Effects of medial amygdaloid lesions on the initiation and the maintenance of muricide in olfactory bulbectomized rats.
In order to elucidate the role of medial amygdala on the initiation and the maintenance of muricide following olfactory bulb lesions, bilateral medial amygdaloid lesions were performed after, prior to, or simultaneously with olfactory bulb lesions. Both the initiation and the maintenance of muricide following olfactory bulb lesions were suppressed by amygdaloid lesions, and this result suggests that the medial amygdala plays a facilitatory role in both the initiation and the maintenance of muricide in olfactory bulbectomized rats.


Genetic Dissection of Rice Ratooning Ability Using an Introgression Line Population and Substitution Mapping of a Pleiotropic Quantitative Trait Locus qRA5.
Ratooning ability is a key factor that influences ratoon rice yield, in the area where light and temperature are not enough for second season rice. In the present study, an introgression line population derived from Minghui 63 as the recipient parent and 02428 as the donor parent was developed, and a high-density bin map containing 4568 bins was constructed. Nine ratooning-ability-related traits were measured, including maximum tiller number, panicle number, and grain yield per plant in the first season and ratoon season, as well as three secondary traits, maximum tiller number ratio, panicle number ratio, and grain yield ratio. A total of 22 main-effect QTLs were identified and explained for 3.26-18.63% of the phenotypic variations in the introgression line population. Three genomic regions, including 14.12-14.65 Mb on chromosome 5, 4.64-5.76 Mb on chromosome 8, and 10.64-15.52 Mb on chromosome 11, were identified to simultaneously control different ratooning-ability-related traits. Among them, qRA5 in the region of 14.12-14.65 Mb on chromosome 5 was validated for its pleiotropic effects on maximum tiller number and panicle number in the first season, as well as its maximum tiller number ratio, panicle number ratio, and grain yield ratio. Moreover, qRA5 was independent of genetic background and delimited into a 311.16 kb region by a substitution mapping approach. These results will help us better understand the genetic basis of rice ratooning ability and provide a valuable gene resource for breeding high-yield ratoon rice varieties.


Unique Bipolar Gene Architecture in the RNA Genome of Influenza A Virus.
The genome of influenza A virus consists of eight single-stranded negative-polarity RNA segments. The eighth segment (NS) encodes the anti-interferon protein NS1 (27 kDa) and the nuclear export protein NEP (14 kDa) via the classic negative-sense strategy. It also contains an additional positive-sense open reading frame that can be directly translated into the negative strand protein 8 (NSP8; 18-25 kDa in different strains). The existence of three or more genes of the opposite polarity in the same locus of a single-stranded RNA appears to be a unique ("economical") type of gene architecture in living organisms. In silico analysis of genomes of human and animal influenza A viruses revealed that the NSP8 gene had emerged in the influenza A virus population about 100 years ago ("young" gene) and is highly evolutionary variable. The obtained experimental data suggest that NSP8 gene is expressed in the infected animals, which strengthens the concept of bipolar (ambisense) strategy of the influenza A virus genome. The high variability of the NSP8 protein suggests that the "young" NSP8 gene is in the process of functional optimization. Further accumulation of mutations may alter the functions of mature NSP8 protein and lead to the emergence of mature bipolar influenza A virus with unexpected properties that would be threatening for humans and animals.


Immunologic memory induced at birth by immunization with inactivated polio vaccine in a reduced schedule.
One hundred forty-one healthy newborns were immunized 24 hours after birth with one dose of inactivated polio vaccine (IPV) of enhanced potency. Following the administration of a second vaccine dose six months later, a considerable proportion of babies responded with neutralizing antibody (NA) to the three poliovirus types. The very rapid occurrence and high antibody titer were indicative of an anamnestic response. Twenty-one infants who still had NA less than 1:4 to one-more poliovirus types after the second vaccine dose responded with very high NA values 7-10 days after a supplementary dose of IPV. It appears that IPV of enhanced potency administered at birth is apt to induce immunologic memory, which should provide the basis for protection against paralytic poliomyelitis in case of exposure to wild poliovirus later in life.


Performance of dose calibrators in Brazilian hospitals for activity measurements.
In order to obtain information on the accuracy of activity measurements in Brazilian hospitals, several intercomparison exercises have been organized since 1998. The first exercise consisted of two intercomparison runs of 131I and 99mTc and had the participation of 21 hospitals localized in Rio de Janeiro city and surroundings. The second, with 131I (47 hospitals) and 123I (12 hospitals), had the participation of hospitals localized in the whole country. The results were analyzed under the statistical point of view and conformity to the norms of Regulatory Authority. These results have shown that such exercises are necessary to improve the quality of the measurements and to identify those instruments that are producing incorrect values.


Sequence of the bacteriophage P22 anti-recBCD (abc) genes and properties of P22 abc region deletion mutants.
The nucleotide sequence of a segment of the bacteriophage P22 chromosome to the left (downstream in the PL operon) of the erf gene was determined. Previous studies (A. C. Fenton and A. R. Poteete, 1984, Virology 134, 148-160) have shown that this region encodes a function that is required for efficient growth of P22 in wild-type, but not in recB- Salmonella. The gene or genes encoding this function were designated abc (anti-recBCD). The DNA sequence reveals three open reading frames that potentially encode polypeptides with molecular weights of 10,900, 11,600, and 6600 (in order of transcription). P22 deletion mutants lacking each of the open reading frames were constructed. In addition, plasmids were constructed placing each of the open reading frames under control of the lac UV5 promoter. The phenotypes of the deletion mutants, and the results of plasmid-phage complementation tests, indicate that Abc activity depends primarily on sequences that encode the 11.6-kDa polypeptide; the 10.9-kDa polypeptide-encoding sequence makes a minor contribution to Abc activity as well. These sequences have been designated abc2 and abc1, respectively. The 6.6-kDa polypeptide is apparently uninvolved.


Muscle injury in rats induces upregulation of inflammatory cytokines in injured muscle and calcitonin gene-related peptide in dorsal root ganglia innervating the injured muscle.
In this study we evaluated the relationships among the behavioral changes after muscle injury, histological changes, changes in inflammatory cytokines in the injured muscle, and changes in the sensory nervous system innervating the muscle in rats. We established a model of muscle injury in rats using a dropped weight. Behavior was assessed using the CatWalk system. Subsequently, bilateral gastrocnemius muscles and dorsal root ganglia (DRGs) were resected. Muscles were stained with hematoxylin and eosin, and inflammatory cytokines in injured muscles were assayed. DRGs were immunostained for calcitonin gene-related peptide (CGRP). Changes of behavior and upregulation of inflammatory cytokines in injured muscles subsided within 2 days of injury. Repaired tissue was observed 3 weeks after injury. However, upregulation of CGRP in DRG neurons continued for 2 weeks after injury. These findings may explain in part the pathological mechanism of persistent muscle pain. Muscle Nerve 54: 776-782, 2016.


Scintigraphic Assessment of Deposition of Radiolabeled Fluticasone Delivered from a Nebulizer and Metered Dose Inhaler in 10 Healthy Dogs.
Aerosolized medications are increasingly being used to treat respiratory diseases in dogs. No previous studies assessing respiratory tract deposition of radiolabeled aerosols have been performed in conscious dogs. Assess respiratory tract deposition of radiolabeled, inhalant corticosteroid (fluticasone propionate labeled with 99m Tc) delivered from a nebulizer and metered dose inhaler (MDI) to healthy dogs. Ten healthy Foxhounds. Prospective, randomized, cross-over pilot study. Initial inhalation method (nebulizer or MDI) was randomly assigned. Treatments were crossed over after a 7-day washout period. Treatments initially were performed using sedation. Dogs were imaged using 2-dimensional planar scintigraphy, with respiratory tract deposition quantified by manual region-of-interest analysis. Deposition calculated as percentage of delivered dose. Six of 10 dogs were randomly selected and reassessed without sedation. Inhalation method had significant effect on respiratory tract deposition (P = 0.027). Higher deposition was achieved by nebulization with mean deposition of 4.2% (standard deviation [SD], 1.4%; range, 1.9-6.1%); whereas MDI treatment achieved a mean of 2.3% (SD, 1.4%; range, 0.2-4.2%). Nebulization achieved higher respiratory tract deposition than MDI in 7 of 10 dogs. No statistical difference (P = 0.68) was found between mean respiratory tract deposition achieved in dogs when unsedated (3.8%; SD, 1.5%) or sedated (3.6%; SD, 1.7%). Study confirms respiratory tract deposition of inhalant medications delivered from a nebulizer and MDI in healthy dogs, breathing tidally with and without sedation. Respiratory tract deposition in these dogs was low compared to reported deposition in adult humans, but similar to reported deposition in children.


Management of Parastomal Recurrence Following Total Laryngectomy.
Parastomal recurrence occurs in around 5% of patients undergoing total laryngectomy for laryngeal squamous cell carcinoma. It carries a poor prognosis which has changed little over the last 50 years, and poses a significant challenge to the head and neck surgeon. At present, surgical excision offers the only realistic chance of cure, although patients must be selected carefully following thorough work-up and in-depth multidisciplinary team discussion. This article provides a review of the literature on the management of parastomal recurrence following total laryngectomy.


Factors affecting electrogram sensing in an insertable cardiac monitor: Insights from surface electrocardiogram mapping analysis.
Fidelity of electrogram sensing may reduce false alerts from an insertable cardiac monitor (ICM). The purpose of this study was to assess the effect of vector length, implant angle, and patient factors on electrogram sensing using surface electrocardiogram (ECG) mapping. Twelve separate precordial single-lead surface ECGs were acquired from 150 participants at 2 interelectrode distances (75 and 45 mm), at 3 vector angles (vertical, oblique, and horizontal), and in 2 postures (upright and supine). A subset of 50 patients also received a clinically indicated ICM implant in 1:1 ratio (Reveal LINQ [Medtronic, Minneapolis, MN]/BIOMONITOR III [Biotronik, Berlin, Germany]). All ECGs and ICM electrograms were analyzed by blinded investigators using DigitizeIt software (V2.3.3, Braunschweig, Germany). The P-wave visibility threshold was set at > 0.015 mV. Logistic regression was used to identify factors affecting P-wave amplitude. A total of 1800 tracings from 150 participants (44.5% [n = 68] female; median age 59 [35-73] years) were assessed. The median P- and R-wave amplitudes were 45% and 53% larger with vector lengths of 75 and 45 mm, respectively (P < .001 for both). The oblique orientation yielded the best P- and R-wave amplitudes, while posture change did not affect P-wave amplitude. Mixed effects modeling found that visible P-waves occur more frequently with a vector length of 75 mm than with 45 mm (86% vs 75%, respectively; P < .0001). A longer vector length improved both P-wave amplitude and visibility in all body mass index categories. There was a moderate correlation of P- and R-wave amplitudes from the ICM electrograms to those from surface ECG recordings (intraclass correlation coefficient 0.74 and 0.80, respectively). Longer vector length and oblique implant angle yielded the best electrogram sensing and are relevant considerations for ICM implantation procedures.


