Anaeramoebae are a divergent lineage of eukaryotes that shed light on the transition from anaerobic mitochondria to hydrogenosomes.
Discoveries of diverse microbial eukaryotes and their inclusion in comprehensive phylogenomic analyses have crucially re-shaped the eukaryotic tree of life in the 21st century.1 At the deepest level, eukaryotic diversity comprises 9-10 "supergroups." One of these supergroups, the Metamonada, is particularly important to our understanding of the evolutionary dynamics of eukaryotic cells, including the remodeling of mitochondrial function. All metamonads thrive in low-oxygen environments and lack classical aerobic mitochondria, instead possessing mitochondrion-related organelles (MROs) with metabolisms that are adapted to low-oxygen conditions. These MROs lack an organellar genome, do not participate in the Krebs cycle and oxidative phosphorylation,2 and often synthesize ATP by substrate-level phosphorylation coupled to hydrogen production.3,4 The events that occurred during the transition from an oxygen-respiring mitochondrion to a functionally streamlined MRO early in metamonad evolution remain largely unknown. Here, we report transcriptomes of two recently described, enigmatic, anaerobic protists from the genus Anaeramoeba.5 Using phylogenomic analysis, we show that these species represent a divergent, phylum-level lineage in the tree of metamonads, emerging as a sister group of the Parabasalia and reordering the deep branching order of the metamonad tree. Metabolic reconstructions of the Anaeramoeba MROs reveal many "classical" mitochondrial features previously not seen in metamonads, including a disulfide relay import system, propionate production, and amino acid metabolism. Our findings suggest that the cenancestor of Metamonada likely had MROs with more classical mitochondrial features than previously anticipated and demonstrate how discoveries of novel lineages of high taxonomic rank continue to transform our understanding of early eukaryote evolution.


Pressor action of pyridine-2-aldoxime in malathion poisoning.
1. Intravenous injections of pyridine-2-aldoxime (PAM) produced a marked, prolonged and dose-related rise in blood pressure in anaesthetized cats treated with malathion (MT) and without malathion (NMT). 2. The pressor effect of PAM was significantly reduced by phentolamine and phenoxygenzamine, but unaffected by hexamethonium. 3. Pretreatment with guanethidine and reserpine almost completely abolished the pressor response to PAM. 4. The results indicate that PAM has a potent sympathomimetic action which appears to be mediated through release of catecholamines from storage sites.


Family factors are associated with psychological distress and smoking status in chronic obstructive pulmonary disease.
The objective of this study was to test three hypotheses in a sample of individuals with chronic obstructive pulmonary disease (COPD): (1) unsupportive family relationships are associated with psychological distress, (2) psychological distress is associated with smoking status and (3) unsupportive family relationships are indirectly associated with smoking status via psychological distress. Cross-sectional data were collected via self-report questionnaires completed by 455 individuals with COPD who had at least a 10-pack-year smoking history. The hypotheses were tested with structural equation modeling. All three hypotheses were supported. Unsupportive family relationships were associated with psychological distress (β=.67, P<.001), psychological distress was associated with smoking status (β=.40, P<.001), and unsupportive family relationships were indirectly associated with smoking status via psychological distress (β=.27, P<.001). Results of this study suggest that family relationships are an important factor to include in future longitudinal research that attempts to elucidate social and psychological influences on smoking behavior.


A descriptive study of mandibular incisor alignment in untreated subjects.
The development of mandibular incisor crowding appears to be a continuous process throughout life, but more evidence is needed to understand why changes occur. In this study, we describe the longitudinal dental changes in untreated children (n = 15) who had records at 3 times and in an untreated adult group (n = 18) (parents) who had records for 2 times. The mean numbers of years between initial and final observations were 29.8 years for the children and 33.7 years for the parents. All subjects were participants in the original Burlington Growth Research Project at the University of Toronto. The following variables were measured to an accuracy of 0.01 mm: overjet, overbite, mandibular intercanine width, mandibular interfirst premolar width, mandibular intermolar width, mandibular arch length, Little's incisor irregularity index, mandibular anterior space analysis, and Carey's space analysis. There were no statistically significant (P >.01) differences between the sexes for the variables measured. Little's irregularity index continued to increase in all groups (P <.01), although this rate appeared to be lower in the parent group. Intercanine and interfirst premolar widths and arch lengths continued to decrease with age. These results underline the importance of studies showing that untreated dentitions change over time. Orthodontic patient education is imperative about retention protocols and late developmental crowding.


Anti-JC virus antibody titres increase over time with natalizumab treatment.
Anti-JC virus antibody status is a risk factor for progressive multifocal leukoencephalopathy after natalizumab treatment in multiple sclerosis. Previous studies have used a cross-sectional approach to conclude that the presence and duration of natalizumab treatment does not influence anti-JCV Ab seropositivity. Using a longitudinal approach, we measured change in anti-JCV Ab results after natalizumab treatment. Anti-JCV Ab results (n = 1154) from the second-generation STRATIFY JCV™ DxSelect™ test were analysed from an observational cohort of MS patients on natalizumab (n = 485; n = 340 with repeat testing; n = 657 repeat tests on natalizumab). Across sequential paired tests, seroconversion rate was greater than seroreversion rate (40/364 (11.0%) versus 18/293 (6.1%); p < 0.05). Moreover, anti-JCV Ab index increased across longitudinal paired tests (mA-B 0.102; paired t(656) = 5.0; p < 0.0001). This magnitude of Ab level increase far exceeds that expected due to increasing age alone. Our data suggest that natalizumab therapy is associated with a significant and substantial increase in anti-JCV Ab index over time. Further work should focus on the underlying mechanisms of this phenomenon, and the clinical relevance to risk stratification.


[Injectable soft tissue fillers: are they medical devices or drugs? Implications for HIV lipodystrophy].
Physical modifications associated to lipodystrophy syndrome in HIV+ patients remain a challenge for management, even in a well controlled chronic infection. Indications, evaluation and filling treatments of facial lipoatrophy are described. Many exogenous filling products are on the market and their use and tolerance profile better known. These medical devices should be closely followed in patients with chronic HIV infection.


Activity of exogenous tyrosol in combination with caspofungin and micafungin against Candida parapsilosis sessile cells.
Fungal quorum-sensing molecules may have an inhibitory effect as adjuvant against Candida biofilms. Therefore, in vitro activity of caspofungin and micafungin was evaluated against Candida parapsilosis biofilms in the presence of tyrosol. Interactions were assessed using fractional inhibitory concentration index (FICI) determination, metabolic activity-based time-kill experiments and scanning electron microscopy (SEM). Tyrosol caused 1-16-fold and 2-32-fold decrease in median caspofungin and micafungin MICs respectively. Based on FICI, synergy was observed in isolates 27001 and 17820 with caspofungin and 27001 with micafungin. In time-kill experiments, the metabolic activity reduction was higher for micafungin compared to caspofungin at 24 h especially when used in 64 and 256 mg l-1 concentrations. In the case of micafungin, the 256 mg l-1 + 1 mmol l-1 combination caused significantly higher decrease in metabolic activity compared to the corresponding concentration alone (256 mg l-1 ) at 24 h (P < 0·05). SEM confirmed the higher killing effect of tested echinocandins with tyrosol. Considerable metabolic activity reduction and cell damage was detected for combinations especially in the case of micafungin. Our findings support the development of new alternative therapeutic strategies against C. parapsilosis biofilms.


Intrapartum fetal abdominal circumference by ultrasonography for predicting fetal macrosomia.
To evaluate the diagnostic value of sonographic measurement of fetal abdominal circumference (AC) for the prediction of fetal macrosomia. A prospective clinical trial was conducted at Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. The study consisted of 361 singleton pregnant women who were admitted for delivery at labor room. All women underwent sonographic measurements of the fetal abdominal circumference (AC) during the early intrapartum period. The AC values were correlated to actual fetal birth weight. The cut-off value of AC for predicting of fetal macrosomia was analyzed. Among 361 cases, the mean maternal age was 29.0 +/- 5.5 years (range, 15-46). The median gestational age was 39 weeks (range, 31-42). The mean fetal birth weight was 3,179.83 +/- 450.91 gm (range, 1,180-4,560). The prevalence of macrosomia was 11.08% (40/361). A cut-off value of abdominal circumference > or = 35 cm was the best predicting of fetal macrosomia. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 87.50%, 84.74%, 85.04%, 41.67%, and 98.19%, respectively. The intrapartum fetal AC measurement was useful in predicting of fetal macrosomia. An AC measurement of > or = 35 cm was the best value of fetal macrosomia prediction.


Inferior oblique transposition for large hypertropia after vertical rectus transposition.
Consecutive vertical deviations occur in 13% to 30% of cases after full tendon vertical rectus transposition (VRT) surgery in adult patients with abducens nerve palsy. We report a 7-year-old boy with congenital abducens nerve palsy who developed a large hypertropia following VRT with posterior fixation sutures. During subsequent surgery, extensive scarring of the vertical rectus muscles was observed, and an inferior oblique nasal anterior transposition was performed. The patient was orthotropic in primary position through 18 months of follow-up. The causes and management options for vertical deviation following VRT are discussed.


Recurrent hypercalcemia and elevated 1,25-dihydroxyvitamin D levels in Hodgkin's disease.
Hypercalcemia has been infrequently associated with Hodgkin's disease. When seen, most cases have been attributable to skeletal invasion by disease. Herein is described a 40-year-old man with a 15-year history of Hodgkin's disease. Each of four disease recurrences was heralded by hypercalcemia occurring in the absence of bone disease or elevation of parathyroid hormone levels. Marked elevations of 1,25-dihydroxyvitamin D levels were observed that paralleled his disease course and response to therapy. The repetitive association of hypercalcemia with an elevation of 1,25-dihydroxyvitamin D in this case provides further evidence of lymphoma-associated production of this vitamin.


Targeting DNA damage repair precision medicine strategies in cancer.
DNA repair targeted therapeutics is a promising precision medicine strategy in cancer. The development and clinical use of PARP inhibitors has transformed lives for many patients with BRCA germline deficient breast and ovarian cancer as well as platinum sensitive epithelial ovarian cancers. However, lessons learnt from the clinical use of PARP inhibitors also confirm that not all patients respond either due to intrinsic or acquired resistance. Therefore, the search for additional synthetic lethality approaches is an active area of translational and clinical research. Here, we review the current clinical state of PARP inhibitors and other evolving DNA repair targets including ATM, ATR, WEE1 inhibitors and others in cancer.


