Pathogen change of avian influenza virus in the live poultry market before and after vaccination of poultry in southern China.
The fifth wave of H7N9 avian influenza virus caused a large number of human infections and a large number of poultry deaths in China. Since September 2017, mainland China has begun to vaccinate poultry with H5 + H7 avian influenza vaccine. We investigated the avian influenza virus infections in different types of live poultry markets and samples before and after genotype H5 + H7 vaccination in Nanchang, and analyzed the changes of the HA subtypes of AIVs. From 2016 to 2019, we monitored different live poultry markets and collected specimens, using real-time reverse transcription polymerase chain reaction (RT-PCR) technology to detect the nucleic acid of type A avian influenza virus in the samples. The H5, H7 and H9 subtypes of influenza viruses were further classified for the positive results. The χ2 test was used to compare the differences in the separation rates of different avian influenza subtypes. We analyzed 5,196 samples collected before and after vaccination and found that the infection rate of AIV in wholesale market (21.73%) was lower than that in retail market (24.74%) (P < 0.05). Among all the samples, the positive rate of sewage samples (33.90%) was the highest (P < 0.001). After vaccination, the positive rate of H5 and H7 subtypes decreased, and the positive rate of H9 subtype and untypable HA type increased significantly (P < 0.001). The positive rates of H9 subtype in different types of LPMs and different types of samples increased significantly (P < 0.01), and the positive rates of untypable HA type increased significantly in all environmental samples (P < 0.05). Since vaccination, the positive rates of H5 and H7 subtypes have decreased, but the positive rates of H9 subtypes have increased to varying degrees in different testing locations and all samples. This results show that the government should establish more complete measures to achieve long-term control of the avian influenza virus.


Acquisition of nicotine self-administration in amphetamine and phencyclidine models of schizophrenia: A role for stress?
Nicotine use and dependence is very high in patients with schizophrenia. One possible reason is that altered dopamine or glutamate activity in schizophrenia enhances the reinforcing effectiveness of nicotine. We used animal models to test the hypothesis that a hyperdopaminergic state (induced by repeated intermittent injections of amphetamine) or altered glutamate function (subchronic injection of phencyclidine, PCP) facilitates spontaneous acquisition of nicotine self-administration in rats. In Experiment 1 animals in an amphetamine-induced sensitized state (AISS) did not differ from saline-injected controls in their acquisition and maintenance of nicotine self-administration. This effect was replicated in experiment 2, but it was also found that AISS rats and saline-injected controls showed higher rates of nicotine self-administration compared to uninjected controls. This difference was maintained across several fixed ratio and progressive ratio schedules of reinforcement. In Experiment 3 PCP treated rats and their saline-injected controls did not differ in nicotine self-administration. However, both groups showed consistently increased responding for nicotine on FR and PR schedules compared to an uninjected control group. Injection-stress appeared to influence the outcomes of these experiments in two ways. Firstly, injection stress potentially masked the impact of the AISS and PCP treatment on nicotine self-administration. Secondly, injection stress itself may have been sufficient to induce plastic changes in dopamine and glutamate systems, and these changes enhanced the acquisition and maintenance of nicotine self-administration. Further investigation is needed into the role of stress in the development of nicotine use and dependence, in the aetiology of schizophrenia and in their co-morbidity.


MRI-induced artifact by a cochlear implant with a novel magnet system: an experimental cadaver study.
To primarily evaluate MRI-induced effects for Ultra 3D cochlear implantation in human cadavers in terms of artifact generation and MR image quality. Three human cadaveric heads were submitted to imaging after unilateral and bilateral cochlear implantation. The 1.5 T MR examination protocol was chosen in accordance with our institutional protocol for the assessment of brain pathology. The maximal signal void size was measured according to each sequence and plane. Two experienced neuro-radiologists and one experienced otoneurosurgeon independently evaluated the MR image quality findings. A 4-point scale was used to describe the diagnostic usefulness of 14 brain structures. Shape and size of the artifacts were found to be highly related to MRI sequences and acquisition planes. MRI sequences and processing algorithms affected the ability to assess anatomical visibility. Image quality appeared either high or assessable for diagnostic purposes in 9 out of 14 of the ipsilateral structures, in at least one plane. Anatomical structures contralateral to the cochlear implant were highly visible in all conditions. Artifact intrusion clearly improved after application of metal artifact-reduction techniques. In the case of bilateral cochlear implant, a mutual interaction between the two implant magnets produced an additional artifact. We performed the first cadaver study aimed at systematically evaluating the MRI-induced artifacts produced by a cochlear implant with a novel four bar magnet system. Specific brain structures can be assessable for diagnostic purposes under 1.5 T MRI, with the cochlear implant magnet in place.


A novel hydrophilic polymer-coated magnetic nanomaterial based on the HILIC strategy for fast separation of glycopeptides and glycosylated exosomes.
Novel hydrophilic poly(N, N-methylenebisacrylamide/1,2-epoxy-5-hexene) coated magnetic nanospheres functionalized with 2-aminopurine (denoted as Fe3O4@poly(MBA/EH)@2AP) for enriching glycopeptides and glycosylated exosomes were successfully obtained using a simple and green method on the basis of the HILIC (hydrophilic interaction liquid chromatography) enrichment strategy. The high density of polar groups endows the material with amazing hydrophilicity, enabling the nanomaterial to successfully capture glycopeptides and glycosylated exosomes within 1 min. Meanwhile, the materials demonstrated great sensitivity (0.01 fmol/μL), good loading capability (125 μg/mg), high selectivity (BSA:HRP = 1000:1), and repeatability (more than 10 times). Besides, the material was applied in the analysis of bio-samples, a total of 290 glycosylated peptides and 184 glycosylation sites mapping to 185 glycoproteins were identified in the serum of uremic patients. Besides, 42 glycopeptides were enriched from the saliva of healthy people. At the same time, it was verified by TEM and western blot that the complete glycosylated exosomes were successfully captured from the serum of the uremic patients. All experiments have demonstrated that Fe3O4@poly(MBA/EH)@2AP has a promising future in practical applications.


Femoroacetabular impingement.
Femoroacetabular impingement (FAI) of the hip is a well-recognized entity that can cause hip pain and limit range of motion. Although there are 2 types of FAI (cam and pincer), these 2 entities most commonly coexist. Plain radiographs and magnetic resonance imaging are commonly used to assess FAI, and play an integral role in diagnosis in conjunction with patient symptoms and clinical examination. Treatment of FAI is also evolving, with arthroscopic management becoming increasingly more popular. This review provides an overview of the proposed etiology, mechanisms, clinical history, imaging, and treatment of FAI.


Lived experiences of depression in autistic children and adolescents: A qualitative study on child and parent perspectives.
Depression is highly prevalent in autistic children and adolescents. Despite this, little is known about the nature of the autistic child's subjective experience of depression and the impact of depression on their lives. We therefore conducted a qualitative study using thematic analysis with 7 autistic children and adolescents and their parents to identify common themes and individual differences. All children had previously experienced at least one depressive episode. Six main themes were identified: (1) Autism related experiences; (2) Difficulties with peer relationships; (3) Co-occurring relationships between anxiety and depression; (4) Impactful pessimism and anhedonia; (5) Impactful difficulties with focus and concentration and (6) Feelings of irritability, including aggressive behaviours. Parent's accounts of their children's experience of depression mirrored the child's perspective. Novel findings included reports of depression related restriction of diet variety and masking of mental health difficulties. Children and parents linked being autistic and developing depression, referring to the difficulties of being autistic in a complex, neurotypical world. These results highlight key challenges that autistic children and their families experience, calling for increased awareness of the impact of depression on autistic young people.


[Qualitative evaluation of blood products records in a hospital].
This study aimed at evaluating the qualitative performance of blood products traceability from paper and electronic medical records in a hospital. Quality of date/time documentation was assessed by detection, for 20minutes or more, of chronological errors and inter-source inconsistencies, in a random sample of 168 blood products transfused during 2009. A receipt date/time was confirmed in 52% of paper records; a data entry error was attested in 25% of paper records, and 21% of electronic records. A transfusion date/time was notified in 93% of paper records, with a data entry error in 26% of paper records and 25% of electronic records. The patient medical record held at least one date/time error in 18% and 17%, for receipt and transfusion respectively. Environmental factors (clinical setting, urgency, blood product category) did not contributed to data error rates. Although blood products traceability has good quantitative results, the recorded documentation is not qualitative. In our study, data entry errors are similar in electronic or paper records, but the global failure rate is lesser in electronic records because omissions are controlled.


Key Role of Amino Acid Repeat Expansions in the Functional Diversification of Duplicated Transcription Factors.
The high regulatory complexity of vertebrates has been related to two rounds of whole genome duplication (2R-WGD) that occurred before the divergence of the major vertebrate groups. Following these events, many developmental transcription factors (TFs) were retained in multiple copies and subsequently specialized in diverse functions, whereas others reverted to their singleton state. TFs are known to be generally rich in amino acid repeats or low-complexity regions (LCRs), such as polyalanine or polyglutamine runs, which can evolve rapidly and potentially influence the transcriptional activity of the protein. Here we test the hypothesis that LCRs have played a major role in the diversification of TF gene duplicates. We find that nearly half of the TF gene families originated during the 2R-WGD contains LCRs. The number of gene duplicates with LCRs is 155 out of 550 analyzed (28%), about twice as many as the number of single copy genes with LCRs (15 out of 115, 13%). In addition, duplicated TFs preferentially accumulate certain LCR types, the most prominent of which are alanine repeats. We experimentally test the role of alanine-rich LCRs in two different TF gene families, PHOX2A/PHOX2B and LHX2/LHX9. In both cases, the presence of the alanine-rich LCR in one of the copies (PHOX2B and LHX2) significantly increases the capacity of the TF to activate transcription. Taken together, the results provide strong evidence that LCRs are important driving forces of evolutionary change in duplicated genes.


Biological specimen bank for smelter workers.
The biological specimen bank was initiated by the department of Environmental Medicine and the department of Medicine at the University of Umeå in 1975. The aims of the bank are to collect information on trace elements in human organs. Special attention is focused on the influence of occupational exposure. Tissue samples are taken from deceased workers from a copper and lead smelter in northern Sweden. Control specimens have been collected from deceased normal individuals from four control areas. Lung, liver and kidney samples are collected with quartz instruments and stored in quartz ampoules to avoid contamination. Other samples, e.g. bone, brain, fat, hair, heart muscle, nails, skin and stomach are taken with common autopsy instruments and stored in acid-washed polyethene vessels. The samples are stored at -20 degrees C. The elements Sb, As, Cd, Cr, Co, La and Se are analyzed by neutron activation analysis, Pb and Zn by atomic absorption spectrophotometry. The findings over time can be related to a number of factors: normal values in tissues, airborne exposure and causes of death. Special attention is paid variation over time, reevaluation of threshold limit values and risk assessment.