Evaluation of monoclonal antibody MIB-1 in the mammary epithelium adjacent to fibroadenomas in premenopausal women treated with tamoxifen.
The purpose of this study was to study the monoclonal antibody MIB-1 in the normal breast epithelium adjacent to a fibroadenoma in women in the luteal phase of the menstrual cycle who were treated with tamoxifen at doses of 10 and 20 mg for 22 days. The proliferative activity of the mammary epithelium adjacent to the fibroadenoma was studied by immunohistochemistry on the basis of the monoclonal antibody MIB-1 (Immunotech, catalog No. 0505, lot 001). The study was randomized and double blind and was conducted on 44 women with fibroadenomas divided into three groups: A (n=16, placebo), B (n=15, tamoxifen, 10 mg), and C (n=13, tamoxifen, 20 mg). Tamoxifen was administered for 22 days starting on the 2nd day of the menstrual cycle, and a biopsy was taken on the 23rd day. Serum estradiol, progesterone, sex hormone binding globulin, follicle-stimulating hormone, luteinizing hormone, and prolactin were measured before treatment (21st and 24th day of the previous menstrual cycle) and on the day of the biopsy. The mean percentage of stained nuclei per 1,000 cells was 9.2 in group A, 4.5 in group B, and 3.2 in group C. The Fisher's test revealed that tamoxifen significantly reduced MIB-1 at doses of 10 and 20 mg compared with the placebo group (p < 0.0001), with no significant differences between doses in terms of proliferative activity (p=0.21). Groups B and C presented a significant increase in progesterone (p=0.038), estradiol (p < 0.001), and sex hormone binding globulin (p=0.001) levels. Elevation of serum follicle-stimulating hormone concentration (p=0.0045) and a fall in prolactin levels (p=0.0055) were observed. We conclude that tamoxifen significantly reduced the proliferative activity of the mammary epithelium at the doses of 10 and 20 mg/day.


An investigation of the variability of judgments of experienced and inexperienced listeners in their use of a screening test of articulation.
This study examines the extent to which the mean, or average degree of agreement, of a group of listeners actually represents the consistency of judgments of all members of that group. Twenty-two experienced and inexperienced judges scored the responses, from tape recordings, of six children with multiple articulation errors on the McDonald Screening Deep Test of Articulation. The intra- and interexaminer reliability of the judges was assessed. Results suggested that, as a group, both experienced and inexperienced listeners were capable of making consistent decisions about children's responses on the Screening Deep Test of Articulation. It was determined, however, that group averages may not reflect accurately the consistency of all members of the group or accurately estimate the population average. Variances for both groups were high and significant differences were found between the variances of the groups. Confidence intervals were reported and their clinical implications discussed.


Biochemical effects of 12-O-tetradecanoylphorbol-13-acetate, retinoic acid, phenobarbital, and 5-azacytidine on a normal rat liver epithelial cell line.
The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), all trans-retinoic acid (RA), 5-azacytidine (5-AC), and phenobarbital (PB) on the activities of seven enzymes and/or isozymes of a diploid rat liver epithelial cell line have been studied. At 0.1 microgram/ml, TPA depressed the specific activities of lactate dehydrogenase and gamma-glutamyl transpeptidase, whereas 2 mM PB depressed gamma-glutamyl transpeptidase and alkaline phosphatase. At 0.01 microgram/ml, RA markedly depressed the activity of NADH-diaphorase and lactate dehydrogenase but enhanced the activity of alkaline phosphatase. Only 2 microM 5-AC caused the most significant shift of lactate dehydrogenase isozyme toward the "muscle"-type isozyme. Histochemical studies revealed that PB and 5-AC induced focal areas of cells with glycogen deposits, but no significant changes in either ultrastructure or alpha-fetoprotein and albumin immunohistochemical staining pattern were observed to suggest hepatocytic differentiation. Although none of the enzymatic changes could be consistently correlated with the effects of these biological modifiers on the cellular growth rate, the effect of RA on NADH-diaphorase, lactate dehydrogenase, and alkaline phosphatase activities was the opposite of the changes observed during carcinogenesis of these rat liver epithelial cells by multiple treatments with N-methyl-N'-nitro-N-nitrosoguanidine. The depression of gamma-glutamyl transpeptidase activity by PB is contradictory to that observed histochemically in hepatocytes in vivo, but such discrepancy may be related to the differences in cell type, growth conditions, or duration of exposure.


Bovine enterovirus CPE at different multiplicities of infection in the absence of viral RNA synthesis.
When bovine enterovirus (BEV) RNA synthesis was inhibited by 2-(alpha-hydroxybenzyl)-benzimidazole (HBB), an increase in MOI was accompanied by an enhancement of cytopathology. Since BEV RNA synthesis is inhibited and BEV protein synthesis is allowed to proceed in the presence of HBB, these results support the concept that proteins play a role in the development of cytopathology independently of viral double-stranded RNA.


A novel geometry-based analysis of hippocampal morphometry in mesial temporal lobe epilepsy.
Hippocampal volumetry is an essential tool in researching and diagnosing mesial temporal lobe epilepsy (mTLE). However, it has a limited ability to detect subtle alterations in hippocampal morphometry. Here, we establish and apply a novel geometry-based tool that enables point-wise morphometric analysis based on an intrinsic coordinate system of the hippocampus. We hypothesized that this point-wise analysis uncovers structural alterations not measurable by volumetry, but associated with histological underpinnings and the neuropsychological profile of mTLE. We conducted a retrospective study in 204 individuals with mTLE and 57 age- and gender-matched healthy subjects. FreeSurfer-based segmentations of hippocampal subfields in 3T-MRI were subjected to a geometry-based analysis that resulted in a coordinate system of the hippocampal mid-surface and allowed for point-wise measurements of hippocampal thickness and other features. Using point-wise analysis, we found significantly lower thickness and higher FLAIR signal intensity in the entire affected hippocampus of individuals with hippocampal sclerosis (HS-mTLE). In the contralateral hippocampus of HS-mTLE and the affected hippocampus of MRI-negative mTLE, we observed significantly lower thickness in the presubiculum. Impaired verbal memory was associated with lower thickness in the left presubiculum. In HS-mTLE histological subtype 3, we observed higher curvature than in subtypes 1 and 2 (all p < .05). These findings could not be observed using conventional volumetry (Bonferroni-corrected p < .05). We show that point-wise measures of hippocampal morphometry can uncover structural alterations not measurable by volumetry while also reflecting histological underpinnings and verbal memory. This substantiates the prospect of their clinical application.


Crowdsourcing Electronic Health Record Improvements at Scale across an Integrated Health Care Delivery System.
Despite widespread adoption of electronic health records (EHRs), these systems have significant room for improved efficiency and efficacy. While the idea of crowdsourcing EHR improvement ideas has been reported, little is known about how this might work across an integrated health care delivery system in practice. Our program solicited EHR improvement submissions during two timeframes across 10 hospitals and 60 clinics in an upper-Midwest integrated health care delivery system. Submissions were primarily collected via an EHR help feature. A total of 262 and 294 submissions were received in 2019 and 2022, with a majority initiated from physicians (73.5 and 46.9%, 2019 and 2022) specializing in family medicine (52.0 and 59.3%). In 2022, the program reached a larger variety of personnel than 2019, with 53.0% of submissions from advanced practice providers, nurses, administrative staff, and other roles (p < 0.0001). Many ideas (36.4 and 50.0% in 2019 and 2022) reflected a lack of user understanding of EHR features and were addressed through training/education. Significant (27.1 and 25.9%) or simple (24.0 and 14.7%) EHR optimizations were required to address most remaining suggestions, with a number part of planned EHR improvement projects already (16.3 and 17.6%). Our experience using a crowdsourcing approach for EHR improvement ideas provided clinicians and staff the opportunity to address frustrations with the EHR and offered concrete feedback and solutions. While previous studies have suggested EHR technology improvements as paramount, we observed large numbers of users having a misunderstanding of EHR features, highlighting the need for improved EHR user competency and training.


Prediction of delayed treatment response in pulmonary tuberculosis: use of time to positivity values of Bactec cultures.
New drugs that can shorten tuberculosis (TB) treatment and target drug resistant strains are urgently needed. A test which could predict patients at risk of a delayed response to treatment would facilitate clinical trials of new anti-tuberculosis drugs. A widely-used test for the assessment of response to treatment is sputum smear examination. Patients who are smear positive after 2 and 3 months of treatment are said to have delayed and significantly delayed treatment responses respectively. Time to positivity (TTP) values of Bactec cultures, from the first 2 weeks of treatment were used to predict delayed and significantly delayed treatment responses in patients with first time pulmonary tuberculosis. Changes in TTP values early in treatment were transformed to a response ratio (r). Values of r that were less than a threshold value (r(c)) indicated patients who were at risk of having delayed or significantly delayed response to treatment. Accuracy of prediction was sensitive to the timing of sputum sampling and adherence to therapy in the first 2 weeks. Based on TTP data from the first 2 weeks of treatment, significantly delayed treatment response could be predicted with a sensitivity of 75% and a specificity of 62% while the positive (PPV) and negative predictive values (NPV) were 14% and 97% respectively. While the high NPV indicates that a large proportion of patients with a satisfactory response to treatment can be reliably identified, the low PPV value underlines the need to use TTP in conjunction with other markers of disease activity to predict unfavourable treatment response in tuberculosis treatment.


Proposal of a novel pipeline involving precise bronchoscopy of distal peripheral pulmonary lesions for genetic testing.
Next-generation sequencing (NGS) has become increasingly more important for lung cancer management. We now expect biopsies to be sensitive, safe, and yielding sufficient samples for NGS. In this study, we propose ultraselective biopsy (USB) with sample volume adjustment (SVA) as a novel method that integrates an ultrathin bronchoscope, radial probe endobronchial ultrasound, and the direct oblique method for ultraselective navigation, and adjustment of sample volume for NGS. Our purpose was to estimate the diagnostic potential and the applicability of USB-SVA for amplicon-based NGS analysis. The diagnostic yield of bronchoscopy in forty-nine patients with malignant peripheral pulmonary lesions (PPLs) was retrospectively analyzed, and amplicon-based NGS analysis was performed on samples from some patients using USB. The diagnostic yields of distal PPLs in the USB group were significantly higher than those in the non-USB group (90.5% vs. 50%, respectively, p = 0.015). The extracted amounts of nucleic acids were at least five times the minimum requirement and the sequence quality met the criteria for the Oncomine™ Target Test. Only the tumor cell content of some samples was insufficient. The feasibility of the pipeline for USB, SVA, and amplicon-based NGS in distal PPLs was demonstrated.