Translation, Validation, and Psychometric Properties of Breastfeeding Self-Efficacy Scale-Short Form Among Iranian Women.
Iranian researchers have investigated breastfeeding self-efficacy and its related factors. However, there is no valid and reliable tool for assessing the breastfeeding self-efficacy of Iranian Farsi-speaking women. To examine the validity and reliability of the Breastfeeding Self-Efficacy Scale-Short Form among Iranian Farsi-speaking mothers. We conducted this cross-sectional study at Izadi teaching hospital in Qom, Iran. Using convenience sampling, we recruited 174 mothers, who completed the questionnaire on the first postnatal day. A forward-backward translation method was used to translate the scale. Cronbach's alpha and item-total characteristics were examined to test reliability. Construct validity was evaluated via principal component analysis (PCA), as well as known-groups validity. The mean (standard deviation) of sample age was 28.33 (5.38). The mean (standard deviation) of breastfeeding self-efficacy score was 54.32 (10.50), ranging from 24-70. Cronbach's alpha (.92), inter-item correlations (.21-.72), and corrected item-total correlations (.44-.75) indicated the adequate reliability of the scale. PCA yielded one component with an eigenvalue of 6.97, explaining 49.8% of the total variance. There was no significant difference in the self-efficacy scores between primiparous and multiparous women. Breastfeeding self-efficacy was not significantly different between the groups in terms of the demographic characteristics. The Farsi version of the Breastfeeding Self-efficacy Scale-Short Form is a valid and reliable instrument for Iranian Farsi-speaking mothers, with sound psychometric properties per the other studies worldwide.


A novel multi-modality imaging phantom for validating interstitial needle guidance for high dose rate gynecological brachytherapy.
To design, manufacture, and validate a female pelvic phantom for multi-modality imaging (CT, MRI, US) to benchmark a commercial needle tracking system with application in HDR gynecological (GYN) interstitial procedures. A GYN needle-tracking phantom was designed using CAD software to model an average uterus from a previous patient study, a vaginal canal from speculum dimensions, and a rectum to accommodate a transrectal ultrasound (TRUS) probe. A target volume (CTVHR ) was designed as an extension from the cervix-uterus complex. Negative space molds were created from modeled anatomy and 3D printed. Silicone was used to cast the anatomy molds. A 3D printed box was constructed to house the manufactured anatomy for structural integrity and to accommodate the insertion of a speculum, tandem, needles, and TRUS probe. The phantom was CT-imaged to identify potential imperfections that might impact US visualization. Free-hand TRUS was used to guide interstitial needles into the phantom. The commercial tracking system was used to generate a 3D US volume. After insertion, the phantom was imaged with CT and MR and the uterus and CTVHR dimensions were verified against the CAD model. The manufactured phantom allows for accurate visualization with multiple imaging modalities and is conducive to applicator and needle insertion. The phantom dimensions from the CAD model were verified with those from each imaging modality. The phantom is low cost and can be reproducibly manufactured with the 3D printing and molding processes. Our initial experiments demonstrate the ability to integrate the phantom with a commercial tracking system for future needle tracking validation studies.


The association between curry-rice consumption and hypertension, type 2 diabetes, and depression: The findings from KNHANES 2012-2016.
We aim to evaluate the association between curry-rice consumption, cardiovascular diseases (CVDs), type 2 diabetes (T2DB), arthritis, and depression. 17,625 participants aged ≥18 years were recruited to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, family history, and food consumption. The association between curry-rice consumption, CVDs, T2DB, arthritis, and depression was examined using multivariable-adjusted analyses. In the logistic model, risks of elevated triglyceride (OR 0.89; 95% CI, 0.82-0.97, p = 0.006), elevated HbA1c (OR 0.81; 95% CI, 0.73-0.91, p < 0.001), and elevated glucose (OR 0.86; 95% CI, 0.79-0.94, p < 0.001) were significantly lower in the high curry-rice consumption group than in the low curry-rice consumption group. Risk of hypertension (OR 0.88; 95% CI, 0.78-0.98, p = 0.044), T2DB (OR, 0.82; 95% CI, 0.68-0.98, p < 0.001), and depression (OR 0.82; 95% CI, 0.70-0.97, p = 0.026) was significantly lower among the high curry-rice consumption group than in the low curry-rice consumption group. These findings were consistent with the results of the analysis when curry-rice consumption was treated as a continuous variable. The potential health benefits resulting from the intake of curry-rice via an ordinary diet could protect the public from the burden of non-communicable diseases (NCDs) and mental health. These results highlight an ongoing need to understand the role of curry-rice in NCDs and mental health.


Uncommon phenotypes of acute myelogenous leukemia: basophilic, mast cell, eosinophilic, and myeloid dendritic cell subtypes: a review.
The potential of the transformed (leukemic) multipotential hematopoietic cell to differentiate and mature along any myeloid lineage forms the basis for the phenotypic classification of acute and chronic myelogenous leukemia. Although most cases of leukemia can be classified phenotypically by the dominant lineage expressed, the genotype within each phenotype is heterogeneous. Thus, covert genetic factors, cryptic mutations, and/or polymorphisms may interact with the seminal transforming genetic mutations to determine phenotype. The phenotype usually is expressed sufficiently to determine the lineage that is dominant in the leukemic clone by light microscopic examination, by cytochemistry of blood and marrow cells, and by immunophenotyping. The basis for the frequency of the AML phenotypes is unclear, although there is a rough concordance with the frequency of marrow precursor cells of different lineages. The least common AML phenotypes are a reflection of the least common blood or marrow cell lineages: acute basophilic, acute mast cell, acute eosinophilic, and acute myeloid dendritic cell leukemia. We discuss the features of these uncommon phenotypes and review the criteria used for their diagnosis.


Specificity of synaptic regeneration in the spinal cord of the larval sea lamprey.
1. Pairs of central neurones in large larval sea lampreys were impaled with micro-electrodes and studied for synaptic connexions in both unoperated control animals and animals which had recovered from complete spinal transection. Two identified classes of neurones served as post-synaptic targets: giant interneurones (g.i.s) and lateral cells (l.c.s). Several identified neurone types were tested as potential sources of presynaptic input. 2. When synaptic potentials had short, fixed latencies they also persisted during activation of the presynaptic cell at 3.3-33.3 Hz and were not eliminated after addition of lamprey saline containing high (20 mM) Ca2+. These presumably represented monosynaptic connexions. Variable-latency responses were eliminated by faster rates of stimulation of the presynaptic cell and were mediated via polysynaptic pathways. 3. In control animals, g.i.s received monosynaptic input from more caudal g.i.s in fourteen of thirty-two tested cell pairs. These excitatory post-synaptic potentials (e.p.s.p.s) were composite electrochemical responses. The amplitudes of the earlier electrical component averaged 1.66 +/- 0.24 mV (mean +/- S.E. of mean) and the amplitude of the later chemical component averaged 0.79 +/- 0.05 mV. 4. In operated larvae, eight of forty-seven g.i.-g.i. pairs separated by the transection scar were connected by monosynaptic composite e.p.s.p.s. In these pairs the electrical component averaged 0.84 +/- 0.17 mV (P less than 0.05 vs. control) and the chemical component averaged 1.56 +/- 0.40 mV. The average conduction velocity between these cells was less than that in control g.i.-g.i. pairs (0.93 +/- 0.11 vs. 1.61 +/- 0.25 m/s; P less than 0.01). 5. The l.c.s showed monosynaptic e.p.s.p.s after activation of a subset of the bulbar Müller neurones (B2-4) in seven of twelve pairs. In behaviourally recovered larvae three of twenty-two similar pairs separated by the transection scar were also connected via monosynaptic e.p.s.p.s. The average conduction velocity between these experimental neurones was also less than that in control bulbar-l.c. pairs (1.03 +/- 0.03 vs. 1.58 +/- 0.09 m/s; P less than 0.001). 6. Several types of neurones were either infrequently linked or never connected to g.i.s or to l.c.s in control larvae. In animals which had recovered from a spinal transection, no synaptic connexions were found from such neurones on to g.i.s or l.c.s respectively, in 124 tested cell pairs. In addition, dorsal cells (intraspinal primary sensory neurones) received no synaptic input upon stimulation of the spinal cord before or after transection.(ABSTRACT TRUNCATED AT 400 WORDS)


Locked twins: a successful outcome.
Twin interlocking is a rare complication that has a high fetal mortality and morbidity rate. We report a successful outcome of locked twins at 32 weeks gestation following spontaneous labor.


Hand dermatitis: uncommon presentations.
Hand dermatitis is a common diagnosis seen in dermatologic and general practice. It can present with typical morphology, but uncommon manifestations are possible. This review reports on common and uncommon presentations of irritant and allergic hand dermatitis focusing on uncommon localizations, time course, and morphology such as follicular, pustular, bullous, ulcerous, exudative erythema multiforme-like, purpuric, lichenoid, pigmented, and depigmented skin lesions. Clinical diagnosis can be challenging. Even histopathology is not always very helpful. Thorough evaluation of the patient's history and investigation of clinical morphology are the cornerstones of diagnosis.


Physiological consequences of mutations in the htpG heat shock gene of Escherichia coli.
Mutation of the heat shock gene, htpG, causes severe defects of several cellular functions in Escherichia coli. A null htpG mutant constructed by gene replacement was impaired in the biosynthesis and secretion of several enzymes, and in biofilm formation and proteolysis. A significant decrease in the activity of β-lactamase in the ΔhtpG mutant was observed at 42°C. The alkaline phosphatase activity in sonicates of cells propagated at this raised temperature was lower in the ΔhtpG mutant than in the wild-type strain. The ability of the ΔhtpG mutant to degrade abnormal proteins was also impaired compared with the wild-type, but was increased at 42°C. Assays based on bioluminescence and crystal violet staining demonstrated that biofilm formation was diminished in the ΔhtpG mutant at the elevated temperature. All these defects can be complemented upon introducing htpG wild allele.


