TRAK(O/T) was 0.82(±0.05), 1.7(±1.04) and 1.41(±0.93) for standard loading, manual optimized and inverse plans, respectively, while this ratio was 1 for the traditional loading pattern. Inverse planning offers good sparing of critical structures without compromising the target coverage. The average loading pattern of the whole patient cohort deviates from the standard Fletcher loading pattern.


Serum MPO levels and activities are associated with angiographic coronary atherosclerotic plaque progression in type 2 diabetic patients.
The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P < 0.001). We categorized these patients with diabetes into MPO level or activity tertile subgroups. Significant differences in the plaque progression ratio and prominent changes in the minimal lumen diameter, stenosis diameter and coronary artery stenosis score were observed across the tertile subgroups of MPO levels and activities (all P < 0.01). Moreover, serum MPO levels and activities correlated significantly with these indices of coronary artery disease severity after adjustment for other risk factors. Multivariable regression analyses revealed that serum MPO levels and activities remained independently associated with plaque progression, in addition to smoking, hypertension and CRP levels (all P < 0.05). Serum MPO levels and activities are significantly associated with coronary atherosclerotic plaque progression in patients with type 2 diabetes.


The response of adrenergic neurones to axotomy and nerve growth factor.
Division of the axons of adrenergic neurones by crushing the postganglionic nerve trunks of rat superior cervical ganglia (SCG) at 6 days of age resulted in a permanent atrophy of the SCG reflected by a persistent decrease in the total protein content and in the activities of the enzymes tyrosine hydroxylase and DOPA decarboxylase. Administration of nerve growth factor (NGF) to rats with unilateral axotomy at a dose of 10 mug/g/day for the period 7-21 days of age resulted in hypertrophy of both normal and axotomised SCG. There was a progressive rise in the total protein content and in the activities of the two enzymes till the end of the treatment period in both SCG. After treatment ceased there was a progressive fall in the total protein content and activities of the two enzymes reaching a stable level after 4 weeks. The level reached for treated unoperated SCG remained elevated when compared to untreated control SCG. Axotomised treated SCG had approximately the same biochemical parameters as untreated control SCG and very much elevated over untreated axotomised SCG. These final levels persisted for at least 56 days after treatment had ceased. Animals showed a persistent ptosis after axotomy at 6 days of age but treatment with NGF resulted in a functional recovery by 11 weeks of age. It is suggested that there is normally a retrograde transfer of a factor durind development from the target cell to the perikarya of the neurone permitting survival if the appropriate connections are made. Failure to make such a contact results in cedd death. The cell death occurring normally, and the cell death resulting from axotomy, can both be prevented by NGF treatment leading to an hypertrophy of both SCG. This consistent with the hypothesis than NGF is the retrograde trophic agent for the sympathetic nervous system in the developing animal.


Serum proprotein convertase subtilisin/Kexin type 9 and vascular disease in type 2 diabetic patients.
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) levels have been suggested as novel atherosclerotic biomarker. PCSK9 plays important roles in the pathogenesis of atherosclerosis by regulating the degradation of low-density lipoprotein receptor as well as different inflammatory pathways. Considering the important prognostic role of arterial stiffness in cardiovascular disease (CVD), the aim of the study is to investigate the correlation between PCSK9 levels and arterial stiffness in a cohort of diabetic patients, without previous CV events. This cross-sectional analysis enrolled 401 Caucasian patients with type II diabetes mellitus (T2DM). PCSK9 levels were measured by ELISA test, arterial stiffness was estimated by measuring carotid-femoral pulse wave velocity (PWV). Patients were divided in three tertiles according to increasing value of PCSK9. From the I to the III tertiles, there was a significant increase in high sensitivity C-reactive protein (hs-CRP), fibrinogen and white blood cells (WBC) and a reduction in estimated glomerular filtration rate (e-GFR). Patients with higher levels of PCSK9 presented increased systolic, diastolic blood pressure, pulse pressure and PWV. PWV was significantly and directly correlated with PCSK9, fibrinogen, age, BMI and PP, and indirectly correlated with diet, lifestyle and e-GFR. Serum PCSK9 was the major predictor of PWV, justifying a 16.9% of its variation. Our study demonstrates a close association between circulating PCSK9 levels and PWV in T2DM subjects without previous CV events even after adjusting for well-known CV risk factor and pharmacological medications. Serum PCSK9 could be a useful biomarker for CV risk stratification in diabetic subjects.


Driving factors on accumulation of cadmium, lead, copper, zinc in agricultural soil and products of the North China Plain.
The accumulation of heavy metals in agricultural soils concerns food security. By using the Geographical Detector, this study investigated the influence of six types of factors (eleven factors) on the accumulation of Cd, Pb, Cu, Zn in agricultural soil and products of the North China Plain and confirmed the dominant factor. The results showed that heavy metals had accumulated in regional agricultural soils and the accumulation of Cd was severe. The accumulation of heavy metals was significantly influenced by policy factors (the management and reduction in usage of fertilizers and pesticides), fertilization factors (application of organic and chemical fertilizers), pesticide factors (application of herbicide and insecticide) and atmospheric deposition factors (heavy metal concentration in atmospheric deposition). The policy factor dominated the other three types of factors. Atmospheric deposition and the excess application of fertilizers and pesticides directly lead to the accumulation of heavy metals. Due to the high concentrations of heavy metals and abundant application amounts, organic fertilizers have contributed high levels of heavy metals to agricultural soils. This study suggests that formulated fertilization and action plans for pesticide reduction could effectively decrease the accumulation of heavy metals in agricultural soils and products in the study area.


Determination of a transmembrane pH difference in chloroplasts with a spin label tempamine.
We present a method for measuring the transmembrane pH difference (deltapH=pHin-pHout) in chloroplasts with a spin label TEMPAMINE (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl) accumulating inside the thylakoids in response to generation of deltapH. Experiments with chloroplasts suspended in the media of different osmolarity demonstrated that most of TEMPAMINE (TA) molecules taken up by chloroplasts were localized in the bulk of the thylakoid lumen. The DeltapH value was determined from the relationship deltapH=lg([H+]in/[H+]out) approximately equal to lg(Cin/Cout), where Cin and Cout are the concentrations of TA inside and outside the thylakoids, respectively. To quantify the internal concentration Cin, we used the threshold nature of the concentration-dependent broadening of the EPR signal from TA. It was demonstrated that spin-exchange interactions between TA molecules caused an observable broadening of the signal only when the concentration of TA exceeded the threshold level, [TA]theta approximately 2.0-2.2mM. The concentration dependencies of the signal parameters (the peak-to-peak amplitude, App, and the linewidth, deltaHpp) were described within a model of the non-homogeneous broadening of an unresolved hyperfine multiplet from the protons of TA molecule. If the concentration of TA inside the thylakoids went beyond the threshold level, the spin-exchange broadening of the EPR signal was accompanied by a reversible decrease in the signal height (parameter deltaA). By measuring the signal behavior at different levels of microwave power, we were able to discriminate between the line broadening effects caused by concentrating TA molecules inside the thylakoids or the light-induced changes in the concentration of oxygen. We developed a general algorithm for determination of the deltapH value and the internal volume of thylakoids, Vin, from the non-linear dependence of parameter deltaA on the concentration C0 of TA in a chloroplast suspension. Advantages of this method are: (i) it avoids the use of a broadening agent; (ii) it allows the internal volume of thylakoids to be evaluated; and (iii) the concentrations of TA used to measure the deltapH are below the range of concentrations that could cause the uncoupling electron transport to ATP synthesis in chloroplasts. Results of our measurements are consistent with the literature data on deltapH determinations by other methods.


