Death receptor ligands, in particular TRAIL, to overcome drug resistance.
The efficacy of chemotherapeutic drugs is hampered by the occurrence of intrinsic and acquired drug resistance. A variety of mechanisms cause drug-resistance. A final common factor, however, is the reduced capacity of drug resistant cells to go into apoptosis following treatment with DNA damaging agents. This is due to defects in apoptotic pathways, for example, changes in p53. The presence of a common factor makes it of interest to search for ways that facilitate the cell to go into apoptosis following exposure to chemotherapeutic drugs. The death receptor ligands tumor necrosis factor (TNF), Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL) are able to induce apoptosis by binding to their cell membrane receptors. Recombinant forms of these ligands are capable to potentiate the effect of chemotherapeutic drugs in vitro and in vivo in the animal model. Based on preclinical toxicity and activity profiling, especially TRAIL is considered to be of interest for clinical use. Systemic treatment of non-human primates with TRAIL did not result in acute toxicity. Animal studies demonstrated antitumor activity of TRAIL and potentiation of the chemotherapy efficacy by TRAIL. Phase 1 studies with TRAIL will therefore be initiated. As TRAIL is supposed to be non-toxic, it will be a major challenge to design surrogate end points to find the optimal dose in the clinic. In analogy to the herceptin therapy, it may be helpful to characterize the tumor of the patient. In addition, ex vivo exposure of the tumor may also be useful to select the proper ligand therapy for the individual patient. For optimal effect it is most likely that ligand therapy will be combined with chemotherapy, but even a combination of ligands for patient treatments can be envisioned. It is to be expected that smart, small molecules targeting these death receptors will be designed in order to lower toxicity and increase antitumor activity.


Electrical storm in patients with transvenous implantable cardioverter-defibrillators: incidence, management and prognostic implications.
The purpose of this study was to determine the precise incidence, therapeutic options and prognostic implications of electrical storm in patients with transvenous implantable cardioverter-defibrillator (ICD) systems. Approximately 50% to 70% of patients treated with an ICD receive appropriate device-based therapy within the first 2 years. Most arrhythmic events require only one appropriate ICD firing for termination. However, some patients receive multiple appropriate shocks during a short period of time, a condition referred to as "arrhythmic or electrical storm." This prospectively designed observational study comprised 136 recipients of transvenous ICDs who were followed for 403+/-242 days. Electrical storm was defined as ventricular tachycardia or fibrillation resulting in device intervention > or = 3 times during a single 24-h period. During follow-up, 57/136 patients (42%) received appropriate ICD therapy. Electrical storm occurred in 14/136 patients (10%) at an average of 133+/-135 days after ICD implantation. The mean number of arrhythmic episodes constituting electrical storm was 17+/-17 (range: 3 to 50; median 8) per patient. In 12 patients, electrical storm required hospital admission. The arrhythmia cluster could be terminated by a combined therapy with beta-blockers and intravenous amiodarone whereas class I antiarrhythmic drugs were only occasionally successful. The cumulative probability of survival as estimated by the Kaplan-Meier method showed that patients with an episode of electrical storm did not have a worse outcome compared to those without such an event. Electrical storm represents a frequent event in patients treated with modern ICDs. It occurs most commonly late after ICD implantation and can be managed by combined therapy with beta-blockers and amiodarone. Electrical storm does not independently confer increased mortality.


Pericardial effusion following conditioning for bone marrow transplantation in acute leukaemia.
We report the details of a young woman in whom pericardial tamponade developed acutely following preparation for allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. The aetiology of the effusion, though uncertain, probably relates to the cumulative cardiotoxicity of cyclophosphamide and irradiation upon a myocardium previously sensitised by anthracycline therapy. As the number of transplant procedures increases, this complication may become more common, and might be avoided by a more critical assessment of cardiac function prior to transplantation, with radionuclide angiography.


Characterization of the novel HLA-C*02:106 allele in a hematopoietic stem cell volunteer donor.
HLA-C*02:106 allele differs from C*02:02:02:01 by a C to T substitution in exon 4.


Rab39 and its effector UACA regulate basolateral exosome release from polarized epithelial cells.
Exosomes are small extracellular vesicles that originate from the intraluminal vesicles of multivesicular bodies (MVBs). We previously reported that polarized Madin-Darby canine kidney (MDCK) epithelial cells secrete two types of exosomes, apical and basolateral exosomes, from different MVBs. However, how these MVBs are selectively targeted to the apical or basolateral membrane remained unknown. Here, we analyze members of the Rab family small GTPases and show that different sets of Rabs mediate asymmetrical exosome release. Rab27, the best-known regulator of MVB transport for exosome release, is specifically but partially involved in apical exosome release, and Rab37, a close homolog of Rab27, is an additional apical exosome regulator. By contrast, Rab39 functions as a specific regulator of basolateral exosome release. Mechanistically, Rab39 interacts with its effector UACA, and UACA then recruits Lyspersin, a component of BLOC-1-related complex (BORC). Our findings suggest that the Rab39-UACA-BORC complex specifically mediates basolateral exosome release.


Proposal for a new tapeworm order, Rhinebothriidea.
The polyphyletic nature of the tapeworm order Tetraphyllidea Carus, 1863 is addressed in part with the establishment of the new order Rhinebothriidea for a subset of the taxa formerly comprising the phyllobothriid subfamily Rhinebothriinae (Platyhelminthes: Eucestoda). Support for the order comes from Bayesian, maximum likelihood, and parsimony analyses of complete ssrDNA and partial (D1-D3) lsrDNA sequence data for 58 cestode species. These data consisted of novel data generated for 40 species in 15 genera of candidate rhinebothriines and the cathetocephalidean species Sanguilevator yearsleyi as well as comparable data taken from GenBank for an additional 18 cestode species in 17 genera. In total, the species analyzed consisted of two Cathetocephalidea, two Litobothriidea, two Lecanicephalidea, three Proteocephalidea, and 49 Tetraphyllidea. The tetraphyllideans consisted of three Onchobothriidae, three Serendipidae, and 43 Phyllobothriidae (one Thysanocephalinae, one Echeneibothriinae, five Phyllobothriinae, 35 candidate Rhinebothriinae and the poorly known Spongiobothrium). This work suggests that some elements of current membership in the group are in need of revision. For example, while inclusion of the echeneibothriine genus Echeneibothrium and the phyllobothriine genera Rhodobothrium and Anthocephalum, and also Spongiobothrium, in the Rhinebothriidea is supported, inclusion of Duplicibothrium and Caulobothrium in the new order is not. Histological sections and scanning electron microscopy of selected members of the study group suggest that the presence of bothridial stalks may serve as an effective morphological feature to characterise the order. The group is restricted to elasmobranchs, and appears to have a particular affinity for Myliobatiformes. The new order includes at least 13 genera. Intraordinal relationships were determined to be insufficiently stable to justify the formal reorganization of rhinebothriidean families at this time.


Conjugal transfer of plasmid and transposon DNA from Escherichia coli into Porphyromonas gingivalis.
Using the broad host-range vector R751 to provide transfer functions, plasmid pVAL-1 and transposon Tn4351 were conjugally mobilized from Escherichia coli into Porphyromonas gingivalis. Transfer frequencies for both elements varied between 10(-6) and 10(-11), depending upon the recipient. The behavior of pVAL-1 and Tn4351 in P. gingivalis was essentially as described previously in Bacteroides spp. These data indicate that plasmid and transposon DNA can be conjugally transferred into P. gingivalis and that these elements can be used to genetically manipulate the organism in examining putative virulence determinants that may participate in the induction or exacerbation of periodontal disease.


Future trends and guidance for the triple bottom line and sustainability: a data driven bibliometric analysis.
This study conducts a comprehensive literature review of articles on the triple bottom line (TBL) published from January 1997 to September 2018 to provide significant insights and support to guide further discussion. There were three booms in TBL publications, occurring in 2003, 2011, and 2015, and many articles attempt to address the issue of sustainability by employing the TBL. This literature analysis includes 720, 132, and 58 articles from the Web of Science (WOS), Inspec, and Scopus databases, respectively, and reveals the gaps in existing research. To discover the barriers and points of overlap, these articles are categorized into six aspects of the TBL: economic, environmental, social, operations, technology, and engineering. Examining the top 3 journals in terms of published articles on each aspect reveals the research trends and gaps. The findings provide solid evidence confirming the argument that the TBL as currently defined is insufficient to cover the entire concept of sustainability. The social and engineering aspects still require more discussion to support the linkage of the TBL and to reinforce its theoretical basis. Additionally, to discover the gaps in the data sources, theories applied, methods adopted, and types of contributions, this article summarizes 82 highly cited articles covering each aspect. This article offers theoretical insights by identifying the top contributing countries, institutions, authors, keyword networks, and authorship networks to encourage scholars to push the current discussion further forward, and it provides practical insights to bridge the gap between theory and practice for enhancing the efficiency and effectiveness of improvements.


Hemispheric contributions toward interoception and emotion recognition in left-vs right-semantic dementia.
The hemispheric contributions toward interoception, the perception of internal bodily cues, and emotion recognition remains unclear. Semantic dementia cases with either left-dominant (i.e., left-SD) or right-dominant (i.e., right-SD) anterior temporal lobe atrophy experience emotion recognition difficulties, however, little is known about interoception in these syndromes. Here, we hypothesised that right-SD would show worse interoception and emotion recognition due to right-dominant atrophy. Thirty-five participants (8 left-SD; 6 right-SD; 21 controls) completed a monitoring task. Participants pressed a button when they: (1) felt their heartbeat, without pulse measurement (Interoception); or (2) heard a recorded heartbeat (Exteroception-control). Simultaneous ECG was recorded. Accuracy was calculated by comparing the event frequency (i.e., heartbeat or sound) to response frequency. Emotion recognition was assessed via the Facial Affect Selection Task. Voxel-based morphometry analyses identified neural correlates of interoception and emotion recognition. Right-SD showed worse interoception than controls and left-SD (both p's < 0.001). Both patient groups showed worse emotion recognition than controls (right-SD: p < .001; left-SD: p = .018), and right-SD showed worse emotion recognition than left-SD (p = .003). Regression analyses revealed that worse emotion recognition was predicted by right-SD (p = .002), left-SD (p = .005), and impaired interoception (p = .004). Interoception and emotion were associated with the integrity of right-lateralised structures including the insula, temporal pole, thalamus, superior temporal gyrus, and hippocampus. Our study provides the first evidence for impaired interoception in right-SD, suggesting that impaired emotion recognition in this syndrome is driven by inaccurate internal monitoring. Further we identified a common neurobiological basis for interoception and emotion in the right hemisphere.