Recurrent artery-to-artery embolism during intravenous t-PA therapy for acute ischemic stroke.
Treatment of acute ischemic stroke with systemic thrombolysis in the presence of a proximal thrombo-embolic source carries a theoretical risk of thrombus fragmentation and recurrent embolization. Intracardiac thrombus has received the most attention as a potential source of recurrent emboli, and in the past, it was considered a relative contra-indication to tissue plaminogen activator (t-PA) treatment. More recent data show that recurrent embolization from a cardiac source during t-PA infusion is rare. This article describes recurrent symptomatic basilar artery embolization during t-PA infusion from acute thrombus in the proximal cervical vertebral artery. This case provides evidence that intravenous t-PA must be used cautiously in the presence of large proximal thrombo-embolic sources and that intraluminal thrombus in a large cervical artery should be considered one such source.


Isolation of neurosecretory granules containing vasotocin, mesotocin, MSEL- and VLDV-neurophysins from goose neurohypophysis.
Neurosecretory granules have been isolated from goose posterior pituitaries and their contents have been analyzed by reverse-phase high-pressure liquid chromatography and polyacrylamide gel electrophoresis. Vasotocin and mesotocin have been identified by their biological activities and their retention times compared with those of synthetic peptides. MSEL- and VLDV-neurophysins have been characterized by their N-terminal sequences, their electrophoretic migrations and their retention times, compared with those of purified goose neurophysins. In contrast to the two-step processing of mammalian provasopressin, processing of the vasotocin - MSEL-neurophysin precursor appears to involve only one cleavage giving the hormone and a "big" MSEL-neurophysin homologous to mammalian MSEL-neurophysin extended by copeptin.


Naturally occurring genotype 2b/1a hepatitis C virus in the United States.
Hepatitis C Virus (HCV) infected patients are frequently repeatedly exposed to the virus, but very few recombinants between two genotypes have been reported. We describe the discovery of an HCV recombinant using a method developed in a United States clinical lab for HCV genotyping that employs sequencing of both 5' and 3' portions of the HCV genome. Over twelve months, 133 consecutive isolates were analyzed, and a virus from one patient was found with discordant 5' and 3' sequences suggesting it was a genotype 2b/1a recombinant. We ruled out a mixed infection and mapped a recombination point near the NS2/3 cleavage site. This unique HCV recombinant virus described shares some features with other recombinant viruses although it is the only reported recombinant of a genotype 2 with a subtype 1a. This recombinant represents a conundrum for current clinical treatment guidelines, including treatment with protease inhibitors. This recombinant is also challenging to detect by the most commonly employed methods of genotyping that are directed primarily at the 5' structural portion of the HCV genome.


A clip-based protocol for breast boost radiotherapy provides clear target visualisation and demonstrates significant volume reduction over time.
The clinical target volume (CTV) for early stage breast cancer is difficult to clearly identify on planning computed tomography (CT) scans. Surgical clips inserted around the tumour bed should help to identify the CTV, particularly if the seroma has been reabsorbed, and enable tracking of CTV changes over time. A surgical clip-based CTV delineation protocol was introduced. CTV visibility and its post-operative shrinkage pattern were assessed. The subjects were 27 early stage breast cancer patients receiving post-operative radiotherapy alone and 15 receiving post-operative chemotherapy followed by radiotherapy. The radiotherapy alone (RT/alone) group received a CT scan at median 25 days post-operatively (CT1rt) and another at 40 Gy, median 68 days (CT2rt). The chemotherapy/RT group (chemo/RT) received a CT scan at median 18 days post-operatively (CT1ch), a planning CT scan at median 126 days (CT2ch), and another at 40 Gy (CT3ch). There was no significant difference (P = 0.08) between the initial mean CTV for each cohort. The RT/alone cohort showed significant CTV volume reduction of 38.4% (P = 0.01) at 40 Gy. The Chemo/RT cohort had significantly reduced volumes between CT1ch: median 54 cm(3) (4-118) and CT2ch: median 16 cm(3), (2-99), (P = 0.01), but no significant volume reduction thereafter. Surgical clips enable localisation of the post-surgical seroma for radiotherapy targeting. Most seroma shrinkage occurs early, enabling CT treatment planning to take place at 7 weeks, which is within the 9 weeks recommended to limit disease recurrence.


prlA-mediated suppression of signal sequence mutations is modulated by the secA gene product of Escherichia coli K-12.
We studied the dependence of prlA-mediated suppression of signal sequence mutations in maltose-binding protein on cellular SecA levels in Escherichia coli. Reduction of SecA levels within the cell had strong positive and negative effects on prlA-mediated suppression, depending on the particular signal sequence mutations involved. This finding suggests that prlA and secA gene products are both components of a common export system.


Managing and treating Sydenham chorea: A systematic review.
Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines for diagnosis and treatment. Resulting from Group A Beta-Hemolytic Streptococcus infection, SC presents various symptoms. This review aims to collect and evaluate available data on SC management to propose a cohesive treatment plan. We searched PubMed, the Cochrane Library, Google Scholar, and ClinicalTrials.gov for literature on SC management from inception until 24th July 2022. Studies were screened by titles and abstracts. Cochrane Collaboration's Risk of Bias tool (RoB-1) assessed Randomized Controlled Trials, while the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated nonrandomized studies. The review includes 11 articles assessing 579 patients. Excluding one study with 229 patients, of the remaining 550 patients, 338 (61.5%) were females. Treatments used were dopamine antagonists in 118 patients, antiepileptics in 198, corticosteroids in 134, IVIG in 7, and PE in 8 patients. Dopamine antagonists, particularly haloperidol, were the primary treatment choice, while valproic acid (VPA) was favored among antiepileptics. Prednisolone, a corticosteroid, showed promising results with weight gain as the only side-effect. Our review emphasizes the importance of immunomodulators in SC, contrasting previous literature. Despite limitations, dopamine antagonists can serve as first-line agents in SC management, followed by antiepileptics. The role of immunomodulators warrants further investigation for conclusive recommendations.


High-power deep-ultraviolet light generation at 266 nm from frequency quadrupling of a picosecond pulsed 1064 nm laser with a Nd:YVO4 amplifier pumped by a 914 nm laser diode.
We report the generation of picosecond pulsed light at a 266 nm wavelength with an average power of 53 W. We developed a picosecond pulsed 1064 nm laser source with an average power of 261 W, a repetition rate of 1 MHz, and a pulse duration of 14 ps, using a gain-switched DFB laser diode as a seed laser and a 914 nm laser-diode-pumped Nd-doped YVO4 power amplifier. We achieved stable generation of 266 nm light with an average power of 53 W from frequency quadrupling using an LBO and a CLBO crystals. The amplified power of 261 W and the 266 nm average power of 53 W from the 914 nm pumped Nd:YVO4 amplifier are the highest ever reported, to the best of our knowledge.


Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients - a study based on a cohort of 19,742 patients.
For a decade, patients have been advised against using high citalopram- and escitalopram-doses due to risk for ventricular arrhythmia and cardiac arrest. Still, these drugs are widely used to treat depression and anxiety especially in older patients. It is unclear why they are cardiotoxic and at what serum concentrations patients are at risk for arrhythmias. Thus, how many patients that are at risk for iatrogenic cardiac arrest is unknown. We studied the arrhythmogenic effects of citalopram, escitalopram and their metabolites on human cardiomyocytes. Concentrations showing pro-arrhythmic activity were compared with observed drug and metabolite serum concentrations in a cohort of 19,742 patients (age 12-105 years) using escitalopram or citalopram in Norway (2010-2019). As arrhythmia-risk is related to maximum serum concentration, this was simulated for different age-groups from the escitalopram patient material. Therapeutic concentrations of both citalopram and escitalopram but not their metabolites showed pro-arrhythmic changes in the human cardiac action potential. Due to age-dependent reduction of drug clearance, the proportion of patients above threshold for arrhythmia-risk increased with age. 20% of patients >65 years were predicted to reach potentially pro-arrhythmic concentrations, following intake of 10 mg escitalopram. All patients that are using escitalopram or citalopram and have genetic disposition for acquired long-QT syndrome, are >65 years, are using additional pro-arrhythmic drugs or have predisposition for arrhythmias, should be monitored with therapeutic drug monitoring (TDM) to avoid exposure to potentially cardiotoxic concentrations. Serum concentrations should be kept below 100 nM, to reduce arrhythmia-risk. This study was funded by The Research Council of Norway (project number: 324062).


Pharmacists' perspectives on school stock inhaler access for children.
Several states in the United States (U.S.) have laws permitting stock inhalers, including short-acting beta-agonist inhalers, such as albuterol, and spacers to be prescribed to, dispensed to, and stocked in schools for use in students in respiratory distress, based on a protocol. This survey study assessed Arizona pharmacists' (1) levels of comfort for dispensing a short-acting beta-agonist inhaler to an individual child versus a stock inhaler to a school, and (2) awareness of the related Arizona state law. Researchers surveyed pharmacists licensed in Arizona who self-reported practicing in an outpatient pharmacy setting. Among 251 pharmacist participants, 62% practiced in a chain community pharmacy. About 80.8% felt comfortable filling a prescription for an albuterol inhaler in a pediatric patient case, whereas only 26.7% felt comfortable filling a prescription for albuterol inhalers to be used as stock inhalers for a given school. Among those who would not fill the stock inhaler prescription, only 5.5% reported awareness of the state law compared to 42.6% of those who would fill it (p < 0.0001). This survey identified a lack of pharmacist awareness of state laws pertaining to stock inhalers for schools.