Pentazocine suppositories for post-operative pain: intramuscular pentazocine injections versus suppositories in a controlled trial in 588 patients.
A between-patient comparison of the analgesic effect of pentazocine 50 mg by suppository and 30--45 mg by intramuscular injection was made in 558 postoperative patients, 54% within 24 hours of operation. The suppositories proved acceptable overall, even though effectiveness was less at half an hour after administration (particularly in those patients with severe initial pain) and there was greater need for further analgesia at one hour. The cost of treatment with suppositories is less than with injections. After the suppositories there were half as many patients asleep at one hour than after injections, and fewer possible side-effects (7 compared to 24).


Loss of glutaminase-positive cortical neurons in Alzheimer's disease.
Phosphate activated glutaminase (PAG) was evaluated in the neocortex of Alzheimer and control cases. Consistent with previously reported results in rat cerebral cortex, pyramidal cells were stained immunohistochemically by a PAG specific polyclonal rabbit antibody, especially in layers II, III and V. An Alzheimer's case showed drastic depletion of PAG-positive pyramidal neurons, especially in layers II and III. Cortical PAG levels by biochemical assay were reduced to 18% of control in a small series of Alzheimer's cases (n = 3), while choline acetyltransferase (ChAT) was reduced to 28% of control in the same tissue samples. PAG staining was also observed in large neurons of the rat neostriatum. Double immunostaining for PAG and ChAT established that these large neurons also contained both enzymes.


Successful targeting in situ of an oncogenic nuclear antigen by hapten induced tumor associated autoantibodies (iTAA).
The abscopal is a hypothesis for treating of non-irradiated tumors after localized radiation therapy. It is associated with the products of tumor-associated gene as autoantibodies (aTAAs) in reaction to the tumor-associated antigens (TAAs), with increasing of anti-MAGEA3 and an relationship between the abscopal effect and immune response. The hapten enhanced local chemotherapy (HELC) was studied to kills tumor and release tumor TAAs, then hapten modify the TAAs to neu-TAAs, to produce tumor autologous antibodies, called induced tumor-associated autoantibodies (iTAAs) that is different from natural TAAs. Since the iTAAs and complement (C) are associated with cancer therapy Immunofluorescence (IF) was applied to evaluate the expression of the iTAAs and C3, C5, C9. Traces resulted in a partial staining of the nucleus in C3's perinuclear reaction. The iTTAs of Survivin, C-MYC, and IMP1 increased significantly in the tumor cells' intranuclear regions (P = 0.02, P = 0.00, P < 0.0001). Koc, zeta, RalA, and p53 had a similar trend in the perinuclear regions (P < 0.0001, P = 0.004, P < 0.0001, P = 0.003). Therefore, we can propose that tumor antigens inside the cancer cells' nuclei are targeted by the iTAAs since the iTAAs binding levels are higher after HELC. The iTAA tagging oncogenic nuclear antigens may play a distinctive role in regulating tumor cell growth.


Evaluation of central corneal thickness after cataract surgery, penetrating keratoplasty and long-term soft contact lens wear.
The aim of this study was to compare central corneal thickness (CCT) between corneas of normal healthy eyes (cNHE), corneas of eyes that had undergone cataract surgery by clear corneal phacoemulsification with implantation of an intracapsular intraocular lens (cIOL), corneal grafts after penetrating keratoplasty (gPK) and corneas of long-term soft contact lens wearers (cCL). The study design was a consecutive cross-sectional trial. CCT was measured using rotating Scheimpflug camera (Pentacam, software version 1.16r04) in 80 cNHE, 79 cIOL, 46 gPK and 78 cCL. Analysis of variance (one-way ANOVA) was performed to compare differences of mean values between these four groups. Pearson's or Spearman's correlation coefficient (r) was determined between CCT value and age, follow up time after penetrating keratoplasty (timePK) or contact lens wearing time (timeCL). Means of CCT measurements were comparable between cNHE (mean CCT±standard deviation, 554±36μm), cIOL (551±40μm) and gPK (534±52μm) as determined by one-way ANOVA. Mean CCT values in cCL (537±37μm) were statistically significantly lower in comparison to cNHE (p=0.026, 95% CI=1.43-31.44). There was no linear correlation between age and CCT values of cNHE and cIOL (p=0.841, r=-0.031 and p=0.931, r=0.011, respectively). No linear relationship was determined between CCT values of cCL and timeCL (p=0.315, r=-0.125). CCT values of gPK did not correlate with timePK (p=0.738, r=0.054). The data reported here indicate that in the same statistical model among CCT values of cNHE, cIOL and gPK only long-term soft contact lenses (CL) wearer have significantly lower CCT measurements.


Phenobarbital and phenytoin effects on somatosensory evoked potentials and spontaneous EEG in normal cat brain.
Chronic oral administration of phenobarbital (PB) and phentyoin was studied in chronically implanted cats. The effects of two dosages (PB, 3 mg/kg and 15 mg/kg; phenytoin, 5 mg/kg and 8 mg/kg) were analyzed with two physiological measures: somatosensory evoked potentials (SEPs) and power spectral analysis of the EEG. The low dosage of PB had no effect on SEPs except those recorded in the mesencephalic reticular formation; high dosage resulted in general SEP attenuation. PB had little effect on the EEG. Phenytoin at both dosages produced three main effects: (1) A negative component in the SEP which appears to be dominant in the dorsal hippocampus was significantly enhanced. (2) EEG changes occurred in the dentatothalamic pathway but not at those electrode locations which recorded fastigiobulbar activity. (3) The EEG changes which did occur were Peak Frequency shifts comparable to those previously reported in humans. The results are interpreted as demonstrating (1) minimal EEG and SEP modifications at the cerebral cortical level due to nontoxic dosages of PB and phenytoin, (2) a selective phenytoin effect on the dentatothalamic outflow of the cerebellum and on the dorsal hippocampus, and (3) a potential usefulness of Peak Frequency analysis as a measure of EEG response to anticonvulsant drugs.


Identification and characterization of a mucosal antimicrobial peptide expressed by the chinchilla (Chinchilla lanigera) airway.
Cationic antimicrobial peptides (APs) are produced at mucosal surfaces and play a key role as a first line of defense against infection. To understand how APs might impact disease progression in otitis media (OM), our goal was to identify and characterize APs expressed by the epithelium lining the uppermost airway of the chinchilla, the established rodent host for the study of the bacterial-viral pathogenesis in OM. Using a molecular approach, we cloned a cDNA encoding a homolog of human beta-defensin 3, designated chinchilla beta-defensin-1 (cBD-1), and found by Northern analysis expression of the corresponding mRNA in nasopharyngeal and tongue mucosae as well as skin. By reverse transcription-PCR, cBD-1 mRNA was also detected in RNA isolated from trachea, lung, and Eustachian tube tissues. The predicted mature form of cBD-1, expressed as a recombinant peptide in Escherichia coli, demonstrated bactericidal activity against the three primary opportunistic pathogens of OM as well as Candida albicans. Continued study of this and other APs will allow us to determine their role in bacterial colonization of the upper airway as well as how viruses might contribute to the pathogenesis of OM by modulating AP expression.


Clinical, patient-reported, radiographic and magnetic resonance imaging findings 11 years after acute posterior cruciate ligament injury treated non-surgically.
Long-term consequences of posterior cruciate ligament (PCL) injury such as persistent posterior tibial translation and risk of osteoarthritis development are unclear. Additionally, little data is available describing the natural history of structural morphology of the ruptured PCL. The purpose of the study was to determine the long-term outcome after non-operatively treated PCL injury. Over 6-years, all acute knee injuries were documented by subacute MRI (median 8 days [5-15, 25th - 75th percentile] from injury to MRI). Twenty-six patients with acute PCL injury were identified of whom 18 (69%) participated in the long-term follow-up after 11 years. Follow-up included radiographic posterior tibial translation (RPTT) determined using the Puddu axial radiograph. weight-bearing knee radiographs, MRI and KOOS (Knee injury and Osteoarthritis Outcome Score). On subacute MRI, 11 knees displayed total and 7 partial ruptures. At 11 (SD 1.9) years, the median RPTT was 3.7 mm (1.5-6.3, 25th - 75th percentile). Seven knees displayed radiographic osteoarthritis approximating Kellgren-Lawrence grade ≥ 2. All follow-up MRIs displayed continuity of the PCL. Patients with more severe RPTT (> 3.7 mm), had worse scores in the KOOS subscales for symptoms (mean difference 14.5, 95% CI 7-22), sport/recreation (30, 95% CI 0-65) and quality of life (25, 95% CI 13-57) than those with less severe RPTT (≤ 3.7 mm). This was also the case for the KOOS4 (22, 95% CI 9-34). Acute PCL injuries treated non-surgically display a high degree of PCL continuity on MR images 11 years after injury. However, there is a large variation of posterior tibial translation with higher values being associated with poorer patient-reported outcomes.


The overlooked oxidative dissolution of silver sulfide nanoparticles by thermal activation of persulfate: Processes, mechanisms, and influencing factors.
The widely occurring silver sulfide nanoparticles (Ag2S-NPs) are regarded as stable Ag species in subsurface environments, where are often disturbed by human activities, such as the application of advanced oxidation technologies (e.g. persulfate based in situ chemical oxidation (PS-ISCO)) in the remediation of contaminated soil and groundwater. However, stability of Ag2S-NPs was rarely investigated referring to these processes. Here, we systematically investigated the dissolution process of Ag2S-NPs in thermal activation of PS system. Results showed that dissolution of Ag2S-NPs fitted the pseudo-first-order kinetics and the kobs increased from 0.017 h-1 to 0.249 h-1 with increasing PS concentration from 2 mM to 10 mM (36 h, 40 °C). Quenching experiments and EPR results showed that sulfate radical (SO4•-) and hydroxyl radical (•OH) were the dominant oxidants in inducing the oxidative dissolution of Ag2S-NPs. XPS analysis showed that surface-bound S2- in Ag2S-NPs was oxidized and transformed into aqueous sulfur species. The released Ag+ may also act as effective catalysts to activate PS and therefore promote the oxidation process. These findings suggest that stability of Ag2S-NPs should be reevaluated to better understand its risk to the ecological system in the subsurface environment where ISCO was widely applied.