Caffeine-diazepam interaction and local cerebral glucose utilization in the conscious rat.
The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of the acute administration of a sedative anticonvulsant dose of diazepam (2 mg/kg) on rat brain energy metabolism. This benzodiazepine was injected to rats chronically treated for two weeks either by caffeine (10 mg/kg/day) or by saline. After the administration of diazepam to saline-treated rats, average glucose utilization of the brain as a whole was reduced by 21% and rates of glucose utilization were deeply decreased in frontal and auditory cortex, mammillary body, lateral thalamus, medial and lateral geniculate. In caffeine-treated rats, the administration of diazepam induced the same effects of brain energy metabolism as in saline-treated rats. The results of the present study indicate that diazepam mainly decreases glucose utilization in structures widely believed to mediate anxiety.


[Material characteristics of bone substance in the proximal area of the tibia with regard to alloplasty].
Since 1977 the tibial part of knee joint prostheses has only been implanted after adequate "straightening" of the tibial plateau, and a tibial "resection" has in most cases been avoided. In the study reported here, the authors examined the bone characteristics after "straightening" and "resection." The results show that the tibial plateau must not be resected too generously if it is to accept a prosthesis. In addition, new data relating to alloarthroplasty were established.


Anal gland adenocarcinoma presenting as painless scrotal swelling in a 73-year-old man: a case report.
A 73-year-old man presented with progressive painless scrotal swelling without systemic, urinary, or anorectal complaints. The scrotal lymphedema was due to massive bilateral metastatic replacement of the superficial inguinal lymph nodes. The primary tumor was an inoperable, rapidly fatal adenocarcinoma arising from the anal glands of the upper canal. Thus, in the evaluation of scrotal swelling of obscure etiology in older patients, occult carcinomas of the anal glands must be considered and appropriate steps taken to establish the diagnosis.


A practical mild, one-pot, regiospecific synthesis of 2,3-disubstituted indoles via consecutive Sonogashira and Cacchi reactions.
[Structure: see text] A practical one-pot, regiospecific three-component process for the synthesis of 2,3-disubstituted indoles was developed via consecutive Pd-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.


Gene expression profile in early stage of retinoic acid-induced differentiation of human SH-SY5Y neuroblastoma cells.
The human SH-SY5Y cell line is an established model for retinoic acid (RA)-induced neural differentiation. We employed a broad human 15K microarray (15,000 genes) and focused Neuroarray (1152 genes) to examine changes in gene expression early in the process of differentiation (6 hr), before morphology or growth changes are observed. 33 P-labeled CDNA probes prepared from RNA extracts of RA-treated and control cultures were hybridized to array membranes, and levels of expression were quantified and compared. In the 15K array, 19 % of the genes were decreased (0.4 % were named genes and the remainder were expressed sequence tags (ESTs) or unknowns), and 9 % were increased (4.2 % named genes). In the Neuroarray, 3 % were decreased and 8 % were increased. Summary gene profiles are presented, which include transcription factors, genes associated with cell cycle, cell shape, neurotransmission, intermediary filaments, and others. The prevalence of down-regulated genes in the broad 15K array and up-regulated genes in the neuro-focused array suggests a pattern shift in gene expression associated with differentiation. The predominance of ESTs among the down-regulated genes indicates a great number of as-yet-unidentified genes are repressed in early stage neural differentiation.


X-linked lymphoproliferative syndrome. Identification of a large family in Switzerland.
Observation of a patient with acquired hypogammaglobulinemia associated with a mononucleosis syndrome led to the identification of one of the largest families affected by the X-linked lymphoproliferative (XLP) syndrome in the world. It is the first such family identified in Switzerland and the largest in Europe. At least nine male subjects over two generations presented phenotypic expressions consistent with the XLP syndrome. Study of the pedigree extending over seven generations suggests that the mutation occurred in the proband's great-grandmother. In the next generation, a second mutation of the X chromosome in one branch of the family resulted in expression of hemophilia A in the children. This remarkably large family, comprising six living obligate female carriers, displays a wide spectrum of the XLP syndrome and offers valuable information for future genetic linkage studies and for genetic counseling.


Reduction in DNA repair capacity following differentiation of murine proadipocytes.
It has been suggested that terminally differentiated mammalian cells have a decreased DNA repair capacity, compared with proliferating stem cells. To investigate this hypothesis, we have examined gamma-ray-induced DNA strand breaks and their repair in the murine proadipocyte stem cell line 3T3-T. By exposure to human plasma, 3T3-T cells can be induced to undergo nonterminal and then terminal differentiation. DNA strand breaks were evaluated using the technique of alkaline elution. No difference was detected among stem, nonterminally differentiated, and terminally differentiated cells in the initial levels of radiation-induced DNA strand breaks. Each of the strand break dose response increased as a linear function of gamma-ray dose. The strand breaks induced by 4 Gy rejoined following biphasic kinetics for each cell type. At each time point examined after irradiation, however, the percentage of strand breaks that had not rejoined in terminally differentiated cells was three to six times greater than in stem cells. The rate of strand break rejoining in nonterminally differentiated cells was of an intermediate value between that of the stem and of the terminally differentiated cells. These results indicate that, at least for 3T3-T cells, differentiated cells have a reduced capacity for DNA repair.


Antibiotic Resistance and Pathogenomics of Staphylococci Circulating in Novosibirsk, Russia.
A total of 394 strains of staphylococci found in humans and pets in Novosibirsk, Siberian Russia, were characterized in terms of antibiotic resistance and corresponding genes. Two coagulase-positive and 17 coagulase-negative species were identified. The majority of isolates, with the exception of S. haemolyticus and hospital S. epidermidis isolates, were sensitive to most of the tested antibiotics, and isolates from pets displayed the lowest level of resistance. Nevertheless, methicillin-resistant (MRS) and/or multidrug-resistant (MDR) isolates were found in all prevailed species, including coagulase-negative. A set of genes corresponding to the detected resistance was identified: mecA (beta-lactam resistance), aac(6')-Ie-aph(2″)-Ia, aph(3')-IIIa, ant(4')-Ia (aminoglycoside-modifying enzymes), ermA/ermC, and msrA (macrolide resistance). Complete genome analysis for ten MDR S. epidermidis and five MDR S. haemolyticus isolates revealed additional antibiotic resistance genes mphC, qacA/qacB, norA, dfrC/dfrG, lnuA, BseSR, and fosB. NorA, dfrC, and fosB were present in all S. epidermidis genomes, whereas mphC and msrA were identified in all S. haemolyticus ones. All investigated MDR S. epidermidis and four of five S. haemolyticus strains were moderate or strong biofilm producers, whereas multiple genes responsible for this function and for virulence and pathogenicity were identified mostly in S. epidermidis, but were less frequently represented in S. haemolyticus.


Adjuvant chemotherapy with 5-fluorouracil and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma.
In this study we explored the effectiveness of adjuvant chemotherapy in node-positive, resected thoracic esophageal squamous cell carcinoma patients. A prospective study of postoperative chemotherapy in N1 esophageal cancer patients who received curative resection was conducted and compared with the historical control group in regard to recurrence rate, patterns of failure, disease-free survival rate, and overall survival rate. The postoperative chemotherapy consisted of cisplatin (60 mg/m2 intravenously) and 5-fluorouracil (1,000 mg/m2 per day) in a continuous infusion for 4 days. Three cycles were administered at 3-week intervals. Forty patients were accrued from January 1998 to January 2003 at Samsung Medical Center for adjuvant chemotherapy. The historical control group consisted of 52 patients who received curative resection but not adjuvant chemotherapy during the same period of time. The 3-year disease-free survival rate was 47.6% in the adjuvant group and 35.6% in the control group (p = 0.049). The estimated 5-year overall survival rates were 50.7% in the adjuvant group and 43.7% in the control group (p = 0.228). The significant predictive factors for tumor recurrence were the number of positive lymph nodes (p = 0.008) and the adjuvant chemotherapy (p = 0.030). This study suggests that the postoperative chemotherapy may prolong disease-free survival in lymph node-positive, curatively resected esophageal cancer patients. The postoperative treatment modality for esophageal cancer patients should be determined according to the lymph node status and a randomized phase III clinical trial is warranted using adjuvant chemotherapy if the esophageal cancer is lymph node-positive.


Comparison of risk factors between human intestinal and gastric Anisakiasis.
Little is known in the difference of host factors between intestinal and gastric anisakiasis. The aim of this study was to investigate the associated factors of intestinal anisakiasis in patient's characteristics and the subsequent variation compared to gastric anisakiasis. At St. Luke's International Hospital in Tokyo, Japan, a retrospective cohort study was conducted from April 2004 to June 2017. All adult patients who were clinically diagnosed as anisakiasis based on Computed Tomography (CT) scan or endoscopy were included, and anti-Anisakis antibodies (IgG and IgA) were measured for serological validation of anisakiasis, strengthen the diagnosis. Anisakiasis was categorized as either intestinal or gastric depending on its affected site. We compared patients' demographics, social history, and physical and laboratory findings between those with intestinal and gastric anisakiasis by bivariate analyses, followed by multivariate analyses. A total of 302 patients were included in this study, where the mean age (SD) was 46.5 (14.4) and 66.6% were male. Ninety-two patients (30.5%) had intestinal anisakiasis. Multivariate regression revealed that patients with intestinal anisakiasis were more 45 years old or older (odds ratio (OR) 3.45, 95% confidence interval (CI): 1.53-7.69), male (OR 2.70, 95% CI: 1.20-6.25) and regular alcohol drinker. In terms of the physical and laboratory findings, patients with intestinal anisakiasis had greater heart rate (OR 2.86, 95% CI: 1.33-6.25), higher total protein (OR 2.86, 95% CI: 1.16-6.67), and higher C-reactive protein (CRP) (OR 11.1, 95% CI: 3.03-33.3). Older males who were regular alcohol drinkers were associated with intestinal anisakiasis, and often heart rate, total protein, and CRP were elevated compared to those of patients with gastric anisakiasis.