National survey on the certification of competence in gynecologic surgical oncology: An AGOF (association of gynecologists in training) study.
Female malignancies can require complex surgeries with expert techniques. A French certification of competence in gynecological cancer surgery has been elaborated in 2021 to certify specialized surgeons. For trainees, this would require a practical curriculum (number of rotations in certain departments), a surgical logbook and the theoretical European exam. The objective of our work was to interrogate trainees in gynecology and obstetrics on their oncological training and their opinion on the certification. We conducted a national French prospective, observational study, using a web-based questionnaire from 06/2021-02/2022. All trainees were interrogated on their overall training in gynecological oncology. The opinion on the certification was assessed for the sub-group willing to specialize in oncological surgical gynecology. One hundred and twenty-five responded, and 66.1% wanted to specialize in surgical oncology. Many had completed one rotation in a specialized gynecological oncology center (45.3%) and in digestive surgery (48.8%). Concerning the theoretical training, 92% of the respondents believed it to be insufficient. Eighty participants (64%) wished to specialize in oncological surgical gynecology and were interrogated on the certification. The majority (65%) thought the three criteria were difficult to achieve but adequate. The most difficult criterium was the practical curriculum (70.5%) followed by the surgical logbook (55.1%) due to inequalities of training amongst French regions. Trainees in gynecology and obstetrics seem ready to take a specialized certification in surgical gynecological oncology to improve patient care. However, they expressed concerns due the disparities amongst regions in accessing certain specialized departments.


Release and elimination of methylmethacrylate monomer after intraocular lens implantation.
The potential for certain constituents in intraocular lenses, such as monomer methylmethacrylate (MMM), to induce toxic effects after intraocular implantation not only depends on their toxic potency, but also on the characteristics of their release, accumulation, and elimination from the aqueous humor. A mathematical estimation taking these factors into account shows that for a lens mass of approximately 15 mg, the concentration of MMM in the aqueous humor amounts to about 10(-4) of the respective concentration in the lens, but that value is maintained for several weeks. Therefore, experiments to test the chemical toxicity of MMM or similar lens compounds in eyes must not only take into account the actual concentration limit but also the time of exposure to the substance.


Response of plasma glicentin to intraduodenal administration of glucose in piglets.
Controversial results concerning the secretion of glicentin prompted us to investigate the response of circulating glicentin to intraduodenal administration of glucose in piglets. A 20% solution of glucose (2 g/kg) was administered into the duodenum of six piglets in a fully conscious state. As blood glucose rose, plasma insulin increased to a peak of 21 +/- 4 microU/ml. Plasma glucagon, determined by C-terminal-specific antiserum, was 70 +/- 30 pg/ml at fasting and slightly increased after the glucose load. Plasma immunoreactive glucagon measured by cross-reacting glucagon antiserum increased from the baseline of 1563 +/- 260 to a peak of 4738 +/- 415 pg/ml at 120 min. Plasma glicentin determined by antiserum R 64 was 463 +/- 81 pmol/l at baseline and reached a peak level of 1081 +/- 174 pmol/l at 90 min. The percent changes of plasma glucagon from the fasting level measured by cross-reacting antiserum and glicentin were 296 and 233%, respectively. There was a significant correlation between plasma glucagon measured by cross-reacting antiserum and glicentin (r = 0.817, P less than 0.001). Chromatography of plasma obtained during glucose load revealed the heterogeneity of glicentin. It can be concluded from the present study that glicentin is clearly secreted in response to intraluminal administration of glucose.


Chimeric human epidermal reconstructs to study the role of melanocytes and keratinocytes in pigmentation and photoprotection.
Chimeric epidermal reconstructs made with Negroid melanocytes and Caucasoid keratinocytes (or vice versa) were studied before and after UVB irradiation to understand the respective roles of these cells in tanning and photoprotection, especially lipoperoxidation and enzymatic defences against free radicals. Using this approach, we have confirmed overall the theory of the epidermal melanin unit. We have also shown that melanocytes of poorly tanning Caucasoids, which have a comparatively higher content of unsaturated fatty acids in their cell membrane, are more prone to the peroxidative effects of UV light, and that keratinocytes participate in photoprotection via phototype-dependent antioxidant enzyme activities, especially for catalase.


'They're survivors physically but we want them to survive mentally as well': health care professionals' views on providing potential late effect information.
The concept of providing personalised care plans for cancer survivors is receiving increasing attention; a recognised element of a care plan is to provide an indication of the risks and consequences of treatment. This paper reports health care professional (HCP) response to providing cancer survivors with information on potential late effects of their cancer treatment. Eighteen HCPs from five cancer centres and three general practices in the UK completed semi-structured interviews which were digitally recorded, transcribed and qualitatively analysed using framework analysis. HCPs' view of health care was that it is currently focused on acute care and needs are responded to as they may arise, including those which are late effects of cancer treatments. The concept of pre-empting a discussion of potential late effects during the survivorship phase was felt to be discordant with this approach and could impact on adjustment to life after cancer treatment. Providing cancer survivors with information on potential late effects requires further consideration. Evidence for survivor preference for late effect information and the benefit afforded to survivors who receive it could inform the practice of HCPs. If a culture of proactivity is to be encouraged regarding discussions of future potential risk, HCPs may need support in considering ways of presenting survivors with reality whilst being mindful of their need to retain hope during the survivorship phase.


Computer simulation of nerve transfer strategies for restoring shoulder function after adult C5 and C6 root avulsion injuries.
Functional ability after nerve transfer for upper brachial plexus injuries relies on both the function and magnitude of force recovery of targeted muscles. Following nerve transfers targeting either the axillary nerve, suprascapular nerve, or both, it is unclear whether functional ability is restored in the face of limited muscle force recovery. We used a computer model to simulate flexing the elbow while maintaining a functional shoulder posture for 3 nerve transfer scenarios. We assessed the minimum restored force capacity necessary to perform the task, the associated compensations by neighboring muscles, and the effect of altered muscle coordination on movement effort. The minimum force restored by the axillary, suprascapular, and combined nerve transfers that was required for the model to simulate the desired movement was 25%, 40%, and 15% of the unimpaired muscle force capacity, respectively. When the deltoid was paralyzed, the infraspinatus and subscapularis muscles generated higher shoulder abduction moments to compensate for deltoid weakness. For all scenarios, movement effort increased as restored force capacity decreased. Combined axillary and suprascapular nerve transfer required the least restored force capacity to perform the desired elbow flexion task, whereas single suprascapular nerve transfer required the most restored force capacity to perform the same task. Although compensation mechanisms allowed all scenarios to perform the desired movement despite weakened shoulder muscles, compensation increased movement effort. Dynamic simulations allowed independent evaluation of the effect of restored force capacity on functional outcome in a way that is not possible experimentally. Simultaneous nerve transfer to suprascapular and axillary nerves yields the best simulated biomechanical outcome for lower magnitudes of muscle force recovery in this computer model. Axillary nerve transfer performs nearly as well as the combined transfer, whereas suprascapular nerve transfer is more sensitive to the magnitude of reinnervation and is therefore avoided.


