Vaccination of European badgers (Meles meles) with BCG by the subcutaneous and mucosal routes induces protective immunity against endobronchial challenge with Mycobacterium bovis.
Mycobacterium bovis is endemic in badger (Meles meles) populations of Ireland and the United Kingdom and infected badgers are a potential source of infection for cattle. In domestic livestock tuberculosis causes economic losses from lost production and the costs associated with eradication programmes, and in addition there is a risk of zoonotic infection. Whereas culling is currently used to control tuberculous badger populations in Ireland, vaccination, if it were available, would be preferred. A study was undertaken to examine the protective responses of badgers vaccinated either by the subcutaneous or mucosal (intranasal and conjunctival) routes with bacille Calmette-Guérin (BCG), when challenged with M. bovis by the endobronchial route. Three groups of badgers were used. The first group (n=4) was vaccinated with approximately 5 x 10(5) colony forming units (cfu) of BCG by subcutaneous injection. In the second group (n=5) badgers were vaccinated via the mucosal route by instilling 1.0 x 10(5)cfu into each conjunctival sac and spraying 1.0 x 10(5)cfu into each nostril (final vaccine dose of 4 x 10(5)cfu). The control (n=5) badgers served as a non-vaccinated group. Twelve weeks post-vaccination all badgers in the three groups were challenged with approximately 10(4)cfu of M. bovis by endobronchial inoculation. At 12 weeks post-infection all badgers were examined post-mortem to assess the pathological and bacteriological responses to challenge. Gross and histological lesions of tuberculosis were seen in all challenged badgers and M. bovis was recovered from all challenged badgers. However, across six of the eight parameters used to measure disease severity, the infection in the vaccinated badgers was significantly less severe than in the control group. The BCG vaccine induced a significant protective effect in the badgers and the protective immunity was generated by subcutaneous and mucosal vaccination.


Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia.
Increasing animal genetic, post-mortem and pharmacological evidence supports a role for the cerebral type 1 cannabinoid (CB1) receptor in the pathogenesis of schizophrenia (SCZ) and/or neural circuit dysfunctions responsible for its symptomatology. Moreover, since important interspecies differences are present in CB1 receptor expression, in vivo human data are of direct interest. We investigated an in vivo CB1 receptor expression in SCZ patients compared to healthy controls (CON), and in relation with psychopathological symptom severity using positron emission tomography (PET) and the selective high-affinity radioligand [(18)F]MK-9470. A total of sixty-seven patients with SCZ, with (SCZ-T, n=51) and without (SCZ-F, n=16) antipsychotic treatment, and 12 age and gender-matched CON were investigated with [(18)F]MK-9470 PET. Parametric modified standardized uptake value (mSUV) images, reflecting CB1 receptor binding, were compared and related to psychopathological symptoms. Compared to CON, there was a significant increase of CB1 receptor binding in SCZ patients in the nucleus accumbens, insula, cingulate cortex, inferior frontal cortex, parietal and mediotemporal lobe. Furthermore, in the SCZ-F group only, CB1 receptor binding was negatively correlated to negative symptoms and to depression scores, especially in the nucleus accumbens. Present findings strongly support that CB1 receptor binding is altered in the mesocorticolimbic circuitry of both SCZ-T and SCZ-F patients, especially in the nucleus accumbens. In SCZ-F patients, it is associated with negative symptoms and depression scores.


"To help a million sick, you must kill a few nurses": nurses' occupational health, 1890-1914.
Although nursing is recognized today as a serious occupational health risk, nursing historians have neglected the theme of occupational health and individual nurses' experience of illness. This article uses the local history of three case study institutions to set nurses' health in a national context of political, social, and cultural issues, and suggests a relationship between nurses' health and the professionalization of nursing. The institutions approached the problem differently for good reasons, but the failure to adopt a coherent and consistent policy worked to the detriment of nurses' health. However, the conclusion that occupational health was somehow neglected by contemporary actors was, nevertheless, erroneous and facilitated omission of the subject from historical studies concentrating on professional projects and the wider politics of nursing. This article shows that occupational health issues were inexorably connected to these nursing debates and cannot be understood without reference to professional projects.


Draft genome sequences for three mercury-methylating, sulfate-reducing bacteria.
The genetic basis for bacterial mercury methylation has been described recently. For insights into the physiology of mercury-methylating bacteria, we present genome sequences for Desulfococcus multivorans strain DSM 2059, Desulfovibrio alkalitolerans strain DSM 16529, and Desulfovibrio species strain X2.


Beliefs about smoking and health: their measurement and relationship to smoking behavior.
A scale was constructed to measure four types of beliefs about smoking and health. According to Krietler and Krietler's (Cognitive Orientation and Behavior, New York, Springer, 1976) cognitive orientation model these four types of beliefs--general beliefs, goal beliefs, self beliefs, and norm beliefs--direct an individual's molar behavior. Four subscales, representing each of the four belief types were found to have moderately high levels of internal consistency and test-retest reliability. Factor analysis indicated a relatively high independence for the two subscales measuring self and goal beliefs, but found some overlap between the two subscales measuring norm and general beliefs. Smokers, former smokers, and nonsmokers were found to differ in predictable ways on the four subscales and the combined scale. Also the length of time that former smokers had been abstinent as well as length of smoking habit and number of cigarettes smoked per day by smokers were found to be related to some of these beliefs. Implications of these findings for smoking cessation intervention programs are discussed.


A phase II study of buparlisib in relapsed or refractory thymomas.
To investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas. This was a single center, single arm, open label phase II trial of buparlisib in patients with recurrent thymoma who have progressed after at least one prior line of treatment. The primary endpoint was objective response rate (complete response [CR] + partial response [PR]). Secondary endpoints included toxicity; progression free survival (PFS); overall survival (OS); disease control rate (DCR), i.e., the percentage of patients who achieve either PR or CR or stable disease [SD] for at least 4 months. Between 10/13/2014 and 1/18/2017, 14 patients with stage IV disease were enrolled. Median age was 58y (23-74). 71% were females and 71% white. All patients had WHO B2 (29%) or B3 (71%) thymoma. Patients received buparlisib for a median of 4.5m (2-33). At a median follow up of 16.6m (2.4-31.3), onr patients (7%) achieved a PR. DCR was 50%. Median PFS was 11.1m (95% CI 2.9 - 18.8). Median OS, updated as of March, 2021 was 22.5m (10.7-31.3). Most common grade 3-4 adverse events related to buparlisib were dyspnea (21%), rash (14%), elevated transaminases (14%), cough (7%), pneumonitis (7%), anxiety (7%), fatigue (7%) and hyperglycemia (7%). Reasons for treatment discontinuation included progression of disease (n= 5), rash (n=4), pulmonary toxicity (n=3), sinusitis (n=1), and disseminated toxoplasmosis plus autoimmune cholangitis (n=1). As of 3/2021, 8 patients have died, 7 due to disease progression and 1 due to central nervous system toxoplasmosis and autoimmune cholangitis. Buparlisib showed modest activity in patients with relapsed or refractory thymomas. Further investigation of PI3K pathway targeted therapy in thymoma is warranted. (clinicaltrials.gov ID: NCT02220855). clinicaltrials.gov, identifier (NCT02220855).


Prevalence of high-risk human papillomavirus in primary squamous cell carcinoma of urinary bladder.
Studies have demonstrated an etiologic role of high-risk human papillomavirus (HR-HPV) infection for epithelial malignancies, including most cervical carcinomas, anogenital cancers, and carcinomas of the head and neck; however, a causative role of HPV infection for bladder cancer is controversial. The purpose of this study was to investigate the prevalence of HR-HPV in primary bladder carcinoma to determine the association between HPV infection and the squamous cell component of urothelial carcinoma of the bladder. Furthermore, we evaluated the utility of p16 overexpression as a surrogate marker for HPV infection in these cancers and the correlation of this with tumor stage. Our study included 33 cases of squamous cell carcinoma (SCC) of the urinary bladder. Tumors deemed primary from the bladder were selected and either showed predominant (>50 %) or pure squamous differentiation. Immunohistochemical study for p16 and HR-HPV by RNA in situ hybridization (ISH) was performed in all cases. p16 expression was detected in 7 cases (28 %, 7/25) of urothelial carcinoma with squamous differentiation and not detected in any of the 8 cases (0%, 0/8) of pure SCC. Detection of HR-HPV by ISH was negative in all 33 cases (0%, 0/33). There was no association between p16 overexpression and the presence of HPV infection in squamous cell carcinomas of the bladder. p16 should not be used as a surrogate marker for evidence of HPV infection. Our study suggests that HPV infection does not play an etiologic role in the development of bladder cancer and should not be used as a diagnostic adjunct for these cases.


Sex-biased genome-editing effects of CRISPR-Cas9 across cancer cells dependent on p53 status.
The CRISPR-Cas9 system has emerged as the dominant technology for gene editing and clinical applications. One major concern is its off-target effect after the introduction of exogenous CRISPR-Cas9 into cells. Several previous studies have investigated either Cas9 alone or CRISPR-Cas9 interactions with p53. Here, we reanalyzed previously reported data of p53-associated Cas9 activities and observed large significant sex differences between p53-wildtype and p53-mutant cells. To expand the impact of this finding, we further examined all protein-coding genes for sex-specific dependencies in a large-scale CRISPR-Cas9 screening dataset from the DepMap project. We highlighted the p53-dependent sex bias of gene knockouts (including MYC, PIK3CA, KAT2B, KDM4E, SUV39H1, FANCB, TLR7, and APC2) across cancer types and potential mechanisms (mediated by transcriptional factors, including SOX9, FOXO4, LEF1, and RYBP) underlying this phenomenon. Our results suggest that the p53-dependent sex bias may need to be considered in future clinical applications of CRISPR-Cas9, especially in cancer.


Interactions between hippocampal penicillin spikes and theta rhythm.
The relationships between theta rhythm and epileptic spikes, evoked by penicillin, were studied in the rat hippocampus. Records were taped and processed off-line, and autocorrelation functions, averages and power spectra of the EEG and frequency histograms of the epileptic spikes were calculated. Results showed that: (1) epileptic spikes tend to occur in a preferred phase of theta rhythm; (2) they provoked a reset of the phase of theta rhythm, acting as internal stimuli; (3) epileptic spikes decreased in frequency and were often abolished when theta rhythm was evoked; (4) these effects appeared to be dependent on the medial septal pathway. These findings indicate the existence of an antagonism between two hippocampal phenomena (epilepsy and theta rhythm). On the other hand, they also seem to be interrelated since the generation of one is accompanied by a reciprocal decrease in the other.