Oxidative stress, DNA damage and antioxidant enzyme activities in the pacific white shrimp (Litopenaeus vannamei) when exposed to hypoxia and reoxygenation.
To evaluate the genotoxic and physiological effects of acute hypoxia on the pacific white shrimp (L. vannamei), shrimps were treated firstly with three dissolved oxygen levels 6.5 ppm (control), 3.0 ppm and 1.5 ppm for 24 h, respectively, and then reoxygenated (6.5 ppm) for 24 h. The changes of superoxide dismutase (SOD) activity, glutathione peroxidases (GPX) activity, malondialdehyde (MDA) concentration and DNA damage in the tissues of gill, hepatopancreas and hemolymph were examined during the period of hypoxia and reoxygenation. The results indicated SOD activity, GPX activity, MDA concentration and DNA damage all increased basically compared with the control during the period of hypoxia except for MDA concentrations in the gill at 12 h and 24 h hypoxia (3.0 ppm), and these parameters were recovered to some degree during the period of reoxygenation. Moreover, the comet assays in the tissues of gill and hepatopancreas showed an obvious time- and dose-dependent response to hypoxia, which indicated comet assay in the two tissues could be used as sensitive biomarker to detect the occurrence of hypoxia. We conclude that acute hypoxia can induce oxidative stress, DNA damage and lipid peroxidation in the tissues of gill, hepatopancreas and hemolymph of L. vannamei and the DNA damage may come from hypoxia-induced oxidative stress.


Camptodactyly: an analysis of sixty-six patients and twenty-four operations.
Camptodactyly is a nontraumatic flexion deformity of the proximal interphalangeal joint. The literature pertaining to its etiology and treatment is reviewed. An analysis of 66 patients with 110 affected hands is discussed with particular reference to the natural history of this deformity and the results of 24 operative procedures. Improvement was noted in less than 20% of 32 patients treated nonoperatively and followed for an average of 30 months. Corrective types of operative procedures in 20 hands resulted in improvement in only 35%. A treatment plan dependent on the age of the patient, the presence or absence of osteocartilagenous changes at the proximal interphalangeal joint, and associated anatomic abnormalities is presented.


High acceleration impulsive rotations reveal severe long-term deficits of the horizontal vestibulo-ocular reflex in the guinea pig.
While there is agreement that unilateral vestibular deafferentation (UVD) invariably produces an immediate severe horizontal vestibulo-ocular reflex (HVOR) deficit, there is disagreement about whether or not this deficit recovers and, if so, whether it recovers fully or only partly. We suspected that this disagreement might mainly be due to experimental factors, such as the species studied, the means chosen to carry out the UVD, or the nature of the test stimulus used. Our aim was to sort out some of these factors. To do this, we studied the HVOR of alert guinea pigs in response to low and high acceleration sinusoidal and high acceleration impulses after UVD by either labyrinthectomy or by vestibular neurectomy. The HVOR in response to high acceleration impulsive yaw rotations was measured before, and at various times after, either unilateral labyrinthectomy or superior vestibular neurectomy. Following UVD, there was a severe impairment of the HVOR for ipsilesional rotations and a slight impairment for contralesional rotations, after either operation. This asymmetrical HVOR deficit in the guinea pig parallels the deficit observed in humans. Between the first measurement, which was made 1 week after UVD, and the last, which was made 3 months after UVD, there was no change in the HVOR. This lack of recovery was the same after labyrinthectomy as after vestibular neurectomy. The HVOR to low and high acceleration sinusoidal yaw rotations were measured after UVD, and the results were compared with those in response to impulsive rotations. For low acceleration sinusoidal rotations (250 degrees/s2), the gain was symmetrical, although reduced bilaterally. As the peak head acceleration increased, the HVOR became increasingly asymmetric. The HVOR asymmetry for sinusoidal rotations was significantly less than for impulsive rotations that had the same high peak head acceleration (2500 degrees/s2). Our results show that the HVOR deficit after UVD is the same in guinea pigs as in humans; that it is the same after vestibular neurectomy as after labyrinthectomy; that it is lasting and severe in response to high acceleration rotations; and, that it is more obvious in response to impulses than to sinusoids.


Establishment of a Highly Sensitive Assay for Detection of Hepatitis E Virus-Specific Immunoglobulins.
Hepatitis E, a liver disease caused by infection with the hepatitis E virus (HEV), is a worldwide emerging disease. The diagnosis is based on the detection of viral RNA and of HEV-specific immunoglobulins (Ig). For the latter, various assays are commercially available but still lack harmonization. In this study, a Luminex-based multiplex serological assay was established that measures the presence of total IgG, IgA, and IgM antibodies, targeting a short peptide derived from the viral E2 protein. For the validation, 160 serum samples with a known HEV serostatus were used to determine the assay cutoff and accuracy. Thereby, HEV IgG- and RNA-positive sera were identified with a sensitivity of 100% and a specificity of 98% (95% confidence interval [CI], 94% to 100%). Application of the assay by retesting 514 serum samples previously characterized with different HEV-IgG or total antibody tests revealed a high level of agreement between the assays (Cohen's kappa, 0.58 to 0.99). The established method is highly sensitive and specific and can be easily implemented in a multiplex format to facilitate rapid differential diagnostics with a few microliters of sample input.


Reproducibility of ECG-gated ultrasound diameter assessment of small abdominal aortic aneurysms.
No standardised ultrasound procedure to obtain reliable growth estimates for abdominal aortic aneurysms (AAA) is currently available. We investigated the feasibility and reproducibility of a novel approach controlling for a combination of vessel wall delineation and cardiac cycle variation. Prospective comparative study. Consecutive patients (N = 27) with an AAA, attending their 6-month control as part of a medical treatment trial, were scanned twice by two ultrasound operators. Then, all ultrasound recordings were transferred to a core facility and analysed by a third person. The AAA diameter was determined in four different ways: from the leading edge of adventitia on the anterior wall to either the leading edge of the adventitia (method A) or leading edge of the intima (method B) on the posterior wall, with both measurements performed in systole and diastole. Inter-operator reproducibility was ± 3 mm for all methods applied. There was no difference in outcome between methods A and B; likewise, end-diastolic measurement did not improve reproducibility in preference to peak-systolic measurement. The use of a standardised ultrasound protocol including ECG-gating and subsequent off-line reading with minute calliper placement reduces variability. This may be of use in developing protocols to better detect even small AAA growth rates during clinical trials.


Randomized trial of two different conditioning regimens for bone marrow transplantation in thalassemia--the role of busulfan pharmacokinetics in determining outcome.
In total, 94 patients with homozygous beta thalassemia were randomized to two different conditioning regimens: busulfan 600 mg/m2 + cyclophosphamide 200 mg/kg or busulfan 16 mg/kg + cyclophosphamide 200 mg/kg and antilymphocyte globulin (47 in each group), for bone marrow transplantation, to see whether increased myeloablation or increased immunosuppression would reduce rejection. Busulfan pharmacokinetics in determining outcome was evaluated. There was no significant difference in engraftment, graft-versus-host disease, rejection, and overall and disease-free survival in the two groups. Systemic exposure to busulfan was significantly higher in the 600 mg/m2 group, but in both groups there was a wide interindividual variation in the busulfan kinetics. Six patients rejected the graft, two in the busulfan 600 mg group and four in busulfan 16 mg group (P = 0.677 CI -0.17, 0.07), but in five patients (pharmacokinetic data not available in one patient) who rejected the graft busulfan first dose trough level (C(min)-1) was below 150 ng/ml while it was above this level in the 66 of 68 patients with successful engraftment (P < or = 0.001). This randomized trial shows that rejection is influenced by busulfan levels and suggests that monitoring of busulfan levels and dose adjustment based on first-dose kinetics may reduce the risk of rejection.


White matter microstructural damage in Alzheimer's disease at different ages of onset.
White matter (WM) microstructural damage and its relationship with cortical abnormalities were explored in early-onset Alzheimer's disease (EOAD) compared with late-onset AD (LOAD) patients. Structural and diffusion tensor magnetic resonance images were obtained from 22 EOAD patients, 35 LOAD patients, and 40 healthy controls. Patterns of WM microstructural damage and cortical atrophy, as well as their relationships, were assessed using tract-based spatial statistics, tractography and voxel-based morphometry. Compared with LOAD, EOAD patients had a more severe and distributed pattern of WM microstructural damage, in particular in the posterior fibers of cingulum and corpus callosum. In both groups with Alzheimer's disease, but especially in LOAD patients, correlations between cingulum and corpus callosum fractional anisotropy and parietal, temporal, and frontal cortical volumes were found. In conclusion, WM microstructural damage is more severe in EOAD compared with LOAD patients. Such damage follows different patterns of topographical distribution in the 2 patient groups.


Egg protein supplementation improved upper body muscle strength and protein intake in community-dwelling older adult females who attended congregate meal sites or adult learning centers: A pilot randomized controlled trial.
Background: Older adults that utilize community-based nutrition services are at higher nutritional risk than the general aging population, yet studies on the efficacy of protein interventions in this population are lacking. Aim: A double-blinded randomized controlled pilot study trial evaluated the impact of egg white protein supplementation on muscle mass, strength, and physical function in predominantly low-income Latina community-dwelling adult females aged 60 or older with reduced muscle strength or function. Methods: Participants (mean age = 73.6 ± 8.3 years) were randomly assigned to receive a daily dried egg white (20 g protein) or isocaloric maltodextrin supplement for 6 months (n = 16 intervention; n = 13 control). The primary outcome measure was appendicular skeletal muscle mass. Secondary outcomes were measures of muscle strength and function and dietary protein intake. Comparisons of baseline demographics were conducted using t-tests and χ2 or Fisher's exact tests. Differences between groups were assessed using general linear models, adjusted for baseline values, and differences within groups were assessed using paired t-tests or Kruskal-Wallis. Results: No significant between-group differences were found for all measures, but protein intake, handgrip strength, and the number of arm curls significantly improved in the intervention group. Under-recruitment of study participants and a high dropout rate impacted the ability of this study to detect significant differences between groups. Conclusion: Daily egg white protein supplementation increases protein intake and supports upper body physical function in older adults, but additional studies are needed to investigate its role in the prevention of age-related muscle mass decline in older adults. Trial #NCT03530774 (https://clinicaltrials.gov/ct2/show/NCT03530774).