Avidin-biotin enhanced reverse passive hemagglutination method for detection of HIV antigens.
A new assay for HIV antigens, the avidin-biotin enhanced reverse passive hemagglutination (AB RPHA) test is described which is suitable for detection of infection in cell culture experiments. This assay is simple to perform and economical, and has sensitivity equal to or greater than that of commercial ELISA assays. The coated red cells used for this assay may be stored in the frozen or lyophilized state.


Introducing brief admissions by self-referral in child and adolescent psychiatry: an observational cohort study in Sweden.
Brief admission by self-referral, a novel crisis intervention designed to reduce suicide and self-harm in adults, was adopted for adolescents in paediatric psychiatry in Malmö, Sweden, in 2018. We aimed to investigate changes in utilisation of emergency psychiatric care. We did an observational longitudinal cohort study in The University Hospital in Malmö, Sweden, which provides the only psychiatric emergency unit with 24 h psychiatric facilities in Region Skåne. Eligible patients were those aged 13-17 years who were admitted to the psychiatric facility, who had at least one emergency visit or admission during the 6 months before admission, and had prominent features of instability and self-harm, corresponding to at least three of the nine criteria for borderline personality disorder as per the DSM-5 as assessed by a paediatric psychiatrist during the admission. Patients with intellectual disabilities, psychosis, or language barriers were excluded. Patients who signed a brief admissions contract between April 1, 2018, and April 30, 2021, were eligible for inclusion in the study. A brief admissions contract allows patients to admit themselves to psychiatric emergency care for a transitory time. The primary outcome measures were the number of emergency visits, emergency admissions, inpatient days, and episodes of coercive (involuntary) care, compared at individual level before and after signing the brief admissions contract until end of follow-up. The number of visits and days were modelled using random-effects Poisson regression models, and the relative changes in the expected numbers of days per time unit were reported as rate ratios (RRs). Of the 928 patients admitted to the psychiatric facility between April 1, 2018, and April 30, 2021, 60 were excluded, and a further 801 did not meet the inclusion criteria for age, previous emergency visits, or having at least three of the nine criteria of borderline personality disorder. 67 patients were eligible for inclusion, but four patients did not sign a contract. 63 patients were included in the study, including 60 females (95%) and three (5%) males, with a mean age of 14·8 years (SD 1·7). Ethnicity data were not collected. Patients were followed up for a median of 13·5 months (IQR 9·2 -19·6). After signing the contract, there was a decrease in the number of emergency visits (RR 0·22 [95% CI 0·15-0·32]; p<0·0001), emergency admissions (RR 0·26 [0·19-0·35]; p<0·0001), inpatient days (RR 0·29 [0·26-0·32]; p<0·0001), and inpatient days including brief admissions (RR 0·44 [95% CI 0·40-0·48]; p<0·0001). Episodes of coercive care did not change significantly (RR 0·99 [95% CI 0·40-2·43]; p=0·98). Psychiatric evaluation due to persistent suicidal ideations immediately after discharge was required for five patients. Our findings suggest that brief admissions can be successfully implemented in paediatric psychiatry and appear to be an effective crisis management method for adolescents, associated with reduced demand for emergency care. Future randomised controlled trials are warranted. Region Skåne Health Care Authority.


Arsenic speciation analysis of human urine using ion exchange chromatography coupled to inductively coupled plasma mass spectrometry.
A sensitive and robust method for the determination of seven inorganic and organic arsenic species was developed using ion exchange chromatography combined with inductively coupled plasma mass spectrometry (IC-ICP-MS). Both anion and cation exchange columns were used in a complementary fashion. Arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were selectively separated by an anion exchange column using sodium hydroxide (NaOH) gradient elution, while monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)) and arsenobetaine (AsB) were separated by a cation exchange column using 70 mM nitric acid as the mobile phase. Baseline separation, high repeatability and low detection limits (0.10-0.75 ng mL(-1)) were achieved. The spiked urine samples were analyzed with this method to evaluate the matrix effect on the method. The results suggest 1-10 dilutions should be made to urine samples before sample injection for the anion exchange analysis to minimize the matrix effect. To validate the method, a new standard reference material (NIST SRM-2670a) was also analyzed. The arsenic species in NIST SRM-2670a were determined by this method, and the sum of their concentrations agreed well with the total arsenic content certified for NIST SRM-2670a. Moreover, this method was applied to measure arsenic species in urine samples from one subject living in New Jersey who drank well water contaminated with arsenic. By this method, two key arsenic metabolites, MMA(III) and DMA(III), were found to be present in these urine samples, which has previously been rarely reported.


Molecular and clinical characterization of PTRF in glioma via 1,022 samples.
Polymerase I and transcript release factor (PTRF) plays a role in the regulation of gene expression and the release of RNA transcripts during transcription, which have been associated with various human diseases. However, the role of PTRF in glioma remains unclear. In this study, RNA sequencing (RNA-seq) data (n = 1022 cases) and whole-exome sequencing (WES) data (n = 286 cases) were used to characterize the PTRF expression features. Gene ontology (GO) functional enrichment analysis was used to assess the biological implication of changes in PTRF expression. As a result, the expression of PTRF was associated with malignant progression in gliomas. Meanwhile, somatic mutational profiles and copy number variations (CNV) revealed the glioma subtypes classified by PTRF expression showed distinct genomic alteration. Furthermore, GO functional enrichment analysis suggested that PTRF expression was associated with cell migration and angiogenesis, particularly during an immune response. Survival analysis confirmed that a high expression of PTRF is associated with a poor prognosis. In summary, PTRF may be a valuable factor for the diagnosis and treatment target of glioma.


Control of drooling by translocation of parotid duct and extirpation of mandibular gland.
A modified Wilkie procedure, consisting of submandibular gland resection and parotid duct transplantation, has proven to be successful in controlling drooling in over 90 per cent of 120 patients with cerebral palsy and/or mental retardation. Follow-up ranges from one to six years. The operation is safe, effective and appears to be permanent.


Insights into oleaginous phenotype of the yeast Papiliotrema laurentii.
Oleaginous yeasts have stood out due to their ability to accumulate oil, which can be used for fatty acid-derived biofuel production. Papiliotrema laurentii UFV-1 is capable of starting the lipid accumulation in the late exponential growth phase and achieves maximum lipid content at 48 h of growth; it is, therefore, interesting to study how its oleaginous phenotype is regulated. Herein, we provide for the first time insights into the regulation of this phenotype in P. laurentii UFV-1. We sequenced and assembled its genome, performed comparative genomic analyses and investigated its phylogenetic relationships with other yeasts. Gene expression and metabolomic analyses were carried out on the P. laurentii UFV-1 cultivated under a nitrogen-limiting condition. Our results indicated that the lipogenesis of P. laurentii might have taken place during evolution after the divergence of genera in the phylum Basidiomycota. Metabolomic data indicated the redirection of the carbon flux towards fatty acid synthesis in response to the nitrogen limitation. Furthermore, purine seems to be catabolized to recycle nitrogen and leucine catabolization may provide acetyl-CoA for fatty acid synthesis. Analyses of the expression of genes encoding certain enzymes involved with the oleaginous phenotype indicated that the NADP+-dependent malic enzyme seems to play an important role in the supply of NADPH for fatty acid synthesis. There was a surprising decrease in the expression of the ACC1 gene, which encodes acetyl-CoA carboxylase, during lipid accumulation. Taken together, our results provided a basis for understanding lipid accumulation in P. laurentii under nitrogen limiting conditions.


Potential or contraindicated drug-drug interactions with antiretroviral therapy in real-world settings in Taiwan.
Given the complex metabolic pathway of antiretroviral therapy (ART), polypharmacy may increase the risk of drug-drug interactions (DDIs). Therefore, we investigated the frequency of DDIs during ART exposure to improve medical care for patients with human immunodeficiency virus (HIV). This was a nationwide cross-sectional study using claims data from the National Health Insurance in Taiwan in 2016. Potential or contraindicated DDIs with recommended first-line ART (1L-ART) or protease inhibitors (PIs) were identified from the University of Liverpool drug interaction database. Fisher's exact or chi-square test was used to determine the significance of categorical variables. A total of 25,863 HIV-infected individuals were identified. Regarding 1L-ART users, patients with contraindicated DDIs accounted for 1-4%, whereas those with potential DDIs accounted for 15-50%. The most frequently coprescribed medications related to potential DDIs were diclofenac and polyvalent cation-containing antacids. Among PI users, 8-10% of them had contraindicated DDIs while 44-50% of them had potential DDIs. The medications related to potential DDIs with PIs were zolpidem, betamethasone, polyvalent cation-containing antacids, and loperamide. Our study showed a low prevalence of contraindicated DDIs in the HIV population; however, more attention should be paid to a high proportion of potential DDIs. Strategies to avoid these DDIs should be implemented if possible. Further research that focuses on the long-term clinical impact of potential DDIs is warranted.


Correction to: Correlation between incidental fat deposition in the liver and pancreas in asymptomatic individuals.
Unfortunately the article was published with a spell error in the co-author names "Ankur Pandy and Pallavi Pandy". The correct co-author names should be Ankur Pandey and Pallavi Pandey".


MI-CAT: A transformer-based domain adaptation network for motor imagery classification.
Due to its convenience and safety, electroencephalography (EEG) data is one of the most widely used signals in motor imagery (MI) brain-computer interfaces (BCIs). In recent years, methods based on deep learning have been widely applied to the field of BCIs, and some studies have gradually tried to apply Transformer to EEG signal decoding due to its superior global information focusing ability. However, EEG signals vary from subject to subject. Based on Transformer, how to effectively use data from other subjects (source domain) to improve the classification performance of a single subject (target domain) remains a challenge. To fill this gap, we propose a novel architecture called MI-CAT. The architecture innovatively utilizes Transformer's self-attention and cross-attention mechanisms to interact features to resolve differential distribution between different domains. Specifically, we adopt a patch embedding layer for the extracted source and target features to divide the features into multiple patches. Then, we comprehensively focus on the intra-domain and inter-domain features by stacked multiple Cross-Transformer Blocks (CTBs), which can adaptively conduct bidirectional knowledge transfer and information exchange between domains. Furthermore, we also utilize two non-shared domain-based attention blocks to efficiently capture domain-dependent information, optimizing the features extracted from the source and target domains to assist in feature alignment. To evaluate our method, we conduct extensive experiments on two real public EEG datasets, Dataset IIb and Dataset IIa, achieving competitive performance with an average classification accuracy of 85.26% and 76.81%, respectively. Experimental results demonstrate that our method is a powerful model for decoding EEG signals and facilitates the development of the Transformer for brain-computer interfaces (BCIs).