[Modal failure analysis and effects in the detection of errors in the transport of samples to the clinical laboratory].
Owing to the decrease in values of biochemical glucose parameter in some samples from external extraction centres, and the risk this implies to patient safety; it was decided to apply an adaptation of the «Health Services Failure Mode and Effects Analysis» (HFMEA) to manage risk during the pre-analytical phase of sample transportation from external centres to clinical laboratories. A retrospective study of glucose parameter was conducted during two consecutive months. The analysis was performed in its different phases: to define the HFMEA topic, assemble the team, graphically describe the process, conduct a hazard analysis, design the intervention and indicators, and identify a person to be responsible for ensuring completion of each action. The results of glucose parameter in one of the transport routes, were significantly lower (P=.006). The errors and potential causes of this problem were analysed, and criteria of criticality and detectability were applied (score≥8) in the decision tree. It was decided to: develop a document management system; reorganise extractions and transport routes in some centres; quality control of the sample container ice-packs, and the time and temperature during transportation. This work proposes quality indicators for controlling time and temperature of transported samples in the pre-analytical phase. Periodic review of certain laboratory parameters can help to detect problems in transporting samples. The HFMEA technique is useful for the clinical laboratory.


Improving the performance of electrocardiogram sub-band coder by extensive Markov system.
The paper reports on a continuation of previous work on the digital coding of 500 samples s-1 ECG at 240 bits s-1. Focus is on six-band sub-band coding (SBC) with extensive Markov system as post-processors for each sub-band signal. An extensive Markov process, which considers both the coding redundancy and the intersample redundancy, utilises the redundancies by predicting the incoming n samples based on the previous m samples that constitute an extensive Markov process state. Both the previous m samples and the incoming n samples are considered as extension codes of the quantisation levels. Simulation results show that a reproduction with an average of signals ratio (SNR) of 27.21 dB or peak SNR of 58.6 dB was achieved at an average bit rate of 0.48 bit per sample, which corresponds to an average compression ratio of 25, whereas under the same signal fidelity, the previous proposed SBC system achieved an average bit rate of 0.714 bit per sample.


Antimicrobial susceptibility and molecular characteristics of 857 methicillin-resistant Staphylococcus aureus isolates from 16 medical centers in Japan (2008-2009): nationwide survey of community-acquired and nosocomial MRSA.
This study is a nationwide survey of all clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, including community-acquired MRSA (CA-MRSA), in Japan. A total of 857 MRSA clinical isolates were collected from the 16 institutions throughout Japan that participated in the survey (2008-2009). The drug susceptibility and staphylococcal cassette chromosome mec (SCCmec) typing and the presence of specific pathogenic genes were evaluated. The isolates comprised SCCmec type II (73.6%), type IV (20%), and type I (6%). The percentage of SCCmec type IV isolates was significantly higher in outpatients than in inpatients. Most of the isolated strains were sensitive to vancomycin (VCM, MIC ≤2 μg/mL), linezolid (MIC ≤4 μg/mL), and teicoplanin (MIC ≤8 μg/mL). Although most strains were sensitive to VCM, the MIC value of VCM for SCCmec type II strains was higher than that for SCCmec type IV strains. Only 4 (2.3%) of 171 SCCmec type IV strains were Panton-Valentine leukocidin (lukS/F-PV)-positive. Thus, this result indicates a unique feature of SCCmec type IV strains in Japan. The information in this study not only is important in terms of local public health but will also contribute to an understanding of epidemic clones of CA-MRSA.


Community mobilization to reduce postpartum hemorrhage in home births in northern Nigeria.
The purpose of this study is to demonstrate the importance of community mobilization in the uptake of a health intervention, namely, community-based distribution of misoprostol to prevent postpartum hemorrhage. Community mobilization to increase access to misoprostol for postpartum hemorrhage prevention was implemented in northwestern Nigeria in 2009. Theories of community participation and the current near-epidemic maternal mortality conditions underpin an approach using modest levels of community involvement. The study was undertaken in five communities around Zaria, Nigeria. Community leaders and selected community members participated in a series of dialogs. Additionally, community education, information and dramas sessions were held. Twenty nine community oriented resource persons (CORPs), 27 drug keepers and 41 traditional birth attendants (TBAs) were involved in the intervention. Postpartum interviews were used to assess the impact of community mobilization efforts and to track use of misoprostol. Multiple logistic regression was used to examine the association between correct use and receiving information regarding misoprostol from TBAs or CORPs. A total of 1875 women were enrolled in the study in 2009. Most women delivered at home (95%) and skilled attendance at delivery was low (7%). Community mobilization efforts reached most women with information about postpartum hemorrhage and misoprostol (88%), resulting in high comprehension of intervention messages. Women identified TBAs and CORPs as the single most important source of information about misoprostol 41% and 31% of the time, respectively. Availability of misoprostol at the community level gave 79% of enrolled women some protection against postpartum hemorrhage which they otherwise would not have had. Although high level community participation in health care interventions is the ideal, this study suggests that even in circumstances where only modest levels of participation can realistically be achieved, community mobilization can have a significant impact on the successful distribution and uptake of a potentially life-saving health intervention, in turn helping promote policy change.


Functional residues essential for the activation of the CB1 cannabinoid receptor.
Recently developed X-ray crystal structures of active state G-protein-coupled receptors have opened the way for detailed examination of the movement of the transmembrane (TM) helices and the specific residues involved in the receptor activation upon ligand binding. Previous modeling studies have indicated that the brain cannabinoid (CB1) receptor binds with a ligand at least in part through a hydrophobic tail on the ligand. This interaction is believed to be similar to the rotameric toggle switch proposed for the β2 adrenergic receptor (β2AR). In the present study, an active state model for the CB1 receptor, guided by the X-ray structure of the active state for β2AR, was constructed with HU210 bound as a ligand. Molecular dynamics (MD) simulations were employed to provide a smooth progression between inactive and active states of the receptor. This model was compared with our previously published CB1 receptor model to identify the functional residues that play key roles in triggering receptor conformational changes upon agonist binding. Movements in TM helices and functional residues are discussed. W279(5.43), contributing to an inward movement of the fifth TM helix (TM5) to the helical core, could serve as another rotameric switch for receptor activation. V282(5.46), interacting with the ligand's hydrophobic C3 alkyl chain, appears to play a key role in TM5 inward movement centered at L286(5.50) and subsequent coupling to V204(3.40). V204(3.40), closely interacting with the TM5 and TM6 hydrophobic patch residues in the middle of the receptor, particularly I290(5.54) and L352(6.44), appears to facilitate helical rearrangements, leading to the breakage of the ionic lock and the rotameric change of Y397(7.53), which are key features of the active state.


Vitamin D signalling pathways in cancer: potential for anticancer therapeutics.
Epidemiological studies indicate that vitamin D insufficiency could have an aetiological role in various human cancers. Preclinical research indicates that the active metabolite of vitamin D, 1alpha,25(OH)2D3, also known as calcitriol, or vitamin D analogues might have potential as anticancer agents because their administration has antiproliferative effects, can activate apoptotic pathways and inhibit angiogenesis. In addition, 1alpha,25(OH)2D3 potentiates the anticancer effects of many cytotoxic and antiproliferative anticancer agents. Here, we outline the epidemiological, preclinical and clinical studies that support the development of 1alpha,25(OH)2D3 and vitamin D analogues as preventative and therapeutic anticancer agents.


Toxicology and pharmacology of bispyridium oximes--insight into the mechanism of action vs Soman poisoning in vivo.
HI-6 was the least toxic and the most efficacious oxime examined against Soman poisoning with a high safety ratio between 26-30. Reactivation of peripheral acetylcholinesterase following Soman poisoning was more important in the beneficial therapeutic action of HI-6 than reactivation of central acetylcholinesterase. HI-6 reactivated Sarin-inhibited but not Tabun-inhibited acetylcholinesterase both peripherally and centrally. HI-6 passes the blood brain barrier as evidenced by its reactivation centrally of Sarin-inhibited acetylcholinesterase. Soman-inhibited enzyme was not aged in vivo by 30 min. In vivo diaphragm acetylcholinesterase was inhibited to a greater extent by Soman, Sarin and Tabun than intercostal muscle acetylcholinesterase. In vitro diaphragm and intercostal muscle acetylcholinesterase had similar IC50 values for Soman. HI-6 has antimuscarinic and antinicotinic activity in addition to its previously reported ganglion blocking activity (Lundy and Tremblay, 1979). These additional pharmacological actions of HI-6 may play a role in the therapeutic action of HI-6 (at the higher concentrations). The results suggest that peripheral acetylcholinesterase in the rat diaphragm is the primary lesion in Soman poisoning. The beneficial action of HI-6 in rats versus Soman poisoning is due to reactivation of diaphragm acetylcholinesterase.


Kinetic analysis of carboxy ester hydrolysis by a dinuclear Zn(II) complex.
A dinuclear Zn(II) complex with hexaaza macrocyclic ligand bearing two 2-hydroxypropyl pendants, 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxypropyl)-tricyclo [22,2,2,2(11,14)]triaconta-11,13,24,26,27,29-hexane (L) was synthesized and studied as a catalyst of the cleavage of 4-nitrophenyl acetate (NA). X-ray diffraction analysis of [Zn(2)LCl(2)]Cl(2)(.)6H(2)O revealed that Zn(II) adopts a trigonal-bipyramidal geometry. The complexation constants of L with Zn(II) have been determined at 298 K by means of potentiometric titration. [Zn(2)H(-2)L](2+) is the dominant species in aqueous solution around pH 8. The Zn(2)L-promoted hydrolysis of NA showed a second-order rate constant of 0.33 M(-1)s(-1) at pH 9.0, and the main promoter species are concluded to be the deprotonated species [Zn(2)H(-2)L](2+).


The Musical Eulogy and Other Functions of Funeral Music.
This article examines the function of music during contemporary funerals in the Netherlands. Using a performance-based approach, this article shows that music adds to the ritual dimension of contemporary funerals, by relating the music to the funeral itself, the deceased person's identity, and to emotions. Zooming in on the music that in contemporary personalized funerals is selected because it is-one way or another-related to the deceased, it will be shown that the lyrical content of this music is less important than social and emotional aspects. Theoretically, the concept of the musical eulogy is introduced as a hermeneutic tool to examine music in ritualized contexts.