Perinatal exposure to low-dose decabromodiphenyl ethane increased the risk of obesity in male mice offspring.
Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants (NBFRs) used to replace DecaBDE, has been frequently detected in the environment and human samples. In this study, we explored its toxic effects on male mouse offspring after perinatal exposure to DBDPE. During the perinatal period, pregnant ICR mice were exposed to DBDPE (100 μg/kg body weight) via oral gavage. After weaning, male offspring were fed on a low-fat diet and a high-fat diet, respectively. We measured and recorded body weight, liver weight, and epididymis fat mass, blood biochemical markers, metabolites changes in liver, and gene expression involved in lipid and glucose homeostasis. The results showed that perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial function and glucose metabolism, furthermore, the use of HFD feeding may further exacerbate these effects. All of these results show that early-life exposure to low doses of DBDPE can promote the development of metabolic dysfunction, which in turn induces obesity.


[Role of endogenous intoxication in multiple organ dysfunction development in cardiosurgical patients in early postoperative period].
to evaluate endogenous intoxication (EI) and multiple organ dysfunction (MOD) in cardiosurgical patients after open heart surgery. twenty six patients with MOD signs and 29 patients with an uneventful postoperative period were studied. MOD severity was assessed with SOFA scoring. EI was quantified with middle molecular weight peptides (MMWP), malondialdehyde and couple triens. on the first postoperative day MOD patients were characterized by high EI (MMWP: +36.7%), while control patients had a mild EI (MMWP: +20.7%). On the 3rd-4th postoperative days in the main group SOFA scores was decreased and EI intensity was increased (MMWP: +43.3%), while in the control group EI fitted the preoperative value. The major defference on the 10th-12th postoperative day was observed. In the main group severity of MOD matched that over the previous period. The intensity of EI remained elevated (MMWP: +30%), while in the control group EI level was equal to the baseline. The correlation analysis showed a positive relationship between EI and MOD pareameters, and positive connection between EI/MOD parameters and cardiopulmonary bypass/aortal occlusion duration. patients with MOD have more considerable EI compared with an uneventful postoperative period. EI increase is one of the main causes of MOD development in cardiac surgery patients. Cardiopulmonary bypass/aortal occlusion potentiate endogenous intoxication and MOD development after cardiac surgery.


Role of interleukin-2 and interleukin-6 in the mitogen responsiveness of T cells from patients with 'common-variable' hypogammaglobulinaemia.
We have assessed the ability of interleukin-2 (IL-2) and interleukin-6 (IL-6) to augment the proliferative response of T lymphocytes from 'common-variable' hypogammaglobulinaemia (CVH) patients and from normal controls, to the mitogens phytohaemagglutinin (PHA) and OKT3. We show that with cells from the control group and from those patients whose T cells respond to PHA within the control range, both IL-2 and IL-6 will significantly augment the response to OKT3. However, in those patients with a T cell defect in which the PHA response is below the control range, neither IL-2 nor IL-6 could restore the PHA or OKT3 response to normal. Responses to IL-2 or IL-6 alone were always in or above the control range.


Melanocyte system for studying stem cell niche.
There are many notions in stem cell biology that lack proof. The stem cell niche is the most typical example. While it is a convenient terminology for designating anything that supports stem cells, the cellular basis of the niche is poorly understood for many stem cell systems. In this chapter, we describe how useful the melanocyte system would be for investigating the molecular and cellular basis of the niche.


Hypertension management in a Cape Peninsula coloured community. A retrospective medium-term assessment.
A retrospective study of the records of a large hypertension clinic at a primary care centre was carried out for the period 1975-1984. A total of 250 patients were selected from a systemic 1-in-2 sample. The objectives were to establish the degree of control, compare the use of a large arm blood pressure (BP) cuff with a standard one, and determine the prevalence of associated diseases and the cost of drug therapy. The mean systolic BP was 163.2 mmHg, with 45% of patients having a systolic BP below 160 mmHg. The mean diastolic BP was 101.2 mmHg with 13% of patients having a diastolic BP below 95 mmHg. The majority of patients were overweight and the large BP cuff was found to be useful.


Bartonella machadoae sp. nov. isolated from wild rodents in the Pantanal wetland.
It has been estimated that 75% of emerging infectious diseases comprise zoonoses, whose majority have free-living animals as reservoirs and are mainly transmitted by arthropod vectors. Although rodents represent important Bartonella reservoirs, there are few studies on the genotypic characterization of Bartonella species commonly found in this taxon and from different Brazilian biomes. Therefore, the present study aimed to investigate the occurrence, isolate and molecularly, morphologically and phenotypically characterize a new Bartonella species infecting free-living rodents sampled in the Brazilian Pantanal, the largest wetland in South America. For this purpose, 129 free-living rodents (79 Thrichomys fosteri, 4 Clyomys laticeps, and Oecomys mamorae) were captured. While blood samples were collected from 57 T. fosteri, 4 C. laticeps and 32 O. mamorae; spleen samples were collected from 22 T. fosteri and 14 O. mamorae. Blood and spleen samples were submitted to a qPCR for Bartonella spp. targeting the nuoG gene, using DNA samples extracted directly from blood/spleen, after passage in pre-enrichment liquid culture, and from colonies obtained from solid culture on chocolate agar. Combining all techniques, occurrence of 24.8% for Bartonella sp. was found among the sampled rodents. One Bartonella isolate (strain 56A) obtained from a T. fosteri's blood sample was closely related to the Bartonella vinsonii complex and selected for Whole Genome Sequencing (WGS) hybrid approach using Illumina NovaSeq and Nanopore sequencing platforms. This strain exhibits a circular 2.7 Mbp genome with an average C+G content of 39% and encoding to 2239 genes. In the phylogenomics based on 291 shared protein-coding genes, this strain was positioned in a unique clade, closely related to Bartonella vinsonii subsp. vinsonii, B. vinsonii subsp. berkhoffii and B. visonii subsp. arupensis. An Average Nucleotide Identity of 85% was found between the obtained isolate and Bartonella species belonging to B. vinsonii complex. These findings supported the separation of this strain, now formally named as Bartonella machadoae sp. nov., from the Bartonella vinsonii complex. In addition, Bartonella machadoae sp. nov. was characterized by capnophilic, microaerophilic and aerobic small rods with absence of pili and flagella. Phylogenetic and distance analyses based on five concatenated molecular markers suggest that Bartonella machadoae may parasite rodents from different Brazilian biomes. In conclusion, we described biochemical, phenotypic and genomic characteristics of Bartonella machadoae nov. sp. isolated from blood samples of T. fosteri rodents from the Brazilian Pantanal.


Chronic granulomatous disease--pieces of a cellular and molecular puzzle.
Chronic granulomatous disease (CGD) is an inherited disorder in which phagocytes are unable to manufacture microbicidal oxidants. The disorder may be classified into subtypes depending upon the mode of transmission (X-linked or autosomal recessive) and the presence or absence of a heme protein designated 'cytochrome b558' (see below). Patients with CGD suffer recurrent deep-seated bacterial infections that respond poorly to therapy, slowly destroy affected tissues and eventually claim the patients' lives. Clinical deterioration is slowed, though not stopped, by the current practice of placing CGD patients on prophylactic antibiotics. Microbicidal oxidant production fails in CGD because of a defect in the enzyme responsible for the production of superoxide (O2-), the single precursor from which all the microbicidal oxidants ultimately arise. This enzyme, the respiratory burst oxidase, is a membrane-bound oxidase that catalyses the one-electron reduction of oxygen to O2- at the expense of NADPH. The oxidase is dormant in resting phagocytes, but comes to life when the phagocytes are exposed to bacteria or other appropriate stimuli. Components related to the respiratory burst oxidase include cytochrome b558 (one of those subunits has recently been shown to be encoded by a gene that is defective in the most common form of CGD), a flavoprotein that participates directly in O2- production, a cytosolic factor needed for the activation of the oxidase, and a group of 48K phosphoproteins. How these components relate to each other and to the O2- -forming activity of the oxidase is currently under active investigation.


A comparison of six epicutaneous devices in the performance of immediate hypersensitivity skin testing.
Six devices commonly used for immediate hypersensitivity epicutaneous skin testing were compared with regard to precision and diagnostic accuracy. Fifteen subjects were tested on the back to 10 mg/ml of histamine phosphate and 50% glycerosaline by prick technique with a smallpox needle (SN), bifurcated needle (BN), Greer "pen" (GP), and blood lancet, and by puncture with the Morrow-Brown needle (MB) and Multi-Test (MT). Five devices were tested in quintuplicate to histamine and once to glycerosaline in each subject; with MT, five histamine and three glycerosaline sites were used. Analysis of the wheal areas obtained with SN, BN, GP, and MB demonstrated comparable degrees of precision (coefficient of variation). The precision of MT was less than the other devices (p less than 0.05). The blood lancet demonstrated intermediate precision. Twenty-two of 45 (49%) of the glycerosaline skin tests performed with MT were falsely positive, significantly more than the other devices (p = 0.0001). We conclude that MB, BN, GP, and SP are comparable devices for use in immediate hypersensitivity skin testing. The low precision and reliability of MT used for testing on the back would appear to make this device less than adequate for diagnostic or research studies. Its high rate of false positive reactions requires caution in interpretation of results when it is used in the clinical diagnosis of allergy.