Identification of a carboxylesterase associated with resistance to naled in Bactrocera dorsalis (Hendel).
Compared to other organophosphate-resistant and -susceptible (S) lines of Bactrocera dorsalis, the carboxylesterase (CBE) BdE5 in the naled-resistant (nal-r) line has been found to possess remarkable quantitative elevation. Our study attempts to identify the role of BdE5 in naled resistance, and we discovered several points of interest. Firstly, activity staining on native PAGE revealed that the percentage of flies with intensive BdE5 bands in the nal-r line was substantially higher than in the S line, indicating that the BdE5 band correlates with naled susceptibility. Secondly, in vitro and in vivo inhibition assays showed that BdE5 was inhibited by naled in both lines; under diagnostic doses of naled, the overall extent of inhibition on CBEs was much greater in the S line than in the nal-r line. Thirdly, NanoLC-nanoESi-MS/MS analysis used the NCBI database to identify and annotate BdE5 as an esterase FE4-like (XP_011200445.1) in B. dorsalis. Fourthly, rapid amplification of cDNA ends was used to obtain the 2012-bp full-length BdE5 cDNA, which contained an open reading frame of 1770bp and encoded a putative protein of 590 amino acid residues. Phylogenetic analysis revealed that BdE5 is a secreted β-esterase (E clade) closely related to CG6414 (NP_570089), a CBE in Drosophila melanogaster. Finally, our relative quantification real-time PCR data showed a significant elevation in transcript levels of the BdE5 gene in nal-r line. Our results confirmed that BdE5 is correlated with naled resistance and provides further understanding about the identification and molecular characteristics of BdE5 in B. dorsalis.


Acute acalculous cholecystitis associated with aortic dissection: report of a case.
Acute acalculous cholecystitis is uncommon, but not rare. Classically, this disease is observed in the intensive care unit associated with major trauma, burns, or surgery. Moreover, comorbidity such as infection, hypertension, and diabetes mellitus is often found. Although the exact pathogenesis is still not fully understood, it may be multifactorial and ischemia seems to play a central role. We herein report an unusual case of acute alithiasic cholecystitis predisposing to a de Bakey type III aortic dissection. A 57-year-old man was referred to our hospital for investigation of persistent right upper abdominal pain with tenderness and fever, associated with a newly diagnosed aortic dissection treated conservatively. The diagnosis of acalculous cholecystitis, which is often difficult to establish, was particularly delayed. An open cholecystectomy was performed, revealing a preperforating gangrenous gallbladder without any stones. The patient was discharged from hospital 9 days postoperatively without any early or late complications. No operative treatment for the aortic dissection was needed.


Preparation and characterization of curdlan/nanocellulose blended film and its application to chilled meat preservation.
In this study, to improve the mechanical and thermal properties of curdlan film, a curdlan/nanocellulose (NC) blended film was prepared and characterized for the first time. NC was successfully prepared from microcrystalline cellulose (MCC) with NaOH/urea treatment. The particle size of NC was observed to be 70-140 nm by cryo-electron microscope (cryo-EM). The blended film was prepared by adding the NC to curdlan solution. The tensile strength (TS) of the blended film reached the maximum value of 38.6 MPa, and the elongation at break (EB) was 40%. The DSC curve showed that the heat absorption peak of the film was 240 °C, indicating that the blended film has good temperature stability. Additionally, some other film properties were also improved, including gas barrier properties and transparency. Obvious morphological and molecular differences between the blended film and the pure curdlan film were discovered by SEM and FTIR analysis. Finally, the blended film was used for the preservation of chilled meat and extended the storage time of meat to 12 days. These results provided a theoretical basis for future application and development of biodegradable film.


Serum proteolytic and antiproteolytic activity in acute pancreatitis.
This study has demonstrated an imbalance between the blood proteolytic and antiproteolytic system in acute pancreatitis. Serum elastase activity is markedly increased and elastase inhibitory capacity is decreased in this disease as compared with those in chronic pancreatitis and the control values. We have found that a return to normal values represents better evidence of resolution than amylase determinations. These results offer the clinician a biochemical guideline for the medical management of acute pancreatitis.


Regulatory properties of brain glutamate decarboxylase.
1. Glutamate decarboxylase is a focal point for controlling gamma-aminobutyric acid (GABA) synthesis in brain. Several factors that appear to be important in the regulation of GABA synthesis have been identified by relating studies of purified glutamate decarboxylase to conditions in vivo. 2. The interaction of glutamate decarboxylase with its cofactor, pyridoxal 5'-phosphate, is a regulated process and appears to be one of the major means of controlling enzyme activity. The enzyme is present in brain predominantly as apoenzyme (inactive enzyme without bound cofactor). Studies with purified enzyme indicate that the relative amounts of apo- and holoenzyme are determined by the balance in a cycle that continuously interconverts the two. 3. The cycle that interconverts apo- and holoenzyme is part of the normal catalytic mechanism of the enzyme and is strongly affected by several probable regulatory compounds including pyridoxal 5'-phosphate, ATP, inorganic phosphate, and the amino acids glutamate, GABA, and aspartate. ATP and the amino acids promote apoenzyme formation and pyridoxal 5'-phosphate and inorganic phosphate promote holoenzyme formation. 4. Numerous studies indicate that brain contains multiple molecular forms of glutamate decarboxylase. Multiple forms that differ markedly in kinetic properties including their interactions with the cofactor have been isolated and characterized. The kinetic differences among the forms suggest that they play a significant role in the regulation of GABA synthesis.


The prolyl isomerase Pin1 interacts with and downregulates the activity of AMPK leading to induction of tumorigenicity of hepatocarcinoma cells.
Pin1 is a unique regulator that catalyzes the conversion of a specific phospho-Ser/Thr-Pro-containing motif in target proteins. Herein, we identified AMP-activated protein kinase (AMPK) as a Pin1-binding protein. Pin1 wild-type, but not Pin1 mutant at serine 16 (S16A), associated with AMPK. Reciprocally, the constitutively active form of AMPK (AMPK-CA), but not the dominant negative form of AMPK (AMPK-DN), interacted with Pin1 wild type. In addition, mutation of Ser176 site in AMPK led to a significant loss of binding between AMPK and Pin1. Ablation of the Pin1 gene in MEFs enhanced AMPK phosphorylation induced by AICAR. Pin1 overexpression in Pin1(-/-) MEFs and SK-HEP-1 cells attenuated AMPK phosphorylation induced by EGF, whereas gene knockdown of Pin1 by siRNA enhanced it. The association between Pin1 and AMPK was increased by EGF, leading to their interaction with protein phosphatase-2A (PP2A). Furthermore, Pin1 increased the PP2A activity induced by EGF. In addition, AMPK-WT and AMPK-CA, but not AMPK-DN, inhibited EGF-induced neoplastic cell transformation of JB6 Cl41 cells and tumorigenicity of SK-HEP-1 cells. The overexpression of Pin1 in JB6 Cl41 cells and SK-HEP-1 cells attenuated the inhibitory effect of AMPK in EGF-induced neoplastic cell transformation of JB6 Cl41 and tumorigenicity of SK-HEP-1 cells, respectively. Taken together, these results indicate that Pin1 plays a pivotal role in EGF-induced carcinogenesis through downregulation of AMPK activity in hepatocarcinoma cells.


Dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the dopamine synthetic pathway in the arcuate nucleus of fetal rats.
This study was aimed to test our hypothesis about dopamine (DA) synthesis by non-DAergic neurons expressing individual complementary enzymes of the DA synthetic pathway in cooperation, i.e. L-dihydroxyphenylalanine (L-DOPA) synthesized in tyrosine hydroxylase (TH)-expressing neurons is transported to aromatic L-amino acid decarboxylase (AADC)-expressing neurons for conversion to DA. The mediobasal hypothalamus of rats at the 21st embryonic day was used as an experimental model because it contains mainly monoenzymatic TH neurons and AADC neurons (>99%) whereas the fraction of bienzymatic (DAergic) neurons does not exceed 1%. The fetal substantia nigra containing DAergic neurons served as a control. DA and L-DOPA were measured by high performance liquid chromatography in: (1) cell extracts of the cell suspension prepared ex tempora; (2) cell extracts and incubation medium after the static incubation of the cell suspension with, or without exogenous L-tyrosine; (3) effluents of the incubation medium during perifusion of the cell suspension in the presence, or the absence of L-tyrosine. Total amounts of DA and L-DOPA in the incubation medium and cell extracts after the static incubation were considered as the indexes of the rates of their syntheses. L-Tyrosine administration caused the increased L-DOPA synthesis in the mediobasal hypothalamus and substantia nigra. Moreover, L-tyrosine provoked an increase of DA synthesis in the substantia nigra and its decrease in the mediobasal hypothalamus. This contradiction is most probably explained by the L-tyrosine-induced competitive inhibition of the L-DOPA transport to the monoenzymatic AADC-neurons after its release from the monoenzymatic TH neurons. Thus, this study provides convincing evidence of cooperative DA synthesis by non-DAergic neurons expressing TH or AADC in fetal rats at the end of the intrauterine development.


Determinants of visitor pro-environmental intentions on two small Greek islands: is ecotourism possible at coastal protected areas?
A relatively under-researched question is whether there is a possibility of influencing environmentally aware tourists regarding ecotourism at destinations that continue to develop under a pattern of mass 'seaside' tourism. Our objective was to assess the pro-environmental intentions of visitors at two small Greek islands, which are within a Natura 2000 site, specifically Paxoi and Antipaxoi. Intentions involved willingness to receive information about the protected area, willingness to accept pro-environmental limitations on recreational experience, and willingness-to-pay a conditional environmental conservation value added tax. In addition, we aimed to identify determinants of visitor pro-environmental intentions among visitor and visit characteristics, visitor satisfaction, and self-reported environmental knowledge, as well as anticipated outcomes of tourism development and suggestions for protected area management. We randomly collected 324 usable questionnaires during the summer season; 242 (74.69 %) by Greek visitors and 82 (25.31 %) by foreign visitors. Visitor satisfaction was quite high; however, visitors reported low levels of environmental knowledge. Our findings showed that the unique characteristics of the destination were not salient among visitors and that there is a lack of effective outreach campaigns, interpretation, and on-site environmental education programs. However, our study revealed high levels of visitor pro-environmental intentions that might support the promotion of ecotourism on the two islands. We provide recommendations based on determinants of visitor pro-environmental intentions, which might assist towards advancing visitor participation in environmental education projects, environmentally responsible behavior among visitors, and financial contribution to environmental conservation by visitors.