Characterization of a rare Unverricht-Lundborg disease mutation.
Cystatin B (CSTB) gene mutations cause Unverricht-Lundborg disease (ULD), a rare form of myoclonic epilepsy. The previous identification of a Portuguese patient, homozygous for a unique splicing defect (c.66G > A; p.Q22Q), provided awareness regarding the existence of variant forms of ULD. In this work we aimed at the characterization of this mutation at the population level and at the cellular level. The cellular fractionation studies here carried out showed mislocalization of the protein and add to the knowledge on this disease.


Comparison of methods for 14N-1H recoupling in 14N-1H HMQC MAS NMR.
1H-detected 14N heteronuclear multiple-quantum coherence (HMQC) magic-angle-spinning (MAS) NMR experiments performed at fast magic-angle spinning (≥50 kHz) are finding increasing application, e.g., to pharmaceuticals. Of importance to the efficacy of these techniques is the recoupling technique applied to reintroduce the 1H-14N dipolar coupling. In this paper, we compare, by experiment and 2-spin density matrix simulations, two classes of recoupling scheme: first, those based on n = 2 rotary resonance, namely R3 and spin-polarisation inversion SPI-R3, and the symmetry based SR412 method and, second, the TRAPDOR method. Both classes require optimisation depending on the magnitude of the quadrupolar interaction, and thus there is a compromise choice for samples with more than one nitrogen site, as is the case for the studied dipeptide β-AspAla that contains two nitrogen sites with a small and large quadrupolar coupling constant. Considering this, we observe better sensitivity for the TRAPDOR method, though noting the marked sensitivity of TRAPDOR to the 14N transmitter offset, with both SPI-R3 and SR412 giving similar recoupling performance.


Distribution of i.v. administered epidermal growth factor in the rat.
The distribution of i.v. injected 125I-labeled epidermal growth factor (EGF) was examined in the rat. The uptake of radioactivity was examined for the following tissues: liver, kidney, skin, stomach, small intestine, colon, brain, submandibular gland, lung, spleen, and testis. 125I-EGF was cleared from the circulation within minutes. At 2.5 min after the injection only 7% of the label was left in the blood. Most of the label was found in the liver (52%), the kidneys (14%), the small intestine (11%) and the skin (7%). The other organs examined contained 1% or less of the radioactivity. The uptake of 125I-EGF per g tissue was markedly higher for the liver and kidneys than for the rest of the organs. By autoradiography 125I-EGF was found in the peripheral parts of the classical liver lobule, in the proximal tubules of the kidneys, in the surface epithelium of the stomach, and in the surface epithelium of the villi in the small intestine. In conclusion the present study showed that small doses of homologous EGF was cleared from the circulation of rats within minutes, mainly by the liver, the kidneys, and the small intestine.


Have the 'black clouds' cleared with new residency programme regulations?
For decades, residents believed to work harder have been referred to as having a 'black cloud'. Residency training programmes recently instituted changes to improve physician wellness and achieve comparable clinical workload. All Internal Medicine residents in the internship class of 2014 at Columbia were surveyed to assess for the ongoing presence of 'black cloud' trainees. While some residents are still thought to have this designation, they did not have a greater workload when compared to their peers.


Assessment of survival benefit after lung transplantation by patient diagnosis.
Lung transplantation has become an established procedure for treating patients with endstage lung disease, resulting in broadening criteria for recipient selection. The survival benefit for some patient groups has yet to be established. We reviewed 653 patients accepted for lung transplantation at our center. Patients were categorized into 6 diagnosis groups: cystic fibrosis (174), obstructive lung disease (163), pulmonary fibrosis (100), Eisenmenger's syndrome (76), pulmonary hypertension (68), bronchiectasis (51), and other (21). Using Cox regression, we estimated the time at which early operative risk of death fell below pre-operative risk levels (crossover point) and the point at which early high post-operative risk was offset by later low risk (equity point). The relative benefits of single lung vs double lung/heart-lung transplantation were assessed for patients with obstructive lung disease and pulmonary fibrosis. Post-operative risk of death fell below pre-operative risk levels for all diagnosis groups, indicating a survival advantage. The equity point was achieved for all distinct diagnosis groups (except Eisenmenger's); this survival benefit was significant for patients with obstructive lung disease, cystic fibrosis, and pulmonary hypertension. Single lung vs double lung/ heart-lung comparisons showed no significant difference in survival benefit. All survival benefit patient groups achieve after lung transplantation, with the exception of patients with Eisenmenger's syndrome, who may have prolonged survival while listed. Differences in survival benefit between single lung and double or heart-lung transplantation are not significant for patients with obstructive lung disease or pulmonary fibrosis.


Cutaneous hyperalgesia: contributions of the peripheral and central nervous systems to the increase in pain sensitivity after injury.
This study assesses the contributions of the peripheral and central nervous systems in the development of hyperalgesia (increased pain sensitivity) after an injury. Experiments were carried out to examine the role of C-fiber afferents, the spinal cord and sympathetic efferents on inflammation, primary hyperalgesia and referred hyperalgesia produced in rats by a heat injury. A peripheral mechanism was indicated since both primary hyperalgesia and inflammation after a heat injury were significantly attenuated by blocking C-fiber afferents with local capsaicin. In addition, a central mechanism was indicated since the spread of hyperalgesia to the paw contralateral to a heat injury was prevented by either spinal anesthesia or the blocking of sympathetic efferents by guanethidine. A further role for central mechanisms was indicated since referred hyperalgesia--the enhancement of self-mutilation (autotomy) of a denervated limb which had previously sustained a heat injury--was reduced by spinal anesthesia or a combined blocking of C-fiber afferents and sympathetic efferents with intrathecal capsaicin + guanethidine. The results strongly suggest that referred hyperalgesia after a heat injury is dependent on increased spinal cord activity. However, autotomy in rats that did not undergo a previous injury was unaffected by either spinal anesthesia or intrathecal capsaicin. This suggests that spinal cord hyperactivity, although it plays a role in hyperalgesia following a heat injury, is not a crucial factor in producing pain and hyperalgesia after a nerve injury.


Relationship between testicular volume and presence of varicocele. A comparative study.
The varicocele, present in many of the male partners of infertile couples continues to generate controversy, particularly as related to its diagnosis and pathophysiology. The purpose of our study was to determine the relationship between testicular volume and the presence or absence of a varicocele. Testicular volume was determined by the use of an orchiometer; the presence of a varicocele was determined by palpation during a Valsalva maneuver. The patients utilized in the study were those seen in our Andrology and General Urology Clinics; 291 patients with varicoceles and 83 control patients (no evidence of varicocele) were used. The left (mean = 21.4 mL) and right (mean = 23.4 mL) testicular volumes of patients with a varicocele were significantly reduced compared with that of the control group (left, mean = 23.4 mL; right, mean = 26.2 mL; p = 0.0041 and p = 0.002, respectively). The testicular volume corrected on the basis of the body mass (V/m2) also was significantly reduced in the varicocele group compared with controls (left p = 0.007; right p = 0.001). Reduced testicular volume relative to body size may be detected prior to actual demonstration of the stress pattern and the presence of a varicocele, and may be useful in early diagnosis. It is suggested that measurement of testicular volume may be a useful adjunct to routine examination of the infertile male.


Pandemic resilience and health systems preparedness: lessons from COVID-19 for the twenty-first century.
The pandemic of COVID-19 disease has acted like a stress test on every aspect of life, but particularly exposed weaknesses of health systems design and capacity. There have been similar pandemics in the past, and the threat of more frequent future pandemics in the twenty-first century is real. It is therefore important to learn the right lessons with regard to health systems preparedness and resilience. The five design features that this paper discusses are related to the organization of primary care services, planned surge capacity in secondary and tertiary care, a robust disease surveillance system that is integrated with the health management information system, adequate domestic capacity in being able to innovate and scale up production and logistics of much needed medical products and a governance approach that recognizes the importance of the health systems being able to continuously learn and adapt to meet changing needs. In addition to this, the organizational capacity of the system to deliver required services would need more investment in financial resources, and a suitable health human resource policy.


DNA methylation in the Alcohol dehydrogenase-1 gene of maize.
Using a battery of methylation-sensitive restriction enzymes, cytosine methylation at 23 sites in a 7.6 kb region surrounding the Alcohol dehydrogenase-1 (Adh1) gene was measured in DNA prepared from immature maize cobs. Both the 5' upstream region and the entire coding region were hypomethylated in the two alleles examined. Methylation in Adh1 is independent of changes in Mutator transposable element methylation. The role of DNA methylation in Adh1 gene regulation is discussed.


The prognostic significance of the cytophotometric DNA content and its relationship with the argyrophilic nucleolar organizer regions (AgNOR) and proliferating cell nuclear antigen (PCNA) in oesophageal cancer.
We examined the DNA pattern, AgNOR number and PCNA-positive ratio (PCNA ratio) from biopsy specimens of oesophageal carcinoma, and attempted to identify any prognostic factors for oesophageal carcinoma. DNA analysis: the cell nuclear DNA content was measured and the distribution pattern of the DNA content was grouped into four types according to the ploidy pattern (n = 182). The survival rate of patients with high-ploidy tumours (type III and IV) was shorter than that for low-ploidy tumours (type II), (P < 0.05). AgNOR number (n = 99) and PCNA ratio (n = 41): the AgNOR number and PCNA ratio were measured from 100 cancer cells in each specimen. Both the high-AgNOR-number patients (> or = 5) and the high-PCNA-ratio patients (> or = 35) demonstrated poorer prognoses than the low-rate patients (P < 0.05). These results suggest that the DNA pattern, AgNOR number and PCNA ratio may thus reflect the proliferative activity of tumours and therefore also offer the possibility of interdependence among these three factors.


Acute Calcium Pyrophosphate Crystal Arthritis is Associated with an Increased Rate of Hip and Knee Joint Surgery.
Acute calcium pyrophosphate (CPP) crystal arthritis is a distinct manifestation of calcium pyrophosphate crystal deposition (CPPD). No studies have specifically examined whether acute CPP crystal arthritis is associated with progressive structural joint damage. The objective of this retrospective cohort study was to evaluate the relative rate of hip and knee joint arthroplasties as an estimate of structural joint damage accrual, in a population of patients with acute CPP crystal arthritis. Data were collected from Waikato District Health Board (WDHB) to identify an acute CPP crystal arthritis cohort with clinical episodes highly characteristic of acute CPP crystal arthritis. Data on hip and knee joint arthroplasties were collected from the New Zealand Orthopaedic Association's (NZOA) Joint Registry. The rate of arthroplasties in the cohort were compared with the age-ethnicity matched New Zealand population. Additional analysis was performed for age, obesity (BMI) and ethnicity. The acute CPP crystal arthritis cohort included 99 patients, 63 were male and the median age was 77 years (interquartile range, 71-82). The obesity rate was 36% with a median BMI of 28.4 kg/m2 (interquartile range, 25.8-32.2), comparable to the New Zealand population. The standardised surgical rate ratio in the cohort versus the age-ethnicity matched New Zealand population was 2.54 (95% CI: 1.39-4.27). Our study identified a considerable increase in the rate of hip and knee joint arthroplasties in patients with episodes of acute CPP crystal arthritis. This suggests CPP crystal arthritis may be a chronic condition, leading to progressive joint damage.