An evaluation of the Dental 3D Multimedia System on dentist-patient interactions: a report from China.
The aim of this study was to evaluate the effect of introducing the Dental 3D Multimedia (D3DM) System on dentist-patient interactions. An initial version of the D3DM developed in a series of researches was applied to the current study. A longitudinal pre-post study was setup: volunteer patients answered questionnaires at three differing intervals during the course of the study: before the introduction of the D3DM during the first visit, after the introduction of the D3DM during the first visit, and after the introduction of the D3DM during the second visit. The questionnaires related to patient satisfaction and covered three main areas of interests: (1) satisfaction with visit components, (2) comprehension about dental issues, and (3) perceptions with regard to dental office computing. Compared with baseline, patient overall satisfaction increased significantly both immediately after the introduction of the D3DM and at the second visit. Patient's satisfaction with dentist's familiarity with them, and satisfaction with dental issues generally increased. On measures of psychological communication and available time, patients generally reported that no changes occurred during visits. A majority of participants reported that they preferred the D3DM more than traditional dentist-patient communication patterns. There were no significant changes in patient perceptions of the computer use over time. the D3DM appeared to have positive effects on dentist-patient communications, improving the mutual understanding between them. There were no significant negative effects directly generated from the computer intervention. Further research is needed to update the current D3DM and investigate how the system might be best implemented in the dental office environment.


The Marine Bacterium Shewanella woodyi Produces C8-HSL to Regulate Bioluminescence.
Quorum sensing (QS), a cell-to-cell communication system involved in the synchronization of bacterial behavior in a cell-density-dependent manner has been shown to control phenotypes such as luminescence, virulence, and biofilm formation. The marine strain, Shewanella woodyi MS32 has been identified as a luminous bacterium. Very little information is known on this bacterium, in particular if its luminescence and biofilm formation are controlled by QS. In this study, we have demonstrated that S. woodyi MS32 emits luminescence in planktonic and sessile conditions. The putative QS regulatory genes homologous to luxI and luxR identified in the S. woodyi MS32 genome, named swoI and swoR, are divergently transcribed and are not genetically linked to the lux operon in contrast with its closest parent Shewanella hanedai and with Aliivibrio fischeri. Interestingly, the phylogenetic analysis based on the SwoI and SwoR sequences shows that a separate horizontal gene transfer (HGT) occurred for the regulatory genes and for the lux operon. Functional analyses demonstrate that the swoI and swoR mutants were non-luminescent. Expression of lux genes was impaired in the QS regulatory mutants. N-octanoyl-L-homoserine lactone (C8-HSL) identified using liquid chromatography mass spectrometry in the wild-type strain (but not in ΔswoI) can induce S. woodyi luminescence. No significant difference has been detected between the wild-type and mutants on adhesion and biofilm formation in the conditions tested. Therefore, we have demonstrated that the luxCDABEG genes of S. woodyi MS32 are involved in luminescence emission and that the swoR/swoI genes, originated from a separate HGT, regulate luminescence through C8-HSL production.


Structural basis of ultraviolet-B perception by UVR8.
The Arabidopsis thaliana protein UVR8 is a photoreceptor for ultraviolet-B. Upon ultraviolet-B irradiation, UVR8 undergoes an immediate switch from homodimer to monomer, which triggers a signalling pathway for ultraviolet protection. The mechanism by which UVR8 senses ultraviolet-B remains largely unknown. Here we report the crystal structure of UVR8 at 1.8 Å resolution, revealing a symmetric homodimer of seven-bladed β-propeller that is devoid of any external cofactor as the chromophore. Arginine residues that stabilize the homodimeric interface, principally Arg 286 and Arg 338, make elaborate intramolecular cation-π interactions with surrounding tryptophan amino acids. Two of these tryptophans, Trp 285 and Trp 233, collectively serve as the ultraviolet-B chromophore. Our structural and biochemical analyses identify the molecular mechanism for UVR8-mediated ultraviolet-B perception, in which ultraviolet-B radiation results in destabilization of the intramolecular cation-π interactions, causing disruption of the critical intermolecular hydrogen bonds mediated by Arg 286 and Arg 338 and subsequent dissociation of the UVR8 homodimer.


Using the common sense model to design interventions for the prevention and management of chronic illness threats: from description to process.
In this article, we discuss how one might use the common sense model of self-regulation (CSM) for developing interventions for improving chronic illness management. We argue that features of that CSM such as its dynamic, self-regulative (feedback) control feature and its system structure provide an important basis for patient-centered interventions. We describe two separate, ongoing interventions with patients with diabetes and asthma to demonstrate the adaptability of the CSM. Finally, we discuss three additional factors that need to be addressed before planning and implementing interventions: (1) the use of top-down versus bottom-up intervention strategies; (2) health care interventions involving multidisciplinary teams; and (3) fidelity of implementation for tailored interventions.


Geometric multigrid to accelerate the solution of the quasi-static electric field problem by tetrahedral finite elements.
The acceleration of the solution of the quasi-static electric field problem considering anisotropic complex conductivity simulated by tetrahedral finite elements of first order is investigated by geometric multigrid.


Nutraceuticals: Definition and Epidemiological Rationale for Their Use in Clinical Practice.
Cardiometabolic risk factors, such as hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, diabetes, and arterial hypertension, are major predictors of the premature development of cardiovascular diseases (CVD). Since CVD prevention needs a life-course approach, beyond dietary and pharmacological treatment, non-pharmacological treatment should be considered an important alternative for patients in primary prevention with mild-moderate cardiometabolic risk factors at low-moderate global risk of CVD. Several functional foods and nutraceuticals are efficacious, safe and well tolerated. However, only some (monacolins of red yeast rice and omega-3 fatty acids) have showed, in long-term randomized clinical trials, a reduction of cardiovascular events.


Association Between CLOCK Gene Variants and Restless Legs Syndrome in Koreans.
Previous studies have suggested various causes of restless legs syndrome (RLS), including iron and dopamine concentrations in the brain. Genetic influences have also been reported in many studies. There is also a possibility that circadian clock genes may be involved because symptoms of RLS worsen at night. We investigated whether CLOCK and NPAS2 gene polymorphisms were associated with RLS. A total of 227 patients with RLS and 229 non-RLS matched controls were assessed according to the International Restless Legs Syndrome Study Group diagnostic criteria. Genotyping was performed using reverse transcription polymerase chain reaction and high-resolution melting curve analyses. Although the genotype distributions of the CLOCK variants (rs1801260 and rs2412646) were not significantly different between patients with RLS and non-RLS controls, the allele frequencies of CLOCK rs1801260 showed marginally significant differences between the two groups (X2 =2.98, p=0.085). Furthermore, there was a significant difference in the distribution of CLOCK haplotypes (rs1801260-rs2412646) between patients with RLS and non-RLS controls (p=0.013). The distributions of allelic, genotypic, and haplotypic variants of NPAS2 (rs2305160 and rs6725296) were not significantly different between the two groups. Our results suggest that CLOCK variants may be associated with decreased susceptibility to RLS.


Adaptive Markov chain Monte Carlo for auxiliary variable method and its application to parallel tempering.
Auxiliary variable methods such as the Parallel Tempering and the cluster Monte Carlo methods generate samples that follow a target distribution by using proposal and auxiliary distributions. In sampling from complex distributions, these algorithms are highly more efficient than the standard Markov chain Monte Carlo methods. However, their performance strongly depends on their parameters and determining the parameters is critical. In this paper, we proposed an algorithm for adapting the parameters during drawing samples and proved the convergence theorem of the adaptive algorithm. We applied our algorithm to the Parallel Tempering. That is, we developed an adaptive Parallel Tempering that tunes the parameters on the fly. We confirmed the effectiveness of our algorithm through the validation of the adaptive Parallel Tempering, comparing samples from the target distribution by the adaptive Parallel Tempering and samples by conventional algorithms.


Frequency and significance of conduction defects in acute myocardial infarction.
The frequency of intraventricular conduction defects was determined in 556 consecutive patients with proven acute myocardial infarction. Complete left bundle branch block was present in 23 patients and carried a high mortality rate (61 per cent). Complete right buldle branch block was the rarest defect to be seen in isolation (8 patients) and carried a lower mortality rate (38%). Lone left anterior hemiblock was present in 72 patients and was associated with a low mortality rate (13 per cent); left posterior hemiblock occurred in 32 patients (mortality rate 19 per cent). In a further 59 patients right bundle branch block with left anterior or posterior hemiblock in addition was present and these patients had a high mortality rate which was greater than isolated right bundle branch block or hemiblock alone. Complete atrioventricular block developed in 51 patients, 26 of whom had prior evidence of intraventricular conduction defect. Despite the use of temporary transvenous pacing, mortality in patients who developed complete heart block was significantly increased whether or not an intraventricular conduction defect was already present. The significance of these findings for the management of patients with myocardial infarction is discussed.


Neutrophil and Neutrophil-to-Lymphocyte Ratio as Clinically Predictive Risk Markers for Recurrent Pregnancy Loss.
We aimed at exploring the value of neutrophil and neutrophil-to-lymphocyte ratio (NLR) as predictive risk markers for recurrent pregnancy loss (RPL) by conducting a retrospective case-control study and a systematic review and meta-analysis. This retrospective case-control study was conducted in an academic hospital from January 2012 to June 2018 and 133 cases of women with RPL and 140 control women. In parallel, we conducted a systematic review and meta-analysis on the value of NLR and neutrophil in RPL risk assessment. Neutrophil and NLR were higher in the women with RPL than those in the controls (median [interquartile range]: 4.32 [3.31-6.18] vs. 3.76 [2.78-4.81], p = 0.001; 2.17 [1.47-3.16] vs. 1.74 [1.40-2.34], p = 0.001). After the cut-off value of the neutrophil and NLR was determined to be 6.3 × 109/L and 3.16, the prevalence of RPL became significantly increased in the high-neutrophil and the high-NLR group compared to the low-neutrophil and the low-NLR group (76.3% vs. 44.2%, p < 0.001; 66.6% vs. 44.5%, p < 0.001). Univariate logistic regression analysis indicated that high-neutrophil and high-NLR were risk factors for RPL, with ORs of 4.06 (95% CI: 1.84-8.95) and 2.49 (95% CI: 1.31-4.71), respectively. Multivariate logistic regression analysis indicated that high-neutrophil was a risk factor for RPL, with OR of 4.91 (95% CI: 1.66-14.50). Meta-analysis of 5 case-control studies (including the present study) indicated that increased neutrophil and NLR may be risk factors for RPL, with SMDs of 0.63 (95% CI: 0.45-0.80) and 0.61 (95% CI: 0.39-0.83). Based on current findings and the meta-analysis, this study indicated that neutrophil and NLR might be valuable for predicting RPL; more studies with large sample are needed to verify this conclusion. The mechanism of the association between neutrophil and RPL needs to be explored in further studies.