Enhanced immunogenic potential of cancer immunotherapy antibodies in human IgG1 transgenic mice.
ADA Anti-Drug Antibodies; BCR B Cell Receptor; BId Idiotype-specific B Cell; BiTE Bispecific T cell Engager; BMC Bone Marrow Chimeric Mice; BSA Bovine Serum Albumin; CDR Complementary Determining Region; CEA Carcinoembryonic Antigen; CIT Cancer Immunotherapy; CitAbs Cancer Immunotherapy Antibodies; DC Dendritic Cell; ELISA Enzyme-Linked Immunosorbent Assay; FcRn Neonatal Fc Receptor; FcyR Fc gamma Receptor; GM-CSF Granulocyte-Macrophage Colony Stimulating Factor; gMFI Geometric Mean Fluorescence Intensity; H Heavy Chain; IC Immune Complex; Id Idiotype; IgA Immunoglobulin alpha; IgG1 Immunoglobulin gamma 1; IL-2 Interleukin 2; IL-2R Interleukin 2 Receptor; IL2v Interleukin 2 Variant; IVIG1 Intravenous Immunoglobulin 1; KLH Keyhole Limpet Hemocyanin; L Light Chain; MAPPs MHC-associated Peptide Proteomics; MHC Major Histocompatibility Complex; PBMC Peripheral Blood Mononuclear Cells; PBS Phosphate Buffered Saline; SHM Somatic Hypermutation; scFv Single-chain Variable Fragment; TCR T cell Receptor; TFc Fc-specific T cell; TId Id-specific T cell; UV Ultraviolet; V Variable.


Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: Reframing the Debate.
Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has been reported in ~5%-10% of critically ill COVID-19 patients. However, incidence varies widely (0%-33%) across hospitals, most cases are unproven, and CAPA definitions and clinical relevance are debated. We reframed the debate by asking, what is the likelihood that patients with CAPA have invasive aspergillosis? We use diagnostic test performance in other clinical settings to estimate positive predictive values (PPVs) and negative predictive values (NPVs) of CAPA criteria for invasive aspergillosis in populations with varying CAPA incidence. In a population with CAPA incidence of 10%, anticipated PPV/NPV of diagnostic criteria are ~30%-60%/≥97%; ~3%-5% of tested cohort would be anticipated to have true invasive aspergillosis. If CAPA incidence is 2%-3%, anticipated PPV and NPV are ~8%-30%/>99%. Depending on local epidemiology and clinical details of a given case, PPVs and NPVs may be useful in guiding antifungal therapy. We incorporate this model into a stepwise strategy for diagnosing and managing CAPA.


Incidence of radiculopathy following lumboperitoneal shunt placement without fluoroscopy for normal pressure hydrocephalus.
Spinal catheter insertion in lumboperitoneal shunt (LPS) surgery for normal pressure hydrocephalus (NPH) can result in radiculopathy due to mechanical irritation of the nerve roots of the cauda equina. Here, we analyzed the position of LPS shunts placed without portable fluoroscopy in 72 patients, a subset of whom developed postoperative radiculopathy. We retrospectively analyzed how frequently 72 consecutive NPH patients experienced radiculopathy following LPS catheter placement performed without intraoperative fluoroscopy. The rate of incorrect catheter placement was 15.3% (11/72 cases). We observed that is, downward placement in 6.9% (5/72 cases), hyperflexion in 6.9% (5/72 cases), and subcutaneous migration in 1.4% (1/72 cases) patients. One patient with initial correct LPS placement developed radicular pain 5-day postoperatively attributed to 1-cm of catheter movement; they recovered simply by utilizing oral analgesics for 1-month duration. LPS insertion without fluoroscopic guidance resulted in a 15.3% risk of spinal catheter displacement. We suggest, therefore, that intraoperative imaging guidance be utilized for the placement of LPS in patients with NPH and/or for other pathology to avoid the 15.3% risk of postoperative radiculopathy.


A modified electroimmunoassay technique for uromucoid in urine.
An electroimmunoassay technique for the estimation of urine uromucoid has been studied in an effort to improve its performance. It was found that strict attention to specimen collection, preservation and storage was important. The conditions used for the production of immunologically active uromucoid subunits utilising sodium dodecyl sulphate were found to be critical, needing rigid standardisation if acceptable precision is to be achieved.


An immunocytochemical analysis of the lateral geniculate complex in the pigeon (Columba livia).
The lateral geniculate complex (GL) of pigeons was investigated with respect to its immunohistochemical characteristics, retinal afferents, and the putative transmitters/modulators of its neurons. The distributions of serotonin-, choline acetyltransferase-, glutamic acid decarboxylase-, tyrosine hydroxylase-, neuropeptide Y- (NPY), substance P- (SP), neurotensin- (NT), cholecystokinin- (CCK), and leucine-enkephalin- (L-ENK) like immunoreactive perikarya and fibers were mapped. Retinal projections were studied following injections of Rhodamine-B-isothiocyanate into the vitreous. Transmitter-specific projections onto the visual Wulst and the optic tectum were studied by simultaneous double-labelling of retrograde tracer molecules and immunocytochemical labelling. The GL can be divided into three major subdivisions, the n. geniculatus lateralis, pars dorsalis (GLd; previously designated as the n. opticus principalis thalami, OPT), the n. marginalis tractus optici (nMOT), and the n. geniculatus lateralis, pars ventralis (GLv). All three subdivisions are retinorecipient. The GLd can be further subdivided into at least five components differing in their immunohistochemical characteristics: n. lateralis anterior (LA); n. dorsolateralis anterior thalami, pars lateralis (DLL), n. dorsolateralis anterior thalami, pars magnocellularis (DLAmc); n. lateralis dorsalis nuclei optici principalis thalami (LdOPT); and n. suprarotundus (SpRt). The LdOPT consists of an area of dense CCK-like and NT-like terminals of probable retinal origin. Three subnuclei (DLL, DLAmc, SpRt) were shown to project to the visual Wulst. Cholinergic and cholecystokinergic relay neurons participated in this projection. The nMOT occupies a position between the GLd and GLv and encircles the rostral pole of n. rotundus and the LA. It is characterized mainly by medium sized NPY-like perikarya which were shown to project onto the ipsilateral optic tectum. Bands of NPY-like fibers in the tectal layers 2, 4, and 7 could at least in part be due to this projection of the nMOT. Most of the antisera used revealed transmitter/modulator-specific fiber systems in the GLv which often showed a layer-specific distribution. Perikaryal labelling was only obtained with glutamic acid decarboxylase. On the basis of its chemoarchitectonics, topography, and connectional pattern, the GLd complex of pigeons is most directly equivalent to the mammalian GLd. However, although the different subdivisions of the avian GLd may represent functionally different channels within the thalamofugal pathway similar to the lamina-specific differentiation within the mammalian geniculostriate projection, direct comparison of subnuclei of birds and mammals is not justified at this time. The nMOT appears similar to the intergeniculate leaflet (IGL) and the avian GLv clearly corresponds in many features to the mammalian GLv.