Intra-septal radiofrequency ablation within the transseptal puncture hole targeting an interatrial connection during a bi-atrial tachycardia.
A 74-year-old man after multiple mitral valve surgeries underwent catheter ablation of a bi-atrial tachycardia (BiAT). Ultra-high resolution activation mapping exhibited a reentrant circuit propagating around the inferior to anterior mitral annulus and right atrial (RA) septum with two interatrial connections. At the transeptal puncture site, continuous fractionated electrograms were recorded during the BiAT, and entrainment pacing revealed a post-pacing interval similar to the tachycardia cycle length, which suggested that the interatrial conduction from the RA to the left atrium (LA) was located just at the transseptal puncture site. A radiofrequency application inside the transseptal puncture hole could successfully eliminate the BiAT. The ablation target for BiATs propagating around the mitral annulus and RA septum is generally the anatomical mitral isthmus (MI). Since the present case had multiple incisions on both the RA and LA septum due to mitral valve surgeries, there was the possibility of the occurrence of a BiAT including the RA and LA septum after performing an MI linear ablation. Therefore, the preferable ablation target for the BiAT in the present case appeared to be the interatrial connection. Ultra-high resolution detailed mapping not only on the atrial endocardium but also in the transseptal puncture hole may be useful for identifying a critical interatrial connection of BiAT circuits.


Prostaglandin F2alpha upregulates uterine immune defenses in the presence of the immunosuppressive steroid progesterone.
Uterine infections often develop in some livestock species during the first luteal phase postpartum. Exogenous prostaglandin F(2alpha) (PGF(2alpha)) induces luteolysis, reduces progesterone, and enables the uterus to resolve infections. However, the effects of PGF(2alpha) on luteal function and on immune functions are confounded. These effects must be disentangled to determine whether alternatives to antibiotic treatments can be successfully developed. Treatments were in a 2 x 2 x 2 factorial arrangement. Main effects were ovariectomy or sham on day 0 (i.e. estrus), exogenous progesterone or sesame oil from day 0 to 11, and exogenous PGF(2alpha) or saline on day 9. Intrauterine inoculations with Arcanobacterium pyogenes and Escherichia coli were administered on day 6. Ewes treated with exogenous PGF(2alpha) either did not have uterine infections, infections were less severe, or infections were resolving when uteri were examined on day 12, despite increased progesterone. Exogenous PGF(2alpha) has effects on the resolution of uterine infections that are independent of its effects on luteal progesterone production.


Na-doping effects on structural evolution and superconductivity in (K1-x Na x )2Cr3As3 (x = 0-1).
In this report, we studied the effects of isovalent Na-doping on the recently discovered quasi-one-dimensional Cr-based unconventional superconductor K2Cr3As3. A series of polycrystalline samples with nominal component (K1-x Na x )2Cr3As3 (x = 0-1) were synthesized by the solid state reaction method. From crystal structure and chemical phase characterizations, we found two distinct chemical phases with the same hexagonal structure but distinguished by different site occupancy of Na+ ions at the two kinds of K-site in the K2Cr3As3 lattice structure. When x ⩽ 0.4, the doped samples form a continuous sosoloid phase of (K1-x Na x )2Cr3As3 with the Na+ ions randomly doping at the K-sites (denoted as α-phase); when x ⩾ 0.5, a novel individual phase of (K0.25Na0.75)2Cr3As3 emerges, in which the Na+ ions selectively occupy all the '3k' sites and the K+ ions occupy the '1c' sites (denoted as β-phase). No chemical phase of Na2Cr3As3 was detected. Superconductivity in these samples was studied by electrical transport and magnetic susceptibility measurements, and it evolves in a much sophisticated manner. In the α-phase, the superconducting T c decreases quickly upon Na-doping. All these α-phase samples have surprisingly low superconducting volume fraction and relatively low T c compared with the undoped K2Cr3As3. However, the β-phase has a clearly enhanced T c up to 7.6 K which locates between the values of K2Cr3As3 and Na2Cr3As3, and exhibits a full superconducting shielding signal.


The detection of doubtful data: the program DOUBT.
The problem of the detection of erroneous data has led us to define the 'doubtful patients' as patients who have a small density. Our program DOUBT computes the densities associated with each patient by using the method of n nearest neighbors. Then the program allows us to define a density limit, and chooses the patients who have a smaller density then the doubtful patients. The remaining patients may be classified by the program.


Left-to-right differences of regional cerebral oxygen saturation and oxygen extraction in preterm infants during the first days of life.
In a prospective study, we monitored simultaneously left and right parieto-frontal-cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE) using near-infrared spectroscopy in 36 very preterm neonates during the first 3 d of life. Simple regression analysis showed a close correlation between left and right rScO2 (r = 0.89, p < 0.01) and cFTOE (r = 0.88, p < 0.01), respectively. The Bland and Altman-determined limits of agreement found overall limits of agreement of -8.5 to +9.5% and of -0.10 to +0.093% between left and right for rScO2 and for cFTOE, respectively. However, we found that during stable systemic oxygenation (i.e., arterial oxygen saturation [SaO2 between 85 and 97%]) the limits of agreement between left and right improved from -7.8 to +8.2% and -0.088 to +0.084 for rScO2 and cFTOE, respectively (all p < 0.05). We conclude that bilateral near-infrared spectroscopy-measured rScO2 and cFTOE can reveal differences up to 10% between left and right hemisphere, especially during unstable arterial saturations, which may indicate uneven cerebral oxygenation.


Precision Medicine and Mysteries in Clinical Microbiology: Rationalizing Epidemiology, Genotype, and Phenotype To Guide Therapeutics.
Whole-genome sequencing (WGS) using MinION was used to characterize high-risk clones of Escherichia coli and Klebsiella pneumoniae harboring bla NDM-5, bla OXA-181, and bla CTX-M-15, as well as Pseudomonas aeruginosa harboring bla NDM, in a patient who received health care in India. Synergy testing demonstrated the activity of aztreonam and ceftazime-avibactam in combination. This case illustrates a "precision medicine" approach where deeper understanding of the genotype through WGS and of the phenotype through synergy testing formed the basis for rational combination therapy.


Angiosarcoma of the heart in an adolescent. A light and electron microscopic and immunohistochemical study.
A cardiac angiosarcoma occurred in the right atrium of a 15-year-old boy. Unusual features included the patient's young age and the antemortem pathologic diagnosis of the tumor.


National analysis of whole blood and component versus component transfusions in civilian trauma patients who underwent a thoracotomy or laparotomy: Toward improving patient outcomes and quality of care.
This study aimed to investigate the associations of whole blood and component versus component transfusions with in-hospital mortality, complication rates, intensive care unit length of stay, and packed red blood cells transfusion volumes in adult civilian trauma patients. We performed a retrospective cohort study of the American College of Surgeons Trauma Quality Program Participant Use File 2016 to 2019 dataset. Adult civilian trauma patients (aged >18 years) sustaining injuries of at least moderate severity who received whole blood and component or component within 4 hours of arrival and underwent thoracotomy or laparotomy were included. Multivariable regression analysis was used to compare outcomes between whole blood and component and component groups. A total of 37,384 patients met eligibility criteria, of which 218 received whole blood and component and 37,166 received component. There was no significant difference in in-hospital mortality between whole blood and component and component groups for those who underwent thoracotomy (adjusted odds ratio = 0.408, P = .413) or laparotomy (adjusted odds ratio = 1.046, P = .857). Thoracotomy patients who received whole blood and component had no difference in 4-hour or 24-hour pack red blood cell volumes (3336 mL vs 3106 mL, P = .754; 3 658mL vs 3,636mL, P = .982), intensive care unit length of stay (10.68 days vs 8.63 days, P = .542), or complications rates compared to those who received component. Laparotomy patients who received whole blood and component had no difference in 4 hour or 24-hour packed red blood cell volumes (2,758 mL vs 2,721mL, P = .927; 3,538 mL vs 3,385 mL, P = .754), intensive care unit length of stay (11.78 days vs 9.90 days, P = .177), or complications rates compared to those who received component. Study findings have indicated that a combined resuscitation with whole blood and component transfusion in adult civilian trauma patients is a viable alternative to component transfusion alone.


Alteration of syncytiotrophoblast mitochondria function and endothelial nitric oxide synthase expression in the placenta of rural residents.
The impact of environmental organophosphate (OP) pesticide exposure on respiratory complexes, enzymatic antioxidant defense activities, and oxidative damage markers in the syncytiotrophoblast and cytotrophoblast mitochondria was evaluated. Placental progesterone (PG) levels and endothelial nitric oxide synthase (eNOS) expression were studied. Samples from women non-exposed (control group-CG) and women living in a rural area (rural group-RG) were collected during pesticide spraying season (RG-SS) and non-spraying season (RG-NSS). In RG-SS, the exposure biomarker placental carboxylesterase decreased and syncytiotrophoblast cytochrome c oxidase activity increased, while 4-hydroxynonenal levels decreased. PG levels decreased in RG-SS and in the RG. Nitric oxide synthase expression decreased in RG, RG-SS and RG-NSS. No significant changes in mitochondrial antioxidant enzyme activities were found. These results suggest that the alteration of syncytiotrophoblast mitochondrial complex IV activity and steroidogenic function may be associated to pesticide exposure. Reduction in placental PG and eNOS expression may account for low newborn weight in RG.