Mulundocandin, a new lipopeptide antibiotic. I. Taxonomy, fermentation, isolation and characterization.
Mulundocandin, a new lipopeptide antibiotic, was isolated from the culture broth of a strain of Aspergillus sydowi No. Y-30462. The antibiotic, obtained as a colorless amorphous powder having the molecular formula C48H77N7O16, is an antifungal antibiotic active against yeasts and filamentous fungi.


Quadruplex knots as network nodes: nano-partitioning of guanosine derivates in supramolecular hydrogels.
Aqueous solutions of guanosine-5'-monophosphates (GMP) - known to form G-quadruplexes and liquid crystal phases - can be induced to turn into high water content gels by the addition of guanosine (Gua). By a combination of Light Scattering (LS) and AFM we show that Gua/GMP hydrogels are microscopically heterogeneous, formed by Gua-rich disordered microcoils of intertwined filaments ("knots") connected by GMP-rich long linear threads. The different thermal stability of knots and threads controls the gel transition.


Effects of salsolinol, a tetrahydroisoquinolone alkaloid, on multiple schedule performance in rats.
Rats were trained to lever press under a multiple fixed-ratio fixed-interval schedule of food reinforcement. Intracerebroventricular injections of salsolinol (1-methyl-6,7-dihydroxytetrahydroisoquinoline), a condensation product of dopamine and acetaldehyde, caused a dose-related decrease in fixed-ratio responding over a dosage range of 15-120 microgram. In contrast, fixed-interval responding was only reduced at the 120 microgram dose and was increased in two of the animals after injection of 15-30 microgram of salsolinol.


Regulation of steroid production and key genes in catfish Heteropneustes fossilis using recombinant gonadotropins.
The two gonadotropins, FSH and LH, stimulate growth and development of the gonads through gonadal biosynthesis of steroid hormones and growth factors. To date, cDNA sequences encoding gonadotropin subunits have been isolated and characterized from a large number of fish species. Recently, we successfully cloned and characterized gonadotropins (LHβ, FSHβ, and GPα) from the pituitary glands of the catfish, Heteropneustes fossilis. In the present study, we describe herein the production of recombinant stinging catfish, H. fossilis (hf) FSH (rhfFSH) and LH (rhfLH) using the methylotrophic yeast P. pastoris expression system. We further explored the hypothesis that the recombinant gonadotropins can modulate the hypothalamus-pituitary-ovarian (HPO) axis genes (avt, it, gnrh2, kiss2, and cyp19a1a) and regulate their transcriptional profile and steroid levels in relation to their annual developmental stage during preparatory and pre-spawning phases under in-vitro conditions. We found that the different concentrations of recombinant rhfFSH and rhfLH significantly stimulated E2 levels in the preparatory and prespawning season, and also upregulated gonadal aromatase gene expression in a dose dependent manner. Our results demonstrate that the yeast expression system produced biologically active recombinant catfish gonadotropins, enabling the study of their function in the catfish.


Evaluation of the presence of major anionic surfactants in marine sediments.
The contamination of aquatic environments has become the focus of increasing regulation and public concern due to their potential and unknown negative effects on the ecosystems. The present work develops a monitoring and statistical study, based on the analysis of variance test (ANOVA) and the multivariable analysis, both for insoluble soap and LAS in order to compare the behavior of different anionic surfactants in this environmental compartment. First, a novel and successfully validated methodology to analyze insoluble soap in these samples is developed. The matrix effect and the comparison of different extraction techniques were also performed. The optimized analytical methodologies were applied to 48 representative samples collected from the Almeria Coast (Spain) and then a statistical analysis to correlate anionic surfactant concentration and several variables associated with marine sediment samples was also developed. The results obtained showed relevant conclusions related to the environmental behavior of anionic surfactants in marine sediments.


IL-27 Modulates Chemokine Production in TNF-α -Stimulated Human Oral Epithelial Cells.
Interleukin-27 (IL-27) is a cytokine which belongs to the IL-12 family. However, the role of IL-27 in the pathogenesis of periodontal disease is uncertain. The aim of this study was to examine the effect of IL-27 on chemokine production in TNF-α-stimulated human oral epithelial cells (TR146). We measured chemokine production in TR146 by ELISA. We used western blot analysis to detect the phosphorylation levels of signal transduction molecules, including STAT1 and STAT3 in TR146. We used inhibitors to examine the role of STAT1 and STAT3 activation. IL-27 increased CXCR3 ligands production in TNF-α-stimulated TR146. Meanwhile, IL-27 suppressed IL-8 and CCL20 production induced by TNF-α. STAT1 phosphorylation level in IL-27 and TNF-α-stimulated TR146 was enhanced in comparison to TNF-α-stimulated TR146. STAT3 phosphorylation level in IL-27-treated TR146 did not change by TNF-α. Both STAT1 inhibitor and STAT3 inhibitor decreased CXCR3 ligands production. STAT1 inhibitor overrode the inhibitory effect of IL-27 on IL-8 and CCL20 production in TNF-α-stimulated TR146. Meanwhile, STAT3 inhibitor did not modulate IL-8 and CCL20 production. IL-27 might control leukocyte migration in periodontal lesion by modulating chemokine production from epithelial cells.


Merozoite surface protein-9 of Plasmodium vivax and related simian malaria parasites is orthologous to p101/ABRA of P. falciparum.
Plasmodium vivax merozoite surface protein-9 (Pvmsp-9) is characterized here along with orthologues from the related simian malarias Plasmodium cynomolgi and Plasmodium knowlesi. We show that although the corresponding MSP-9 proteins do not have acidic-basic repeated amino acid (aa) motifs, they are related to the Plasmodium falciparum acidic-basic repeat antigen (ABRA) also known as p101. Recognition of this new interspecies Plasmodium MSP family stems from the prior identification of related MSP termed PvMSP-185, PcyMSP-150, and PkMSP-110 on the surface of P. vivax, P. cynomolgi and P. knowlesi merozoites. A clone containing the nearly complete P. knowlesi gene encoding PkMSP-110/MSP-9 provided a hybridization probe and initial sequence information for the design of primers to obtain the P. vivax and P. cynomolgi orthologues using polymerase chain reaction (PCR) amplification strategies. The P. vivax, P. cynomolgi and P. knowlesi msp-9 genes encode proteins that range in calculated molecular mass from 80 to 107 kDa, have typical eukaryotic signal peptides and diverse repeated motifs present immediately upstream of their termination codon. Another feature conserved among these proteins, including the P. falciparum ABRA protein, is the positions of four cysteine residues near the N-terminus, suggesting this conservation maintains structural and perhaps functional characteristics in the MSP-9 family. Rabbit polyclonal antisera raised against recombinantly expressed N-termini of P. knowlesi and P. vivax MSP-9 cross-react with the counterpart proteins in immunofluorescence and immunoblot assays. Comparative interspecies investigations of the potential role(s) of Plasmodium MSP-9 in merozoite invasion of erythrocytes and as a malaria vaccine candidate can now be pursued.


Molecular mechanism and biological functions of c-Jun N-terminal kinase signalling via the c-Jun transcription factor.
The regulation of c-Jun transcriptional activity by Jun N-terminal kinase (JNK) has become a paradigm for understanding how mitogen-activated protein (MAP) kinase signalling pathways elicit specific changes in gene transcription through selective phosphorylation of nuclear transcription factors. Selective phosphorylation of c-Jun by JNK is determined by a specific docking motif in c-Jun, the delta region, which enables JNK to associate physically with c-Jun. Analogous MAP kinase docking motifs have subsequently been found in several other transcription factors, indicating that this is a general mechanism for ensuring specificity of signal transduction. Genetic and biochemical studies in mice, flies and cultured cells have provided evidence that signals relayed by JNK through c-Jun regulate a range of cellular processes including cell proliferation, tumourigenesis, apoptosis and embryonic development. Despite these advances, in most cases, the genes or programs of gene expression downstream of JNK and c-Jun, which control these processes, have not been defined. Here, we review the current understanding of the molecular basis and biological consequences of JNK signalling via c-Jun and highlight some of the mechanistic issues, which remain to be resolved.


Differential role of histamine in mediating stress-induced changes in central dopaminergic neuronal activity in the rat.
The role of histamine in mediating restraint stress-induced alterations in dopaminergic neuronal activity and alpha-melanocyte-stimulating hormone (alpha MSH) secretion was evaluated in male rats. Dopaminergic neuronal activity was estimated by measuring concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain regions containing terminals of these neurons. Physical restraint increased DOPAC concentrations in nucleus accumbens and decreased DOPAC concentrations in the intermediate lobe of the pituitary, but was without effect on DOPAC concentrations in either the striatum or median eminence. These data indicate that restraint stress increases mesolimbic, decreases periventricular-hypophysial, and is without effect on nigrostriatal or tuberoinfundibular dopaminergic neuronal activity. Neither depletion of neuronal histamine by alpha-fluoromethylhistidine, blockade of H1 receptors by mepyramine, nor blockade of H2 receptors by zolantidine prevented the stress-induced increase in DOPAC concentrations in the nucleus accumbens suggesting that histaminergic neurons are not major contributors to stress-induced increases in mesolimbic dopaminergic neuronal activity. In contrast, alpha-fluoromethylhistidine- and mepyramine-, but not zolantidine-treatment prevented the stress-induced decrease in DOPAC concentrations in the intermediate lobe. Restraint stress increased alpha MSH secretion; this increase was not prevented by alpha-fluoromethylhistidine, mepyramine, or zolantidine. These data indicate that histaminergic neurons mediate the stress-induced decrease in periventricular-hypophysial dopaminergic neuronal activity through an action at H1 receptors, but do not effect stress-induced alpha MSH secretion.


Immune recognition of tumor cells in mice infected with Pichinde virus.
Pichinde virus (PV), a member of the Arenaviridae family, protects mice from a lethal inoculation with the sarcoma 180 (S180) tumor cell line. Virus replication, which is required for protection, occurs primarily in the spleen and tumor. During the first 4 days, elevated natural killer (NK) cell activity parallels an increase in serum interferon in PV-infected mice. On day 7 after infection virus-specific cytotoxic T cells (CTLs) are found in the mouse. This strong response peaks on day 13 and gradually declines over the next 17 days. The tumor-specific CTL response appears more slowly and is less intense than the virus-specific response, especially in the uninfected mouse. However, CTLs from either type of mouse recognize PV-infected tissue culture S180 target cells better than uninfected ones. Even though the primary tumor-specific immune response appears weak, mice that have cleared both virus and tumor are refractory to a subsequent challenge with S180 cells and rapidly produce tumor-specific CTLs. Thus, our data indicate a number of ways in which virus infection could lead to immune elimination of tumors: (1) Virus-induced interferon stimulates NK-cell activity, which in turn could control tumor load until a specific response is mounted against the S180 cells; (2) early onset of the tumor-specific T-cell response could be brought about by viral-enhanced tumor antigen presentation to the immune system; and (3) the tumor-specific T-cell response could be augmented through a "bystander' phenomenon involving factors associated with T cells responding specifically and vigorously to the virus itself.