Adaptation, isolation by distance and human-mediated transport determine patterns of gene flow among populations of the disease vector Aedes taeniorhynchus in the Galapagos Islands.
The black salt-marsh mosquito (Aedes taeniorhynchus) is the only native mosquito in the Galapagos Islands and potentially a major disease vector for Galapagos wildlife. Little is known about its population structure, or how its dynamics may be influenced by human presence in the archipelago. We used microsatellite data to assess the structure and patterns of A. taeniorhynchus gene flow among and within islands, to identify potential barriers to mosquito dispersal, and to investigate human-aided transport of mosquitoes across the archipelago. Our results show that inter-island migration of A. taeniorhynchus occurs frequently on an isolation by distance basis. High levels of inter-island migration were detected amongst the major ports of the archipelago, strongly suggesting the occurrence of human-aided transport of mosquitoes among islands, underlining the need for strict control measures to avoid the transport of disease vectors between islands. The prevalence of filarial nematode infection in Galapagos flightless cormorants is correlated with the population structure and migration patterns of A. taeniorhynchus, suggesting that A. taeniorhynchus is an important vector of this arthropod-borne parasite in the Galapagos Islands. Therefore mosquito population structure in Galapagos may have the potential to influence mosquito-borne parasite population dynamics, and the subsequent impacts of such pathogens on their host species in the islands.


Oral prostaglandin E analogues induce intestinal migrating motor complexes after a meal in dogs. Evidence for a central mechanism.
The effects of oral, intravenous, and intracerebroventricular administration of synthetic derivatives of prostaglandins E1 (misoprostol) and E2 (enprostil) on postprandial gastrointestinal motility were investigated in dogs chronically fitted with strain gauge transducers on the antrum and the proximal and middle jejunum. Synthetic prostaglandin E analogues administered orally at a dose of 20-50 micrograms/kg 15 min before the meal did not modify the postprandial pattern of gastric contractions but suppressed the spontaneous postprandial irregular activity on the jejunum and induced a cyclic pattern of migrating motor complexes for 4-6 h after the meal. These postprandial migrating motor complexes induced by prostaglandin E were propagated between the two recording sites and had a period similar to that observed in the fasted state. However, the duration of phase 2 was significantly increased and the amplitude of the phase 3 decreased. This jejunal cyclic motor pattern was reproduced by administration of synthetic prostaglandin E derivatives either intravenously (4-10 micrograms/kg) 15 min before the meal or intracerebroventricularly (50 ng/kg) 1 h after the meal. The intestinal migrating motor complex activity observed after oral administration of synthetic prostaglandin E derivatives was abolished by the previous intracerebroventricular (40 micrograms/kg) but not intravenous (200 micrograms/kg) administration of SC-19220, a receptor antagonist of prostaglandin E. These results suggest that oral administration of synthetic prostaglandin E1 (misoprostol) or prostaglandin E2 (enprostil) analogues before a meal induces postprandial migrating motor complexes on the jejunum in dogs through a mechanism involving central prostaglandin receptors.


Flight morphology of Neotropical butterflies: palatability and distribution of mass to the thorax and abdomen.
We test whether palatability of Neotropical butterflies is associated with distribution of mass to the thorax and abdomen. Thoracic mass is predominantly muscle mass, whereas abdominal mass includes organs of digestion, food storage, and reproduction. To escape from predation, butterflies palatable to the rufous-tailed jacamar (Galbula ruficauda) use fast, erratic flight, whereas unpalatable butterflies have defensive chemicals and slow, regular flight patterns. We adjusted for effects of phylogeny and report partial correlations for two levels of analysis: 1) comparisons among-lineage means, which test for correlations between traits of distantly related lineages, and 2) comparisons among deviations from lineage means (or within lineages), which test for correlations between traits of more closely related species.Among lineages for both males (n=10 lineages) and females (n=9), palatability and thoracic mass were positively correlated, whereas palatability and abdominal mass were negatively correlated. An inverse correlation between thoracic and abdominal mass is a consequence of the two segments composing 75% of the total body mass. Predation, indexed by palatability, may select for increased flight speed and thoracic mass at the expense of the abdomen, but relative flight speed and thoracic mass were not significantly correlated.Within lineages (n=45 species for each sex), thoracic mass was uncorrelated with palatability in both sexes. Relative flight speed correlated positively with thoracic mass and negatively with body mass. Palatability and abdominal mass were negatively correlated for males but not females. Hence differences between the sexes in mass distribution suggest differences in reproductive constraints and predation stress.


Age-related changes in human skeletal muscle microstructure and architecture assessed by diffusion-tensor magnetic resonance imaging and their association with muscle strength.
Diffusion-tensor magnetic resonance imaging (DT-MRI) offers objective measures of muscle characteristics, providing insights into age-related changes. We used DT-MRI to probe skeletal muscle microstructure and architecture in a large healthy-aging cohort, with the aim of characterizing age-related differences and comparing these to muscle strength. We recruited 94 participants (43 female; median age = 56, range = 22-89 years) and measured microstructure parameters-fractional anisotropy (FA) and mean diffusivity (MD)-in 12 thigh muscles, and architecture parameters-pennation angle, fascicle length, fiber curvature, and physiological cross-sectional area (PCSA)-in the rectus femoris (RF) and biceps femoris longus (BFL). Knee extension and flexion torques were also measured for comparison to architecture measures. FA and MD were associated with age (β = 0.33, p = 0.001, R2 = 0.10; and β = -0.36, p < 0.001, R2 = 0.12), and FA was negatively associated with Type I fiber proportions from the literature (β = -0.70, p = 0.024, and R2 = 0.43). Pennation angle, fiber curvature, fascicle length, and PCSA were associated with age in the RF (β = -0.22, 0.26, -0.23, and -0.31, respectively; p < 0.05), while in the BFL only curvature and fascicle length were associated with age (β = 0.36, and -0.40, respectively; p < 0.001). In the RF, pennation angle and PCSA were associated with strength (β = 0.29, and 0.46, respectively; p < 0.01); in the BFL, only PCSA was associated with strength (β = 0.43; p < 0.001). Our results show skeletal muscle architectural changes with aging and intermuscular differences in the microstructure. DT-MRI may prove useful for elucidating muscle changes in the early stages of sarcopenia and monitoring interventions aimed at preventing age-associated microstructural changes in muscle that lead to functional impairment.