Post-column derivatization system for the fluorimetric determination of guanidino compounds with ninhydrin by reversed-phase ion-pair high-performance liquid chromatography.
A post-column derivatization system for the fluorimetric determination of guanidino compounds by high-performance liquid chromatography was developed. A mobile phase containing ninhydrin was used as the fluorigenic reagent. Ten guanidino compounds were separated within 25 min on a Nucleosil C8 (5 microns) column (15 cm X 4.6 mm I.D.) by isocratic, reversed-phase ion-pair chromatography and detected as fluorophors derived from condensation with ninhydrin in an alkaline stream. In this simplified system only two pumps required to deliver the mobile phase and the alkaline solution. This method was applied to serum from patients on haemodialysis therapy.


Recent developments with karyoplast regeneration and nuclear transplantation.
Karyoplasts and cytoplasts prepared by cytochalasin-induced enucleation techniques were used in the development of systems for large-scale nuclear transplantation and the regeneration of karyoplasts to reform whole viable cells. Ten to 20% of a preparation of mouse L929 karyoplasts remained viable. These bodies, purified from whole cells, cytoplasts, and nonviable karyoplats, contained less than 10% of the cytoplasm in whole cells. By the technique of mass nuclear transplantation, up to 40% of a culture of cytoplasts could be renucleated by fusion of karyoplasts to a monolayer of enucleated cells. More than 5 x 10(5) renucleated or true cytoplasmic-nuclear hybrid cells could be prepared from a single cytoplast monolayer culture.


Pressureless sintering and mechanical properties of hydroxyapatite/functionalized multi-walled carbon nanotube composite.
This work aims to study the optimum sintering conditions of hydroxyapatite/functionalized multi-walled carbon nanotube (HA/f-MWCNT) composite with improved mechanical properties for bone implant applications using a pressureless sintering technique. The carboxyl functional group (COOH) introduced by the acid treatment on the MWCNT surface by which HA molecules are grafted onto the surface of functionalized MWCNT with strong interfacial bonding. The composite exhibits a lower hemolytic rate of 1.27%. The flexible nature of f-MWCNT makes them bend and attached to the HA grains, indicates that f-MWCNT bear significant stress by sharing a portion of the load and it leads to improve their mechanical properties. The maximum Vickers hardness of 3.6GPa is obtained for the HA/f-MWCNT composite sintered at 1100°C, whereas the highest compressive strength of 481.7MPa and fracture toughness of 2.38MPa.m(1/2) achieved after sintering at 1150°C. This study demonstrated that HA/f-MWCNT composite create suitable structures by vacuum pressureless sintering technique to satisfy the mechanical requirements for bone tissues.


Spontaneous discharge originates in the dorsal root ganglion at the onset of a painful peripheral neuropathy in the rat.
The activity of myelinated primary afferents was recorded from the dorsal roots 1-3 days after creation of a painful peripheral neuropathy in rats. The effects on spontaneous discharge of acute transections at various points along the injured sciatic nerve and the dorsal root were determined, as were the effects of K+ channel blockers applied topically to two putative sites of impulse origin: the injured region of the nerve and the dorsal root ganglion (DRG). Transections just proximal to the nerve injury and just distal to the DRG failed to halt the discharge, but spontaneous discharge disappeared when the transection was made just proximal to the DRG (i.e. between the DRG and recording electrode). K+ channel blockers (4-aminopyridine and gallamine triethiodide) applied to the DRG increased the frequency of spontaneous discharge or initiated activity from silent fibers. Applications of K+ channel blockers to the injured region of the nerve were without effect. Thus, the spontaneous discharge and the sensitivity to K+ channel blockade seen in A beta and A delta primary afferents at the time of the onset of the neuropathic pain syndrome appear to originate in the DRG.


Origin of cholinergic nerves to the rat major cerebral arteries: coexistence with vasoactive intestinal polypeptide.
The distribution and density of vasoactive intestinal polypeptide (VIP) immunoreactive and acetylcholinesterase (AChE)-containing nerves around the cerebral arteries was studied by using whole mounts with or without lesioning the sphenopalatine ganglia. Abundant VIP immunoreactive and AChE-containing nerves were observed around the cerebral blood vessels in normal rats especially in the anterior circulation of the cerebral arteries. VIP-immunoreactivity and AChE-staining was also demonstrated in neurons within the sphenopalatine ganglia. Lesions of the sphenopalatine ganglia resulted in a marked reduction of both VIP-immunoreactivity and AChE activity. In many neurons, coexistence of both VIP and AChE was revealed. These results demonstrate that cholinergic neurons from the sphenopalatine ganglia innervate the cerebral vasculature at the base of the brain, and that VIP and AChE coexists within the same fibers.


The risk of psychiatric disorders among Finnish ART and spontaneously conceived children: Finnish population-based register study.
Evidence regarding the psychiatric morbidity of children born after Assisted Reproductive Techniques (ART) is inconsistent and limited. While normal mental well-being for ART children is usually reported, concerns are still being raised. Previous studies examine only some psychiatric disorders, but not all of them, ignore the impact of multiplicity, and limit the follow-up time to childhood. We examined all psychiatric diagnoses for singletons until their young adulthood. The aim was to study whether the risk of psychiatric disorders differs between ART and spontaneously conceived (SC) singletons until young adulthood. This retrospective Finnish population-based register study includes all ART and SC live-born children born in Finland during 1990-2013 and their hospital care in 1990-2014 (n = 1,425,975 of which 1,385,956, 97.2% were singletons). After excluding multiples, the final population included 17,610 ART and 1,368,346 SC singletons in 1990-2013 from the Finnish Medical Birth Registry. These data were linked to the Finnish Hospital Discharge Registry with the child's and mother's encrypted IDs. ART singletons had fewer psychiatric diagnoses (ART 10.2%, n = 1796, SC 12.0%, n = 164,408), but they received their diagnoses earlier (mean 8.3 years old, SD 5.0) than SC singletons (mean 10.5 years old, SD 5.7). After adjusting for confounding factors, ART singletons had an increased likelihood of getting a psychiatric diagnosis until young adulthood and the results were similar for boys (adjusted hazard ratios [aHR] = 1.16, 95% confidence interval (CI) 1.10-1.24) and girls (aHR = 1.25, 95% CI 1.16-1.35). We conclude that ART children receive their psychiatric diagnoses earlier than SC children, in particular during childhood and early adolescence. After adjusting for confounding factors ART children a slightly increased likelihood of any psychiatric diagnosis compared to SC controls.


Improvement of energy recovery potential of wet-refuse-derived fuel through bio-drying process.
This paper proposes novel wet-refuse-derived fuel (Wet-RDF) bio-drying process with the variation of initial organic substrate and moisture content. The bio-drying was carried out using 0.3 m3 lysimeter aerated continuously at different rates. Two conditions of Wet-RDF feedstock tested included: Experiment A ‒ 37% organic substrate and 58% moisture content with an initial heating value of 2,889 kcal/kg; and Experiment B ‒ 28% organic substrate and 35% moisture content with an initial heating value of 4,174 kcal/kg. The bio-drying was performed in both experiments under negative ventilation mode and non-ventilation mode, the ventilation mode was set at the aeration rates of 0.2 m3/kg/day and 0.4 m3/kg/day. The results suggest that the optimum aeration rate was 0.4 m3/kg/day, achieving a 30% moisture reduction and a 60% heating value increase from their initial values. As a result, the improved wet-RDF qualified for the local cement industry's standard in terms of heating value.


Insight into visible light-driven photocatalytic degradation of diesel oil by doped TiO2-PS floating composites.
TiO2-pearlstone (PS) floatable photocatalysts were synthesized using a facile sol-gel method and confirmed by XRD, N2 adsorption-desorption, SEM, EDX, TEM, FT-IR, XPS, and UV-vis DRS measurements. It has been found that the photocatalysts composed of anatase TiO2 deposited on the surface of PS and formed mesoporous structure. By N or B/N doping, the band gap of the photocatalyst has been narrowed. The obtained floatable photocatalysts can be applied to solar light-driven remediation of oil-contaminated water. Diesel oil was chosen as the model pollutant to evaluate the photocatalytic activity. The results showed B/N-TiO2-PS exhibited the highest photocatalytic activity for diesel oil under visible light irradiation, which is 48 % removal rate for 9 h. The reaction rate constant k of B/N-TiO2-PS is 0.08423 h(-1), which is four times larger than that of pure TiO2-PS. Moreover, the characteristic of floatable makes the photocatalysts easier to separate and reuse, which showed great potential for practical applications in the field of environmental cleanup and solar energy conversion.


Primary oocyte transcriptional activation of aqp1ab by the nuclear progestin receptor determines the pelagic egg phenotype of marine teleosts.
In marine teleosts, the aqp1ab water channel plays a vital role in the development of the pelagic egg phenotype. However, the developmental control of aqp1ab activation during oogenesis remains to be established. Here, we report the isolation of the 5'-flanking region of the teleost gilthead seabream aqp1ab gene, in which we identify conserved cis-regulatory elements for the binding of the nuclear progestin receptor (Pgr) and members of the Sox family of transcription factors. Subcellular localization studies indicated that the Pgr, as well as sox3 and -8b transcripts, are co-expressed in seabream oogonia, whereas in meiosis-arrested primary growth (pre-vitellogenic) oocytes, when aqp1ab mRNA and protein are first synthesized, the Pgr appears to be completely translocated from the ooplasm into the nucleus. By contrast, sox9b is highly expressed in more advanced oocytes, coinciding with a strong depletion of aqp1ab transcripts in the oocyte. Functional characterization of wild-type and mutated aqp1ab promoter constructs, using mammalian cells and Xenopus laevis oocytes, demonstrated that aqp1ab transcription is initiated by the Pgr, which is activated by the progestin 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P), the natural ligand of the seabream Pgr. In vitro incubation of seabream primary ovarian explants with the follicle-stimulating hormone or 17,20β-P confirmed that progestin-activated Pgr enhanced Aqp1ab synthesis via the aqp1ab promoter. However, transactivation assays in heterologous systems showed that Sox transcription factors can potentially modulate this mechanism. These data uncover the existence of an endocrine pathway involved in the early activation of a water channel necessary for egg formation in marine teleosts.