Malaria According to GARP: A New Trail towards Anti-disease Vaccination.
Naturally acquired anti-Plasmodium falciparum immunity protects first and foremost against severe disease. Raj et al. have established a tantalizing path towards an anti-disease vaccine by identifying glutamic acid-rich protein (GARP) antibodies as signatures of protection against severe malaria in Tanzanian children and demonstrating efficacy in blood cultures and monkey trials.


Review of the genus Craspedolcus Enderlein sensu lato in China, with the description of a new genus and four new species (Hymenoptera, Braconidae, Braconinae).
A new genus is split off the genus Craspedolcus Enderlein, 1920 (Hymenoptera, Braconidae, Braconinae): Maculibracongen. n. with type species Maculibracon abruptussp. n. The genus Craspedolcus Enderlein sensu stricto is redefined, a key to both genera and to their species in China, Thailand and Vietnam is included. Craspedolcus obscuriventris Enderlein, 1920, (syn. n.) is a new synonym of Craspedolcus vagatus (Smith, 1858), as Ipobracon maculicosta Enderlein, 1920 and Iphiaulax bhotanensis Cameron, 1907 of Maculibracon simlaensis (Cameron, 1899), comb. n. The genus Craspedolcus is recorded from China for the first time with two species: Craspedolcus fraternus Enderlein, 1920, and Craspedolcus politussp. n. The genus Maculibracon is represented by three species in China: Maculibracon simlaensis (Cameron, 1899), comb. n. (also present in Vietnam), Maculibracon heisp. n. and Maculibracon luteonervissp. n. and a fourth species is described from Thailand: Maculibracon abruptussp. n.Hybogaster zebripterae Wang & Chen, 2008, from China (Fujian) is transferred to Iphiaulax Foerster, 1863, (comb. n.) and the following names are new combinations in Maculibracongen. n.: Bracon lepcha Cameron, 1899; Bracon phaedo Cameron, 1899; Bracon simlaensis Cameron, 1899; Iphiaulax bhotanensis Cameron, 1907; Iphiaulax laertius Cameron, 1903; Iphiaulax leptopterus Cameron, 1903; Iphiaulax lineaticarinatus Cameron, 1907; Ipobracon lissotomus Roman, 1914; Ipobracon maculicosta Enderlein, 1920 and Iphiaulax pallidicornis Roman, 1914. Craspedolcus montezuma (Cameron, 1887) is provisionally transferred to the genus Digonogastra Viereck, 1912.


Frequency distribution of the number and amplitude of electromyographic waveforms of the masseter muscle during sleep in patients with a clinical diagnosis of sleep bruxism.
This study aimed to clarify frequency distribution of number and peak amplitude of electromyographic (EMG) waveforms of sleep bruxism (SB) in outpatients with clinical diagnosis of SB (probable bruxer: P-bruxer). Subjects were 40 P-bruxers. Masseteric EMG during sleep was measured at home using a wearable EMG system. EMG waveforms with amplitude of more than two times the baseline and with duration of 0.25 s were extracted as SB bursts. Clusters of bursts, i.e. SB episodes, were also scored. There were large variations among the subjects in numbers of SB bursts and episodes and in burst peak amplitude. As for burst peak amplitude within a subject, a wide right-tailed frequency distribution was shown with the highest frequency at the class of 5-10% maximum voluntary contraction. The number and amplitude of SB waveforms for P-bruxers were distributed over a wide range, indicating the existence of large individual differences.


An evidence map of psychosocial interventions for the earliest stages of bipolar disorder.
Depression, schizophrenia, and bipolar disorder are three of the four most burdensome problems in people aged under 25 years. In psychosis and depression, psychological interventions are effective, low-risk, and high-benefit approaches for patients at high risk of first-episode or early-onset disorders. We review the use of psychological interventions for early-stage bipolar disorder in patients aged 15-25 years. Because previous systematic reviews had struggled to identify information about this emerging sphere of research, we used evidence mapping to help us identify the extent, distribution, and methodological quality of evidence because the gold standard approaches were only slightly informative or appropriate. This strategy identified 29 studies in three target groups: ten studies in populations at high risk for bipolar disorder, five studies in patients with a first episode, and 14 studies in patients with early-onset bipolar disorder. Of the 20 completed studies, eight studies were randomised trials, but only two had sample sizes of more than 100 individuals. The main interventions used were family, cognitive behavioural, and interpersonal therapies. Only behavioural family therapies were tested across all of our three target groups. Although the available interventions were well adapted to the level of maturity and social environment of young people, few interventions target specific developmental psychological or physiological processes (eg, ruminative response style or delayed sleep phase), or offer detailed strategies for the management of substance use or physical health.


Progressive neuropsychiatric problems following institution of highly active antiretroviral therapy.
A 31 year old HIV infected woman developed neuropsychiatric problems soon after starting highly active antiretroviral therapy (HAART). Despite modifying and subsequently stopping HAART her condition progressively worsened. Cranial magnetic resonance imaging revealed multiple areas of abnormal signal suggestive of either a vasculitis or demyelination.


Predicting county-scale maize yields with publicly available data.
Maize (corn) is the dominant grain grown in the world. Total maize production in 2018 equaled 1.12 billion tons. Maize is used primarily as an animal feed in the production of eggs, dairy, pork and chicken. The US produces 32% of the world's maize followed by China at 22% and Brazil at 9% ( https://apps.fas.usda.gov/psdonline/app/index.html#/app/home ). Accurate national-scale corn yield prediction critically impacts mercantile markets through providing essential information about expected production prior to harvest. Publicly available high-quality corn yield prediction can help address emergent information asymmetry problems and in doing so improve price efficiency in futures markets. We build a deep learning model to predict corn yields, specifically focusing on county-level prediction across 10 states of the Corn-Belt in the United States, and pre-harvest prediction with monthly updates from August. The results show promising predictive power relative to existing survey-based methods and set the foundation for a publicly available county yield prediction effort that complements existing public forecasts.


Cyto-histo correlation and false-negative urine: Before and after the Paris system for reporting urinary cytology.
The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.


Evaluation of HASTE T2 weighted image with reduced echo time for detecting focal liver lesions in patients at risk of developing hepatocellular carcinoma.
To compare the image quality and performance of half-Fourier acquisition single-shot turbo spin echo (HASTE) sequences, using compressed sensing (HASTE-CS) and deep-learning based reconstruction (HASTE-DL) in detecting focal liver lesions (FLLs), to those of T2-weighted image using BLADE sequence (T2WI) in patients at risk of developing hepatocellular carcinoma (HCC). This retrospective study included patients at risk of developing HCC who underwent liver MRI including HASTE-DL, HASTE-CS, T2WI and DWI between January and June 2020. Three radiologists independently reviewed the image quality along with FLL detection in the three T2-based sequences and DWI. Reference lesion characterization was done using the complete set of MRI sequences according to the Liver Imaging Reporting and Data System (LI-RADS) v2018. A total of 227 patients with 88 of whom had FLLs (n = 194, mean size 11.7 ± 10.9 mm) were included. HASTE-DL yielded the highest overall image quality, followed by HASTE-CS and T2WI (3.4 ± 0.5, 3.1 ± 0.6, 2.4 ± 0.5, respectively, P < 0.001 for all). In the detection of FLLs, HASTE-DL showed significantly higher sensitivity than T2WI (51.5 % vs 43.6 %, P = 0.007) whereas HASTE-CS and T2WI bore respectively little difference (P > 0.017) on per-patient basis. For LR-4, -5, -M lesions, HASTE-DL had significantly higher figure of merit than that of T2WI (0.58 vs 0.52, P < 0.001) in per-lesion basis. HASTE-DL demonstrated better image quality and higher performance for FLL detection than conventional T2WI in patients at risk of developing HCC.


Characterization of the Met326Ile variant of phosphatidylinositol 3-kinase p85alpha.
Phosphatidylinositol 3-kinase is a key step in the metabolic actions of insulin. Two amino acid substitutions have been identified in the gene for the regulatory subunit of human p85alpha, Met-326Ile, and Asn-330Asp, and the former has been associated with alterations in glucose/insulin homeostasis. When the four human p85alpha proteins were expressed in yeast, a 27% decrease occurred in the level of protein expression of p85alpha(Ile/Asp) (P = 0.03) and a 43% decrease in p85alpha(Ile/Asn) (P = 0.08) as compared with p85alpha(Met/Asp). Both p85alpha(Ile/Asp) and p85alpha(Ile/Asn) also exhibited increased binding to phospho-insulin receptor substrate-1 by 41% and 83%, respectively (P < 0.001), as compared with p85alpha(Met/Asp). The expression of p85alpha(Ile) was also slightly decreased and the binding to insulin receptor substrate-1 slightly increased in brown preadipocytes derived from p85alpha knockout mice. Both p85alpha(Met) and p85alpha(Ile) had similar effects on AKT activity and were able to reconstitute differentiation of the preadipocytes, although the triglyceride concentration in fully differentiated adipocytes and insulin-stimulated 2-deoxyglucose uptake were slightly lower than in adipocytes expressing p85alpha(Met). Thus, the Met-326Ile variant of p85alpha is functional for intracellular signaling and adipocyte differentiation but has small alterations in protein expression and activity that could play a role in modifying insulin action.


Adenosine-adenosine deaminase modulation of histamine release from human basophils in vitro.
Since extracellular adenosine is a physiologically important regulator of adenylate cyclase and cell function in various mammalian tissues, we have examined the effect of adenosine on histamine release from human basophils. Adenosine inhibited IgE-mediated histamine release by its ability to increase leukocyte cyclic AMP levels; the same concentrations of adenosine which inhibited histamine release increased the cyclic AMP level of mixed leukocytes. Inhibition of histamine release was also observed with an adenosine deaminase (ADA) inhibitor [erythro-9-(2-hydroxy-3-nonyl)-adenine: EHNA] in the presence of autologous serum. We suggest that the adenosine-ADA system normally modulates histamine release and that this contributes to the severe combined immune deficiency (SCID) associated with a lack of ADA.