The mole of pallido-thalamic transmission investigated with intracellular recording from cat thalamus.
Pallido-thalamic transmission was studied by intracellular recording from neurons in the ventrolateral (VL) and ventroanterior (VA) nuclei of the thalamus in cats anesthetized with pentobarbital. Stimulation of the entopeduncular nucleus (ENT) produced short latency, inhibitory postsynaptic potentials in the VL-VA neurons (1.60 ms on average). When stimuli were applied closer to the VL-VA region along the pallido-thalamic pathway, i.e., to the rostral Forel's field, the IPSP latency was significantly reduced. Linear regression analysis of the IPSP latency against conduction distance between different stimulating the recording positions indicated that the IPSP was produced through a monosynaptic pathway at a conduction velocity of 5 to 11 m/s. The neurons which received IPSPs from the ENT distributed in the rostromedial VL and in the rostral VA, whereas relay cells responding only to the contralateral brachium conjunctivum were found in the caudal VL and in the dorsolateral portion of the rostral VL-VA complex. Reciprocal convergence of pallidal and cerebellar impulses were observed in only a small number of cells, which were located in the border between the two neuron groups. Recording of extracellular field potentials and focal stimulation within and around the rostral VL also indicated that the fiber potentials arose from the ENT nucleus and propagated along a bundle of fibers which terminated within the rostromedial VL-VA complex. These results are all explicable by assuming that the entopeduncular neurons are inhibitory in nature and so inhibit thalamic neurons monosynaptically.


Learning in the honey bee waggle dance.
The waggle dance of honey bees is a classic example of complex behavior and communication in animals. Despite long being considered a completely fixed and innate behavior, recent work is showing a role for social learning in tuning components of the waggle dance in naïve bees.


Overexpression of RNA helicase p68 protein in cutaneous squamous cell carcinoma.
RNA helicase p68 is a prototypic DEAD-box RNA helicase. Recent studies indicate that p68 plays important role in cancer development and progression. However, the role of p68 protein expression in cutaneous squamous cell carcinoma (SCC) remains unknown. To elucidate the expression of p68 protein in cutaneous SCC. The level of p68 protein was examined by double immunofluorescent staining in 24 samples of human cutaneous SCC tissue specimens and their adjacent tissues and in 6 normal foreskin samples to compare the expression of p68 with that of Ki-67. Overexpression of p68 protein was seen in all 24 SCC cases (100%), whereas very low expression of p68 was detected in normal foreskin. Moreover, p68 protein expression was higher in cases of cutaneous SCC with metastasis than in cases without metastasis. Additionally, p68 had a similar expression pattern to that of Ki-67. The high frequency of p68 expression in cutaneous SCC indicates that p68 might be involved in the development and progression of cutaneous SCC.


Decrease of intracellular ATP content downregulated UCP2 expression in mouse hepatocytes.
Mitochondrial uncoupling protein 2 (UCP2) plays an important role in regulating energy metabolism. We previously reported that UCP2 expression in steatotic livers is increased which leads to diminished hepatic ATP stores and renders steatotic hepatocytes vulnerable to ischemic damage. In this study, reagents that inhibit the production of ATP were used to mimic an ischemic state in the liver in order to investigate the effects of decreased intracellular ATP levels on UCP2 expression in a murine hepatocyte cell line (HEP6-16). Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), an oxidative phosphorylation uncoupler, was found to decrease intracellular ATP levels in a dose- and time-dependent manner. Relatively high concentrations of FCCP from 8 to 80 microM were required to reduce the intracellular concentration of ATP. The inhibitory effect of FCCP on intracellular ATP was significantly potentiated by 2-deoxy-D-glucose, an inhibitor of glycolysis that when administered alone had no negative effect on cellular ATP levels in mouse hepatocytes. Decreased intracellular ATP levels were accompanied by lower UCP2 mRNA expression. Upon removal of FCCP and/or 2-deoxy-D-glucose and reculture with normal medium, ATP and UCP2 mRNA levels returned to normal within a few hours. Mitochondrial membrane potential in HEP6-16 cells was dissipated by 80 microM FCCP but not 8 microM FCCP, suggesting that the downregulation of UCP2 expression by FCCP was not related to mitochondrial potential changes. Consequently, the in vitro manipulation of ATP stores is consistent with the in vivo observations associated with ischemia/reperfusion injury.


[Effectiveness of a programme based on a virtual reality game for cognitive enhancement in schizophrenia].
To evaluate the effectiveness of a programme based on a virtual reality game to improve cognitive domains in patients with schizophrenia. A randomized controlled trial was conducted in 40 patients with schizophrenia, 20 in the experimental group and 20 in the control group. The experimental group received 10 sessions with Nintendo Wii(®) for 5 weeks, 50 minutes/session, 2 days/week in addition to conventional treatment. The control group received conventional treatment only. Statistically significant differences in the T-Score were found in 5 of the 6 cognitive domains assessed: processing speed (F=12.04, p=0.001), attention/vigilance (F=12.75, p=0.001), working memory (F=18.86, p <0.01), verbal learning (F=7.6, p=0.009), visual learning (F=3.6, p=0.064), and reasoning and problem solving (F=11.08, p=0.002). Participation in virtual reality interventions aimed at cognitive training have great potential for significant gains in different cognitive domains assessed in patients with schizophrenia.


Immunological Paradigms, Mechanisms, and Models: Conceptual Understanding Is a Prerequisite to Effective Modeling.
Most mathematical models that describe the individual or collective actions of cells aim at creating faithful representations of limited sets of data in a self-consistent manner. Consistency with relevant physiological rules pertaining to the greater picture is rarely imposed. By themselves, such models have limited predictive or even explanatory value, contrary to standard claims. Here I try to show that a more critical examination of currently held paradigms is necessary and could potentially lead to models that pass the test of time. In considering the evolution of paradigms over the past decades I focus on the "smart surveillance" theory of how T cells can respond differentially, individually and collectively, to both self- and foreign antigens depending on various "contextual" parameters. The overall perspective is that physiological messages to cells are encoded not only in the biochemical connections of signaling molecules to the cellular machinery but also in the magnitude, kinetics, and in the time- and space-contingencies, of sets of stimuli. By rationalizing the feasibility of subthreshold interactions, the "dynamic tuning hypothesis," a central component of the theory, set the ground for further theoretical and experimental explorations of dynamically regulated immune tolerance, homeostasis and diversity, and of the notion that lymphocytes participate in nonclassical physiological functions. Some of these efforts are reviewed. Another focus of this review is the concomitant regulation of immune activation and homeostasis through the operation of a feedback mechanism controlling the balance between renewal and differentiation of activated cells. Different perspectives on the nature and regulation of chronic immune activation in HIV infection have led to conflicting models of HIV pathogenesis-a major area of research for theoretical immunologists over almost three decades-and can have profound impact on ongoing HIV cure strategies. Altogether, this critical review is intended to constructively influence the outlook of prospective model builders and of interested immunologists on the state of the art and to encourage conceptual work.


Association of healthcare costs with per unit body mass index increase.
The objective of this study was to quantify the healthcare costs per unit increase in body mass index (BMI). This cross-sectional study included 35,932 employees and spouses in a manufacturing company who participated in an indemnity/PPO plan and one health risk appraisal during 2001 and 2002. Within the BMI range of 25 to 45 kg/m, medical costs and pharmaceutical costs increased dollar 119.7 (4%) and dollar 82.6 (7%) per BMI unit, respectively, adjusted for age and gender. The adjusted medical costs related to diabetes and heart disease increased by dollar 6.2 and dollar 20.3 per BMI unit. The likelihood of having any medical claim increased 11.6% per BMI unit for diabetes and 5.2% for heart disease. Each unit increase in BMI is associated with higher healthcare costs and increased likelihood of having claims for most major diagnostic codes and for diabetes and heart diseases.


Incidence, clinicopathological features, and clinical outcomes of low HER2 expressed, inoperable, advanced, or recurrent gastric/gastroesophageal junction adenocarcinoma.
According to the DESTINY-Breast04 trial, treating patients with breast cancer and low human epidermal growth factor receptor 2 expressions (HER2-low) varies from that of those with no HER2 expression. However, it is interesting to know if HER2-low indicates for anti-HER2 therapy in the gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Hence we conducted this study to assess the incidence, clinicopathological features, and treatment outcomes of patients with HER2-low G/GEJ adenocarcinoma. This was a single-center, retrospective observational study. Patients with previously untreated G/GEJ adenocarcinoma were classified based on their HER2 status using immunohistochemistry (IHC) with or without in situ hybridization (ISH) as follows: HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-), and HER2-positive (IHC2+/ISH+ or 3+). In total, 734 patients with G/GEJ adenocarcinoma were divided into three groups (HER2-negative, n = 410; HER2-low, n = 154, and HER2-positive, n = 170). The intestinal-type histology, peritoneal metastasis, and higher serum carcinoembryonic antigen (CEA) levels differed significantly among patients with negative, low, and positive HER2 statuses: intestinal-type histology (21.0%, 44.2%, and 59.8%, respectively), peritoneal metastasis (56.3%, 44.8%, and 21.8%, respectively), and higher serum CEA level (32.2%, 41.6%, and 56.5%, respectively). Improved survival was observed in the HER2-positive group than in the HER2-negative G/GEJ adenocarcinoma group [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.59-0.89; P = 0.002]. However, the prognoses of the HER2-low and HER2-negative groups were similar (HR = 1.01, 95% CI 0.82-1.23; P = 0.843). Patients with HER2-low G/GEJ adenocarcinoma exhibited intermediate and distinct characteristics than those in the HER2-negative group. Similarly, the HER2-low group's prognosis was worse than that of the HER2-positive group. Therefore developing novel therapeutic strategies targeting HER2-low G/GEJ adenocarcinoma is required.