Oxidative damage to neutrophils in glutathione synthetase deficiency.
Several episodes of neutropenia were observed in a child with glutathione synthetase deficiency (5-oxoprolinuria). Studies of the patient's glutathione-deficient neutrophils were undertaken to examine the responses of the cells to oxidative stress associated with phagocytosis. The patient's neutrophils contained 10--20% of normal glutathione content. Circulating neutrophils in infection-free periods appeared less mature than normal by morphologic criteria, suggesting increased cell turnover. The cells ingested particles, responded to chemotactic stimuli, and oxidized 1-14C glucose normally. However, following ingestion of particles, the cells accumulated excess hydrogen peroxide compared with normal cells, and showed impaired protein iodination and bacterial killing. Electron micrographs revealed damage to microtubules and membranous structures in the patient's neutrophils during phagocytosis. The level of glutathione in the cells appears inadequate to protect against peroxide generated during normal cell function, and the cells are thus damaged and rendered less effective in bacterial killing. The data provide evidence for a protective role of glutathione in normal neutrophil function.


Human exposure to environmental polychlorinated dibenzo-p-dioxins and dibenzofurans: an exposure commitment assessment for 2,3,7,8-TCDD.
Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) are released into the environment from the use of chemicals contaminated with PCDDs/PCDFs, the improper disposal of contaminated production wastes and incineration/other high-temperature processes. Certain congeners are extremely stable compounds which are persistent in the environment once released. An assessment is made of the sources of human exposure to one particular dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Representative values of 2,3,7,8-TCDD concentrations in the background environment and in man are selected from available data or, when not available, inferred from other relevant information. A pathway analysis is performed utilizing the exposure commitment method. Normal dietary intake of 2,3,7,8-TCDD is quite variable depending primarily on consumption of contaminated fish. Representative intake for the average adult of 0.1 ng day-1 may be associated with a human body burden of 100 ng (approximately 7 ng 2,3,7,8-TCDD kg-1 adipose tissue). The inferred biological half-time of this compound in the body is approximately 5 years. The exposure evaluation also accounts for secondary pathways to man of 2,3,7,8-TCDD in air and drinking water. Estimates of transfer factors obtained from the representative background levels should be generally relevant and may be applied to more specific cases of exposure.


An anomaly in the active site region of thymidylate synthase.
A putative thyA gene from Escherichia coli was cloned into a high expression vector and the thymidylate synthase produced was purified to homogeneity. Comparison of the monomer molecular weight of this protein with that of authentic E. coli thymidylate synthase revealed the two to differ, suggesting that they were derived from different sources. This was confirmed by Ochterlony immunodiffusion analysis, which revealed that while the unknown thymidylate synthase formed a precipitin band with guinea pig antibody to the putative E. coli synthase, pure E. coli TS did not. In addition, the specific enzyme activity of the purified unknown thymidylate synthase was about 4-fold higher than that of the pure authentic enzyme. Sequence analysis of the active site peptide revealed that the amino acid linked to the carboxyl end of the active site cysteine was valine. The only instance where this has been found in the 11 thymidylate sequences reported so far is in the thyP3 sequence of the Bacillus subtilis phage-3T. In all the other cases, a histidine has been found in this position. Amino end group sequence analysis of the unknown synthase for about 30 residues confirmed the close identity of this protein to that of the B. subtilis phage thymidylate synthase. To determine whether the replacement of the active site histidine with a valine enhances the activity of the resulting thymidylate synthase, we affected this change in T4-phage thymidylate synthase by site-directed mutagenesis and found that instead of an increase in activity there was an 80 percent decrease.


Relationship between the liver and lymphocytotoxic alloantibodies in inbred rats. Specific absorption by nonparenchymal liver cells.
Liver allografts have a privileged status with regard to hyperacute rejection. In this experimental study, we have used extracorporeal liver hemoperfusion in sensitized rats in order to analyze reactions between lymphocytotoxic antibodies and the liver. In sensitized BN rats, a donor-specific (Lewis) extracorporeal liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. The decrease in the level of antibodies could be due to massive absorption of antibodies by the liver or to release of major histocompatibility complex antigens in a soluble form. Immunofluorescent examination of the hemoperfused liver revealed important deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. On the contrary, in control rats in which a third-party (DA) liver hemoperfusion was performed, heart allograft survival was less prolonged, the decrease in the level of lymphocytotoxic antibodies was not significant, and the deposits of IgG and C3 were much less evident. The level of circulating immune complexes was unchanged after a donor-specific or a third-party liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies on nonparenchymal liver cells.


Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections.
There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα-remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.


Sexual dimorphism in the human vocal fold innervation.
This study investigated the sexual dimorphism in the recurrent laryngeal nerve (RLN) and thyroarytenoid (TA) muscle, which control the vocal fold. The RLN and TA were bilaterally studied in human specimens obtained from necropsies (seven men and seven women). Analysis of the morphometric parameters showed that the RLN of the men were significantly larger, as shown by the intraperineural area (42.5%) (P=0.006), total number of fibers (38.0%) (P=0.0002), axonal area (34.3%) (P=0.0001), axonal diameter (19.0%) (P=0.0001), and the area of the nerve occupied by myelinated fibers (34.9%) (P=0.001). By contrast, in women, our results showed that the area of the RLN occupied by endoneurial connective tissue was larger (5.7%) (P=0.001). Estimation of the fiber area and shape coefficient showed that the histologic organization of TA is similar in men and women. These results may contribute toward enhancing our understanding about the voice neurobiology.


Measurement of Integrin Activation and Conformational Changes on the Cell Surface by Soluble Ligand and Antibody Binding Assays.
Soluble ligand and conformation-dependent antibody binding assay of integrins on the cell surface is an effective approach to evaluate the activation status of integrins in live cells. The ligands or antibodies are usually labeled with biotin or a fluorescent dye and incubated with integrin-expressing cells in suspension. The cell-bound ligands and antibodies are then detected by flow cytometry. Here we describe the detailed protocols of soluble ligand or antibody binding assay for αIIbβ3, αVβ3, α5β1, and αLβ2 integrins that are transiently or stably expressed in the model cell lines such as HEK293 or CHO-k1 cells.


The transcriptional factors CDX2 and FOXA1 in chordomas.
Chordomas are rare osseous tumors believed to originate from notochordal remnants through brachyury activation. CDX2 and FOXA1 are both induced by brachyury, but their expression has not been studied in chordomas. We retrospectively studied the immunohistochemical expression of these two factors in 57 chordomas, finding that CDX2 is not expressed in these tumors. FOXA1 expression was found in 7 (12.3%) tumors. No association of FOXA1 expression with clinical factors was found. Thus, CDX2 expression is not a feature of chordomas, while a limited expression of FOXA1 is seen.


Resident Involvement in Plastic Surgery: Divergence of Patient Expectations and Experiences with Surgeon's Attitudes and Actions.
As surgical educators, we need to balance the training of our future colleagues against the best possible outcomes and expectations of our patients. Although the legal and ethical standards for disclosure regarding trainee involvement in delivery of surgical care are well established, it is unclear if patient experiences reflect current principles of medical ethics. The attitudes and behavior of surgeons regarding informed consent and patient expectations about resident involvement also remain uncertain. One hundred and five patients surveyed within 6 weeks following their surgery to assess their experiences and expectations regarding resident involvement in their surgery. Three hundred and eight-three members of the Canadian Society for Plastic Surgery received online surveys concerning their attitudes and behaviors regarding the involvement of residents and fellows in trauma, elective, and cosmetic surgery. Only half of patients were informed that residents may be involved in their surgery and only half were aware if it occurred. This is consistent with the finding that only half of surgeons indicate that specifically requesting consent for trainee involvement during surgery is required for residents to assist or operate. If specifically asked, most patients would agree to have a resident assist in their surgery, but the majority would not agree to have the resident perform the surgery. This is contrary to the finding that more than two-thirds of surgeons report willingness for the trainee to operate independently, with supervision, on trauma or elective patients. Two-thirds of patients felt it was essential that they specifically be asked for permission regarding resident involvement and that this question should be posed by the primary surgeon. Interestingly, only half of surgeons report that patients can decline trainee involvement in their trauma or elective surgery, but the majority of surgeons reported that cosmetic surgery patients could decline resident involvement. Patients also indicated that they would be upset if they subsequently found out that residents assisted or performed their surgery without their specific consent. Canadian plastic surgeons indicate a clear commitment to intraoperative surgical training of residents and fellows, although this willingness declines precipitously when it involves cosmetic surgery patients. Unfortunately, the reported attitudes and behaviors of the surgeons are not consistent with the expectations of their patients, or the legal and ethical demands regarding informed consent.


A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.
The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed. In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively. This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.


Fine needle aspiration cytology in the work-up of mammographic and ultrasonographic findings in breast cancer screening: an attempt at differentiating in situ and invasive carcinoma.
This study evaluated the results of fine needle aspiration cytology (FNAC) from the first four years of organized mammography screening for breast cancer in Oslo, particularly our policy in differentiating in situ and invasive carcinoma. Lesions were aspirated directly, ultrasound guided, by stereotaxic device or biopsy localization plate. All lesions were aspirated by cytopathologists working with the radiologists at the breast diagnostic centre. Smears were evaluated immediately for assessment of adequacy and a preliminary diagnosis was given to the surgeon. When FNAC revealed malignancy, diagnostic terms were as follows: (1) invasive carcinoma; (2) ductal carcinoma in situ of comedo type (high nuclear grade), cannot evaluate infiltration; (3) ductal carcinoma in situ of low nuclear grade and (4) papillary tumour, cannot evaluate infiltration. There were 953 cases, 70% of which were nonpalpable. Insufficient material was obtained in 5.8%. Absolute and complete sensitivity were 81% and 91%, respectively. Specificity was 85%. There were 448 histologically proven carcinomas. 383 of these were invasive. 362 carcinomas (in situ and invasive) (80.8%) were diagnosed directly on FNAC. Distinction between invasive and in situ carcinoma was possible in 294 of 320 directly diagnosed invasive carcinomas (91.8%). PPV of a diagnosis of invasive carcinoma was 97%. Our data showed that definitive cytological diagnosis of invasive carcinoma was possible in more than 90% of fully diagnostic smears and allowed definitive primary surgery in these women.