A convenient method for simultaneous quantification of multiple phytohormones and metabolites: application in study of rice-bacterium interaction.
Simultaneous analysis of multiple functional-related phytohormones and their metabolites will improve our understanding of interactions among different hormones in the same biologic process. A method was developed for simultaneous quantification of multiple phytohormones, abscisic acid, indole-3-acetic acid (IAA), jasmonic acid (JA), and salicylic acid, hormone conjugates, IAA-aspartic acid, JA-isoleucine, and methyl JA, and phytoalexins, momilactone A, naringenin, and sakuranetin. This method combines a convenient procedure for preparing filtrated crude extracted samples and a sensitive quantification assay using ultra fast liquid chromatography-electrospray ionization tandem mass spectrometry (UFLC-ESI-MS). With this method, we determined the dynamic profiles of defense-related phytohormones, hormone metabolites, and phytoalexins in the interaction of rice with Xanthomonas oryzae pv. oryzae (Xoo), which causes bacterial blight, one of the most devastating diseases of rice worldwide. This UFLC-ESI-MS method is convenient, sensitive, reliable, and inexpensive for quantification of multiple phytohormones and metabolites compared to current methods. The results obtained by application of this method in studying rice-bacterial interaction provide a basis for understanding the molecular mechanisms of rice defense responses.


Neutron resonance absorption imaging of simulated high-level radioactive waste in borosilicate glass.
We performed a preliminary study of neutron resonance absorption imaging to investigate the spatial distribution of constituent elements in borosilicate glasses containing simulated high-level radioactive waste, in which elemental inhomogeneities affect the physical and chemical stabilities of the glass. Dips generated by the resonance absorptions of Rh, Pd, Na, Gd, Cs, and Sm were observed in the neutron transmission spectra of the glass samples. The spatial distributions of these elements were obtained from the neutron transmission images at the resonance energies. The distributions of Rh and Pd visualized the sedimentation of these platinum group elements. In contrast, the lanthanides (Gd and Sm) and Cs were uniformly dispersed. These results show that neutron resonance absorption imaging is a promising tool for characterizing borosilicate glasses and investigating the vitrification mechanism of high-level radioactive waste.


Higher urea-to-albumin ratio is associated with mortality risk in critically ill COVID-19 patients.
This study aimed to evaluate the ability of the urea-to-albumin ratio (UAR) to predict mortality in critically ill coronavirus disease 2019 (COVID-19) patients. This retrospective study included adult patients admitted with COVID-19 at two intensive care units (ICUs) at the University Hospital. Serum urea and albumin concentrations at ICU admission were used to calculate the UAR. All patients were followed up during hospitalization, and the ICU mortality rate was recorded. Two hundred and eleven patients were evaluated. The mean age was 57.8 ± 15.5 years, and 54% were male. Approximately 84.4% of patients were considered to be at nutritional risk by the NRS 2002, and the median UAR was 18.3 (10.5-34.8). The length of stay in the ICU was 10 (6-16) days, 38.4% of the patients required dialysis, and 64.9% died. Age, male sex, need of hemodialysis, lactate level, and inflammatory parameters were associated with higher mortality. Patients non-survivors had a higher UAR (23.7 [13.6-41.8] vs. 10.9 [8.5-16.8]; p < 0.001). The cutoff point with the best performance of UAR in the ROC curve for predicting mortality was ≥12.17 (AUC: 0.7201; CI 95%: 0.656-0.784). Additionally, the risk of mortality was 2.00-fold in the group of patients with UAR ≥12.17 (HR: 2.00 CI: 1.274-3.149; p = 0.003) and remained significant after adjusted analyzes (models 1 and 2). Our data suggest that a UAR ≥12.17 increased the risk of mortality by 2.00-fold in critically ill COVID-19 patients.


Effect of vancomycin on Staphylococcus epidermidis adherence to poly(methyl methacrylate) intraocular lenses.
To study the adherence of Staphylococcus epidermidis in variable loads (10(8) cfu/mL and 10(3) cfu/mL) to poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) and to evaluate the effect of vancomycin treatment on S epidermidis adherence to the IOL. L.V. Prasad Eye Institute, Hyderabad, India. The study was designed in 2 parts. Phase I: Twelve PMMA IOLs were soaked in a solution of S epidermidis, randomized to 10(8) cfu/mL or 10(3) cfu/mL. They were rinsed or rinsed and vortexed and cultured. Phase II: Twelve IOLs were treated with vancomycin (10 mg/mL), randomized to before and after treatment with S epidermidis. Staphylococcus epidermidis adhered to all portions of the IOL with 10(8) cfu/mL and 10(3) cfu/mL bacterial loads. Treatment with vancomycin reduced S epidermidis adherence. Pretreatment of an IOL with vancomycin or a suitable antibiotic agent appears to reduce bacterial adherence to the IOL. Placement of a sustained-release device that could release an antibiotic agent over a specific period, reducing the incidence of postcataract endophthalmitis, should be studied.


Ontogeny of vasotocin-expressing cells in zebrafish: selective requirement for the transcriptional regulators orthopedia and single-minded 1 in the preoptic area.
The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog arginine vasopressin, influence a wide range of physiological and behavioral responses, including aspects of sexual and social behaviors, osmoregulation, stress response, metabolism, blood pressure, and circadian rhythms. Here, we demonstrate that, in zebrafish (Danio rerio), the vasotocin precursor gene arginine vasotocin-neurophysin (avt) is expressed in two domains in the developing embryo: the dorsal preoptic area and the ventral hypothalamus. In the dorsal preoptic area, avt-expressing cells are intermingled with isotocin-neurophysin (ist) -expressing cells, and these neurons project to the neurohypophysis (posterior pituitary). In the dorsal preoptic area, the transcriptional regulators orthopedia b (otpb) and simple-minded 1 (sim1) are required for expression of both avt and ist. In contrast, otp and sim1 are not required for avt expression in the ventral hypothalamus. Thus, the development of these two avt expression domains is influenced by separate gene regulatory networks.


Can demographic histories explain long-term isolation and recent pulses of asymmetric gene flow between highly divergent grey fox lineages?
Secondary contact zones between deeply divergent, yet interfertile, lineages provide windows into the speciation process. North American grey foxes (Urocyon cinereoargenteus) are divided into western and eastern lineages that diverged approximately 1 million years ago. These ancient lineages currently hybridize in a relatively narrow zone of contact in the southern Great Plains, a pattern more commonly observed in smaller-bodied taxa, which suggests relatively recent contact after a long period of allopatry. Based on local ancestry inference with whole-genome sequencing (n = 43), we identified two distinct Holocene pulses of admixture. The older pulse (500-3500 YBP) reflected unidirectional gene flow from east to west, whereas the more recent pulse (70-200 YBP) of admixture was bi-directional. Augmented with genotyping-by-sequencing data from 216 additional foxes, demographic analyses indicated that the eastern lineage declined precipitously after divergence, remaining small throughout most of the late Pleistocene, and expanding only during the Holocene. Genetic diversity in the eastern lineage was highest in the southeast and lowest near the contact zone, consistent with a westward expansion. Concordantly, distribution modelling indicated that during their isolation, the most suitable habitat occurred far east of today's contact zone or west of the Great Plains. Thus, long-term isolation was likely caused by the small, distant location of the eastern refugium, with recent contact reflecting a large increase in suitable habitat and corresponding demographic expansion from the eastern refugium. Ultimately, long-term isolation in grey foxes may reflect their specialized bio-climatic niche. This system presents an opportunity for future investigation of potential pre- and post-zygotic isolating mechanisms.


The First Complete Genome Sequences of Hepatitis C Virus Subtype 2b from Latin America: Molecular Characterization and Phylogeographic Analysis.
The hepatitis C virus (HCV) has remarkable genetic diversity and exists as eight genotypes (1 to 8) with distinct geographic distributions. No complete genome sequence of HCV subtype 2b (HCV-2b) is available from Latin American countries, and the factors underlying its emergence and spread within the continent remain unknown. The present study was conducted to determine the first full-length genomic sequences of HCV-2b isolates from Latin America and reconstruct the spatial and temporal diversification of this subtype in Brazil. Nearly complete HCV-2b genomes isolated from two Brazilian patients were obtained by direct sequencing of long PCR fragments and analyzed together with reference sequences using the Bayesian coalescent and phylogeographic framework approaches. The two HCV-2b genomes were 9318 nucleotides (nt) in length (nt 37-9354). Interestingly, the long RT-PCR technique was able to detect co-circulation of viral variants that contained an in-frame deletion of 2022 nt encompassing E1, E2, and p7 proteins. Spatiotemporal reconstruction analyses suggest that HCV-2b had a single introduction in Brazil during the early 1980s, displaying an epidemic history characterized by a low and virtually constant population size until the present time. These results coincide with epidemiological data in Brazil and may explain the low national prevalence of this subtype.


Phosphorus availability to maize as influenced by organic manures and fertilizer P associated phosphatase activity in soils.
Laboratory incubation and green house studies were conducted to compare the P availability of organic manures and P uptake from organic manures by maize. Various organic manures viz. Poultry manure (PM), Farmyard manure (FYM), Green manure (GM) and Crop residue (CR) and graded levels of fertilizer P were applied in Samana sandy loam and Ladhowal silt loam soils and incubated for 7, 15, 30, 60 and 90 days. Samples were analyzed for P availability, P uptake and alkaline phosphatase activity. The overall, phosphatase activity, Paranitrophenyl phosphate (PNP h(-1)g(-1)), in the Ladhowal silt loam soil was higher than in the Samana sandy loam soil. As the level of inorganic P increased, the release of PNP h(-1)g(-1) soil also increased. Among different organic manures, PM registered the highest enzyme activity followed by FYM, GM and CR. Compared to 7 days incubation a slightly higher increase in PNP was noticed in samples from 90 days incubation in both soils. The differential phosphatase activity in the organic manures was further reflected in dynamic P availability. The highest amount of Olsen extractable P was in PM-treated soil followed by FYM, GM and field pea crop residue. Organic manure addition along with inorganic P, irrespective of the source, increased the Olsen extractable P throughout the incubation period. Total P uptake by maize increased with the increasing level of inorganic P in both soils. The highest uptake was obtained in PM-treated soil and lowest in the CR-amended soil. We conclude that PM more readily supplies P to plants than other organic manure sources.