A new theoretical model deriving planetary boundary layer height in desert regions and its application on dust devil emissions.
Planetary boundary layer height (PBLH) is one of the major factors influencing the occurrence of dust storms and dust devils in desert regions; however, the existing planetary boundary layer parameterization schemes are largely limited to reflect the actual diurnal cycles of PBLH in desert regions, which further affects the global dust-aerosol emission evaluation. A new theoretical model deriving PBLH applicable to the desert areas is developed based on heating effect of dust aerosols and the method calculating PBLH by the vertical profile of virtual potential temperature, and then parameterized by observations at the desert regions in northern China (defined as new PBLH scheme). The results show that the simulated PBLH by the new scheme agrees better with the observations compared to the available PBLH schemes in the WRF model, such as Yonsei University scheme (YSU), Asymmetric Convection Model 2 scheme and Shin-Hong scale-aware scheme. The PBLHs derived from those three schemes might be replaceable by the new scheme due to the great improvement. The normally used YSU scheme and the new PBLH scheme are further applied to evaluate dust-devil emissions, despite the consistent unimodal distribution and similar spatial distribution in daily dust-devil emissions from two schemes in comparison with the measured occurrence frequency of dust devils, the new PBLH scheme improves the emission at the episodes from 09:00 to 18:00 LST (Local Standard Time) with greater magnitude relative to the YSU scheme, and demonstrates more significant differences near the peak-emission time, leading to approximate 1.5 times higher in the summer emission of dust devils. The results imply that the existing schemes underestimate about 5% of the contribution of dust devil emissions to the total amount of dust aerosols, and the new scheme can evaluate better, and provide new insight to understand the impact of the aerosol on climate effect.


Variability of requirements to fermentation media in Claviceps purpurea strains.
The alkaloid-synthesizing activity of the saprophytic Claviceps purpurea strains was variable. This fact was partly due to different requirements of the cultures to nutritional conditions. Not only single strains, but also formation of intra- and extracellular alkaloids differed in this respect. In case of extracellular alkaloids, the influence of medium was more expressive. A positive correlation between accumulation of cell polysaccharides and the level of intracellular alkaloids was evident. Constant or decreasing cell proteins were favourable for alkaloid formation.


Orthogonal-field-alternation gel electrophoresis banding patterns of DNA from yeasts.
Chromosomal DNAs from various yeast species were separated by orthogonal-field-alternation gel electrophoresis (OFAGE). To this end we developed a spheroplasting and lysis method to obtain intact DNA from both ascomycetous and basidiomycetous yeasts. The OFAGE banding patterns of 22 ascomycetous and four basidiomycetous yeast strains were compared. The strains represented species from the genera: Brettanomyces, Candida, Cryptococcus, Filobasidiella, Geotrichum, Hansenula, Kluyveromyces, Pachysolen, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Saccharomycodes, Saccharomycopsis, Schizosaccharomyces and Zygosaccharomyces. Variations occurred in the number of bands and their positions in the gel, not only among strains of different genera but also among species from the same genus and even between varieties of the same species. The ascomycetous yeasts, with the exception of Saccharomyces cerevisiae, only showed one to five bands of DNA larger than 1000 kilobase pairs (kb) in general none smaller. The patterns of the four basidiomycetous yeasts revealed also a few large DNA bands but in addition one to six bands ranging in size from 500 to 1000 kb, with the exception of a single smaller chromosome in Rhodotorula mucilaginosa. From the OFAGE banding patterns of strains studied here it appears that in Sacch. cerevisiae the partitioning of DNA over chromosomes is unique. But rather than the large number of chromosomes, the presence of four chromosomes with less than 500 kb of DNA is characteristic for Sacch. cerevisiae.


Associations among dietary zinc intakes and biomarkers of zinc status before and after a zinc supplementation program in Guatemalan schoolchildren.
The associations among dietary zinc intakes and biomarkers of zinc status are unknown in apparently healthy children at high risk for zinc deficiency. To assess associations among zinc-related parameters in a sample of Guatemalan school-aged children. We assessed total dietary intakes and biomarkers of zinc status before and after receiving 6 months of zinc supplementation or placebo in 691 Guatemalan schoolchildren aged 6 to 11 years. Most of the children also received zinc-fortified milk from a government program that started shortly after the trial began. We assessed associations between zinc intakes and serum zinc, alkaline phosphatase (ALP), and albumin. At baseline, the prevalence of serum zinc < 65 microg/dL and dietary zinc intake below Estimated Average Requirements (EAR) (< 4 and < 7 mg/day for children < 9 and > or = 9 years, respectively) were 21.6% and 39.4%, respectively. Pearson correlations between serum zinc concentration and dietary zinc intake, serum ALP, and serum albumin were r = 0.07, 0.15, and 0.07, respectively. At the 6-month follow-up, low serum zinc and low total (diet plus fortified milk) zinc intakes were observed in 1.2% and 0.0% of children in the zinc-supplemented group and 4.0% and 34.1% in the placebo group, respectively. Pearson correlations between serum zinc concentration and total zinc intake, serum ALP, and serum albumin were 0.10, 0.06, and -0.11 in the zinc-supplemented group and -0.04, 0.05, and 0.01 in the placebo group, respectively. Zinc intake was inconsistently associated with markers of serum zinc concentration. Zinc fortification or supplementation attenuated the associations.


Medico-Legal Topics in Emergency Cardiology.
The workup and diagnosis of cardiovascular emergencies represent the present and future risk to emergency physicians. Eliciting and documenting key details of a cardiovascular complaint, as well as following established standards for accurate and timely diagnosis of emergencies, is central to the medico-legal aspects of cardiovascular emergencies. Key elements of documentation include history, physical exam, diagnostic workup, and medical decision making. Key elements of medical malpractice include the existence of a legal duty, breach of the legal duty, causation, and presence of damages. All 4 legal elements must be present for medical malpractice to be proven in a court of law.


tRNA-derived fragments as new players in regulatory processes in yeast.
For a very long time, RNA molecules were treated as transistory molecules, by which the genetic information flows from DNA to proteins; the model proposed in the 1960s accepted that proteins are both the products and the regulators of gene expression. Since then, thousands of reports proved that RNAs should be thought about as the factors that do control gene expression. The pervasive transcription has been reported in many eukaryotic organisms, illustrating a highly interwoven transcriptome organization that includes hundreds of previously unknown noncoding RNAs. The key roles of noncoding RNAs (microRNAs and small interfering RNAs) in gene expression regulation are no longer surprising, as are new classes of noncoding RNAs constantly being discovered. Transfer RNAs (tRNAs) are the second most abundant type of RNAs in the cell. Advances in high-throughput sequencing technologies exposed the existence of functional, regulatory tRNA-derived RNA fragments (tRFs), generated from precursor and mature tRNAs. These tRF molecules have been found to play central roles during stress and different pathological conditions. Herein, we present the critical assessment of the discoveries made in the field of tRNA-derived fragments in the past 15 years in various pathogenic and nonpathogenic yeast species.


Transitory alkali exposure on meibomian gland orifices induces meibomian gland dysfunction.
To determine pathological changes of meibomian glands (MGs) after transient exposure of the rat eyelid margin to alkali solution. Filter paper infiltrated with 1 N sodium hydroxide solution was applied to the eyelid margin of Sprague-Dawley rats for 30 s under general anesthesia, without touching the conjunctiva, after which the ocular surface and eyelid margin were examined by slit-lamp microscopy. In vivo confocal microscopy and stereomicroscopy were subsequently applied to observe MG morphology on day 5, day 10 and day 30 post alkali injury. Eyelid cross-sections were processed for H&E staining, Oil red O staining and immunofluorescent staining. After alkali injury, there was marked plugging of MG orifices, telangiectasia and hypertrophy of the eyelid margin, while corneal epithelium was intact at post-injury days 5 and 10. However, 30 days after alkali injury, mild corneal epithelial damage was observed. Degeneration of MG acini was observed at days 5 and became aggravated at days 10 and 30, along with MG duct dilation and acini loss. Oil red O staining showed lipid accumulation in the dilated duct. Inflammatory cell infiltration and the presence of apoptotic cells was seen in the MG loci 5 days post injury, but diminished at days 10 and 30. Cytokeratin 10 expression was increased in dilated duct, while cytokeratin 14, PPAR-γ, Ki67 and LRIG1 expression were decreased in the acini of injured loci. Transitory alkali exposure of the rat eyelid margin obstructs the MG orifice and induces pathological changes of MG dysfunction.


Caregiving for older adults with hip fractures: Exploring the perspectives of caregivers, providers and decision-makers in Ontario, Canada.
Caregivers play an important role in providing physical, emotional and social support to individuals with hip fracture. This study sought to explore perceptions of caregiving for older adults with hip fractures by comparing experiences of caregivers, providers and decision-makers. Semi-structured interviews were conducted both in-person and by telephone with caregivers, providers and decision-makers (n=32) from one rural and one urban hospital selected from two health regions in Ontario, Canada. Interviews were audio-recorded and transcribed verbatim. The data were coded descriptively and interpretively, and compared within and across participants types. Three main themes reflected tensions between caregivers and providers/decision-makers. Firstly, differing expectations of caregiver roles were identified. Several caregivers wanted more participation in the decision-making process but often felt excluded, while others expressed feeling stressed due to the expectations placed on them. Conversely, providers and decision-makers often described caregivers needing to strike a balance between providing supportive care while avoiding becoming too involved. Secondly, different expectations of what the healthcare system and providers could provide, with tensions particularly around timing of discharge were noted. Finally, there were differing perceptions of information needs. Providers spoke about the importance of providing education to caregivers and perceived themselves to be providing appropriate education. However, caregivers often described poor communication and not having a clear understanding of next steps and the care plan. Managing and tailoring expectations, improving communication (e.g., content, timing) and the consistency of information shared with caregivers from different providers could facilitate more positive caregiving experiences and interactions.


Determination of sensitivity of some food pathogens to spice extracts.
Spices are primarily used as flavor enhancers and have attracted attention as natural food preservatives since their antimicrobial effects were determined. In the present study, the antimicrobial effects, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values on 5 important food-borne pathogenic bacteria were investigated in 20 different types of spices that are not commonly used. The results indicated that Hibiscus (Hibiscus sabdariffa) was the most effective against Listeria monocytogenes (26.37 mm zone diameter) and Staphylococcus aureus (24.15 mm zone diameter) (P < 0.05) followed by the chebulic myrobalan (Terminalia chebula) (21.34 ± 0.35 and 23.85 ± 1.69 mm diameter zone respectively) (P < 0.05). Likewise, Hibiscus (H. sabdariffa) showed the lowest MICs and MBCs concentration values on five important food-borne pathogens (L. monocytogenes) MIC; 0.187 mg/L, MBC; 0. Thus, this study determined that spices with antimicrobial activities can be used as natural preservatives.