Monoclonal antibodies to canine adenoviruses 1 and 2 that are type-specific by virus neutralization and immunofluorescence.
Monoclonal antibodies were produced against the Mirandola strain of canine adenovirus Type 1 (CAV-1) and the Manhattan strain of canine adenovirus Type 2 (CAV-2). The monoclonal antibodies were used in vitro in virus neutralization (VN) assays and in indirect fluorescent antibody (IFA) tests to examine several strains of each virus type. Out of 36 monoclonal antibodies produced against the Mirandola strain, 18 were type-specific for CAV-1 by IFA and 13 of those neutralized the virus in vitro. The other 18 antibodies bound both CAV-1 and CAV-2 by IFA; however, 7 of those specifically neutralized only CAV-1. The 160 monoclonal antibodies made against the Manhattan strain of CAV-2 yielded 77 type-specific antibodies by IFA, of which 39 neutralized only CAV-2 in vitro. The remaining 83 antibodies recognized both CAV-1 and CAV-2 by IFA, with 3 of those neutralizing both viral types. The hemagglutination inhibition (HI) test was performed on a selected monoclonal antibody from each specificity group. Although Type 1 CAV could be readily differentiated from Type 2 CAV by using type-specific monoclonal antibodies in the IFA or VN tests, strains within each type could not be differentiated. This is the first report of neutralizing monoclonal antibodies for a mammalian adenovirus.


Antioxidant and antimicrobial effects of essential oils from two salvia species with in vitro and in silico analysis targeting 1AJ6 and 1R4U proteins.
The Middle Atlas is a Moroccan territory that serves as an abode to plants with incredible biodiversity, of which aromatic and medicinal plants that have been of folkloric use are a significant component. However, their effective utilization in modern medicine requires the characterization of their phytochemicals to facilitate their entry into drug discovery pipelines. Hence, this study aimed to characterize and investigate the antioxidant activity and antimicrobial effects of the essential oils (EOs) of Salvia lavandulifolia subsp. mesatlantica and Salvia officinalis L. by use of in vitro and in silico assays. Ten phytochemicals were identified in the EOs of S. lavandulifolia, while twenty phytochemicals were identified in S. officinalis. Camphor was the most abundant compound in both species, comprising 26.70% and 39.24% of the EOs of S. lavandulifolia and S. officinalis, respectively. The EOs of both plants exhibited significant DPPH free radical scavenging activity, with S. lavandulifolia and S. officinalis showing estimated scavenging rates of 92.97% and 75.20%, respectively. In terms of Ferric Reducing Antioxidant Power (FRAP), S. officinalis demonstrated a higher value (72.08%) compared to that of S. lavandulifolia (64.61%). Evaluation of the antimicrobial effects of the EOs of S. officinalis and S. lavandulifolia against microorganisms revealed bactericidal activities against Proteus mirabilis and Bacillus subtilis at low concentrations. It showed bactericidal activities against Staphylococcus aureus and Candida albicans at a relatively higher concentration. Molecular docking of antioxidant and antimicrobial proteins offers significant insights into ligand-protein interactions, facilitating the development of innovative therapeutics from the current study. Ultimately, this study identified the phytochemical composition of S. lavandulifolia and S. officinalis and highlighted their potential for therapeutic discovery.


Structure modification and property improvement of plant cellulose: Based on emerging and sustainable nonthermal processing technologies.
Cellulose has attracted high attention due to its advantages of abundant resources, renewable and biodegradable. Modification of natural plant cellulose has become a hot topic worldwide. Conventional chemical modification methods commonly cause great damage to the environment. The current review presents the effects of innovative, eco-friendly and sustainable nonthermal processing technologies on cellulose structure and properties. Typical techniques include high pressure processing, cold plasma, ultrasonic and irradiation treatment. Their superiorities in the modification of cellulose are highlighted, and the advantages and limitations of nonthermal processing technologies for plant cellulose modification are also discussed. Nonthermal processing technologies can improve cellulose functional properties by playing an important role in the chemical bonds of the molecular chains, crystalline regions or amorphous parts through energy or active particles generated in the process, or promoting the crosslinking and graft copolymerization of cellulose molecules. The development of modified cellulose functional materials will have wider applications.


Five years' experience with continuous ambulatory or continuous cycling peritoneal dialysis in children.
In 93 children, end-stage renal disease was treated with the new dialytic methods of continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD) over 5 years. Modality survival rates at 36 months with CAPD, CCPD, or both were 20%, 93%, and 87%, respectively. Use of CCPD as the primary dilaytic method increased during the study period. The peritonitis rate was one episode per 11.8 patient treatment months and was similar with both CAPD and CCPD. Gram-positive organisms were cultured in 34% of these episodes of peritonitis. Staphylococcus aureus peritonitis was associated with a recurrence rate of 40% and led to catheter replacement in 45% of the episodes. Peritoneal membrane failure necessitating switching to hemodialysis was related to peritonitis in three patients. Of the 74 peritoneal catheters that required replacement, 70% were infected. Serial serum levels of urea nitrogen, potassium, calcium, phosphorus, albumin, and alkaline phosphatase remained stable, whereas serum creatinine level rose slightly over time. Episodes of hyperkalemia, hypercalcemia, and hyperphosphatemia were observed at a frequency of one episode per 12.2, 4.6, and 2.5 treatment months, respectively. Blood transfusions were required in once per 1.5 and 3.3 treatment months in seven anephric patients and in 35 patients with their own kidneys, respectively (P = 0.05). In prepubertal patients who received CAPD or CCPD for greater than 1 year, little or no improvement in growth occurred in relationship to either chronologic or bone age.


Vertical changes of PM2.5 driven by meteorology in the atmospheric boundary layer during a heavy air pollution event in central China.
Regional PM2.5 transport is a crucial factor affecting air quality, and the meteorological mechanism in the atmospheric boundary layer (ABL) has not been fully understood over the receptor region in the regional transport of air pollutants. Based on the intensive vertical measurements of air pollutants and meteorology in the ABL during a transport-induced heavy air pollution event in Xiangyang, an urban site over a receptor region in central China, we investigated the meteorological mechanism in vertical PM2.5 changes in the ABL for heavy air pollution over the receptor region. Driven by northerly winds, regional PM2.5 transport was built from upstream northern China to downstream central China, where the observed ABL structures were unstable throughout the air pollution event. We assessed the ABL structures with meteorological and PM2.5 profiles at growth, maintenance, and dissipation stages, and elucidated the mechanism of regional PM2.5 transport inducing air pollution over the receptor region with the contribution of thermal and mechanical factors. The regional PM2.5 transport was concentrated in the upper ABL over the downwind receptor region with high PM2.5 concentrations at altitudes of 600-800 m, where the transported PM2.5 peaks were downwards mixed by vertical wind shear, forming the vertical PM2.5 transport from the upper ABL to near-surface in the growth stage; the weakened winds and less unstable structures in the ABL favored the sustained pollution with slight vertical PM2.5 changes in the maintenance stage, which was dominated by thermal factors with 87 % contribution; the removal of PM2.5 was triggered by increasing winds from the upper ABL, activating the dissipation of heavy PM2.5 pollution with the mechanical effect accounting for 60 % in the dissipation stage. These findings could improve our understanding of ABL's influence on air pollution over the receptor region with implications for the regional transport of air pollutants in environmental changes.


Data on methane concentration collected by underground coal mine sensors.
Coal mining requires working in hazardous conditions. Miners in an underground coal mine can face several threats, such as, e.g. methane explosions. To provide protection for people working underground, systems for active monitoring of production processes are typically used. One of their fundamental applications is screening dangerous gas concentrations (methane in particular) to prevent spontaneous explosions. Such a system is the source of the data set containing raw data collected at an underground coal mine. The data is collected from 28 different sensors placed at various locations around the coal mine. All the attributes except one are numeric, and the examples collected form a time series. This data set can be used in a variety of analytical tasks, including classification, regression, time series and stream data analysis.


Comparative mitogenomics and phylogenetics of the family Carangidae with special emphasis on the mitogenome of the Indian Scad Decapterus russelli.
Carangids are abundant and commercially important marine fish that contribute to a significant portion of the fisheries in many parts of the world. In the present study, we characterized the complete mitogenome of the Indian scad, Decapterus russelli and performed a comprehensive comparative mitogenomic analysis of the family Carangidae. The comparative mitogenomics provided valuable insights into the structure, variability, and features of the coding and non-coding regions that evolved across species over millions of years. The structural features of tRNAs revealed changes in the frequency of mismatched and wobble base pairs, which is reflected in the base composition of H and L strands. The highly conserved sequence motif of the mTERF binding site in carangids over the ~ 400 MYA of their divergence demonstrated the functional importance of these sites. The control region of carangids was characterized by the presence of discontinuous repeat units with a high rate of sequence divergence in the form of base substitutions, insertions, and deletions. The maintenance of secondary structures in the control region independent of the rapid evolution of primary structure suggested the effect of selective constraints on their maintenance. Maximum likelihood (ML) and Bayesian inference (BI) phylogeny revealed a similar topology consistent with previous taxonomic studies. The extant carangids diverged through the evolutionary events experienced during the Cretaceous, Paleogene, and Neogene periods.


Investigation of reversible metal ion (Li+, Na+, Mg2+, Al3+) insertion in MoTe2 for rechargeable aqueous batteries.
In this work, we report the electrochemical reactivity of MoTe2 for various metal ions with special emphasis on Al3+ ion storage in aqueous electrolytes for the first time. A stable discharge capacity of 100 mA h g-1 over 250 cycles at a current density of 1 Ag-1 could be obtained for the Al3+ ion, whereas inferior storage capacities were shown for other metal ions.


Effect of estrogen on the elongation rate and number of RNA chains being synthesized in uterine nucleoli.
Administration of estradiol (E2) to ovariectomized mature rats resulted in a time-dependent increased transcriptional activity of uterine nucleoli isolated from hormone-treated animals compared to uterine nucleoli isolated from control animals. Early (4 h) E2 stimulation of uterine nucleolar transcription, resulted from an increased rate of elongation of chain growth on preinitiated nucleolar RNA with no significant effect of E2 on the number of nucleolar RNA chains being synthesized. Longer (24 h) treatment of animals with hormone resulted in both significant increased numbers of uterine nucleolar RNA chains in the act of synthesis and increased rate of elongation of nucleolar RNA chain growth. Salt extraction (150 mM NaCl) of uterine nucleoli isolated from 4 h E2-treated animals decreased transcriptional activity to the level observed in nucleoli isolated from control animals. The loss in nucleolar transcriptional activity from salt extraction was due to decreased rate of elongation of nucleolar RNA synthesis with no significant effect on the number of RNA chains being synthesized. Salt extracts from nucleoli isolated from 4 h E2-treated animals, but not control animals, contained factor(s) capable of stimulating the rate of elongation of nucleoli isolated from control animals to elongation rates observed in unextracted nucleoli isolated from 4 h E2-treated animals. Synthesis and phosphorylation of a high molecular weight uterine nucleolar protein(s) was seen after 4 h of E2 treatment with the nucleolar phosphoprotein(s) salt extractable.