Regulation of biofilm formation in Yersinia pestis.
Plague biofilm development is controlled by positive (HmsT) and negative (HmsP) regulators. The GGDEF-domain protein HmsT appears to have diguanylate cyclase activity to synthesize bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) from 2 GTP molecules. The EAL domain of HmsP has phosphodiesterase activity and likely degrades c-di-GMP. This second messenger molecule probably influences biofilm development by activating the glycosyl transferase activity of HmsR. Here we demonstrate the in vitro pH optimum for phosphodiesterase activity of HmsP and that an alanine substitution in residue L508, D626, or E686 within the EAL domain affects this enzymatic activity and the biological function of the protein. Finally, protein-protein interactions and the cytoplasmic location of the enzymatic domains of HmsT and HmsP are evaluated.


Enantioselective resolution of 2-arylpropionic acid derivatives employing immobilization of lipase from Bacillus subtilis strain Kakrayal_1 (BSK-L).
This work studied the enantioselective resolution of 2-arylpropionic acid derivatives employing immobilization of lipase produced by Bacillus subtilis strain Kakrayal_1 (BSK-L). The efficient immobilization of lipase on modified silica gel was confirmed by Fourier transform infrared spectroscopy. Tethering of lipase facilitated the enhancement of physiochemical properties and stability of enzyme. Covalently immobilized enzyme retained 85% of residual activity even on reuse after 10th reaction cycle. Validation of immobilized lipase for enantioselective resolution of 2-arylpropionic acid derivatives led to 47.8% conversion efficiency with 87% enantiomeric excess (ee) for ketoprofen, and 27.3% conversion efficiency with 75% ee for flurbiprofen. The enantioselective resolution using immobilized lipase (BSK-L) was superior to free and commercially procured lipase, which suggest a potential application of immobilized lipase in the pharmaceutical/chemical industry.


Chagas Disease in a Non-endemic Country: A Multidisciplinary Research, Bologna, Italy.
Global processes have brought about a substantial change in the epidemiological landscape of Chagas disease, spreading it to non-endemic areas. Italy is the second country in Europe in terms of Latin American migrants and expected infection rate. Given that scenario, the Bologna University Teaching Hospital undertaken a study aimed at providing preliminary data on the prevalence and investigating the knowledge and the subjective perceptions of Chagas disease, migration pathways and other relevant ill-health experiences. A cross-sectional study was undertaken in association with an ethnographic research. Between November 2010 and May 2013 Chagas disease testing was offered to people who attended the hospital and data were collected to investigate the broader socio-demographic and cultural factors. 151 individuals were screened for anti T. cruzi antibodies; 12 of them, 10 Bolivians and 2 Argentinians, were seroreactive, resulting in an overall prevalence of 7.94 %. Both the quantitative and the qualitative analysis revealed a degree of heterogeneity in terms of knowledge and perceptions of the disease as well as of migration pathways. The results are comparable with those reported by previous studies with similar characteristics and highlight the relevance of such public health issue in a non-endemic context. Moreover, the interdisciplinary approach has greatly helped to unveil the complex social and cultural implications of Chagas disease, to explain the subjective ill-health experiences, and to understand the ways in which the broader socio-economic and cultural context affects an intervention and its potential for success or failure.


Anti-Malassezia-Specific IgE Antibodies Production in Japanese Patients with Head and Neck Atopic Dermatitis: Relationship between the Level of Specific IgE Antibody and the Colonization Frequency of Cutaneous Malassezia Species and Clinical Severity.
Atopic dermatitis of the head and neck (HNAD) is recognized as a separate condition. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate atopic dermatitis (AD), especially HNAD. In the present study, we investigated the relationships between the levels of specific IgE antibodies, colonization frequency of eight predominant Malassezia species, and clinical severity in 61 patients with HNAD (26 mild, 24 moderate, and 11 severe cases). As clinical severity increased, the levels of specific IgE antibodies against eight Malassezia species also increased. Species diversity of the Malassezia microbiota in scale samples from patients was analyzed by nested PCR using species-specific primers. The clinical severity of HNAD was correlated with the total level of specific IgE antibodies against Malassezia species and the number of Malassezia species detected.


The interaction of the visuo-spatial and the vestibular system depends on sensory experience in development.
In hearing individuals, vestibular and visuo-spatial functions seem to be functionally linked. Previous studies have suggested that congenitally deaf individuals are at a higher risk for vestibular problems, which in hearing adults have often been found to be associated with impairments in visuo-spatial processing. However, communicating in a sign language provides extensive practice in visuo-spatial processing, which might counteract negative effects of vestibular impairments. Here, we investigated whether the functional link between vestibular and visuo-spatial functions is mandatory, that is whether it is impenetrable to experience or context, or whether it is dependent on specific sensory and cognitive experiences. To this end, we tested a group of congenitally deaf native signers and a group of hearing nonsigners on mental rotation and balance tasks. Compared to hearing nonsigners, mental rotation was superior in the deaf signers in conditions crucial for sign language comprehension. By contrast, the balance performance of the group of deaf signers was impaired. While in the group of hearing nonsigners, balance skills correlated with mental rotation abilities, no such relationship was observed in the group of deaf signers. These results suggest that the link between vestibular and visuo-spatial functions is not fixed but can be altered or even cancelled out by certain sensory or cognitive experiences, such as the acquisition of a sign language.


Clinical stage I and II endometrial carcinoma treated with surgery and/or radiation therapy: analysis of prognostic and treatment-related factors.
This is an analysis of 266 patients with clinical stage I and II endometrial carcinoma treated with curative intent at the University of Florida between October 1964 and December 1980. There was a minimum 5-year follow-up. Thirty-nine patients who died of intercurrent disease less than 5 years from treatment were excluded from analysis of pelvic disease control and determinate disease-free survival. All patients were included in the analysis of complications. Pelvic disease control and determinate disease-free survival rates at 5 years were 91 and 88%, respectively, for stage I and 84 and 68% for stage II. There was no apparent difference in the rates of local control and survival or in the incidence of complications when comparing preoperative with postoperative radiation therapy. Tumor grade, stage, depth of myometrial invasion, and history of exogenous estrogen use or abnormal estrogen balance were of prognostic significance. Data on pelvic disease control, survival, and treatment complications are outlined, and management guidelines are discussed.


Immunohistochemical localization of gamma-aminobutyric acid- and aspartate-containing neurons in the rat deep cerebellar nuclei.
The immunohistochemical localization of gamma-aminobutyric acid (GABA)- and aspartate-containing neurons was evidenced in the rat deep cerebellar nuclei, using purified antisera to GABA and aspartate, respectively. Most GABA-containing neurons had small cell bodies and were scattered unevenly throughout the deep cerebellar nuclei. The medial cerebellar nucleus had a few GABA-containing cell bodies and interpositus and lateral nuclei contained many GABA-containing cell bodies. GABA-containing terminals were distributed throughout the nuclei. A large number of various-sized aspartate-containing cells were present in the deep cerebellar nuclei and most of these cells were large or medium-size. Aspartate-containing cells in the medial, interpositus and lateral nucleus were surrounded by GABA-like immunoreactive terminals, thereby suggesting the modulation of aspartate-containing neurons by GABA-ergic fibers from Purkinje cells.