Volatile compounds produced in smoked bacon inoculated with potential spoilage bacteria.
Volatile organic compounds (VOCs) produced during meat storage are mainly derived from the decomposition of meat components and the metabolism of spoilage bacteria. VOCs produced in sterile bacon model substrate inoculated or un-inoculated with spoilage bacteria, Staphylococcus xylosus (P2), Leuconostoc mesenteroides (P6), Carnobacterium maltaromaticum (P9), Leuconostoc gelidum (P16) and Serratia liquefaciens (P20), previously isolated, were identified by headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). Furthermore, combinations of the strains (Pm) were also obtained. In total, 54 volatile compounds, including aldehydes, alcohols, phenols, ketones, alkanes, alkanes, organic acids, esters and so forth, were determined after 45 days of storage in bacon inoculated with potential spoilage bacteria using the HS-SPME/GC-MS method. VOC concentrations of alcohols and organic acids in groups inoculated with bacteria were remarkably higher (P < 0.05) compared to that in control samples. Specifically, some VOCs are closely related to the metabolic activity of the inoculated bacterial strains; for example, 2,3-butanediol was associated with P2, P16 and P20, and acetic acid was mainly related to P6 and P9. The results of partial least squares regression indicated that there was a high correlation between the electronic nose sensors and VOCs of smoked inoculated potential spoilage bacteria. These compounds are potentially important for predicting deterioration of smoked bacon. © 2023 Society of Chemical Industry.


Involving junior doctors in medical article publishing: is it an effective method of teaching?
Having peer-reviewed articles published in medical journals is important for career progression in many medical specialties. Despite this, only a minority of junior doctors have the skills in the area of medical article publishing. The aim of this study was to assess junior doctors' views concerning being involved in medical article publishing and whether they perceive involvement as an effective method of teaching. A cross-sectional survey was administered to a convenience sample of doctors who had been involved in medical article publishing. Questions concerned training and involvement in publishing as junior doctors, effects on education and training, is it an effective method of teaching and should publishing be part of their education and training program. Questions used the 5-point Likert scale. Of the 39 doctors, 37 (94.9%) doctors responded. Only one-third of respondents agreed that they had adequate training or involvement in medical article publishing during their undergraduate medical training. Many (78.4%) agreed that it was difficult to get published as a junior doctor. Publishing as a junior doctor improved knowledge about publishing, understanding of the topic and interest in the field of study for 92, 92 and 73% of respondents, respectively. Many (89%) agreed that publishing made them eager to publish more. Most (76%) agreed that it was likely to encourage interest in a postgraduate career in that field of study. A majority (92%) felt that involvement in medical article publishing is an effective method of teaching and it should be a part of the junior doctors' education and training program. Junior doctors feel that involvement in medical article publishing contributes to learning and education and is an effective method of teaching. This supports the need to incorporate such training into the junior doctors' education and training program.


Prevalence of hearing loss and clinical otologic manifestations in patients with 22q11.2 deletion syndrome: A literature review.
Hearing loss and otitis media are frequently reported in patients with 22q11.2 deletion syndrome. Our objective was to review the current literature on the prevalence of hearing loss and otologic manifestations in patients with 22q11.2 deletion syndrome. Systematic review. We conducted a systematic search in PubMed and Embase combining the term "22q11.2 deletion syndrome" and synonyms with "hearing loss" and "otologic manifestations" and synonyms. We screened title/abstract and full text of all retrieved articles on pre-defined in- and exclusion criteria. The remaining articles were assessed on risk of bias. Outcome measures included the prevalence of hearing loss and otologic manifestations such as otitis media. Our search yielded 558 unique studies of which a total of 25 articles were included for critical appraisal and data extraction. Twenty-one studies reported on hearing loss, and 21 studies on otologic manifestations. The prevalence of hearing loss varied from 6.0% to 60.3%, where in most studies conductive hearing loss was most prevalent. Rates of recurrent or chronic otitis media varied from 2.2% to 89.8%. Although a very broad range in prevalences is reported in different studies, hearing loss and recurrent or chronic otitis media are frequently present in patients with 22q11.2 deletion syndrome. Regular check-ups and audiometric testing are advised in these patients.


Annojahnin from Annona jahnii: a possible precursor of mono-tetrahydrofuran acetogenins.
A new cytotoxic Annonaceous acetogenin, annojahnin (1), was isolated from the twigs of Annona jahnii (Annonaceae) by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C-37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings, bearing a keto group at C-10, and possessing a double bond located two methylenes away from a vicinal diol. The structure and absolute configuration of 1 were elucidated by 1H and 13C NMR, COSY, and single-relayed COSY and from chemical derivatives. 4-Deoxy-18/21-trans-annomontacin 10-one (4) and 4-deoxy-18/21-cis-annomontacin-10-one (5), two semisynthetic mono-THF acetogenins, were prepared from 1 by reactions that mimic the biogenetic pathways. These acetogenins showed selective cytotoxicities, comparable or superior to adriamycin, among six human solid tumor cell lines. Reduction of the 10-keto of 1, to the racemic 10-OH derivative (3), retained the bioactivities as did the conversion of 1 to 4 and 5.


Volatile organic compounds (VOC), formaldehyde and nitrogen dioxide (NO2) in schools in Johor Bahru, Malaysia: Associations with rhinitis, ocular, throat and dermal symptoms, headache and fatigue.
This paper studied associations between volatile organic compounds (VOC), formaldehyde, nitrogen dioxide (NO2) and carbon dioxide (CO2) in schools in Malaysia and rhinitis, ocular, nasal and dermal symptoms, headache and fatigue among students. Pupils from eight randomly selected junior high schools in Johor Bahru, Malaysia (N=462), participated (96%). VOC, formaldehyde and NO2 were measured by diffusion sampling (one week) and VOC also by pumped air sampling during class. Associations were calculated by multi-level logistic regression adjusting for personal factors, the home environment and microbial compounds in the school dust. The prevalence of weekly rhinitis, ocular, throat and dermal symptoms were 18.8%, 11.6%, 15.6%, and 11.1%, respectively. Totally 20.6% had weekly headache and 22.1% fatigue. Indoor CO2 were low (range 380-690 ppm). Indoor median NO2 and formaldehyde concentrations over one week were 23μg/m3 and 2.0μg/m3, respectively. Median indoor concentration of toluene, ethylbenzene, xylene, and limonene over one week were 12.3, 1.6, 78.4 and 3.4μg/m3, respectively. For benzaldehyde, the mean indoor concentration was 2.0μg/m3 (median<1μg/m3). Median indoor levels during class of benzene and cyclohexane were 4.6 and 3.7μg/m3, respectively. NO2 was associated with ocular symptoms (p<0.001) and fatigue (p=0.01). Formaldehyde was associated with ocular (p=0.004), throat symptoms (p=0.006) and fatigue (p=0.001). Xylene was associated with fatigue (p<0.001) and benzaldehyde was associated with headache (p=0.03). In conclusion, xylene, benzaldehyde, formaldehyde and NO2 in schools can be risk factors for ocular and throat symptoms and fatigue among students in Malaysia. The indoor and outdoor levels of benzene were often higher than the EU standard of 5μg/m3.


Inhibition of histone deacetylase1 induces autophagy.
Autophagy is a process where cytoplasmic materials are degraded by lysosomal machinery. Histone deacetylase (HDAC) inhibitors induce autophagy, and HDAC6, one of class II HDAC isotypes, is directly involved in autophagic degradation in the cell. However, it is unclear if class I HDAC isotype such as HDCA1 is involved in this process. To investigate if class I HDAC isotype is involved in autophagy, a specific class I HDAC inhibitor and an siRNA of HDAC1 were used to treat HeLa cells. Autophagic markers were then investigated. Both inhibition and genetic knock-down of HDAC1 in the cells significantly induced autophagic vacuole formation and lysosome function. Moreover, disruption of HDAC1 leads to the conversion of LC3-I to LC3-II. Together, these results demonstrate that HDAC1 could play a role in autophagy and specific inhibition of HDAC1 can induce autophagy.


[Assessment of laboratory diagnostic network in the implementation of the Program for Viral Hepatitis Prevention and Control in São Paulo State, Brazil, 1997-2012].
to assess the performance of the diagnostic network in the implementation process of the Program for Viral Hepatitis Prevention and Control in São Paulo State, Brazil, from 1997 to 2012. evaluation study based on documentary research and structured interviews, combined with a historical series analysis of indicators developed to assess the implementation process of the program, using data from the Department of the Brazilian National Health System. from 1997 to 2012, the serology, biopsy and molecular biology diagnostic networks showed an increase in the coefficients of coverage of 7.4, 7.3, and 62.0 times, respectively, with an increase in cases detection and treatment access. despite the effective implementation of the diagnostic network, there is a need to review the search strategy for new cases, and access to liver biopsy, still insufficient to the program demand.