Effects of social isolation, loneliness and frailty on health outcomes and their possible mediators and moderators in community-dwelling older adults: A scoping review.
Over the past decade, the quantity and quality of social relationships in later life have become one of the main challenges facing an aging society. Our aims were to map and synthesize the literature addressing the effects of loneliness, three aspects of social isolation, including social networks, social support, and social participation, and frailty on health outcomes and their mediators and moderators among older adults. We conducted a scoping review and searched for articles published in English and French from 2001 up to 2019 in the following databases: Medline, Embase, CINAHL Plus, Scopus, Web of Science and PsycINFO. Our database search initially resulted in 4001 articles of which 1832 were excluded; 26 were eligible. Most of the included studies revealed associations between social isolation, loneliness and frailty. The majority of studies found evidence of associations between frailty and their adverse outcomes; however, only few studies found a relationship between social isolation and health outcomes. In spite of the established link between frailty and adverse outcomes, no study looked at how social isolation and loneliness can alter adverse outcomes of frailty. No study investigated the role of frailty or social isolation and loneliness as a mediator on the pathway related to health. Evidence is limited in examining the role of frailty or social isolation and loneliness as a moderator and mediator. Longitudinal research combining both social isolation and loneliness are warranted to explore whether social isolation or loneliness has more deleterious effects on frailty and health outcomes.


Live-cell imaging and analysis reveal cell phenotypic transition dynamics inherently missing in snapshot data.
Recent advances in single-cell techniques catalyze an emerging field of studying how cells convert from one phenotype to another, in a step-by-step process. Two grand technical challenges, however, impede further development of the field. Fixed cell-based approaches can provide snapshots of high-dimensional expression profiles but have fundamental limits on revealing temporal information, and fluorescence-based live-cell imaging approaches provide temporal information but are technically challenging for multiplex long-term imaging. We first developed a live-cell imaging platform that tracks cellular status change through combining endogenous fluorescent labeling that minimizes perturbation to cell physiology and/or live-cell imaging of high-dimensional cell morphological and texture features. With our platform and an A549 VIM-RFP epithelial-to-mesenchymal transition (EMT) reporter cell line, live-cell trajectories reveal parallel paths of EMT missing from snapshot data due to cell-cell dynamic heterogeneity. Our results emphasize the necessity of extracting dynamical information of phenotypic transitions from multiplex live-cell imaging.


New oral anticoagulants after acute coronary syndrome.
New oral anticoagulants (NOACs) have been developed that may further decrease the mortality and morbidity of ACS by complementing antiplatelet therapy. Optimal use of these agents can be achieved by maximum reduction in thrombotic events at the minimum bleeding risk when combining a long-term oral anticoagulant with anti-platelet therapy in patients with coronary heart disease. Although, based on the pharmacokinetics and -dynamics of NOACs, these agents could improve the current management of ACS patients, multiple trials consistently demonstrate a trend toward increased major and clinically relevant non major bleeding almost diminishing the benefits in reduction of ischemic events. Therefore, some critical issues need to be further evaluated in future trials.


Computed terahertz near-field mapping of molecular resonances of lactose stereo-isomer impurities with sub-attomole sensitivity.
Terahertz near-field microscopy (THz-NFM) could locally probe low-energy molecular vibration dynamics below diffraction limits, showing promise to decipher intermolecular interactions of biomolecules and quantum matters with unique THz vibrational fingerprints. However, its realization has been impeded by low spatial and spectral resolutions and lack of theoretical models to quantitatively analyze near-field imaging. Here, we show that THz scattering-type scanning near-field optical microscopy (THz s-SNOM) with a theoretical model can quantitatively measure and image such low-energy molecular interactions, permitting computed spectroscopic near-field mapping of THz molecular resonance spectra. Using crystalline-lactose stereo-isomer (anomer) mixtures (i.e., α-lactose (≥95%, w/w) and β-lactose (≤4%, w/w)), THz s-SNOM resolved local intermolecular vibrations of both anomers with enhanced spatial and spectral resolutions, yielding strong resonances to decipher conformational fingerprint of the trace β-anomer impurity. Its estimated sensitivity was ~0.147 attomoles in ~8 × 10-4 μm3 interaction volume. Our THz s-SNOM platform offers a new path for ultrasensitive molecular fingerprinting of complex mixtures of biomolecules or organic crystals with markedly enhanced spatio-spectral resolutions. This could open up significant possibilities of THz technology in many fields, including biology, chemistry and condensed matter physics as well as semiconductor industries where accurate quantitative mappings of trace isomer impurities are critical but still challenging.


Transferring critical pediatric patients from emergency department to intensive care: A quality improvement initiative.
Transfer of care, moving hospitalized patients between care areas, is a critical point of vulnerability for healthcare organizations. Patient information handoff is an essential activity occurring frequently in hospital environments. Poor communication has been linked with adverse events and poor patient outcomes. This evidence-based quality project aimed to enhance the handoff process between the Emergency Department (ED) and Pediatric Intensive Care Unit (PICU) by standardizing transfer of care steps. This was accomplished through customizing a reporting tool to contain all the information the receiving department deemed necessary for safe patient care. A customized situation, background, assessment, recommendation (SBAR) form handoff tool was developed for ED to PICU transfers. This SBAR tool included information that PICU nurses identified as critical to transfer of care. Nurse perceptions were surveyed pre- and post-implementation. Patient safety event reports were tracked to evaluate events related to transfer of care before and after the practice change. An increased number of PICU nurses agreed the customized handoff tool was complete and organized. Additionally, more nurses agreed that handoff gave all information needed to safely care for critically ill patients transferred from the ED. Lastly, bedside patient checks increased, and patient safety events related to transfer of care decreased. This project demonstrated that implementation of a standardized transfer of care process coupled with a customized handoff tool increased PICU nurse perceptions that handoff was organized, and all information needed to safely care for critically ill patients was conveyed. Transfer of care processes between the ED and PICU should be standardized. The use of customized tools may improve information exchange between nurses and ensure that all vital patient information is communicated.


Plasma vitamins E and A and risk of bladder cancer: a case-control analysis.
Current results on the association between serum micronutrients and bladder cancer risk have been inconsistent. We assessed plasma vitamin E (alpha-tocopherol, and gamma-tocopherol), vitamin A (retinol), and bladder cancer risk using data collected from a case-control study. Epidemiologic data were collected via in-person interview. Plasma concentrations of alpha-tocopherol, gamma-tocopherol, and retinol were determined by a high-performance liquid chromatography assay. Multivariate logistic regression analyses were used to estimate bladder cancer risk in association with plasma vitamins E and A. 386 bladder cancer patients and 389 age-, gender-, and ethnicity-matched controls were included in the study. The mean plasma alpha-tocopherol and retinol were significantly lower in cases than in controls (alpha-tocopherol: 23.93 microg/ml vs. 27.48 microg/ml, P < 0.001; retinol: 1.41 microg/ml vs. 1.53 microg/ml, P < 0.001). There was a significant reduction in bladder cancer risk associated with increasing plasma alpha-tocopherol level (Adjusted OR: 0.91; 95% CI: 0.85-0.97). In quartile analysis, using subjects with the lowest alpha-tocopherol level as the reference group, the adjusted ORs and 95% CIs for the second, third, and fourth quartiles were 0.75 (0.50-1.14), 0.69 (0.46-1.05), and 0.50 (0.32-0.78), respectively (P for trend = 0.003). Increased retinol level was also associated with reduced risk with OR of 0.57 (95% CI: 0.40-0.81). The ORs and 95% CIs for the second, third, and fourth quartiles were 0.92 (0.61-1.39), 0.66 (0.43-1.01), and 0.62 (0.40-0.95), respectively, with significant dose-response trend (P for trend = 0.01). Finally, there were significant correlations between plasma levels and dietary intakes for the three micronutrients. Our results suggest potential protective effect of alpha-tocopherol and retinol on bladder cancer risk. Future large prospective studies are needed to confirm the findings.


A 'Chinese Spring' wheat (Triticum aestivum L.) bacterial artificial chromosome library and its use in the isolation of SSR markers for targeted genome regions.
A bacterial artificial chromosome (BAC) library was constructed from the bread wheat (Triticum aestivum L.) genotype 'Chinese Spring' ('CS'). The library consists of 395,136 clones with an estimated average insert size of 157 kb. This library provides an estimated 3.4-fold genome coverage for this hexaploid species. The genome coverage was confirmed by RFLP analysis of single-copy RFLP clones. The CS BAC library was used to develop simple sequence repeat (SSR) markers for targeted genome regions using five sequence-tagged-site (STS) markers designed from the chromosome arm of 3BS. The SSR markers for the targeted genome region were successfully obtained. However, similar numbers of new SSR markers were also generated for the other two homologous group 3 chromosomes. This data suggests that BAC clones belonging to all three chromosomes of homologous group 3 were isolated using the five STS primers. The potential impacts of these results on marker isolation in wheat and on library screening in general are discussed.


Are olive pomace powders a safe source of bioactives and nutrients?
The olive oil industry generates significant amounts of semi-solid wastes, namely olive pomace. Olive pomace is a by-product rich in high-value compounds (e.g. dietary fibre, unsaturated fatty acids, polyphenols) widely explored to obtain new food ingredients. However, conventional extraction methods frequently use organic solvents, while novel eco-friendly techniques have high operational costs. The development of powdered products without any extraction step has been proposed as a more feasible and sustainable approach. The present study fractionated and valorized the liquid and pulp fraction of olive pomace obtaining two stable and safe powdered ingredients, namely a liquid-enriched powder (LOPP) and a pulp-enriched powder (POPP). These powders were characterized chemically, and their bioactivity was assessed. LOPP exhibited a significant amount of mannitol (141 g kg-1 ), potassium (54 g kg-1 ) and hydroxytyrosol derivatives (5 mg g-1 ). POPP exhibited a high amount of dietary fibre (620 g kg-1 ) associated with a significant amount of bound phenolics (7.41 mg GAE g-1 fibre DW) with substantial antioxidant activity. POPP also contained an unsaturated fatty acid composition similar to that of olive oil (76% of total fatty acids) and showed potential as a reasonable source of protein (12%). Their functional properties (solubility, water-holding and oil-holding capacity), antioxidant capacity and antimicrobial activity were also assessed, and their biological safety was verified. The development of olive pomace powders for application in the food industry could be a suitable strategy to add value to olive pomace and obtain safe multifunctional ingredients with higher health-promoting effects than dietary fibre and polyphenols. © 2020 Society of Chemical Industry.