Vaccination of koalas during antibiotic treatment for Chlamydia-induced cystitis induces an improved antibody response to Chlamydia pecorum.
Chlamydia infection and disease are endemic in free-ranging koalas. Antibiotics remain the front line treatment for Chlamydia in koalas, despite their rates of treatment failure and adverse gut dysbiosis outcomes. A Chlamydia vaccine for koalas has shown promise for replacing antibiotic treatment in mild ocular Chlamydia disease. In more severe disease presentations that require antibiotic intervention, the effect of vaccinating during antibiotic use is not currently known. This study investigated whether a productive immune response could be induced by vaccinating koalas during antibiotic treatment for Chlamydia-induced cystitis. Plasma IgG antibody levels against the C. pecorum major outer membrane protein (MOMP) dropped during antibiotic treatment in both vaccinated and unvaccinated koalas. Post-treatment, IgG levels recovered. The IgG antibodies from naturally-infected, vaccinated koalas recognised a greater proportion of the MOMP protein compared to their naturally-infected, unvaccinated counterparts. Furthermore, peripheral blood mononuclear cell gene expression revealed an up-regulation in genes related to neutrophil degranulation in vaccinated koalas during the first month post-vaccination. These findings show that vaccination of koalas while they are being treated with antibiotics for cystitis can result in the generation of a productive immune response, in the form of increased and expanded IgG production and host response through neutrophil degranulation.


Intestinal and hepatic response to combined partial hepatectomy and small bowel resection in mice.
Both partial-hepatectomy (PHx) and massive small bowel resection (SBR) are strong mitogenic signals to the remnant liver and intestine, respectively. This study tested the hypothesis that PHx was an additive signal for intestinal adaptation after massive SBR. Male mice underwent either sham SBR or 50% proximal SBR. Mice from these two groups were then subjected to a 70% PHx or sham PHx. After 3 days, parameters of intestinal adaptation and liver regeneration were recorded in the remnant intestine and liver, respectively. Intestinal adaptation following SBR occurred normally, but was not enhanced after concomitant PHx. On the other hand, SBR impaired the regenerative ability of the liver following PHx. Intestinal adaptation after SBR takes priority over liver regeneration after PHx. These data implicate a hierarchy with regard to adaptive alterations to organ loss and endorse an important role for the intestinal mucosa in the regulation of hepatic regeneration.


Two CRISPR-Cas systems in Methanosarcina mazei strain Gö1 display common processing features despite belonging to different types I and III.
The clustered regularly interspaced short palindromic repeats (CRISPR) system represents a highly adaptive and heritable defense system against foreign nucleic acids in bacteria and archaea. We analyzed the two CRISPR-Cas systems in Methanosarcina mazei strain Gö1. Although belonging to different subtypes (I-B and III-B), the leaders and repeats of both loci are nearly identical. Also, despite many point mutations in each array, a common hairpin motif was identified in the repeats by a bioinformatics analysis and in vitro structural probing. The expression and maturation of CRISPR-derived RNAs (crRNAs) were studied in vitro and in vivo. Both respective potential Cas6b-type endonucleases were purified and their activity tested in vitro. Each protein showed significant activity and could cleave both repeats at the same processing site. Cas6b of subtype III-B, however, was significantly more efficient in its cleavage activity compared with Cas6b of subtype I-B. Northern blot and differential RNAseq analyses were performed to investigate in vivo transcription and maturation of crRNAs, revealing generally very low expression of both systems, whereas significant induction at high NaCl concentrations was observed. crRNAs derived proximal to the leader were generally more abundant than distal ones and in vivo processing sites were clarified for both loci, confirming the previously well-established 8 nt 5' repeat tags. The 3'-ends were more diverse, but generally ended in a prefix of the following repeat sequence (3'-tag). The analysis further revealed a 5'-hydroxy and 3'-phosphate termini architecture of small crRNAs specific for cleavage products of Cas6 endonucleases from type I-E and I-F and type III-B.


Binding of Fab-horseradish peroxidase conjugates by charge and not by immunospecificity.
The influence of horseradish peroxidase (HRP) charge on Fab-HRP conjugates was investigated. Rabbit nonimmune Fab coupled via periodate or glutaraldehyde to Sigma HRP type VI (pI greater than 10) were cationic (positively charged) as determined by analytical isoelectric focusing. These conjugates and HRP type VI alone stippled the basal laminae and collagen fibers in Bruch's membrane of the rat eye in a pattern identical to anionic (negative) sites. Binding was not present after the anionic sites were removed by enzyme digestion prior to immunolabeling or when HRP type VIII (anionic with pI 3.6) was used in an Fab-HRP conjugate or in an unbound form. These results indicate that anionic HRPs should be used in Fab-HRP preparations if a nonspecific binding to anionic sites is possible.


Fusarium species (section Liseola) occurrence and natural incidence of beauvericin, fusaproliferin and fumonisins in maize hybrids harvested in Mexico.
Fusarium species can produce fumonisins (FBs), fusaric acid, beauvericin (BEA), fusaproliferin (FUS) and moniliformin. Data on the natural occurrence of FBs have been widely reported, but information on BEA and FUS in maize is limited. The aims of this study were to establish the occurrence of Fusarium species in different maize hybrids in Mexico, to determine the ability of Fusarium spp. isolates to produce BEA, FUS and FBs and their natural occurrence in maize. Twenty-eight samples corresponding to seven different maize hybrids were analyzed for mycobiota and natural mycotoxin contamination by LC. Fusarium verticillioides was the dominant species (44-80%) followed by F. subglutinans (13-37%) and F. proliferatum (2-16%). Beauvericin was detected in three different hybrids with levels ranging from 300 to 400 ng g(-1), while only one hybrid was contaminated with FUS (200 ng g(-1)). All samples were positive for FB1 and FB2 contamination showing levels up to 606 and 277 ng g(-1), respectively. All F. verticillioides isolates were able to produce FB1 (13.8-4,860 μg g(-1)) and some also produced FB2 and FUS. Beauvericin, FUS, FB1 and FB2 were produced by several isolates including F. proliferatum and F. subglutinans and co-production was observed. This is the first report on the co-occurrence of these toxins in maize samples from Mexico. The analysis of the presence of multiple mycotoxins in this substrate is necessary to understand the significance of these compounds in the human and animal food chains.


Discrepancy among acute guideline levels for emergency response.
Acute guidance values are tools for public health risk assessment and management during planning, preparedness and response related to sudden airborne release of hazardous chemicals. The two most frequently used values, i.e. Acute Exposure Guidance Levels (AEGL) and Emergency Response Planning Guideline (ERPG), were compared in qualitative and quantitative terms. There was no significant difference between the general level of AEGL and ERPG values, suggesting the two systems are equally precautious. However, the guidance values diverged by a factor of 3 or more for almost 40% of the substances, including many of high production volume. These deviations could be explained by differences in selection of critical effect or critical study and in a few cases differences in interpretation of the same critical study. Diverging guidance values may hamper proper risk communication and risk management. Key factors for broad international acceptance of harmonized values include transparency of the decision process, agreement on definition of toxicological tiers, and a target population including sensitive groups of the general population. In addition, development of purely health based values is encouraged. Risk management issues, such as land use and emergency response planning should be treated separately, as these rely on national legislation and considerations.


Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy.
Atomic force microscopy (AFM) has been used to measure the strength of bonds between biological receptor molecules and their ligands. But for weak noncovalent bonds, a dynamic spectrum of bond strengths is predicted as the loading rate is altered, with the measured strength being governed by the prominent barriers traversed in the energy landscape along the force-driven bond-dissociation pathway. In other words, the pioneering early AFM measurements represent only a single point in a continuous spectrum of bond strengths, because theory predicts that these will depend on the rate at which the load is applied. Here we report the strength spectra for the bonds between streptavidin (or avidin) and biotins-the prototype of receptor-ligand interactions used in earlier AFM studies, and which have been modelled by molecular dynamics. We have probed bond formation over six orders of magnitude in loading rate, and find that the bond survival time diminished from about 1 min to 0.001 s with increasing loading rate over this range. The bond strength, meanwhile, increased from about 5 pN to 170 pN. Thus, although they are among the strongest noncovalent linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds in fact appear strong or weak depending on how fast they are loaded. We are also able to relate the activation barriers derived from our strength spectra to the shape of the energy landscape derived from simulations of the biotin-avidin complex.


Effectiveness of multidisciplinary interventions to improve the quality of life for people with Parkinson's disease: a systematic review.
To conduct a systematic review and critically evaluate the literature on the effectiveness of multidisciplinary interventions to improve quality of life for people with Parkinson's disease. An electronic search of the following publication databases was performed for records from 1995 to 2011: CINAHL PLUS (EBSCO), Joanna Briggs Institute, Pubmed, Web of Science (ISI), psycINFO, Scopus and Cochrane library. The keywords used were Parkinson's disease, nursing, allied health, doctor, intervention, quality of life, rehabilitation, multidisciplinary team and their various combinations. Key terms were matched to MeSH subject headings and exploded where relevant to include all subheadings and related terms to each key term used. 1808 articles were initially identified based on our selection criteria and the reference list of these articles was hand searched. Nine studies were included after this sifting process and critiqued by two reviewers. Three randomised controlled trials and 6 non-randomised cohort studies were included. For these studies the level of evidence ranged from the Scottish Intercollegiate Network (SIGN) level of 1- to 2-. The outcome measures assessed were heterogeneous, including measures of disability of disease, stage of disease and various quality of life measures. The evidence quantifying positive and sustained effects of multidisciplinary interventions to improve quality of life for people with Parkinson's disease is inconclusive. There has been relative lack of controlled experimentation to quantify therapy outcomes. The studies reviewed were varied and lacked long-term follow-up to quantify retention of the intervention. It is recommended that interventions to improve quality of life are tested in randomised controlled trials using standardised outcome measures, adequately powered samples and longer follow-up periods to assess intervention sustainability.


The specificity of Bleulerian and Schneiderian symptoms: a critical reevaluation.
Schneider's FRS's seem to carry diagnostic weight for schizophrenia when "massively" present and when known organic psychoses are excluded. However, at least 10 per cent of affectively ill probands, especially manics, have also been shown to have at least one FRS. The main problems in their clinical application is their low sensitivity (on the average less than 50 per cent), and the possibility that those without extensive training in the phenomenologic approach may overendorse their presence, thereby diluting the specificity of the test.


Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus.
A subgroup of COVID-19 patients develop very severe disease with requirement for ICU treatment, ventilation, and ECMO therapy. Laboratory tests indicate that the immune and clotting system show marked alterations with hyper-activation, hyper-inflammation, cytokine storm development. Furthermore, organ-specific biomarkers demonstrate the involvement of cardiac muscle, kidney, and liver dysfunction in many patients. In this article the use of laboratory biomarkers is discussed with regard to their use for diagnosis, disease progression, and risk assessment.


A pH-neutral electrolyzed oxidizing water significantly reduces microbial contamination of fresh spinach leaves.
There are growing demands globally to use safe, efficacious and environmentally friendly sanitizers for post-harvest treatment of fresh produce to reduce or eliminate spoilage and foodborne pathogens. Here, we compared the efficacy of a pH-neutral electrolyzed oxidizing water (Ecas4 Anolyte; ECAS) with that of an approved peroxyacetic acid-based sanitizer (Ecolab Tsunami® 100) in reducing the total microbial load and inoculated Escherichia coli, Salmonella Enteritidis and Listeria innocua populations on post-harvest baby spinach leaves over 10 days. The impact of both sanitizers on the overall quality of the spinach leaves during storage was also assessed by shelf life and vitamin C content measurements. ECAS at 50 ppm and 85 ppm significantly reduced the bacterial load compared to tap water-treated or untreated (control) leaves, and at similar levels (approx. 10-fold reduction) to those achieved using 50 ppm of Ecolab Tsunami® 100. While there were no obvious deleterious effects of treatment with 50 ppm Tsunami® 100 or ECAS at 50 ppm and 85 ppm on plant leaf appearance, tap water-treated and untreated leaves showed some yellowing, bruising and sliming. Given its safety, efficacy and environmentally-friendly characteristics, ECAS could be a viable alternative to chemical-based sanitizers for post-harvest treatment of fresh produce.


Screening for Fusarin C production by European isolates of Fusarium species.
A total of 137Fusarium isolates were screened forin vitro production of the mutagenic metabolite fusarin C, using a simple thin layer chromatographic method. It has been proven thatFusarium species (F. culmorum, F. graminearum, F. crookwellense, F. sporotrichioides, F. poae, F. tricinctum, andF. Avenaceum) isolated from European agricultural crops and soils are able to produce fusarin C. No fusarin C production was detected among isolates ofF. arthrosporioides, F. acuminatum, or F. equiseti.Results obtained by High-Performance Liquid Chromatography (HPLC) analyses of fungal extracts show that up to 26 chromatographic peaks having UV spectra similar to that of fusarin C are produced. It is not known if any of these metabolites are as mutagenic as fusarin C.


Detection of gamma radiation processed onion during storage using propidium iodide based fluorescence microscopy.
The determination of absorbed dose in gamma radiation processed onion (treated with 20-100 Gy for sprout inhibition) during storage is an important regulatory requirement to control unfair practices. To address this problem, a microscopy based method was developed using propidium iodide (PI) staining of onion adaxial epidermis. A proportional radiation dose dependent increase in nuclei count was observed during ambient (26 ± 2 °C) and low (2 ± 1 °C) temperature storage. The method was validated and dose of radiation could be determined accurately in stored onions using blind tests. During mechanism studies, boron-dipyrromethene (BODIPY) dye staining and malondialdehyde (MDA) estimation showed dose dependent increase in peroxidation of membrane lipids. The fluorescein diacetate (FDA) stained onion adaxial epidermis showed decrease in fluorescence indicating lowering of physiological activity. Enzyme peroxidase (POD), phenylalanine ammonia lyase (PAL) activities and phytochemicals (phenolics, flavonoids, ascorbic acid and pyruvic acid) did not change significantly with increasing dose of gamma radiation.


Predictors of cardiometabolic risk among adults with cerebral palsy.
To examine the independent association between various anthropometric indicators and standard clinical markers of cardiometabolic health risk among adults with cerebral palsy (CP). Cross-sectional study. Clinical center for CP treatment and rehabilitation. Adults with CP (N=43) with a mean age ± SD of 37.3±13.2 years, and Gross Motor Function Classification System (GMFCS) levels of I-V. Not applicable. Adults with CP were assessed for body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), and serum lipid profiles. Data were analyzed with multiple regression analysis and general linear models, and are reported as means ± SDs. Mean BMI was 29.1±7.8kg/m(2). BMI was not associated with any measures of cardiometabolic risk. Using GMFCS categories (2 groups: GMFCS levels I-III and IV-V), BMI was significantly lower among GMFCS levels IV-V (24.2±6.2kg/m(2)) versus GMFCS levels I-III (30.1±7.6kg/m(2)). WC and WtHR were not correlated with any cardiometabolic outcomes. Conversely, measures of WHR were independently associated with various indices of risk, including total cholesterol to high-density lipoprotein (HDL) cholesterol ratio (r=.45; P<.05), HDL cholesterol (r=-.51; P<.01), and triglycerides (r=.40; P<.05), suggesting that greater WHR was indicative of elevated risk. It is likely that WHR represents a stronger predictor of risk, because this measure was robustly and independently associated with 3 primary clinical markers of cardiometabolic health in adults with CP.


[Clinical observation on treatment of cerebral infarction by combined therapy of acupuncture with extremities tissue separating manipulation].
To observe the curative effect of combined treatment of extremities tissue separating manipulation (ETSM) and acupuncture on cerebral infarction (CI). CI patients were randomly divided into 3 groups. Group A was treated with drug-therapy only, Group B was treated with drug-therapy plus acupuncture and Group C was treated with drug-therapy plus ETSM and acupuncture. All patients were treated for 15 successive days for evaluating curative effect. The cured-markedly effective rate, total effective rate and nerve function deficit score after treatment was 28.6% , 71.4% and 17.57 +/- 1.51 scores in Group A, 48.4%, 80.6% and 13.97 +/- 1.38 scores in Group B, and 81.3%, 93.7% and 11.00 +/- 1.51 scores in Group C, respectively. Significant difference was shown in comparison of Group A with Group B, also in comparison of Group C with Group A and B (All P <0.05). ETSM combined acupuncture has a good therapeutic effect on CI.


Implementation of ensemble machine learning algorithms on exome datasets for predicting early diagnosis of cancers.
Classification of different cancer types is an essential step in designing a decision support model for early cancer predictions. Using various machine learning (ML) techniques with ensemble learning is one such method used for classifications. In the present study, various ML algorithms were explored on twenty exome datasets, belonging to 5 cancer types. Initially, a data clean-up was carried out on 4181 variants of cancer with 88 features, and a derivative dataset was obtained using natural language processing and probabilistic distribution. An exploratory dataset analysis using principal component analysis was then performed in 1 and 2D axes to reduce the high-dimensionality of the data. To significantly reduce the imbalance in the derivative dataset, oversampling was carried out using SMOTE. Further, classification algorithms such as K-nearest neighbour and support vector machine were used initially on the oversampled dataset. A 4-layer artificial neural network model with 1D batch normalization was also designed to improve the model accuracy. Ensemble ML techniques such as bagging along with using KNN, SVM and MLPs as base classifiers to improve the weighted average performance metrics of the model. However, due to small sample size, model improvement was challenging. Therefore, a novel method to augment the sample size using generative adversarial network (GAN) and triplet based variational auto encoder (TVAE) was employed that reconstructed the features and labels generating the data. The results showed that from initial scrutiny, KNN showed a weighted average of 0.74 and SVM 0.76. Oversampling ensured that the accuracy of the derivative dataset improved significantly and the ensemble classifier augmented the accuracy to 82.91%, when the data was divided into 70:15:15 ratio (training, test and holdout datasets). The overall evaluation metric value when GAN and TVAE increased the sample size was found to be 0.92 with an overall comparison model of 0.66. Therefore, the present study designed an effective model for classifying cancers which when implemented to real world samples, will play a major role in early cancer diagnosis.


Dynamic characteristics of near-surface spontaneous combustion gas flux and its response to meteorological and soil factors in coal fire area.
Accurate identification of the early stages of coal-fire combustion is important for effectively controlling the spread of coal fires. CO2 and CO, as characteristic gases in the early stage of coal fire combustion, can be effectively monitored by in-situ monitoring near the surface. However, in the previous in-situ monitoring methods, the influence of surface meteorological and soil factors on the release law of characteristic gases is often ignored. Therefore, this paper considers the complexity of the geological conditions in the coal fire area, a system, and equipment for obtaining the near-surface CO2 and CO variation laws in the early stage of coal fire combustion proposed by the concentration gradient method (CGM). The system and equipment realize the simultaneous online coupling of multi-area and multi-parameter data and conduct field investigations on the Wuda coal fire area. The results show that in the early stage of coal combustion, the change patterns of CO2 and CO concentrations in different regions are anomalous, and the CO2 concentration was higher than the CO concentration. The CO2 and CO concentrations in shallow soil increased with the increase of soil depth, and compared with other areas, the CO2 and CO concentration was the highest. The shallow soil and CO2 were identified as the key areas and characteristic gases for identifying the early stage of coal-fire combustion. The CO2 flux (CF) of different shallow soil depths decreased with increased soil layer depth. Variation of soil-surface CO2 flux (S-SCF) estimated by flux extrapolation method (FLEM). The change of S-SCF is controlled by meteorological and soil factors, and there is a certain connection between it and the "respiration phenomenon" in the fissure area. Thus, this study provides a theoretical basis for effectively identifying the early stages of coal-fire combustion.


Concentration-dependent energy transfer studies in ternary dye mixture of Stilbene-420, Coumarin-540 and Nile Blue.
The energy transfer studies in the case of ternary dye mixture [Stilbene-420 (donor)+Coumarin-540 (intermediator)+Nile Blue (acceptor)] have been done and discussed through optical gain characteristics at various acceptor concentrations under nitrogen laser excitation. The concentration of the other two dyes were kept constant. It is observed that the concentration of the acceptor dye plays a very critical role in energy transfer dye laser (ETDL) as small change in its concentration varies the intensity of the laser output in the red region by large amount. Also, the highest laser output in the red region is obtained when the concentration of the acceptor dye is slightly higher than that of the intermediator dye. The present studies are helpful in deciding the optimum concentration of the acceptor dye to be used in ternary dye mixture for maximum gain and tuning range. The ternary dye mixture under study provides an ETDL tuning range up to 700 nm.