Pictorial adaptation of the quality of recovery 15 scale and psychometric validation into a pediatric surgical population.
Patient reported outcomes measures (PROMS) are important endpoints to measure patient health status in the perioperative setting. However, there are no good tools to measure PROMS in the pediatric surgical population. Patients 7 to 17 years old undergoing surgery were included and followed up for 1 day after surgery (POD1). At POD1 the patients were asked to rate their overall postoperative recovery using a 100-mm visual analog scale (VAS). The primary outcome was the pediatric QoR-15 score on postoperative day 1 (POD1). 150 patients completed the study. The mean (SD) pediatric QoR-15F scores were 132.1 (14.1) and 111.0 (27.0), preoperatively and on POD1, respectively. Convergent validity confirmed with Pearson (r) correlation between the postoperative pediatric QoR-15F and the patient-rated global recovery assessment was 0.72 (95% confidence interval [0.63-0.79]; p < 10-16). Concerning reliability, internal consistency of the pediatric QoR-15 assessed by Cronbach's alpha was 0.90. The test-retest concordance correlation coefficient was 0.92; 95% CI [0.83-0.96]. Split-half alpha was 0.74. The pictorial pediatric version of the QoR-15F showed good validity, reliability, responsiveness, acceptability and feasibility. This PROMS should be considered for clinical care and research in the perioperative pediatric patient setting.Trial Registration: NCT04453410 on clinicaltrials.gov.


Internal carotid artery variations in velocardiofacial syndrome patients and its implications for surgery.
Medially displaced internal carotid arteries in velocardiofacial syndrome carry a risk during pharyngeal flap surgery. This study was designed to evaluate the frequency of medially deviated internal carotid arteries in both velocardiofacial syndrome patients and the general pediatric population and to assess the minimum distance to the pharyngeal walls to define the potential risk of internal carotid artery injury during pharyngeal surgery. Twenty-three consecutive patients with velocardiofacial syndrome who underwent posterior pharyngeal flap surgery and 21 control subjects who did not have velocardiofacial syndrome but who underwent oropharynx magnetic resonance imaging were reviewed. Medial deviation of at least one internal carotid artery was documented in 10 velocardiofacial syndrome patients (43.5 percent), compared with three patients (14.3 percent) in the control group (p=0.034). The mean±SD minimum distance to the posterior pharyngeal wall was 3.78±1.86 mm in velocardiofacial syndrome patients and 9.17±2.94 mm in the control group (p=0.014). Only one patient had significant medial dislocation of the internal carotid artery, and the closest distance from the pharyngeal wall was 0.86 mm. In velocardiofacial syndrome patients, medial dislocation of the internal carotid artery was common, and the minimum distance to the pharyngeal wall was short compared with the control group. However, in most of the authors' patients, the course of the cervical portion of the internal carotid artery is irrelevant to pharyngeal flap surgery. The authors conclude that preoperative vascular imaging study is not cost-effective in velocardiofacial syndrome patients but that intraoperative use of ultrasound imaging is still valuable for the purpose of planning pharyngeal flap surgery. Risk, II.


[Incidence of oxyuriasis in a schoolchild population in Milan, with socio-economic correlations. Verification of the therapeutic effectiveness of pyrantel pamoate].
440 children aged between 3 and 5 were examined for Oxyuriasis in three schools of Milan during three different days. 31% of the children resulted parasited by Enterobius vermicularis: a clear correlation between parasitosis and socio-economic condition has been demonstrated. Treatment with "pirantel pamoate" has been proved effective in 88% of the cases.


5-Substituted 1H-pyrrolo[3,2-b]pyridines as inhibitors of gastric acid secretion.
A series of novel 1H-pyrrolo[3,2-b]pyridines was prepared relying on a copper iodide catalyzed cyclization of 2-prop-1-ynylpyridin-3-amines. A structure-activity relationship was established focusing on the influence of the substitution pattern in position 1, 3, and 5 of the heterocycle on anti-secretory activity, lipophilicity, and pK(a) value. Some of the compounds proved to be potent inhibitors of the gastric acid pump.


Depression, diabetes and metabolic-nutritional factors in elderly Hispanics.
To examine the relationship of depression to metabolic and nutritional risk factors in older Hispanics. Crossectional study. Subjects were part of a community-based, cognitive evaluation project that examined 301 subjects in the Eastern San Fernando Valley of Southern California. Two elderly Hispanic groups: 53 clinically depressed, with memory complaints but not demented subjects, and 33 generally healthy, cognitively asymptomatic subjects. The results of functional and nutritional questionnaires, a medical and neurological examination, 12-hour fasting clinical laboratory tests, MRI or CT scans, and neuropsychological testing. Both groups were nearly identical along socio-demographic variables. However, the depressed group differed significantly from the general healthy group not only in percent of diabetics (38% vs.18%), but in the amount of poorly controlled diabetes, and the depressed group consumed about half the amount of fish that the generally healthy group did. This study suggests that factors such as poorly controlled diabetes combined with low consumption of foods high in omega-3 fatty acid content such as sea fish may be associated with an increased risk of developing depression in late life. These factors may be socio-economically and culturally influenced and are therefore amenable to modification.


Inhibitory pathway from the frontal cortex to the hypothalamic ventromedial nucleus in the rat.
Stimulation of the dorsal frontal cortex (area 10, FCtx) evoked two negative waves with short latencies (N1 and N2) followed by a large, longlasting positive wave (P) in the ventromedial nucleus (VMH) as well as in the more dorsal structures in the hypothalamus and the ventral thalamus. Since the N1 followed high frequency stimulation, it was concluded to be due to antidromic activity. Double or triple pulse stimulation summated the P, and reduced the amplitude of the negative waves of the second and the third responses. VMH neuronal discharges were also decreased during the time course of the P. Therefore, the P was concluded to be composed of the IPSPs. VMH neuronal discharges were frequently superimposed on the N2, indicating the origin of this wave to be EPSPs. Strychnine reduced or blocked the inhibition of the VMH neurons caused by not only FCtx stimulation but also glycine application. The results indicate that the VMH receives both excitatory and inhibitory projections from the FCtx, and the inhibition may be transmitted by glycine.


Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases.
Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (mEGFR and mKRAS) are useful biomarkers in resected non-small cell lung cancer (NSCLC). We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012. mEGFR was observed in 103 patients (12.2%), and mKRAS in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for mKRAS (OS: 43 months; TTR: 19 months) compared with mEGFR (OS: 67 months; TTR: 24 months) and wild-type patients (OS: 55 months; disease-free survival (DFS): 24 months). Patients with KRAS G12V exhibited worse OS and TTR compared with the entire cohort (OS: KRAS G12V: 26 months vs 60 months; DFS: KRAS G12V: 15 months vs 24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR): 0.43 (confidence interval: 0.28-0.65), P<0.0001 for OS; HR: 0.67 (0.48-0.92), P=0.01 for TTR). Risk of recurrence was significantly lower for non-KRAS G12V (HR: 0.01, (0.001-0.08), P<0.0001). mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences.


Detection of non-covalent interaction of single and double stranded DNA with peptides by MALDI-TOF.
DNA-histone interaction facilitates packaging of huge amounts of DNA in the confined space of the nucleus. The importance of this interaction underscores the need for new analytical techniques to acquire a better understanding of nuclear dynamics. Electrospray-ionization mass spectrometry made it possible to investigate non-covalently-bound biopolymers. We are enlarging the scope of available analytical tools by studying non-covalent interaction between single and double stranded DNA and peptides with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The interaction is an ionic one, between the negatively charged sugar-phosphate backbone of single stranded DNA and positively charged side chains of Arg- and Lys-rich peptides as demonstrated by Vertes' group with the dipeptides Arg-Lys and His-His. We replicated Lecchi and Pannell's work, which showed that double stranded DNA could be seen by MALDI using 6-aza-2-thiothymine (ATT) as matrix. We tried various peptides and found that as was demonstrated in DNA-histone interaction, a certain ratio and arrangement of basic residues was needed in order to generate ionic binding between DNA and peptide. We tested various single and double stranded DNA with the peptide of choice, and found that other variables such as pH value of solution, ionic strength, and matrix system did play a role.


Fingermark visualisation on thermal paper - A comparison among different procedures as an outcome of the 2018 collaborative exercise of the ENFSI Fingerprint Working Group.
In 2018 the Fingerprint Working Group (EFP-WG) of the European Network of Forensic Science Institutes (ENFSI) undertook a collaborative exercise (CE) with the aim of assessing the ability in developing fingermarks on an item constituted of a thermal layer. The test was prepared and managed by the officially established advisory group. The characteristics of the CE are summarised. Different approaches emerged from the outcomes showing on average valid results. What is evident from data is that the preliminary inspection is highly advisable especially for the thermal side exploiting specific combinations of wavelengths and filters. In general, better performances were achieved by laboratories using multiple processing techniques. Conversely, few laboratories were capable to reach the expected results with only one step process. Finally, data does not support the use of cyanoacrylate, powders, and iodine on this specific substrate.


CT-guided interstitial HDR-brachytherapy for recurrent glioblastoma multiforme: a 20-year single-institute experience.
To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM). Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient's median age was 57.1 years (14-82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42 cm3 (2-207 cm3). The prescribed HDR dose was median 40 Gy (30-50 Gy) delivered in twice-daily fractions of 5.0 Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated. At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%). For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity.


Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke.
While gelatinase (MMP-2 and -9) activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown. Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9) expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change. The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke.


Nanotechnology in the Fabrication of Protein Microarrays.
Protein biochips are the heart of many medical and bioanalytical applications. Increasing interest of protein biochip fabrication has been focused on surface activation and subsequent functionalization strategies for the immobilization of these molecules.


Induction of oestrus and ovulation by means of prostaglandin and gonadoliberin (GnRH) treatment in an old mare barren for two breeding seasons.
A 17-year-old Nooitgedacht mare was presented in mid-summer after failing to conceive during the previous 2 breeding seasons. The mare conceived to service during a PG-induced oestrus when synthetic GnRH was used to induce ovulation.