Single-Centre Real-World Study on Drug Survival and Effectiveness of Brodalumab for Treatment of Psoriasis and Psoriatic Arthritis.
Clinical trials have established the efficacy of brodalumab in treatment of psoriasis and psoriatic arthritis. Real-world evidence is needed to fully evaluate the drug. Here we investigate drug survival and clinical effectiveness of brodalumab in patients with psoriasis and psoriatic arthritis in a real-world setting. This was a retrospective single-centre study enrolling patients receiving brodalumab for psoriasis at the Department of Dermatology, Aarhus University Hospital, Denmark. The primary endpoints were drug survival, reasons for discontinuation, percentage of patients achieving a Psoriasis Area and Severity Index (PASI) ≤ 2 and clinical effectiveness against psoriatic arthritis. Eighty-three patients were included (mean age 49.2 ± 17.4 years, 59.0% male, 9.6% bio-naïve, mean baseline PASI 10.9 ± 6.9). Twenty-seven patients discontinued treatment primarily due to ineffectiveness and adverse events (AEs). Kaplan-Meier-estimated 1-year drug survival was 65.7%. An absolute Psoriasis Area and Severity Index (PASI) ≤ 2 was achieved by 68.2% of patients at end of follow-up, by 70.0% at weeks 12-17 and by 76.2% after 40-60 weeks of treatment. Neither drug survival nor PASI ≤ 2 was associated with baseline PASI ≥ 10, body mass index ≥ 30, previous treatment with > 2 biologics or other IL-17 inhibitors in particular (P > 0.05). Psoriatic arthritis remission or partial remission was achieved by 10 out of 18 patients with psoriatic arthritis; treatment failure was reported in 5 patients. Brodalumab was effective against psoriasis and psoriatic arthritis in a real-world setting. The drug survival was lower than reported in other real-world settings.


[In situ visual imaging and in vivo distribution of head and neck squamous cell carcinoma in mice by near-infrared fluorescent quantum dots epidermal growth factor receptor monoclonal antibody probe].
To investigate the in situ visualization imaging and the in vivo distribution of the near-infrared fluorescent quantum dots (QDs) epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) probe in head and neck squamous cell carcinoma (HNSCC). QDs with an emission wavelength of 800 nm (QD800) was conjugated with EGFR mAb to produce QD800-EGFR mAb. QD800-EGFR mAb was co-cultured with BcaCD885 squamous cancer cell line for 30 min and observed with laser scanning confocal microscope (LSCM). QD800-EGFR mAb was injected into HNSCC animal model through the tail vein, and the in situ visualization imaging and the in vivo distribution of QD800-EGFR mAb was analyzed at different time points. BcaCD885 squamous cell carcinoma in the head and neck can be imaged clearly and visually after intravenous injection of QD800-EGFR mAb probe, these fluorescence signals lasted for 24 h. The most complete tumor images with maximal signal-to-noise ratio were observed from 30 min to 6 h after injection of the probe. In vivo tissue distribution studies demonstrated that QD800 aggregated mostly in liver. QD800 aggregation decreased with time in tumors, and QD800 didn't aggregate in heart, brain, intestine, lung and stomach. The QD800-EGFR mAb probe can clearly produce visual images in head and neck cancer. It has promising prospects in visualization in vivo imaging and individual treatment of head and neck cancer.


Chemical sulfonation and anticoagulant activity of acharan sulfate.
Acharan sulfate is a glycosaminoglycan prepared from the giant African snail, Achatina fulica. This polysaccharide has a repeating disaccharide structure of -->4)-2-deoxy-2-acetamido-alpha-D-glucopyranose (1-->4)-2-sulfo-alpha-L-idopyranosyluronic acid (1-->). Its structure is related to heparin and heparan sulfate but is distinctly different from all known members of these classes of glycosaminoglycans. Because of its structural similarities to heparin, chemically modified acharan sulfate was studied to understand the chemical structure effected its anticoagulant activity. After de-N-acetylation, acharan sulfate was N-sulfonated using either chlorosulfonic acid-pyridine or sulfur trioxide-trimethylamine complex. The sulfate level in these products ranged from 22 to 24%(w/w), significantly less than that of heparin at 36%. The molecular weight of both N-sulfoacharan sulfates were comparable with that of heparin. In vitro anticoagulant activity assays showed that N-sulfoacharan sulfate derivatives were moderately active for the inhibition of thrombin and neither product showed any measurable anti-factor Xa activity. The differences in the activities of N-sulfoacharan sulfates produced by these two methods are probably ascribable to a small level of concomitant O-sulfonation obtained when using chlorosulfonic acid-pyridine.


The impact of mandibular advancement on articulation, resonance and voice characteristics in Flemish speaking adults: a pilot study.
Bilateral saggital split osteotomy (BSSO) of the mandible is a frequently performed mandibular orthognathic procedure, used to resolve mandibular disharmonies. Literature review showed contradictory findings regarding the effect of the orthognathic surgery on speech characteristics. The purpose of the present study was to determine a detailed analysis of the articulation, resonance and voice characteristics after BSSO with mandibular advancement for the treatment of Class II malocclusions using objective and subjective assessment techniques (perceptual evaluations, Dysphonia Severity Index, nasalance scores) in eight subjects. The findings of the present study indicate that before and after BSSO with mandibular advancement three types of articulation disorders may predominate in the Flemish language: the incorrect production of the trill sound /r/ and the /s/ sound and devoicing of the /z/. After orthognathic surgery most patients showed an identical articulation pattern (normal or disturbed pattern) as in the presurgical condition. In this study the BSSO with mandibular advancement had no significant impact on the nasality characteristics and the nasalance values probably due to the competent velopharyngeal valving in the presurgical condition. And, as expected the vocal quality revealed no significant difference. The maxillofacial surgeon and the speech language pathologist must be aware of the persistency of these preoperative articulation errors in the postsurgical condition.


Medical school curriculum in the digital age: perspectives of clinical educators and teachers.
There is a need to reexamine Singapore's medical school curricula in light of the increasing digitalization of healthcare. Notwithstanding Singapore's digital competitiveness, there is a perceived gap in preparing its medical students for the digital age. Furthermore, limited research has evaluated the extent to which skills in using digital technologies should be taught to medical students in Asian medical schools to prepare them for future clinical practice- a gap that is filled by this study. Using Singapore as a case study, it explores the views of some local clinical educators and teachers towards the need to impart skills in digital technologies to medical students. It also offers recommendations on ways to balance the clinicians' concerns about these technologies with the digital competencies needed for clinical practice. Findings were drawn from individual interviews with 33 clinical educators and teachers from Singapore's public and private healthcare sectors. They were recruited using purposive sampling. Data were interpreted using qualitative thematic analysis. Participants included vice deans of education from all three local medical schools and senior consultants from a wide variety of disciplines. Overall, they acknowledged two benefits of equipping students with skills in digital technologies including promoting the culture of innovation and improving work efficiency. However, they also highlighted four main concerns of imparting these skills: (i) erosion of basic clinical skills, (ii) neglect of a generalist approach to healthcare characterized by holistic management of patients, inter-professional collaboration, and commitment to breadth of practice within each specialty, (iii) rapid pace of technological advances, and (iv) de-personalisation by technology. The findings show that medical students in Singapore would benefit from a curriculum that teaches them to use digital technologies alongside core clinical skills.


Upregulatory effects of cefpimizole natrium on human leukocytes.
Cefpimizole natrium (CPIZ), an antibiotic belonging to the cephalosporins, was examined regarding its influence on neutrophil functions. Neutrophil superoxide (O2-) generation increased by intravenous CPIZ in patients with maxillofacial diseases. In vitro examination revealed that CPIZ directly stimulates neutrophils to generate O2- in a dose-dependent manner, though the induction ability is not as strong as phorbol myristate acetate (PMA). Protein kinase C (PKC) activity in the neutrophil plasma membrane increased after CPIZ treatment, while the activity in the cytosol fraction decreased. CPIZ cooperated with biological response modifiers (BRMs) such as sizofilan, lentinan, OK-432, rIL-2 and rIFN-gamma in neutrophil O2- generation. Non-specific cytotoxicity against K562 cells and candida cells was also enhanced by neutrophil pretreatment with both CPIZ and one of the BRMs except for sizofilan and rIL-2. From these results it can be concluded that CPIZ directly enhanced neutrophil O2- generation and that these CPIZ activations are further beneficial to protection against bacterial infections.


Forecast of peak attainment and imminent decline after 2017 of oral cancer incidence in men in Taiwan.
Oral cancer is the fourth most common cancer among men in Taiwan. The age-standardized incidence rate of oral cancer among men in Taiwan has increased since 1980 and became six times greater in 2014. To enable effective public health planning for oral cancer, research on the projection of oral cancer burden is essential. We conducted an age-period-cohort analysis on the incidence of oral cancer among men in Taiwan from 1997 to 2017 and extrapolated the trend to 2025. We found that the period trends for young adults aged between 25 and 44 have already peaked before 2017; the younger, the earlier, and then the trends declined. The cohort trends have peaked roughly at the 1972 birth cohort and then declined for all ages. Despite the increasing trend in the age-standardized incidence rate for oral cancer among men in Taiwan from 1997 to 2017, we forecast a peak attained, an imminent decline after 2017, and a decrease of 8.4% in age-standardized incidence rate from 2017 to 2025. The findings of this study contribute to developing efficient and comprehensive strategies for oral cancer prevention and control.