Bacteriophage Isolation, Purification, and Characterization Techniques Against Ubiquitous Opportunistic Pathogens.
Healthcare-associated infection with "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) is a global health crisis due to their extensive intrinsic antibiotic resistance and the ability to quickly acquire resistance determinants. Alternative treatment options are required to combat this crisis, and one possibility is the use of bacteriophages, or viruses that strictly infect the pathogenic bacteria. Currently, there is a renaissance in research and development into the use of phages to target multi-, extensively, and pan-resistant bacterial infections in humans, known as phage therapy. Using A. baumannii as an example, this article describes the isolation and purification of bacteriophages from sewage and soil samples, as well as general methods used in phage research such as precipitation of phages using polyethylene glycol, host range analysis, single-cell burst size determination, DNA extraction, and restriction fragment length polymorphism analysis. © 2022 National Research Council Canada. Current Protocols © 2022 Wiley Periodicals LLC. Reproduced with the permission of the Minister of Innovation, Science, and Industry. Basic Protocol 1: Isolation of bacteriophages against A. baumannii from sewage samples Alternate Protocol 1: Isolation of bacteriophages against A. baumannii from soil samples Support Protocol 1: Titering a bacteriophage stock Basic Protocol 2: Purification of phage to an axenic working stock Support Protocol 2: Liquid propagation of bacteriophage Basic Protocol 3: Host range analysis using the spot plate method Basic Protocol 4: Single burst size analysis Alternate Protocol 2: One-step growth curve Basic Protocol 5: Precipitation of bacteriophage using PEG 6000 Basic Protocol 6: DNA extraction from dsDNA bacteriophages Basic Protocol 7: Restriction fragment length polymorphism analysis of novel phage genomes.


Complete Coding Sequences of One H9 and Three H7 Low-Pathogenic Influenza Viruses Circulating in Wild Birds in Belgium, 2009 to 2012.
The complete coding sequences of four avian influenza A viruses (two H7N7, one H7N1, and one H9N2) circulating in wild waterfowl in Belgium from 2009 to 2012 were determined using Illumina sequencing. All viral genome segments represent viruses circulating in the Eurasian wild bird population.


Insights into the Role of Erythrina corallodendron L. in Alzheimer's Disease: in Vitro and in Silico Approach.
Alzheimer's disease (AD) is a major health problem. Cholinergic transmission is greatly affected in AD. Phytochemical investigation of the alkaloid rich fraction (AF) of Erythrina corallodendron L leaves resulted in isolation of five known alkaloids: erysodine, erythrinine, 8-oxoerythrinine, erysovine N-oxide and erythrinine N-oxide. In this study, eysovine N-oxide was reported for the second time in nature. AF was assayed for cholinesterase inhibition at the concentration of 100 μg mL-1 . AF showed a higher percent inhibition for butyrylcholinesterase enzyme (BuChE) (83.28 %) compared to acetylcholinesterase enzyme (AChE) (64.64 %). The isolated alkaloids were also assayed for their anti-BuChE effect. In-silico docking study was done for the isolated compounds at the binding sites of AChE and BuChE to determine their binding pattern and interactions, also molecular dynamics were estimated for the compound displaying the best fit for AChE and BuChE. In addition, ADME parameters and toxicity were predicted for the isolated alkaloids compared to donepezil.


Safety Procedures to Work with West Nile Virus in Biosafety Level 3 Facilities.
West Nile virus (WNV) can cause severe and sometimes fatal disease, but we do not have treatments or therapeutics to manage these outcomes. Since its introduction to the USA in 1999, WNV has been handled in a biosafety level 3 laboratory to decrease risk to researchers, requiring strict safety protocols and important considerations with planning experiments. Recent changes in US guidelines suggest that WNV can be handled at a lower biosafety level due to its endemicity in the USA and generally minor symptoms, but some research still requires the use of the agent at biosafety level 3. This chapter will briefly discuss the considerations of biosafety when working with WNV.


Rigid endoscopy in ENT practice. Appraisal of the diagnostic yield in a district general hospital.
A 10-year retrospective survey of 204 elective rigid oesophagoscopic examinations in the ENT unit of a District General Hospital is reported. One Hundred and Forty Five (71 per cent) were normal and there was marked preponderance of normal endoscopy in patients under 60 years old. Clinical examination was usually unhelpful but barium studies were found to complement oesophagoscopy in reaching a diagnosis. There were six complications of oesophagoscopy, two following normal examinations.


Toxicity of aerosol propellants in the respiratory and circulatory systems. VII. Influence of pulmonary emphysema and anesthesia in the rat.
Experimental induction of pulmonary emphysema caused an increase in sensitivity of the rat to toxicity from inhalation of propellants. The emphysematous rat showed an exaggerated reduction in pulmonary compliance in response to inhalation of trichlorofluoromethane (FC 11). In emphysematous and non emphysematous rats without anesthesia the inhalation of FC 11 caused tachycardia, arrhythmias and other abnormalities in the electrocardiogram. The tachycardiac response was eliminated by induction of barbiturate anesthesia, which increased the sensitivity of the heart to occurrence of abnormalities in the electrocardiogram in response to inhalation of FC 11 as well as of dichlorodifluoromethane (FC 12) and difluoroethane (FC 152a). The acceleration in heart rate in response to inhalation of FC 11, hypoxia or hypercapnea was prevented by prior treatment with a beta-blocking drug.


Atrial Tachyarrhythmias After Cardiac Transplantation.
Cardiac transplant recipients demonstrate a unique substrate for atrial tachyarrhythmias owing to the surgical techniques involved. Surgical modification of the atria during transplant surgery has both proarrhythmic and antiarrhythmic effects detailed in this paper. Cavotricuspid isthmus-dependent right atrial flutter is the most common arrhythmia identified. Atrial fibrillation is uncommon owing to obligatory surgical pulmonary vein isolation. Donor hearts can also contain pre-existing accessory pathways or dual AV nodal physiology causing supraventricular tachycardia for which adenosine treatment is not recommended, but catheter ablation is curable.


Reproductive health of young adults with physical disabilities in the U.S.
Previous research shows reduced cervical and breast cancer screening among women with physical disabilities. However, other indicators of reproductive health have been largely ignored. We aimed to compare the reproductive health of young adults in the U.S. with and without physical disabilities in a nationally-representative sample. Data are from 13,819 respondents aged 18-26 who participated in Waves I (1994-1995) and III (2001-2002) of the National Longitudinal Study of Adolescent Health (Add Health). Using logistic regression, we examined associations between physical disability and multiple reproductive health indicators including sexually transmitted infection (STI) testing, STI diagnosis, receipt of a gynecologic exam, and cervical cancer screening. Analyses were stratified by sex and adjusted for the complex study design. We identified 5.8% of respondents as having a physical disability. In multivariate analyses, females with physical disabilities had lower odds of having a Pap smear in the past 12 months than females without disabilities (OR=0.77; 95% CI: 0.61, 0.97). Physical disability was not associated with other reproductive health indicators among females or males. We found few differences in examined reproductive health indicators of young adults with and without physical disabilities, but findings suggest differences in some screening services that merit additional study.


Diabetic Foot Ulcers and Cardiac Autonomic Neuropathy.
Diabetic foot ulcers (DFUs) and cardiac autonomic neuropathy (CAN) are severe complications of diabetes mellitus (DM). Both DFU and CAN are associated with increased risk of major cardiovascular events and mortality. Because of the clinical impact of both these conditions, it is important to establish what effect the presence of CAN has on DFU outcomes. This is a narrative review of original research articles identified through an electronic search of PubMed, Scopus, and Google scholar databases until June 2021 exploring CAN in individuals with DFUs. We explored prevalence, patient outcomes (DFU healing and amputation), and mortality. Evidence suggests that the prevalence of CAN is high, ranging from 43% to 66% among those with DFUs. The presence of CAN may also increase the odds of developing DFUs. A single-center, prospective, observational study has suggested that the presence of CAN significantly reduces DFU healing time. The impact on amputation is indeterminate, with conflicting reports from studies reporting either no or increased risk. On the basis of limited evidence, CAN may be associated with increased mortality in individuals with DFUs. The interplay between CAN and DFUs is poorly understood from current literature. Given the high prevalence of CAN in individuals with DFUs and the potential for suboptimal outcomes, further high-quality studies are required to determine future management approaches when both conditions coexist and to establish whether early CAN screening in individuals with diabetes at high risk of foot ulceration may ultimately improve their outlook.


Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis.
Recent evidence suggests that astrocytes may be a potential new target for the treatment of epilepsy. The glial water channel aquaporin-4 (AQP4) is expressed in astrocytes, and along with the inwardly-rectifying K(+) channel K(ir)4.1 is thought to underlie the reuptake of H(2)O and K(+) into glial cells during neural activity. Previous studies have demonstrated increased seizure duration and slowed potassium kinetics in AQP4(-/-) mice, and redistribution of AQP4 in hippocampal specimens from patients with chronic epilepsy. However, the regulation and role of AQP4 during epileptogenesis remain to be defined. In this study, we examined the expression of AQP4 and other glial molecules (GFAP, K(ir)4.1, glutamine synthetase) in the intrahippocampal kainic acid (KA) model of epilepsy and compared behavioral and histologic outcomes in wild-type mice vs. AQP4(-/-) mice. Marked and prolonged reduction in AQP4 immunoreactivity on both astrocytic fine processes and endfeet was observed following KA status epilepticus in multiple hippocampal layers. In addition, AQP4(-/-) mice had more spontaneous recurrent seizures than wild-type mice during the first week after KA SE as assessed by chronic video-EEG monitoring and blinded EEG analysis. While both genotypes exhibited similar reactive astrocytic changes, granule cell dispersion and CA1 pyramidal neuron loss, there were an increased number of fluorojade-positive cells early after KA SE in AQP4(-/-) mice. These results indicate a marked reduction of AQP4 following KA SE and suggest that dysregulation of water and potassium homeostasis occurs during early epileptogenesis. Restoration of astrocytic water and ion homeostasis may represent a novel therapeutic strategy.


Hybrid registration of prostate and seminal vesicles for image guided radiation therapy.
Fiducial markers are a good surrogate for the prostate but provide little information on the position and orientation of the seminal vesicles (SVs). Therefore, a more advanced localization method is warranted if the SVs are part of the target volume. The purpose of this study was to develop a hybrid registration technique for the localization of the prostate and SVs. Twenty prostate patients implanted with 2 or 3 elongated fiducial markers had cone beam computed tomography (CBCT) scans acquired at every fraction. The first step of the hybrid registration was to localize the prostate by CBCT-to-planning-CT alignment of the fiducial markers, allowing both translations and rotations. Using this marker registration as a starting point, the SVs were registered based on gray values, allowing only rotations around the lateral axis. We analyzed the differential rotation between the prostate and SVs and compared the required SV margins for 3 correction strategies. The SV registration had a precision of 2.7° (1 standard deviation) and was successful for 96% of the scans. Mean (M), systematic (Σ), and random (σ) differences between the orientation of the prostate and SV were M = -0.4°, Σ = 7.2°, and σ = 6.4°. Daily marker-based corrections required an SV margin of 11.4 mm (translations only) and 11.6 mm (translations + rotations). Rotation corrections of the SVs reduced the required margin to 8.2 mm. We found substantial differences between the orientation of the prostate and SVs. The hybrid registration technique can accurately detect these rotations during treatment. Rotation correction of the SVs allows for margin reduction for the SVs.