Effects of positive pressure in odontogenic keratocysts.
Intracystic fluid pressure is thought to be involved in odontogenic cyst growth. In this study, we investigated the effects of positive pressure on the expression of interleukin-1alpha (IL-1alpha), matrix metalloproteinases (MMPs), and prostaglandin E2 (PGE2) in odontogenic keratocysts to determine whether this pressure stimulates inflammatory cytokine production and signaling of osteoclastogenic events. Positive pressure enhanced the expression of IL-1alpha mRNA and protein in odontogenic keratocyst epithelial cells, and increased the secretion of MMP-1, MMP-2, MMP-3, and PGE2 in a co-culture of odontogenic keratocyst fibroblasts and the epithelial cells. The pressure-induced secretions were inhibited by an interleukin-1 receptor antagonist. Recombinant human interleukin-1alpha (rhIL-1alpha) increased the secretion of MMP-1, MMP-2, MMP-3, and PGE2 in the fibroblasts. Furthermore, in the fibroblasts, rhIL-1alpha enhanced the expression of macrophage colony-stimulating factor (M-CSF) mRNA, and rhIL-1alpha-induced PGE2 increased the expression of nuclear factor kappaB ligand (RANKL) mRNA. Thus, positive pressure may play a crucial role in odontogenic keratocyst growth via stimulating the expression of IL-1alpha in epithelial cells.


SIRT1 prevents cigarette smoking-induced lung fibroblasts activation by regulating mitochondrial oxidative stress and lipid metabolism.
Cigarette smoking (CS) is a strong risk factor for idiopathic pulmonary fibrosis (IPF). It can activate lung fibroblasts (LF) by inducing redox imbalance. We previously showed that clearing mitochondrial reactive oxygen species (mtROS) protects against CS-induced pulmonary fibrosis. However, the precise mechanisms of mtROS in LF need further investigation. Here we focused on mtROS to elucidate how it was regulated by CS in LF and how it contributed to LF activation. We treated cells with 1% cigarette smoking extract (CSE) and examined mtROS level by MitoSOX™ indicator. And the effect of CSE on expression of SIRT1, SOD2, mitochondrial NOX4 (mtNOX4), fatty acid oxidation (FAO)-related protein PPARα and CPT1a and LF activation marker Collagen I and α-SMA were detected. Nile Red staining was performed to show cellular lipid content. Then, lipid droplets, autophagosome and lysosome were marked by Bodipy 493/503, LC3 and LAMP1, respectively. And lipophagy was evaluated by the colocalization of lipid droplets with LC3 and LAMP1. The role of autophagy on lipid metabolism and LF activation were explored. Additionally, the effect of mitochondria-targeted ROS scavenger mitoquinone and SIRT1 activator SRT1720 on mitochondrial oxidative stress, autophagy flux, lipid metabolism and LF activation were investigated in vitro and in vivo. We found that CS promoted mtROS production by increasing mtNOX4 and decreasing SOD2. Next, we proved mtROS inhibited the expression of PPARα and CPT1a. It also reduced lipophagy and upregulated cellular lipid content, suggesting lipid metabolism was disturbed by CS. In addition, we showed both insufficient FAO and lipophagy resulted from blocked autophagy flux caused by mtROS. Moreover, we uncovered decreased SIRT1 was responsible for mitochondrial redox imbalance. Furthermore, we proved that both SRT1720 and mitoquinone counteracted the effect of CS on NOX4, SOD2, PPARα and CPT1a in vivo. We demonstrated that CS decreased SIRT1 to activate LF through dysregulating lipid metabolism, which was due to increased mtROS and impaired autophagy flux. These events may serve as therapeutic targets for IPF patients.


Management of an unusual left coronary artery to right ventricular fistula in a neonate.
Congenital coronary arterial fistula is a rare cause of congestive heart failure in neonates. We describe a neonate who developed early symptoms because of an unusually large left coronary artery to right ventricular fistula. Computed tomography and coronary angiography delineated anatomy and facilitated successful surgical closure.


Mitosis of the Hofbauer cell: possible implications for a fetal macrophage.
Human chorionic villi from placentae collected during the first half of pregnancy were examined by light microscopy and transmission electron microscopy. In serial semithin sections mitoses of Hofbauer cells, as well as those of other cellular components of the villous stroma, were generally easily identified. In some cases, when the Hofbauer cells showed very few vacuoles, thin sections were helpful in differentiating this cell type from the fixed stromal cells. Hofbauer cells in mitotic division were not uncommon, but were irregularly distributed. Mitosis of the Hofbauer cells could be a mechanism involved in maintaining the permanent presence in the chorionic villi of cell subpopulations with different origins and functions. Another explanation for the mitotic division of these cells could be that they are a self-renewing population independent of fetal monocytes which appear later in gestation in chorionic villi. In addition, mitosis of the Hofbauer cells could allow a rapid increase in their numbers when required by the local microenvironment.


Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity.
Soluble progranulin (PGRN) is known to directly regulate regulatory T cells; however, whether PGRN levels are elevated in patients with rheumatoid arthritis and affect the regulatory subsets of B cells remain unknown. In this study, a total of 80 RA patients and 60 healthy controls were studied. Serum progranulin levels were determined using enzyme-linked immune-sorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of serum PGRN as a biomarker for distinguishing patients with RA. CD19(+)CD5(+)GrB(+) B cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). Serum progranulin levels in RA patients (median, 59.4 ng/mL) and in RA patients DAS28 > 5.1 (median, 71.98 ng/mL) were much higher than those in normal controls (median, 46.3 ng/mL; P < 0.001). The area under the ROC curve for progranulin levels was 0.705 for RA versus normal controls and the area under the ROC curve for progranulin levels in RA patients DAS28 > 5.1 was 0.977 versus normal controls (P < 0.001). Interestingly, serum progranulin and DAS28, CRP, ESR were all positively correlated in RA patients (P < 0.001). The number of CD19(+)CD5(+)GrB(+) B cells was significantly higher in RA patients (P < 0.05); however, the level of Breg cells was not related to PGRN (P > 0.05). Our findings indicated that induction of PGRN expression may play a role in RA immune reaction and PGRN levels could be a useful biomarker in RA inflammatory response, but irrelated with Breg cell levels.


Pancreatic structure and function in the immature reserpinized rat.
Immature rats were reserpinized to determine whether the model used for adults may be suitable for the study of pancreatic exocrine insufficiency seen in infants with cystic fibrosis. Rats were reserpinized by injections either into pregnant dams or into newborn rats. The dose of reserpine used by others was lethal to immature rats, so lower doses were used. Pancreas from 1-day-old fetal-treated pups was hypoplastic, but concentration of chymotrypsinogen was elevated. At age 7 days hyperplasia was seen. When rats were reserpinized as neonates, hypoplasia and decrease in all parameters measured was observed at age 7 days. Progressive recovery occurred during the following 2 weeks in both groups. Electron microscopic study of the fetal-treated 24-hr-old pancreas revealed evidence of acinar cell degeneration with the presence of abnormal zymogen granules. At age 7 days the pancreas from neonatal-treated rat pups appeared to have a reduced number of granules. At ages 14 and 21 days the pancreas was similar to that seen at age 7 days except that the granules were larger and some acinar lumina were filled with a finely granular, homogeneously dense material. It is concluded that prenatal and neonatal reserpinization of rats induces changes in pancreas similar to those found in cystic fibrosis.


The lived experience of a mind-body intervention for people living with HIV.
Stress and anxiety are significant problems for individuals living with HIV. Mind-body therapies such as progressive muscle relaxation training and guided imagery (PMRT-GI) are effective in treating stress and anxiety in chronically ill persons. The purpose of this study was to identify key elements of an effective and culturally acceptable PMRT-GI intervention for economically disadvantaged persons with HIV. PMRT-GI was provided to 24 participants from African American, White, and Hispanic backgrounds. Using Colaizzi's phenomenological method, participants were interviewed about their experiences with PMRT-GI. Responses were tape-recorded, read, and reread; significant phrases and sentences were identified; meanings were formulated; and results were validated with participants. Five themes emerged: another world, feeling content, ease in muscle tension, one-on-one, and soft music. Background information and past experience with complementary and alternative methods were obtained.


Bovine herpesvirus-1: comparison and differentiation of vaccine and field strains based on genomic sequence variation.
Bovine herpesvirus-1 (BoHV-1) causes significant disease in cattle including respiratory, fetal diseases, and reproductive tract infections. Control programs usually include vaccination with a modified live viral (MLV) vaccine. On occasion BoHV-1 strains are isolated from diseased animals or fetuses postvaccination. Currently there are no markers for differentiating MLV strains from field strains of BoHV-1. In this study several BoHV-1 strains were sequenced using whole-genome sequencing technologies and the data analyzed to identify single nucleotide polymorphisms (SNPs). Strains sequenced included the reference BoHV-1 Cooper strain (GenBank Accession JX898220), eight commercial MLV vaccine strains, and 14 field strains from cases presented for diagnosis. Based on SNP analyses, the viruses could be classified into groups having similar SNP patterns. The eight MLV strains could be differentiated from one another although some were closely related to each other. A number of field strains isolated from animals with a history of prior vaccination had SNP patterns similar to specific MLV viruses, while other field isolates were very distinct from all vaccine strains. The results indicate that some BoHV-1 isolates from clinically ill cattle/fetuses can be associated with a prior MLV vaccination history, but more information is needed on the rate of BoHV-1 genome sequence change before irrefutable associations can be drawn.


Spin-Vibronic Control of Intersystem Crossing in Iodine-Substituted Heptamethine Cyanines.
Spin-orbit coupling between electronic states of different multiplicity can be strongly coupled to molecular vibrations, and this interaction is becoming recognized as an important mechanism for controlling the course of photochemical reactions. Here, we show that the involvement of spin-vibronic coupling is essential for understanding the photophysics and photochemistry of heptamethine cyanines (Cy7), bearing iodine as a heavy atom in the C3' position of the chain and/or a 3H-indolium core, as potential triplet sensitizers and singlet oxygen producers in methanol and aqueous solutions. The sensitization efficiency was found to be an order of magnitude higher for the chain-substituted than the 3H-indolium core-substituted derivatives. Our ab initio calculations demonstrate that while all optimal structures of Cy7 are characterized by negligible spin-orbit coupling (tenths of cm-1) with no dependence on the position of the substituent, molecular vibrations lead to its significant increase (tens of cm-1 for the chain-substituted cyanines), which allowed us to interpret the observed position dependence.