Impact of Clinical and Endoscopic Features on the Development of Metachronous Colorectal Advanced Serrated Lesions.
High-risk adenomas predict metachronous advanced adenomatous neoplasia. Limited data exist on predictors of metachronous advanced serrated lesions (mASLs). We analyzed clinical and endoscopic predictors of mASLs. In this retrospective cohort study, adults with >1 outpatient colonoscopy between 2008 and 2019 at a tertiary center were included. Serrated lesions (SLs) included sessile SLs (SSLs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). Patient and endoscopic characteristics were obtained using electronic medical records. Five-year cumulative incidence of mASL (HP ≥10 mm, SSL ≥10 mm or with dysplasia, any TSA) and factors associated with mASL were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. A total of 4990 patients were included and 45.4% were women. Mean age was 60.9 ± 9.2 years and median follow-up time was 3.7 years. Female sex and active smoking were associated with mASL. Endoscopically, any SSL and TSA were associated with mASL. The 5-year cumulative incidence for mASL was 26% (95% confidence interval [CI], 18%-32%) for SSL ≥10 mm, 17% (95% CI, 3.5%-29%) for HP ≥10 mm, 21% (95% CI, 0%-42%) for 3-4 SSLs <10 mm, 18% (95% CI, 0%-38%) for TSA, and 27% (95% CI, 3.6%-45%) for SSL with low-grade dysplasia. Baseline synchronous nonadvanced SL and nonadvanced adenoma were not associated with mASL. Our data support current recommendations for a 3-year surveillance interval in patients with baseline SSL ≥10 mm, SSL with dysplasia, and TSA. A 3-year interval may be more appropriate than 3-5 years for patients with baseline HP ≥10 mm or 3-4 SSLs <10 mm. Patients with synchronous nonadvanced SLs and adenomas do not appear to be at increased risk of mASL.


Wide excision of perineal Hailey-Hailey disease with healing by secondary intention.
In this paper we advocate secondary healing for closure of large perineal wounds following full thickness skin excision for the treatment of Hailey-Hailey disease.


Thromboxane A2 is the major arachidonic acid metabolite of human cortical hydronephrotic tissue.
Human cortical hydronephrotic microsomes converted [14C] arachidonic acid to [14C] thromboxane B2 as the major metabolic product. Using [14C] PGH2 as substrate, similar enzymatic conversions were noted with HHT greater than TXB2 less than 6KPGF1 alpha greater than PGE2 greater than PGE2 alpha as the major products. Inhibition of thromboxane synthetase with imidazole 5 mM reduced thromboxane B2 production by 60% and the major product then was 6 keto PGF1 alpha. After addition of imidazole, the metabolic profile showed PKPGF1 alpha greater than PGE2 greater than HHT greater than PGF 2 alpha. Control experiments were carried out using normal cortical tissue obtained from kidneys removed surgically for carcinoma of kidney and rejected for transplantation secondary to fracture as a consequence of blunt trauma. These control kidneys, while they demonstrated an ability to generate thromboxane B2 in vitro, had much less activity than hydronephrotic kidneys and with PGH2 as substrate PGE2 greater than TxB2. In addition, inhibition with imidazole produced mainly PGE2. Thus, like the rabbit and rat, there is enhanced thromboxane and prostacyclin synthesis in human ureteral obstruction and are, therefore, potential vasoactive compounds which may in part be responsible for the hemodynamic alterations occurring in human obstructive uropathy.


[Pediatric intensive care in Latin America].
To describe the practice of pediatric intensive care in Latin America and compare it with two European countries. Analysis of data presented by member countries of the Sociedad Latinoamericana de Cuidado Intensivo Pediátrico (SLACIP), Spain and Portugal, in the context of a Symposium of Spanish and Portuguese - speaking pediatric intensivists during the Fifth World Congress on Pediatric Intensive Care. Pediatric intensive care units (PICUs). Pediatric intensivists in representation of each member country of the SLACIP, Spain and Portugal. None. Each country presented its data on child health, medical facilities for children, pediatric intensive care units, pediatric intensivists, certification procedures, equipment, morbidity, mortality, and issues requiring intervention in each participating country. Data from 11 countries was analyzed. Nine countries were from Latin America (Argentina, Colombia, Cuba, Chile, Ecuador, Honduras, México, Dominican Republic and Uruguay), and two from Europe (Spain and Portugal). Data from Bolivia and Guatemala were partially considered. Populational, institutional, and operative differences were identified. Mean PICU mortality was 13.29% in Latin America and 5% in the European countries (P=0.005). There was an inverse relationship between mortality and availability of pediatric intensive care units, pediatric intensivists, number of beds, and number of pediatric specialty centers. Financial and logistic limitations, as well as deficiencies in support disciplines, severity of diseases, malnutrition, late admissions, and inadequate initial treatments could be important contributors to mortality at least in some of these countries. There are important differences in population, morbidity and mortality in critically ill children among the participating countries. Mortality shows an inverse correlation to the availability of pediatric intensive care units, intensive care beds, pediatric intensivists, and pediatric subspecialty centers.


Ethnicity and health outcomes among people with epilepsy participating in an epilepsy self-management RCT.
People with epilepsy (PWE) may experience negative health events (NHEs) such as seizures, emergency room visits, and hospitalizations, with ethnic and racial minorities disproportionately affected. Epilepsy self-management may reduce NHEs; however, few reports examine self-management outcomes in racial minorities. Using data from a longitudinal 6-month randomized controlled trial (RCT) of 120 PWE, this analysis compared African-American and Whites at baseline, 10 weeks and 24 weeks after receiving the "Self-management for people with epilepsy (SMART) and a history of NHEs" self-management program. The primary RCT outcome was number of NHEs. At baseline, compared to Whites, African-Americans had less education (p = 0.02) and greater depressive severity (p = 0.04). Both African-American and Whites generally improved with SMART, and there were no racial differences in NHE counts or other outcomes' responses. Given known racial disparities in epilepsy care, it may be particularly important to reach out to minority PWE with self-management programs.


Beyond the Lennard-Jones model: a simple and accurate potential function probed by high resolution scattering data useful for molecular dynamics simulations.
Scattering data, measured for rare gas-rare gas systems under high angular and energy resolution conditions, have been used to probe the reliability of a recently proposed interaction potential function, which involves only one additional parameter with respect to the venerable Lennard-Jones (LJ) model and is hence called Improved Lennard-Jones (ILJ). The ILJ potential eliminates most of the inadequacies at short- and long-range of the LJ model. Further reliability tests have been performed by comparing calculated vibrational spacings with experimental values and calculated interaction energies at short-range with those obtained from the inversion of gaseous transport properties. The analysis, extended also to systems involving ions, suggests that the ILJ potential model can be used to estimate the behavior of unknown systems and can help to assess the different role of the leading interaction components. Moreover, due to its simple formulation, the physically reliable ILJ model appears to be particularly useful for molecular dynamics simulations of both neutral and ionic systems.