Placental lactogen-like proteins in the rabbit placenta.
Rabbit placentae and embryos at days 11 and 12 were analyzed by two-dimensional gel electrophoresis and by light microscopic histology for the presence of placental lactogen-like proteins. Immunoblotting and immunohistochemistry were performed by using a goat anti-human placental lactogen serum as well as a monoclonal mouse anti-human prolactin immunoglobulin; the results were similar. In the gel electrophoresis of placental tissue, three protein spots at pH 5.6 and 43, 39, and 35 kDa were immunostained; they were absent in the embryo. Immunoresponse was restricted to the cytotrophoblast. Immunofluorescent cells were mainly found on the proximal parts of the placental trabeculae.


A Model for Life-Story Work: Facilitating the Construction of Personal Narrative for Foster Children.
The life-story work model is an interactive model of the self and the external systems interconnected by attunement, facilitated by an individual's construction of self. It is posited that the co-construction of the life-story is a critical aspect of the development of self and therefore plays an important role in the attunement one experiences within the nexus of the two systems.


A novel study on amyloid β peptide 40, 42 and 40/42 ratio in Saudi autistics.
We examined whether plasma concentrations of amyloid beta (Aβ) as protein derivatives play a central role in the etiology of autistic features. Concentrations of human Aβ (1-42), Aβ (1-40), and Aβ (40/42) in the plasma of 52 autistic children (aged 3-16 years) and 36 age-matched control subjects were determined by using the ELISA technique and were compared. Compared to control subjects, autistic children exhibited significantly lower concentrations of both Aβ (1-40) and Aβ (1-42) and lower Aβ (40/42) concentration ratio. Receiver operating characteristics curve (ROC) analysis showed that these measurements of Aβ peptides showed high specificity and sensitivity in distinguishing autistic children from control subjects. Lower concentrations of Aβ (1-42) and Aβ (1-40) were attributed to loss of Aβ equilibrium between the brain and blood, an imbalance that may lead to failure to draw Aβ from the brain and/or impairment of β- and γ- secretase's concentration or kinetics as enzymes involving in Aβ production.


Nitrogen and sulfur co-doped graphene quantum dot-modified electrode for monitoring of multivitamins in energy drinks.
A glassy carbon electrode was modified with nitrogen and sulfur co-doped graphene quantum dots immobilized in chitosan for the monitoring of multivitamins. The graphene quantum dots were synthesized using a simple citric acid/l-cysteine pyrolysis procedure. The co-doping with nitrogen and sulfur in the graphene matrix was confirmed by spectroscopic techniques. Electron microscopy results showed that the synthesized quantum dots had a diameter of 3.4 ± 1.4 nm. Electrochemical techniques showed excellent current responses to vitamin oxidation provided by the modified electrode compared to the bare electrode. The parameters of square wave voltammetry were optimized in order to obtain the best current responses and to study the electrochemical oxidation of vitamins. The calibration plots for vitamins B2, B6 and B12 were constructed in 0.1 mol L-1 sodium acetate buffer (pH 5.0) with limits of detection of 0.30, 30.1 and 0.32 nmol L-1, respectively. Lastly, the modified electrode was effectively implemented in the quantification of vitamins in classic and fruit-based energy drink samples.


Serum dipeptidyl peptidase activities as a possible marker of oral cancer.
Serum glycyl-l-prolyl 4-methyl-coumaryl-7-amide (gly-pro-MCA) hydrolase (DPP IV) and L-lysyl-L-alanyl beta-naphthylamide (lys-ala-beta NA) hydrolase (assumed to be DPP II) activities were measured in patients with oral squamous cell carcinoma and healthy subjects. The mean serum DPP IV activity of all cancer patients was significantly (P less than 0.001) decreased, compared with that of healthy subjects. Although there was no significant difference between the stages by International Union Against Cancer (UICC) classification (1978), DPP IV levels tended to change dynamically, reflecting the clinical status during therapies. The serum DPP IV activity of patients with a fair prognosis was significantly elevated toward the normal range, whereas the activity of patients with a poor prognosis was significantly decreased (P less than 0.05). In contrast, the mean serum lys-ala-beta NA hydrolytic activity of cancer patients was significantly (P less than 0.001) increased, compared with that of healthy subjects, and was changed reciprocally to DPP IV activity. The correlation of these two serum enzyme activities with tumor weights also was observed in animal models using nude mice transplanted with human KB carcinoma cells and hamsters transplanted with BHK21 cells. These results indicate that these serum enzyme levels may become an aid for the diagnosis of malignant tumors and for estimating the prognosis of the patients.


[Adrenergic receptors in the liver parenchyma in children with chronic hepatitis].
In the present study adrenergic receptors have been investigated in liver parenchyma, obtained at the resection of extrahepatic portal hypertension children without parenchymal affection (control group, n-7) and the resection of children in parenchymal affection (group of chronic hepatitis children, n-6). It has been shown, that the binding of beta-adrenergic radioligand 3H-dihydroalprenolol (3H-DHA) in liver parenchyma membranes of both control and chronic hepatitis groups was saturable and showed high affinity. The Scatchard analysis of the binding data indicated that the binding site was characterized by Kd and Bmax of 1.2 +/- 0.5 nM, 261.2 +/- 50 fmol/mg, respectively, for the control group; and 0.9 +/- 0.15 nM, 68.5 +/- 18.8 fmol/mg, respectively, for the group of chronic hepatitis patients; (mean+SEM). The binding of alpha 1-adrenergic antagonist 3H-prazosin (3H-PRZ) in liver parenchyma was also saturable and showed high affinity. The binding site is characterized by Kd = 0.6 +/- 0.12 nM, Bmax = 92.8 +/- 8.0 fmol/mg, for the control group; and Kd = 0.8 +/- 0.15 nM, Bmax = 195.0 +/- 22.0 fmol/mg, for the group of chronic hepatitis. It has been found that the number of binding sites of 3H-DHA significantly decreased and the number of binding sites of 3H-PRZ did not change in chronic hepatitis liver parenchyma in comparison with the control group. The results obtained suggest the important role of beta-adrenergic receptors in the pathogenesis of chronic hepatitis and in liver regeneration in children.


Novel insights into the pleiotropic effects of human serum albumin in health and disease.
Human serum albumin is the principal protein in human serum. It participates in regulation of plasma oncotic pressure and transports endogenous and exogenous ligands such as thyroxine, free fatty acids, bilirubin, and various drugs. Therefore, studying its ligand binding mechanism is important in understanding many functions of the protein. This review discusses the pleiotropic biochemical effects and their relevance to physiologic functions of albumin. Although HSA is traditionally recognized for its ligand transport and oncotic effects in human circulation, our studies have revealed its participation in several other important physiological functions. In some instances, it may function as a catalyst. Pleiotropic properties of HSA have been exploited by development of recombinant HSA and its mutants, and the use of these recombinant proteins in studies with various biochemical and biophysical techniques. These studies allowed us to obtain new insights on the diverse roles of HSA in human physiology. The following aspects of HSA were discussed in this review: 1) HSA and its mutants' role in thyroxine transport, 2) structural details of the ligand binding functions of HSA to ligands such as warfarin, digoxin, halothane anesthetics, nitric oxide, bilirubin, free fatty acids, etc, and 3) the formation of modified albumin during myocardial ischemia, its diagnostic significance, and HSA's role in cardiovascular disease. The appreciation and understanding of structural details and new physiological roles has provided a renewed interest in HSA research. Specific structural information gained on various mechanisms of HSA-ligand interaction can be used to develop a model to better understand protein-drug interactions, aid in the development of new drugs with improved pharmacokinetic effects, and ultimately be used to improve the quality of healthcare. This article is part of a Special Issue entitled Serum Albumin.


Characteristics of clinical measurements between biomechanical responders and non-responders to a shoe designed for knee osteoarthritis.
The purpose of this study was to investigate the characteristics of biomechanical and clinical measurements in relation to the knee adduction moment when wearing a standard shoe and a shoe design for individuals with knee osteoarthritis (Flex-OA). Kinematic and kinetic data were collected from thirty-two healthy individuals (64 knees) using a ten camera motion analysis system and four force plates. Subjects performed 5 walking trials under the two conditions and the magnitude of individuals' biomechanical responses where explored in relation to the clinical assessment of the Foot Posture Index, hip rotation range, strength of hip rotators, and active ankle-foot motion, all of which have been described as possible compensation mechanisms in knee osteoarthritis. Significant reductions in the first peak of the knee adduction moment (KAM) during stance phase (9.3%) were recorded (p<0.0001). However, despite this difference, 22 of 64 knees showed either no change or an increased KAM, indicating a non-response or negative-response to the Flex-OA shoe. Significant differences were observed between the responder and non-responder subgroups in the hip rotation range ratio (p=0.044) and the hip rotators strength ratio (p=0.028). Significant differences were seen in clinical assessments of hip rotation range and hip rotator strength between responders and non-responders using a cut-off of 0.02Nm/kg change in the KAM.


Review of the Pollination System by Small Diverse Insects.
Many studies have evaluated and categorized the pollination systems of plants in different regions. These studies resulted in the definition of new pollination systems, such as that by small diverse insects (SDI). Although SDI systems are frequent in tropical communities, we know little about the species of plants and pollinators that compose these systems. This study synthesized knowledge of SDI systems through a systematic review of the literature, in order to characterize the composition of plants and pollinator species related to this pollination system. Most studies of SDI systems were carried out in tropical rainforest communities, and used a variety of terminologies and concepts. We found 362 plant species assigned to the SDI system, distributed in 76 families and 35 orders. These species are mainly trees and have inconspicuous greenish flowers, and most are hermaphroditic or dioecious. Few studies provided information on the composition of pollinators, which encompassed small and large insects; beetles, wasp, flies, and bees were the most frequent groups. We suggest adoption of the term "pollination system by diverse insects" instead of "small diverse insects." We discuss conceptual aspects and questions for studies with this pollination system.