[The action of a homologous series of ubiquinols on lipid peroxidation in brain mitochondrial and synaptosomal membranes].
The effects of inhibition of ubiquinols and ubiquinones with various length of isoprenoid chain on the lipid peroxidation in membranes of brain mitochondria and synaptosomes were studied. The efficiency of inhibition effects of ubiquinols depends on the length of isoprenoid chain. Ubiquinols with shorter isoprenoid chains demonstrated more effective inhibition.


The impact of oral health on nutritional status.
In this article, the author argues that the assessment of oral health in older people is important as it can indicate signs and symptoms of oral and systemic disease.


Time course of hepatitis A virus antibody titer after active and passive immunization.
To investigate the antibody titer necessary to prevent hepatitis A virus infection, either 15 or 7.5 mg/kg of immune serum globulin was injected into 10 antihepatitis A virus negative volunteers and their serum antihepatitis A virus titers were observed for 28 wk. In addition, antibody titers were observed for 96 wk in a phase 1 clinical trial of a hepatitis A vaccine. The two studies were then compared to assess the immunogenicity of the vaccine and the persistence of the antibody. Serum-neutralizing antibody titers that were greater than or equal to 4 (considered as positive) persisted for 18 wk and 14 wk after the injection of 15 and 7.5 mg/kg of globulin, respectively. Hepatitis A virus vaccine recipients showed adequate neutralizing antibody titers, with the groups receiving 1, 0.5 and 0.25 micrograms/dose showing titers of 4(5.5), 4(4.7) and 4(4), respectively, at 18 mo after the third inoculation. These findings suggested that effective blood antibody titers were likely to be retained in the 1.0 micrograms or 0.5 micrograms/dose groups for at least several years. Moreover, the serum antihepatitis A virus titers demonstrated by a modified radioimmunoassay changed in parallel with the neutralizing antibody titers in the volunteers injected with globulin.


Faculty appointments and the record of scholarship.
Academic review committees would benefit from more details about the contributions made by individual researchers to papers with multiple authors, and also from more information about other types of scholarly communication.


Chromosomes and their relationship to nuclear components during the cell cycle in Chinese hamster cells.
Chromosomes and their relationship to nuclear components during various phases of the cell cycle were studied with different fixation, embedding, and enzyme techniques. The results showed that interphase chromosomes may have oriented in such a way that a given locus became associated with the nuclear membrane. Some chromosomes also appeared to interact with the nucleolus. The nuclear matrix materials, however, were distributed between the chromosomes and formed a delineating boundary for the chromosomes. These matrix materials, furthermore, formed channel-like structures within the nucleus and towards the cytoplasm through their interaction with nuclear pore complexes. During mitosis, chromosomes were encapsulated with material that appeared to be derived from the matrix, disintegrated residues and fragments of the nuclear envelope, the lamina, and nucleolar material. These chromosome-associated materials seen in mitosis appeared to serve as foci for formation of new nuclear components in subsequent interphase.


The Crosstalk between Hepatocytes, Hepatic Macrophages, and Hepatic Stellate Cells Facilitates Alcoholic Liver Disease.
Choi et al. (2019) explored the pathogenesis of alcohol-induced de novo lipogenesis in mice with ALD to reveal a novel mechanism of cannabinoid 1 receptor (CB1R)-SREB1-dependent triglyceride synthesis that requires crosstalk between hepatocytes and HSCs. Using genetic and pharmacological inhibition of the key components of the xCT-glutamate→mGluR5-2-AG→CB1R-SREBP1-FASN paracrine communication system, Choi et al. identified potential new targets for drugs for ALD.


A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder.
Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, -20.0; 160 mg, -19.9) vs. placebo (-14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.


Evidence of multiple reassortment events of feline-to-human rotaviruses based on a rare human G3P[9] rotavirus isolated from a patient with acute gastroenteritis.
A rare human/feline-like rotavirus G3P[9] strain, CAU14-1-262, from a 2-year-old girl with severe gastroenteritis was isolated and sequenced. The 11 gene segments of the CAU14-1-262 strain possessed a novel genotype constellation, G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6, which was identified for the first time. Phylogenetic analysis of this strain identified the following genome origins: VP7, VP4, VP6, VP1-VP3, NSP1, NSP2, and NSP4 genes possessed an AU-1-like genotype 3 constellation with high sequence identity to those of the feline and human/feline-like rotaviruses; NSP5 possessed a H6 lineage, with highest sequence identity to the human/feline-like E2541 strain; and the NSP3 gene possessed a Wa-like genotype 1 constellation with high sequence identity to those of the of human rotaviruses. These results provided evidence of multiple reassortment events in G3P[9] rotavirus CAU14-1-262 and possibility of feline-to-human interspecies transmission.


Profilin1 Regulates Trophoblast Invasion and Macrophage Differentiation.
Unexplained recurrent spontaneous abortion (URSA) has been associated with the dysfunction of trophoblasts and decidual macrophages. Current evidence suggests that profilin1 (PFN1) plays an important role in many biological processes. However, little is known about whether PFN1 is related to URSA. Herein, the location of PFN1 was detected by immunohistochemistry, and the level of PFN1 was detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. The proliferation of trophoblasts was detected by CCK8 and 5-ethynyl-2'-deoxyuridine assays, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays were used to detect apoptosis of trophoblasts. The migration and invasion ability of trophoblasts was assessed by using the wound-healing test and transwell test. Polarization of macrophages was detected in macrophages cultured in trophoblast conditioned medium. PFN1 expression was observed in cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts and was decreased in the villous tissue of patients with URSA. The migration and invasion ability and cell viability of trophoblastic cell lines that underwent PFN1 knockdown significantly decreased, and apoptosis increased. Opposite findings were observed after the overexpression of PFN1 in trophoblastic cells. In addition, PFN1 could regulate trophoblast function through phosphatidylinositol 3-kinase/AKT signal transduction rather than mitogen-activated protein kinase signaling pathways. Finally, knockdown of PFN1 in trophoblasts promoted tumor necrosis factor-α secretion to induce macrophage polarization to M1 phenotype, mediated by the NF-κB signaling pathway. These findings indicate that PFN1 has a broad therapeutic potential for patients with URSA.


Fidelity of Interventions to Reduce or Prevent Stress and/or Anxiety from Pregnancy up to Two Years Postpartum: A Systematic Review.
Intervention fidelity refers to whether an intervention is delivered as intended and can enhance interpretation of trial outcomes. Fidelity of interventions to reduce or prevent stress and anxiety during pregnancy and postpartum has yet to be examined despite inconsistent findings for intervention effects. This study systematically reviews use and/or reporting of intervention fidelity strategies in trials of interventions, delivered to (expectant) parents during pregnancy and postpartum, to reduce or prevent stress and/or anxiety. MEDLINE, Embase, CINAHL, PsychINFO, and Maternity and Infant Care were searched from inception to March 2019. Studies were included if they were randomised controlled trials including pregnant women, expectant fathers and/or partners during pregnancy, and/ or parents within the first two years postpartum. The National Institutes of Health Behavior Change Consortium checklist was used to assess fidelity across five domains (study design, provider training, delivery, receipt, enactment). Sixteen papers (14 interventions) were identified. Average reported use of fidelity strategies was 'low' (45%), ranging from 17.5 to 76%. Fidelity ratings ranged from 22% for provider training to 54% for study design. Low levels of intervention fidelity may explain previous inconsistent effects of stress and anxiety reduction interventions. Important methodological areas for improvement include intervention provider training, fidelity of comparator conditions, and consideration of non-specific treatment effects. Increased methodological rigour in fidelity enhancement and assessment will improve intervention implementation and enhance examination of stress and anxiety reduction and prevention interventions delivered during pregnancy and the postpartum.


Utility of rapid on-site evaluation in procurement of adrenal gland tissue biopsies.
While the number of adrenal biopsies has increased due to more "incidentalomas" were detected by widespread use of imaging studies, there have been very limited studies to evaluate the utility of rapid on-site evaluation (ROSE) in obtaining adequate core needle biopsy (CNB) tissue for diagnosis of adrenal lesions. We retrospectively reviewed all percutaneous adrenal CNB cases with available ROSE for a 12-year period in our institute in order to assess the usefulness of ROSE in adrenal CNB sampling. A total of 83 cases were identified in our database. The majority of cases (52/83, 63%) were diagnosed as metastatic malignancies with the lung being the most common primary site. Adrenal hyperplasia/adenoma was the most common primary adrenal lesion. The concordance between the ROSE interpretations and CNB final diagnoses is 80%. The interpretation errors accounted for majority (11/17, 65%) of the discordant cases. ROSE assessment during adrenal CNB procedures is a helpful tool for obtaining adequate diagnostic tissue. Pathologists should be familiar with adrenal cytology in order to reduce interpretation errors at ROSE.


Association of Patient-Provider Teach-Back Communication with Diabetic Outcomes: A Cohort Study.
The purpose of this study is to examine the patterns of patient teach-back experience (also known as "interactive communication loop") and determine its association with risk for diabetic complications and hospitalization, and health expenditures among individuals with diabetes. A retrospective cohort study of 2901 US adults aged 18 years or older with a confirmed diagnosis of diabetes was conducted using data from the 2011 to 2016 Longitudinal Medical Expenditure Panel Survey. Survey-design adjusted multivariable models were used to examine whether having patient teach-back experience at the baseline year (Year 1) is associated with development of diabetic complications, hospitalization, and health expenditure at follow-up year (Year 2). Health expenditures were adjusted for inflation and expressed in 2017 US dollars. All adjusted models included patient sociodemographic and clinical characteristics. Analyses found that patients with teach-back experience were less likely to develop diabetic complications (adjusted odds ratio [AOR], 0.70; 95% CI, 0.52-0.96) and be admitted to the hospital due to diabetic complications (AOR, 0.51; 95% CI, 0.29-0.88) at 1-year followup. Patients having teach-back experience also had a significantly smaller increase in total expenditures of $1920 compared with those not having teach-back of $3639 (a differential change of -$1579; 95% CI, -$1717 to -$1443; P < .001). Teach-back could be an effective communication strategy that has potential to improve health outcomes, resulting in savings in diabetes care.