Differential immunogenic and neurogenic inflammatory responses in an allergic mouse model exposed to low levels of formaldehyde.
It is suspected that exposure to low levels of formaldehyde induces or aggravates airway inflammation mediated by immunological and neurological reactions. To clarify the effect of this exposure on allergic inflammatory responses, we exposed female C3H/He mice to 0, 80, 400, or 2000ppb formaldehyde for 12 weeks. When mice were immunized with ovalbumin (OVA) and then exposed to formaldehyde, the numbers of total bronchoalveolar lavage cells, macrophages, and eosinophils in the mice exposed to 2000ppb formaldehyde were significantly increased compared to 0ppb controls. However, the production of interleukin-1beta from bronchoalveolar lavage fluid of these mice decreased significantly. Immunization with OVA significantly increased the production of nerve growth factor, but exposure to 80 and 400ppb formaldehyde significantly reduced the nerve growth factor levels in bronchoalveolar lavage fluid of the immunized mice. In in vitro study, markedly increased lipopolysaccharide-stimulated interferon-gamma production in culture supernatants of spleen cells from 2000ppb formaldehyde-exposed, nonimmunized mice, and significantly increased OVA-stimulated monocyte chemoattractant protein-1 production in culture supernatants of spleen cells from 400 and 2000ppb formaldehyde-exposed, immunized mice were observed. Exposure to 400ppb formaldehyde induced significant decreases in anti-OVA IgG1 and IgG3 antibody productions in plasma, whereas anti-OVA IgE antibody production was not affected. In addition, the levels of nerve growth factor in plasma of 80 and 400ppb formaldehyde-exposed, immunized mice significantly decreased compared to 0ppb control, immunized mice. These results provide the first experimental evidence that low levels of long-term formaldehyde inhalation can induce differential immunogenic and neurogenic responses in allergic mice.


Can breast MRI predict pathologic response following neoadjuvant chemotherapy for breast cancer? A retrospective cohort study.
For patients treated with neoadjuvant chemotherapy (NAC) for breast cancer, it is standard of care to perform pre- and post-NAC imaging to evaluate response to therapy prior to surgery. In this study we assess outcome metrics of magnetic resonance imaging (MRI) following NAC. We conducted a retrospective analysis of patients with invasive breast cancer who underwent a breast MRI before and after NAC between 2016 and 2021 at a single, multisite academic institution. All breast MRI studies were characterized as either radiologic complete response (rCR) or non-rCR. Corresponding surgical pathology reports were reviewed and categorized as pathologic complete response (pCR) or non-pCR. We defined a positive test as having residual enhancement on MRI (non-rCR) and a positive outcome as having residual disease on final surgical pathology (non-pCR). There were 225 patients included in the study (mean age 52 ± 12 years). Breast cancer receptor distribution was HR+/HER2- (n = 71, 32%), HR+/HER2+ (n = 51, 23%), HR-/HER2- (n = 72, 32%), and HR-/HER2+ (n = 31, 14%). In total, 78 (35%) had rCR and 77 (34%) had pCR; 43 (19%) had both rCR and pCR. The overall accuracy rate was 69% (156/225), sensitivity 76% (113/148), specificity 56% (43/77), positive predictive value 77% (113/147), and negative predictive value 55% (43/78). The PPV was significantly associated with receptor status (p = 0.004). No patient or imaging characteristics were associated with sensitivity. Breast MRI only moderately predicts pathologic response for invasive breast cancer treated with NAC (overall accuracy 69%). PPV is significantly associated with receptor status.


Microstructural fingerprints of phase transitions in shock-loaded iron.
The complex structural transformation in crystals under static pressure or shock loading has been a subject of long-standing interest to materials scientists and physicists. The polymorphic transformation is of particular importance for iron (Fe), due to its technological and sociological significance in the development of human civilization, as well as its prominent presence in the earth's core. The martensitic transformation α→ε (bcc→hcp) in iron under shock-loading, due to its reversible and transient nature, requires non-trivial detective work to uncover its occurrence. Here we reveal refined microstructural fingerprints, needle-like colonies and three sets of {112}<111> twins with a threefold symmetry, with tell-tale features that are indicative of two sequential martensitic transformations in the reversible α→ε phase transition, even though no ε is retained in the post-shock samples. The signature orientation relationships are consistent with previously-proposed transformation mechanisms, and the unique microstructural fingerprints enable a quantitative assessment of the volume fraction transformed.


Isolation of myelin basic protein-reactive T-cell lines from normal human blood.
T-Cell lines which responded by proliferation to the autoantigen, myelin basic protein (MBP), were isolated from the blood of six of nine normal humans. These T-cell lines could be maintained in in vitro culture for up to 2 months through the use of Interleukin 2 and repeated MBP stimulation. Optimal antigen-induced proliferation required both antigen and antigen-presenting cells found in the adherent cell population of autologous peripheral blood mononuclear cells (PBM). The T-cell lines were predominantly of the helper phenotype (OKT3+, OKT4+, OKT8-) and responded to both human and guinea pig myelin basic protein.


[PROSPERE randomized controlled trial: laparoscopic sacropexy versus vaginal mesh for cystocele POP repair].
Cystocele is a frequent and invalidating type of genital prolapse in woman. Sacropexy using synthetic mesh is considered the surgical gold standard, and the laparoscopic approach has supplanted the open abdominal route because it offers the same anatomical results with a lower morbidity. The use of mesh through the vaginal route may have many advantages: easiness to perform, shorter operative time and recovery, but may increase morbidity. In France, both laparoscopic sacropexy and vaginal mesh are commonly used to treat cystoceles. The French Haute Autorité de santé (HAS) has highlighted the lack of evaluation of safety assessment for vaginal meshes. The main objective of the study is to compare the morbidity of laparoscopic sacropexy with vaginal mesh for cystocele repair. The primary endpoint will be the rate of surgical complications greater or equal to grade 2 of the Clavien-Dindo classification at 1-year follow-up. The secondary aims are to compare the functional results in the medium term (sexuality, urinary and bowel symptoms, pain), the impact on quality of life as well as anatomical results. PROSPERE is a randomized controlled trial conducted in 12 participating French hospitals. 262 patients, aged 45 to 75years old, with cystocele greater or equal to stage 2 of the POP-Q classification (isolated or not) will be included. Exclusion criterias are a previous surgical POP repair, and inability or contra-indication to one or the other technique. We have designed this study to answer the question of the choice between laparoscopic sacropexy and vaginal mesh for the treatment of cystocele. The PROSPERE trial aims to help better determine the indications for one or the other of these techniques, which are currently based on subjective choices or school attitudes. This is the reason why competent authorities have asked for such studies.


Attempted suicide among the aged.
Although the rate for suicide in old age is high, the rate for attempted (unsuccessful) suicide is low. Among the elderly, suicide-attempt groups have more physical disorders, more psychoses, and more psychopathologic findings, and are under-represented demographically. Fifty percent of the elderly suicide attempters have organic brain syndrome (OBS), compared to only 5-10 percent of the "normal" population over age 60. Among what might be expected to be a high-risk suicide population, OBS apparently interferes with the success of suicide attempts by impairing coordination, planning, determination, and awareness of reality.


Carbonyl Activation by Selenium- and Tellurium-Based Chalcogen Bonding in a Michael Addition Reaction.
In the last years the use of chalcogen bonding-the noncovalent interaction involving electrophilic chalcogen centers-in noncovalent organocatalysis has received increased interest, particularly regarding the use of intermolecular Lewis acids. Herein, we present the first use of tellurium-based catalysts for the activation of a carbonyl compound (and only the second such activation by chalcogen bonding in general). As benchmark reaction, the Michael-type addition between trans-crotonophenone and 1-methylindole (and its derivatives) was investigated in the presence of various catalyst candidates. Whereas non-chalcogen-bonding reference compounds were inactive, strong rate accelerations of up to 1000 could be achieved by bidentate triazolium-based chalcogen bond donors, with product yields of >90 % within 2 h of reaction time. Organotellurium derivatives were markedly more active than their selenium and sulphur analogues and non-coordinating counterions like BArF 4 provide the strongest dicationic catalysts.


CAJAL enables analysis and integration of single-cell morphological data using metric geometry.
High-resolution imaging has revolutionized the study of single cells in their spatial context. However, summarizing the great diversity of complex cell shapes found in tissues and inferring associations with other single-cell data remains a challenge. Here, we present CAJAL, a general computational framework for the analysis and integration of single-cell morphological data. By building upon metric geometry, CAJAL infers cell morphology latent spaces where distances between points indicate the amount of physical deformation required to change the morphology of one cell into that of another. We show that cell morphology spaces facilitate the integration of single-cell morphological data across technologies and the inference of relations with other data, such as single-cell transcriptomic data. We demonstrate the utility of CAJAL with several morphological datasets of neurons and glia and identify genes associated with neuronal plasticity in C. elegans. Our approach provides an effective strategy for integrating cell morphology data into single-cell omics analyses.


Emotional responses to subcortical electrical stimulation in psychiatric patients.
Subcortical electrical stimulation was applied to the prospective surgical target area during 158 stereotactic operations in 135 psychiatric patients. The following target areas were studied: rostral cingulum below and in front of the genu of the corpus callosum (52 cases) genu (46) cingululum just above the genu (11) middle cingulum (6) anterior internal capsule (33) subcaudate region, 'substantia innominata' (10 cases). Forty-seven per cent of the cases reacted to stimulation with subjective emotional sensory responses. Stimulation of differ targets had significantly different results. Responses were obtained most frequently from the cingulum and genu, and least frequently from the anterior capsule and subcaudate regions. Stimulation of the rostral cingulum often caused 'negative' responses, i.e. an increase in or the appearance of anxiety and tension (11/15 cases). The opposite was true of the adjacent genu of the corpus callosum; on stimulation of this structure anxiety and tension disappeared or diminished (18/19 cases). Schizophrenic patients experienced such 'positive' responses significantly more often than non-schizophrenics. In non-anesthetized patients autonomic reactions were very rare.