Rapid recovery of structure and function of the cholinergic synapses in the cat superior cervical ganglion in vivo following stimulation-induced exhaustion.
Cat superior cervical ganglia (SCG) were tetanically stimulated in vivo at 30-100 Hz until neural transmission was exhausted, and then were allowed to rest and recover. Changes in their cholinergic synapses were examined electrophysiologically and morphologically during the time of tetanic stimulation and during recovery. For morphometric analysis the presynaptic terminal was subdivided into two areas: an area directly over the active zone, termed zone-I, (bounded by a hemicircle with a diameter equivalent to the active zone length), and the remaining preterminal area, termed zone-II. In control ganglia before stimulation synaptic vesicle density in zone-I (SVD-I) averaged 90 microns-2 and the number of vesicles actually attached to the active zone (SVA) averaged about 2.5 per single profile of nerve terminal. Upon stimulation, the postganglionic potential immediately began to decline in amplitude and disappeared after 1 min of stimulation. Simultaneously, SVD-I declined to less than 35 microns-2 and SVA declined to less than 1 per section. Thereafter, stimulation was terminated and the ganglion was allowed to rest. Recovery of the postganglionic potential was monitored by stimulation at 1 Hz. The postganglionic potential reached control levels after only 1 min of rest. Likewise, the structural parameters, SVD-I and SVA, also rapidly recovered, reaching control levels after only 30 sec of rest, slightly faster than the postganglionic potential. This illustrates that stimulation-induced fatigue of transmitter output and depletion of synaptic vesicles recover to the control level at a high rate in synapses of the cat SCG with a normal supply of blood. In fact, morphological recovery may be slightly faster than electrophysiological recovery. Mechanisms of vesicle formation and migration to the presynaptic area are discussed in light of these observations.


Evidence for an enhanced role of GABA inhibition in visual cortical ocular dominance of cats reared with abnormal monocular experience.
The effects of microiontophoretic bicuculline, a gamma-aminobutyric acid (GABA) antagonist, on the ocular dominance of visual cortical neurons were compared in normal cats and cats reared with abnormal monocular visual experience (monocular deprivation, surgical strabismus, and monocular deprivation after dark rearing). Cells that were monocular prior to drug application showed disinhibitory effects on ocular dominance far more frequently than originally binocular cells in all rearing conditions. When the total population of neurons was considered there were marked differences among rearing conditions: only 17% of cells showed change in ocular dominance in normal cats whereas over 50% showed changes in cats reared with abnormal monocular visual experience. These results indicate that GABA inhibition plays an enhanced role in cats with abnormal cortical ocular dominance. The results are interpreted in the context that the GABA system is passively biased by alterations in the pattern of excitatory input to contribute to abnormal patterns of ocular dominance.


Bladder neck obstruction secondary to Brunn's cyst.
A large solitary Brunn's cyst caused a ball-valve type of obstruction of the bladder neck in a 29-year-old man without endoscopic or histological evidence of bladder inflammation. Unroofing and drainage restored normal voiding. The histopathological features of Brunn's nests are reviewed.


Incorporating Prostate-specific Membrane Antigen Positron Emission Tomography in Management Decisions for Men with Newly Diagnosed or Biochemically Recurrent Prostate Cancer.
Prostate-specific membrane antigen (PSMA) is a promising molecular target for prostate cancer (PCa) that has allowed the development of a novel diagnostic approach to PCA in the primary and recurrent settings. To summarize available data and recommendations regarding the use of PSMA in newly diagnosed and recurrent PCa via a narrative review. A literature review was conducted using MEDLINE (via PubMed) and Scopus. The search strategy included meta-analyses, reviews, and original studies on staging and restaging with 68Ga-PSMA positron emission tomography (PET)/computed tomography (CT). Studies comparing PSMA-targeted imaging and conventional imaging suggest superior performance of PSMA-targeted imaging in primary and recurrent PCa, albeit with several clinically relevant limitations. Pretreatment 68Ga-PSMA PET/CT allowed more accurate PCa staging in compared to routine practice for high-risk cases, and identified a number of otherwise unknown metastatic lesions. In biochemically recurrent PCa, PSMA PET can reveal sites of recurrence with greater sensitivity and specificity than conventional imaging, potentially detecting a major proportion of occult disease. This review will help providers in applying the most up-to-date and relevant literature to (1) determine which patients truly have oligometastatic disease and (2) ascertain who is most likely to experience a meaningful response to local consolidation in the biochemical recurrence setting. Data on PSMA diagnostic studies in primary and recurrent PCa highlight the accuracy and clinical application of PSMA PET. While this review and the evidence to date might lead to a perception of superiority in metastasis directed therapy, fundamental lack of phase III clinical trials with clinically meaningful outcomes are yet to be determined. PSMA (prostate-specific membrane antigen) scans have shown great promise for initial evaluation of prostate cancer (PCa) and in detection of PCa recurrence. The benefits are more apparent for initial staging of PCa. There are more limited clinical trial results for PCa recurrence on how best to use this new technique to guide cancer treatment.


Role of envelope proteins of paramyxoviruses in the modification of cell membrane antigens.
Adsorption of paramyxoviruses to separated membranes of tumor cells produces neoantigens that are immunogenic in syngeneic mice (xenogenization). Thus it became possible to study this process by using modified virus or virus fractions. Membranes with adsorbed viral derivatives produced an immune response which was measured by cytotoxic and complement fixing antibodies and the appearance of autoimmune disease. The effect of viral preparations with reduced F (fusion) protein activity was compared to treatment of membranes with equivalent amounts of active or inactive virus as measured by hemagglutination. Viral preparations without hemolytic activity showed diminished adsorption to membranes and the immune response was reduced. Triton X 100 and desoxycholate extracted from membranes immunogenic material with associated paramyxovirus antigens.


An improved device for continuous intraventricular infusions prevents the introduction of pump-derived toxins and increases the effectiveness of NGF treatments.
The recent demonstrations of the ability of nerve growth factor (NGF) to protect and promote the welfare of certain cholinergic neurons in the adult CNS have increased the need for safe, accurate, and reliable procedures for intracerebral administration of protein and other experimental agents. Osmotic minipumps have been used to infuse NGF into the lateral ventricle of adult rats, but a sustained and harmless performance of such infusions has not been fully evaluated. The study reported here has led to (i) the recognition that cytotoxic substances, released from some minipumps into the infusion fluid, may be responsible for various degrees of periventricular tissue damage, and (ii) the redesigning of an infusion device which, among other modifications, uses the osmotic pump to propel infusion fluid into the ventricle but prevents pump-derived materials from entering the infusate itself. Besides several other advantages, the modified infusion device has permitted the demonstration that NGF can fully protect experimentally axotomized medial septum cholinergic neurons and can do so with less variability than previously observed and without creating tissue damage.


Cross-linked fibrin in the nasal fluid of patients with the common cold.
To determine whether adherent material found on the walls of the paranasal sinuses during common colds might be fibrin clot, we examined the nasal fluid (a surrogate for sinus secretion) of 11 young adults with experimentally induced rhinovirus colds and that of 4 control subjects for the presence of fibrin. The mean concentration (+/- the standard error) of insoluble fibrin (measured as D-dimer) in subjects with rhinovirus colds increased from a baseline level of 0.8+/-0.4 microgram/mL to a peak of 2.4+/-0.7 microgram/mL (P=.0008) on day 4 after inoculation of the virus, but the fibrin concentration remained at baseline levels in the 4 uninfected control subjects.