Protein aggregates in extracorporally perfused rabbit kidneys.
Eighteen rabbit kidneys were perfused ex vivo for 1 h with allogeneic blood, and in 16 a solution of xenogeneic aggregate-free, aggregated or antibody-complexed protein was added to the perfusate 5 min after the start (human immunoglobulins or serum albumin, partly cationized, were used). The kidneys were examined by light and electron microscopy and the human and rabbit immunoglobulin (or albumin) precipitates were detected by direct immunofluorescence and ultrastructural immunohistochemistry. In 13 kidneys the perfusion produced small segmental glomerular endocapillary aggregates of platelets, leukocytes, and granular precipitates reactive with both anti-rabbit and anti-human antibodies. No typical deposits were seen in mesangium or in periphery of glomerular capillaries but rabbit Ig penetrated to the inter- and subepithelial spaces of proximal convoluted tubules. Three kidneys perfused by cationized aggregated human Ig (or by cationized albumin-antialbumin complexes) exhibited a destructive lesion with rapid breakdown of blood flow and massive global endocapillary plugs of similar ultrastructure but with focal endothelial sloughing. Pericapillary granular precipitates of human and rabbit Ig were seen in these kidneys. When the blood with cationized Ig aggregates was used for perfusion of two further kidneys extensive endocapillary aggregates with endothelial damage reappeared but the extracapillary penetration and precipitation were lacking and the blood flow largely improved. Membrane polyanion of podocytes stained by colloidal iron was preserved even in close proximity of cationized complex precipitates. Thus, in the ex-vivo perfusion model the preformed neutral aggregates did not penetrate through the glomerular capillary wall and were not phagocytized by mesangial cells. The cationized aggregates induced rapid circulatory failure with massive platelet clumping and granular pericapillary "humps" ultrastructurally different from the deposits of human and experimental immune complex glomerulonephritis.


Photon counting imaging and centroiding with an electron-bombarded CCD using single molecule localisation software.
Photon event centroiding in photon counting imaging and single-molecule localisation in super-resolution fluorescence microscopy share many traits. Although photon event centroiding has traditionally been performed with simple single-iteration algorithms, we recently reported that iterative fitting algorithms originally developed for single-molecule localisation fluorescence microscopy work very well when applied to centroiding photon events imaged with an MCP-intensified CMOS camera. Here, we have applied these algorithms for centroiding of photon events from an electron-bombarded CCD (EBCCD). We find that centroiding algorithms based on iterative fitting of the photon events yield excellent results and allow fitting of overlapping photon events, a feature not reported before and an important aspect to facilitate an increased count rate and shorter acquisition times.


Replication of primate foamy viruses in natural and experimental hosts.
Foamy viruses (FVs) are common apathogenic retroviruses readily spread by horizontal transmission in nonhuman primate and some other mammalian host populations. Primate FV infections have been known for half a century, i.e., 15 years before the definition of retroviruses and another 15 years before the detection of primate immune deficiency viruses. The emerging interest in human retroviruses included primate FV, and although the role of human hosts for FV was greatly overestimated temporarily, enthusiastic researchers compiled invaluable data on molecular biology and classic as well as molecular epidemiology of these viruses. It has been shown that lytic FV infection in a wide range of cell cultures is in great contrast to the silent state of the infection in animals. Once transmitted by saliva via biting, FVs reside in all tissues as DNA copies, but their replication is untraceable except in oral submucosal cells, which are thought to supply the virus for transmission. FVs have not definitely been associated with any disease, regardless of viral phylogenetic differences. Various primate and nonprimate species have been used for studies on the natural carrier state and primary infection. Experimental infections have mostly proven to be inefficient in primates as well as lower laboratory animals. However, investigation of the immune response in FV-infected animals has only partly explained the control of FV replication in the animal host. Thus, the biological role of FV remains an enigma to be resolved in the future.


Human cystatin C, a cysteine proteinase inhibitor, inhibits bone resorption in vitro stimulated by parathyroid hormone and parathyroid hormone-related peptide of malignancy.
The effect of human recombinant cystatin C, a cysteine proteinase inhibitor, on bone resorption in vitro was evaluated. Bone resorption was assessed by analyzing the release of 45Ca and 3H from mouse calvarial bones prelabeled in vivo by injections with 45Ca or [3H]proline, respectively. In 24 h cultures, cystatin C (50 micrograms/ml) significantly inhibited the release of 45Ca and 3H stimulated by parathyroid hormone (PTH, 15 nmol/liter) or parathyroid hormone-related peptide of malignancy (PTHrP, 15 nmol/liter). The degree of inhibition caused by cystatin C in these 24 h cultures was similar to that caused by calcitonin (30 ng/ml). The inhibitory effect of cystatin C on 45Ca release induced by PTH was sustained in 96 h cultures, whereas the initial inhibition caused by calcitonin was transient. Cystatin C, 10-100 micrograms/ml, caused a dose-dependent inhibition of PTH (15 nmol/liter), and PTHrP (15 nmol/liter) stimulated 45Ca release. Addition of 50 micrograms/ml of cystatin C to mouse bone cultures inhibited the release of 45Ca induced by PTH and PTHrP at a wide range of submaximal and maximal concentrations of hormones (0.01-10 nmol/liter). No effect of cystatin C on 45Ca release in dead bones could be observed, nor did the inhibitor decrease the release of calcium in control bones. The inhibition by cystatin C on PTH-induced mineral mobilization was reversible. Cystatin C (1-100 micrograms/ml) did not affect protein synthesis or mitotic activities in mouse calvarial bones as assessed by the incorporation of [3H]proline and [3H]thymidine, respectively. These data show that cystatin C is a potent inhibitor of mineral mobilization and matrix degradation in cultured bones stimulated to resorb by PTH and PTHrP and that this effect is not due to general cytotoxicity.


Incidence of extubation failure and its predictors among adult patients in intensive care unit of low-resource setting: A prospective observational study.
Previous studies have found an association between various predictors and extubation failure (EF) in intensive care units (ICUs). However, this problem remains unexplored in low-resource settings, where predicting the extubation outcomes are more challenging. This study investigates the incidence of EF and its predictors among patients who received mechanical ventilation (MV). This is a prospective observational study of 123 patients' ≥ 18 years of age receiving MV for ≥ 48 hours and tolerated spontaneous breathing trials (SBTs) in the ICU of a low-resource setting. We collected data on the baseline characteristics and clinical profiles before and after SBTs. Patients were categorized into extubation failure (EF) and extubation success (ES) groups. Multivariate logistic regression analyses were performed to identify independent predictors for EF. A p-value < 0.05 is considered statistically significant. We included 123 patients, and 42 (34.15%) had developed EF. The identified predictors for EF: Moderate to copious secretions (adjusted odds ratio [AOR]: 3.483 [95% confidence interval [CI] 1.10-11.4]), age > 60 years of age ([AOR]: 4.157 [95% CI 1.38-12.48]), and prolonged duration of MV ≥ 10 days ([AOR]: 4.77 [95% CI 1.55-14.66]). Moderate to copious secretions, patients > 60 years of age, and prolonged duration of MV ≥ 10 days were the best predictors of EF. Based on our findings, we recommend that the identified predictors could help in the decision-making process of extubation from MV.


Detailed IgG and IgE antibody patterns during immunotherapy with honey bee venom.
Fourteen patients with a known honey bee venom (HBV) allergy were followed during 1-2 years of immunotherapy. HBV-specific IgG antibody levels increased in all patients but one. HBV-specific IgE antibodies decreased slightly during the first year of therapy. The ratio HBV-specific IgG-/IgE showed a marked increase during the first year for most of the patients, and a further increase during the second year in the four patients followed that long. As could be expected an increased radiostaining was found after 1 year of treatment to all important allergens in IgG CRIE, but after 2 years a sustained or increased radiostaining was obtained to phospholipase (PLA) alone. A decreased radiostaining might more easily be seen with weaker immunogens.


A role for CO(2) and bicarbonate transporters in metabolic exchanges in the brain.
Acid-base transporters are linked to the energy metabolism via the end product of oxidative metabolism, carbon dioxide, together with carbonic anhydrase activity. In a tissue such as the brain, where some cells (neurones) are high-energy consumers when active, and other cells (astroglial cells) are destined for homeostatic and trophic tasks, transport systems may complement each other and cooperate in order to maintain physiological functions. Here, some aspects of the coupling of metabolite shuttling and acid/base-dependent transport in neurones and glial cells are discussed.


Multimodality therapy for lung cancer invading the chest wall: A study of the French EPITHOR database.
According to a nation-based study, we intend to report the data of the patients operated on for lung cancer invading the chest wall, taking into consideration the completion of induction chemotherapy (Ind_CT), induction radiochemotherapy (Ind_RCT) or no induction therapy (0_Ind). All patients with a primary lung cancer invading the chest wall who underwent radical resection from 2004 to 2019 were included. Superior sulcus tumors were excluded. Overall, 688 patients were included: 522 operated without induction therapy, 101 with Ind_CT and 65 with Ind_RCT. Postoperative 90-day mortality was 10.7% in the 0_Ind group, 5.0% in the Ind_CT group, 7.7% in the Ind_RCT group (p = 0.17). Incomplete resection rate was 14.0% in the 0_Ind group, 6.9% in the Ind_CT group, 6.2% in the Ind_RCT group (p = 0.04). In the 0_Ind group, 70% of the patients received adjuvant therapies. Overall survival (OS) analysis disclosed the best long-term outcomes in the Ind_RCT group (5-year OS probability: 56.5% versus 40.0% and 40.5% for 0_Ind and Ind_CT groups, respectively; p = 0.035). At multivariable analysis, Ind_RCT (HR = 0.571; p = 0.008), age > 60 years old (HR = 1,373; p = 0.005), male sex (HR = 1.710; p < 0.001), pneumonectomy (HR = 1.368; p = 0.025), pN2 status (HR = 1.981; p < 0.001), ≥3 resected ribs (HR = 1.329; p = 0.019), incomplete resection (HR = 2.284; p < 0.001) and lack of adjuvant therapy (HR = 1.959; p < 0.001) were associated with OS. Ind_CT was not associated with survival (HR = 0.848; p = 0.257). Induction chemoradiation therapy seems to improve survival. Therefore, the present results should be confirmed by a prospective randomized trial testing the benefit of induction radiochemotherapy for NSCLC invading the chest wall.


Presence of arbuscular mycorrhizal fungi in South Florida native plants.
The roots of 27 species of South Florida plants in 15 families (including one cycad, six palms, one Smilax, and 19 dicotyledons) native to pine rockland and tropical hardwood hammock communities were examined for arbuscular mycorrhizal fungi (AMF). These plants grow in the biologically diverse but endangered Greater Everglades habitat. Roots from field-grown and potted plants were cleared and stained. All 27 species had AMF and include 14 species having an endangered or threatened status. The Paris-type colonization occurred in two species in the families Annonaceae and Smilacaceae. The Arum-type occurred in 22 species in the families Anacardiaceae, Arecaceae (Palmae), Boraginaceae, Cactaceae (questionable), Euphorbiaceae, Fabaceae, Lauraceae, Melastomataceae, Polygalaceae, Rubiaceae, Simaroubaceae, Ulmaceae, and Zamiaceae. Three species in the families Fabaceae, Lauraceae, and Simaroubaceae had a mix of Paris- and Arum-types. The results have implications for the restoration of these endangered plant communities in the Everglades.