The role of metabolism in Th17 cell differentiation and autoimmune diseases.
T helper 17 cells (Th17) have been associated with the pathogenesis of autoimmune and inflammatory diseases, which makes them become a sharp focus when the researchers are seeking therapeutic target for these diseases. A growing body of evidence has suggested that cellular metabolism dictates Th17 cell differentiation and effector function. Moreover, various studies have disclosed that metabolism is linked to the occurrence of autoimmune diseases. In this article, we reviewed the most recent findings regarding the importance of metabolism in Th17 cell differentiation and autoimmune diseases and also discussed the modulation mechanisms of glycolysis, fatty acid and cholesterol synthesis, and amino acids metabolism for Th17 cell differentiation. This review summarized the potential therapeutic or preventing strategies for Th17 cell-mediated autoimmune diseases.


Calcitonin and granulation tissue formation in the rat. An experimental study.
The effects of systemically administered calcitonin (CT) on granulation tissue development were compared using viscose cellulose sponges as wound model in the rat. The ingrowth of new granulation tissue was analyzed for the contents of various connective tissue components (total nitrogen, hydroxyproline, DNA, and RNA) and for the differential counts of the cells infiltrating the sponges. The results indicate that up to 4 weeks postoperatively (p.o.) CT did not affect the net amount of collagen, measured as hydroxyproline, total nitrogen, aminosugars nor the dynamics of differentiation and viability of the invading cells. The present observation that CT has negligible effects, if any, on the early stages of connective tissue formation and on the cell population indicates that surgical procedures could be carried out safely during systemic CT therapy without an increased risk of wound complications.


Redefining the projectional and clinical anatomy of the duodenojejunal flexure in children.
The duodenojejunal flexure (DJF) is an important surgical landmark that enables the pediatric surgeon to establish whether normal intestinal rotation has occurred. The degree of variation in the position of the DJF has not been studied in the pediatric population, and there have been only limited studies on adults. The aim of the present study was to determine the position and relationships of the DJF in infants and children utilizing cross-sectional imaging. Computer tomography scans of 120 children were divided into three age groups and systematically analyzed. The DJF position was measured in relation to the vertebral body level, midline, anterior-posterior distance from the vertebral body, transpyloric plane, and mesenteric vessels. The position of the third part of the duodenum and the length of the mesenteric root were also determined. There was considerable variation in the DJF position with respect to the above landmarks in all three age groups. The vertebral body level of the DJF was centered on L1, but ranged between T11 and L3. In 3% of children with normal rotation the SMA/SMV relationship was abnormal. The third part of the duodenum was consistently found to be retromesenteric. The length of the mesenteric root ranged from 7 to 22 cm, and generally lengthened with increasing age. Owing to its variable position in infants and children, the DJF on its own may not be a reliable landmark for establishing normal intestinal rotation. Assessing for normal rotation is multifaceted and further comparative studies are required to characterize the anatomical features of normal and abnormal rotation.


Edwardsiella piscicida YccA: A novel virulence factor essential to membrane integrity, mobility, host infection, and host immune response.
YccA is a hydrophobic protein with seven transmembrane domains. The function of YccA is largely unknown in pathogenic bacteria. Edwardsiella piscicide (formerly known as E. tarda) is an aquatic pathogen that can infect various economically important fish, including flounder (Paralichthys olivaceus) and tilapia (Oreochromis niloticus). In this study, we investigated the role of YccA in E. piscicida by the construction of a mar kerless yccA in-frame mutant strain, TX01ΔyccA. We found that (i) in comparison to the wild type TX01, TX01ΔyccA exhibited markedly compromised tolerance to high temperature and tobramycin; (ii) deletion of yccA significantly impaired the integrity of the cell membrane and retarded bacterial biofilm formation and mobility; (iii) deficiency of yccA reduced bacterial adhesion and invasion of fish cells and immune tissues, while the introduction of a trans-expressed yccA gene restored the lost virulence of TX01ΔyccA; and (iv) host immune responses induced by TX01 and TX01ΔyccA were different in terms of reactive oxygen species (ROS) levels and expression levels of cytokines. Taken together, the results of our study indicate that YccA is a novel virulence factor of E. piscicida, and YccA is essential for bacterial pathogenicity through evasion of the host's innate immune functions.


Lower respiratory tract virus findings in mechanically ventilated patients with severe community-acquired pneumonia.
The role of viral infections in the etiology of severe community-acquired pneumonia (SCAP) was prospectively evaluated from 2008 to 2012 at a university-level intensive care unit. Clinical data and microbiological tests were assessed: blood cultures, urine pneumococcal and legionella antigens, Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies from paired serums, and respiratory virus detection by multiplex, real-time polymerase chain reaction (PCR) from nasopharyngeal swabs and lower tracheal specimens via intubation tube. Of 49 mechanically ventilated SCAP patients (21 men and 28 women; median age, 54 years), the etiology was identified in 45 cases (92%). There were 21 pure bacterial infections (43%), 5 probably pure viral infections (10%), and 19 mixed bacterial-viral infections (39%), resulting in viral etiology in 24 patients (49%). Of 26 viruses, 21 (81%) were detected from bronchial specimens and 5 (19%) from nasopharyngeal swabs. Rhinovirus (15 cases, 58%) and adenovirus (4 cases, 15%) were the most common viral findings. The bacterial-viral etiology group had the highest peak C-reactive protein levels (median, 356 [25th-75th percentiles, 294-416], P = .05), whereas patients with probably viral etiology had the lowest peak procalcitonin levels (1.7 [25th-75th percentiles, 1.6-1.7]). The clinical characteristics of pure bacterial and mixed bacterial-viral etiologies were comparable. Hospital stay was longest among the bacterial group (17 vs 14 days; P = .02). Viral findings were demonstrated in almost half of the SCAP patients. Clinical characteristics were similar between the pure bacterial and mixed bacterial-viral infections groups. The frequency of viral detection depends on the availability of PCR techniques and lower respiratory specimens.


Paneth cells drive intestinal stem cell competition and clonality in aging and calorie restriction.
Calorie restriction has been recently shown to increase intestinal stem cell competition and to reduce mutation fixation in young mice. However, the impact of aging on this process is unknown. By employing Confetti reporter mice, here we show that, unexpectedly, old mice have more intestinal stem cell (ISC) competition than young mice. Moreover, differently from what observed in young mice, calorie restriction, when applied at late-life, decreases this process. Importantly, we also observed a strong correlation between the ISC competition and Paneth cell number. In vivo analysis and in vitro organoid experiments indicated that Paneth cells play a major role in driving intestinal stem cell competition and crypt clonality. Taken together, our results provide evidence that increasing the number of Paneth cells can increase the number of competitive ISCs, representing a valuable therapeutic target to delay fixation of mutated intestinal stem cells.


Manual QT interval measurement with a smartphone-operated single-lead ECG versus 12-lead ECG: a within-patient diagnostic validation study in primary care.
To determine the accuracy of QT measurement in a smartphone-operated, single-lead ECG (1L-ECG) device (AliveCor KardiaMobile 1L). Cross-sectional, within-patient diagnostic validation study. Patients underwent a 12-lead ECG (12L-ECG) for any non-acute indication in primary care, April 2017-July 2018. Simultaneous recording of 1L-ECGs and 12L-ECGs with blinded manual QT assessment. OUTCOMES OF INTEREST: (1) Difference in QT interval in milliseconds (ms) between the devices; (2) measurement agreement between the devices (excellent agreement <20 ms and clinically acceptable agreement <40 ms absolute difference); (3) sensitivity and specificity for detection of extreme QTc (short (≤340 ms) or long (≥480 ms)), on 1L-ECGs versus 12L-ECGs as reference standard. In case of significant discrepancy between lead I/II of 12L-ECGs and 1L-ECGs, we developed a correction tool by adding the difference between QT measurements of 12L-ECG and 1L-ECGs. 250 ECGs of 125 patients were included. The mean QTc interval, using Bazett's formula (QTcB), was 393±25 ms (mean±SD) in 1L-ECGs and 392±27 ms in lead I of 12L-ECGs, a mean difference of 1±21 ms, which was not statistically different (paired t-test (p=0.51) and Bland Altman method (p=0.23)). In terms of agreement between 1L-ECGs and lead I, QTcB had excellent agreement in 66.9% and clinically acceptable agreement in 93.4% of observations. The sensitivity and specificity of detecting extreme QTc were 0% and 99.2%, respectively. The comparison of 1L-ECG QTcB with lead II of 12L-ECGs showed a significant difference (p=<0.01), but when using a correction factor (+9 ms) this difference was cancelled (paired t-test (p=0.43) or Bland Altman test (p=0.57)). Moreover, it led to improved rates of excellent (71.3%) and clinically acceptable (94.3%) agreement. Smartphone-operated 1L-ECGs can be used to accurately measure the QTc interval compared with simultaneously obtained 12L-ECGs in a primary care population. This may provide an opportunity for monitoring the effects of potential QTc-prolonging medications.


Continuous nerve block versus thoracic epidural analgesia for post-operative pain of pectus excavatum repair: a systematic review and meta-analysis.
Surgery to repair pectus excavatum (PE) is often associated with severe postoperative pain, which can impact the length of hospital stay (LOS). While thoracic epidural analgesia (TEA) has traditionally been used for pain management in PE, its placement can sometimes result in severe neurological complications. Recently, paravertebral block (PVB) and erector spinae plane block (ESPB) have been recommended for many other chest and abdominal surgeries. However, due to the more severe and prolonged pain associated with PE repair, it is still unclear whether continuous administration of these blocks is as effective as TEA. Therefore, we conducted this systematic review and meta-analysis to demonstrate the equivalence of continuous PVB and ESPB to TEA.


Comparison of current and past surgical smoke control practices.
In 2010, we teamed with AORN to repeat a simple web-based survey on surgical smoke control practices first conducted in 2007. This survey of AORN members assessed the level of compliance with established surgical smoke control measures (ie, use of wall suction with an in-line particulate filter, use of a smoke evacuator, use of an N95 or other National Institute for Occupational Safety and Health-approved respirator) in various medical specialties and facilities throughout North America, as well as the extent to which compliance rates may have changed since 2007. Survey responses indicate that while the use of wall suction as a control measure has increased for nearly all procedures, progress in the adoption of other control measures has been mixed, with improvement for some procedures, no change for most procedures, and a decrease in compliance for a few procedures.