Diaphragmatic herniation following total gastrectomy: review of the long-term experience of a tertiary institution.
Diaphragmatic herniation (DH) is a rare but potentially fatal event after total gastrectomy (TG). Despite being life-threatening, risk factors for postoperative DH have yet to be elucidated. We conducted a retrospective analysis to identify clinical characteristics of patients developing DH after TG, along with a comprehensive review of the published literature. Among 1361 consecutive patients undergoing TG for esophagogastric cancer between 1985 and 2013 in Toranomon Hospital, those requiring surgical intervention for postoperative DH were included. We also conducted a PubMed literature search on DH following TG. Five patients (four males, one female), with a median age of 68 at DH surgery, were identified. Intervals between TG and DH repair ranged from 2.9 to 189.0 (median, 78.1) months. Four patients had needed emergency surgery. Three patients had undergone open TG and two others laparoscopic TG, suggesting a significantly higher incidence of DH after laparoscopic TG (3/1302 vs. 2/59, p = 0.017). The diaphragmatic crus incision, creating the space for esophagojejunostomy, had been performed in all cases. The literature yielded seven relevant publications (16 patients). Intervals between TG and DH reduction ranged from 2 days to 36 months. All operations for DH had been carried out emergently. The risk of DH persisted after TG. DH is potentially a very late complication of TG, presenting as a surgical emergency. Laparoscopic TG was suggested to be a risk factor for postgastrectomy DH. Incising the crus might also be a predictor of DH. Measures to prevent DH, e.g., appropriate closure of the crus, would be recommended in minimally invasive TG.


Pre-pandemic social isolation as a predictor of the adverse impact of the pandemic on self-rated health: A longitudinal COVID-19 study in Japan.
Many studies have found adverse effects of the coronavirus disease pandemic on health. Irrespective of being infected by the coronavirus, lockdowns and other measures to restrict mobility have worsened an individual's subjective health assessment. Unlike previous studies, this study examined how pre-pandemic social isolation (in the form of no interaction with others and having no social support) affected the impact of the pandemic on self-rated health in Japan. To this end, we estimated fixed-effects models using 4172 observations of 2086 individuals obtained from a three-wave Internet nationwide survey conducted in January/February 2019 and February 2020 (before the pandemic), in March 2021 (when the pandemic-related state of emergency was effective in four prefectures and just after it was lifted in six prefectures), and in October/November (a full month after the state of emergency was lifted in all prefectures). The state of emergency raised the probability of reporting poor health by 17.8 (95% confidence interval [CI]:1.9-33.8) percentage points among the participants who had not interacted with others before the pandemic, compared with only 0.7 (95% CI: -3.1-4.5) percentage points among other participants. Similar results were obtained in the absence of social support prior to the pandemic. In conclusion, pre-pandemic social isolation was detrimental to health, suggesting that policy measures are needed to avoid social isolation to increase the resilience of public health to external shocks.


Boosting Hydrogen Peroxide Electrosynthesis via Modulating the Interfacial Hydrogen-Bond Environment.
Designing highly efficient and stable electrode-electrolyte interface for hydrogen peroxide (H2 O2 ) electrosynthesis remains challenging. Inhibiting the competitive side reaction, 4 e- oxygen reduction to H2 O, is essential for highly selective H2 O2 electrosynthesis. Instead of hindering excessive hydrogenation of H2 O2 via catalyst modification, we discover that adding a hydrogen-bond acceptor, dimethyl sulfoxide (DMSO), to the KOH electrolyte enables simultaneous improvement of the selectivity and activity of H2 O2 electrosynthesis. Spectral characterization and molecular simulation confirm that the formation of hydrogen bonds between DMSO and water molecules at the electrode-electrolyte interface can reduce the activity of water dissociation into active H* species. The suitable H* supply environment hinders excessive hydrogenation of the oxygen reduction reaction (ORR), thus improving the selectivity of 2 e- ORR and achieving over 90 % selectivity of H2 O2 . This work highlights the importance of regulating the interfacial hydrogen-bond environment by organic molecules as a means of boosting electrochemical performance in aqueous electrosynthesis and beyond.


Subunits of the Snf1 kinase heterotrimer show interdependence for association and activity.
The Snf1 kinase and its mammalian orthologue, the AMP-activated protein kinase (AMPK), function as heterotrimers composed of a catalytic alpha-subunit and two non-catalytic subunits, beta and gamma. The beta-subunit is thought to hold the complex together and control subcellular localization whereas the gamma-subunit plays a regulatory role by binding to and blocking the function of an auto-inhibitory domain (AID) present in the alpha-subunit. In addition, catalytic activity requires phosphorylation by a distinct upstream kinase. In yeast, any one of three Snf1-activating kinases, Sak1, Tos3, or Elm1, can fulfill this role. We have previously shown that Sak1 is the only Snf1-activating kinase that forms a stable complex with Snf1. Here we show that the formation of the Sak1.Snf1 complex requires the beta- and gamma-subunits in vivo. However, formation of the Sak1.Snf1 complex is not necessary for glucose-regulated phosphorylation of the Snf1 activation loop. Snf1 kinase purified from cells lacking the beta-subunits do not contain any gamma-subunit, indicating that the Snf1 kinase does not form a stable alphagamma dimer in vivo. In vitro kinase assays using purified full-length and truncated Snf1 proteins demonstrate that the kinase domain, which lacks the AID, is significantly more active than the full-length Snf1 protein. Addition of purified beta- and gamma-subunits could stimulate the kinase activity of the full-length alpha-subunit but only when all three subunits were present, suggesting an interdependence of all three subunits for assembly of a functional complex.


Versatile multi-constrained planning for thermal ablation of large liver tumors.
The surgical planning of large hepatic tumor ablation remains a challenging task that relies on fulfilling multiple medical constraints, especially for the ablation based on configurations of multiple electrodes. The placement of the electrodes to completely ablate the tumor as well as their insertion trajectory to their final position have to be planned to cause as little damage to healthy anatomical structures as possible to allow a fast rehabilitation. In this paper, we present a novel, versatile approach for the computer-assisted planning of multi-electrode thermal ablation of large liver tumors based on pre-operative CT data with semantic annotations. This involves both the specification of the number of required electrodes and their distribution to adequately ablate the tumor region without damaging too much healthy tissue. To determine the insertion trajectory of the electrodes to their final position, we additionally incorporate a series of medical constraints into our optimization, which allows a global analysis where obstacles such as bones are taken into account and damage to healthy tissue is mitigated. Compared with the state-of-the-art method, our method achieves compact ablation regions without relying on assumptions on a potential needle path for optimal global search and, hence, is suitable for guiding clinicians through the planning of the tumor ablation. We also demonstrate the feasibility of our approach in various experiments of clinical data and demonstrate that our approach not only allows completely ablating the tumor region but also reducing the damage of healthy tissue in comparison to the previous state-of-the-art method.