Errors in Patient History in Hospital Records.
Ghan-Shyam Lohiya MD provided medico-legal opinions as a Qualified Medical Evaluator (Occupational Medicine & Toxicology) supporting a related workers' compensation death claim. Dr G. Lohiya received partial payments for his services from Gallagher Bassett Services Company (workers' compensation insurance adjuster for the patient's employer). Sonia Krishna MD, Sapna Lohiya and Sunita Lohiya MD: No actual or potential, real or perceived conflict of interest in the drugs, devices or procedures described in the enclosed manuscript. A patient died of renal failure related to treatment of a hand contusion with ibuprofen and valdecoxib. Her hospital records revealed several incorrect and mutually conflicting statements about seven historical items in the Initial Evaluation Reports authored by five treating physicians. There were errors of commission (relying on imperfect memory, acquiescing erroneous information), and errors of omission (failure to proofread transcribed reports, question and resolve contradictory statements in sister reports, obtain correct history, and review prior medical records). Such errors wrongly implied that patient had preexisting conditions (advanced renal failure, diabetes mellitus, hypertension, asthma and alcoholism) which caused her death, and negatively impacted her workers' compensation claim. Incorrect allergy history was also noted. Preventive measures are suggested. At the 53rd Quarterly Grand Rounds in Costa Mesa, California.


Impact of oral lipid and glucose tolerance tests on the postprandial concentrations of angiopoietin-like proteins (Angptl) 3 and 4.
The postprandial regulation of angiopoietin-like proteins (Angptls) and their expression in adipocytes is poorly characterized. Circulating Angptl3 and 4 were analyzed in healthy individuals undergoing either an oral lipid tolerance test (OLTT; n = 98) or an oral glucose tolerance test (OGTT; n = 99). Venous blood was drawn after 0, 2, 4, and 6 h during OLTT and after 0, 1, and 2 h during OGTT. Anthropometric and laboratory parameters were assessed and concentrations of Angptls were quantified by enzyme-linked immunosorbent assay. Angptl gene expression in 3T3-L1 adipocytes and in murine adipose tissues and cellular fractions was analyzed by quantitative real-time PCR. Angptl3 concentrations significantly decreased while Angptl4 levels continuously increased during OLTT. Both proteins remained unaffected during OGTT. Angptl3 and Angptl4 were expressed in murine subcutaneous and visceral AT with higher mRNA levels in mature adipocytes when compared to the stroma-vascular cell fraction. Both proteins were strongly induced during 3T3-L1 adipocyte differentiation and they were unresponsive to glucose in mature fat cells. Adipocyte Angptl3 (but not Angptl4) mRNA expression was inhibited by the polyunsaturated fatty acids arachidonic acid and docosahexaenoic acid, whereas nine types of dietary fatty acids remained without any effect. There is evidence of short-time regulation of Angptl3/4 levels upon metabolic stress. Angptl4 expression is high and Angptl3 expression is low in AT and restricted mainly to mature adipocytes without any differences concerning fat compartments. Whereas dietary fatty acids and glucose are without any effect, omega-3/-6-polyunsaturated fatty acids inhibited Anptl3 expression in adipocytes.


An Initial Investigation into Naturally Occurring Loss- and Gain-Framed Memorable Breast Cancer Messages.
Memorable message research examines interpersonal messages "…remembered for extremely long periods of time and which people perceive as a major influence on the course of their lives" (Knapp, Stohl, & Reardon, 1981, p. 27). They can also guide actions, such as health behaviors. This exploratory research examined self-reported memorable messages about breast cancer to determine if they were framed, emphasizing either the benefits (gain-framed) or the costs (loss-framed) of a behavior. About one-fourth of the messages were framed, with most being gain-framed. The messages tended to emphasize early detection actions. Study limitations and implications for future research are discussed.


The evaluation of factors affecting antibody response after administration of the BNT162b2 vaccine: a prospective study in Japan.
The aim of this study was to evaluate the antibody reaction after administration of the BNT162b2 vaccine, and to reveal the factors that affect antibody production. This prospective study was carried out in the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Tokyo, Japan, from April 15, 2021 to June 09, 2021. All our hospital's workers who were administered the BNT162b2 vaccine as part of a routine program were included in this study. We calculated the anti-SARS-CoV-2 spike-specific antibody titter (1) before vaccination, (2) 7 to 20 days after the first vaccination, and (3) A total of 7 to 20 days after the second vaccination. The low-antibody titer group (LABG) was defined as the group having less than 25 percentiles of antibody titer. Univariate and Multivariate logistic regression analysis were performed to ascertain the effects of factors on the likelihood of LABG. A total of 374 participants were eventually included in our study, and they were divided into 94 LABG and 280 non-LABG. All samples showed significant antibody elevation in the second antibody test, with a mean value of 3,476 U/mL. When comparing the LABG and non-LABG groups, the median age, blood sugar, and HbA1c were significantly higher in the LABG group. The rates of participants with low BMI (<18.5) and high BMI (>30) were significantly higher in the LABG group. The proportion of chronic lung disease, hypertension, diabetes, dyslipidemia, autoimmune disease, and cancer were significantly higher in the LABG group. Although there was no significant difference confirmed with respect to the exercise hours per day, the proportion of participants that did not perform outdoor exercises was significantly higher in the LABG group. The time interval between the second vaccination and the second antibody test, and between the first and the second vaccination was significantly longer in the non-LABG group. In the multivariate logistic regression analysis, older than 60 years, the past history of hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Again, our single-center study demonstrates that older than 60 years, hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Evidence from multi-center studies is needed to develop further vaccination strategies.


Laparoscopic-assisted bowel resections in inflammatory bowel disease: state of the art.
The objectives of this paper are to review the rational, the present results and future of laparoscopic-assisted bowel surgery in patients with inflammatory bowel disease (IBD). Only a few centres in the world report on laparoscopic bowel resection in IBD that include stoma surgery, ileocolic resection, left, right and (sub)total colectomy for Crohn's disease, and subtotal or restorative total proctocolectomy (ileal pouch anal procedures). The combined series report conversion rates between 2.5% and 22.2%. Ileocolic resection, stoma creation, stricturoplasty and segmental small bowel resection are associated with an acceptable length of surgery, but laparoscopic(-assisted) total colectomy or restorative proctocolectomy still demand up to 4-6 hours of operative time. The few randomised studies addressing laparoscopic-assisted (segmental) bowel surgery versus conventional surgery demonstrated significantly less pain, a quicker return to self-care and a shorter hospital stay. The results of the series reporting on laparoscopic-assisted (ileo)colectomy in IBD are similar to those from these randomised studies. Laparoscopic-assisted subtotal colectomy and restorative proctocolectomy have no benefit compared with conventional surgery other than superior cosmesis. Morbidity of laparoscopic (ileo)colectomy in IBD is low, that of laparoscopic-assisted subtotal colectomy and restorative proctocolectomy remains to be seen. The various laparoscopic bowel resections done in IBD are all feasible. The first series describing laparoscopic surgery for IBD indicate that laparoscopic-assisted segmental (ileo)colectomy is safe and is the preferred approach provided it is done in a centre specialised in the treatment of IBD and by skilled laparoscopic surgeons beyond the learning curve. Until now, laparoscopic-assisted subtotal colectomy and restorative proctocolectomy do not have the same short-term benefits as seen in other laparoscopic colorectal procedures. Patients with inflammatory bowel disease (IBD) have a high life-time risk of having abdominal surgery and reoperations. The proposed advantages of laparoscopic surgery in this group of young patients might be higher than in patients with other colorectal diseases. Minimal physiologic insult in patients who already are under significant physiologic stress, less adhesion formation and superior cosmesis are important benefits over time. In a time where patient's demands will increase, the future of laparoscopic colonic surgery in IBD looks assured.


Retention of phospholipid acyl groups is not characteristic of neoplastic cells in culture.
Phospholipid acyl group retention of normal and mouse sarcoma virus transformed cell lines has been examined. The cells were fed [1-14C]oleate for 24 h and then grown to non-radioactive medium for 4 days. Both the transformed rat and mouse cell lines continued to release 14C-labeled fatty acids and phospholipids into the culture medium similarly to the uninfected cells, and showed shifts in 14C between phospholipid subclasses. Thus, the phospholipid acyl group stability reported for L cells is not characteristic of oncogenic cells in culture.


Mechanical right ventricular dyssynchrony in patients after atrial switch operation for transposition of the great arteries.
Recent data suggest potential benefits of cardiac resynchronization therapy in the management of right ventricular (RV) dysfunction in congenital heart disease. The aim of this study was to determine the nature, prevalence, and functional implications of mechanical RV dyssynchrony in patients after Senning or Mustard procedures for transposition of the great arteries. Twenty-eight patients (mean age 21.1 +/- 3.5 years) at 19.9 +/- 3.2 years after atrial switch operations and 29 healthy controls were studied. The times from the onset of QRS to peak systolic strain (T epsilon) at the base of and the mid RV free wall, the ventricular septum (VS), and the left ventricular (LV) free wall were determined using tissue Doppler echocardiography. Intraventricular mechanical delay was defined as Delta T epsilon(RV-VS) and interventricular mechanical delay as Delta T epsilon(RV-LV). In patients, the magnitude of RV intra- and interventricular mechanical delay was correlated with cardiac magnetic resonance-derived RV volumes and ejection fractions (n = 26) and treadmill exercise testing parameters (n = 20). Compared with controls, patients had significantly longer Delta T epsilon(RV-VS) (48.1 +/- 50.9 vs 17.0 +/- 16.1 ms, p <0.001) and Delta T epsilon(RV-LV) (63.1 +/- 49.5 vs 19.0 +/- 12.9, p <0.001). Nine patients (32%) exhibited RV dyssynchrony (Delta T epsilon(RV-VS) >49 ms, control mean +/- 2SD), and 16 patients (57%) showed interventricular dyssynchrony (Delta T epsilon(RV-LV) >45 ms). In patients, RV intra- and interventricular mechanical delay was correlated negatively with the RV ejection fraction (both r = -0.42, p = 0.03) and percentage predicted maximum oxygen consumption (r = -0.50, p = 0.03, and r = -0.52, p = 0.02, respectively) and positively with minute ventilation/carbon dioxide production slope (r = 0.49, p = 0.03, and r = 0.56, p = 0.01, respectively). In conclusion, RV dyssynchrony is common in young adults after atrial switch operations and is associated with RV systolic dysfunction and impaired exercise performance.